Refractive Surgery [3 ed.] 0323547699, 9780323547697

Table of contents :
Cover
Refractive Surgery
Copyright Page
Video Table of Contents
Foreword
Foreword to the First Edition
Preface
List of Contributors
Dedication
1 Terminology, Classification, and History of Refractive Surgery
Introduction: Why Do Patients Choose Refractive Surgery?
Emmetropia, Ametropias, and Presbyopia
Classification of Refractive Procedures
Keratorefractive Surgery
Keratorefractive Procedures: Myopia and Myopic Astigmatism
Laser Procedures
Laser Procedures for Myopia
Laser Procedures for Myopic Astigmatism
Incisional Procedures: A Historical Perspective
Incisional Procedures for Myopia
Incisional Procedures for Myopic Astigmatism
Nonlaser Lamellar Procedures for Myopia: A Historical Perspective
Corneal Implants for Myopia
Hyperopia and Hyperopic and Mixed Astigmatism
Laser Procedures
Laser Procedures for Hyperopia
Laser Procedures for Hyperopic and Mixed Astigmatism
Incisional Procedures for Hyperopia
Nonlaser Lamellar Procedures for Hyperopia
Thermal Procedures for Hyperopia
Aphakia
Presbyopia
Monovision
Conductive Keratoplasty
Multifocal Corneal Ablation and PresbyLASIK
Corneal Inlays
Hybrid
Lenticular and Scleral Refractive Surgical Procedures
Clear Lens Extraction
Phakic Intraocular Lenses
Bioptics
Aphakia
Presbyopia
Multifocal Intraocular Lenses
Accommodating and Pseudo-Accommodating Lenses
Phaco-Ersatz
Scleral Relaxation and Scleral
Summary
References
2 Corneal Wound Healing Following Keratorefractive Surgery
Introduction
Radial Keratotomy
Cellular Mechanism of Refractive Regression After Radial Keratotomy and Role of Corneal Myofibroblast
Excimer Laser Refractive Surgery
Wound-Healing Response Following Excimer Laser Photorefractive Keratectomy
Epithelium
Keratocyte Apoptosis
Stromal Repair
Myofibroblasts, Regression, and Haze After Photorefractive Keratectomy
Wound Healing After LASIK
Epithelium
Keratocyte Apoptosis
Stromal Wound Healing
References
3 Physiologic Optics for Refractive Surgery
Introduction
Geometric Optics
Prisms and Lenses
Images and Vergence
Magnification
Refractive Errors of the Human Eye
Emmetropia
Myopia
Hyperopia
Astigmatism
Correction of Refractive Errors and Visual Distortions
Oblique Astigmatism
Image Magnification
Lens Effectivity
Preoperative Optical Considerations for Refractive Surgery
Contact Lens Wear
Vertex Distance
Anisometropia and Aniseikonia
Cycloplegic Refraction
Hyperopia
Diabetes
Pupil Size
Extraocular Motility Examination
Accommodation
Spectacle Overcorrection of Myopia
Intraoperative Optical Considerations of Refractive Surgery
Optical Axis, Nodal Points, and Visual Axis
Pupil, Optical Zones, and the Chief Ray
Line of Sight and Pupillary Axis
Angles Kappa and Lambda
Pupil Eccentricity
Foveal Eccentricity
Summary of the Role of the Visual Axis and the Optical Zone
Pupillary Dilation
Recommended Technique for Optimal Centration in Corneal Refractive Surgical Procedures
Optical Considerations After Refractive Surgery
Pupil Size
Oval Topographic Zones After Astigmatic Surgery
Topographic Maps
Astigmatic Dial
Prescribing Spectacles After Refractive Surgery
Spasm of Accommodation
Convergence Insufficiency
Presbyopia
Prescribing for Presbyopia After Refractive Surgery
Fluctuating Vision
Unequal Amplitude of Accommodation
Bifocal Type
References
4 Corneal Topography
Introduction
Curvature
Elevation Topography
Interpretation of Posterior Surface Elevation Topography
Functional Corneal Representations Derived From Shape
Refractive Power Maps
Functional Optical Zone
Anterior Corneal Wavefront Aberrations
Topographic and Tomographic Technologies
Conclusions
References
5 Wavefront Analysis
Introduction
History of Wavefront: The Debate Concerning the Phenomenon of Light
Wavefront Theory
What Is a Wavefront?
How Does a Wavefront Propagate?
What Is Diffraction?
Diffraction and Fourier Transform
Ocular Aberrations
Wavefront Measurement
Outgoing Reflective Aberrometry Using Hartmann–Shack Wavefront Analyzers
Wavefront Study With Retinal Imagery
Tscherning Analyzing System
Retinal Ray Tracing
Ingoing Adjustable Refractometry
Double-Pass Aberrometry (Slit Skiascopy/OPD Scan Device)
Accuracy and Repeatability of Wavefront Measurements
Wavefront Analysis and Map Interpretation
Principles of Wavefront Reconstruction
Use of Zernike Polynomials in Wavefront Sensing
Principles of the Wavefront Decomposition Into Zernike Polynomials
Wavefront Interpretation Based on Zernike Polynomial Decomposition
Application to the Wavefront Interpretation
Statistical Variation of Aberration in Healthy Eyes
Variation of Aberration After Refractive Surgery
Variations of Aberration With Aging
Measures of Optical Performance of the Eye
Pupil Plane Metrics: Wavefront Map Metrics
Vergence Maps
Image Plane Metrics
Point-Spread Function
Optical Transfer Function, Modulation Transfer Function, Phase Transfer Function
Relations Between Point Spread Function and Optical Transfer Function
Metrics and Polychromatic Light
Prediction of Subjective Refraction From Wavefront Aberration Maps Vision Quality Metrics
Conclusion
References
6 Optical Coherence Tomography in Refractive Surgery
Introduction
Instruments
Scanning Protocols and Measurements
Applications in Refractive Surgery
Preoperative Evaluation
Postoperative Evaluation
OCT Angiography
Further Reading
7 Excimer Lasers
Introduction
Lasers: General Physical Principles
Principles of Laser Emission
Laser–Cornea Interactions
Properties of the Excimer Laser
Laser Beam Generation
Gaseous Medium
Beam Homogenization
Beam Delivery System
Full-Beam Systems (Fig. 7.2)
Scanning Slit Delivery
Flying Spot
Computer
Work Area
Parameters of the Laser Beam
Pulse Duration
Pulse Frequency
Pulse Energy
Fluence
Rate of Ablation
Effects of the Excimer Laser on Corneal Tissue
Molecular Effects
Mutagenicity
Tissular Effects
Eye Tracker
Eye Movements During Refractive Corneal Photoablation
Eye Tracker Function
Eye Movement Recording
FDA-Approved Excimer Lasers (2006 to Present)
Topography and Wavefront-Based Treatments in Excimer Lasers
Topography-Guided Laser Refractive Surgery
Wavefront-Based Laser Refractive Surgery
Topography-Guided Ablation Profiles Compared to Wavefront-Based Treatments
Conclusions
References
8 Laser and Mechanical Microkeratomes
Introduction
Mechanical Microkeratomes
Laser Microkeratomes: The Femtosecond Lasers
Physical Principles of the Femtosecond Laser
Corneal Interactions With the Femtosecond Laser
Corneal Flap Preparation With the Femtosecond Laser
Advantages and Disadvantages of the Femtosecond Laser
Comparison Between Mechanical Microkeratome and Femtosecond Laser
Conclusions
References
9 Crosslinking Instrumentation
Introduction
Crosslinking Equipment: Common Architecture and Internal Parts
UV-Light Source
Wavelength Selection
Temperature Influence on Wavelength
Temperature Influence on Power Output
The UV Light Optical Beam Delivery System
Optical Output Power Density Distribution
Optical Beam Aiming and Positioning, Auxiliary Aiming Beam
Optical Beam Spot Size
The Main Electronic Control System
Main Processor, Display, and Keyboard
Watchdog Circuit
The Power Control Block, Current Sensor, Main Photodiode Led Control Loop
Continuous and Pulsed Power Control
Auxiliary Devices
Interlock Device
Sound Emission
Aiming Beam, or Alignment Auxiliary System Control
Eye Tracker
Regulatory and Normative Requirements
A Survey of Crosslinking Platforms on the Market
Nonphotoactivated Crosslinking Agents
References
10 Ocular Diseases of Importance to the Refractive Surgeon
Introduction
Blepharitis and Meibomitis
Anterior Blepharitis
Meibomitis and Meibomian Gland Dysfunction
Bacterial Conjunctivitis and Keratitis
Chronic Bacterial Conjunctivitis and Keratitis
Viral Conjunctivitis and Keratitis
Tear Abnormalities and Exposure Keratitis
Tear Film Abnormalities
Neurotrophic Keratitis
Exposure Keratopathy
Immunologic Diseases of the Conjunctiva and Cornea
Ocular Allergic Diseases
Allergic Conjunctivitis
Atopic Keratoconjunctivitis
Giant Papillary Conjunctivitis
Ocular Mucous Membrane Pemphigoid
Connective Tissue Disease and Systemic Vasculitides
Developmental Abnormalities of the Cornea
Megalocornea
Microcornea
Oval Cornea
Sclerocornea
Posterior Keratoconus
Keratoglobus
Keratoconus
Other Noninflammatory Corneal Thinning Disorders
Epithelial Corneal Dystrophies
Map-Dot Fingerprint Dystrophy
Meesmann Dystrophy
Reis–Bückler Dystrophy
Band Keratopathy
Glaucoma
Ocular Hypertension and Primary Open-Angle Glaucoma
Pigment Dispersion Syndrome and Pigmentary Glaucoma
Steroid-Induced Glaucoma
Congenital Glaucoma
Chorioretinal Disorders
Myopic Macular Degeneration
Lattice Degeneration of the Retina
Retinal Detachment
Other Peripheral Retinal Degenerations
White Without Pressure
Cobblestone Degeneration
Peripheral Pigmentary Degeneration
Idiopathic Multifocal Choroiditis
Choroidal Hemorrhages/Effusions
Choroidal Folds
Acquired Retinoschisis
Nanophthalmos and Uveal Effusions
Inherited Retinal Degenerations
Optic Nerve Disorders
Optic Disc Drusen
Nonarteritic Anterior Ischemic Optic Neuropathy
Systemic Associations
Diabetes Mellitus
Transient Refractive Shifts
Myopic Shifts
Hyperopic Shifts
Permanent Myopia
Myopia and Diabetic Retinopathy
Acquired Immunodeficiency Syndrome
Albinism
Wagner and Stickler Syndromes
Marfan Syndrome
Weill–Marchesani Syndrome
Down Syndrome
Gyrate Atrophy
Cerebral Palsy
References
11 Patient Evaluation for Refractive Surgery
Introduction
Philosophical Issues
Guidelines for Patient Selection
Absolute Contraindications
Ocular Hypertension and Glaucoma
Connective Tissue Disease
Corneal Dystrophies
Patient Expectations
Relative Contraindications
Dry Eye
Diabetes Mellitus
Human Immunodeficiency Virus
Previous Ocular Surgery
After Retinal Detachment Surgery
After Cataract Surgery
After Penetrating Keratoplasty
Guidelines for Preoperative Examination
Assessment of Contraindications and Appropriateness for Surgery
Assessment of Patient Needs and Expectations
Review of Risks and Benefits
Reading Materials
Questionnaire
Time Interval Between Eyes
Preoperative Examination
Discontinuance of Contact Lens Wear
Refraction
Keratometry
Computer-Assisted Videokeratography
Wavefront Aberrometry Measurement
Contrast Sensitivity and Glare Testing
Pupillary Size
Ocular Dominance
Ocular Motility Issues
Pachymetry and Specular Microscopy
Informed Consent
References
12 Preoperative Evaluation of Keratoconus and Ectasia
Introduction
Guidelines for Preoperative Examination
Corneal Cross-Linking
Definition of Progression
Corneal Cross-Linking Techniques Guideline
Clinical Evaluation
Topography Evaluation
Prognostic Factors
Intracorneal Ring Segments
Prognostic Factors
Refractive Evaluation
Corneal Tomography/Topography Evaluation
ICRS Indications
Surgical Plan and Patient Preparation
Nomogram
Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty
Introduction
Deep Anterior Lamellar Keratoplasty
Donor Characteristics for Keratoplasty
Phakic Intraocular Lens for Corneal Ectasia
Location of Phakic Intraocular Lenses
Lens Size
Posterior Chamber Phakic Intraocular Lenses Vault
Anterior Chamber Phakic Intraocular Lenses Vault
Indications for Phakic Intraocular Lens
Implantation Criteria
Indications
Relative Indications
Contraindications
Anterior Segment Optical Coherence Tomography
References
13 LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism
Introduction
Pure Myopia (Video 13.1)
LASIK for Low to Moderate Myopia
LASIK in High Myopia
Reducing the Magnitude of the Treatment (Intended Undercorrection)
Reducing the Programmed Optical Zone
Use of Multizone/Multipass or Aspheric Profiles of Ablation
Reducing the Thickness of the Corneal Flap
Pure Hyperopia (Video 13.1)
Outcomes of Hyperopic LASIK
Simple, Compound, and Mixed Astigmatic Errors (Video 13.1)
Simple Astigmatism
Simple Hyperopic Astigmatism
Simple Myopic Astigmatism
Relation Between Negative and Positive Cylindrical Ablations
Compound Myopic, Hyperopic, and Mixed Astigmatism
Hyperopic and Mixed Astigmatism
Compound Myopic Astigmatism
Sequential Strategy
Elliptical Strategy
Strategy to Optimize the Clinical Outcomes of Astigmatic Treatments
Topography-Guided Ablations
Rationale for Topography-Guided Ablations With LASIK
Q-Based and Wavefront-Guided Ablations
Rationale for Q-Based and Wavefront-Guided Ablation With LASIK
Q-Based Ablations
Wavefront-Guided Ablations
Characteristics of Custom-Q Profile of Ablation
Characteristics of Wavefront-Guided Profile of Ablation
Prerequisites for Successful Q-Based and Wavefront-Guided Ablations
Q-Based Ablations
Wavefront-Guided Ablations
Quality of Wavefront Reconstruction
Quality of Ablation Profile Calculation
Quality of Ablation Profile Delivery
Quality in Minimizing Excessive Unexpected Corneal Response in Custom Q and Wavefront-Guided Corrections
Results of Q-Based and Wavefront-Guided Lasik Procedures
References
14 LASIK and TopoLink for Irregular Astigmatism
Introduction
The Technique of TopoLink
Examples of Topolink (Videos 1 to 3)
Patient 1: Irregular Astigmatism After Penetrating Keratoplasty and Astigmatic Keratotomy
Patient 2: Irregular Astigmatism
Patient 3: Decentered Ablation
Results of TopoLink in Repair Procedures
References
15 LASIK Complications and Their Management
Introduction
Intraoperative Complications
Inadequate Exposure
Suction Loss (Videos 4 to 6)
Corneal Epithelial Defect
Incomplete or Irregular Cut (Video 7)
Decentered Flaps
Free Cap (Video 1)
Buttonhole (Videos 8 and 9)
Pizza Slicing
Limbal Hemorrhage
Intraoperative Complications Specific to Femtosecond Laser LASIK
Vertical Gas Breakthrough
Anterior Chamber Bubbles (Video 3)
Opaque Bubble Layer
Early or Hard Opaque Bubble Layer
Late or Soft Opaque Bubble Layer
General Photoablation-Related Complications
Decentration
Overcorrection and Undercorrection
Early Postoperative Complications
Interface Debris
Flap Displacement and Flap Folds (Video 2)
Flap Striae and Folds (Video 13)
Loss of the Flap/Cap
Diffuse Lamellar Keratitis
Pressure-Induced Stromal Keratopathy
Infectious Keratitis
Epithelial Ingrowth (Videos 10 to 12)
Central Toxic Keratopathy
Late Postoperative Complications
Induced or Iatrogenic Keratectasia
Night Vision Problems and Glare
Transient Light Sensitivity Syndrome
Rainbow Glare
LASIK-Associated Dry Eye and Neurotrophic Epitheliopathy
References
16 Small-Incision Lenticule Extraction (SMILE)
Introduction
Principles Behind SMILE
Surgical Techniques for SMILE (Video 16.1)
Preoperative Considerations
Patient Selection
Centration
Incision Technique
Appropriate Laser Pulse
Shape of the Incision
Centering Accuracy of the Incision
Other Important Considerations
Thickness of Lenticule Cap
Corneal Wound Healing After SMILE
Corneal Biomechanics
Literature Review
Inclusion Criteria
Results
Predictability, Safety, and Efficacy
Intraoperative Complications
Postoperative Complications
Explanation of the Graphs (Dry Eye)
Corneal Biomechanics
Further Areas of SMILE Applicability
References
17 Small-Incision Lenticule Extraction (SMILE) Complications and Their Management
Introduction
Theoretical Advantages and Limitations of SMILE
Advantages
Limitations
How to Avoid Complications
Difficulties in Obtaining Suction
Preparation for Lenticule Extraction
Lenticule Dissection and Extraction
Flushing the Interface
Management of Intraoperative Complications
Decentration
Suction Loss
Difficult Dissection of the Lenticule
Black Spots
Lenticule Tears and Retained Lenticular Fragments
Cap Tear
Epithelial Abrasions
Management of Postoperative Complications
Diffuse Lamellar Keratitis
Infection
Epithelium and Other Foreign Bodies in the Interface
Interface Fluid Collection
Ectasia
Dry-Eye Syndrome
Undercorrection and Overcorrection and Retreatment Options
References
18 Photorefractive Keratectomy
Introduction
Excimer Laser Physics and Beam Tissue Interaction
Postoperative Care
PRK Complications to Consider
References
19 LASEK and Epi-LASIK
Introduction
Definition and Terminology
Theoretical Advantages of LASEK
Alcohol-Assisted Epithelial Removal
Effect of Alcohol on Epithelial Cell Survival In Vitro
Transmission Electron Microscopy of Corneal Epithelium Specimen
Use of Mitomycin C to Avoid Haze
Surgical Techniques
Azar Flap Technique
Camellin Technique
Vinciguerra Butterfly Technique
Alternatives to Alcohol-Assisted Epithelial Removal
Epi-LASIK
Introduction
The Original Surgical Procedure
Postoperative Care
Epi-LASIK Clinical Results
Gel-Assisted Epithelial Removal (McDonald Technique)
Trans-epithelial Photorefractive Keratectomy
Epi-Bowman Keratectomy
Clinical Outcomes of LASEK
Retreatments
Complications
LASEK vs Photorefractive Keratectomy and Epi-LASIK
LASEK vs LASIK
Summary of Clinical Reports
Summary and Future Applications/Corneal Cross-Linking
References
20 Phototherapeutic Keratectomy (PTK) and Intralamellar PTK
Introduction
Excimer Laser Advantages and Safety
Phototherapeutic Keratectomy and Intralamellar PTK Indications
Surgical Planning and Technique
Preoperative Evaluation
Preoperative Preparation
Laser Treatment and General Surgical Techniques
IL-PTK: Surgical Technique (Fig. 20.5)
Elevated Central Corneal Nodules (Video 20.4)
Multiple Surface Irregularities
Corneal Dystrophies (Videos 20.1 and 20.6)
Recurrent Corneal Erosions (Videos 20.2 and 20.3)
Corneal Scars
Infectious Keratitis
Refractive Surgery Complications
Prismatic Photokeratectomy
Postoperative Management
Corneal Wound Healing
Complications From PTK and Intralamellar PTK
Refractive Complications
Early Postoperative Complications
Late Postoperative Complications
Outcomes of PTK: Major Studies and Specific Diseases
Corneal Dystrophies
Recurrent Corneal Erosions
Corneal Scars (Video 20.5)
Refractive Surgery
Visual Acuity Outcomes in Lamellar Keratoplasty
Excimer Laser and Lamellar Keratoplasties
References
21 Principles of Corneal Cross-Linking
Introduction
Basic Principles
Cross-Linking for Keratoconus
Cross-Linking Beyond Keratoconus
References
22 Epithelium Off and Transepithelial Cross-Linking
Introduction
Basic Principles of Corneal Cross-Linking
Basic Research Results
Standard Cross-Linking Procedure: Epi-Off Cross-Linking (Video 22.1)
Rapid Accelerated Technique
Transepithelial Cross-Linking
Cross-Linking Results
Alternative Uses of Corneal Cross-Linking
Infections
Pseudophakic Bullous Keratopathy
References
23 Orthokeratology
Introduction
Changes in Refraction and Visual Acuity
Topographic Corneal Curvature Changes
Anterior Segment Changes
Orthokeratology for Myopia Control
Other Corneal Changes
Corneal Pigmented Arc
Fibrillary Lines
Corneal Staining
Lens Binding
Microbial Keratitis in Orthokeratology
Patient Acceptance
References
24 Radial and Astigmatic Keratotomy
Introduction
Success and Failure of Radial Keratotomy
Astigmatic Keratotomy
Limbal Relaxing Incisions
Mechanism of Action
Patient Selection
Astigmatic Power
Steeper Corneal Meridian
Front-Cutting Blade
Mechanized Arcuate Keratomes and Femtosecond Lasers
Surgical Technique
AK-LASIK
Complications
Infection
Perforation
Undercorrection
Overcorrection
Rotation of Axis With Residual Astigmatism
Irregular Astigmatism
Recurrent Erosions and Superficial Punctate Keratitis
References
25 Conductive Keratoplasty and Laser Thermokeratoplasty
Introduction
Historical Background
Response of Corneal Collagen to High Temperature
Laser Thermokeratoplasty
Holmium:YAG Lasers
Contact Holmium:YAG
Noncontact Holmium:YAG
Clinical Outcomes of LTK
Conductive Keratoplasty
Conductive Keratoplasty Procedure (Video 25.1)
Visual Outcomes
Visual Acuity
Safety
Stability
Patient Satisfaction
References
26 The Intrastromal Corneal Ring Segments
Introduction
Results of Clinical Trials With the Intrastromal Corneal Ring
Nonfunctional Eye Study
Sighted Eye Studies
Removal and Exchanges (Video 26.5)
Prognosis Factors
Surgical Technique (Videos 26.1 to 26.3)
Therapeutic Applications (Video 26.4)
References
27 Intraocular Lens Calculations After Keratorefractive Surgery
Introduction
Source of Error in K-Reading Following Corneal Refractive Surgery
Present Methods for K-Reading After Corneal Refractive Surgery
Clinical History Method
Example
Hard Contact Lens Method
Example
Calculation of the Corneal Dioptric Power by Measuring the Anterior Corneal Curvature
Example
Direct Measurement of the Total Corneal Power Using Modified Effective Index of Refraction
Example
Posterior Corneal Curvature Method
Discussion
References
28 Phakic Intraocular Lens Power Calculations
Introduction
Van der Heijde’s Equation and Holladay’s Equation
Azar/Wong Simplified Phakic IOL Formula
Effective Lens Position
Anterior Chamber Depth
Keratometry and Refractive Index
White-to-White Distance
Mathematical Analysis of the Predictability of Different Types of PIOL
Preoperative Refraction
Vertex Distance
Effective Lens Position and Anterior Chamber Depth
Keratometry and Refractive Index
Bioptics and Piggyback IOL
Bioptics
Piggyback IOL
IOL Calculations After PIOL Implantation
Summary
References
29 Refractive Lens Exchange
Introduction
Pearls in Surgical Technique
IOL Power Calculation
Main Indications and Outcome
Conclusions
References
30 Iris-Fixated Phakic Intraocular Lenses
Introduction
Lens Designs
Indications and Contraindications
Surgical Procedure
Preparation
IOL Power Calculation
Preoperative Miosis
Operative Technique (Videos 30.1 and 30.3)
Incision Techniques
Incision Size
Paracenteses
Viscoelastic Material
Introduction of the Phakic IOL Into the Anterior Chamber
Guaranteeing Pupillary Miosis
Centration and Fixation of the IOL
Iridectomy/Iridotomy
Wound Closure
Particularities of the Toric and Foldable Models
The Toric Lens
The Artiflex Lens (Video 30.2)
Removal of the Viscoelastic Material
Postoperative Management
Outcome and Complications
Functional Outcome
Results for Myopia
Results for Hyperopia
Results for Astigmatism
Optical Quality After Artisan Implantation
Complications
Anterior Chamber Inflammation
Glaucoma
Impact on the Crystalline Lens
Endothelium Tolerance
Iris Changes
Miscellaneous
Conclusions
References
31 Posterior Chamber Phakic Intraocular Lens
Introduction
Lens Design
Preoperative Evaluation
Surgical Technique (Video 31.1)
Preparation and Anesthesia
Surgical Procedure
Inserting the Implant With an Injector (Fig. 31.1)
Inserting the Implant With Forceps (Fig. 31.2)
Functional Results
Predictability
Visual Acuity
Stability
Quality of Vision
Halos
Anatomic Outcome
Early Postoperative Complications
Decentration of the Implant
Early Postoperative Intraocular Pressure Rise
Long-Term Postoperative Outcome
Endothelial Cell Damage
Subclinical Inflammation
Pigmentary Dispersion
Elevated Intraocular Pressure
Cataractogenesis
Advantages and Disadvantages
References
32 Complications of Phakic Intraocular Lenses
Introduction
Anterior Chamber IOLs
Historic Angle-Supported Models
Baikoff‘s Lens Models
ZSAL Models
Phakic 6 IOL
Foldable Lenses
Duet Kelman Lens
Acrysof Phakic Implant (Cachet, Alcon)
GBR Vivarte Lens
Current Anterior Chamber IOLs: Iris-Fixated Models
Posterior Chamber IOLs
Sulcus-Supported Models
Zonular-Supported Models
Conclusions
References
33 Phakic Intraocular Lens Explantation (PIOL)
Introduction
Cataract Formation
Endothelial Cell Loss
Decentration/Dislocation of PIOL
Pupillary Ovalization
Pupillary Block Glaucoma
Pigment Dispersion
Retinal Detachment
Endophthalmitis
Preoperative Assessment
Phakic Intraocular Lens Exchange
Simple PIOL Removal
Bilensectomy
IOL Calculation in Bilensectomy
Surgical Technique (Videos 33.1 to 33.3)
Angle-Supported PIOL
Iris-Fixated PIOL
Posterior Chamber PIOL
Bilensectomy Results
References
34 Physiology of Accommodation and Presbyopia
Introduction
Accommodation
Historical Background
Current Understanding of Accommodation
Presbyopia
Lenticular Causes of Presbyopia
Extralenticular Causes of Presbyopia
Limitations to the Understanding of Accommodation and Presbyopia
Conclusion
References
35 Monovision
Introduction
Achieving Monovision
Ideal Monovision Result
Visual Performance in Monovision
Binocular Visual Acuity
Interocular Blur Suppression
Stereoacuity
Contrast Sensitivity
Peripheral Vision and Visual Fields
Binocular Depth of Focus
Phorias
Task Performance
Factors Influencing Monovision Success
Preoperative Patient Evaluation
Monovision Trial
Determining the Eye for Distance
Determining the Degree of Add
Crossed Monovision
References
36 Scleral Surgery for Presbyopia
Introduction
Scleral Expansion Segments— Manual Approach
Scleral Expansion Segments—Automated Approach: VisAbility Micro-Insert
Complications of Manual Surgery
Clinical Outcomes of Manual Surgery
Clinical Outcomes of Automated Approach
Other Scleral Expansion Procedures
Anterior Ciliary Sclerotomy
Laser Scleral Expansion
LaserACE Approach
Scleral Expansion and Glaucoma
References
37 Multifocal Corneal Surgery for Presbyopia
Introduction
Theoretical Considerations
Depth of Focus and Optical Aberrations
What Is Multifocality?
Multifocality Versus Monovision
Pseudoaccommodation: The Importance of Corneal Multifocality and Optical Aberrations
Asphericity Modulation
Practical Consequences
General Considerations
Corneal Multifocal Profile of Ablation
Early Techniques
Spherical Aberration and Multifocality in Practice
Changing the Ocular Spherical Aberration With Laser Corneal Ablation
Current Proposed Methods
Peripheral Near Addition Zone
Central and Paracentral Near Addition
Clinical Recommendations for Successful Multifocal Cornea
Limitations of Current Treatments and Future Orientations
References
38 Corneal Implants and Inlays
Introduction
Principles of Corneal Inlays
FDA-Approved Corneal Inlays in Use
KAMRA Inlay (Video 38.1)
Indications and Contraindications for KAMRA Inlay Implantation
KAMRA Inlay Safety and Efficacy
Postoperative Complications for KAMRA Inlay
Raindrop Inlay
Indications and Contraindications for Raindrop Inlay Implantation
Raindrop Inlay Safety and Efficacy
Postoperative Complications for Raindrop Inlay
Presbia Flexivue Microlens Inlay
Flexivue Microlens Inlay Safety and Efficacy
References
39 Multifocal Intraocular Lenses
Introduction
Optics of Multifocality (Videos 39.1 and 39.2)
In vitro Optical Quality
Visual Acuity
Depth of Field
Contrast Sensitivity
Photic Phenomena (Glare and Halos)
Spectacle Use
Posterior Capsular Opacification
Patient Satisfaction and Quality of Life
Final Considerations
References
40 Refractive Surgical Procedures to Restore Accommodation
Introduction
Accommodation: The Helmholtz Theory
Presbyopia: The Loss of Accommodation With Age
Presbyopia Correction: an Overview
Traditional Techniques
Pseudo-Accommodating IOLs
Restoration of Accommodation
Lens Refilling
The Development of Lens Refilling
The Challenges of Lens Refilling
Surgical Technique
Material
Optics
Secondary Cataract
The Status of Lens Refilling: Where Are We Today?
The Accommodation Club
References
41 Smart Intraocular Lenses, Accommodating and Pseudoaccommodating Intraocular Lenses for Presbyopia
Introduction
Smart Intraocular Lenses
Single-Optic, Flexible Haptic Support
Crystalens Surgical Technique
Other Single-Optic Systems
Dual-Optic System, Telescoping Intraocular Lens
Dynamic Optic (Lens Refilling)
Magnetic Lens System
Other Concepts
Light Adjustable Lens
Accommodating Optical Shift Concepts
Conclusion
References
42 Postkeratoplasty Astigmatism
Introduction
Pathogenesis of Postkeratoplasty Astigmatism
Preoperative Factors
Operative Factors
Suturing Technique
Management of Significant Postkeratoplasty Astigmatism
Management of Astigmatism While Sutures Are In: Suture Manipulation
Selective Suture Removal
Suture Adjustment
Management of Astigmatism After Suture Removal
Relaxing Incisions (Video 42.2)
Operative Technique
Femtosecond Laser-Assisted Arcuate Keratotomy (Video 42.1)
Wedge Resections
Operative Technique
Femtosecond Laser-Assisted Wedge Resection (Video 42.3)
Excimer Laser
Toric Intraocular Lenses
References

Citation preview

Refractive Surgery Third Edition

Dimitri T. Azar, MD, MBA

Distinguished University Professor and B.A. Field Chair of Ophthalmic Research, University of Illinois at Chicago, Chicago, IL, USA; Senior Director and Ophthalmology Lead Verily Life Sciences (formerly Google) San Fransisco, CA, USA

Associate Editors

Damien Gatinel, MD, PHD

Head Department of Anterior Segment and Refractive Surgery, Rothschild Foundation Paris, France

Ramon C. Ghanem, MD, PHD

Director of Cornea and Refractive Surgery Department Sadalla Amin Ghanem Eye Hospital Joinville, Brazil

Suphi Taneri, MD

Director, Center for Refractive Surgery Department of Ophthalmology at St. Franziskus Hospital Münster, NRW, Germany; Associate Professor of Ophthalmology Eye Clinic, Ruhr University Bochum, NRW, Germany For additional online content, visit expertconsult.inkling.com

First edition 1997 © Appleton & Lange Second edition 2007 © Elsevier Inc. Copyright © 2020, Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications. It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. ISBN: 978-0-323-54769-7 E-ISBN: 978-0-323-55116-8

Content Strategists: Russell Gabbedy, Kayla Wolfe Content Development Specialists: Trinity Hutton, Joanne Scott Publishing Services Manager: Deepthi Unni Project Manager: Nayagi Athmanathan Design: Amy Buxton Illustration Manager: Teresa McBryan Illustrators: David Gardner, Danny Pyne, Paul Kim, MS, CMI, Matrix Art Services Marketing Manager: Claire McKenzie

Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1

Video Table of Contents

8.1 8.2 8.3 13.1 14.1 14.2 14.3 15.1 15.2 15.3 15.4 15.5 15.6 15.7 15.8 15.9 15.10 15.11

IntraLase Femtosecond Laser LASIK Ramon C. Ghanem LDV Femtosecond Laser-Assisted LASIK Ramon C. Ghanem Microkeratome-Assisted LASIK (Moria SBK) Ramon C. Ghanem Excimer Laser Ablation Patterns Ramon C. Ghanem Topography-Guided PRK for Hyperopia After Radial Keratotomy Ramon C. Ghanem Topography-Guided Transepithelial PRK for Keratoconus Regularization Ramon C. Ghanem Topography-Guided Transepithelial PRK for Central Scar After Foreign Body Ramon C. Ghanem Free Cap in Microkeratome-Assisted-LASIK, Ablation, and Flap Repositioning Ramon C. Ghanem Reposition in Slit Lamp of Early Flap Dislocation After LASIK Ramon C. Ghanem Anterior Chamber Gas Bubbles After Corneal Flap Creation With a Femtosecond Laser Dimitri T. Azar, José de la Cruz, Ramon C. Ghanem Suction Loss During Flap Creation With a Femtosecond Laser Dimitri T. Azar and Ramon C. Ghanem Incomplete LASIK Flap Due to Suction Loss Ramon C. Ghanem Flap Tear After Suction Loss Due to Mechanical Block in Microkeratome LASIK Ramon C. Ghanem Flap Adhesions in Femtosecond Laser LASIK + Alcohol-Assisted-PRK After 3 Months Ramon C. Ghanem Buttonhole Flap Dimitri T. Azar and Ramon C. Ghanem Transepithelial PTK With Prophylactic MMC After Buttonhole LASIK Flap Dimitri T. Azar and Ramon C. Ghanem Treatment of Epithelial Ingrowth With Fibrin Glue Adhesive Vinícius Coral Ghanem Treatment of Epithelial Ingrowth Dimitri T. Azar and Ramon C. Ghanem

15.12

Removal of Epithelial Ingrowth Island After Femtosecond Laser LASIK Ramon C. Ghanem 15.13 Treatment of Flap Folds After LASIK Dimitri T. Azar and Ramon C. Ghanem 16.1 Standard SMILE Technique Using Double-Ended Dissector With Taneri Spoon Tip Suphi Taneri 17.1 Preparation of Lenticule With SMILE Double-Ended Dissector With Taneri Spoon Tip Suphi Taneri 17.2 Epithelial Abrasion on Cap Surface at the Sidecut Suphi Taneri 17.3 Suction Loss Before Preparation of Sidecut. Manually Performed Incision With Diamond Knife Suphi Taneri 17.4 Incomplete Lenticule Preparation by the Laser Due to Conjunctiva Sucked Into the Interface Between Cornea and Action Cone Suphi Taneri 17.5 Suction Loss Before Preparation of Sidecut Suphi Taneri 17.6 Epithelial Abrasion on Cap Surface Suphi Taneri 17.7 Epithelial Cells Within SMILE Interface Suphi Taneri 18.1 PRK for Hyperopia With Mechanical Epithelial Removal and MMC Ramon C. Ghanem 18.2 Alcohol-Assisted PRK Retreatment After LASIK Ramon C. Ghanem 18.3 Topography-Guided Transepithelial PRK for Irregular Astigmatism and Central Corneal Scarring After Foreign Body Accident Ramon C. Ghanem 19.1 LASEK Technique Suphi Taneri 19.2 Epi-LASIK Suphi Taneri 20.1 OCT-Guided Trans PTK + PRK for Granular Dystrophy Ramon C. Ghanem 20.2 PTK in Recurrent Epithelial Erosion Syndrome Ramon C. Ghanem v

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Video Table of Contents 

20.3 20.4 20.5 20.6 22.1 24.1 25.1 26.1 26.2

26.3 26.4 26.5 30.1

PTK for Epithelial Erosion Syndrome Due to EBMD in a Patient With Previous LASIK Ramon C. Ghanem Focal PTK for Apical Leucoma Syndrome Vinícius C. Ghanem Manual Keratectomy and PTK for Corneal Scars After Pterygium Surgery Ramon C. Ghanem Transepithelial PTK in Avellino Dystrophy Dimitri T. Azar and Ramon C. Ghanem Epi-off Cross-linking Ramon C. Ghanem Radial Keratotomy Emir A. Ghanem Conductive Keratoplasty “Light Touch Technique” Dimitri T. Azar and Ramon C. Ghanem Keraring Implantation for Keratoconus Regularization—Manual Technique Ramon C. Ghanem LDV Z8 Femtosecond Laser-Assisted 300 Degrees Cornealring Implantation for Advanced Keratoconus Ramon C. Ghanem Intralase Femtosecond Laser-Assisted INTACS Implantation Dimitri T. Azar and Ramon C. Ghanem Ferrara Ring ICRS for High Astigmatism After Keratoplasty Ramon C. Ghanem ICRS Explantation Ramon C. Ghanem Artisan for Myopia With VacuFix Enclavation Ramon C. Ghanem

30.2

Artiflex Implantation With Enclavation Needle in a Patient With Keratoconus Ramon C. Ghanem 30.3 ARTISAN for Hyperopia After Radial Keratotomy Ramon C. Ghanem 31.1 Posterior Chamber Phakic IOL Implantation in High Myopia Jean L. Arne 32.1 Traumatic Dislocation and Successful Re-enclavation of an ARTISAN Phakic IOL Ramon C. Ghanem 33.1 ARTISAN Bilensectomy Veronica Vargas Fragoso and Jorge L. Alió 33.2 Phakic IOL Exchange Veronica Vargas Fragoso and Jorge L. Alió 33.3 Bilensectomy Veronica Vargas Fragoso and Jorge L. Alió 38.1 KAMRA Corneal Inlay Damien Gatinel 39.1 Diffractive Trifocal Intraocular Lens Implantation Ramon C. Ghanem 39.2 Toric Extended Depth of Focus Intraocular Lens Implantation Ramon C. Ghanem 42.1 Femtosecond Laser Arcuate Keratotomy for High Astigmatism After DALK Ramon C. Ghanem 42.2 Manual Arcuate Keratotomy for High Astigmatism After DALK Ramon C. Ghanem 42.3 Femtosecond Laser-Assisted Wedge Resection After Penetrating Keratoplasty Ramon C. Ghanem and Dimitri T. Azar

Foreword

Richard Wagner worked for nearly 30 years to complete the tetralogy of The Ring—from 1848 to 1876 until the premiere in Bayreuth, starting in Dresden and continuing in Switzerland and Bayreuth, the hometown of my grandfather. You may ask what The Ring has in common with Dimitri Azar’s book on refractive surgery. First, Dimitri and I share the passion for Wagner’s music. Second, it also took nearly 30 years to make refractive surgery, especially laser vision correction, an accepted subdiscipline in ophthalmology—30 years seems to be an acceptable time to create a masterpiece. Third, many of the primers in modern refractive surgery happened also in Germany and Switzerland (e.g., phototherapeutic keratectomy [PTK], wavefront-optimized treatments, wavefront-guided treatments, topography-guided ablation, small-incision lenticule extraction [SMILE], corneal cross-linking, and customized cross-linking). When laser refractive surgery commenced by the end of the 1980s, it was considered “the dark side of ophthalmology”—by the way, for good reasons. Meanwhile, refractive success rate and complication rate has outperformed soft contact lenses. Typical refractive success rates (± 0.5D) of myopic LASIK are around 94%, comparable or better with

the 95% confidence interval of spherical refraction. This means that we can’t make the success rate any better; it is as good as the refraction that needs to be corrected. Regarding complications, the paper of Masters et al. showed clearly that, at the latest, after 3 years the risk of microbial keratitis is higher with contact lenses compared to LASIK. But it took refractive surgery 30 years to appear at the bright side of ophthalmology! This book arrives, therefore, at the right time. The list of the authors reads like a “who’s who” of refractive surgery, and each of the chapters is worth reading. In addition, it covers the whole spectrum and includes new techniques (SMILE, customized cross-linking) as well as traditional procedures, such as PRK and keratotomies. Thank you, Dimitri, for writing and collecting so many original articles, and thus creating a standard book on modern refractive surgery! Theo Seiler, MD, PhD Institut für Refraktive und Ophthalmo-Chirurgie (IROC) Stockerstrasse, Zürich 2018

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Foreword to the First Edition Evolution of medical information progresses inexorably, though sometimes unpredictably. The lifetime of a major new clinical concept often lasts no longer than one to three decades and then, new or revitalized ideas emerge, and like juggernauts, vigorously plow ahead, casting aside preexisting beliefs that stand in their way. Their rate of growth, interestingly, is akin to that of a new colony of microorganisms (i.e., an S-shaped curve with an initial slow phase, followed by exponential and sometimes explosive growth, finally terminating in a plateau, or, in some case, a final steep descent and even extermination). For example, the last quarter of the 20th century may reasonably be considered the golden age of vitreous surgery, at least as we now know it. This is not to say that we have seen the final innovative ideas in this arena; indeed, we are about to enter the important derivative activities utilizing vitreoretinal surgical technique, such as submacular surgery, retinal cell transplants, drug delivery, and hopefully, gene transfer. The age of initial revolutionary ideas, however, occurred in the early 1970s, and many of the later concepts and techniques should be considered important refinements instead of epiphanies. Now, with the passage of time, the field of refractive surgery rises and glows, piquing our interests and challenging our priorities. These refractive ideas promise to rejuvenate both therapeutic and cosmetic approaches to ocular problems that, according to conventional wisdom, have previously been considered technically, economically, or ethically insurmountable. As in the case of most such innovations involving human health and its associated commercial enterprises, there is a spectrum of opinion, with enthusiastic advocates and their understandable hyperbole recognizable at one end and died-in-the-wool naysayers at the other extreme. Of course, the “truth” lies somewhere in the middle. With history in mind, one can predict that ingenious ideas, instruments, and surgical procedures will rather quickly and dramatically proliferate in this emerging field. Darwinian natural selection influenced, sometimes regrettably but unavoidably, by the marketplace will have its say and, within a decade or so, refractive surgery will evolve more completely. Eventually, the public will become well served by a combination of properly evaluated surgical procedures and superbly trained eye surgeons. This process requires a continual sifting of new concepts and techniques. Through repeated trial and error that are enhanced by ethical, objective, and wise evaluation of scientifically obtained clinical data, a mature discipline will emerge that benefits patients who are carefully selected, informed, treated, and followed up. In the early stages of its evolution, now about to enter the exponential phase of growth, the field of refractive viii

surgery needs to undergo some periodic respites that allow both the evaluation and teaching of new ideas and data that have become available to date. Herein lies the value of Dimitri Azar and his welcome book. During his several years at the Wilmer Eye Institute, Dr. Azar displayed the set of attributes required of an editor and author of a compendium whose goals include promulgating new surgical ideas for the therapists of both today—tomorrow; namely, highly developed ethics, communicative skills, intellectual prowess, and technical virtuosity. He is also well endowed with the combination of exuberance and perseverance that are necessary both for proselytizing favorable principles and practices and simultaneously promoting the caution that is essential whenever patients are subjected to revolutionary interventions that have not been wholly vindicated. Indeed, as pointed out by the author: We must continue to validate refractive surgical procedures by ensuring their predictability and reproducibility through controlled and well-designed scientific investigations. Dr. Azar’s imprimatur is evident throughout this book— his ideas, his original writings and illustrations, and, of course, his selection of outstanding American and international authors. Importantly, the authors represent both younger and older refractive surgeons—gay blades and experienced savants, so to speak. Both groups have much to offer, and, as they themselves would be quick to admit, their valuable offerings represent information which is state-ofthe-art, but which, of necessity, is in dramatic flux. Future editions (and one hopes there will be several) will reflect the result of careful clinical scrutiny; some current ideas that are fervently propounded will die, and better ones will evolve. Perhaps the very vigilant among us would wish to be clairvoyant before embarking on this journey, utilizing a crystal ball to predict what the future of this field foretells; on the other hand, the excitement and much of the value of unpredictable and presently unfathomable new ideas would be lost. We should look to the future, therefore, with pleasure and bated breath, but also with judicious circumspection. There will be many opportunities for appropriate mid-course corrections. For the moment, however, this book is an outstanding contemporary summary of refractive surgery for both the neophyte and the sophisticate. It is the forerunner of an epoch of eye surgery that will occupy our minds and our operating rooms for years to come. Morton F. Goldberg, MD Director and Chairman The Wilmer Ophthalmological Institute Baltimore, Maryland September 1996

Preface

The original idea of publishing a comprehensive multiauthor “Refractive Surgery” textbook materialized in 1996, while I was on the faculty of the Wilmer Institute, witnessing and documenting, the renaissance of the field. More than two decades later, refractive surgery is still advancing, with the development of more precise and sophisticated applications. As in previous editions, the third edition of this book maintains the essential backbone of the refractive surgery story. Advancements in technology have expanded the options for refractive surgical vision correction and improved clinical outcomes. Correspondingly, the number of procedures performed has continued to increase. This third edition describes the principles and practice of refractive surgery. We describe advances in various surgical techniques, their indications, patient selection, limitations, and complications. We have abridged the introductory and corneal healing, corneal inclusions and orthokeratology sections, and we have updated the Optics chapters and included an overview of anterior segment optical coherence tomography (OCT) in refractive surgery. The lamellar surgery section now encompasses laser in situ keratomileusis (LASIK), Q-based and wavefront-guided custom LASIK, TopoLink and small-incision lenticle extraction (SMILE). We added a collagen cross-linking section and expanded the sections of refractive intraocular lenses (IOLs), phakic IOLs, and presbyopia surgery. Many chapters continue to benefit from illustrative surgical and educational videos as well as high-resolution representative photographs and illustrations. Emphasizing the visual nature of refractive surgery, several figures representing comprehensive themes are composites, often presented in single illustrations. This textbook would not have been possible without the contributions of the associate editors, Drs. Damien Gatinel, Ramon Ghanem, and Suphi Taneri. Their contributions have broadened the scope of this book and have provided an international, world-wide perspective of refrac-

tive applications. Nor would it have been possible without the continued energy and commitment of Joanne Scott, Nayagi Athmanathan, Trinity Hutton, Russell Gabbedy, and the publishing team at Elsevier, who approached the third edition with unfailing enthusiasm, keeping up with our constant revisions to incorporate and update new topics and techniques, as rapid developments in the field of refractive surgery showed few signs of abating. As we dedicate this textbook to our families and teachers, we express our gratitude to the contributors who gave their valuable time, writing and revising manuscripts with dedication. The breadth and the depth of this edition are attributable to the collective expertise of more than 75 refractive surgeons and researchers who contributed chapters, generously sharing their knowledge and expertise, and made helpful suggestions throughout the process of producing this volume. I would also like to acknowledge the valuable assistance of Pushpanjali Giri. Her relentless communication with the publisher and with contributors was paramount in keeping the project on schedule. When I wrote the closing coda to the second edition, I was transitioning from the Massachusetts Eye and Ear Infirmary and the Schepens Eye Research Institute at Harvard Medical School to the Department of Ophthalmology and Visual Sciences, and the Lions of Illinois Eye Research Institute, at the University of Illinois at Chicago (UIC). I write this preface, more than a decade later, as I start a new chapter in my career assuming new responsibilities in San Francisco as Senior Director of Ophthalmic Innovations and Ophthalmology Lead at Alphabet Verily Life Sciences. I am indebted to my many colleagues, fellows, residents, and students at UIC for their friendship and unwavering support while I was engaged in the production of this book. Dimitri T. Azar, MD, MBA San Francisco, CA, 2019

ix

List of Contributors

The editor(s) would like to acknowledge and offer grateful thanks for the input of all previous editions’ contributors, without whom this new edition would not have been possible.

Elena Albé, MD

Consultant Eye Clinic, ISTITUTO CLINICO HUMANITAS, Rozzano, MI, Italy

Jorge L Alió, MD, PhD

Professor and Chairman of Ophthalmology Vissum Alicante, Spain Miguel Hernández University of Alicante, Spain

Norma Allemann, MD

Adjunct Professor, Head of Discipline Department of Ophthalmology, Federal University of São Paulo—UNIFESP Clinical Volunteer Faculty in Ophthalmology— Department of Ophthalmology & Visual Sciences— University of Illinois at Chicago—UIC

Mazen Amro, MD

Ophthalmologist Université Libre de Bruxelles, Brussels, Belgium Erasmus Hospital, Brussels, Belgium

Jean-Louis Arné, MD

Professor Emeritus Head of Ophthalmology Department, Paul Sabatier University, Toulouse, France

M. Farooq Ashraf, MD, FACS

Medical Director The Atlanta Vision Institute, Atlanta, GA, USA

Janine Austen Clayton, MD

NIH Associate Director for Research on Women’s Health Director NIH Office of Research on Women’s Health, Bethesda, MD, USA

Nathalie F. Azar, MD

Clinical Professor and Director of Pediatric Ophthalmology University of Illinois at Chicago, Department of Ophthalmology, Chicago, IL, USA x

Dimitri T. Azar, MD, MBA

Distinguished University Professor and B.A. Field Chair of Ophthalmic Research University of Illinois at Chicago, Chicago, IL, USA; Senior Director and Ophthalmology Lead Verily Life Sciences (formerly Google), San Fransisco, CA, USA

Richard E. Braunstein, MD

Miranda Wong Tanga Associate Professor of Clinical Ophthalmology Harkness Eye Institute, New York, NY, USA

Salim I. Butrus, MD

Clinical Professor Department of Ophthalmology, Georgetown University and George Washington University, Washington, DC, USA

Florence Cabot, MD

International Clinical Cornea Fellow Anne Bates Leach Eye Hospital and Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USA

Jonathan Carr, MD, MA(Cantab), FRCOphth Medical Director Lasik Plus—Paramus, Paramus, NJ, USA

Fábio H. Casanova, MD, PhD

Director, Memorial Oftalmo Recife Eye Center, Brazil

Wallace Chamon, MD

Professor Department of Ophthalmology and Visual Sciences, Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil; Clinical Volunteer Faculty Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, IL, USA

List of Contributors

Philippe Chastang, MD

Corneal and Refractive Surgical Specialist Chirurgie Oculaire Et Réfractive Consultation Cabinet; Formerly, Fondation Ophthalmologique A. de Rothschild, Paris, France

Pauline Cho, PhD, FAAO, FBCLA

Pushpanjali Giri, BA

Research Specialist Department of Ophthalmology, University of Illinois at Chicago, Illinois Eye and Ear Infirmary, Chicago, Illinois, USA

Andrzej Grzybowski, MD, PhD, MBA

Professor School of Optometry, The Hong Kong Polytechnic University, Hong Kong, SAR, China

Professor of Ophthalmology Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland Foundation Ophthalmology, Poznan, Poland

José de la Cruz, MD

Shilpa Gulati, MD

Roberto Fernández-Buenaga, MD, PhD

Rosario Gulias-Cañizo, MD, MSc

Cornea Fellow UIC Department of Ophthalmology and Visual Sciences, The University of Illinois Eye Center, Chicago, IL, USA Consultant Ophthalmologist Vissum Madrid, Spain

Jorge Alió-del Barrio, MD, PhD Consultant Ophthalmologsit Vissum Alicante, Spain

Ana Mercedes García-Albisua, MD

Department of Ophthalmology and Visual Sciences, Illinois Eye and Ear Infirmary, University of Illinois at Chicago, Chicago, IL, USA Research Coordinator Research Department, Universidad Nacional Autónoma de México, Asociación Para Evitar la Ceguera en México “Hospital Dr. Luis Sánchez Bulnes”, Mexico City, CDMX, Mexico

Joelle Hallak, PhD

Second-Year Cornea Fellow, Chief Resident Cornea and Refractive Surgery, Asociación Para Evitar la Ceguera en México “Hospital Dr. Luis Sánchez Bulnes”, Mexico City, México

Assistant Professor Executive Director Ophthalmic Clinical Trials and Translational Center, Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Morgan, Chicago, IL

Damien Gatinel, MD, PHD

Rola N. Hamam, MD

Emir Amin Ghanem, MD

David R. Hardten, MD

Head Department of Anterior Segment and Refractive Surgery, Rothschild Foundation, Paris, France Ophthalmologist Sadalla Amin Ghanem Eye Hospital, Joinville, SC, Brazil

Marcielle A. Ghanem, MD

Refractive Surgery Department, Sadalla Amin Ghanem Eye Hospital, Joinville, SC, Brazil

Ramon C. Ghanem, MD, PhD

Director of Cornea and Refractive Surgery Department Sadalla Amin Ghanem Eye Hospital, Joinville, Brazil

Vinícius Coral Ghanem, MD, PhD

Ophthalmologist and Medical Director, Department of Ophthalmology Sadalla Amin Ghanem Eye Hospital, Joinville, SC, Brazil

Assistant Professor of Ophthalmology Department of Ophthalmology, University of Beirut, Beirut, Lebanon Director of Refractive Surgery Minnesota Eye Consultants Adjunct Associate Professor of Ophthalmology University of Minnesota, Minneapolis, MN, USA

Everardo Hernández-Quintela, MD, MSc, FACS Chief of Service Department of Cornea and Refractive Surgery Services, Universidad Nacional Autónoma de México Asociación Para Evitar la Ceguera en México, Hospital Dr. Luis Sánchez Bulnes, Mexico City, CDMX, Mexico

Peter S. Hersh, MD, FACS

Cornea and Laser Eye Institute—Hersh Vision Group Professor of Clinical Ophthalmology, Director of Cornea and Refractive Surgery Rutgers Medical School Visiting Research Collaborator Princeton University, Princeton, NJ, USA

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List of Contributors 

Arthur Ho, MOptom, PhD, FAAO

Chief Scientist and Innovation Officer Brien Holden Vision Institute, Sydney, NSW, Australia; Visiting Professorial Fellow School of Optometry and Vision Science, University of New South Wales; Voluntary Professor of Ophthalmology University of Miami, Miller School of Medicine, Miami, FL, USA

Thanh Hoang-Xuan, MD

Professor of Ophthalmology University of Paris, American Hospital; Formerly, Fondation Ophthalmologique A. de Rothschild, Paris, France

Brien A. Holden, PhD, DSc, OAM

Formerly Deputy CEO Vision Cooperative Research Centre, The University of New South Wales, Sydney, NSW, Australia

Sandeep Jain, MD

Michael C. Knorz, MD

Professor of Ophthalmology FreeVis LASIK Center, Klinikum Mannheim, Mannheim, Germany

Jeffrey C. Lamkin, MD Private Practice Akron, OH, USA

François Malecaze, MD, PhD

Professor of Ophthalmology Hospital Purpan, Toulouse, France

Fabrice Manns, PhD

Professor of Biomedical Engineering and Ophthalmology Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL; Chairman of the Department of Biomedical Engineering, University of Miami College of Engineering, Coral Gables, FL

Professor of Ophthalmology Cornea Service Director, Cornea Translational Biology Laboratory Director, Dry Eye Service and oGVHD Service University of Illinois at Chicago, Department of Ophthalmology, Chicago, IL, USA

Marguerite B. McDonald, MD, FACS

Elias F. Jarade, MD

Optometrist Laser Eye Medical Center, Dubai, United Arab Emirates

Ophthalmologist, Cornea and Refractive Surgeon Beirut Eye & ENT Specialty Hospital, Beirut, Lebanon

Joel Adrien D. Javier, MD Clinical Consultant Bausch & Lomb, Singapore

James V. Jester, PhD

Professor of Ophthalmology and Biomedical Engineering University of California, Irvine, Irvine, CA, USA

Piotr Kanclerz, MD, PhD

Medical Doctor Department of Ophthalmology, Medical University of Gdańsk, Gdańsk, Pomorskie, Poland

Vikentia J. Katsanevaki, MD, PhD

Clinical Professor of Opthalmology NYU School of Medicine; Tulane University School of Medicine, New Orleans, LA, USA

Françoise C. Abi Nader, MD

Ioannis G. Palliakaris, MD, PhD

Dean and Professor of Ophthalmology Vardinoyannion Eye Institute of Crete/Institute of Vision and Optics, University of Crete Medical School, Voutes, Crete, Greece

Jean-Marie Parel, IngETS-G, PhD, FAIMBE, FARVO

Henri and Flore Lesieur Chair in Ophthalmology Ophthalmic Biophysics Center, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL; Vision Cooperative Research Center, University of New South Wales, Sydney, Australia

Head of Refractive Department Vardinoyannion Eye Institute, University of Crete Medical School, Crete, Greece

Kévin Pierné, MD

Johnny M. Khoury, MD

Antony M. Poothullil, MD

Assistant Professor of Ophthalmology Director, Refractive Surgery Division American University of Beirut Medical Centre, Beirut, Lebanon

Practitioner in Ophtalmology Hospital Purpan, Toulouse, France Kaiser Permanente, Ophthalmology, Portland, OR, USA

List of Contributors

Ana Belén Plaza-Puche

Optometry Office of the Research Development & Innovation Department, Vissum Alicante, Spain

Cynthia J. Roberts, PhD

Professor of Ophthalmology & Visual Science and Biomedical Engineering Martha G. and Milton Staub Chair for Research in Ophthalmology The Ohio State University, Columbus, OH, USA

Renan Rodrigues, MD

Ophthalmologist, Post-doctoral Student Department of Ophthalmology/Cataract and Refractive Surgery Division, Federal University of São Paulo (UNIFESP)/ São Paulo Hospital/ UNIFESP, São Paulo, SP, Brazil; Co-founder of CONUS—Keratoconus Center

Walter Stark, MD

Boone Pickens Professor of Ophthalmology The Director of the Stark-Mosher Center for Cataract and Corneal Services The Wilmer Eye Institute, The Johns Hopkins Hospital, Baltimore, MD, USA

Mario Antonio Stefani, PhD

R&D Board Chairman R&D Medical Division, Opto Eletrônica S/A, São Carlos, SP, Brazil

Leon Strauss, MD, PhD

Instructor The Wilmer Eye Institute, The Johns Hopkins University, School of Medicine, Baltimore, MD, USA

Suphi Taneri, MD

Professor and Head of Ophthalmology and Visual Sciences in the UIC College of Medicine Chicago, IL, USA

Director, Center for Refractive Surgery Department of Ophthalmology at St. Franziskus Hospital, Münster, NRW, Germany; Associate Professor of Ophthalmology Eye Clinic, Ruhr University, Bochum, NRW, Germany

Mirwat Sami, MD, FACS

Vance Thompson, MD

Mark Rosenblatt, MD, PhD

Houston Eye Associates, Houston, TX, USA

Valeria Sánchez-Huerta, MD, FACS

Head of Academics Department of Cornea and Refractive Surgery Services, Universidad Nacional Autónoma de México Asociación Para Evitar la Ceguera en México “Hospital Dr. Luis Sánchez Bulnes”, Mexico City, CDMX, Mexico

David J. Schanzlin, MD

Partner, Gordon Schanzlin New Vision Institute Professor of Clinical Ophthalmology (Emeritus) University of California, San Diego, San Diego, CA, USA

Theo G. Seiler, MD

Department of Ophthalmology, University of Bern, Bern, Switerland

Theo Seiler, MD, PhD

Professor and Chairman Institut für Refraktive und Ophthalmo-Chirurgie (IROC), University of Zurich, Zurich, Switerland

Ashish G. Sharma, MD, FACS

Retina Consultants of Southwest Florida Fort Myers, Florida, USA

Director of Refractive Surgery Vance Thompson Vision Professor of Ophthalmology University of South Dakota Sanford School of Medicine, Sioux Falls, SD, USA

Josep Torras, MD

Department of Ophthalmology, Mutua Terrassa Hospita, Barcelona, Spain

Kazuo Tsubota, MD

Professor and Chairman Department of Ophthalmology, Keio University School of Medicine, Tokyo, Japan

Veronica Vargas

Refractive Surgery Fellow Department of Investigation, Development and Innovation at Vissum Alicante, Alicante, Spain

Frédéric Vayr, MD

Corneal and Refractive Surgical Specialist Institut Laser Vision, Noémie de Rothschild; Formerly, Fondation Ophthalmologique A. de Rothschild, Paris, France

Steven M. Verity, MD

Professor Department of Ophthalmology, Cornea/External Disease and Keratorefractive Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA

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List of Contributors 

Jayne S. Weiss, MD

Associate Dean of Clinical Affairs Chair, Department of Ophthalmology Herbert E Kaufman MD Endowed Chair Professor of Ophthalmology, Pathology and Pharmacology Louisiana State University School of Medicine, LSUHSC, New Orleans, LA, USA

Albert Chak-Ming Wong, MBChB (CUHK), MRCSEd, MMedSc (HK), MMed (Ophth), FCOphthHK, FHKAM (Ophth), FRCSEd (Ophth) Clinical Assistant Professor (Honorary) The Jockey Club School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong; Director Department of Ophthalmology, Albert Eye Centre, Tsim Sha Tsui, Kowloon, Hong Kong

Sonia H. Yoo, MD

Professor of Ophthalmology Anne Bates Leach Eye Hospital and Ophthalmic, Biophysics Center, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, FL, USA

Bavand Youssefzadeh, DO

Ophthalmology Associate Physician Cornea/Refractive Department, Gordon Schanzlin New Vision Institute, San Diego, CA, USA

Dedication To Lara, Nicholas, and Alexander; To Nathalie, for sharing my profession with dedication and excellence, my long days with patience and assistance, my leisure with cheerfulness and laughter, and my happy moments with affection and optimism; and for providing Alexander, Nicholas, and Lara with wonderful roots and magnificent wings; To all my fellows and residents for being the source of my learning and inspiration; To Ilene, Fred, Mort, Claes, Bob, Michael, and Andy for their friendship and mentorship; And in memory of my loving parents; I can no longer see them with my eyes, but I see the light they have brought to the world still shining, long after they have gone. Dimitri T. Azar, MD, MBA To my teachers, students, family, and friends. To the curious minds. Damien Gatinel, MD, PHD I dedicate this work to my dear family for their constant inspiration and support. With reverence to my grandfather, Sadalla Amin Ghanen, in memoriam; to my beloved parents, Emir Amin Ghanem and Cleusa Coral-Ghanem, models of wisdom, courage, dedication, and professional ethics; to my brother Vinícius, a friend at all times, a professional colleague, and an example to be followed. to Marcielle, my great love and mother of our sons, Nicolas, Henrique, and Gabriel; and, finally, to two great mentors, Professors Newton Kara-José and Dimitri T. Azar. Ramon C. Ghanem, MD To my father and mother for their unconditional love, to Anneanne, Remziye Teyze, Ertug Amca in memoriam, and Ufuk Hala for their loving support, to Nicola for passionately sharing her life with me, to Mavi-Nur and Sinan for adding fun and excitement, and to Heinrich Gerding, Kunibert Krause in memoriam, H. Burkhard Dick, and Dimitri T. Azar Suphi Taneri, MD

1 

Terminology, Classification, and History of Refractive Surgery SHILPA GULATI, ANTONY M. POOTHULLIL, AND DIMITRI T. AZAR

Introduction: Why Do Patients Choose Refractive Surgery? Patients desire refractive surgery for a variety of reasons. For patients seeking laser in situ keratomileusis (LASIK) or surface ablation, the most common motivation is a desire to decrease contact lens or spectacle use.1–3 Some individuals require improvement in their uncorrected visual acuity (UCVA) because of their careers. Others have ocular or medical conditions that make contact lens wear difficult or dangerous. Some prefer to be free of glasses or contacts when engaging in sports and recreation. Presbyopic patients may want to be able to read clearly without glasses. Still others have anisometropia or spectacle-related anisophoria such that corrective spectacle lenses result in prominent eyestrain and an unacceptable degree of discomfort. Cosmetic appearance may also be a reason for surgery. The number of refractive surgical procedures available to patients has increased dramatically since the early days of radial keratectomy (RK) and keratomileusis. Recent developments are discussed in this textbook, including customized LASIK, small-incision lenticule extraction (SMILE), presbyopic implants, and multifocal IOLs. Patients who have had LASIK for the correction of myopia are generally very happy. In a survey by Miller et al., approximately 85% were at least “very pleased” with their refractive outcome and 97% said they would decide to have the procedure performed again.4 Factors that correlated well with patient satisfaction were postoperative improvements in UCVA, decreased cylindrical correction, and absence of side effects, such as dry eye. While this may be comforting, it is important to remember that the vast majority of refractive surgery is performed on patients with excellent corrected visual acuity and a decrease in quality of vision is ultimately undesirable. With continued advancements of refractive procedures, we can minimize complications, improve outcomes, and educate our patients and ourselves. 2

Emmetropia, Ametropias, and Presbyopia The successful performance of refractive surgery demands a thorough understanding of the optics of the human eye. The refractive power of the eye is predominantly determined by 3 variables: the power of the cornea, the power of the lens, and the length of the eye. In emmetropia, these 3 components combine in such a way as to produce no refractive error. When an eye is emmetropic, a pencil of light parallel to the optical axis and limited by the pupil focuses at a point on the retina (i.e., the secondary focal point of an emmetropic eye is on the retina; Fig. 1.1). The “far point” in emmetropia (defined as the point conjugate to the retina in the nonaccommodating state) is optical infinity. Eyes with refractive errors can have abnormalities in one or more of the above variables, or all variables can be in the normal range but incorrectly correlated, resulting in a refractive error. For example, an eye with an axial length in the upper range of normal may be myopic if the corneal variable is also in the steeper range of normal. In a myopic eye, a pencil of parallel rays is brought to focus at a point anterior to the retina. This point, the secondary focal point of the eye, is in the vitreous. Rays diverging from the far point of a myopic eye will be brought to focus on the retina without the aid of accommodation. The hyperopic eye, on the other hand, brings a pencil of parallel rays of light to focus at a point behind the retina. Accommodation of the eye may produce enough additional plus power to allow the light rays to focus on the retina. Rays converging toward the far point farther behind the eye will be focused on the retina while accommodation is relaxed. For full correction of myopia and hyperopia, a distance corrective lens placed in front of the eye must have its secondary focal point coinciding with the far point of the eye so that the newly created optical system focuses parallel rays onto the retina.

CHAPTER 1  Terminology, Classification, and History of Refractive Surgery

3

TABLE Classification of Lenticular and Scleral 1.1  Refractive Procedures

M

MyA H

CLE

+

+

PIOL

+

+

Bioptics

+

Multifocal

+

+

+

Accommodative IOL

+

+

+

F2 Far point = x (A) Emmetropia

Far point

+

+

HA

+

MxA A

+

P

+

Phaco-Ersatz

+

Scleral relaxation, expansion

±

A, Aphakia; CLE, clear lens extraction; H, hyperopia; HA, hyperopic astigmatism; IOL, intraocular lens; M, myopia; MxA, mixed astigmatism; MyA, myopic astigmatism; P, presbyopia; PIOL, phakic intraocular lenses.

(B) Myopia

F2

with spectacles can simply remove their glasses for improved reading vision. Latent hyperopes, on the other hand, use their accommodative reserve for clear distance vision; as the amplitude of accommodation wanes with age, reading difficulties emerge.

(C) Myopia

Classification of Refractive Procedures F2

(D) Hyperopia

• Fig. 1.1  Schematic diagrams of emmetropia, myopia, and hyperopia. (A) In emmetropia, the far point is at infinity, and the secondary focal point (F2) is at the retina. (B and C) In myopia, the far point is in front of the eye and the secondary focal point, F2, is in the vitreous. (D) In hyperopia (bottom), the secondary focal point, F2, is located behind the eye. (Modified with permission from Azar DT, Strauss L. Principles of applied clinical optics. In: Albert D, Jakobiec F, eds. Principles and Practice of Ophthalmology. Philadelphia: WB Saunders; 1994.)

Astigmatism may be caused by a toric cornea or, less frequently, by astigmatic effects of the native lens of the eye. Astigmatism is regular when it is correctable with cylindrical or spherocylindrical lenses so that pencils of light from distant objects can be focused on the retina. Otherwise, the astigmatism is irregular. Visual acuity is expected to decline for the different degrees of astigmatism. Astigmatism of 0.50 to 1.00 diopters (D) usually requires some form of optical correction. An astigmatic refractive error of 1.00 to 2.00 D decreases uncorrected vision to the 20/30 to 20/50 level, whereas 2.00 to 3.00 D may decrease UCVA to the 20/70 to 20/100 range.5 Presbyopia is the age-related loss of accommodation. Onset of presbyopia will vary with the refractive error and its method of correction. For example, myopes corrected

Refractive surgery procedures are undergoing constant development and modification. In the late 1990s, LASIK has essentially replaced RK as the preferred treatment for patients with myopia. More recently, SMILE and multifocal IOLs have gained increasing popularity and phakic intraocular lenses (PIOLs) have undergone numerous modifications for the treatment of higher degrees of myopia or hyperopia. With an expanding repertoire of options, it is important to have an organized understanding of the surgical techniques that are available to the refractive surgeon. Refractive surgery procedures for the correction of myopia, hyperopia, presbyopia, and astigmatism achieve emmetropia by modifying the optical system of the eye. In this chapter, we have divided surgical techniques into 2 broad categories: keratorefractive (corneal-based) and lenticular or scleral surgical procedures. Keratorefractive techniques surgically alter the cornea without entering the anterior chamber and are the main type of refractive surgery performed today. The lenticular or scleral refractive procedures include intraocular techniques, such as the insertion of multifocal, accommodating, and adjustable lenses, and extraocular methods, such as scleral relaxation or expansion procedures for presbyopia (Table 1.1).

Keratorefractive Surgery Keratorefractive surgeries rely on at least five major methods to reshape the corneal surface: lasers, incisions, corneal implants, thermal procedures, and nonlaser lamellar surgery.

4 se c t i o n I

Introduction

All procedures induce corneal changes by affecting the corneal stroma. Excimer lasers are used to subtract tissue from the stroma and modify corneal shape. With incisional surgery, a blade is used to make precise cuts into the stroma. These incisions result in wound gape, altering the corneal surface contour, resulting in changes in the refractive power of the cornea. Corneal implants can be placed into the corneal stroma to change corneal shape. Thermal techniques cause focal changes in stromal collagen architecture in order to change corneal contour. At present, thermal methods are limited to the correction of hyperopia or presbyopia. Nonlaser lamellar surgeries add or subtract tissue from the cornea in order to reshape it. With lamellar addition procedures, donor corneal tissue is transplanted to the host cornea. Lamellar subtraction procedures involve two stages: (1) lamellar stromal dissection and (2) removal of stromal tissue. Many of these procedures have the unintended side effect of reducing corneal tensile strength. Our understanding of corneal biomechanics has increased and has allowed us to develop safer keratorefractive procedures for our individual patients.6–9

More commonly, the laser is used to perform corneal stromal ablation under a lamellar flap, termed laser in situ keratomileusis (LASIK).

Laser Procedures for Myopia In PRK, the excimer laser is applied to the anterior surface of the cornea for reshaping (Fig. 1.2). The laser may be used

Keratorefractive Procedures: Myopia and Myopic Astigmatism Myopia is the most common visually significant refractive error, with a rising prevalence of 25% to 40% in Western countries.10,11 In the United States, the prevalence of myopia has doubled in the last 30 years and pathologic myopia (over 8.00 D) has risen eightfold.12 Numerous procedures have been developed to treat myopia by altering the corneal curvature. The cornea is responsible for 60% of the eye’s refractive power; small changes in curvature can produce significant refractive changes. Corneal procedures correct myopia by flattening the anterior curvature or changing the index of refraction of the cornea. All keratorefractive procedures for the treatment of myopia modify the corneal thickness to produce anterior curvature alterations except for RK, in which the corneal curvature is flattened by tectonic weakening without changing the central thickness.13

Laser Procedures The excimer laser, a 193-nm argon fluoride (ArF) beam, has become the technology of choice for keratorefractive surgeons worldwide. A major advantage of the laser is its ability to precisely ablate tissue with submicron pulses. The excimer laser-ablated surface has the potential of being smoother than that obtainable by other surgical techniques. Since its introduction in 1983 by Trokel and Srinivasan for linear keratectomy, the excimer laser procedure has undergone a rapid evolution.14 Myopic excimer laser treatments achieve their effect by flattening the central cornea. The laser can reshape the cornea by ablating the anterior corneal surface, as in photorefractive keratectomy (PRK) or laserassisted subepithelial keratectomy (LASEK or epi-LASEK).

•

Fig. 1.2  Schematic illustration of myopic photorefractive keratectomy. The shaded area refers to the location of tissue subtraction. More stromal tissue is removed in the central as compared to the paracentral region.

CHAPTER 1  Terminology, Classification, and History of Refractive Surgery

to remove the corneal epithelium. Alternatively, the epithelium may be removed by scraping with a surgical blade or by using dilute ethanol and a cellulose sponge. For myopia of 1 D to 7 D, PRK has been shown to result in a high rate of preservation of best corrected visual acuity (BCVA) and minimal complications. In most series, 90% of patients achieve 20/40 or better uncorrected acuity and are within 1 D of emmetropia. In this moderate myopia group, the initial overcorrections generally regress toward emmetropia over several months, with stabilization after 6 to 12 months. Highly myopic patients often regress 6 to 12 months after surface PRK, presumably because of stromal regeneration and/or epithelial hyperplasia, which cause resteepening of the ablated zone.15 Dense subepithelial haze occurs rarely but is greater in PRK treatments exceeding 6 D and may reduce the BCVA. Mitomycin C has been applied during PRK treatments in order to decrease the incidence of haze formation.16 Artola et al. found that induced corneal aberrations after PRK for myopia created a multifocality that enhanced near acuity, which may delay the onset of presbyopic symptoms. However, this multifocality also reduced the quality of the retinal image for distance at low contrast.17 LASEK and epi-LASIK are modifications of the PRK procedure in which the corneal epithelium is preserved, displaced prior to surface ablation, then replaced after laser application. Advantages over PRK include decreased postoperative discomfort, reduced postoperative scarring, and faster visual recovery. Prior to laser application, the epithelium is treated with 15% to 20% ethanol. This treatment weakens hemidesmosomal attachments between the corneal epithelium and the underlying Bowman membrane. The epithelial sheet can then be easily displaced and protected by moving it outside of the ablation zone. Following stromal ablation, the epithelial sheet is returned to its original location, covering the ablated area.18 Pallikaris et al. have described epi-LASIK, using an automated blade to remove the corneal epithelium mechanically, without the application of alcohol. They suggest that this technique should provide improved comfort and decreased haze formation compared to PRK, and histologic studies show better preservation of the corneal epithelial sheet when compared to LASEK.19,20 LASIK is a two-stage procedure that combines lamellar surgery with laser application. It has become the most widely performed refractive procedure in the United States. Its main advantages over surface ablation procedures include faster visual recovery, less postoperative discomfort, and decreased incidence of postoperative corneal scarring or haze in patients with higher refractive errors. During LASIK, an anterior corneal flap is created and then is lifted, the excimer laser is applied to the stromal bed, and the flap is returned to its original position (Fig. 1.3). The corneal flap can be created with either a microkeratome or an intrastromal laser. Microkeratomes are affixed to the globe via a suction device and the blade is passed via a manual or automated mechanism. The femtosecond (FS) laser is a solid-state laser with a 1053-nm wavelength that can be

5

Myopic LASIK

• Fig. 1.3

  Schematic illustration of myopic and hyperopic laser in situ keratomileusis. A superficial corneal flap is raised. The shaded area refers to the location of tissue subtraction under the flap. After treatment, the flap is repositioned.

used to photodisrupt the corneal stroma with a preset depth and pattern. When used for LASIK, the laser creates the corneal flap prior to excimer laser application.21 Customized corneal ablations use Q-based or “wavefront” aberrometers to detect and treat both spherocylindrical error and higher-order aberrations (HOAs) that can affect visual acuity. At the time of publication, these devices are approved in the United States for the treatment of myopic and astigmatic refractive errors. These custom lasers offer the possibility of improved vision compared to traditional excimer lasers because they address additional factors that may be contributing to blur in an individual’s optical system.22 A study of 132 eyes undergoing LASIK using the NIDEK Advanced Vision Excimer Laser (NIDEK) showed that fewer HOAs were induced when compared to noncustom LASIK, and 93% achieved uncorrected vision of at least 20/20. Preoperative sphere and cylinder ranged to −8.25 D and −3 D, respectively.22

Introduction

6 se c t i o n I

corneal biomechanics. Long-term follow-up has demonstrated a reduction in HOAs and minimal refractive regression, though some potential advantages, such as improved biomechanical stability and postoperative inflammation, have yet to be established.

Laser Procedures for Myopic Astigmatism Compound myopic astigmatism can be treated with negative or positive cylinder ablation. Negative cylinder ablation flattens the central cornea in both the flat and the steep meridians. Positive cylinder ablation may allow a larger optical zone with no change in the central depth of ablation.24 One study examined 74 eyes with compound myopic astigmatism treated with the Meditec MEL 10 G-Scan (Zeiss) excimer laser. Patients were followed for 1 year and had myopia from −4.50 D to −9.88 D and astigmatism up to 4.00 D. At 1 year, mean postoperative spherical equivalent was −0.49 and mean cylinder refraction was 0.59.25

Incisional Procedures: A Historical Perspective In the early 1970s, RK was performed by ophthalmologists in the Soviet Union, including Beliaev,26 Yenaliev,27 and Fyodorov and Durnev.28–31 RK was performed for the first time in the United States in 1978.32,33 The RK procedure for myopia places deep, radial, corneal stromal incisions, which weaken the paracentral and peripheral cornea and flatten the central cornea. Refractive power of the central cornea is reduced and myopia is decreased (Fig. 1.6). The surgeon can control the refractive effect by adjusting three variables: central optical zone, incision number, and incision depth.

Incisional Procedures for Myopia

• Fig. 1.4

 

Small-incision lenticule extraction (SMILE).

SMILE is a refractive procedure in which an FS laser is used to create a corneal stromal lenticule, which is extracted whole through a 2- to 3-mm incision (Fig. 1.4). Outcomes have been noted to be similar to those of LASIK: in a metaanalysis by Zhang et  al.23 comparing SMILE and FS-assisted LASIK (FS-LASIK) in 1101 eyes, no significant difference was found in refractive outcomes. SMILE was found to result in higher postoperative corneal sensitivity but fewer dry-eye symptoms than FS-LASIK. The biomechanical stability after SMILE surgery is expected to be greater than that after LASIK and may be comparable to PRK and LASEK. Fig. 1.5 compares RK, PRK, LASIK, and SMILE

RK achieves the best results in patients with low and moderate degrees of myopia (up to 5 D). In patients with higher amounts of myopia (6–10 D), the response to surgery is much more variable34–43 and undercorrection is more common. The age of the patient partially determines the upper limit of attainable correction. Older patients achieve a greater correction by approximately 0.75 D to 1.00 D per 10 years of age exceeding 35 years.44 Other patient variables may affect outcomes but are difficult to quantitate. For example, reports show that a premenopausal female with a flat cornea, low intraocular pressure, and a small corneal diameter may achieve less correction than would be generally predicted for a particular RK technique.45–47 RK has been studied thoroughly, most notably by the National Eye Institute (NEI)–funded, multicenter Prospective Evaluation of Radial Keratotomy (PERK) study, a collaborative effort of 9 clinical centers. Predictability of results remains problematic.35–45 Early studies of predictability showed that about 70% of eyes have a residual refractive error within ±1 D of the predicted result and 90% within ±2 D.45–49 Later studies, with a staged approach, report 80% to 90% of eyes within 1 D of emmetropia.49–51 Stability of refraction after radial keratotomy is also inadequate.52–54 The 10-year PERK results revealed long-term

CHAPTER 1  Terminology, Classification, and History of Refractive Surgery

A

B

C

D

7

• Fig. 1.5

  Simulated displacements in corneal shape on the surface resulting from the four refractive surgical procedures at a normal intraocular pressure of 15 mm Hg. The dark-red areas involve maximum displacements (>0.5 mm) outwards (body expansion), and the dark-blue areas involve zero displacement near the constrained boundary of the models. The “preoperative surface” is displacement of the normal cornea. (A) Radial keratectomy: maximum displacements located at middle incisions; (B) photorefractive keratectomy: maximum displacement at central cornea; and (C) LASIK and (D) SMILE: maximum displacements located around the central cornea (unit: mm). (From Shih P-J, Wang I-J, Cai W-F, Yen J-Y. Biomechanical simulation of stress concentration and intraocular pressure in corneas subjected to myopic refractive surgical procedures. Sci Rep. 2017;7(1):13906. doi:10.1038/s41598-017-14293-0.)

instability of refractive errors; 43% of eyes changed refractive power in the hyperopic direction by 1 D or more (hyperopic shift) between 6 months and 10 years.52 RK has essentially been replaced by newer excimer laser keratorefractive procedures. In 2003, one survey showed that 4% of cataract and refractive surgeons performed RK, down from 46% in 1996.53

Incisional Procedures for Myopic Astigmatism Naturally occurring astigmatism is very common and up to 95% of eyes may have some clinically detectable astigmatism in their refractive error.55 Between 3% and 15% of the general population has astigmatism greater than 2 D.56 Although there is some variability, approximately 10% of the population can be expected to have naturally occurring astigmatism greater than 1 D, where the quality of UCVA might be considered unsatisfactory.9,57 Surgically induced astigmatism can occur following cataract surgery. The incidence of astigmatism following extracapsular cataract extraction greater than 2 D is approximately 25% to 30%.58,59 With clear corneal incision phacoemulsification procedures, the incidence of astigmatism is much less. Beltrame et al. showed 0.66 D to 0.68 D of surgically induced astigmatism 3 months after phacoemulsification through a 3.5-mm clear cornea incision.60 Astigmatic keratotomy (AK) involves performing transverse (also called tangential, or T) cuts in an arcuate or

straight fashion perpendicular to the steep meridian of astigmatism (Fig. 1.7A). AK offers the patient a very good chance of significant improvement by correcting astigmatic errors.61–63 In general, patients with greater than 1.5 D of astigmatism may be candidates for AK. Deeper and longer incisions closer to the center of the cornea produce greater effect, but cuts beyond 75 degrees are not recommended. Effects of cuts increase dramatically with age. This procedure is now performed with the femtosecond laser and, rarely, with a diamond blade. Relaxing incisions in the steep meridian were developed by Troutman (Fig. 1.7B). These decrease astigmatism in the steep meridian, but the results can be unpredictable.64,65 This procedure may be combined with wedge resection or suturing in the flat meridian. These techniques have been used to correct postkeratoplasty astigmatism and surgically induced astigmatism at the time of cataract surgery.65–67 A study of 52 eyes showed a mean astigmatic change of −0.8 D in patients who had clear cornea cataract surgery with placement of limbal relaxing incisions (LRIs). The control group of 47 eyes had a mean astigmatic change of +0.50 D.68 The Ruiz procedure, now rarely used, employs trapezoidal cuts, four transverse cuts inside two radial incisions (Fig. 1.7C). Although important in its time, stacking multiple rows of astigmatic incisions is no longer felt to be prudent because of poor predictability. A pair of tangential

8 se c t i o n I

Introduction

A

B

5mm

7mm

C • Fig. 1.7

Correction of myopic astigmatism. (A) Astigmatic keratotomy. (B) Limbal relaxing incision. (C) Ruiz procedure.

• Fig. 1.6

  In radial keratotomy, radial incisions are placed in the cornea (top), resulting in forward bowing of the midperipheral cornea and compensatory flattening of the central cornea (middle). Postoperative appearance of radially symmetric spokes can be appreciated (bottom).

or arcuate incisions achieves significant correction. Additional incisions have minimal added benefit.

Nonlaser Lamellar Procedures for Myopia: A Historical Perspective Lamellar procedures for myopia involve corneal lamellar dissection combined with the addition or subtraction of corneal stromal tissue to result in overall flattening of corneal curvature. Nonlaser lamellar techniques include keratomileusis, automated lamellar keratoplasty, and epikeratophakia.

 

Keratomileusis refers to carving or chiseling the cornea. The first reported clinical results were published in 1964 by Jose Barraquer, and keratomileusis was first performed in the United States in 1980 by Swinger.69–71 For myopia, keratomileusis involves excision of a lamellar button (lenticule) of the patient’s cornea with a microkeratome, reshaping the lamellar button such that the central corneal curvature is flattened, and replacing it in position with or without sutures. Automated lamellar keratoplasty (ALK), also called keratomileusis in situ, was initially developed for higher myopia (Fig. 1.8). ALK uses a mechanized microkeratome to remove a plano lenticule (corneal cap) or to create a hinged corneal flap. A second pass of the microkeratome in the stromal bed resects a disc of central corneal stroma, and the corneal cap or flap generally is replaced on the stromal bed without sutures. The lenticule, at the time of the first pass, can be secured by a small residual hinge of tissue (flap) to minimize the possibility of losing the cap.

CHAPTER 1  Terminology, Classification, and History of Refractive Surgery

9

The procedure enables correction of large degrees of myopia (5 D to 18 D), but major problems include irregular astigmatism, unpredictability, and long visual recovery time (freezing damages tissue).72–75 Corrections beyond 18 D require greater tissue resections, resulting in instability and unpredictability.71,72 Clinically significant irregular astigmatism can occur in 10% to 15% after ALK, but this may decrease with time.73,76,77 Epikeratoplasty (also known as epikeratophakia and onlay lamellar keratoplasty) was introduced by Kaufman, Werblin, and Klyce at the LSU Eye Center in the late 1970s and early 1980s.78,79 It involves removal of the epithelium from the patient’s central cornea and preparation of a peripheral annular keratotomy. No microkeratome is used. A lyophilized donor lenticule (consisting of the Bowman layer and anterior stroma) is reconstituted and sewn into the annular keratotomy site (Fig. 1.9).80 Theoretical advantages of epikeratophakia are its simplicity and reversibility.81 This procedure is capable of correcting greater degrees of myopia than keratomileusis, but irregular astigmatism, delayed visual recovery, and prolonged epithelial defects are common.77,82

Corneal Implants for Myopia Synthetic materials can be embedded between corneal stromal lamellae to correct myopia. Intracorneal rings can be threaded into a peripheral midstromal tunnel or placed in a peripheral lamellar microkeratome bed to effect flattening of the central cornea.83,84 Their advantage lies in the avoidance of manipulation of the central cornea and visual axis (Fig. 1.10). Studies have also examined synthetic intracorneal lens implants that are placed in a centrally dissected corneal stromal pocket for the correction of aphakia and myopia (Fig. 1.11).85 These lenses have high indices of refraction and are made of materials such as polysulfone.86–88

Hyperopia and Hyperopic and Mixed Astigmatism Although hyperopia affects approximately 40% of the adult population,89,90 it is much less visually significant than myopia. The great majority of young hyperopes regard their eyes to be optically normal. They may experience early presbyopia and manifest hyperopia in their mid- to late thirties. Hyperopia may also be the result of overcorrection following radial keratotomy for myopia. This may require surgical intervention, but a waiting period of approximately 1 year may be necessary.91 Many of the keratorefractive procedures used for hyperopia are similar in design to those used to treat myopia but act to increase the cornea’s refractive power.

Laser Procedures • Fig. 1.8  Automated lamellar keratoplasty. Schematic illustration of in situ automatic corneal reshaping of the keratomileusis bed. The shaded area refers to the location of tissue subtraction. A corneal button is raised using a microkeratome (top). A second pass modifies the stromal bed to allow corneal flattening after replacing the cap (middle).

Excimer laser techniques—such as PRK, LASEK (or epiLASEK), and LASIK—can be used to treat hyperopia. An ablation pattern allows for maximum ablation in the midperiphery for an overall steepening of the optical zone. At present, custom corneal ablations are not approved for hyperopic corrections in the United States.

10 10 se c t i o n I

Introduction

• Fig. 1.9  Schematic illustration of epikeratoplasty. A preshaped donor lenticule (bottom) is sutured to the recipient stromal bed to correct myopia (left) and hyperopia (right). The shaded areas refer to the locations of tissue subtraction.

Laser Procedures for Hyperopia

Patients with low degrees of hyperopia treated with LASIK achieve more predictable results and achieve refractive stability more quickly than those with higher amounts of hyperopia (> 5 D).92,93 Stability with hyperopic LASIK is usually reached by 3 months.14 One study has compared LASEK and PRK for the treatment of hyperopia of up to 5.0 D. LASEK patients experienced less postoperative pain, decreased haze, faster visual recovery, and greater refractive stability compared to patients with hyperopic PRK.94 Laser Procedures for Hyperopic and Mixed Astigmatism

Hyperopic astigmatism occurs when both meridians are focused behind the retina. Patients with this profile can be treated in minus-cylinder or plus-cylinder format. When treating in minus-cylinder format, both meridians are flattened centrally, with the steeper meridian being flattened more. In plus-cylinder format, both meridians undergo peripheral steepening, with the flatter meridian being steepened more. Azar and Primack showed that plus-cylinder ablations spare more tissue when treating hyperopic astigmatism.95 A study of 124 eyes with hyperopic astigmatism treated with the Alcon LADARVision excimer laser showed results similar to those with hyperopic spherical treatment, with 53.1% achieving 20/20 uncorrected visual acuity at 12 months with a small overcorrection of the cylinder.96 In patients with mixed astigmatism, one meridian must be flattened and the other must be steepened because one meridian is in focus in front of the retina and the other

behind the retina. Treatments that combine hyperopic sphere with myopic cylinder treatments or hyperopic cylinder with myopic cylinder treatments spare the most tissue.95 In a study by Salz and Stevens,96 65 patients with mixed astigmatism were treated with the Alcon LADARVision excimer laser. Uncorrected visual acuity was 20/20 in 52% at 12 months.

Incisional Procedures for Hyperopia Hexagonal keratotomy, devised by Mendez in 1985, is an incisional treatment for hyperopia consisting of circumferential connecting hexagonal peripheral cuts around a clear 4.5-mm to 6.0-mm optical zone. This procedure allows the central cornea to steepen, thereby decreasing hyperopia (Fig. 1.12).97 A second procedure using nonintersecting hexagonal incisions was described by Casebeer and Phillips in 1992.98 A study in 1994 of 15 eyes reported complications that included glare, photophobia, polyopia, fluctuation in vision, overcorrection, irregular astigmatism, corneal edema, corneal perforation, bacterial keratitis, and endophthalmitis.99 These authors concluded that hexagonal keratotomy was unpredictable, unsafe, and had high rates of complications.99

Nonlaser Lamellar Procedures for Hyperopia ALK, keratophakia, and epikeratophakia have been used to treat hyperopia. In hyperopic ALK (also known as keratomileusis), a deep lamellar keratectomy is performed with a microkeratome, elevating a corneal flap. The stromal bed subsequently develops ectasia under the flap, which

CHAPTER 1  Terminology, Classification, and History of Refractive Surgery

11

• Fig. 1.11  Schematic illustration of an intracorneal lens inlay. The synthetic lens is placed in the corneal stroma after creation of a lamellar flap (illustrated here) or within a lamellar pocket (not shown).

A •

Fig. 1.12  Conductive keratoplasty (CK). Spot algorithm used to predict the effect of CK. A greater effect is obtained with neutralpressure CK.

B • Fig. 1.10

  Corneal intrastromal ring segments. (A) The ring is placed in the stroma (top) resulting in central flattening (middle); the central cornea is not manipulated (bottom). (B) Photograph of intrastromal segments (arrows).

is replaced without additional surgery. Alternatively, the stromal side of the resected disc is remodeled into a convex hyperopic lenticule that, when placed in the original stromal bed, results in steepening of the central cornea. Hyperopic ALK has poor predictability and the risk of progressive ectasia limits its usefulness. Homoplastic ALK has been performed to hyperopia from 4 D to 10 D. In this procedure, the microkeratome removes a small disc (80–100 mm in thickness, 5–7 mm in diameter) that is discarded and replaced by a 350- to 400-µm thick donor lenticule (generated using the microkeratome). The safety

12 se c t i o n I 12

Introduction

and efficacy of hyperopic and homoplastic ALK have not been fully established.100 Keratophakia is a technique developed by Barraquer for treating high hyperopia or aphakia. A lamellar keratectomy is first performed on the patient’s cornea using a microkeratome. Donor corneal tissue is then shaped into a lens after removal of the epithelium, Bowman layer, and anterior stroma. This donor lens is placed intrastromally within the recipient and the anterior lamellar cap is sutured in place. This process creates a steeper anterior cornea and increases refractive power. Synthetic intracorneal lenses have also been developed for implantation in the lamellar bed but are investigational. Hyperopic epikeratophakia uses a prepared donor lenticule without microkeratome removal of tissue. Although theoretically safer than keratomileusis, it lacks predictability and may induce irregular astigmatism.101

Thermal Procedures for Hyperopia Thermal energy can be used to shrink collagen of the corneal stroma and increase central corneal power. When applied to the paracentral or peripheral cornea, these techniques result in increased central corneal curvature and peripheral corneal flattening. Three methods are described: radial intrastromal thermokeratoplasty, laser thermokeratoplasty, and conductive keratoplasty. Radial intrastromal thermokeratoplasty shrinks the peripheral and paracentral stromal collagen, producing a peripheral flattening and a central steepening of the cornea to treat hyperopia. Radial thermokeratoplasty (hyperopic thermokeratoplasty [HTK]) for the correction of hyperopia was developed in the then Soviet Union in 1981 by Fyodorov. A retractable cautery probe tip produces a series of preset-depth (≈ 95%) stromal burns in a radial pattern similar to that used in RK.41,102–105 Although an initial reduction in hyperopia was observed, lack of predictability and significant regression are problems.41,102–105 However, there may be less induced astigmatism with radial thermokeratoplasty than with hyperopic ALK or hexagonal keratotomy.106 Solid-state infrared lasers, like the holmium:yttrium aluminum garnet (Ho:YAG) laser, have been used in a peripheral intrastromal radial pattern (laser thermokeratoplasty [LTK]) to treat hyperopia of 4 D and less.107 LTK works by causing thermal shrinkage of stromal collagen in the paracentral cornea, with a resultant steepening of the central corneal curvature, thereby reducing hyperopia. Recent work on human eyes has demonstrated appropriate topographic changes with at least short-term stability.108 This laser energy can be delivered by a handheld probe or slit beam system and appears most useful for limited amounts of hyperopia and hyperopic astigmatism. However, the long-term effects and refractive stability of Ho:YAG LTK are unknown. Conductive keratoplasty (CK) is a technique that has been recently approved by the US Food and Drug Administration (FDA) for the treatment of hyperopia and presbyopia. CK uses a special probe to deliver radiofrequency wave energy to the deep stroma of the midperipheral cornea,

causing focal shrinkage of collagen fibers, steepening the central cornea and flattening the periphery (see Fig. 1.12). Applications are made in concentric 6-, 7-, or 8-mm circles; the amount of effect depends on the number of spots placed. At the present time, CK has been approved for the treatment of hyperopia (0.75–3.25 D, with no more than 0.75 D of astigmatism) and presbyopia in emmetropes and hyperopes (by induction of myopia, −1.00 D to −2.00 D).107,108

Aphakia Most aphakic patients who are intolerant of contact lenses or simply desire refractive correction undergo secondary intraocular lens placement. Aphakic patients who are at high risk for intraocular procedures may benefit from keratorefractive surgery. These procedures for the treatment of aphakia are similar to nonlaser lamellar techniques, such as keratophakia and epikeratoplasty or corneal implants for high hyperopia. As described before, keratophakia involves the intrastromal placement of donor stromal tissue that has been shaped into a lens. The donor tissue lens is thicker in the center than in the periphery. Epikeratophakia has been described previously for myopia and hyperopia and involves sewing a donor lenticule to the anterior surface of the prepared cornea. Widespread use of epikeratophakia is limited because of problems with epithelial healing and graft clarity. Its main use is in the correction of aphakic children aged 1 to 8 years who are spectacle and contact-lens intolerant, in order to avoid amblyopia. The highest success rates in epikeratophakia have been reported in the treatment of 8- to 18-year-old patients with aphakia.109 Intracorneal lens implants are under investigation. Advantages include improved refractive quality and predictability and faster visual recovery when compared to nonlaser lamellar techniques for aphakia. In addition, corneal implants eliminate the risks associated with the use of human donor tissue. Materials such as hydrogel85 or fenestrated polysulfone,110 with a high index of refraction, have been studied. Steinert et al. reviewed the use of a hydrogel implant (lidofilcon A) in patients with aphakia, followed over 2 years. A total of 88% of these patients had a refraction within 3 D of plano. Complications included loss of BCVA, irregular astigmatism, and irregular microkeratome resections in some patients.111

Presbyopia Near vision correction is an especially important consideration when planning refractive surgery in the presbyopic age group. Myopic patients may experience difficulty with near vision if their refractive error is fully corrected. Undercorrected myopes may experience less-than-optimal distance vision but may retain some of their ability to see clearly at near distances. Keratorefractive procedures for presbyopia include monovision, a procedure that leaves a residual myopic correction in one eye, and multifocal corneal ablation, a procedure that is still in development.

CHAPTER 1  Terminology, Classification, and History of Refractive Surgery

13

Monovision Monovision improves near vision by giving one eye a slightly myopic correction, usually −1 D to −2 D. The other eye is corrected fully for distance. Myopia remaining in the dominant eye is called uncrossed monovision, and myopia remaining in the nondominant eye is called crossed monovision. Monovision treatments can be applied to myopes, hyperopes, and emmetropes. For patients with myopia, the “near” eye is not treated for the full amount of myopic refractive error; rather, it is left with a residual myopic correction. In hyperopes, myopia must be created by “overcorrecting” the near eye. Keratorefractive options to achieve monovision have expanded in the past decade and include PRK, LASIK, and conductive keratoplasty. One challenge to creating monovision with laser and conductive procedures is irreversibility. Following monovision treatment, patients must adapt to its effect. Monovision patients have been found to perform relatively worse with low levels of illumination, nearthreshold levels of stimuli, and tasks requiring good depth perception.112,113 However, among patients who underwent PRK and LASIK monovision correction, between 88% and 96% were satisfied with their visual outcome.114,115

Conductive Keratoplasty While conductive keratoplasty was approved in the United States for the treatment of presbyopia in emmetropes, the advantages that it offers being a nonincisional, nonablative approach are limited by a high rate of refractive regression. In a retrospective consecutive single-surgeon study, Ayoubi et al.116 compared FS-LASIK and conductive keratoplasty for monovision treatment of the nondominant eye in presbyopic emmetropic patients. FS-LASIK monovision provided stable correction with less induced astigmatism and HOA; the retreatment rate was 3% after FS-LASIK compared to 50% after CK (P ni sini = sinr

ni nr

Refractive Errors of the Human Eye Emmetropia

Snell’s Law

i

Magnification characteristics of optical systems may be defined in several ways. Where an image is formed of an object, linear magnification may be defined to be the quotient of the sizes, measuring perpendicular to the optical axis, of image and object. Measuring along the optical axis, the quotient of image and object sizes is called axial magnification and is found to be the square of the linear magnification described earlier. Considering the eye’s view through optical systems, it is useful to speak of angular magnification, the quotient of the angles subtended at the eye, or more precisely at its first principal plane by an object as viewed with and without the optical system, respectively.

nr ni

r

The nonaccommodating emmetropic eye brings any pencil of parallel rays (e.g., from a point on an object at optical infinity) to focus at some point on the retina. The secondary focal plane of such an eye is located on the retina and the far-point plane (defined as the points conjugate to the retina in the nonaccommodating state) is at optical infinity, that is, far away.

Myopia • Fig. 3.2

  When light travels from one medium to another with a lower index of refraction, the rays are bent away from the normal to the surface. A critical angle of incidence (i) may be reached if the angle of refraction (r) reaches 90°. Light rays striking the surface with an angle of incidence greater than the critical angle will be completely reflected. (Reprinted with permission from Azar DT, Strauss L. Principles of applied clinical optics. In: Albert D, Jakobiec F, eds. Principles and Practice of Ophthalmology. 3rd ed. Philadelphia, PA: W. B. Saunders; 2008.)

(+)

F2 Image

F1 Object

The myopic eye brings pencils of parallel rays to focus at points anterior to the retina. The secondary focal point of the eye is in the vitreous. Rays diverging from a point on the far-point plane of the eye will be brought to focus on the retina without the aid of accommodation. For instance, a −2.00 D myope who is capable of 1 D of accommodation reads without effort at a half meter and can keep the image clear up to one-third of a meter by accommodating. The spectacle correction of myopia involves placing a diverging lens in front of the eye so that the secondary focal point of the lens coincides with the far point of the eye. Pencils of parallel rays striking the lens will diverge when they leave the lens as though they originated from the far point of the eye; hence, they will be brought to focus on the retina. Refractive surgical correction of myopia is achieved by flattening the front surface of the eye. When the myopic error is fully corrected, pencils of parallel rays are brought to focus on the retina.

Hyperopia f

• Fig. 3.3

f

Ray tracing to determine image size and location using primary and secondary focal points of a converging lens. (Reprinted with permission from Azar DT, Strauss L. Principles of applied clinical optics. In: Albert D, Jakobiec F, eds. Principles and Practice of Ophthalmology. 3rd ed. Philadelphia, PA: W. B. Saunders; 2008.)  

The hyperopic eye brings pencils of parallel rays of light to focus at points behind the retina. Accommodation of the eye may produce enough additional plus power to bring a parallel (or even a diverging) pencil of rays to focus on the retina.

40 40 se c t i o n II

Optics, Topography, Wavefront and Imaging

Astigmatism Astigmatism of the eye’s optical system may be caused by asymmetry of the cornea or, less frequently, of the lens. Astigmatism is regular when it is correctable with a spherocylindrical lens so that pencils of light from distant objects can be focused on the retina. Otherwise, the astigmatism of the eye is called irregular. Fortunately, naturally occurring refractive error of the eye tends to be the result of toricity of the cornea and lens and is therefore regular, so that spherocylindrical corrective lenses allow acuity similar to that found in emmetropic eyes. Regular astigmatism is with the rule when the steepest (most refracting) meridian lies near 90°. It is correctable by a spherocylindrical lens with pluscylinder, whose axis lies near 90°, or minus-cylinder, with axis near 180°. When the steepest meridian is near the 180° meridian, the eye’s astigmatism is termed against the rule and is correctable by plus-cylinder, with axis at 180°, or minus-cylinder, with axis at 90°. When astigmatism is regular, but the principal meridians do not lie close to 90° and 180°, the astigmatism is termed oblique.

Correction of Refractive Errors and Visual Distortions Eyes with myopia, hyperopia, and largely regular astigmatism are commonly corrected to approximately 20/20 acuity with spectacles. Aside from the cosmetic and practical inconveniences, what are the drawbacks of spectacle correction? Minus lenses minify the perceived image by roughly 2% per diopter. To the extent that the minus power is astigmatic, the minification is meridionally unequal, thereby distorting the image. Minification is somewhat beneficial because the periphery is brought into view. Plus lenses, on the other hand, magnify the image but create a peripheral scotoma between what is viewed inside and what is viewed outside the spectacle frame. The farther away from the optical center the line of sight deviates, the more prism is encountered—hence, the well-known pincushion and barrel distortions encountered with spectacle correction of high myopia and hyperopia, respectively. Off-axis viewing and lens tilt produce changes of the effective sphere and cylinder. These effects are greater with higher-power lenses, of course, and may be particularly disturbing when the two eyes have markedly different refractive errors.

Oblique Astigmatism Binocular spectacle correction of oblique astigmatism distorts each eye’s view and, when the axes are not the same, tilts the perceived three-dimensional field. The perceived tilt occurs when both eyes are corrected and disappears when either eye is occluded. Differential meridional minification and misperception of tilt can be reduced, at the expense of clarity, by decreasing the cylinder power and by rotating the axis of the correcting cylinders toward 90° or 180°.

It is important to identify this situation prior to surgery. When tailoring refractive surgery for a patient whose spectacle adaptation has required such compromises, the surgeon needs to know what the actual refractive error is rather than the compromise prescription that is in the spectacles. It may be that some patients who have long-standing adaptation to spectacle-induced distortion and tilt experience discomfort for some time when they have these distortions removed through surgery or contact lens wear. Until readaptation occurs, absence of optical distortion may be perceived by the patient as a disturbing change in binocular spatial sense.

Image Magnification Anisometropic patients may seek refractive surgery because their spectacles produce symptoms related to aniseikonia and anisophoria. By reducing the anisometropia, surgery may give long-term relief. Regarding myopic spectacle minification, when optical correction is moved from the spectacle plane to the cornea by contact lenses or surgery, a larger retinal image of the Snellen chart is formed on the retina so that if the optical resolving power (i.e., clarity of image) is preserved, there should be an artifactual improvement of Snellen acuity. One may therefore reason that postoperative acuity should be compared with preoperative rigid contact lens correction in order to judge the effect of the surgery on the optical quality of the eye. This is not a new idea; recall that the preimplant cataract surgeon could hold a plus lens several inches in front of an aphakic eye so that the patient could read hugely magnified 20/20 letters, viewed one at a time, through the resulting telescope.

Lens Effectivity Two lenses of unequal power at unequal distances from the eye may each give exact distance correction of that eye so long as each focuses parallel pencils of rays at the eye’s far point. When a near object is viewed through the same two lenses, vergence calculations show that the amount of accommodation required to focus the diverging rays on the retina is quite different. For instance, a spectacle-corrected myope accommodates less to read a book at 25 cm than the same myope corrected with contact lenses. This notion, that the near effectivity of distance-corrective lenses depends on vertex distance, is of great interest to the practitioner considering the advisability of contact lenses or refractive surgery for the incipiently presbyopic myope who stands to lose the benefits of the near effectivity of minus spectacles.

Preoperative Optical Considerations for Refractive Surgery Contact Lens Wear For the cornea to return to its natural shape, soft contact lens wear should be discontinued for 3 to 7 days and rigid

CHAPTER 3  Physiologic Optics for Refractive Surgery: An Overview

lens wear for 3 weeks prior to conventional refractive procedures. A longer period of contact lens discontinuation may be needed prior to wavefront-guided surgery.

Vertex Distance For refractive error over 5 D, vertex distance should be measured from the rear surface of a corrective lens in order to calculate the refractive power at the cornea. Frames are often not actually worn at 13.75 mm, the reference distance for the phoropter.

Anisometropia and Aniseikonia Knapp’s rule tells us that with purely axial anisometropia, which may occur in cases of unilaterally high myopia, equal image sizes on the two retinas are achieved when each refractive error is corrected with a spectacle lens placed at the anterior focal point of the eye, which is about 16 mm in front of the cornea. The geometric-optics argument for this does not consider the possibility that the highly myopic eye may have stretched-apart spacing of photoreceptors, which would tend to minify the view. If these anisometropes do not have disturbing aniseikonia with spectacles, might they after keratorefractive surgery? Placement of a corrective contact lens should allow preoperative investigation of this possibility and adequate counseling to the unilaterally highmyopic patient about possible postoperative discomfort and adaptation. Aniseikonia may be unavoidable in refractive surgery of the preoperatively iseikonic bilateral high myope. After surgery of one eye, the other eye may require contact lens wear as the only remedy for aniseikonia until the second eye has similar surgery. Thus when discussing the risks of surgery preoperatively, contact-lens-intolerant patients with high myopia should be apprised of the difficulties they might face.

Cycloplegic Refraction Refraction is repeated after cycloplegia to discover whether accommodation has been active during the previous “dry” refraction, in which case the cyclopleged eye will show less myopia. For example, a young person with spasm of accommodation would in this manner be identified before surgery; thus the surgical plan would be based on the true refractive error. However, there may be a shift with cycloplegia toward greater myopia, which is caused by spherical aberration as the peripheral optics of the eye are exposed by dilation (Fig. 3.4).

Hyperopia When cyclopleged, the hyperopic eye has insufficient plus power to focus the image of a distant object on the retina. Gazing at distance without cycloplegia, the least plus required for clear distance vision is termed absolute hypero-

41

Spherical aberration

Central ray Peripheral rays

• Fig. 3.4

  Spherical aberration. Rays of light striking the periphery of a spherical lens are bent more than the central rays. (Reprinted with permission from Azar DT, Strauss L. Principles of applied clinical optics. In: Albert D, Jakobiec F, eds. Principles and Practice of Ophthalmology. 3rd ed. Philadelphia, PA: W. B. Saunders; 2008.)

pia. The most plus the eye can accept without blurring of the image is the manifest hyperopia. The diopters between the least and most accepted plus constitute the amount of hyperopia that is facultative. If accommodation is not as relaxed after fogged refraction as it is with cycloplegia, the difference between the manifest and cycloplegic refractions is considered the amount of hyperopia that is latent. As a hyperopic patient advances in age, absolute hyperopia approaches manifest hyperopia (which, in turn, increases to approach the cycloplegic hyperopia). Under ideal circumstances, surgery for hyperopia should aim at correcting most of the cycloplegic refractive error, the difficult point here being the assessment of the tenacity of the accommodative tone that constitutes the latent portion of the hyperopia.

Diabetes The diabetic lens may fluctuate in size and curvature with changes in blood sugar. Diabetic candidates for keratorefractive surgery need to be identified to assess the stability of refractive error and rule out the existence of diabetic retinopathy. Diabetes is a relative contraindication for elective corneal surgery given that a duplicated basement membrane, recurrent erosions, and persistent epithelial defects occur more frequently in the diabetic corneal epithelium than in the nondiabetic one.

Pupil Size The size of the entrance pupil (the image of the pupil transmitted through the cornea) should be estimated in brightly and dimly lit conditions. If the entrance pupil is larger than the postsurgical optical zone in dim but photopic conditions, then an annulus of cornea surrounding the optical zone will transmit light waves to the fovea. We may then be concerned that focus through this annulus is significant and is not the same as it is through the central cornea. The wavefront error due to peripheral irregularity may degrade the foveal image. This is represented by abnormal foveal point spread function. The Styles–Crawford effect gives the notion that the orientation of photoreceptors favors reception of light passing through the central cornea, encouraging hope that the noncentral cornea will cause little image

42 se c t i o n II 42

Optics, Topography, Wavefront and Imaging

degradation even when the entrance pupil is large enough to allow these photons to reach the fovea obliquely.

Extraocular Motility Examination Extraocular muscle examination, including measurements of the amplitudes of convergence and divergence, can prove helpful prior to keratorefractive surgery. Distance and near cover and alternate cover tests reveal tropias and phorias. Polarized lens stereopsis tests and tests such as red–green Worth lights, which give less stimulus to fusion, may be used to evaluate the degree and stability of fusion and presence of suppression. Keratorefractive surgery may result in reduction or increase in accommodative demands in various circumstances. The spectacle-corrected myope brought to emmetropia by surgery will experience increased demand at near because of the loss of near effectivity of distancecorrective minus lenses. To the extent that myopia is undercorrected, accommodative demand at near will be reduced, giving relief to the presbyope but possibly constituting a cause of concern for someone less presbyopic who has convergence insufficiency. A young esophore with a low reserve of fusional divergence might become symptomatic if overcorrection of myopia, resulting in hyperopia, creates an increased demand for accommodation with its associated accommodative convergence. Measuring the amplitudes of convergence and divergence (far and near, with or without accommodation) with prisms helps to predict whether a change of accommodative demand is likely to stress a weakness of convergence or divergence. If the patient is to function without glasses after surgery, there will be no spectacles in which to grind prisms.

Accommodation Assessment of the amplitude of accommodation before surgery allows the refractive surgeon to formulate a plan for near vision that may include, for instance, the undercorrection of myopia of one or both eyes. In general, the difference in diopters between least and most spheres accepted with clear vision while gazing at a distant target is the amplitude of accommodation. Measuring the near point while wearing myopic spectacles will tend to overestimate the amplitude of accommodation because of the near effectivity discussed earlier. Unequal or unusually small amplitudes suggest traumatic injury, drug effects, third cranial nerve paresis, lack of effort, spasm of accommodation, or erroneous distance refraction. One may expect a myope or anisometrope with natural monovision who has not bothered to wear glasses to have developed lower amplitude of accommodation than usual, whereas a long-time uncorrected hyperope will probably have built up greater amplitude than usual.

Spectacle Overcorrection of Myopia The spectacle overminused myope with presbyopic symptoms may become nonpresbyopic when the unnecessary

minus is removed. Discovery of the overminused state may require cycloplegia or at least prolonged fogging with plus lenses during refraction, as the patient may have sustained the extra accommodative tone for years. The patient should be given a new pair of lenses, and surgery should be delayed if the excess minus power of the previous spectacle lens has been a diopter or more. Patients will find that the correct glasses are not as functionally impairing as the overminused lenses were, but they may still desire surgical correction. The surgery should be based on the cycloplegic refraction if the cycloplegic manifest is accepted. This situation requires great care in choosing the amount of correction; even after surgery, some of these patients will be unable to relax accommodative tone so that correction based on the cycloplegic preoperative refraction may persistently be felt to be insufficient. The surgeon may then be faced with the patient’s demand for further surgery based on this residual accommodative tone, leading to the patient being deliberately converted from an overcorrected myope to a latent hyperope! The overminused bifocal wearer similarly will complain at a younger age of blur in the middle distance and will regain use of the amplitude of accommodation with a corrected distance prescription.

Intraoperative Optical Considerations of Refractive Surgery An improperly located refractive surgical procedure can cause glare, irregular astigmatism, monocular diplopia, ghost images, poor contrast sensitivity, and unpredictable refractive outcomes.15,16 The proper centration of corneal procedures was the subject of considerable debate. Several authors proposed centering techniques that were based on the incorrect assumption that the refraction of light entering the eye is centered on the visual axis.17–19 However, the visual axis, while useful for theoretical calculations of image sizes in a model eye, has little to do with the refractive elements encountered by rays of light traveling through the eye. In fact, the visual axis of an eye with a markedly eccentric pupil may not pass through the pupil at all; instead, it may pass through the iris! Walsh and Guyton20 and Uozato and Guyton21 noted that rays of light passing through the optical elements of the eye must pass through the entrance pupil of the eye.

Optical Axis, Nodal Points, and Visual Axis The optical axis of an aligned optical system is the line passing through the center of curvature of each optical element comprising the system.22 A ray striking the primary nodal point leaves the secondary nodal point with an identical inclination to the optical axis (Fig. 3.5).23 The human eye is not an aligned optical system; thus there is no straight line that can describe the optical axis, there are no true nodal points, and schematic models such as the Gullstrand schematic eye and reduced schematic eye are of little use in

CHAPTER 3  Physiologic Optics for Refractive Surgery: An Overview

n n1

xis Visual a a

F Pupillary

a

axis

l

xis

Visual a

Object

43

Fixation light

Corneal center of curvature

E

Line of sight

Light reflex

• Fig. 3.5

  Gullstrand schematic eye demonstrating conjugate pair of nodal points (n, n1). A ray of light with an angle α to the optical axis and passing through the primary nodal point (n) will leave the secondary nodal point (n1) at the same angle a. The visual axis is the line connecting the point of fixation (object) through the nodal points of the eye to the fovea (F).

• Fig. 3.7  Schematic diagram of the anterior segment of the eye, viewed from the top, to demonstrate pupillary axis and angle lambda. E is the center of the entrance pupil. The true pupil is closer to the center of curvature than the entrance pupil. Light reflex is the corneal light reflex.

True pupil Entrance pupil Limiting ray

Lim

itin

Exit pupil Retina

Chie

gr

ay

f ray

Object

Image

• Fig. 3.6

  Schematic representation of the three pupils of the eye (entrance pupil, true pupil, and exit pupil). The chief ray and limiting rays for a single object point are also indicated.

explaining or predicting the behavior of a significantly decentered system—for example, the optical system of a patient with a markedly eccentric pupil or an abnormally large-angle lambda.

Pupil, Optical Zones, and the Chief Ray The true pupil is an aperture that limits the amount of light passing through an optical system. The entrance pupil of the eye is the virtual image of the true pupil formed by the refractive properties of the aqueous and the cornea, whereas the exit pupil is the image of the true pupil formed by the refractive properties of the crystalline lens and the vitreous humor. When we look at a person’s eye, we see the entrance pupil. Clinical measurements of the pupil actually measure the entrance pupil. The entrance pupil is approximately 14% larger than, and 0.3 mm anterior to, the true pupil (Fig. 3.6).24 The exit pupil can be viewed from the posterior pole of the eye. The optical zone is the area of the cornea overlying the entrance pupil.16 The optical zone is the part of the cornea that refracts the light rays forming the foveal image. The

chief ray is a ray emanating from an object point that passes through the center of the entrance pupil (see Fig. 3.6).25 The limiting rays are the bundle of rays emanating from an object point that pass just inside the edge of the entrance pupil. The limiting rays are the same throughout the optical system; that is, the same light rays are limiting rays as they pass through the entrance pupil, the true pupil, and the exit pupil. When the retinal image is blurred, the chief ray defines the center of the blur circle (assuming a round pupil with a spherical refractive error), and the limiting rays define the edge of the blur circle for each object point.

Line of Sight and Pupillary Axis The line of sight is the line connecting the fixation point with the center of the entrance pupil (Fig. 3.7).24 The line of sight corresponds to the chief ray of the light emanating from the fixation point. In an aligned optical system with a round pupil centered on the optical axis, the line of sight is equivalent to the optical and visual axes. In the eye, with its noncentered optics, the line of sight is not equivalent to the visual or optical axes, which are not determinable. The pupillary axis is the line perpendicular to the cornea that passes through the center of the entrance pupil (see Fig. 3.7). This line will pass through the center of curvature of the anterior corneal surface. The pupillary axis can be located by centering the corneal light reflex in the center of the patient’s pupil while the examiner sights monocularly from directly behind the light source.

Angles Kappa and Lambda Clinicians often refer to the angle between a coaxially sighted corneal light reflex and the pupillary center as the angle kappa. In fact, the angle kappa is the angle between the nonexistent visual axis and the pupillary axis; thus it is not possible to measure such an angle in the eye. The angle between the line of sight and the pupillary axis, which can

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be measured clinically (see Fig. 3.7), is referred to as the angle lambda.22 In normal subjects, the angle lambda is typically 3° to 6°.22 Light reaching the fovea is, by definition, refracted within the optical zone; thus corneal power is relevant only in this location. An error in centration can produce unpredictable corneal curvature in the optical zone, leading to poor refractive outcomes in patients with markedly decentered optical systems. Maloney16 calculated that if a 4-mm optical zone (overlying a 4-mm entrance pupil) is decentered 1 mm, only 70% of the light rays falling on the retina will have passed through the optical zone. The optical zone must be larger than the entrance pupil to provide glare-free vision. The minimum optical zone diameter increases with increasing pupil size, desired glarefree visual field angle, and anterior chamber depth.26 For a patient with a 4-mm pupil to have a 15° glare-free visual field, the diameter of the clear optical zone must be at least 5.38 mm.21 O’Brart et al.27 performed 4-mm photorefractive keratectomy (PRK) ablations in one eye and 5-mm ablations in the other eye of 33 patients. The patients were more likely to complain of glare or decreased night vision in the eye with the 4-mm ablation zone. The authors did not attempt to determine whether errors in centration contributed to the glare.

Pupil Eccentricity How does the eye create an image on the fovea when the pupil is eccentric? To answer this question, decenter the pupil in the optical system described earlier (Fig. 3.8). Even if the rays traveling along the visual axis are blocked, the eye will still form a focused foveal image of the object. The bundle of rays from the object must pass through, and be refracted by, the optical zone of the cornea. The same bundle of rays must pass through the entrance pupil to reach the fovea. In a living eye, the photoreceptors will reorient their long axis toward the center of an eccentric pupil, not toward the visual axis.28,29 The image of the object does not move as the pupil is decentered because the optical system of the eye forms an image on the fovea regardless of pupil location. To demonstrate that an eccentric pupil does not move the image and necessitate a compensatory eye movement to maintain fixation, perform the following simulation (Fig. 3.9): cut a strip of paper 1 cm wide and 3 cm long and place a pinhole opening near one end of the strip. Close one eye and fixate on a target across the room. Place the pinhole before the open eye and move it from side to side and up and down, simulating different degrees of pupil eccentricity. As long as the pinhole aperture stays within the entrance pupil of the viewing eye, the image remains stationary regardless of aperture movement. (The simulation does not exactly match the situation in the eye, as the extra “pupil” is in front of, rather than behind, the cornea. When the pinhole is moved beyond the edge of the entrance pupil of the viewing eye, the image disappears. In addition, a

CI

LR

CC

A

Eccentric pupil CI

F

CC LR

B • Fig. 3.8  Locating the center of a corneal procedure in a reduced schematic eye. (A) Centered optical system (all optical elements are aligned). CI is the corneal intercept of the line connecting the fixation target with LR, the corneal light reflex, which in this case coincides with the corneal intercept of the visual axis and the geometric center of the cornea. CC is the center of curvature of the cornea. (B) All optical elements are aligned except for an eccentric pupil. The shaded area indicates the path of light from the fixation target to F, the fovea. Note that CI is not included within the shaded area; therefore it does not participate in the refraction of the light reaching the fovea.

Object

F

• Fig. 3.9

  Demonstration of consequences of an eccentric pupil. F is the fovea. The shaded area indicates the path of light through the pinhole aperture and pupil; the solid line indicates the straight line from object to fovea; dotted arrows indicate movement of the pinhole occluder.

subject with an uncorrected refractive error may note slight movement.)

Foveal Eccentricity Now, consider a different scenario: a model eye with centered optical elements and a centered pupil but with an

CHAPTER 3  Physiologic Optics for Refractive Surgery: An Overview

45

Pupillary Dilation

F Scar

A

Eccentric pupil F Scar

B • Fig. 3.10

  A model eye with centered optical elements and a central corneal scar. (A) Central pupil. The light striking the scar is scattered as it passes through the entrance pupil. F is the fovea. (B) Eccentric pupil. The light striking the scar is scattered, but the scattered rays of light do not participate in forming a foveal image. The light that forms the foveal image does not pass through the scar, and a sharp foveal image is formed by the clear optical zone over the eccentric entrance pupil.

eccentric fovea (Fig. 3.10). For foveal fixation, the optical axis will not be aligned with the fixation point. In the model eye, this misalignment of the optical and visual axes is referred to as a positive- or negative-angle kappa. (For the reasons stated earlier, the term angle lambda is more appropriate when this occurs clinically.) When the optical axis is misaligned in this way, light rays emanating from the fixation point pass through the entrance pupil of the eye and are brought into focus on the fovea. Once again, it is the optical zone over the entrance pupil of the eye, not the area of cornea overlying the visual axis, that is acting on the light rays of interest.

Summary of the Role of the Visual Axis and the Optical Zone It is apparent from the situations described earlier that the visual axis is of no use in locating the bundles of light refracted by the eye. Thus even if the human eye were a perfectly aligned optical system and even if one could determine exactly the intercept of the visual axis with the cornea, this would not matter to the surgeon planning a corneal refractive procedure. The only part of the cornea that matters is the optical zone: the area of the cornea overlying the entrance pupil of the eye. We therefore agree with the conclusion of others that the center of the entrance pupil is the proper centration point for corneal refractive surgical procedures.16,21,26,30–32

Only the rays passing through the entrance pupil of the eye centered about the chief ray contribute to the formation of a foveal image. For this reason, a refraction can vary depending on the amount of pupillary dilation, without regard to the state of accommodation. The natural pupil center shifts nasally and superiorly with miosis.33 Schwartz-Goldstein et al.34 noted a systematic decentration of PRK inferonasally and attributed this to the preoperative use of pilocarpine. A careful manifest refraction in an examination room with modest lighting to produce 3- to 4-mm natural pupils may be the best to compare with the cycloplegic refraction. Therefore both a manifest refraction and a dilated refraction should be performed, especially in patients with eccentric or irregular pupils or in patients whose pupils dilate eccentrically. This extra step can help the surgeon identify patients who may develop problems postoperatively when different lighting levels cause variability in the postoperative refraction.

Recommended Technique for Optimal Centration in Corneal Refractive Surgical Procedures Based on the optical principles and experimental results described earlier, we recommend the following procedure for optimal centration of corneal surgical procedures. The surgeon must keep in mind that although this recommended procedure is most consistent with modern understanding of the optics of the eye, experimental evidence and published clinical data are lacking in this area, especially in patients with markedly decentered optical systems. The patient should fixate a light or target that is coaxial with the examiner’s sighting eye. This can easily be accomplished by placing a fixation spot in the exact center of one of the viewing tubes of the microscope. A 1- or 2-mm mark will not interfere significantly with the microscope optics. Errors from any potential decentration of the surgeon’s pupil are negligible.16 If already available, Osher’s optical centering device may also be used as a coaxial fixation target, but the instructions that describe how to mark the corneal light reflex should be disregarded. Marked miosis displaces the entrance pupil center,33 which may increase unwanted optical aberrations when the pupil redilates after surgery. Therefore the pupil should be in a natural state, not under the influence of any pharmacologic agents. Adjust the intensity of the light in the operating microscope until the pupil diameter is 3 to 4 mm. Klyce and Smolek32 advise marking the center of the entrance pupil at three different pupil sizes, using different light intensities to increase precision. If the three marks do not coincide, we recommend using the mark placed at a pupil diameter of 3 to 4 mm. Occlude the patient’s nonoperative eye and ask the patient to fixate on the target. The surgeon must sight monocularly through the tube containing the fixation spot. The

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surgeon should then mark the cornea overlying the center of the pupil as seen through the operating microscope, ignoring the corneal light reflex. Centration errors are less likely to be symptomatic if a larger ablation zone is used.

Optical Considerations After Refractive Surgery Pupil Size According to the geometric-optical reasoning discussed earlier, when the entrance pupil is larger, the less central cornea becomes relevant for foveal vision. The Styles– Crawford effect argument states that these rays of oblique incidence are less visually significant on the retina. Night myopia, however, is a well-recognized entity dependent on noncentral rays, with the more myopic refractive error of the eye attributed to the greater plus power of the peripheral lens, which is exposed as the pupil dilates. If the peripheral lens is optically important in dim light, is not the peripheral cornea as well? Modifying the cornea from prolate to oblate shape—that is, making the cornea flatter in the center and steeper in the periphery—should contribute to the myopic shift occurring with pupil dilation and the peripheral zones of both the lens and the cornea curving or refracting more than the central regions. The optical importance of peripheral corneal irregularity and scars and of central corneal haze are subjects of investigation. Should the surgery produce irregular astigmatism of the central cornea, the effect on uncorrected and spherocylindrical-spectacle-corrected vision is uncertain. The consequences of decentration of surgery are also a matter of interest, as these may bring irregularity, scattering, or diffraction into the more fovea-relevant zone. Occasionally, after a long period, there is a diurnal fluctuation of refractive error after radial keratotomy, leading to increased myopia in the morning. Spectacles may be prescribed as the patient’s needs dictate.

Oval Topographic Zones After Astigmatic Surgery Successful surgery for astigmatism creates a spherical central corneal zone. The outline of this spherically surfaced region has oval isopters, the narrower aspect being the meridian where the difference in curvature between central and peripheral cornea is greatest. In conditions in which the pupil is large enough for the peripheral cornea to become relevant, the resulting second image or blur may be noticeable, particularly as sharp and blurred details vary with tortion of the eye or object being observed. Unlike the patient with uncorrected astigmatism whose vision is blurred, these patients have a clearer image created by the central zone so that the blurred effects may be readily perceived in contrast to the sharper aspect of the image. The combination of relatively sharp focus and a second image may be more disturbing than more diffuse blur.

Topographic Maps Frequently, the axis of astigmatism obtained after retinoscopy and subjective refraction (including refinement using a Jackson cross-cylinder) may be different from that obtained by topographic maps. In such situations, it is helpful to repeat the subjective refraction, beginning with the axis and power suggested by the topographic maps. Lenticular astigmatism should be suspected if there are significant disparities between the topography and subjective findings.

Astigmatic Dial The astigmatic dial provides an indication of axis and power of cylinder. The test is used when retinoscopy and the Jackson cross-cylinder fail to reveal astigmatism or seem to give untrustworthy results, as occurs in some patients with irregular postoperative astigmatism. The patient is asked, while fogged to about 20/40 acuity, to identify the lines that appear blackest and sharpest. The minus-cylinder axis is determined by multiplying the smaller “hour” number by 30. Minus-cylinder is added until the lines appear equally blurred. The plus-cylinder axis is 90° from the minuscylinder axis described earlier. Each step of plus-cylinder must be accompanied by a step of minus sphere.

Prescribing Spectacles After Refractive Surgery Because many patients may still need occasional spectacle correction after surgery, the spectacle prescription of a young postoperative patient may be deliberately allowed 0.25 to 0.50 D more minus than is needed for emmetropia at infinity so that sharpest vision may be achieved with a small amount of accommodative tone. This is most helpful for blunting postoperative diurnal fluctuation and aiding the patient to achieve better acuity for those tasks requiring sharpest distance vision. In the event that cycloplegia is required to confirm a daytime distance refraction, an aperture can be placed before the eye to simulate a less dilated pupil by blocking the peripheral rays. Regarding near vision, on the one hand, a large pupil in dim light causes increased myopia, requiring less add through involvement of the steeper peripheral cornea; on the other hand, in bright light, the pupil may be small enough for a pinhole-effect improvement of the range of accommodation.

Spasm of Accommodation The inability to relax the ciliary muscle suitably is termed spasm of accommodation. This may cause blurred vision, asthenopia, headache, or seeming increase in myopia. As in cases of uncorrected hyperopia or astigmatism, spasm of accommodation may develop in overcorrected myopes. With prolonged reading, the prepresbyopic adult may develop spasm of accommodation with consequent blurred

CHAPTER 3  Physiologic Optics for Refractive Surgery: An Overview

distance vision and discomfort. Iridocyclitis, anticholinesterase drugs used for glaucoma, and psychogenic stress may also cause spasm of accommodation. Exophoria may elicit convergence that is neurologically tied to accommodation. To treat accommodative spasm, one may correct astigmatism with spectacles; give as much plus as acceptable in a dry refraction; prescribe reading glasses or bifocals; or, if necessary, prescribe a period of pharmacologic cycloplegia.

Convergence Insufficiency Suppose that a young, spectacle-corrected myope has borderline convergence insufficiency and that surgical undercorrection of myopia produces discomfort with near vision because accommodation and, hence, accommodative convergence is decreased so that the inadequate fusional convergence is stressed. In this case, correcting the residual myopia with spectacles or further surgery may be required to remove the cause of the discomfort.

Presbyopia Having worn spectacles that undercorrect myopia, a presbyope may first encounter difficulty with near focus when the spectacles are changed to give full correction. The increase in demand for accommodation is even greater if the new full correction is accomplished at the cornea by contact lenses or corneal surgery, thereby losing the neareffectivity benefit of myopic spectacles. Moreover, the option of removing the spectacles for near vision is lost as well. The bifocal wearer who has been underminused has been seeing the middle distance rather than distant objects clearly through the top of the bifocals. If fully corrected with keratorefractive surgery, the middle distance, which was clear, may be blurred with and without reading glasses. The patient may decide either to get used to this or to obtain task-appropriate spectacles.

Prescribing for Presbyopia After Refractive Surgery General considerations are as follows: beginning with an add typical for the patient’s age, the resulting range of accommodation is measured and the add is adjusted to bring the patient’s near tasks within the zone of clarity and comfort. The standard tables of adds typical for various ages may suggest adds larger than necessary for patients who have had refractive surgery, whose corneas may cause a multifocal effect. Usually, the patient is best served by placing most of the range of clarity farther away than the chosen working distance, choosing a lesser add. This avoids blur of the middle distance and provides a larger range of accommodation.

Fluctuating Vision When fluctuating refractive error is found after surgery, such as the diurnal change seen after radial keratotomy, a

47

high-riding progressive add may provide useful adaptability for near vision, the appropriate add being found as needed.

Unequal Amplitude of Accommodation Eyes with unequal visual acuities, but equal amplitudes of accommodation, should be given equal adds. On the other hand, when the amplitudes of accommodation are unequal, adds are prescribed so that each eye is using approximately half of its respective amplitude of accommodation for clarity at the desired reading distance. The presumption here is that this amount of accommodation will be produced by equal accommodative innervation of the two eyes. The very anisometropic patient whose eyes have different ranges of accommodation may require unequal adds; the more myopic eye will need less plus in its bifocal segment. Patients with horizontal phorias require special consideration because more or less reading add may aggravate their phorias; adding or taking away increments of add in a trial frame may enable such a patient to judge a comfortable balance of focusing requirements and fusional amplitudes. If the presbyope has an esophoria, a stronger add will minimize accommodative convergence. On the other hand, the patient with exophoria may benefit from a slightly weaker add so that accommodative convergence will be stimulated. Patients with large cylindrical errors may require crosscylinder subjective near refraction, as tortion of the globe may occur with convergence and down gaze.

Bifocal Type Bifocal segments may be either round-top or flat-top. Image jump occurs with the abrupt change of prism power encountered as the line of sight crosses into a round-top segment. Flat-top segments minimize image jump on myopic and hyperopic spectacles. Image displacement increases as the object is viewed through the peripheral parts of a lens in the manner governed by Prentice’s rule. Flat-top segments minimize image displacement on myopic spectacles but accentuate it on hyperopic spectacles. The surgically undercorrected myope benefits from a flat-top segment with minimal jump (because the optical center of the add is near the top of the segment) and minimized prismatic displacement effect of the add (counterbalanced by the opposite effect of the underlying minus lens). The surgically overcorrected myope, now hyperopic, must choose between the two problems: a flat-top segment gives minimal jump and more displacement, while a round-top segment causes image jump with less displacement. In general, the top of the segment is usually approximately at the lower limbus. The segment height may be placed farther down for a first pair of bifocals in order to minimize the obstruction of distance vision. The segment may be placed higher in bifocals used primarily for reading as well as in pediatric cases of esodeviation. As the patient looks downward, the two eyes should enter the top of the segments simultaneously, which may require the optician to

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place segment heights so as to match facial asymmetry. Horizontal decentration of segments may be adjusted to assist the patient who has a horizontal phoria. Meridional anisometropia at the 180° axis (vertical power meridian) of the underlying distance correction gives the eyes increasingly unequal amounts of vertical prism as gaze turns down far enough to use the bifocal or trifocal. The difference in prism encountered may induce a symptomatic phoria or diplopia. Prentice’s rule states that the inequality of power in the vertical meridian multiplied by the distance below the optical center (in centimeters) is the induced vertical prism. One may expect that a new, induced phoria of 1.5 to 2 prism diopters is likely to cause problems. This may be minimized by slabbing off prism from the more myopic lens, compromising the underlying distance refraction, occluding one segment with translucent tape, lowering the optical centers of the distance correction, or using differing segment types for the two eyes. Of course, many of the potential problems of bifocal use may be avoided with single-vision reading glasses. When the amplitude of accommodation is small enough so that a useful near-vision bifocal segment cannot give clarity in the intermediate range, an intermediate correction may be desirable, given as trifocals (usually one-half the full add), progressive-add bifocals, or separate intermediatezone spectacles. The patient with an alternating tropia and suppression may be given a stronger add for one eye and a weaker add for the other eye, choosing at will to view the clearer of the two images. The range of accommodation may appear larger after keratorefractive surgery, after which the cornea has multifocal effect.

References 1. American Academy of Ophthalmology. Ophthalmology, Clinical Optics, Refraction, and Contact Lenses: Basic and Clinical Science Course. Section 3. San Francisco, CA: 2016. 2. Azar DT, Strauss L. Principles of applied clinical optics. In: Albert D, Jakobiec F, eds. Principles and Practice of Ophthalmology. 3rd ed. Philadelphia, PA: WB Saunders; 2008. 3. Bennett AG, Rabbetts RB. Clinical Visual Optics. London: Butterworths; 1985. 4. Duane TD, Jaeger EA, eds. Clinical Ophthalmology. Philadelphia, PA: Harper & Row; 1988. 5. Garcia GE. Handbook of Refraction. 4th ed. Boston, MA: Little, Brown; 1989. 6. Guyton DL. Continuing Ophthalmic Education: Retinoscopy: Minus Cylinder Technique. Philadelphia, PA: American Academy of Ophthalmology; 1986. 7. Guyton DL. Continuing Ophthalmic Video Education: Retinoscopy: Plus Cylinder Technique. Philadelphia, PA: American Academy of Ophthalmology; 1986. 8. Guyton DL. Continuing Ophthalmic Video Education: Subjective Refraction: Cross-Cylinder Technique. Philadelphia, PA: American Academy of Ophthalmology; 1987. 9. Michaels DD. Visual Optics and Refraction: A Clinical Approach. 3rd ed. St Louis, MO: CV Mosby; 1985. 10. Milder B, Rubin M. The Fine Art of Prescribing Glasses Without Making a Spectacle of Yourself. 2nd ed. Gainesville, FL: Triad Scientific Publishers; 1991.

11. Moses RA, Hart WM, eds. Adler’s Physiology of the Eye. 8th ed. St. Louis, MO: CV Mosby; 1987. 12. Rubin ML. The sliding lens paradox or the unexpected effect of longitudinal (‘to-and-fro’) motion of plus spectacle lenses. A treatise on lens effectivity. Surv Ophthalmol. 1974;17:180–195. 13. Rubin ML. Optics for Clinicians. 3rd ed. Gainesville, FL: Triad Scientific Publishers; 1978. 14. Sloane AE, Garcia GE. Manual of Refraction. 3rd ed. Boston, MA: Little, Brown; 1979. 15. Binder PS. Optical problems following refractive surgery. Ophthalmology. 1986;93:739–745. 16. Maloney RK. Corneal topography and optical zone location in photorefractive keratectomy. Refract Corneal Surg. 1990;6: 363–371. 17. Uozato H, Makino H, Saishin M, Nakao S. Measurement of visual axis using a laser beam. In: Breinin GM, Siegel IM, eds. Advances in Diagnostic Visual Optics. Berlin: Springer-Verlag; 1983:22. 18. Steinberg EB, Waring GO III. Comparison of two methods of marking the visual axis on the cornea during radial keratotomy. Am J Ophthalmol. 1983;96:605. 19. Thornton SP. Surgical armamentarium. In: Sanders DR, Hofman RF, Salz JJ, eds. Refractive Corneal Surgery. Thorofare, NJ: Slack; 1986:134–135. 20. Walsh PM, Guyton DL. Comparison of two methods of marking the visual axis on the cornea during radial keratotomy. Am J Ophthalmol. 1984;97:660–661, Letter. 21. Uozato H, Guyton DL. Centering corneal surgical procedures. Am J Ophthalmol. 1987;103:264–275. 22. Lancaster WB. Terminology in ocular motility and allied subjects. Am J Ophthalmol. 1943;26:122. 23. Ogle KN. Optics. 2nd ed. Springfield, IL: Charles C Thomas; 1968:149. 24. Bennett AG, Francis JL. The eye as an optical system. In: Davson H, ed. The Eye. New York, NY: Academic Press; 1962:101. 25. Fry GA. Geometrical Optics. Philadelphia, PA: Chilton; 1969:110. 26. Roberts CW, Koester CJ. Optical zone diameters for photorefractive corneal surgery. Invest Ophthalmol Vis Sci. 1993;34: 2275–2281. 27. O’Brart DPS, Gartry DS, Lohmann CP, Kerr-Muir MG, Marshall J. Excimer laser photorefractive keratectomy for myopia: comparison of 4.00- and 5.00-millimeter ablation zones. J Refract Corneal Surg. 1994;10:87–94. 28. Bonds AB, Macleod DIA. A displaced Stiles–Crawford effect associated with an eccentric pupil. Invest Ophthalmol Vis Sci. 1978; 17:754. 29. Enoch JM, Laties AM. An analysis of retinal receptor orientation. II. Prediction for physiologic tests. Invest Ophthalmol Vis Sci. 1971;10:959. 30. Mandell RB. The enigma of corneal contour. CLAO J. 1992;18: 267–273. 31. Cavanaugh TB, Durrie DS, Riedel SM, Hunkeler JD, Lesher MP. Centration of excimer laser photorefractive keratectomy relative to the pupil. J Cataract Refract Surg. 1993;19(suppl): 144–148. 32. Klyce SD, Smolek MK. Corneal topography of excimer laser photorefractive keratectomy. J Cataract Refract Surg. 1993;19(suppl): 122–130. 33. Fay AM, Trokel SL, Myers JA. Pupil diameter and the principal ray. J Cataract Refract Surg. 1992;18:348–351. 34. Schwartz-Goldstein BH, Hersh PS. Corneal topography of phase III excimer laser photorefractive keratectomy: optical zone centration analysis. Ophthalmology. 1995;102:951–962.

4 

Corneal Topography CYNTHIA J. ROBERTS

Introduction Corneal topography provides an assessment of the anterior corneal surface shape, and corneal tomography includes an assessment of the posterior corneal surface shape, pachymetry, as well as biometry of the anterior segment. Elevation and curvature are mathematically related; both can be calculated with any topographic/tomographic technology.1,2 The apex of the cornea is defined relative to curvature, as the point with the greatest curvature, and the vertex is defined relative to elevation, as the highest point on the corneal surface.1 However, after myopic refractive surgery, the corneal apex no longer has the greatest curvature. In addition, the highest point is a function of the plane against which it is measured, making this indeterminate as well. Therefore for the purposes of this chapter, the center of any topographic map will be referred to as the central corneal topography (CT) axis.

Curvature Curvature is mathematically defined as the rate of change of the tangent vector with respect to the arc length. Practically, this means that the curve that has the most bend over the shortest distance has the greatest curvature. To determine the curvature of a three-dimensional surface, such as a cornea, planes of intersection must be defined. The most common planes of intersection are termed the tangential planes, which all include the central CT axis.3,4 Each point on the corneal surface has two principal curvatures, which represent the maximum and minimum curvatures through the point. The best illustration of this concept is at the center of the cornea, where the difference in curvature between the flat and steep meridians through the center represents astigmatism of the cornea. Similarly, there are two principal curvatures at each noncentral point. For each point, a plane of intersection that is perpendicular to the tangential plane and includes the surface normal is termed a sagittal (or transverse) plane.4,5 The tangential and sagittal planes are illustrated in Fig. 4.1. For most topographic and tomographic systems, only the curvature in the tangential planes of intersection is calculated and displayed. By definition, curvature must be measured in units of inverse-millimeters. The radius of curvature at a point is

defined as the inverse of curvature; thus it is measured in millimeters. In other words, the greater the curvature, the shorter is the radius of curvature. For purposes of corneal topography, curvature is converted to units of diopters (D) using the familiar keratometric formula given in Eq. (1), which dates back to von Helmholtz and Gullstrand.6 (1 − 1.3375) r × 1000,

(1)

where r is the radius of curvature in millimeters. Although this formula is appropriate for the central measurement of keratometry, it presents a few problems of interpretation for topography, which measures a much larger region, approximately 8 to 10 mm of the corneal surface. The keratometric formula is valid only in the center of the cornea, where curvature is directly proportional to power.7 This will be discussed further in the Functional Representations section. Unfortunately, corneal topography/tomography manufacturers often incorrectly label curvature maps as power maps. Even though common, this terminology should not be adopted, as it is very misleading. It is critical to differentiate curvature from power to avoid misinterpretation of postoperative maps and their impact on vision. The most commonly used topographic curvature maps are axial maps and tangential curvatures maps.5 Synonyms for tangential curvature include meridional, instantaneous, or local curvature. Tangential curvature is converted to diopters using Eq. (1). Axial curvature is the average of tangential curvature over an interval from the CT axis to the surface point along the corresponding tangential plane of intersection.8 Axial curvature is converted to diopters using Eq. (2): (1 − 1.3375) a × 1000,

(2)

where a is the axial distance in millimeters and represents the distance along the surface normal from the surface point to the intersection with the CT axis, as illustrated in Fig. 4.2. In the center of the map, the axial and tangential curvatures are equivalent. However, because the axial curvature is essentially a running average of the tangential curvature, it smooths any extreme values of curvature. Therefore noncentral areas of flattening on the tangential map are steeper on the axial map and noncentral areas of high curvature on the tangential map are flatter on the axial map. For the special case of surfaces of rotational symmetry, the axial 49

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Light ray

Tangential or meridional plane

R1

Sagittal or transverse plane

R2

Tangential or meridional plane C

• Fig. 4.1

Schematic illustration of the meridional (tangential) and transverse (sagittal) planes of an optical surface. R1 is the radius of curvature in the tangential plane. R2 is the radius of curvature in the sagittal plane. C is the center of curvature in the tangential plane. (Adapted from Gao Y. Polynomial Modeling of the Corneal Surface to Improve the Measurements of Topography [Dissertation]. Columbus, OH: Ohio State University; 1994.)  

S1 C1 C2 A1

Reference A2

Axis

S2

• Fig. 4.2  The center of curvature of surface point S1 is C1, and the radius of curvature is the length of the segment between the two points. The axial curvature is relative to the reference axis, and axial distance of S1 is the length of the segment between S1 and A1, demonstrating how axial curvature underestimates areas of high curvature. Analogously, axial curvature overestimates areas of lower curvature, as illustrated by surface point, S2 with center of curvature, C2 and axial distance S2–A2.

• Fig. 4.3

  An example of the axial (right) and meridional (tangential) maps (left) of a normal cornea.

distance is equivalent to the radius of curvature and the axial curvature is equivalent to the tangential curvature. Examples of common clinical topographies are shown in Figs. 4.3 through 4.6, demonstrating the difference between axial and tangential curvature maps. Once again, the tangential and axial topographic maps represent diopters of curvature, not power.

• Fig. 4.4  An example of the axial (left) and meridional (tangential) maps (right) of postoperative myopic laser in situ keratomileusis (LASIK). Note that the paracentral steepening is shown only by the meridional map. The extremes in curvature are reduced by the averaging nature of the axial map.

• Fig. 4.5  An example of the axial (left) and meridional (tangential) maps (right) of an astigmatic cornea.

Elevation Topography As previously described, curvature is the spatial rate of change of slope, which itself is the spatial rate of change of surface height, or elevation. Unlike curvature, however, elevation (height) requires a reference from which to

CHAPTER 4  Corneal Topography

A

B

C

D

51

• Fig. 4.6  An example of the axial (left) and meridional (tangential) maps (right) of a keratoconic cornea.

measure. This is analogous to determining the height of a mountain, which can be measured relative to the ground at its base, or relative to sea level, or even relative to the center of the earth. The choice depends on the purpose. A mountain climber needs to know the height of the mountain above its base to determine how far to climb. However, the same climber also needs to know the height of the mountain above sea level to determine whether supplemental oxygen will be necessary in the higher altitudes of the climb. Both references are ultimately necessary. Similarly, corneal elevation can be measured relative to different references, including a plane, a sphere, an asphere, or a toric surface. Which is the best choice for the corneal reference? Just like the mountain, the answer depends on the application. First, it is important to remember that the choice of a reference is not an attempt to model the corneal surface. Rather, it simply provides a baseline against which to measure. A plane reference provides a surface of constant elevation as the baseline. However, since the major shape of the cornea is its overall curvature, use of a plane reference does not allow details to be appreciated. This is analogous to looking at the earth from space. The curvature of the earth can easily be observed, but the details of the surface topography, including the tallest mountains, are difficult to see. This is illustrated for two corneas in Figs. 4.7A and 4.7B. Despite the dramatic differences in surface shape for a keratoconic cornea and a postrefractive surgery cornea, it is not possible to differentiate the two corneas using a reference plane. The most common reference for corneal elevation is the best-fit sphere (BFS). The term “best-fit” means that an error minimization approach is used to determine the radius and center of the sphere. The BFS reference is quite convenient for a number of reasons. First, it provides a constant radius of curvature reference, which produces characteristic patterns of shape for various conditions, such as astigmatism, postrefractive surgery, or keratoconus. Second, due to the nature of the mathematical fit, the BFS can be considered a measure of the average curvature of the region over which the sphere is fit, with about half of the corneal surface fitting above the sphere and half fitting below the sphere.

BFS = 48.10D, 7.02 mm

• Fig. 4.7

BFS = 39.59D, 8.53 mm

The surface height relative to a plane for a keratoconic cornea (A) and a postmyopic refractive surgery cornea (B). Note that using a plane reference is not useful for determining characteristic patterns since the overall curvature of the cornea dominates. The corresponding elevation maps relative to a best-fit sphere are given for the keratoconic cornea (C) and postmyopic refractive surgery case (D). Note the best-fit sphere (BFS); thus the overall curvature is greater for the keratoconic cornea.  

These two concepts are illustrated in Figs. 4.7C and 4.7D. The topographies are not readily identified as keratoconus and postoperative myopic refractive surgery. The characteristic pattern of keratoconus has a high zone in elevation, corresponding to the region of high curvature at the location of the conus, surrounded by low areas of elevation. The characteristic pattern of postoperative myopic refractive surgery has a low zone in central elevation, corresponding to the central flattened zone, surrounded by a high zone corresponding the paracentral steepening. The relationship of the highs and lows in an elevation map to the highs and lows of curvature depends on the pattern of elevation. A central area that fits below the sphere and is circumscribed by higher zones is flatter than the reference sphere, similar to the myopic refractive surgery case already described. This is not a concavity or a depression; it is simply lower than the sphere, as illustrated schematically in Fig. 4.8. A central area that fits higher than the sphere has greater curvature than the sphere. In the case of astigmatism, however, the relationship between high versus low and steep versus flat is opposite, since these corneas usually fit with one meridian above the sphere and one meridian below, with a close match to the reference sphere in the center. In the periphery, the half of the cornea that fits above the BFS is the flat meridian and the half that fits below is the steep meridian. This is illustrated in Fig. 4.9, which shows both anterior and posterior surfaces having with-therule astigmatism. The steeper meridian is low (shown by the

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Reference sphere

Cornea

A

Cornea

Reference sphere

B

• Fig. 4.8

  Schematic illustration of a best-fit sphere to a centrally flat cornea (top), such as a postoperative myopic laser in situ keratomileusis (LASIK) patient, and the best-fit sphere to a centrally steep cornea (bottom), such as in keratoconus. Blue areas show negative values on an elevation map and red areas show positive values on an elevation map. Note that the cornea remains convex in the center on the top map even with negative elevation values. It is important to also note that flat areas are not always low on an elevation map. Peripheral low areas, such as in astigmatism, represent the meridian with the greatest curvature, such as in Fig. 4.9.

• Fig. 4.9

  Normal with-the-rule astigmatism, demonstrating the relationship between surface representations. Top left is the anterior elevation map and top right is the posterior elevation map. Both elevation maps demonstrate the same with-the-rule astigmatism, with the steepest axis below the sphere and the flat axis above the sphere. The bottom left is the tangential curvature map, also showing with-the-rule astigmatism. The bottom right is the pachymetry map.

blue colors), since it has greater curvature than the reference sphere and therefore falls away from the center faster than the reference sphere. Other references that are used include a user-defined sphere, an asphere, and a toric, usually in an attempt to fit as close as possible to the shape of the cornea. The disadvantage of all of these surfaces as a baseline reference is that characteristic patterns are not as readily apparent since part of the shape of the cornea is embedded in the reference. The average curvature of the corneal surface is no longer represented by the radius of the BFS. The importance of the choice of reference is given in Figs. 4.9 and 4.10, which show both the anterior and posterior elevation maps of an astigmatic cornea. Both the anterior and posterior elevation

• Fig. 4.10  Illustration of the importance of using a best-fit sphere by fitting the anterior best-fit sphere (R = 7.68 mm) to the posterior surface (A) and the posterior best-fit sphere (R = 6.40 mm) to the anterior surface (B). In both surfaces that are not best fit, the details of the surface shape are lost owing to the nonoptimal reference sphere.

maps show with-the-rule astigmatism, with the steep meridian at 90° fitting lower than the reference sphere. The color scales are the same for both anterior and posterior maps, giving the impression that the surfaces are similar, except that the astigmatism looks more prominent on the posterior surface. However, the BFS is quite different between the two surfaces. The posterior has much greater curvature than the anterior surface, which is evident in the 6.88-mm posterior reference sphere and the 8.33-mm anterior reference sphere. The lesson to be learned from this analysis is that the magnitude of the reference sphere is critical for interpretation of the elevation maps. Since elevation topography requires a reference, comparisons between maps must be done with care. For example, a 20-µm elevation above an 8.5-mm sphere is not the same as a 20-µm elevation above a 6.5-mm sphere. Similarly, pre- and postoperative comparisons must also be done with care owing to the likelihood of inconsistent references. A good method for comparing pre- and postoperative maps is by subtracting them. However, a fitting protocol must be chosen. If the pre- and postoperative surfaces are fit at the apex, then the assumption is that the apex was not modified, which is clearly invalid for the anterior surface after a myopic procedure. For this case, a peripheral fit is the best choice. What about the posterior surface? The influence of fitting protocols for interpretation of posterior surface topography is described in the next section.

Interpretation of Posterior Surface Elevation Topography Many articles have been published describing the specter of ectasia after refractive surgery.9 Misinterpretation of posterior surface elevation topography, however, may give a false impression regarding decompensation. The fitting protocol used to align the preoperative map to the postoperative map

CHAPTER 4  Corneal Topography

may have a significant impact on the appearance of the difference map. This has been demonstrated on a population of 2380 post–laser in situ keratomileusis (LASIK) patients with both preoperative and 6-months postoperative Orbscan II (Bausch and Lomb) tomography.10 Software version 2.0 was utilized to avoid the known posterior surface edge tracking error in software version 3.0 or higher.11 Three fitting protocols were used to provide evidence of peripheral swelling into the anterior chamber rather than central bulging of the posterior surface, as shown in Fig. 4.11. Peripheral inward swelling of the posterior surface results in central steepening and increased elevation that can be misinterpreted as ectasia. This is illustrated in Fig. 4.12.

Central bulge

Forward vault

Post

Post

Pre

Pre

Pre

Post

A

B

C

• Fig. 4.11

  Potential schematic models for increased central posterior curvature and elevation. Model (A) demonstrates central bulging. Model (B) demonstrates forward vaulting. Model (C) demonstrates peripheral inward movement, which indirectly causes the central posterior cornea to increase curvature.10

Inward peripheral swelling

Resultant fit

All-over fit

Apex fit

Peripheral fit

• Fig. 4.12

53

  The clinical result of using three fitting protocols for pre- to postoperative comparisons on each of the three models presented in Fig. 4.11. The top row represents the result of an all-over fit of the pre- and postoperative posterior surface, which would result in a central high zone and a peripheral low zone for all three models. The posterior surface elevation average difference map on the far right shows the average result of subtracting 2380 pre- and postoperative myopic laser in situ keratomileusis (LASIK) posterior surfaces, demonstrating a central high zone and a peripheral low zone, which is consistent with all three models. The second row represents an apex fit f or subtraction o f the pre- and postoperative posterior surface, which would result in a central neutral zone for all three models. The posterior surface elevation average difference map on the far right shows the average result of fitting 2380 pre- and postoperative myopic LASIK posterior surfaces, demonstrating a central neutral zone, which is consistent with all three models. The bottom row represents a peripheral fit for subtraction of the pre- and postoperative posterior surface, which would result in an all-over high zone for both the central bulging and forward vault models. However, for the peripheral inward swelling model, the fit would produce a central high zone and a peripheral low zone. The posterior surface elevation average difference map on the far right shows the average result of fitting 2380 pre- and postoperative myopic LASIK posterior surfaces, demonstrating a central high zone, which is consistent with only the inward peripheral swelling model.10

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Changes in the posterior surface curvature and elevation in the early postoperative period after LASIK have also been reported with both the GALILEI Dual Scheimpflug Analyzer (Ziemer)12 and with Pentacam (Oculus) tomography.13,14 Note that the study with the Pentacam initially reported no difference in the posterior surface between the preoperative and postoperative periods,13 but with reanalysis using paired statistics, a difference was found within the first postoperative month.14 This change was reduced when comparing the 1-month to 1-week time points. Therefore the pattern that early changes in the posterior surface resolve over time is consistent between devices. This would allow postoperative detection of ectasia on the posterior surface prior to affecting vision, since the epithelium would mask early changes in the anterior surface, where the majority of refraction occurs. Early ectasia might be indicated if a pattern of increasing posterior changes over time were detected rather than the normal postoperative course of decreasing posterior changes relative to the preoperative state.

Functional Corneal Representations Derived From Shape From the previously described surface shape representations, functional information can be derived related to the image-forming capabilities of the cornea. Light that impinges on the anterior cornea is refracted at the surface as a function of corneal shape and index of refraction and then propagated though the stroma. Light is further refracted by the posterior corneal surface and, subsequently, the crystalline lens. However, the majority of the refractive power of the eye lies at the anterior surface owing to the large difference in index of refraction between air and the first surface. The propagating light can be analyzed using multiple approaches depending on the clinician’s preference and the specific application.

Refractive Power Maps Optical power refers to the ability of a lens to focus light, with higher power correlating to greater refraction and lower power correlating to less refraction. Power is inversely proportional to focal length, which is defined as the distance from the anterior lens surface, along the optical axis, to the point where the refracted ray intersects the optical axis. Thus a smaller focal length is associated with higher power and a longer focal length is associated with lower power. The cornea can be modeled as a single refracting surface for the purpose of determining the contribution of the anterior surface to the overall power of the eye’s optical system. Corneal refractive power at a point is defined as a function of the inverse of the distance from the corneal vertex to the location where the refracted ray intersects the optical axis.7,15 This is illustrated in Fig. 4.13, for a target at infinity with

C B A Optical axis

c

b

a

• Fig. 4.13

  A schematic illustration of positive spherical aberration for a prolate ellipsoidal surface, going from a lower to higher index of refraction. The farther from the optical axis a parallel ray impinges on the single refracting surface, the greater the angle of incidence and the greater the Snell’s law refraction. This generates greater optical power in the periphery than in the center.

incoming parallel rays of light, and described mathematically by Eq. (3): P = n [ y + x(tan(q i − q t ))],

(3)

where the angle of incidence, qi = sin-1(x/a); n•sin(qt) = sin(qi); qt is the transmitted, refracted angle; a is the axial distance; n is the index of refraction; and x and y are 2-dimensional spatial coordinates. As can be seen in Fig. 4.13, light rays near the center of the cornea have a small angle of incidence relative to the surface normal; thus the refracted angle is also quite small. For this paraxial case, the sine of the angle can be approximated by the angle itself, sin(q) ~ q, and Eq. (3) can be simplified to Eq. (2). In addition, also near the center of the cornea, the axial distance is approximately equal to the radius of curvature, a ~ r. Under these conditions, Eq. (3) simplifies to Eq. (1). In contrast, light rays in the paracentral and peripheral cornea have a larger angle of incidence relative to the surface normal; thus the refracted angle is larger. In addition, the farther from the center, the greater is the difference between axial distance and radius of curvature.16 Therefore for the case of noncentral corneal surface points, neither approximation is appropriate and Eq. (3) must be used to calculate power. A comparison of the dioptric values for a prolate ellipsoid with eccentricity = 0.5, between Eqs. (1), (2), and (3), is given in Fig. 4.14. Note that the central value for all three maps is the same. The paraxial central region, where all three equations provide nearly the same values, corresponds to the region where all three maps have the same color. Eqs. (1) and (2) show decreasing curvature values from the center to the periphery; only Eq. (3) shows increasing power from the center to the periphery, indicative of positive spherical aberration. If either Eq. (1) or Eq. (2) were used beyond the central 1 to 2 mm to describe power, not only would the magnitude be inaccurate but also the direction of change. This reinforces the notion that both tangential and axial dioptric maps represent curvature, not power. The index of refraction most often used for the calculation of corneal refractive power is the keratometric index of

CHAPTER 4  Corneal Topography

A • Fig. 4.14

B

55

C

Three representations of a prolate ellipsoid with 0.5 eccentricity: (A) the refractive power maps based on the keratometric index of refraction and Eq. (3), (B) the axial curvature map based on Eq. (2), and the meridional (tangential) curvature map (C) based on Eq. (1). The paraxial region corresponds to the central green region common to all three maps. Outside of this region, curvature and power are not directly proportional.  

refraction, 1.3375, which attempts to take into account the negative power of the posterior cornea. Therefore any refractive power map based on an index of refraction of 1.3375 must be considered a total corneal power map, not an anterior surface power map. For example, a cornea with a central radius of curvature of 7.5 mm corresponds to a refractive power of 45 D. However, the anterior surface alone has a power of over 50 D, which can be calculated using the corneal index of refraction of 1.376. This presents problems when comparing preoperative corneal refractive power maps to postoperative corneal refractive power maps. Mandell showed approximately 11% error in calculating the surgically induced dioptric power difference if the index of refraction of 1.3375 is used under the assumption that only the anterior surface was surgically modified.17 Some topographic systems allow the user to choose an index of refraction for refractive power display, which allows greater flexibility for interpreting postoperative results.

Functional Optical Zone There are many definitions of functional optical zone (FOZ), or effective optical zone, in the literature.18–22 However, there is no consensus as to how to define the area of the cornea that produces the arguable concept of “useful vision.” The FOZ is often determined from curvature or even elevation maps. However, as previously discussed, both curvature and elevation maps relate directly to shape, not function. Therefore FOZ size should fundamentally be based on a functional representation rather than curvature or elevation. An approach has been described for determining FOZ from topographic measurements, which correlates with specific wavefront aberrations measured with an ocular wavefront sensor.23 The FOZ is calculated on the refractive power map using a region-growing algorithm that is based on a Bayesian classifier. The first step is to locate the seed area, which is defined as the flattest area bounded by a 2-mm diameter circle for myopic corrections or the steepest area bounded by a 2-mm diameter circle for hyperopic corrections.24,25 A threshold criterion is established based on

• Fig. 4.15

  Four examples of functional optical zone calculation after myopic laser in situ keratomileusis (LASIK), demonstrating how the region-growing algorithm conforms to various shapes depending on the pattern of the refractive power map.

the mean refractive power of the seed area and the standard deviation of the refractive power of the entire map. The region-growing algorithm starts from the seed point and continues until the threshold criterion is met. The final result produces the coordinates of the seed point as the center of the FOZ and the major and minor axes of the FOZ. It has been reported that the decentration of the FOZ correlates significantly with coma measured by a wavefront sensor, and the difference between the average magnitude of refractive power inside the FOZ versus outside the FOZ correlates significantly with spherical aberration as measured by a wavefront sensor.23 Several examples of the potential shapes of the FOZ are given in Fig. 4.15 for postoperative myopic refractive surgery.

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Anterior Corneal Wavefront Aberrations Maps of corneal wavefront can be calculated by ray tracing incoming parallel light rays through the anterior corneal surface and then decomposing the propagating wavefront using a Zernike polynomial analysis in a similar manner to that used in ocular wavefront sensors.26–29 In this way, induced aberrations due to refractive surgery can be analyzed at the corneal level, where they were created. Corneaderived wavefront aberrations can be useful to explain visual outcomes and complaints. Several topography systems provide corneal wavefront calculations.

Topographic and Tomographic Technologies The first technology to have been developed for the measurement of corneal surface shape, and still widely used, is Placido topography.30–33 A series of concentric rings are reflected from the corneal surface; the image of these rings is captured for analysis. Distortions in the mires can be analyzed to determine slope. From slope, all other surface representations can be calculated. The advantage of Placido technology is that the accuracy and performance are well documented, and the principles are familiar to most clinicians. The disadvantage is that the measurement is confined to the anterior surface only. Two types of systems are available for tomographic analysis of the cornea. One uses two scanning vertical slits, with 20 slit images acquired from each direction, for a total of 40 slit images, with overlap in a 7-mm diameter central area.34 The second technology uses a rotating slit, for a total of 30 to 60 slit images that are acquired based on the Scheimpflug imaging principle.5 The advantage of slit imaging systems is that they are able to acquire data on both the anterior and posterior corneal surface as well as the anterior surface of the crystalline lens. Posterior surface and pachymetry measurements are important to the refractive surgeon for surgical planning and postoperative evaluation. The disadvantage of slit imaging systems is that their accuracy is not well documented, especially for the posterior surface. The challenge is the lack of calibrated dual-surface models manufactured from materials that mimic cornealscattering properties.

Conclusions Corneal topography and tomography remain valuable tools for the refractive surgeon in planning and evaluating outcomes of ablative procedures. Any refractive practice without access to corneal topography is incomplete at best, even in the presence of high-resolution wavefront sensing. The wavefront sensor is unable to determine the source of the reported aberrations, whether it is the cornea or the lens, or even the source of induced corneal aberrations with refractive surgery, whether central or paracentral.

However, ray tracing through the surfaces measured with corneal tomography can provide corneal aberrations, with an understanding of their relationship to change in shape. Direct analysis of the corneal surfaces will allow a complete evaluation of the surgically induced modifications in shape and thus vision. Posterior surface analysis might lead to early detection of ectasia, with possible intervention prior to vision being affected. Ultimately, shape and vision are intimately linked; corneal topography/tomography allows understanding of how both are affected by refractive surgery.

References 1. American National Standards Institute. ANSI Z80.23-1999, Corneal Topography Systems – Standard Terminology, Requirements. New York, NY: American National Standards Institute, Inc; Approved October 18, 1999 2. Roberts C. Principles of corneal topography. In: Elander R, Rich L, Robin J, eds. Principles and Practice of Refractive Surgery. Philadelphia, PA: WB Saunders; 1997:475–498. 3. Roberts C. Corneal topography: a review of terms and concepts. J Cataract Refract Surg. 1996;22:624–629. 4. Bennett AG. Aspheric contact lens surfaces. Ophthal Opt. 1968;8:1037–1040, 1297–1300, 1311; 9:222–230. 5. Roberts CJ, Liu J, eds. Corneal Biomechanics: From Theory to Practice. Amsterdam: Kugler Publications; 2016. 6. von Helmholz H, Gullstrand A. Procedure of the rays in the eye imagery—laws of the first order. Appendix II. In: Southall JPC, ed. Helmholtz’s Treatise on Physiological Optics. New York, NY: The Optical Society of America; 1924:304. 7. Roberts C. The accuracy of ‘power’ maps to display curvature data in corneal topography systems. Invest Ophthalmol Vis Sci. 1994;35:3525–3532. 8. Klein SA, Mandell RB. Shape and refractive powers in corneal topography. Invest Ophthalmol Vis Sci. 1995;36:2096–2109. 9. Wolle MA, Randleman JB, Woodward MA. Complications of refractive surgery: ectasia after refractive surgery. Int Ophthalmol Clin. 2016;56:127–139. 10. Grzybowski D, Roberts C, Mahmoud A, Chang J. Model for nonectatic increase in posterior corneal elevation after ablative procedures. J Cataract Refract Surg. 2005;31(1):72–81. 11. Roberts C, Mahmoud A, Castellano D. Evaluation of the performance of the posterior edge tracker of the Orbscan II Corneal Topographer. Assoc Res Vision Ophthalmol. 2003;2548. 12. Smadja D, Santhiago MR, Mello GR, Roberts CJ, Dupps WJ Jr, Krueger RR. Response of the posterior corneal surface to myopic laser in situ keratomileusis for different amount of ablation depth. J Cataract Refract Surg. 2012;38(7):1222–1231. 13. Nishimura R, Negishi K, Saiki M, et al. No forward shifting of posterior corneal surface in eyes undergoing LASIK. Ophthalmology. 2007;114:1104–1110. 14. Roberts CJ, Dupps WJ Jr. Paired vs. unpaired significance testing: how improper statistical analysis altered interpretation of posterior surface changes after LASIK. J Cataract Refract Surg. 2014;40:858–861. 15. Bennett AG, Francis JL. The eye as an optical system. In: Davson H, ed. The Eye. New York, NY: Academic Press; 1965. 16. Roberts C. Characterization of the inherent error in a spherically biased corneal topography system in mapping a radially aspheric surface. J Refract Corneal Surg. 1994;10:103–116.

CHAPTER 4  Corneal Topography

17. Mandell RB. Corneal power correction factor for photorefractive keratectomy. J Refract Corneal Surg. 1994;10:125–128. 18. Maloney RK. Corneal topography and optical zone location in photorefractive keratectomy. Refract Corneal Surg. 1990;6: 363–371. 19. Gangadhar DV, Talamo JH. Corneal topography: adjunctive use in keratorefractive surgery. In: Azar DT, ed. Refractive Surgery. Stanford, CT: Appleton & Lange; 1997:174–175. 20. Holladay J, Janes JA. Topographic changes in corneal asphericity and effective optical zone after laser in situ keratomileusis. J Cataract Refract Surg. 2002;28(6):942–947. 21. Boxer Wachler BS, Huynh Vu N, El-Shiaty AF, Goldberg D. Evaluation of corneal functional optical zone after laser in situ keratomileusis. J Cataract Refract Surg. 2002;28(6):948–953. 22. Nepomuceno RL, Boxer Wachler BS, Scruggs R. Functional optical zone after myopic LASIK as a function of ablation diameter. J Cataract Refract Surg. 2005;31(2):379–384. 23. Mahmoud AM, Roberts CJ, Castellano D, Lembach RG. Functional optical zone size measured after LASIK. Assoc Res Vision Ophthalmol. 2004;45:221. 24. Mahmoud AM, Roberts C, Herderick EE, Lembach RG, Markakis G. The Cone Location and Magnitude Index (CLMI). Invest Ophthalmol Vis Sci. 2001;42(suppl 4):4825. 25. Qazi M, Roberts C, Mahmoud A, Pepose J. Topographic and biomechanical differences between hyperopic and myopic laser in situ keratomileusis. J Cataract Refract Surg. 2005;31(1):48–60. 26. Wang L, Dai E, Koch DD, Nathoo A. Optical aberrations of the human anterior cornea. J Cataract Refract Surg. 2003;29(8): 1514–1521.

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27. Vinciguerra P, Camesasca FI, Calossi A. Statistical analysis of physiological aberrations of the cornea. J Refract Surg. 2003;19(2): S265–S269. 28. Smolek MK, Klyce SD. Zernike polynomial fitting fails to represent all visually significant corneal aberrations. Invest Ophthalmol Vis Sci. 2003;44(11):4676–4681. 29. Buzzonetti L, Iarossi G, Valente P, Volpi M, Petrocelli G, Scullica L. Comparison of wavefront aberration changes in the anterior corneal surface after laser-assisted subepithelial keratectomy and laser in situ keratomileusis: preliminary study. J Cataract Refract Surg. 2004;30(9):1929–1933. 30. Klyce SD. Computer assisted corneal topography: High resolution graphic presentation and analysis of keratoscopy. Invest Ophthalmol Vis Sci. 1984;25:1426–1435. 31. Maguire LJ, Singer DE, Klyce SD. Graphic presentation of computer-analyzed keratoscope photographs. Arch Ophthalmol. 1987;105:223–230. 32. Wilson SE, Verity SM, Conger SL. Accuracy and precision of the corneal analysis system and the topographic modeling system. Cornea. 1992;11:28–35. 33. Koch DD, Wakil JS, Samuelson SW, Haft EA. Comparison of the accuracy and reproducibility of the keratometer and the Eyesys Corneal Analysis System Model I. J Cataract Refract Surg. 1992;18:342–347. 34. Cairns G, McGhee CNJ. Orbscan computerized topography: attributes, applications, and limitations. J Cataract Refract Surg. 2005;31(1):205–220.

5 

Wavefront Analysis DAMIEN GATINEL

Introduction The development of new instrumentation to measure human optical aberrations and the recent refinements in the excimer laser delivery systems have opened a new era in vision correction: patient-customized, wavefront-guided treatment. It has been known for a long time that the normal human eye suffers from many monochromatic aberrations that degrade retinal image quality.1–4 Current ophthalmic lenses correct defocus and astigmatism but still leave uncorrected additional aberrations. The pattern of these aberrations varies among individuals and reduces the optical performance of the eye for pupil diameters larger than 3 mm.3 Well-developed techniques previously proposed5 and developed in astronomy6 have been employed to estimate the aberration of the eye.3 In 1997, using adaptive optics, Liang et al. corrected optical aberrations beyond sphere and cylinder and provided normal eyes with supernormal optical quality4; similar results were obtained by other authors.7 The use of wavefront technology has since come into focus due to recent rapid advancements in technology to measure the optical properties of the human eye.8 The application of wavefront-sensing technology might enable the noninvasive observation of living retinal cone cells,9 the measurement of central nervous visual function by eliminating higher-order aberrations using adaptative optics, and the implementation of higher-order correction in everyday vision through intraocular lenses,10 customized contact lenses,11 or laser refractive surgery.12 Custom corneal ablation procedures involve the use of wavefront analysis to measure the aberrations of the eye beyond sphere and cylinder and to direct the photoablation on the cornea. Although conventional laser procedures increase higherorder aberrations,13–15 wavefront-guided profiles of ablation aim to correct both spherocylindrical ametropia and highorder aberrations to optimize the postoperative patient’s visual function. The limits of ocular performance are determined by the quality of the retinal image and by neural architecture and function. At maximal image quality, visual acuity should reach 20/8,16 or between 20/12 and 20/5, depending on pupil size,17 which is more than the usual 20/20 visual acuity. To achieve this “super vision,” two conditions must be present: the eye must be free of optical 58

aberrations and the pupil must be dilated to minimize the effects of diffraction. The cornea is the principal optical component of the human eye. Modern aberrometers are equipped with a corneal topographer system. Such instruments enable computation of the effect of the anterior and/or posterior corneal contribution to the ocular wavefront and, by subtraction, the effect of internal optics (the crystalline lens, or an intraocular lens in pseudophakic eyes). Clinicians are more familiar with the geometric conception of light propagating in a rectilinear fashion as rays. For a better understanding, this chapter will briefly describe some optical principles related to the field of optical aberration and diffraction that derive from the wave properties of light. After discussing the basics of the wavefront theory, we will show how it can be used to predict the optical performance of the human eye.

History of Wavefront: The Debate Concerning the Phenomenon of Light The exact nature of light has been an intriguing subject. From ancient times, many scientists have experimented with light in order to better understand its true nature.18 Among them, Willibrord Snell first formulated what is expressed today as Snell’s law of refraction to describe the properties of light propagation in optical media: ni sin i = nr sin r . This formula is discussed in Chapter 3. In 1690, Christiaan Huygens postulated that light originates from a pulsing source. From the source, pulses of light energy expand into space and create change in the substance that he called “ether,” which was supposed to surround us and be present in any substance. According to Huygens’s theory, light propagation showed similarities with that of fluid and gasses (Fig. 5.1). The concept of light emanating from a pulsing source raised the important point that energy would fluctuate as it propagates. When the distance from the source increases, the energy propagates in a parallel direction (Fig. 5.2). The light emanating from the point source at infinity would then appear to the observer’s eye as a flat wavefront.

CHAPTER 5  Wavefront Analysis

59

A wavefront propagates like the surface ripples that emanate from the point of impact of a stone tossed into a tank of water (Fig. 5.3). In a homogeneous medium, a monochromatic light source emits wavefronts that propagate at a constant speed in all directions from the source. At a given moment, the points in space located at the same distance from that source are in the same state of the value of the electromagnetic field. The wavefront is the envelope of these points and would be spherical in this case (Figs. 5.4 and 5.5).

How Does a Wavefront Propagate?

• Fig. 5.1

  According to the Huygens’ principle, every point on a propagating wavefront serves as the source of spherical secondary wavelets such that the wavefront at some later time is the envelope of these wavelets. The secondary wavelets have the same frequency and speed as that of the wave emanating from the source S when they propagate in the same (isotropic) medium. Fresnel later successfully modified Huygens’s principle, adding the concept of interference.

This is equivalent to the parallel light rays emanating from infinity. Here, the rays represent the direction of propagation of the wavefronts and are mutually perpendicular. Geometric optics embraces the concept of the light ray and wavefront of Huygens. It has allowed the design of many optical instruments, such as telescopes and microscopes. The earlier Newtonian concept of light particles was refined two centuries later (in 1905) by Albert Einstein with the introduction of the photon as the smallest particle of light that retains the information from the initial source. This important step allowed explanation of some observed physical properties of light and prediction of the properties and feasibility of laser systems. Both ideas of light as a wave and light as a particle remain today as the wave/particle dualism in optics. Optical aberrations and diffraction are physical events that derive from the wave properties of light. We will first review these properties and then study the principles of wavefront-guided ablations.

Wavefront Theory What Is a Wavefront? A wave, being a light wave or a sound wave, is defined by its frequency (number of oscillations per unit of time) and its propagation speed. The wavelength of a monochromatic light wave is a function of these two parameters. The visible spectrum corresponds to wavelengths between 400 and 700 nm.

The consecutively emitted wavefronts by a monochromatic light source are separated by equal time intervals. This property allows one to prove the law of refraction of Snell (known as Snell-Descartes in France; Fig. 5.6). Refraction occurs when the wavefront meets a different environment and its rate of spread is reduced. If a wavefront of light propagates in the empty medium, the speed propagation is designated as “c.” If a planar wavefront is refracted by a plano lens, its speeds decrease proportionally to the value of the refractive index of the lens (Fig. 5.7). As the frequency is unchanged, the wavelength is reduced in the lens. When the surface of the plano lens is parallel to the wavefront envelope, no phase shift will appear and the shape of the wavefront will be unchanged as it exits from the lens. When the surface of the plano lens is not parallel to that of the incident wavefront, the latter will undergo a deviation but no shape modification. Because of the skewed position of the lens as compared to that of the wave, part of it will undergo the reduction in speed while the other part still moves on at unchanged speed. This will cause a change in the position of the whole wavefront (Fig. 5.8). If a planar wavefront propagates through a planar convex lens, the optical path will be different for the wave entering the lens at a different location (the optical path will be maximal in the center of the lens). The lens introduces a retardation of the phase of the central portion of the wavefront relative to its edges. This will cause the emerging wavefront to converge (Fig. 5.9). Thus given a flat wavefront traveling through a perfect convex lens, the resulting emerging wavefront will be changed to spherical so that all the light rays perpendicular to the wavefront come exactly in one point. The wavefront distortion can be considered as a phase retardation distribution relative to its most advanced point. After having traveled in a homogeneous medium (constant refractive index), the wavelengths that have the longest path will exit later than those with a shorter path. This difference in optical path can be expressed in microns. When different colors of light propagate at different speeds in a medium, the refractive index is wavelength dependent. A well-known example is the glass prism that disperses an incident beam of white light at equal angles. Because the various optical media have a different refractive

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DENSE AND HOMOGENEOUS MEDIA

DESTRUCTIVE INTERFERENCE

INCIDENT WAVEFRONT

CONSTRUCTIVE INTERFERENCE

• Fig. 5.2  The principle of Huygens was completed and mathematically formulated by Fresnel at the beginning of the nineteenth century, including the concept of interference. This concept explained that there was no wave reissued “backward” by “light vibration” contiguous sources. In a dense homogeneous medium, there is little or no light scattered sideways or backward. Earth’s atmosphere contains millions of molecules in a cube whose side lengths would be equal to that of a visible light wavelength (e.g., 500 nm). This is related to the size of the molecules in the nanometer range, while the visible light wave is of the order of a micron. Consider that a plane wave propagates in a medium dense and homogeneous, composed of many contiguous atoms, represented here schematically by dots. At the level of atoms, the light is absorbed and reemitted by electrons. This phenomenon is responsible for changes in the phase of the wavefront, which can then appear as slowed in the propagation media (the index of refraction is proportional to the slowdown of the transmitted wave). Perpendicular to the propagation direction, we can form many pairs of atoms separated by half a wavelength (atoms are about a thousand times smaller than the relevant visible wavelength). Given the principle of Huygens, each atom reemits the incident wave in all directions. Thus in a perpendicular direction from the main direction the light spread, there is destructive interference for each of these pairs of atoms, which explains the absence of lateral diffusion of the light. Given the principle of conservation of energy, there cannot be constructive interference in all directions. In a sparse environment (e.g., upper atmosphere), because of the scarcity of the atoms and molecules, the phenomenon of interference disappears. Then, there are random encounters between light and atoms of lateral reemissions, which can show that they are proportional to the fourth power of the frequency of the considered light wave. Blue (higher frequency) is more scattered than red, which explains the color of the sky: our eyes perceive a bluish hue because the blue wavelength is more scattered laterally and toward the ground.

index for each wavelength of light, chromatic aberration in the human eye is the result of the different focus location for different wavelengths. Thus chromatic aberrations correspond to departures from perfect imaging that are owing to dispersion and make their appearance only in polychromatic light. They cause a diminution of the retinal image contrast.19 However, there is a larger gain when monochromatic aberrations are corrected without correcting chromatic aberration than when polychromatic aberrations are corrected alone.20 There is currently no practical solution to correct for polychromatic aberrations; we will consider only the field of the correction of monochromatic aberration in the rest of this chapter.

What Is Diffraction? Diffraction involves the bending of waves around obstacles. It is generally guided by Huygens’s principle, which states that every point on a wavefront acts as a source of tiny wavelets that move forward with the same speed as the wave; the wavefront at a later instant is the surface that is tangent to the wavelets. The presence of an obstacle induces a distortion in the wavefront propagation (Figs. 5.10 and 5.11). Thus it is impossible to obtain a perfectly spherical wavefront. In the case of the diffraction by an aperture, the narrower the aperture, the greater the effect on the wavefront that has propagated beyond the aperture. Conversely,

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A

A

B

B • Fig. 5.3  (A) When a stone is tossed into a tank of water, the surface ripples emanate from the point of impact and spread out in twodimensional circular waves. This imagery can be extended to three dimensions, where a small pulsating sphere surrounded by a fluid would generate pressure variations propagating outward as a spherical wave as it expands and contracts. (B) Three-dimensional representation of light propagation showing the wavefronts as concentric spheres that increase in diameter as they expand out into the surrounding space of an idealized point source of light, S. Rays are orthogonal trajectories of the wavefront (one ray is represented as a dotted line emanating from S).

A

B

• Fig. 5.5  As a spherical wavefront propagates, its radius increases. A small area of the incoming wavefront, located at a far distance from the source, closely resembles a flat portion of a plane wave: at a given time, all the surfaces on which the disturbance has a constant phase form a set of planes, each perpendicular to the direction of propagation (A). For a “perfect eye” (diffraction limited), the optical paths of all the rays emitted by a single point source are identical: the light oscillates an identical number of times from the source to the fovea. The planar wavefronts are converted into spherical wavefronts centered on the fovea (B).

C

D

• Fig. 5.4  A propagating wavefront of light can be defined by the locus of the points lying in the same optical path from the source (A, C). When the optical path length is the same for all the rays emitted by a source (A), they interfere constructively to produce a sharp image of the source (B). When the optical path length is different for the emitted rays (C), they arrive at different phases; the system is aberrated and the image suffers from degradation (D).

the larger the entrance pupil in an optical system, the less diffraction will impact the image quality.21 Diffraction alone causes a minimum blurred image called an Airy disk. It represents the “spread” of the incident light caused by pupil diffraction and makes perfect stigmatism practically impos-

sible with any diaphragm optical system. The diffraction phenomenon is wavelength dependent. The longer the wavelength, the narrower the aperture and the larger the light spread. Aberrations in the optical system of the eye counteract the improvements in resolution that are expected

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NORMAL TO THE SURFACE

• Fig. 5.6

  In the left media, the wavefront moves at speed vi. In the right media, with a higher refractive indice, the propagation speed (vr) is reduced. The wavefront forms an angle θi with normal to the surface and is deflected with an angle θr after refraction. Given the principle of Huygen’s, the time taken by light to go from C to B is the same as for getting from A to D. This time equals distance divided by the speed, and one may write: CB/vi = AD/vr. According to the geometry of the figure and observing that θi is equal to the angle (CAB) and θi is equal to the angle (ABD), one can express that the distance CB = AB sin(θi) and that the distance AD = AB sin(θr). The first equation becomes AB sin(θi)/Vi = AB sin(θr)/vr. We can simplify by AB and multiply by a constant c (speed of light in a vacuum) and get that sin(θi) c/vi = sin(θr) c/vr. The ratio between the speed of light in a vacuum and light in the medium is equal to the index of refraction of the medium: ni = c/vi = 1 if the incident medium is air and nr = c/vr. Finally, we obtain that sin(θi) = sin(θr) nr.

• Fig. 5.8  When a beam of light impinges on a glass interface of indice nt at a non-null angle, the transmitted wavefront is slower than the incident electromagnetic wave because the atoms in the region of the surface of the transmitting medium reradiate the wavelets at a slower speed. These wavelets combine constructively to form a refracted beam that is bent as it crosses the boundary. The fact that the incident rays are bent is called refraction. The path actually taken by light in going from point A to point B is the shortest optical path length: OPL = ni × OA + nr OB. Differential calculus leads to the expression: ni × sin(θi) = nr × sin(θr).

• Fig. 5.9  When a portion of wavefront (WF) passes through a material of nonuniform thickness, it is distorted. Because the thickness varies, it causes the rays having the same OPL to bend and take on a spherical shape beyond the lens. In this example, the lens acts as a refracting device that converts a beam of plane waves into converging spherical waves. This assertion is equivalent to the geometrical optics assertion that when a parallel bundle of rays passes through a converging lens, the point to which it converges is a focal point of the lens (insert).

• Fig. 5.7  Representation of a beam of light traveling in a vacuum at a speed c and impinging on a glass interface at a null angle. The glass atoms scatter light; the transmitted wave propagates with an effective speed, less than c. In addition, the wavelength of light decreases in the glass plate, but the oscillation of the wave (frequency) remains constant. When the wave emerges from the glass, its speed is c again.

according to diffraction theory with increasing pupil size. In the normal eye well corrected for sphere and cylinder, higher-order aberrations that are unmasked by the pupil dilation will start to degrade the image quality more than diffraction for pupil diameters greater than 3 mm. The diffraction phenomenon, which is consubstantial of the wave properties of light, can be used for the design of multifocal diffractive intraocular optics (IOLs). In such design, diffraction is not initiated by the passage of light through a pupil or its deviation by an obstacle but

CHAPTER 5  Wavefront Analysis

A

63

B • Fig. 5.10  The diffraction causes the deviation of light from rectilinear propagation, which is not caused by refraction or reflection. Diffraction occurs when the wavelength is large compared to the aperture (A); the waves then spread out at large angles into the region beyond the obstruction. According to the Huygens–Fresnel principle, every unobstructed point of a wavefront serves as a source of spherical secondary wavelets. Thus the multiple wavelets emitted from the aperture interfere constructively or destructively beyond the aperture (B). When the aperture is very small, the parallel beam is reduced to a wave that propagates in all directions (A). The larger the aperture, the less diffraction will take place (B).

f

f

S

A

L

L

f

f *

S

B

L

*

L

PSF

C

• Fig. 5.11  As opposed to the geometrical optics, where light rays propagate in rectilinear fashion (A), physical optics deals with light waves emanating from a source (B). Because of the diffraction caused by the edges of the aperture, the transmitted wavefront is slightly distorted beyond the aperture (*). This causes the irradiance produced by any optical system with one or multiple diaphragms to take the form of a blurred spot over a finite area (B). This patch of light in the image plane is called the point-spread function (PSF). Diffraction thus destroys stigmatism (C). Schematic representation of the irradiance produced by the optical system free of aberrations, which corresponds to the diffraction figure of the input source. When no aberrations are present, an Airy pattern is formed in the image plane.

rather by the controlled spatial modulation of the IOL thickness.

Diffraction and Fourier Transform The Fourier transform has become a powerful analytical tool in diverse fields of science. In some cases, the Fourier transform can provide a means of solving unwieldy equations that describe dynamic responses to electricity, heat, or light. In other cases, it can identify the regular contributions to a

fluctuating signal, thereby helping to make sense of observations in astronomy, medicine, and chemistry. Light waves can be represented as periodic oscillations of the electromagnetic field. Fourier analysis (or spectral, or harmonic, analysis) indicates that any periodic function can be fairly well approximated by the sum of a series of sinusoidal terms. Given a periodic function (wave) in the space domain, it is possible to break it up into its Fourier components. The Fourier transform accomplishes this by breaking down the original time-based waveform into a series of sinusoidal

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Complex signal Coefficients 0.1 0.3 0.08

Harmonics x x x

Sin θ Sin 2θ Sin 3θ

0.4 0.3 θ (degree)

0.2 0.1 0

-0.1 -0.2

-0.3 -0.4

0

50

100

150

200

250

300

350

Amplitude

0.3

Fourier spectrum 0.1 0.08

Frequency

• Fig. 5.12

Any periodic signal (full line) can be broken down into fundamental harmonics selectively weighted (dotted lines). Conversely, the addition of the weighted fundamentals allows reconstruction of the original signal. This is the basis of Fourier analysis.  

terms, each with a unique magnitude, frequency, and phase.22 This process, in effect, converts a waveform in the time domain that is difficult to describe mathematically into a more manageable series of sinusoidal equations. The Fourier spectrum can be represented by displaying the frequency along one axis and the magnitude (or amplitude) along a second axis. Plotting the amplitude of each sinusoidal term versus its frequency creates a power spectrum, which is the response of the original waveform in the frequency domain. Inversely, the original periodic function can be synthesized by putting the proper spectral components together. Fourier series are generally the sums of many waves of many frequencies. To illustrate this concept, we can take as an example the decomposition of a sound or any periodic signal in its different harmonics (Fig. 5.12). The ear formulates a transform by converting sound—the waves of pressure traveling over time and through the atmosphere—into a spectrum, a description of the sound as a series of volumes at distinct pitches. The brain then turns this information into perceived sound. The sound can be reconstructed with fidelity by adding the harmonics that were present in the initial decomposition. This may also allow studying the effect of

the removal (filtering) of a particular harmonic (i.e., remove a particular optical aberration). When a plane parallel beam of monochromatic light is incident upon a small aperture, the diffraction pattern observed at a very large distance from the aperture along the optical axis will contain a very good approximation of the Fourier transform of the aperture function. These conditions (large distance between the aperture and the plane of observation of the diffractive pattern) are termed of Fraunhofer type (Fraunhofer diffraction). The Fourier transform can also be displayed in the focal plane of a lens following the diffractive aperture.23 If light is generated by a monochromatic source, such as a laser, the light waves that are generated are derived from the same source and exhibit a fixed relationship between their phases. This kind of light is said to be coherent and interference will be an important factor to consider. In daily life, light waves are emitted by effective independent sources (sun, lightbulbs, and so on). Even if these sources were monochromatic, the relations between the waves converging to the image plane would vary randomly. The quantity determining the net effect of these random superpositions is the average light irradiance. Thus at optical wavelength, the only detectable optical signal is the irradiance that is proportional to the square of the Fourier transform of the optical disturbance within the aperture (Fraunhofer irradiance), which corresponds to the point spread function for incoherent imaging. Simply put, in examining the optical properties of the human eye, the application of these concepts allows prediction of how the light emanating from a single point source will be imaged on the retina by combining the effects of both diffraction and ocular aberrations. This is achieved mathematically by computing the square of the Fourier transform of the ocular wavefront within the exit pupil. The inspection of the retinal point spread function is of clinical importance, as the light spread pattern may provide insights to some visual disturbances such as halos and monocular diplopia.

Ocular Aberrations Paraxial optics, or first-order optics, rely on the assumption that the height of incident light rays from the optical axis is small and that the considered optical systems are free of aberrations. In such idealized conditions, spherical surfaces yield perfect imagery. Real-life optical systems such as the human eye are not perfect; the description of their optical properties falls out of the paraxial domain. The departures of the idealized conditions of paraxial optics are known as higher-order aberrations. Two main types of aberration can be distinguished: chromatic aberrations (which arise from the fact that the refractive index is actually a function of frequency or color) and monochromatic aberrations. The latter fall into subgroupings, such as spherical aberration and coma. The monochromatic optical aberrations of optical systems increase as the incident ray height increases (Fig. 5.13).

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65

on the fovea. Depending on the amount of this spreading, a reduction in contrast sensitivity and visual acuity can result (Figs. 5.16 and 5.17). There have been only a few studies on the second- and higher-order aberrations of the eye in the peripheral visual field.26,27 These studies show that optical aberration increases rapidly away from the fixation axis. We will focus on the aberrations impairing foveal vision.

Wavefront Measurement

• Fig. 5.13  Spherical aberration of a lens. Rays striking the surface at a greater distance above the axis are focused nearer the vertex. Those rays are stopped when the pupil is narrow. When the pupil is large, the marginal rays are bent too much and focus in front of the paraxial rays. The distance between the axial intersection of a ray and the paraxial focus is known as the longitudinal spherical aberration. Spherical aberration shifts the light out of the central disk to the surrounding rings. If a screen is placed at the focal plane of such a lens, the image of a point source will appear as a bright central spot on the axis surrounded by a symmetrical halo delineated by the cone of marginal rays. The envelope of the refracted rays is called a caustic.

The normal emmetropic eye is free of aberration when its pupil diameter is less than 2.5 mm. At that pupil diameter size, the diffraction by the edges of the pupil is the only factor that governs the size of the retinal image of a point source. When the pupil diameter increases, the quality of the retinal image decreases owing to the increase in optical aberrations4,24 (Fig. 5.14). However, for an eye that would be free of optical aberration, the quality of the retinal image would increase when the pupil dilates owing to the reduction of the effect of diffraction. Such an eye would be said to be diffraction limited. A signal must be sampled with a frequency at least twice the frequency of the signal itself. The retinal surface is tiled with photoreceptors of discrete areas (Fig. 5.15). This imposes an upper limit to the resolution capacity of the human eye, which is called the Nyquist limit. The sampling frequency of the foveal cone mosaic is about 120 c/deg. The Nyquist limit, or maximum detectable frequency without error, is thus half the sampling frequency. Therefore the foveal cones offer a maximal sampling rate of about 60 c/ deg (equivalent to a 20/10 line on a letter acuity chart).25 When spatial frequencies that exceed this limit are formed on the retina, they cannot be correctly interpreted and the image is said to be aliased. In the human eye, these aliases form irregular shapes. Ocular aberrations are usually quantified in terms of a wavefront aberration that is expressed in microns. They result in an increased spread of the light emanating from an incoherent light point source imaged by a fixating patient

Analysis of human ocular optical aberration relies on the pioneering work of Hartmann and Tscherning in the nineteenth century.28,29 Hartmann described the principles of “outgoing” objective wavefront analysis. After reflexion of an incident coherent monochromatic light wave on the fovea, the outgoing wavefront is captured outside of the eye on a charge coupled device (CCD) matrix. The analyzed wavefront corresponds to the conjugated effects of all the ocular media (vitreous, crystalline lens, cornea, and tear film). Conversely, Tscherning wavefront measuring machines allow the study of wavefront distortion through the analysis of the image of a distorted projected mire on the retina (ingoing reflective aberrometry). A similar principle is used today by sequential laser ray tracing systems. Automated skiascopy using infrared light projected through a rotative slit scanning can also be used to study the optical path differences and obtain a wavefront reconstruction. Other devices soliciting subjective patient participation, such as spatially resolved refractometry (ingoing aberrometry), are not used for clinical examinations. All of these systems share a common principle: the wavefront analysis is performed through the study of the distortion of an emitted signal. Because of their widespread use, the wavefront reconstruction using the Hartmann–Shack system will be presented here.

Outgoing Reflective Aberrometry Using Hartmann–Shack Wavefront Analyzers These machines are based on the Scheiner disk principle, named after a seventeenth-century philosopher and astronomer. This ingenious apparatus allowed detection of the blur caused by the optical aberrations of the eye (Fig. 5.18). This technique was refined by the consecutive work of Hartmann and Shack.30 The principal steps leading to wavefront detection and analysis are the following (Figs. 5.19–5.23): • emission of an incident light ray centered on the fovea • detection of the reflected wavefront out of the eye using a microlenslet array • focalization of the wavefront on a CCD device by each microlenslet (the wavefront is broken down on different contiguous portions) • The location of the spot corresponding to the portion of the refracted wavefront is compared to the reference location (that corresponds to a flat/nonaberrated wavefront).

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A

B

C

D

E

F

G

H

• Fig. 5.14  Wavefront (A, C, E, G) and point-spread functions (B, D, F, H) as a function of the pupil diameter for a typical uncorrected slightly simple hyperopic astigmatic eye (OPD scan, Nidek). Note the increase of the wavefront error RMS value with pupil dilation, in great part due to the increase in high-order aberrations (A, C, E, G). The point spread function (PSF) represents how a single object is imaged by the optical system; at 3 mm, it resembles a diffraction-limited PSF (B). When the pupil dilates, high-order optical aberrations unmask and inspection of the corresponding respective PSFs reveals asymmetric enlargement (D, F, H). WF, Wavefront.

CHAPTER 5  Wavefront Analysis

• Fig. 5.15  For an eye limited only by diffraction and chromatic aberration, the image of an optotype falling on the photoreceptors requires one photoreceptor line per dark and light bar to be detected. In the fovea, the cones are equally spaced and the distance between two adjacent cone areas is about 3  µm. If the size of the letter is decreased, undersampling by the foveal cones would occur and the pattern would not be correctly detected. In the represented conditions, the visual acuity of this eye would be approximately 20/10.

• Fig. 5.17  For a given spatial frequency (defined by the number of light and dark bars per degree of visual field), the perceived image has a lower contrast owing to the presence of diffraction and possible optical aberrations after passing through the eye optical system. The contrast of the observed vertical sinusoidal grating can reduce to its threshold, that is, the value to which the subject is not able to discern its orientation.

A

B • Fig. 5.16

67

  In an eye with no optical aberrations (A), the point-spread function (PSF) corresponds to an Airy disk pattern. If the source is made with two components, such as the bars of a Snellen E letter, two juxtaposed Airy patterns will result. When these patterns overlap, a certain amount of ambiguity exists in deciding when the two systems are individually discernible or to be resolved. Lord Rayleigh’s criterion states that the sources are resolved when the center of one Airy disk falls on the minimum of the other Airy disk pattern (A, yellow and purple PSF). This condition is achieved in the top part of the figure. The retinal image is sharper, and the area under the modulation transfer function (MTF) curve is maximal (A). In the presence of optical aberrations (B), the PSF is broader and the alignment is less precise, resulting in a blurred Snellen E letter and reduced area under the MTF curve.

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• Fig. 5.21

  By contrast, an aberrated eye reflects a distorted wavefront (WF). The slope of the wavefront is different in front of each lenslet.

• Fig. 5.18  The Hartmann aberrometer derives from the seventeenthcentury Scheiner disk. The optical path length is related to the number of times the light wave must oscillate traveling from one point to another. When aberrations are present, the optical path of rays emanating from a single point source will differ to the fovea. The observer will see two images instead of one. When there are no optical aberrations (insert), the OPL is the same for all the light rays traveling from the object point to the image point.

• Fig. 5.22

  The local slope of the wavefront is different in front of each lenslet. The measure of the displacement of each spot from its corresponding lenslet axis allows the computation of the local slope of the wavefront. A mathematical integration of the slopes leads to the three-dimensional reconstruction of the wavefront envelope.

• Fig. 5.19

  Reflected light from a point source on the retina will emerge from a perfect eye as a plane wave. This reflected wavefront (WF) is then focused by a lenslet array in a perfect lattice of point images. This focusing is achieved in the plane of the entrance pupil of the eye.

A

• Fig. 5.20  When no optical aberrations are present, each image focused by a given lenslet falls on the optical axis of the lenslet. WF, Wavefront.

B

C • Fig. 5.23

D

Examples of CCD video of a Hartmann-Shack wavefront sensor after focusing of the array of lenslets of different altered wavefronts: (A) diffraction-limited eye, (B) defocus, (C) coma, and (D) spherical aberration.  

CHAPTER 5  Wavefront Analysis

A

69

B • Fig. 5.24  (A) Diagrammatic illustration of the laser dot matrix of a Tscherning aberrometer (wavelight, Tscherning aberrometer). (B) Retinal snapshot after projection of the laser grid on the fovea. The location of the centroids (colored spots) is performed by the software. This dot pattern map is then compared to a reference pattern map of an eye without aberration.

• The average slope of each wavefront portion is calculated. • Mathematical integration calculus allows reconstruction of the three-dimensional shape of the wavefront envelope using Zernike polynomials. These polynomials are selectively weighted depending on their respective contribution to wavefront distortion. The number of Zernike polynomials and the number of microarray lenslets limit the accuracy of the wavefront detection. For an ideal eye, emmetropic and free of any monochromatic aberration (diffraction-limited eye), the emerging wavefront is flat. There is no deviation from the expected location of the spots imaged by the microarray lenslets because each refracted portion of the wavefront is flat and parallel to the lenslet. If the wavefront was measured “in the eye,” it would theoretically be spherical and centered on the fovea. When aberrations are present, they cause a geometric shift of the spots away from their reference position. The amount of deviation is directly related to the slope of the wavefront.

• Fig. 5.25

  Wavefront analysis using laser ray tracing: a laser collimated beam (L) is shone through different locations of the entrance pupil (ingoing aberrometry) after mirror deflections (M). During the scan of the pupil, the deviation of the position of each ray from its reference position Δ(xy) is registered sequentially on a numerical camera (C). The reference axis is shown in red. In subjective aberrometry, the subject adjusts the incident angle of light until the retinal spot intersects the reference spot.

Wavefront Study With Retinal Imagery The deformed signal is measured at the retinal level.

Tscherning Analyzing System A coarse array of light rays is obtained from the filtration of a 532-nm laser radiation through a perforated mask. Each beam has a diameter of 0.5  mm. The rays are projected on the retina on a surface of approximately 1 mm2 (Fig. 5.24). The image is then imaged on a CCD camera through the 0.9-mm central area of the cornea that is assumed to be free of optical aberrations. The retinal spot pattern is analyzed and compared to the theoretical distribution of an aberration-free eye. The displacement of the retina spots from their aberration-free position is used to calculate the wavefront envelope.

Retinal Ray Tracing The procedure is analogous to that of the Tscherning procedure, but the spots are distributed sequentially to avoid reconstruction errors, especially for highly aberrated eyes (Fig. 5.25).

Ingoing Adjustable Refractometry The rays are emitted through different precise locations in the entrance pupil, similar to the principle of the Scheiner disk. If aberrations are present, double images will be perceived by the patient. The angle of deviation necessary to superimpose the image on the retina is proportional to the local wavefront distortion.

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Double-Pass Aberrometry (Slit Skiascopy/OPD Scan Device)

Use of Zernike Polynomials in Wavefront Sensing

This apparatus is based on retinoscopic principles. A slit of light is scanned into the eye along different meridians over the full pupil. The timing and scan rate of the reflected light is analyzed by an array of photo detectors to determine the wave aberrations along these meridians. This technology enables reconstruction of the wavefront in eyes with high ametropias.

In the field of adaptive optics, Zernike polynomials are particularly useful for wavefront decomposition. These functions are usually represented in a pyramid (Fig. 5.26). They are normalized and expressed on the unit pupil disk, and the human ocular pupil is also circular. These functions are defined in a Cartesian conventional system centered on the

Accuracy and Repeatability of Wavefront Measurements Several studies address the repeatability of static wavefront measurements.31,32 The repeatability decreases with pupil misalignment errors, short-term variation in the actual ocular aberrations, tear film rupture, and small drifts in the measuring equipment.20 The accuracy of wavefront measurement may be variable depending on the type of wavefront sensor used. The spots associated with the lenslet array in a Shack–Hartmann sensor can overlap when a patient has a very distorted wavefront. This can be addressed by increasing the dynamic range of the system. High resolution is also important to accurately analyze an eye that has fine structure aberrations. Ray-tracing instruments may be sensitive to saccadic eye movements, especially if they have a long scan time. The spots being analyzed by ray-tracing instruments are being imaged by the eye and the instruments must make some assumptions regarding the shape of the retina.

Wavefront Analysis and Map Interpretation Principles of Wavefront Reconstruction The total wavefront is converted in the sum of elementary aberrations that are selectively weighted. The preferred surface fitting method to characterize the wavefront envelope characteristics at this time uses Zernike polynomials. Reconstruction of the wavefront using Zernike polynomials allows the extraction of useful information.33 This mathematical expansion has been used extensively in optics and astronomy to decompose the optical aberrations of an optical system into well-described aberrations. These aberrations include sphere and cylinder, but Zernike analysis also allows extraction of higher-order aberrations, such as coma and spherical aberration, that is, Zernike terms above the third order. This concept derives from the Fourier decomposition but, rather than using simple sine/cosine functions, relies on the use of Zernike functions. The attentive reader will notice the implementation of sine/cosine functions (whose frequency corresponds to the azimuthal frequency) in every nonrotationally symmetric Zernike polynomial expressed in polar form (Table 5.1).

Z00

ZERNIKE PYRAMID Z 11

Z1-1

Fritz ZERNIKE (1888 – 1966) Nobel : 1953

Z3-3

Z5-5

Z6-6

Z40

Z6-2

Z33

Z42

Z51

Z5-1

Z5-3

Z6-4

Z31

Z3-1

Z4-2

Z4-4

Z22

Z20

Z2-2

Z60

Z44

Z53

Z62

Z55

Z64

Z66

• Fig. 5.26  Colorscale representation of the first 28 Zernike polynomials (sixth radial order). Rotationally symmetric polynomials (piston, defocus, spherical aberration) are located in the central column. Oriented polynomials (i.e., having no rotational invariance) are disposed by pairs having the same radial order and absolute value but opposite sign azimuthal frequency. The selective weighting of each coefficient of a given pair allows for tuning of the orientation and amplitude of the aberration. The mean value of each mode (except for the piston) is 0. Each mode as a unit vector. In a two-dimensional (2D) Cartesian domain, one could plot two unit vectors along the X and Y axis, which would be orthogonal and with a norm (length) equal to 1. In a threedimensional (3D) domain, you could add a third unit vector along the Z axis, which is orthogonal to the X and Y axis. In such 3D space, any vector can be decomposed on a weighted sum of the X, Y, and Z axis unit vectors. In the “Zernike polynomial domain,” one extends such a concept to a space with more than three dimensions. Each of these dimensions has its own unit vector, represented by a particular Zernike mode. Each of these dimensions would be perpendicular (orthogonal) to all the other ones. In such a multidimensional space, wavefront error would correspond to a particular vector, which could be broken down in a sum of weighted unit vectors (i.e., Zernike mode). The weight of each mode corresponds to the root mean square (RMS) coefficient of a Zernike wavefront decomposition. The spatial shape of some Zernike modes to some ocular affection. For example, keratoconus, which is characterized by some corneal vertical asymmetry, will easily induce vertical coma Z 3 ± 1, in which the wavefront error carries asymmetry between the superior and inferior half of the pupil domain. The coefficient of the coma term would be negative in most cases, as the wavefront error would show relative inferior retardation (owing to the low decentered apex) and superior relative advance. It may not be surprising to find high levels of trefoil Z 3 ± 3 or tetrafoil Z 4 ± 4, or any higher-foils Z n ± n = m in eyes that have been operated on with techniques such as radial keratotomy. Horizontal coma Z 31 and trefoil Z 33 are frequently seen in advanced pterygium owing to nasal corneal tear film distortion, and other issues.

CHAPTER 5  Wavefront Analysis

TABLE The Implementation of Sine/Cosine Functions in Nonrotationally Symmetric Zernike Polynomials 5.1  (Expressed in Polar Form)

Term

Cartesian Form

Polar Form

1

1

Z

0 0

Z

−1 1

4y

4ρ sin( θ )

Z

1 1

4x

4ρ cos(θ )

Z

−2 2

6 ( 2 xy )

6ρ2 sin( 2θ )

Z 02

3 (2 x 2 + 2 y 2 − l )

32(ρ2 − 1)

Z 22

6( x2 − y2 )

6ρ2 cos( 2θ )

Z 3−3

8 (3 x 3 y − y 3 )

8ρ3 sin( 3θ )

Z 3−3

8 (3 x 2 y − y 3 − 2 y )

8 ( 3ρ3 − 2ρ)sin( θ )

Z13

8 ( 3 x 3 − 3 xy 2 − 2 x )

8 ( 3ρ3 − 2ρ)cos(θ )

Z 33

8 ( x 3 − 3 xy 2 )

8ρ3 cos( 3θ )

Z 4−4

10 ( 4 x 3 y − 4 xy 3 )

10ρ4 sin( 4θ )

Z 4−2

10 ( 8 x 3 y + 8 xy 3 − 6 xy )

10 ( 4ρ4 − 3ρ2 sin( 2θ )

Z 04

5 (6 x 4 + 12 x 2 y 2 + 6 y 4 − 6 x 2 − 6 y 2 + 1)

5 (6ρ4 − 6ρ2 + 1)

Z 24

10 ( 4 x 4 − 3 x 2 + 3 y 2 4 y 4 )

10 ( 4ρ4 − 3ρ2 )cos( 2θ )

Z 44

10 ( x 4 − 6 x 2 y 2 + 4 y 4 )

10ρ4 cos( 4θ )

Z 5−5

12 ( 5 x 4 y − 10 x 2 y 3 + y 5 )

12ρ5 sin( 5θ )

Z 5−3

12 (15 x 4 y + 10 x 2 y 3 − 5 y 5 − 12 x 2 y + 4 y 3 )

12 ( 5ρ5 − 4ρ3 )sin( 3θ )

Z 5−1

12 (10 x 4 y + 20 x 2 y 3 + 10 y 5 − 12 x 2 y − 12 y 3 +

12 (10ρ5 − 12ρ3 + 3ρ)sin( θ )

Z15

12 (10χ5 + 20 x 3 y 2 + 10 xy 4 − 12 x 3 − 12 xy 2 = 3 )

12 (10ρ5 − 12ρ3 + 3ρ)cos(θ )

Z 35

12 ( 5 x 5 − 10 x 3 y 2 − 15 xy 4 − 4 x 3 + 12 xy )

12 ( 5ρ5 − 4ρ3 )cos( 3θ )

Z 55

12 ( x 5 − 10 x 3 y 2 + 5 xy 4 )

12ρ5 cos( 5θ )

Z 6−6

14 (6 x 5 y − 20 x 3 y 3 + 6 xy 5 )

14ρ6 sin( 6θ )

Z 6−4

14 ( 24 x 5 y − 24 xy 5 − 20 x 3 y + 20 xy 3 )

14 (6ρ6 − 5ρ4 )sin( 4θ )

Z 6−2

14 ( 30 x 5 y + 60 x 3 y 3 + 30 xy 5 − 40 x 3 y − 40 xy 3 + 12 xy )

14 (15ρ6 − 20ρ4 + 6ρ2 )sin( 2θ )

Z 60

7 ( 20 x 6 + 60 x 4 y 2 + 60 x 2 y 4 + 20 y 6 − 30 x 4 − 60 x 2 y 2 − 30 y 4 + 12 x 2 + 12 y 2 + 1)

7 ( 20ρ6 − 30ρ4 + 12ρ2 − 1)

Z 62

14 (15 x 6 + 15 x 4 y 2 − 15 x 2 y 4 − 15 y 6 − 20 x 4 + 6 x 2 − 6 y 2 )

14 (15ρ6 − 20ρ4 + 6ρ2 )cos( 2θ )

Z 64

14 (6 x 6 − 30 x 4 y 2 − 30 x 2 y 4 + 6 y 6 − 5 x 4 + 30 x 2 y 2 − 5 y 4 )

14 (6ρ6 − 5ρ4 )cos( 4θ )

Z 66

14 ( x 6 − 15 x 4 y 2 + 15 x 2 y 4 − y 6 )

14ρ6 cos(6θ )

Z7−7

16 (7 x 6 y − 35 x 4 y 3 + 21x 2 y 5 − y 7 )

16ρ7 sin(7θ )

Z7−5

16 ( 35 x 6 y − 35 x 4 y 3 + 63 x 2 y 5 + 7 y 7 − 30 x 4 y + 60 x 2 y 3 − 6 y 5 )

16 (7ρ7 − 6ρ5 )sin( 5θ )

Z7−3

16 (63 x 6 y + 105 x 4 y 3 + 21x 2 y 5′ − 21y 7 − 90 x 4 − 60 x 2 y 3 + 30 y 5 + 30 x 2 y − 10 y 3 )

16 ( 21ρ7 − 30ρ5 + 10ρ3 )sin( 3θ )

Z7−1

16 ( 35 x 6 y + 105 x 4 y 3 + 105 x 2 y 5′ + 35 y 7 − 60 x − 120 x 2 y 3 − 60 y 5 + 30 x 2 y + 30 y 3 − 4y)

16 ( 35ρ7 − 60ρ5 + 30ρ3 − 4ρ)sin( θ )

Z17

16 ( 35 x 7 + 105 x 5 y 2 + 105 x 3 y 4 + 35 xy 6 − 60 x − 120 x 3 y 2 − 60 xy 4 + 30 x 3 + 30 xy 2 − 4x)

16 ( 35ρ7 − 60ρ5 + 30ρ3 − 4ρ)cos(θ )

Z73

16 ( 21x 7 − 21x 5 y 2 − 105 x 3 y 4 − 63 xy 6 − 30 x 5 + 60 x 3 y 2 + 90 xy 4 + 10 x 3 − 30 xy 2 )

16 ( 21ρ7 − 30ρ5 + 10ρ3 )cos( 3θ )

Z75

16 (7 x 7 − 63 x 5 y 2 − 35 x 3 y 4 + 35 xy 6 − 6 x 5 + 60 x 3 y 2 − 30 xy 4 )

16 (7ρ7 − 6ρ5 )cos( 5θ )

Z77

16 ( x 7 − 21x 5 y 2 + 35 x 3 y 4 − 7 xy 6 )

16ρ7 cos(7θ )

71

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center of the ocular entrance pupil (Fig. 5.27). The first Zernike polynomials have a physical practical interpretation because they correspond to classical optical aberrations. Each Zernike function can be expressed in polar coordinates (r, theta), where r is the distance from the pupil center and theta its azimuthal angle, as the product of a polynomial function in r and a cosine or sine function in theta (Figs. 5.28 and 5.29). The degree n of a polynomial is defined as the highest value of the rn term of the polynomial function. The polynomials can be selectively weighted by a coefficient expressed in microns to reflect their relative role in the wavefront distortion (Fig. 5.30). The sum of all the

weighted polynomials allows reconstruction of the total wavefront. Low-order terms correspond to Zernike polynomials of maximal degree n = 2. It comprises the Zernike modes related to piston (null aberration), tilt (prismatic deviation), and sphere and cylindrical defocus refractive error.

• Fig. 5.27

• Fig. 5.28  Representation of triangular astigmatism (trefoil) with the (trefoil) Z3-3 polynomial on the normalized unit pupil disk (green ring). The envelope of this polynomial is equal to the product of a third-order polynomial radial function (ρ3), where ρ is the distance from the center, and a trigonometric function with an azimuthal frequency of 3 (sin 3θ), where θ corresponds to the angle with the horizontal line.

  Aberrations are measured with respect to the line of sight as reference axis. The line of sight passes through the pupil center and is equivalent to the path of the foveal chief ray. Therefore aberrations are defined over the entrance pupil of the eye in a conventional righthanded coordinate system in Cartesian and polar forms. OD, Right eye; OS, left eye.

Principles of the Wavefront Decomposition Into Zernike Polynomials Because the number of lenslets is finite, the wavefront is first reconstructed as a mesh with planar facets. A

Wavefront error polar coordinates system Green : « Zero » reference level Pupil edge

Z

Advanced r r

0°

Retarded Front view

Side view

• Fig. 5.29  In the polar coordinates system representation (ANSI recommendation), the wavefront error depicts the optical path difference (in microns) with a reference surface. This representation corresponds to the optical path difference with a flat wavefront (green level). Each color step represents a phase shift of 1 µm. The zero level is the mean of the wavefront, which is the plane that separates into two equal components the relative phase advances and phase retardations. The height of that mean with regard to the lowest point (the most retarded point of the wavefront error) corresponds to the root mean square (RMS) value of the first Zernike term, named the piston.

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73

Primary spherical aberration

Reference level

A

Z40 = √5 (6r4 − 6r2 + 1) Normalization factor

Radial function

• Fig. 5.31

Example of a radially symmetric Zernike mode (primary spherical aberration). Interestingly, in the Seidel classification, primary spherical aberration only contains terms in r4, whereas Zernike primary spherical aberration contains some defocus (term in −6r2). The sign of this defocus is negative. To satisfy the need of orthogonality, Zernike coefficients are said to be balanced. They contain a mixture of various radial degree terms, which makes them orthogonal to one another. Zernike polynomials parcel various radial degree terms within the same radial function. That fourth-order (or primary) spherical aberration contains second-degree radial terms can cause some discrepancy between the Zernike and refraction defocus interpretation.  

B • Fig. 5.30

  For a given term, the root mean square (RMS) coefficient is calculated as the root of the mean of the sum of the squared distance to the median of the wavefront. It is expressed in microns.

mathematical smoothing is performed before Zernike decomposition. The number of polynomials used in the decomposition depends on the highest degree that is considered by the wavefront analyzing system. The primary goal of decomposition is to determine the value of the coefficients for each Zernike mode. It is achieved by computerized matrix calculation, in which the difference between the actual measured wavefront and the Zernike polynomial sum must be minimized. The coefficients are thus calculated so that the sum of the square of the difference in elevation with the reference surface is minimized. Each RMS (root mean square) coefficient for a given Zernike term corresponds to its contribution to the total standard deviation of the wavefront. The decomposition into Zernike polynomials is an approximation of the measured wavefront. It can suffer from imprecision or mistakes, especially for highly distorted wavefronts (optical zone decentration, advanced keratoconus, and so on).34 It should not be forgotten that the process of wavefront reconstruction gives rise to an expansion that contains an array of aberrations (each corresponding to a particular Zernike term when Zernike polynomials are used for the fitting process) that, in fact, interact positively or negatively when summed to approximate the initial wavefront shape. Thus the optical consequences of the total wavefront distortion cannot be foreseen as the net sum of the optical effect of each aberration present in the wavefront reconstruction. The analytical expression of some Zernike modes comprises terms of various radial degrees. For example, the fourth-order spherical aberration term (Z40) contains both second- and fourth-power radial terms (i.e., r2 and r4 terms; Fig. 5.31). Hence, the interpretation of the relation between low- and and high-order terms and the spherocylindrical expression of the refractive error must be taken with caution. The value of the pupil diameter on which the wavefront reconstruction is performed is crucial. The variation of

the coefficients with the pupil diameter is exponential and proportional to the radial order n of the Zernike polynomial.35,36 To allow comparison, the pupil diameters must be identical between different examinations. The direct value of the RMS coefficient of a given polynomial or group of polynomials does not reflect directly the quality of vision. Some aberrations compensate with others, and for the same magnitude, some aberrations are more detrimental than others for visual acuity. In particular, because they contain low-order terms in their polynomial function, Zernike modes located near the center of the pyramid seem to be more detrimental to visual acuity than modes located near the edges.

Wavefront Interpretation Based on Zernike Polynomial Decomposition The presence of optical aberrations induces the departure of a flat disk of the wavefront as analyzed by the Hartmann– Shack system. The first Zernike polynomials correspond with classical optical aberrations (Fig. 5.32). The Zernike functions are mutually orthogonal, and the RMS wavefront error of each function is given by its coefficient. Consequently, a Zernike expansion provides a convenient accounting scheme in which the total RMS wavefront error is equal to the square root of the sum of the squares of the individual coefficients in the Zernike spectrum of a wavefront aberration map. These individual coefficients can be listed by their radial order number n: • Aberration with n = 0. Corresponds to the piston term (constant phase shift) that does not induce image distortion. • Aberration with n = 1. Corresponds to tilt. Tilt is prismatic error. It causes the ideal wavefront to remain ideal in shape but tilted relative to its original position. It arises

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A

B

C D

E F

G • Fig. 5.32

0 1 0   (A) Piston (Z0 ); (B) tilt aberration: Z1 ; (C) defocus aberration (Z2 ); (D) cylindrical: defocus cylindrique (Z22); (E) coma aberration (Z31); (F) trefoil aberration (triangular astigmatism) (Z33); (G) spherical aberration (Z40).

CHAPTER 5  Wavefront Analysis

from the differences in the mean angulation of the constitutive ocular elements. • Aberration with n = 2. Corresponds to defocus and astigmatism, that is, spherocylindrical ametropia. The defocus induces a parabolic distortion of the ideal flat wavefront (Fig. 5.33). Second-degree astigmatism is an azimuthal variation of this parabolic distortion with axis symmetry (Fig. 5.34). The selective weighting of each of the two polynomials corresponding to second-degree astigma-

Defocus No defocus

Myopic defocus

Rayons parallËles Èmis par une source ponctuelle distante

75

tism allows determination of both the magnitude and the axis (Fig. 5.35). • Aberration with n = 3. The polynomials that correspond to third radial order degree aberrations are named coma and trefoil in the Zernike classification. They reflect the presence of an asymmetry in the refractive properties of the eye that can be the consequence of asymmetry, irregularity, tilt, or decentration of the ocular surfaces (Fig. 5.36). • No anatomic feature common to all eyes might be responsible for third-order aberrations. The axes of these orientated aberrations seem to be randomly distributed, although a slight tendency for the coma axis to be vertically oriented has been reported.37 They often increase after laser in situ keratomileusis (LASIK) or photorefractive keratectomy (PRK), which can reflect a relative

air

• Fig. 5.33  The light rays are an abstraction that makes it possible to materialize the direction of the local propagation of the light waves. The wavefront is another abstraction that allows mathematical calculations to be made. Locally, the wavefront and rays are mutually perpendicular (the rays can be understood as the path taken by a single photon). An optical system forms an image by refracting the light rays. Light, conceptualized as a light wave, travels in media of different geometry and refractive indices. In denser media, the wavelength decreases (the celerity of light is reduced, but while light rays slow down, their oscillation frequency remains unchanged). The optical distance (or optical path) corresponds to the number of wavelengths between the source and the plane of the image. If this distance is identical for each of the rays, the image formed is “perfect” because it benefits from a maximum constructive interference. The envelope of the incident plane wavefront thus becomes spherical in an emmetropic eye (centered on the fovea) and vice versa. For a short-sighted eye (myopia), the wavefront incident (or emitted from the fovea) remains spherical (parabolic in first approximation). It is centered on the fovea in the eye when it is emitted by a source at the punctum remotum (located at a finite distance in myopic eyes).

• Fig. 5.35

  The second-order astigmatism is expressed as a linear combination of the Z2−2 and Z22 Zernike polynomials. The resulting function has the same envelope whose particular amplitude and orientation are given by the respective values of the c2−2 and c22 coefficients. With-the-rule and against-the-rule astigmatism can be quantified with c22 only (c2−2 = 0).

Third-degree Zernike coma-like aberrations Second-degree Zernike astigmatism

Relative phase delay Relative phase advance

COMA Keratoconus apex

• Fig. 5.34  Schematic representation of a pure astigmatic wavefront emerging from a theoretical eye with high corneal toricity. The phase advance is maximal along the steep meridian, since the optical path from the fovea to the corneal is the shortest along that direction.

• Fig. 5.36  Schematic representation of a pure astigmatic wavefront emerging from a theoretical eye with high corneal asymmetry (e.g., keratoconus). The wavefront emerging from the inferior half of the pupil is then retarded by the inferior corneal bulging.

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imprecision in treatment centration. Trefoil is often associated with a significant amount of irregular and asymmetric corneal toricity. • Aberration with n = 4. Spherical aberrations correspond to a difference in the focalization of the rays entering the periphery of the entrance pupil from the rays located in the central pupillary area (paraxial conditions). Spherical aberration coefficient value C40 is biased toward positive values in healthy eyes. Spherical aberration as defined by the Zernike mode Z40 induces an effect in the central region of the pupil that is in the opposite direction to that of the defocus Z20 of the same sign. Thus when having the same sign, these aberrations counterbalance to leave the central pupil with a flatter aberration function than occurs for either aberration separately. This may explain why the correction of spherocylindrical refraction with spectacle lenses based on the results of subjective refraction would not leave a null Zernike term coefficient value for C20 but instead leaves a value that varies systematically with pupil diameter and with the Zernike coefficient for spherical aberration in a way that maximizes visual acuity37 (Fig. 5.37). Fourth-order aberrations do increase after corneal refractive surgery. They usually become more positive after conventional corneal surgery for myopia and less positive or negative after hyperopic corneal surgery. This is due to the conjugation of the small optical zone size and the suboptimal asphericity of the postoperative anterior corneal profile. • Aberrations with n >4. These reflect the presence of nonsystematized optical aberrations that contribute to the deformation of the wavefront envelope. Their rate is

usually low and their role in visual performance degradation is usually small but can become significant in some special conditions such as irregular scarring, incisional surgery, and penetrating keratoplasty.

Application to the Wavefront Interpretation The overall shape of the wavefront is the reflection of the optical aberrations that distort its edges. Schematically, when there is an important spherical ametropia, the shape of the analyzed wavefront is close to a paraboloid whose orientation is related to the sign of the ametropia. Central retardation corresponds to myopia, whereas edge retardation corresponds to hyperopia. The presence of astigmatism induces a slight axial asymmetry when moderate. Pure astigmatism is associated with a strong asymmetry (one meridian being flat, the other curved; Fig. 5.38). Mixed astigmatism is associated with the presence of a saddle-shaped wavefront. The presence of a spherocylindrical ametropia dictates the overall shape of the wavefront, because the rate of highorder aberration is usually much lower. In emmetropic patients, the central portion of the wavefront is usually flat, and distortions prevail at the edges of the pupil (Fig. 5.39). The mathematical extraction of higher-order aberrations allows visualization of the isolate effects of these aberrations. The contribution of higher-order aberrations to the wavefront distortion is better visualized on the higher-order wavefront map, where first- and second-order aberrations are removed. Coma and trefoil induce an asymmetric distortion of the wavefront envelope (Fig. 5.40). Spherical aberration induces a distortion of the central area of the wavefront relative to its edges. A purely spherically altered wavefront would have a “sombrero” shape. In some conditions, asymmetry can be visible on the total wavefront map as an effect of the presence of a large amount of higher-order aberrations.

• Fig. 5.37

  The total wavefront is decomposed into two Zernike terms of the same sign (defocus Z20 and Z40). When the pupil is constricted (dotted line), the sum of these aberrations is beneficial (the wavefront distortion is minimum in the center). This is due to the mathematical characteristics of the Zernike spherical aberration term (Z40). It contains some second radial degree terms (r^2) that cancel with the defocus (Z20) terms. In this example, the suppression of one of these aberrations would be detrimental for vision. This particular wavefront shape is frequently encountered after myopic corneal refractive procedures, especially when the optical zone diameter is less than that of the scotopic pupil.

• Fig. 5.38

  Pure refractive hyperopic astigmatism is expressed by a combination of Z20 and Z22 polynomials, with c22 = 2xc20. Mixed astigmatism with null spherical equivalent can be expressed by a combination of Z2−2 and Z22 (null mean defocus).

CHAPTER 5  Wavefront Analysis

• Fig. 5.39

  Wavefront map obtained with the Zywave Hartmann–Shack aberrometer (Bausch & Lomb) in a patient complaining of poor night vision with a starburst through a naturally dilated pupil of 6.6 mm. The photopic uncorrected visual acuity is 20/15. The left color map corresponds to the total wavefront display. The large green central area reflects the absence of significant defocus. The trilobe distortion of the edges of the pupil suggests the presence of the trefoil aberration. The total root mean square (RMS) deviation of the wavefront is 0.50 mm, among which 0.48 are caused by higher-order aberrations than spherical aberrations.

Contribution of higher-order (n ≥ 3 aberrations) Contribution of low (n ≤ 2) aberrations

• Fig. 5.40

  Most available aberrometers allow visualization of the total wavefront (left) and the higher-order (right) wavefront separately. In this example, the wavefront of a mild myopic patient with against-the-rule astigmatism is depicted. In the convention used by this device (Zywave Hartmann–Shack aberrometer, Bausch & Lomb), red colors correspond to phase-retarded wavefront areas and bluish colors correspond to phase-advanced areas. Note the change in magnitude for the central scale. The overall shape of the total wavefront is governed by the presence of both spherical and cylindrical defocus. Vertical coma accounts for most of the higher-order wavefront distortion; it is responsible for the asymmetric phase distribution.

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Statistical Variation of Aberration in Healthy Eyes When monochromatic aberrations are measured along the line of sight of healthy eyes from large cohorts of individuals, the population averages of Zernike coefficients are nearly zero except for spherical aberration,37,38 which is usually biased toward positive values. However, for any particular eye, the coefficient of any Zernike term is rarely zero, any individual being equally likely to have positive or negative aberration owing to biologic random variability. In 200 eyes of 100 healthy individuals, Thibos et al. found, using Hartmann–Shack aberrometry, that the average amount of higher-order aberrations present for a 7.5-mm pupil was equivalent to the wavefront error produced by less than a 1 diopter of defocus.37 These authors and others38 disclosed 4 the presence of significant bilateral symmetry from the correlation of aberrations between right and left eyes. Statistical correlation has also been found within the aberration of an eye, particularly those having the same meridional frequency, such as vertical prism and coma, horizontal prism and coma, defocus, and spherical aberration. These correlations probably reflect the way the set of Zernike functions are constructed to retain orthogonality as opposed to the set of Seidel aberrations.

Variation of Aberration After Refractive Surgery The appearance of visual complaint—such as halos, glare, and monocular diplopia after corneal refractive surgery— has long been correlated with the induction of optical aberrations39 (Figs. 5.40 and 5.41). The increase in corneal and/ or total aberrations after different refractive surgical techniques—such as radial keratotomy (RK),40 PKR,41 and LASIK14—has been extensively reported. The magnitude of this increase is positively correlated with the importance of the treated ametropia. The increase in the magnitude of high-order aberrations is also proportional to the pupil diameter15 and is responsible for a decrease in contrast sensitivity.42–45 Coma-like and spherical aberrations are the most predominantly increased optical aberrations postoperatively. Several mechanisms may explain the increase in the amount of high-order aberrations with conventional excimer laser refractive procedures. An excessive variation of the corneal asphericity toward oblateness or prolateness after myopic and hyperopic ablations, respectively, an insufficient effective optical zone size,46,47 and an imperfect centration48 have been invoked to explain the postoperative increase in high-order aberrations. The theoretical prediction of the variation of the corneal asphericity within the optical zone after excimer laser ablation has received much attention. We were the first to demonstrate that the postoperative corneal surface should be more prolate within the optical zone after myopic Munnerlyn spherically based photoablation for initially prolate corneas.49 This finding has been confirmed by several authors50–53 and is in contradic-

tion to the corneal oblateness commonly measured postoperatively. Biomechanical corneal response, wound healing, and laser fluence variation with the corneal declivity explain this discrepancy.52,54

Variations of Aberration With Aging Several studies have reported a compensation of the aberration of the anterior cornea by the aberration of the crystalline lens, particularly in young adults.55–58 The spherical aberration of the cornea is usually positive, whereas the young crystalline lens exhibits a negative spherical aberration. Such corneal and internal balance has also been reported for coma.57 Fig. 5.42 shows an example of corneal and internal balance of high-order aberration in a young patient. Cross-sectional studies show an increase of total optical aberrations of the eye with age.59 Part of this is due to an increase in corneal aberration with aging. The crystalline lens spherical aberration becomes less negative with aging.56,60 This produces a decrease in the balance between corneal and internal spherical aberration and a net increase of total spherical aberration. The optical quality is further degraded by the scattering of intraocular structures that increases with aging. When cataract develops, it causes glare, light loss, and decreased contrast sensitivity due to scattering. These symptoms can be eliminated by the replacement of the cataractous lens with an intraocular lens (IOL). Conventional IOLs have equiconvex or biconvex spherical surfaces and suffer from positive spherical aberration when inserted in the eye, as has been shown in in vitro measurement using eye models.61 However, consistent data in the literature show that conventional pseudophakic IOLs fail to restore the potential maximal optical quality because of imperfect centration, tilt, and increased positive spherical aberration owing to the addition of the positive corneal spherical aberration of the IOL to that of the cornea.62,63 Lenses with optimized aspheric design could improve the optical performance in balancing the positive corneal spherical aberration, provided that tilt and decentration of the optic of the IOL are controlled. The natural pupil myosis occurring with age may reduce the impact of the increase in optical aberrations with aging.64 Further studies are required to investigate the potential benefit of increased optical aberrations, which may increase the depth of focus by induced multifocality and thus be beneficial in nonaccommodating eyes.

Measures of Optical Performance of the Eye Visual performance is a broad term that can be defined by how well a visual task of interest can be performed by a given individual or group of individuals.65 Knowing the wave aberration of an eye is only one prerequisite to assessing the patient’s optical performance. Appropriate metrics derived from the wave aberration should allow the clinician

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79

A

B • Fig. 5.41

  (A) Elevation and tangential specular topography of the left eye of a patient operated with LASIK for a −5 D myopia (Orbscan, Bausch & Lomb) revealing marked inferotemporal decentration. The patient complains of monocular diplopia, and night halos and starbursts. Best spectacle-corrected visual acuity is 20/30 with +0.50 (−0.50 × 125°). (B) The wavefront examination reveals the presence of a large amount of higher-order aberrations. The total root mean square (RMS) for high-order aberrations is 1.33 mm, of which 1.24 mm are due to other aberrations than spherical aberration Z40. The asymmetry in the total and higher-order wavefront maps reflects the presence of odd order aberrations, which arise from the irregularity of the anterior corneal profile.

to choose the best strategy to improve the vision in each patient. For example, it could be used to determine whether a customized wavefront correction would benefit more than a conventional one in a given patient, or to link certain visual disturbances, such as glare or halos, to an optical cause. Currently, the most common method for describing the wavefront error of the eye is the normalized Zernike expansion.66 The complex interactions of wave aberrations at low

levels of optical error and how these interactions impact visual performance were investigated by various authors.67–70 At low levels of whole-eye aberrations (less than 0.25 equivalent diopters [D]), the RMS wavefront error cannot account for an observed two-line variation in visual performance.67 The visual impact of low levels of aberration was assessed by observing how a fixed amount of RMS error loaded into single Zernike modes (second through fourth radial orders) impacted the letter acuity of an individual.68

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• Fig. 5.42  Example of good corneal/internal compensation of high-order aberrations in a young subject. There is important cancellation of most of the third- and fourth-order corneal aberrations by internal aberrations (OPD scan and OPD station, Nidek).

• Fig. 5.43

  Image simulations of the impact of 0.35 µm of root mean square (RMS) for various individual modes of the Zernike expansion through the sixth radial order over a 6-mm pupil. The modes having lower azimuthal frequency (located near the center of the pyramid) have a larger effect than modes having higher azimuthal frequency (located near the edges of the pyramid).

These experiments revealed that 0.25 mm of aberration over a 6-mm pupil reduced visual acuity by an amount that depended on which Zernike mode contained the wavefront error. Modes near the center of each radial order had a greater impact on visual performance (more letters lost) than modes near the edge of the pyramid (Fig. 5.43). However, real eyes do not exhibit single-mode aberrations. Applegate et al. conducted experiments to investigate

how low levels of RMS wavefront error split between two Zernike modes affect visual acuity.67 The experiment was performed by varying the relative proportion of the wavefront error attributable to each of two Zernike modes while keeping total RMS wavefront error constant at 0.25 mm over a 6-mm pupil. A variation in high-contrast visual acuity of nearly two lines on a log MAR chart was observed despite the fact that the total RMS error was held constant at 0.25 mm over a 6-mm pupil (a fixed equivalent dioptric error of 0.19 D). The magnitude of the loss was dependent on which aberration modes were combined and in what ratio. Thus RMS wavefront error and equivalent dioptric error cannot predict the manner in which the Zernike modes combination significantly impacts measured acuity. RMS wavefront error, which specifies only the standard deviation of the wavefront error over the pupil, does not contain any information as to how this wavefront error is distributed within the pupil (Fig. 5.44). High-contrast visual acuity is a classic method, but not the only way, to test visual performance. The optical quality of a given element of any optical system is not restricted to its limit of resolution, just as a high-fidelity sound system is not properly evaluated on the basis of its upper frequency cutoff. The establishment of pertinent metrics of visual quality is a mandatory step to optimize vision correction, and metrics other than high-contrast visual acuity are thus necessary to determine the impact of the wavefront error on the visual performance. These metrics are numerous and their interest may vary depending on visual task or patient lifestyle. They can be

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81

B

A

• Fig. 5.44  (A, B) Interaction between defocus and spherical aberration: opposite signs (left) and same signs (right). In this example, for the same amount of defocus, the sign of spherical aberration will dramatically modify the final image quality, although the total root mean square (RMS) is the same in both cases. (When adding aberrations, this is the variance, which is the squared RMS, not the RMS itself that adds.) This is shown with the simulation of the image of the optotype E. Although the variance of both wavefronts is the same, the distribution of the distortion is very different. Zernike modes can interact strongly with each other to determine the final image quality. When aberrations combine in flattening the central portion of the wavefront, they may sometimes increase acuity more than would be expected from the individual components.

classified into two categories: pupil plane metrics and image plane metrics. Pupil plane metrics are defined by qualities of the shape of the wave aberrations in the pupil plane. Image plane metrics can be subdivided into metrics based on the point spread function or metrics based on the optical transfer function.65 Neural processing is plastic and may affect the visual performance over time. In some metrics, neural weighting can be added to mimic the effects of the neural system, providing a fuller description of the visual process. Numerous metrics have been proposed; their full description and mathematical description are complex and beyond the scope of this chapter. We refer the interested reader to reports from Marsack and Hamam.71,72 In this chapter, we will study only the principle of the most widely used metrics at this writing.

Pupil Plane Metrics: Wavefront Map Metrics A perfect optical system has a flat wavefront aberration map. Metrics of wavefront quality aim at describing the degree of wavefront flatness. An aberration map is flat if its value is constant or if derivative quantities, such as its slope or curvature, are zero across the entire pupil. Thibos et al.65 proposed to use scalar metrics based on these three elements: the wavefront aberration map, the slope map, and the curvature map. In addition to these metrics defined on the whole pupil area, other metrics of wavefront quality can be defined based on pupil fraction elements. Pupil fraction is defined as the fraction of the pupil area for which the optical quality of the eye is acceptable. The criteria for deciding if the wavefront over a subaperture is good could

be based on the wavefront aberration function. The larger the pupil fraction, the more of the light entering the eye will contribute to a good-quality retinal image.

Vergence Maps Vergence maps provide an alternative description of the errors of the wavefront. Wavefront vergence can be calculated as the radial wavefront slope normalized by the radial distance from the pupil center. Vergence maps are similar in concept to the refractive power map in corneal topography and may have more clinical appeal for clinicians. They display the local variation of the total ocular refractive power (Fig. 5.45). In an emmetropic eye, the local fluctuations of the local vergence within the pupil area correspond to the effect of higher-order wavefront phase errors. The interpretation of the vergence map is straightforward but can be related to the presence of specific aberration Zernike modes (Fig. 5.46).

Image Plane Metrics A point object can be imaged into a compact, high-contrast retinal image by a perfect optical system. The image of such a point object is called a point-spread function (PSF).

Point-Spread Function The function that describes how an imaging system alters an object point as it transfers it from object to image plane can be called a spread function. The ocular PSF is the light distribution intensity of the retinal image of a point object. It combines the effect of both the diffraction and aberrations (Figs. 5.47 and 5.48). Because of the latter, the image

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Vergence maps Diopters

Diopters

• Fig. 5.45

  The vergence maps show the variations of the refraction within the pupil. On the left, a theoretical and perfect eye: all the rays are focused in the plane of the retina. On the right, a real eye, emmetropic. This map reveals that for an emmetropic eye (12/10 sc), the imperfections of any biologic system induce local fluctuations in the optical power (vergence) within the pupillary area. These variations are insufficient to provide a multifocality capable of supplementing an accommodative defect. These fluctuations around emmetropia are induced by high-degree aberrations.

Myopic shift toward the pupil center = Negative spherical aberration

• Fig. 5.46

  Left: Vergence map obtained with the OPD Scan III aberrometer (Nidek) in an eye presenting with nuclear cataract (inset). This map, expressed in diopters, displays the presence of a myopic gradient toward the center of the pupil. This myopic shift is due to the increase of the refractive indice of the dense cataract nucleus. This gradient of power within the pupil area corresponds to the presence of negative spherical aberration (coefficient listed #12 c40 = −0.283 for a 6-mm pupil). In this example, there is an increased multifocality within the pupil area. Similar vergence maps can be observed after multifocal refractive surgery (i.e., “presbyLASIK”) in which the profile of ablation intends to induce a “near zone” in the central area of the pupil.

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• Fig. 5.47  Relation between the wavefront aberration, light rays, and the retinal point-spread function (PSF) of an optical imaging system. Top: In the absence of aberration, the wavefront is nearly spherical. The incoming light is focused in one point, that is, rays are converging in the plane of focus, the PSF is compact, and its spread is owing only to the diffraction by the pupil aperture. Bottom: When aberrations are present, they distort the wavefront from a perfect spherical shape. The light rays are not converging in one single plane. The PSF is broadened. The departure of the wavefront from a pure spherical shape is plotted as a color map. Hotter colors correspond to advanced regions; colder colors correspond to retarded regions.

A

B • Fig. 5.48

  (A) Representation of the computed point-spread function (PSF) for different monochromatic aberrations (Zywave Hartmann–Shack aberrometer, Bausch & Lomb). (B) Comparison between a diffraction limited PSF and a high-order aberrated PSF (Zywave Hartmann–Shack aberrometer, Bausch & Lomb). On the right, the retinal image of the point source when the eye is corrected for defocus and astigmatism is blurred owing to the presence of different high-order aberrations. These aberrations cannot be corrected by spectacles and result in a degradation of the quality of the retinal image.

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points will be more spread and broadened than an idealized object point. Any object can be represented as a collection of point sources, each of which is imaged as a PSF by the optics of the eye. The image is the result of the convolution of each of these PSFs. It is a fundamental parameter in the evaluation of any optical imaging system and provides a direct measurement of the retinal image quality.73 In the absence of scattering, the PSF is directly related to the wavefront aberration function truncated by the pupil aperture via a Fourier transform. The more compact and symmetric, the higher the image fidelity. Treating an object as a two-dimensional array of points of varying intensity, the PSF determines the manner whereby each point of object intensity is changed to a point of image intensity. The operation that conceptually performs a point-to-point translation from object to the retinal image plane (taking into account the magnification, diffraction, and aberration spreading by the eye’s exit pupil) is called the convolution operation.23 The more the PSF is enlarged, the more the image irradiance pattern points will overlap each other, thus decreasing the resolution on the true points (Fig. 5.49). Rayleigh criteria are used to assess the maximal theoretical resolution of the eye based on the PSF (Fig. 5.50). Two light point sources will be just resolvable if in the fovea the central maximum of PSF of the first point coincides with the first minimum of irradiance of the irradiance of the other point. Scalar metrics of image quality that are designed to capture the dual attributes of compactness and contrast can be used in an attempt to quantify the quality of the PSF in aberrated eyes. Low values of spatial compactness metrics (e.g., the value of a diameter of a circular area centered on a PSF peak that captures 50% of the light energy, or the value of the average width of every cross-section of the PSF) indicate a compact PSF of good quality. Conversely,

I

I

large values of contrast metrics indicate a high-contrast PSF of good quality. The Strehl ratio is a measure of the peak height of the PSF and is expressed as a ratio between the peak height of the PSF over the peak height for the same optical system if it were diffraction limited. Therefore the best possible value for the Strehl ratio is 1 (Fig. 5.51). In healthy eyes, its value is usually much lower owing to the presence of optical aberrations. Other contrast metrics have been proposed, such as the standard deviation of intensity values in the PSF (normalized to diffraction-limited value), which measures the variability of intensities at various points in the PSF. The PSF can optionally be weighted by

• Fig. 5.50  The Rayleigh criterion states that two light point sources will be just resolvable if in the fovea the central maximum of the pointspread function (PSF) of the first point coincides with the first minimum of irradiance of the other point. The radius of the first dark concentric ring surrounding the central intensity peak of a PSF (or Airy disc) is inversely proportional to the pupil size for a diffraction-limited eye (no optical aberrations). To be diffraction limited, a system must have less than one-fourteenth of a wavelength of monochromatic aberrations.

Object

PSF

PSF

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Image

• Fig. 5.49  Convolution is an operation that allows generation of a simulation of a blurred image. Any object is composed of an infinite array of point sources, each having its respective intensity. Convolution gives to each corresponding point in the image the shape of the pointspread function (PSF). This illustration shows the convolution of the same object points by two different PSFs. The sharper PSF (left) degrades the image less than the broader PSF (right).

A • Fig. 5.51

B

  Strehl ratio. In (A), the PSF is diffraction limited. In (B), the peak height of the point-spread function (PSF) is reduced because of the effect of optical aberrations. The Marechal criteria state that an optical system is well corrected when the Strehl ratio is greater than or equal to 0.80.

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Z

I (z,0)

Fourier transform

I (z,a) Fourier transform

A

X

B • Fig. 5.52

  (A) This two-dimensional picture can be assimilated as a two-dimensional distribution of the irradiance I (x, z). (B) Schematic representation of the pattern of the irradiance distribution along two arbitrary lines (plotted in black) and their respective decompositions in spatial frequencies (plotted in blue) via a Fourier transform (only the first spectral components are shown). Each line of the image has its own spectrum of spatial frequencies.

a Stiles–Crawford apodization, which describes the variation of the light efficiency as a function of the ray height in the entrance pupil owing to wave-guide properties of the foveal cones.

Visual acuity / minutes of arc / cycles per degree 60 cycles per degree

Optical Transfer Function, Modulation Transfer Function, Phase Transfer Function We have already considered an object as a collection of point sources that will each give rise to a PSF. We can also represent the same object through a different perspective, as a source of light waves with particular values of spatial frequencies.73 Complex objects viewed by the eye can be decomposed as the summation of sinusoidal gratings of different frequencies, orientations, modulations, and phases (Fig. 5.52). The number of spacings (or cycles) per unit interval in a specimen is referred to as the spatial frequency, which is usually expressed in quantitative terms of the periodic spacings (spatial period) found in the specimen. A common reference unit for spatial frequency is the number of line pairs per millimeter. As an example, a continuous series of black-and-white line pairs with a spatial period measuring 1 mm per pair would repeat 10 times every centimeter and therefore have a corresponding spatial frequency of 10 lines per centimeter. The maximal visual acuity of the human eye can be measured in spatial frequency, that is, as the number of cycles per degree that contains the smallest spacing (cycle) that the eye can discern (Fig. 5.53). Thus the impact of the eye’s optics on any object can be analyzed through its effects on the phase and modulation of each spatial frequency contained in any object. This approach is helpful in providing some figure of merit applicable to the entire operating frequency range.23

0.5 min = 1/120° 1 cycle = Visual acuity = 1/0.5 = 2 = 20/10

• Fig. 5.53

  The power of resolution can be expressed in numbers of cycles solved per degree. The minimum angle of resolution is 30/ (number of cycles per degree). Resolving 30 cycles per degree is equivalent to a visual acuity of 10/10. The maximal theoretical visual acuity of the human eye is close to resolving 60 cycles per degree (this limit is set by both the pupil diffraction and retinal sampling).

The optical transfer function (OTF) describes how the individual frequency constituting the objects is transformed by the eye into the corresponding harmonic components of the image. This concept is derived from standard conventions utilized in electrical engineering that relate the degree of modulation of an output signal to a function of the signal frequency. Ideally, the OTF transfers all frequencies without any modulation. Since optical theory tells us that any object can be decomposed as the sum of gratings of various spatial frequencies, contrasts, phases, and orientations, we may think of the optical system of the eye as a filter that lowers the contrast and changes the relative position of each grating in the object spectrum as it forms a degraded retinal image.

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75% (light gray)

Contrast = 50%

25% (dark gray)

Spatial frequency (retinal plane)

Spatial frequency (object) 100 (white) Contrast = 100% 0 (black)

• Fig. 5.54

  The contrast of the object (a given spatial frequency) is 100%. Owing to diffraction and possible optical aberrations, the contrast of the spatial image frequency is reduced (to 50% in this example).

Thus the OTF is a metric of image quality in the frequency domain. The OTF is defined mathematically as the Fourier transform of the PSF (Fraunhofer irradiance) in imaging with coherent light. It thus represents the spatial frequency spectra of the eye’s PSF. Grating patches would always produce sinusoidal images no matter how aberrated the eye, whereas point objects can produce an infinite variety of PSF images. Consequently, aberrations can modulate the image of a grating patch in two different ways: they can reduce the contrast or translate the image sideways to produce a phase shift (Fig. 5.54). The amount of contrast attenuation and phase shift both depend on the grating’s spatial frequency. The variation of image contrast with spatial frequency for an object with 100% contrast is called a modulation transfer function (MTF). The MTF is a quantitative measure of image quality that is far superior to any classic resolution criteria because it describes the ability of the eye to transfer object contrast to the image. It corresponds to the ratio of image contrast to object contrast as a function of the spatial frequency of a sinusoidal grating (Figs. 5.55 and 5.56). The MTF describes the contrast at each spatial frequency, usually normalized to range from 0 to 1, 0 being gray (no contrast), 1 being perfect black/white contrast. If an object grating of a given spatial frequency is imaged by the eye, the intensity contrast of adjacent bars in the image at the same spatial frequency will be given by the transfer function. Perfect imagery of black/white motives corresponds to a transfer function of 1. Conversely, when the transfer is 0, the bars in the image will undergo a complete washout and appear as continuous shades of gray (Fig. 5.57). If no aberrations were present in an eye, the MTF would be related to the size of the diffraction pattern, which is a function of the pupil aperture size and the wavelength of

illumination. The larger the pupil size, the higher the transfer ratio and the spatial frequency at which the modulation goes to 0. This reflects the reduction of the diffraction effects with the increase of the pupil diameter. However, real eyes are aberrated, and these aberrations will have a significant impact on the MTF (Fig. 5.58). The MTF is an extremely sensitive measure of image degradation. A lens having a quarter wavelength of spherical aberration (that would barely be discernible by the eye) would reduce the MTF by as much as 0.2 (loss of 20% of contrast) at the midpoint of the spatial frequency range. In a system with astigmatism or coma, different MTF curves are obtained that correspond to various azimuths in the image plane through a single image point. MTF curves can be either polychromatic or monochromatic. Polychromatic curves show the effect of any chromatic aberration that may be present. The variation of image phase shift with spatial frequency is called a phase transfer function (PTF). The PTF displays the phase shift of the image with respect to the object as a function of spatial frequency (Fig. 5.59). When there is no optical aberration, the location of the object and the image is identical or displaced by the same amount (no phase shift), resulting in a net position shift for the image without degradation of image quality. If the PTF is linear with frequency, it represents a simple lateral displacement of the image as would be observed with an aberration such as geometric distortion. When the phase response deviates from ideal linear behavior, some components will be shifted to a greater degree than others, resulting in image degradation. A phase shift of 180° produces a reversal of image contrast for the concerned spatial frequency. This means that dark becomes light and light becomes dark (contrast reversal). This reversal can occur owing to aberration in the optical system, such as coma. Together, the MTF and PTF comprise the eye’s OTF. A theoretical perfect optical system (not suffering from

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Image Aberrated Perfect eye eye

Normalized MTF 1.0 0.8

(A)

0.6

(B)

0.4

Cutoff frequency

0.2 0 0.2

0.4

0.6

0.8

1.0 Object

Normalized spatial frequency

• Fig. 5.55

The averaged normalized modulation transfer function (MTF) is plotted for two different eyes for the same pupil aperture and the same wavelength. (A) An ideal aberration-free/diffraction-limited eye: the curve (blue) dips slightly below the straight line. A normalized spatial frequency of unity corresponds to the diffraction limit. Maximum contrast is apparent when the spatial frequencies are low (large features). It decreases as the spatial frequencies become higher (smaller features). The diffraction effects induce a limitation at high frequencies. In the image, bright highlights will not appear as bright as they do in the specimen, and dark or shadowed areas will not appear as bright as they do in the specimen. The eye (or one of its optical components) quality is measured by how closely the real MTF curves approach this ideal curve. (B) In an aberrated eye, the MTF curve (purple) dips more and is below the diffraction limited MTF curve. In this example, both eyes have the same cutoff frequency (the best maximum contrast visual acuity would be identical). The contrast is lower at all lower spatial frequencies as compared to the diffraction-limited eye. Said differently, this aberrated eye transfers contrast less effectively at all spatial frequencies than the “perfect” diffraction-limited eye, as shown to the left of the graph for selected spatial frequencies.  

• Fig. 5.56

  A vertical sinusoidal grating of chosen spatial frequency is shown as an object. After passing through the eye, the gratings have less contrast. The modulation transfer function (MTF) plots the change in contrast relative to the original object. The object contrast or modulation can be defined as: Modulation (M) = (Imax − Imin)/(Imax + Imin). Modulation is typically less in the image than in the specimen. It varies as a function of the spatial frequency. By definition, the MTF is described by the following equation: MTF = Image Modulation/Object Modulation. It is an expression of the contrast alteration observed in the image.

diffraction or aberration) would have an MTF of unity at all spatial frequencies, while simultaneously having a PTF of 0. The OTF, MTF, and PTF are two-dimensional functions that can be plotted centered on the pupil center. They can

be displayed on a one-dimensional graph by averaging across hemimeridians (radial averaging). The Strehl ratio can be computed in the frequency domain since the area under the OTF curve is equal to the PSF height, assuming there is no phase shift (in which case the OTF is equal to the MTF). The phase appears to carry an important part of the information of the image that is necessary for a correct perception of the image.74 Aberrations such as defocus, astigmatism, and coma affect the PTF differently, thus providing different changes in the shape of the retinal image depending upon image frequency content. Vision quality metrics that directly incorporate the PTF may thus allow better quantification of vision quality.74

Relations Between Point Spread Function and Optical Transfer Function Certain fundamental relationships exist between the PSFs and OTFs. Their mathematical description is beyond the scope of this chapter and derives from the linear systems theory. Briefly, the eye is assimilated to an optical system that transforms an input function (the fixated two-dimensional scene) into an output function (the two-dimensional image). Any object incoherently illuminated can be thought of in two ways: as a two-dimensional array of points of varying brightness or as a two-dimensional array of periodic

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High-pass filter

B

A

Low-pass filter

• Fig. 5.57  (A) Portrait of the Montparnasse tower and adjacent district in Paris. Upper left corner: Theoretical plot of the radially averaged modulation transfer function of the camera that took the picture. (B) The process of altering the frequency spectrum of the image is known as spatial filtering. Here, the high frequencies have been filtered out (zero contrast). Shades of gray appear and the sharp boundaries have vanished. Note that the gratings present on the Montparnasse tower and other buildings are no longer visible. (C) By removing the low-frequency components (low-pass filtering), the resulting image is then composed of only the sharper details. Only the mid-spatial and high-spatial frequencies are present in the resulting image.

C

1.00 Asymmetric point spread function Luminance

0.60

0.40

Pupil: 3mm

0.20 0.00

Pupil: 6mm 0

5

10 15 20 25 30 35 40 45 50 55 60 Spatial frequency (cpd)

• Fig. 5.58  Radially averaged modulation transfer functions computed from the high-order aberrations only for a normal eye analyzed for two pupil diameters (3 mm, 6 mm). The transfer of contrast from object to image is slightly lower for the 6-mm conditions as compared to the 2-mm condition over most of the visible range of spatial frequencies. This optical loss is in great part the consequence of the increase of the high-order aberrations. cpd, Cycles per degree.

Phase shift

Object

Spread function Luminance

Modulation transfer

0.80

Image

• Fig. 5.59  Asymmetric aberrations produce an asymmetric pointspread function (PSF). This introduces a phase shift as shown here with the slight right translation of the harmonic output after convolution of the harmonic input with an asymmetric PSF. The phase shift of the sinusoid depends upon the spatial frequency. (Adapted from Hecht E. Fourier optics. In: Optics. 4th ed. San Francisco, CA: Addison Wesley; 2002:553, fig. 11.48.)

CHAPTER 5  Wavefront Analysis

structures of various spatial frequencies. Thus there are two routes to image formation by the eye, the first using the PSF and linear superposition via the convolution operation, the second using spatial frequencies and Fourier transformations. At the limit of resolution, adjacent PSFs start to overlap, decreasing the ability to distinguish between individual intensities. Narrower-intensity distributions can be distributed more closely and still be resolved by the eye. This implies that a narrow PSF corresponds to a high spatial frequency. Therefore there is a relationship between the minimum closeness of resolvable image points and the maximal spatial frequencies that can be imaged. In fact, the OTF, a measure of spatial frequency response for an optical system, is the mathematical Fourier transform of the PSF. The description of how the system images a single point (impulse) of monochromatic light corresponds to the

Spatial distribution of object intensity (Object)

Fourier transform Inverse Fourier transform

(Convolution) Point spread function

Object intensity spectrum (Spatial frequencies) (Multiplication)

Fourier transform

Optical transfer function

Inverse Fourier transform = Spatial distribution of image intensity (Object)

A

B

Fourier transform Inverse Fourier transform

= Image intensity spectrum (Spatial frequencies)

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impulse response. It translates each point of the object plane to a geometrically appropriate point in the image plane. In performing this imaging function, the optics of the eye transfer with some alteration the spatial frequency information of the object plane to the image plane. Fig. 5.60 summarizes the relations between these imaging functions. Fig. 5.61 illustrates a complicated case of LASIK with poor postoperative optical outcome.

Metrics and Polychromatic Light The wavefront aberration is defined for a monochromatic light radiation. It is possible to compute the value of a given metric as a weighted average of the results for each wavelength in a polychromatic source in which the weighting function is the luminous efficiency function that describes

• Fig. 5.60  (A) Relations between imaging functions with incoherent light. The optical transfer function (OTF) is analogous to the point-spread function (PSF) from which it can be obtained via a Fourier transform: it represents how the eye selectively attenuates each of the spatial frequencies present in the object intensity spectrum. (B) The two routes for image formation in an eye with 0.25 D of defocus. One route in this diagram means calculating the two-dimensional Fourier transform (spectrum) of the object. The obtained spatial frequency spectrum is then multiplied by the OTF of this eye to produce the spatial frequency spectrum of the image intensity distribution in space. An inverse Fourier transform of that product specifies the spatial distribution of the positive image intensity in space. In this example, the defocus introduces a marked reduction of the contrast for higher spatial frequencies. Two examples of the gratings constituting the original object are shown with their corresponding location on the two-dimensional Fourier diagram (circles). The loss of information predominating for the higher frequencies results in the loss of details in the reconstructed image. The second route from object to image for a system with incoherent illumination involves the use of the PSF of the eye. The object is treated as a two-dimensional array of points of varying intensity. The PSF determines how each point of object intensity is changed to a point of image intensity (convolution operation). Due to the diffraction and aberration (here, defocus), the image irradiance pattern points overlap each other and decrease the resolution of the true points.

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a

b

c

d

A a

b

c

d

B • Fig. 5.61

  (A) Corneal topography and wavefront analysis (left eye) of a 27-year-old patient 1 month after uneventful LASIK. Despite uncorrected visual acuity of 20/20, the patient is dissatisfied and complains of persistent starburst, halos, and permanent monocular diplopia (OPD Scan, Nidek). He reports severe visual performance degradation at night. The preoperative refraction was −3 (−1.5 × 0°). The postoperative axial specular corneal topography (a) shows slight superior and nasal decentration with residual toricity. The pattern of the total wavefront map (c) shows second-order astigmatism. High-order wavefront map (b) is mainly aberrated by trefoil and coma. The Zernike histogram chart (d) reveals a high amount of high-order aberrations (0.695 µm), mostly represented by coma (0.355 µm) and trefoil (0.528 µm). (B) The point-spread function (PSF) of the same patient is computed for total (a) and high-order only (b) aberrations. The convolution of each of these PSFs with an EDTRS chart is shown on the lower part of the diagram as a simulated retinal image (OPD station, Nidek). Note the “ghosting shadows” around the optotypes owing to the combined effects of high-order aberrations.

CHAPTER 5  Wavefront Analysis

1.00 Ave D. limited

Modulation transfer

0.80

0.60

0.40

Pupil: 3mm Pupil: 6mm

0.20

0.00

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C • Fig. 5.61, cont’d

10 15 20 25 30 35 40 45 50

55 60

Spatial frequency (cpd)

(C) The radially averaged modulation transfer functions computed for the high-order aberrations are shown for small and large pupils (OPD scan and OPD station, Nidek). The transfer of contrast from object to images is from three to eight times lower for the 6-mm pupil condition compared to the 3-mm condition over most of the visible range of spatial frequencies. These optical losses are the consequences of the high amount of high-order optical aberrations owing to treatment decentration as the pupil diameter increases. cpd, Cycles per degree.

how visual sensitivity to monochromatic light varies with wavelength. Polychromatic metrics of image quality for point objects can be defined by substituting polychromatic images for monochromatic images. Using this approach, polychromatic luminance PSF is calculated as a weighted sum of each of the monochromatic spread functions. For example, for a well-corrected achromatic system, polychromatic MTF can be computed by weighted averaging of monochromatic MTFs. The change in image chromaticity and object chromaticity could theoretically be investigated using this kind of approach.65

Prediction of Subjective Refraction From Wavefront Aberration Maps Vision Quality Metrics Converting the wavefront aberration map into an optimum spherocylindrical prescription is not a straightforward task for several reasons. The human eye suffers from polychromatic and monochromatic aberrations that prevent light from any polychromatic or monochromatic source from perfectly focusing on the retina into an image point. The optimum spherocylindrical prescription is influenced by the presence of high-order aberrations. Fitting the aberrated wavefront with a quadratic function that would be equivalent to its best spherocylindrical approximation and thus lead to directly assessing the optimal refraction is not a valid approach because of the possible different fitting methods that would each provide different answers. For example, should all the points of the pupil be weighted equally or

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should the fitting function priority match the wavefront pupil center portion (paraxial wavefront portion)? Another legitimate approach consists of determining the criteria that would account for maximized visual quality for distant objects. However, none of the methods that aim to quantify the quality of the wavefront aberration function or the quality of the retinal image has been universally endorsed by the scientific and clinical community to assess optical quality at the time of this writing. Thus chromatic aberration, pupil weighting, and variability of the subjective refraction must be taken into account to predict the best subjective refraction from a monochromatic aberration map. Recent investigations have shown promising results and provided valid answers to some questions. Thibos et al.65 demonstrated that paraxial curvature matching of the wavefront aberration map was the most accurate method for determining the spherical equivalent error, whereas least-squares fitting of the wavefront was one of the least accurate methods. As emphasized earlier, the parceling of low-order terms in r^2 in high-order Zernike modes may account for the relative imprecision of wavefront fitting and lower Zernike modes for the subjective refraction. However, this conclusion was reached through bias compensations between the fitting and the clinical refraction methods. Other pupil and image metrics were reasonably accurate and among the most precise. These results may make wavefront methods the new gold standard for specifying conventional and/or optimal corrections of refractive errors. This will represent a very important contribution and make wavefront analysis an indispensable tool for the clinician and refractive surgeon. The combined use of vergence maps (for clinical evaluation) and wavefront phase error maps (enabling quantitative and qualitative assessments) may provide a more comprehensive approach to exploring the optical properties of human eyes (Fig. 5.62).

Conclusion In recent years, wavefront aberrometers have been gradually moving into the mainstream of ophthalmology practice as powerful diagnostic tools to address visual complaints of optical origin. By measuring and correcting not only the spherical and cylindrical components of refraction but also the aberrations of the visual system that may affect visual performance, attaining optical visual outcomes beyond those currently achieved by conventional refractive, subtractive, or additive surgical procedures may be possible. Many issues still remain unresolved as this field continues to advance. Wavefront aberrometers measure only monochromatic aberrations, whereas our eyes are able to see a polychromatic world. In the future, the discrepancy between the measured monochromatic wavefront and the actual polychromatic wavefront may be of help in finding the precise amount of higher-order aberrations to correct. The ideal flat wavefront for high fidelity may be optimal for young patients with intact accommodative abilities, whereas

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Wavefront error (high order only)

Vergence map (high order only)

A

B • Fig. 5.62

  (A) The wavefront phase error displays the local wavefront phase departures from a perfect wavefront, 6.8-mm pupil (left) owing to high-order aberrations. The vergence maps plot the fluctuation of local refractive power errors. Note that there is a spatial relationship between the two maps, embedded in a Y-shaped vertical trefoil dominant aberration phase and vergence map error. (B) Summary display to investigate the optical quality of this eye presenting with some visual disturbances characterized by the perception of a Y-shaped spiculae around bright lights in mesopic conditions. This is affected by some residual level of trefoil aberration after correction of low-order aberrations for a 6.8-mm mesopic pupil diameter (OPDscan III, Nidek). Note the shape of the point-spread function, which is owing to the trefoil aberration (upper row, left). The modulation transfer curves for 3 different subpupil apertures are shown (upper row, middle). A simulated retinal image of a Snellen chart is plotted (upper row, right). The photopic and mesopic pupil perimeters are delineated (lower row, left). The root mean square coefficients of main grouped Zernike modes are reported (lower row, middle). The impact on a “Siemens star,” composed as a radially arranged set of black-and-white sectors, allows simple inspection of the impact of aberrations on specific orientations for these gratings (lower row, right). Note: This is the right eye of the author of this chapter.

CHAPTER 5  Wavefront Analysis

adjusted shape designed to increase the depth of focus may be preferable for some presbyopic patients. The functional needs of the patient will have to be taken into consideration to truly optimize wavefront refractive surgical strategies, and adaptative optic capabilities will certainly have to be accessible to achieve these tasks.

References 1. Howland HC, Howland B. A subjective method for the measurement of monochromatic aberrations of the eye. J Opt Soc Am A. 1977;67:1508–1518. 2. Walsh G, Charman WN, Howland HC. Objective technique for the determination of monochromatic aberrations of the human eye. J Opt Soc Am A. 1984;1:987–992. 3. Liang J, Grimm B, Goelz S, et al. Objective measurement of wave aberrations of the human eye with the use of a Hartmann– Shack wavefront sensor. J Opt Soc Am A. 1994;11:1949–1957. 4. Liang J, Williams DR. Aberrations and retinal image quality of the normal human eye. J Opt Soc Am A. 1997;14:2873–2883. 5. Babcock HW. The possibility of compensating astronomical seeing. Publ Astron Soc Pac. 1953;65:229–236. 6. Fugate RQ, Fried DL, Ameer GA, et al. Measurement of atmospheric wavefront distortion using scattered light from a laser guide-star. [Letter] Nature. 1991;3532:144–146. 7. Yoon GY, Williams DR. Visual performance after correcting the monochromatic and chromatic aberrations of the eye. J Opt Soc Am A. 2002;19:266–275. 8. Guirao A, Porter J, Williams DR, et al. Calculated impact of higher order monochromatic aberrations on retinal image quality in a population of human eyes: erratum. J Opt Soc Am A. 2002;19: 620–628. 9. Roorda A, Williams DR. The arrangement of the three cone classes in the living human eye. [Letter] Nature. 1999;397:520–522. 10. Bellucci R. Optical aberrations and intraocular lens design. In: Buratto L, Werner I, Zanini M, Apple DJ, eds. Phacoemulsification: Principles and Techniques. 2nd ed. Thorofare, NJ: Slack; 2002:454–455. 11. Guirao A, Williams DR, Cox IG. Effect of rotation and translation on the expected benefit on an ideal method to correct the eye’s higher order aberrations. J Opt Soc Am A. 2001;18: 1003–1015. 12. Huang D. Physics of customized corneal ablation. In: MacRae SM, Krueger RR, Applegate RA, eds. Customized Corneal Ablation: The Quest for Super Vison. Thorofare, NJ: Slack; 2001:51–56. 13. Moreno-Barriuso E, Lloves JM, Marcos S, et al. Ocular aberrations before and after myopic corneal refractive surgery: LASIK-induced changes measured with laser ray tracing. Invest Ophthalmol Vis Sci. 2001;42:1396–1403. 14. Oshika T, Klyce SD, Applegate RA, et al. Comparison of corneal wavefront aberrations after photorefractive keratectomy and laser in situ keratomileusis. Am J Ophthalmol. 1999;127:1–7. 15. Martinez CE, Applegate RA, Klyce SD. Effect of pupillary dilation on corneal optical aberrations after photorefractive keratectomy. Arch Ophthalmol. 1998;116:1053–1062. 16. Applegate RA. Limits to vision: can we do better than nature? J Refract Surg. 2000;16:S547–S551. 17. Schwiegerling J. Theoretical limits to visual performance. Surv Ophthalmol. 2000;45:139–146. 18. Hecht E. Optics. A Brief History. Boston, MA: Addison, Wesley, Longman; 1998:3–10.

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19. Thibos LN. Calculation of the influence of lateral chromatic aberration on image quality across the visual field. J Opt Soc Am A. 1987;4:1673–1680. 20. Williams DR, Porter J, Yoon G, et al. How far can we extend the limits of human vision? In: Krueger RR, Applegate RA, MacRae SM, eds. Wavefront Customized Visual Corrections: The Quest for Super Vision II. Thorofare, NJ: Slack; 2004:19–38. 21. Applegate RA, Hilmantel G, Thibos LN. Assessment of visual performance. In: Krueger RR, Applegate RA, MacRae SM, eds. Wavefront Customized Visual Corrections: The Quest for Super Vision II. Thorofare, NJ: Slack; 2004:65–75. 22. Wilson GR. Fourier series and spectra in one dimension for functions of finite period. In: Wilson GR, ed. Fourier Series and Optical Transform Techniques in Contemporary Optics: An Introduction. New York, NY: John Wiley; 1995:23–53. 23. Wilson GR. The diffraction of light and Fourier transforms in two dimensions. In: Wilson GR, ed. Fourier Series and Optical Transform Techniques in Contemporary Optics: An Introduction. New York, NY: John Wiley; 1995:99–129. 24. Guirao A, Porter J, Williams DR, et al. Calculated impact of higher-order monochromatic aberrations on retinal image quality in a population of human eyes: erratum. J Opt Soc Am A. 2002;19:620–628. 25. Williams DR. Topography of the foveal cone mosaic in the living human eye. Vision Res. 1988;28:433–454. 26. Navarro R, Moreno E, Dorronsoro C. Monochromatic aberrations and point spread functions of the human eye across the visual field. J Opt Soc Am A. 1998;15:2522–2529. 27. Gustafsson J, Terenius E, Buchheister J, et al. Peripheral astigmatism in emmetropic eyes. Ophthalmic Physiol Opt. 2001;21: 393–400. 28. Tscherning M. Die monochromatischen Aberrationen den menschlichen. Auges Z Psychol Physiol Sinn. 1894;6:456–471. 29. Hartmann J. Bemerkungen über den Bau und die Justierung von Spektographen. Zeitschrift fur Instrumentenkunde. 1900;20:47. 30. Platt BC, Shack R. History and principles of Shack-Hartmann wavefront sensing. J Refract Surg. 2001;17:S573–S577. 31. Davies N, Diaz-Santana L, Lara-Saucedo D. Repeatability of ocular wavefront measurement. Optom Vis Sci. 2003;80: 142–150. 32. Thibos LN, Bradley A. Variation in ocular aberrations over seconds, minutes, hours, days, months, and years. In: Krueger RR, Applegate RA, MacRae SM, eds. Wavefront Customized Visual Corrections: The Quest for Super Vision II. Thorofare, NJ: Slack; 2004:109–113. 33. Born M, Wolf E. Principles of Optics. 7th ed. Cambridge, UK: Cambridge University Press; 1999. 34. Klyce SD, Karon MD, Smolek MK. Advantages and disadvantages of the Zernike expansion for representing wave aberration of the normal and aberrated eye. J Refract Surg. 2004;20:S537–S541. 35. Schwiegerling J. Scaling Zernike expansion coefficients to different pupil sizes. J Opt Soc Am A Opt Image Sci Vis. 2002;19: 1937–1945. 36. Gatinel D, Malet J, Azar DT, et al. Effects of the pupil constriction on the wavefront Zernike terms. Invest Ophthalmol Vis Sci. 2003;44:E-Abstract 966. 37. Thibos LN, Hong X, Bradley A, et al. Statistical variation of aberration structure and image quality in a normal population of healthy eyes. J Opt Soc Am A. 2002;9:2329–2348. 38. Porter J, Guirao A, Cox IG, et al. The human eye’s monochromatic aberrations in a large population. J Opt Soc Am A. 2001;18:1793–1803.

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39. Holladay JT, Dudeja DR, Chang J. Functional vision and corneal changes after laser in situ keratomileusis determined by contrast sensitivity, glare testing, and corneal topography. J Cataract Refract Surg. 1999;25:663–669. 40. Applegate RA, Howland HC, Sharp RP, et al. Corneal aberrations and visual performance after radial keratotomy. J Refract Surg. 1998;14:397–407. 41. Verdon W, Bullimore M, Maloney RK. Visual performance after photorefractive keratectomy: a prospective study. Arch Ophthalmol. 1996;114:1465–1472. 42. Seiler T, Kaemmerer M, Mierdel P, et al. Ocular optical aberrations after photorefractive keratectomy for myopia and myopic astigmatism. Arch Ophthalmol. 2000;118:17–21. 43. Marcos S. Aberrations and visual performance following standard laser vision correction. J Refract Surg. 2001;17:S596–S601. 44. Mutyala S, McDonald MB, Scheinblum KA, et al. Contrast sensitivity evaluation after laser in situ keratomileusis. Ophthalmology. 2000;107:1864–1867. 45. Hersh PS, Shah SI, Holladay JT. Corneal asphericity following excimer laser photorefractive keratectomy. Ophthalmic Surg Lasers. 1996;27:421–428. 46. Boxer Wachler BS, Huynh VN, El-Shiaty AF, et al. Evaluation of corneal functional optical zone after laser in situ keratomileusis. J Cataract Refract Surg. 2002;28:948–953. 47. Holladay JT, Janes JA. Topographic changes in corneal asphericity and effective optical zone after laser in situ keratomileusis. J Cataract Refract Surg. 2002;28:942–947. 48. Mrochen M, Kaemmerer M, Mierdel P, et al. Increased higherorder optical aberrations after laser refractive surgery: a problem of subclinical decentration. J Cataract Refract Surg. 2001;27: 362–369. 49. Gatinel D, Hoang-Xuan T, Azar DT. Determination of corneal asphericity after myopia surgery with the excimer laser: a mathematical model. Invest Ophthalmol Vis Sci. 2001;42:1736–1742. 50. Marcos S, Cano D, Barbero S. Increase in corneal asphericity after standard laser in situ keratomileusis for myopia is not inherent to the Munnerlyn algorithm. J Refract Surg. 2003;19:S592–S596. 51. Huang D, Tang M, Shekhar R. Mathematical model of corneal surface smoothing after laser refractive surgery. Am J Ophthalmol. 2003;135:267–278. 52. Hersh PS, Fry K, Blaker JW. Spherical aberration after laser in situ keratomileusis and photorefractive keratectomy: clinical results and theoretical models of etiology. J Cataract Refract Surg. 2003;29:2096–2104. 53. Cano D, Barbero S, Marcos S. Comparison of real and computersimulated outcomes of LASIK refractive surgery. J Opt Soc Am A Opt Image Sci Vis. 2004;21:926–936. 54. Anera RG, Jimenez JR, Jimenez del Barco L, et al. Changes in corneal asphericity after laser refractive surgery, including reflection losses and nonnormal incidence upon the anterior cornea. Opt Lett. 2003;28:417–419. 55. Artal P, Guirao A, Berrio E, et al. Compensation of corneal aberrations by the internal optics in the human eye. J Vis. 2001;1:1–8. 56. Artal P, Guirao A. Contributions of the cornea and lens to the aberrations of the human eye. Opt Lett. 1998;23:1713–1715.

57. Artal P, Berrio E, Guirao A, et al. Contribution of the cornea and internal surfaces to the change of ocular aberrations with age. J Opt Soc Am A Opt Image Sci Vis. 2002;19:137–143. 58. Kelly JE, Mihashi T, Howland HC. Compensation of corneal horizontal/vertical astigmatism, lateral coma, and spherical aberration by internal optics of the eye. J Vis. 2004;4:262–271. 59. McLellan JS, Marcos S, Burns SA. Age-related changes in monochromatic wave aberrations of the human eye. Invest Ophthalmol Vis Sci. 2001;42:1390–1395. 60. Smith G, Cox MJ, Calver R, et al. The spherical aberration of the crystalline lens of the human eye. Vis Res. 2001;41: 235–243. 61. Marcos S, Barbero S, McLellan JS, et al. Optical quality of the eye and aging. In: Krueger RR, Applegate RA, MacRae SM, eds. Wavefront Customized Visual Corrections: The Quest for Super Vision II. Thorofare, NJ: Slack; 2004:101–108. 62. Guirao A, Redondo M, Geraghty E, et al. Corneal optical aberrations and retinal image quality in patients in whom monofocal intraocular lenses were implanted. Arch Ophthalmol. 2002;120: 1143–1151. 63. Barbero S, Marcos S, Jiménez-Alfaro I. Optical aberrations of intraocular lenses measured in vivo and in vitro. J Opt Soc Am A Opt Image Sci Vis. 2003;20:1841–1851. 64. Calver RI, Cox MJ, Elliott DB. Effect of aging on the monochromatic aberrations of the human eye. J Opt Soc Am A Opt Image Sci Vis. 1999;16:2069–2078. 65. Thibos LN, Hong X, Bradley A, et al. Accuracy and precision of objective refraction from wavefront aberrations. J Vis. 2004;4:329–351. 66. Thibos LN, Applegate RA, Schwiegerling JT, et al. Standards for reporting the optical aberrations of eyes. Trends Opt Photonics. 2000;35:232–244. 67. Applegate RA, Marsack JD, Ramos R, et al. Interaction between aberrations to improve or reduce visual performance. J Cataract Refract Surg. 2003;29:1487–1495. 68. Applegate RA, Ballentine C, Gross H, et al. Visual acuity as a function of Zernike mode and level of root mean square error. Optom Vis Sci. 2003;80:97–105. 69. Applegate RA, Sarver EJ, Khemsara V. Are all aberrations equal? J Refract Surg. 2002;18:S556–S562. 70. Cheng X, Bradley A, Thibos LN. Predicting subjective judgment of best focus with objective image quality metrics. J Vis. 2004;4:310–321. 71. Marsack JD, Thibos LN, Applegate RA. Metrics of optical quality derived from wave aberrations predict visual performance. J Vis. 2004;4:322–328. 72. Hamam H. A new measure for optical performance. Optom Vis Sci. 2003;80:175–184. 73. Roorda A. A review of basic wavefront optics. In: Krueger RR, Applegate RA, MacRae SM, eds. Wavefront Customized Visual Corrections: The Quest for Super Vision II. Thorofare, NJ: Slack; 2004:9–18. 74. Sarver EJ, Applegate RA. The importance of the phase transfer function to visual function and visual quality metrics. J Refract Surg. 2004;20:S504–S507.

6 

Optical Coherence Tomography in Refractive Surgery NORMA ALLEMANN

Introduction Anterior segment optical coherence tomography (OCT) has been incorporated into clinical practice in refractive surgery to customize preoperative selection and to improve postoperative evaluation and follow-up.

Instruments The first models of anterior segment OCT used the timedomain principle with an approximate axial resolution of 18 µm and a 20,000 A-scans/sec scanning speed, allowing a wide image of the anterior segment (16 × 6 mm) with a possible scanning protocol with a higher-resolution scan of the cornea (5 × 5 mm). Spectral-domain OCT was then developed; the first instruments increased axial resolution to 5 µm and the scanning speed to 26,000 A-scans/sec at the expense of scan width (6 mm). Wider scans, higher resolution, and faster acquisition are requirements. Swept-source spectral domain OCT was incorporated into instruments, allowing a faster scanning speed (30,000–100,000 scans/sec), higher resolution (2.5–5 µm), and a larger scanning width. OCT instruments used for posterior segment evaluation can be adapted with lenses in order to evaluate the anterior segment. Morphologic evaluation and quantitative evaluation of the cornea and the anterior chamber are available in all instruments capable of imaging the anterior segment. Different OCT manufacturers have different approaches to the imaging technique of the anterior segment. Some instruments are able to image anterior and posterior segments and some instruments are dedicated only to the anterior segment, with 3-dimensional reconstruction and corneal topography based on OCT.

Considering OCT angiography, the anterior segment vasculature can be evaluated modifying parameters of the equipment (as segmentation) to focus the structure to be studied: iris, corneal, or conjunctival vasculature. This technique is susceptible to the microsaccadic eye movements generating movement artifacts that could be compensated by a built-in eye-tracking system.

Scanning Protocols and Measurements • Pachymetry map: Central, paracentral, and peripheral corneal thickness with information on average, minimum, and maximum thickness (Figs. 6.1A and 6.1B). Differential maps can be calculated when preoperative and postoperative scans are available. Pachymetry maps are displayed in sections and diameters from the central part of the cornea to the periphery. • Epithelial map: Epithelium thickness is evaluated in different quadrants and distances to the center (Figs. 6.1C to 6.1E). Differential maps can be calculated when preoperative and postoperative scans are available. • Flap and stromal bed thickness can be measured with the flap caliper from central to periphery and displayed (Fig. 6.2A). Differential maps can be calculated when preoperative and postoperative scans are available. • Anterior chamber depth: Measurement of the distance between the endothelial face of the cornea and the anterior face of the crystalline lens (Fig. 6.2B). • Internal anterior chamber diameter (Fig. 6.2B): Distance measured from the endothelium to the anterior lens capsule. • Lens rise: Measurement of the perpendicular distance between the anterior pole of the crystalline lens and a horizontal line joining the 2 scleral spurs on a horizontal scan. In a normal eye, “lens rise” can increase by 20 µm 95

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D C

E • Fig. 6.1

  Quantitative analysis of the cornea in refractive surgery candidates. (A–D) SS-OCT, DRI OCT Triton OCT, Topcon. (A) Upper right shows the horizontal corneal scan, inferior left shows the direction of the scan from nasal to temporal, upper left shows the overlay of the area scanned in the anterior segment image. Inferior right: Display of the 12 corneal scans taken to generate the pachymetry map (scale 300 to 800 µm, pachymetry varying from 500 to 580 µm). (B) Correspondent pachymetry map generated. (C) Each of the 12 corneal scans was analyzed to determine epithelium thickness (inferior) and one scan showing how epithelium was outlined (upper) by the software. (D) Correspondent epithelial map thickness map (30 to 80 µm). (E) SD-OCT, Avanti TR-Vue XR, Optovue. Anterior segment image with the representation of the scan orientation, vertical from inferior to superior (upper left), measurement details (inferior left) for pachymetry and epithelium thicknesses (minimum pachymetry: 516 µm; minimum epithelium thickness: 52 µm); correspondent image of the 6.0 mm vertical central scan of the cornea (upper right), and representation of the pachymetry map on the left (average central pachymetry = 525 µm, mean thickness displayed for 2.0, 5.0, and 6.0 mm zones in 8 sectors); and epithelium thickness map to the right (mean central epithelium thickness: 56 µm, display for 2.0, 5.0, and 6.0 mm zones in 8 sectors). (Courtesy Tecn. Claudio Zett Lobos.)

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C

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E • Fig. 6.2

  (A) Postoperative images after myopic laser in situ keratomileusis procedure. Flap and correspondent stromal bed thicknesses are displayed from central to periphery. Measurements adjacent to the central part are considered more reliable: flap varied from 163 to 180 μm and stromal bed thickness varied from 329 to 293 μm. (B) Anterior chamber depth was measured from endothelium to crystalline lens: 3.20 mm; central corneal thickness: 480 μm, and internal anterior chamber diameter: 12.70 mm. (C) Safety distance measured from endothelium to central and anterior border of the phakic intraocular lens (IOL). In the example, an angle-supported phakic IOL. Central safety distance: 1.77 mm (left side) and 1.64 mm (right side). Lens vault or the distance of the phakic IOL to the crystalline lens is also measured: 0.86 mm. (D) Angle-supported phakic IOL. Ideal safety distance of the phakic IOL to the endothelium is higher than 1.5 mm, displayed in green. A safety distance smaller than 0.5 mm, displayed in red, would be indication for IOL explantation. (E) Posterior chamber phakic IOL. Lens vault measured: 0.71 mm.

•

• • •

per year and can be related to complications seen in anterior segment phakic intraocular lenses (PIOLs). Safety distance: Distance measured from the endothelium to the anterior surface of the anterior chamber intraocular lens (IOLs; phakic or aphakic lens; Figs. 6.2C and 6.2D). Lens vault: Distance measured from the posterior face of the PIOL to the crystalline lens (Figs. 6.2C and 6.2E). Distance measured from scleral spur to scleral spur or posterior chamber internal diameter: Significant in the preoperative planning of posterior chamber PIOLs. Calipers: Measurements of any structure can be provided using manually placed calipers.

Applications in Refractive Surgery Qualitative/morphologic and quantitative assessment of the anterior chamber is relevant in the preoperative selection of candidates for corneal and intraocular refractive surgery and in the postoperative follow-up.

Preoperative Evaluation • Corneal pachymetry map: The pachymetry map is not usually integrated with the keratometric map. There are systems that display the pachymetry map acquired by anterior segment optical coherence tomography

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(ASCOT) integrated with corneal topography acquired by the topographer when acquisition is performed in both machines in order to generate a combined map. Epithelial thickness map: Preoperative acquisition is needed in order to follow epithelial thickness during the follow-up of corneal procedures (surface and lamellar procedures (photorefractive keratectomy [PRK] and laser in situ keratomileusis [LASIK]). Anterior chamber depth: Important in the preoperative evaluation of PIOL implantation, decisive in anglesupported PIOLs and evaluated with care in iris-fixated and posterior chamber PIOLs. Angle opening: Used as screening for PIOLs that cannot be implanted in a shallow angle. Anterior chamber diameter: Can be used to determine the total diameter of angle-supported PIOLs. Posterior chamber diameter or sulcus-to-sulcus: Used to determine adequate total diameter of posterior chamber PIOLs. Crystalline lens rise: A positive anterior lens vault is related to a potential angle closure and can be assessed preoperatively in order to detect this condition or to have this information in order to follow this parameter in the postoperative period. In the preoperative evaluation of PIOLs, angle opening, iris configuration, and patency of laser peripheral iridotomies can be evaluated.

A

Postoperative Evaluation • Radial and astigmatic keratotomy incisions: Scar depth, posterior stroma thickness, and epithelial plugs can be identified using AS-OCT. Complications at local microperforation sites can be identified when there is no posterior stroma left. Epithelial plugs, epithelial hyperplasia, and hypertrophic scars can be detected. • PRK and different surface procedures: Differential maps can compare preoperative and postoperative corneal thickness; the difference is related to the treatment obtained or to the depth of ablation (Figs. 6.3A and 6.3B). • Pachymetry differential maps can add information about the ablation profile, which can be useful in evaluating the keratometry map. Epithelial thickness changes over time are related to mechanical changes of epithelium remodeling (Fig. 6.3C). • Lamellar corneal refractive surgery, mechanical microkeratome, or LASIK or a LASIK-like flap with a small-incision lenticule extraction (SMILE): Flap, epithelial, and stromal bed thicknesses can be evaluated progressively in the follow-up to assess corneal remodeling. Differential total corneal and stromal thickness is related to the ablation depth (Fig. 6.4A). When planning reoperation after LASIK, stromal bed thickness is key to detecting safety when measuring the stromal bed, usually higher than 250 µm (Fig. 6.4B). Stromal bed thickness is considered

B

C • Fig. 6.3

  (A) Preoperative assessment of a candidate for myopic photorefractive keratectomy (PRK) (SE = –5.00 D). Central corneal thickness is displayed in the pachymetry map (left): 500 µm, and the stromal map (right) shows 452 µm centrally. (B) Postoperative evaluation. Central total corneal thickness (left): 425 µm; stromal thickness (right): 381 µm. The difference of preoperative and postoperative pachymetry is related to excimer laser ablation depth: 500 to 425 µm: 75 µm ablation depth. (C) Seven-days postoperative after PRK, central pachymetry (left): 438 µm; irregular epithelial thickness map, central epithelial thickness: 57 µm. Healing can be monitored in the serial evaluation of epithelium thickness map. (Courtesy Tecn. V. Belén López V.)

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A

B

C D • Fig. 6.4

  (A) Preoperative (inferior left) and postoperative (upper left) scans are compared and generate a differential map (right). Central corneal thickness change: –87 μm, which can be compared to ablation depth. (B) Postoperative evaluation of flap (central flap thickness: 133 μm) and stromal bed thickness (central: 267 μm). (C) Biomicroscopy of LASIK interface epithelial ingrowth seen as a whitish deposit at the interface. (D) Correspondent optical coherence tomography scan demonstrates highly reflective material at and above the interface. Interface is seen as a continuous linear interface in the anterior stroma.

an important risk factor for post-LASIK ectasia. Complications in flap architecture, flap healing problems, diffuse lamellar keratitis or infectious keratitis, interface debris or fluid, and epithelial interface ingrowth (Fig. 6.4C and D) can be detected using anterior segment optical coherence tomography (ASOCT). Buttonhole flap complication can be identified as an interruption of the stromal interface and the area involved can be detected. When inflammation is involved, generally there is local thickening of the flap and/or the stromal bed. When scarring is involved (epithelial ingrowth and interface debris), highly reflective material is deposited in the interface. When fluid is incarcerated in the interface, ASOCT can detect a hyporeflective collection in the flap interface. Flap architecture and healing can be addressed with OCT. • Corneal inlay procedures can be evaluated using ASOCT to detect the inlay’s position, inlay thickness, and anterior and posterior stroma thicknesses. Changes over time

can be detected, such as flap thinning, flap interface debris, and complications as inlay material changes and deposits. • Angle-supported PIOLs: Anterior chamber anatomy, follow-up evaluation of parameters, such as safety distance to the endothelium (central and peripheral; Figs. 6.5A and 6.5B), IOL thickness and positioning in relation to the pupil (IOL centration), lens vault (distance from IOL to the crystalline lens; Figs. 6.5C and 6.5D), haptics position, changes to angle opening, and changesto iris morphology (iris atrophy). Serial evaluation can detect IOL dislocation (Fig. 6.5E) and gradual pupil ovalization. Haptics’ footplates can cause significant compression of the iris in rigid PIOL models; progression of these changes over time can determine IOL dislocation. Foldable IOLs usually do not cause iris deformation (Figs. 6.5F and 6.5G) but can be associated to larger rotation in the anterior chamber. Localized changes in corneal pachymetry can suggest intermittent

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F • Fig. 6.5

  Angle-supported phakic intraocular lenses (IOLs). Rigid model (Nuvita), biomicroscopy (A) and optical coherence tomography (OCT) scan (B) with central safety distance to endothelium: 2.08 mm and central lens vault to the crystalline lens: 0.86 mm. In this model, the haptics are placed anteriorly to the iris without deformation and can be seen at the right part of the image as two faint semicircular structures. Model with foldable optic and rigid haptics (Vivarte), biomicroscopy (C), and OCT scan (D) showing a thicker optic (280 µm), its proximity to the iris plane and to the crystalline lens (0.42 mm). (E) Flexible model (Vivarte) dislocated in relation to the pupil, causing a change in the safety distance at the left part of the image: 0.95 mm, parameter considered below the recommended value of 1.5 mm. Foldable model (Cachet) biomicroscopy (F) and OCT scan (G) showing a well centered IOL.

CHAPTER 6  Optical Coherence Tomography in Refractive Surgery

endothelial touch, which can occur with either flexible or rigid IOL models. Oversized angle-supported IOLs tend to cause iris and angle deformation; undersized IOLs tend to rotate. • Iris-fixated IOLs: A severe early complication of this model is pupillary block. ASOCT is important to evaluate the relationship of the IOL to the structures of the anterior chamber (Figs. 6.6A and 6.6B). Over time, OCT helps to monitor safety distance, lens vault, and the relation of the laser iridotomy to the haptic plate. Progressive proximity of the crystalline lens to the PIOL (lens rise) can usually be observed when there is cataract formation. Iris tucking at the distal part of the haptics has to be observed. Rigid and foldable iris-fixated PIOLs can dislocate (Figs. 6.6C and 6.6D) and determine endothelial cell touch and uveitis. • Posterior chamber PIOLs: In the early postoperative period, the position of the PIOL in relation to the pupil and the distance from the IOL to the crystalline lens are important measurements (Figs. 6.7A and 6.7B). The haptics of posterior chamber PIOLs cannot be evaluated by ASOCT because there is light attenuation caused by

the iris. Lens vault is the most important parameter to detect oversized IOLs. When lens vault is higher than 750 µm, the surgeon may consider IOL exchange or rotation (Figs. 6.7B and 6.7C). Undersized IOLs tend to dislocate; ASOCT can detect the margin of the optic displaced in relation to the pupillary margin. Mydriasis can help to increase the evaluation. PIOL plates can block laser iridotomies and OCT can detect this condition, which is usually related to ocular hypertension.

OCT Angiography OCT angiography was developed to promote evaluation of the vasculature of the choriocapillaris and the retina, but the anterior segment can be evaluated if default parameters are changed. Further development in scanning protocols to evaluate the anterior segment vasculature will improve the technique. In the late postoperative evaluation of anterior chamber PIOLs (angle-supported and iris-fixated), changes in iris vasculature can be detected possibly related to a chronic contact to the iris, and changes can be detected using OCT angiography (Figs. 6.8A and 6.8B).

B

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  Iris-fixated phakic intraocular lenses. (A, B) Rigid model (Artisan or Verisyse), biomicroscopy (A) and optical coherence tomography scan showing the position at the iris plane thus closer to the crystalline lens. Lens vault: 0.29 mm. (C, D) Rigid model, 1 day after spontaneous dislocation with endothelial touch inferiorly. Central safety distance: 1.91 mm. Inferior safety distance: 0.24 mm, below the recommended.

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C • Fig. 6.7  Posterior chamber phakic intraocular lenses (IOLs). (A) Biomicroscopic image under mydriasis showing a phakic IOL placed posteriorly to the iris and anteriorly to the crystalline lens. The distance of the IOL to the lens (lens vault) can be evaluated at slit-lamp examination. (B) Correspondent optical coherence tomography scan demonstrates an increased lens vault: 1200 μm. (C) One month after the IOL repositioning surgical procedure, lens vault remains normal: 530 μm.

A

B • Fig. 6.8

  Anterior chamber angle-supported phakic intraocular lens, rigid model (Nuvita). Nineteen years postoperative period, normal visual acuity and endothelial cell count. (A) Biomicroscopy showing pupil ovalization, temporal iris atrophy not related to haptic positioning. (B) Avanti XR, Optovue optical coherence tomography angiography of the iris demonstrate an irregular pattern of the iris vessels (usually radially disposed) at the temporal area. (Courtesy Tecn. Claudio Zett Lobos.)

CHAPTER 6  Optical Coherence Tomography in Refractive Surgery

Further Reading 1. Alio JL, Abbouda A, Peña-Garcia P. Anterior segment optical coherence tomography of long-term phakic angle-supported intraocular lenses. Am J Ophthalmol. 2013;156(5):894–901. 2. Allemann N, Coleman DJ, Pavlin CJ, Huang D. Imaging the anterior segment: high-frequency ultrasound and anterior segment OCT. J Ophthalmol. 2013;2013:398715. doi:10.1155/ 2013/398715. 3. Ang M, Sim DA, Keane PA, et al. Optical coherence tomography angiography for anterior segment vasculature imaging. Ophthalmology. 2015;122(9):1740–1747. 4. Baikoff G, Lutun E, Wei J, Ferraz C. Refractive phakic IOLs: three different models and contact with the crystalline lens. Na AC-OCT study. J Fr Ophthalmol. 2005;28(3):303–308. 5. Chandapura RS, Shetty R, Shroff R, Shilpy N, Francis M, Sinha Roy A. OCT layered tomography of the cornea provides new insight on remodeling after photorefractive keratectomy. J Biophotonics. 2018;11(2). 6. Goto S, Maeda N, Koh S, et al. Prediction of postoperative intraocular lens position with angle-to-angle depth using anterior segment optical coherence tomography. Ophthalmology. 2016; 123(12):2474–2480. 7. Güell JL, Morral M, Gris O, Gaytan J, Sisquella M, Manero F. Evaluation of verisyse and artiflex phakic intraocular lenses during accommodation using visante optical coherence tomography. J Cataract Refract Surg. 2007;33(8):1398–1404. 8. Momighi S, Chen R, Hamzeh N, Khatibi N, Lin SC. Qualitative evaluation of anterior segment in angle closure disease using anterior segment optical coherence tomography. J Current Ophthalmol. 2016;28(4):170–175. 9. Izatt JA, Hee MR, Swanson EA, et al. Micrometer-scale resolution imaging of the anterior eye in vivo with optical coherence tomography. Arch Ophthalmol. 1994;112(12):1584–1589. 10. Klaproth OK, Rehemann J, Kohnen T. Dynamic positional change and defocus curve of a phakic foldable anterior-chamber angle-supported intraocular lens during accommodation. Ophthalmol. 2013;20(7):1373–1379. 11. Li P, An L, Reif R, Shen TT, Johnstone M, Wang RK. In vivo microstructural and microvascular imaging of the human corneoscleral limbus using optical coherence tomography. Biomed Opt Express. 2011;2(11):3109–3118.

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12. Li Y, Tan O, Brass R, Weiss JL, Huang D. Corneal epithelial thickness mapping by fourier-domain optical coherence tomography in normal and keratoconic eyes. Ophthalmology. 2012;119(12):2425–2433. 13. McNabb RP, Farsiu S, Stinnett SS, Izatt JA, Kuo AN. Optical coherence tomography accurately measures corneal power change from laser refractive surgery. Ophthalmology. 2015;122(4): 677–686. 14. Radhakrishnan S, Rollins AM, Roth JE, et al. Real-time optical coherence tomography of the anterior segment at 1310 nm. Arch Ophthalmol. 2001;119(8):1179–1185. 15. Reinstein DZ, Archer TJ, Gobbe M. Epithelial thickness up to 26 years after radial keratotomy: three-dimensional display with artemis very high-frequency digital ultrasound. J Refract Surg. 2011;27(8):618–624. 16. Roberts PK, Goldstein DA, Fawzi AA. Anterior segment optical coherence tomography angiography for identification of iris vasculature and staging of iris neovascularization: a pilot study. Curr Eye Res. 2017;42(8):1136–1142. 17. Rocha KM, Krueger RR. Spectral-domain optical coherence tomography epithelial and flap thickness mapping in femtosecond laser-assisted in situ keratomileusis. Am J Ophthalmol. 2014;158(2):293–301. 18. Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95(3):335–339. 19. Stahl JE, Durrie DS, Schwendeman FJ, Boghossian AJ. Anterior segment OCT analysis of thin intralase femtosecond flaps. J Refract Surg. 2007;23(6):555–558. 20. Stonecipher K, Ignaciob TS, Stonecipher M. Advances in refractive surgery: microkeratome and femtosecond laser flap creation in relation to safety, efficacy, predictability, and biomechanical stability. Curr Opin Ophthalmol. 2006;17(4):368–372. 21. Tan TE, Liu YC, Javasinghe LS, Mehta JS. Intraoperative optical coherence tomography vault measurement in posterior chamber phakic intraocular lens implantation. J Refract Surg. 2017;33(4):274–277.

7 

Excimer Lasers JOELLE HALLAK, PHILIPPE CHASTANG, FRÉDÉRIC VAYR, AND THANH HOANG-XUAN

Introduction The possibility of using the excimer laser for the cornea was first raised in the early 1980s.1,2 Using Munnerlyn’s equation, which established a relationship between the change in refractive power and the amount of corneal tissue ablated,3 McDonald showed that stable correction of primate corneas could be obtained by refractive photokeratectomy without compromising corneal transparency.4 The US Food and Drug Administration (FDA) authorized the first clinical study of myopic refractive photokeratectomy on nine legally blind eyes in 1988; the first sighted eye was treated later in the same year.5 The technology has advanced since then through 6 generations (Table 7.1),6 gradually extending refractive indications to all types of ametropia (spherical and cylindrical) with increasing reliability and safety. The technology is still evolving rapidly and advances have led to the development of customized ablation profiles, with the current goal to treat high-order optical aberrations and to avoid inducing unwanted ones. The reduction of induced aberrations has become the main focus in modern laser refractive surgery. Laser platforms with a small spot size as a key factor have been designed.6 The treatment of high hyperopic refractive errors and presbyopia remain challenging. Today, excimer laser profiles can be classified into: topography-guided, wavefrontguided, wavefront-optimized, and aspheric or Q-factoradjusted profiles.7,8 In this chapter, we will describe the principles and properties of excimer lasers, along with summarizing the various conventional excimer laser treatments and custom-guided (topography- and wavefront-based) treatments.

Lasers: General Physical Principles Principles of Laser Emission Light emission is linked to a phenomenon known as atomic relaxation, when an excited electron in an atom returns to its initial energy level. This leads to the emission of a 106

photon whose energy corresponds precisely to this energy differential. When photon emission is provoked by the arrival of other photons with the same energy as the photon emitted by de-excitation of the target atom, this “stimulated emission” produces coherent (in phase), monochromatic (a single wavelength) radiation. Lasers (the word is an acronym of light amplification by stimulated emission of radiation) are based on this phenomenon. It amplifies light and focuses it into a narrow unidirectional beam, allowing its energy to be delivered to a small, very precise target. The production of laser radiation requires an active medium that differs according to the type of laser, an excitation system (electrical stimulators), and a system to amplify the emitted radiation. This amplifier is known as a resonance chamber and is usually composed of two reflective surfaces. One surface is totally opaque while the other is only partially opaque, allowing laser energy to escape from the chamber. Luminescence (fluence) is responsible for the effects of laser radiation on matter. It is measured in joules per square centimeter (J/cm2).

Laser–Cornea Interactions There are four types of interaction between laser radiation and the cornea: absorption, transmission, reflection, and dispersion. Reflection and dispersion are weak phenomena on the cornea. The respective importance of absorption and transmission depends on the wavelength of the laser beam. Transmission is maximal at wavelengths between 400 and 1600 nm; this is the case of argon and yttrium-aluminumgarnet (YAG) lasers, which pass through the cornea without significant interactions. Absorption becomes predominant at wavelengths below 350 nm. This is the principal effect used for photoablative corneal surgery. Absorption itself can be broken down into three distinct effects: photothermal, photodisruptive, and photochemical. The photothermal effect is linked to the molecular vibrations induced by photonic energy and results in a temperature increase. The photodisruptive effect follows ionization. It emerges only at very high wavelengths of the micron

CHAPTER 7  Excimer Lasers

order (infrared). This is the mechanism of action of the YAG and femtosecond (FS) lasers. The photochemical effect usually occurs at short wavelengths. There are two principal types of photochemical effect: photoradiation and photoablation. The property used for refractive surgery is photoablation, which is obtained with ultraviolet radiation associated with very high energies. The action is very superficial (a few microns) at these very short wavelengths. The photonic energy exceeds that of chemical bonds, meaning that compounds are dissociated and tissue components are vaporized (Fig. 7.1). The shorter the pulse, the lower the risk of a thermal effect. With flying spot excimer lasers, which have a high pulse frequency, thermal

TABLE Various Generations of Excimer Lasers 7.1 

Generation

Feature

1st generation

Preclinical

2nd generation

Broad beam laser, fixed optical zone

3rd generation

Broad beam laser, variable optical zone multizone treatment

4th generation

Flying spot laser, built-in tracker, hyperopic treatment

5th generation

Customized wavefront (guided, optimized) treatments

6th generation

Faster ablation rates and tracking systems, lower biologic interaction, more variables under control, pupil size, advanced ablation profiles, cyclotorsion control, online pachymetry

Adapted from El Bahrawy M, Alió JL. Excimer laser 6th generation: state of the art and refractive surgical outcomes. Eye Vis (Lond). 2015;2:6.

effects are limited by the small size of the spots and by the fact that consecutive pulses are delivered at regular distances, giving the target site the time to cool off between impacts. The photoablative effect causes bleeding and therefore cannot be used to treat vascularized tissues.

Properties of the Excimer Laser Laser Beam Generation Gaseous Medium All excimer (combination of “excited dimer”) lasers are based on the same light-emitting mechanism: the reaction between a rare gas and a halogen. Excimer lasers employed in refractive corneal surgery use a gaseous mixture of argon and fluorine. An inert gas, helium, serves for energy transfer. Under the effect of strong electrical discharges (pulsed mode), electrons of the argon–fluoride (ArF) atoms move to a higher energy level; the excited atoms form an unstable molecule known as a dimer. The latter then returns to its stable state, emitting high-energy photons with a wavelength of 193 nm. Pulsed emission offers more power than continuous emission does. The ArF combination is chosen because it has the following properties: highly energetic photons, weak penetration into adjacent tissues, minimal thermal effects, a very regular impact surface, strong absorption by water, and lack of mutagenicity. Latest resonance chambers used to amplify photon emission are in ceramic. They generate highly fluent emissions, between 180 and 200 mJ/cm2.

Beam Homogenization Homogenization consists of narrowing the beam that emerges from the resonance chamber and maximizing crosssectional power uniformity. The beam is passed through an optical system consisting of mirrors, lenses, and prisms. Masks are used to select the central part of the beam, which has the highest and most constant energy. This beam

Plume effect

Excimer beam Photon energy 6.4 eV

0.25 µm Binding energy 3.5 eV

A • Fig. 7.1

B

Corneal tissue

107

C

Photoablation

  Mechanism of photoablation following absorption of excimer laser energy by the cornea. The photon energy (6.4 eV) exceeds the energy of molecular bonds. Molecular fragments are ejected at high speeds. A single impact removes about 0.25 µm.

108 se c t i o n III 108

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homogenization process entails a certain loss of power. The smaller the number of optical interfaces, the lower the energy loss. Each manufacturer has a proprietary homogenization system.

Beam Delivery System Once homogenized, the laser beam must be formatted to the desired photoablative effect. There are three main types of beam delivery system: full beam, scanning slit, and flying spot.

Full-Beam Systems (Fig. 7.2) These were used in first-generation lasers. Full beams offer more rapid treatment (for a given frequency) and are less sensitive to decentering. However, they are more difficult to homogenize and, therefore yield less regular ablation surfaces. Bystander thermal effects are also a problem. In addition, the shock wave generated by these lasers has been implicated in the higher frequency of central islands.9 A diaphragm or ablative mask must be used for refractive treatment. Customized treatment of complex shapes is impossible.

Scanning Slit Delivery A diaphragm is placed between the eye and a full beam, creating a rectangular beam with a smaller width (10 mm × 1 mm) and improving homogeneity. The ablation masks have a rotary motion, allowing the beam to scan in different directions (Fig. 7.3). These modifications overcome some of the disadvantages of full-beam systems while preserving their principal advantages (rapid treatment and low sensitiv-

ity to decentering).10 All types of ametropia can be corrected with scanning slit systems. It is now possible to divide each slit into several small rectangles. Such systems resemble flying spot systems and, theoretically, offer the possibility to treat complex, irregular shapes.

Flying Spot In this case, the beam is small and circular (between 0.6 and 2.0 mm in diameter). Only the most central, homogeneous part of the beam is used. The beam direction is controlled by pivoting mirrors (Fig. 7.4A). The target is ablated by repeated delivery of a large number of pulses, each pulse removing only a very small area of tissue. A very high pulse frequency is necessary to reduce overall treatment time, particularly when the spots are very small. The spots must be precisely dispersed in order to avoid thermal effects. An active eye tracker is crucial, as this type of system is very sensitive to decentering. The cross-sectional energy profile of each spot is generally Gaussian, to obtain smooth ablation surfaces. An interval of half a spot diameter between adjacent spots offers a regular depth of ablation between the two peaks. The main advantage of flying spot lasers is that they can provide asymmetric ablation profiles when coupled with corneal topography or wavefront analyzers. The capacity of these systems to correct complex irregularities increases as spot size decreases.11

Computer A computer controls the laser’s key parameters. In particular, fluence must remain constant throughout the procedure, which is achieved by modifying the power of the

Broad beam

Diaphragms

Myopia

• Fig. 7.2

Myopic astigmatism

Broad-beam delivery systems. Ablative diaphragms or masks are placed between the full beam and the cornea in order to obtain the desired refractive profile.  

CHAPTER 7  Excimer Lasers

1 2 3 4 5 6 7 8 9 10 Pulses

109

1 2 3 4 5 6 7 8 9 10 Pulses

1

3

2

A • Fig. 7.3

B

Rotary slit delivery system. This system combines corneal scanning by a fine rectangular slit (10 × 1 mm) with 120 degrees of rotation of the slit every n pulses and gradual opening of a motorized diaphragm. The schemas show an example of spherical myopic treatment: (A) passages 1 and 2; (B) passage 3.  

electrical discharges in the resonance chamber to compensate for the gradual degradation of the gaseous mixture. The computer is also used to choose the refractive or therapeutic mode, the ablation profiles (according to the refraction), and the diameters of the optical and transition zones. For customized ablation profiles, the computer integrates the corneal topography or wavefront data and calculates the optimal ablation profile accordingly.

theory, high frequencies are to be avoided, as thermal effects on the cornea start to emerge at 1 Hz. A compromise must be reached, however, as the treatment will take too long if the pulse frequency is too low. With full-beam lasers, the ideal frequency is between 10 and 50 Hz. The use of high frequencies with flying spot lasers is limited by the heat generated by each impact, which must be allowed to dissipate before hitting the same spot again.

Work Area

Pulse Energy

The operating table, microscope, and consoles differ with each system. The operating table must allow the patient’s head to be positioned correctly. The microscope must offer an adequate focal range and magnification, especially for laser in situ keratomileusis (LASIK) surgery. The focal length varies for each laser and must be sufficient to allow the flap to be cut with a mechanical microkeratome in good condition.

The energy delivered per broad beam pulse ranges between 10 and 250 mJ according to the laser. The energy difference between impacts can reach 10%. During a typical refractive procedure using a broad beam laser involving about 50 impacts, the total depth variation is ±0.1% (corresponding to about 0.1 D) and is negligible in clinical practice.

Parameters of the Laser Beam The 193-nm photon beam has a number of characteristic physical parameters. Variations in these parameters can modify both the photoablative effects on the target site and the bystander effects on adjacent corneal tissue.

Pulse Duration The pulses last from 4 to 25 ns, the excited dimer being highly unstable (half-life, 9–23 ns). Shorter pulses have lower thermal effects, limiting the consequences for adjacent tissue.

Pulse Frequency Pulse frequency (number of pulses emitted per second) varies from 10 to 1000 Hz, depending on the model. In

Fluence The photoablation threshold at the surface of the cornea is about 50 mJ/cm2 at a wavelength of 193 nm. Below this threshold, the photoablative action is irregular and incomplete. Each pulse with a fluence above this threshold ablates a precise amount of corneal tissue. The amount of tissue ablated per pulse increases in nonlinear fashion relative to fluence, up to a value of about 600 mJ/cm2, beyond which an increase in fluence no longer increases the amount of tissue photoablated by each pulse. Different lasers have fluences between 100 and 360 mJ/cm2, the optimal range.

Rate of Ablation Each laser possesses its own mean ablation rate per impact, ranging from 0.25 µm to 0.6 µm. A number of factors can influence the ablation rate. Each histologic layer of the cornea responds differently to laser radiation. Thus the epithelium ablates more rapidly than the stroma, which ablates

110 110 se c t i o n III

LASIK Techniques and Complications

2

1

3

A

B •

Fig. 7.4  Flying spot delivery system. (A) (1) Small laser beam; (2) mirror in X axis; (3) mirror in Y axis. A small laser spot sweeps the cornea. The pulse frequency must be high because of the small spot size (0.6-mm to 2-mm diameter). Spot mobility is ensured by a set of pivoting mirrors. No diaphragm or ablative mask is necessary for refractive ablation profiles. (B) Adjacent impacts must be offset by half a beam diameter so that the spatial sum of the energy profiles yields a constant ablation rate and a regular ablation substrate.

composition). These ruptured bonds cannot reform if the photon density exceeds a critical threshold. The formation of high-energy molecular fragments is accompanied by marked expansion and the creation of a hot gas (about 500°C). The molecular fragments are ejected at supersonic speeds (1000–3000 m/s) in a plume. This plume evacuates excess energy, thereby avoiding thermal damage to the residual tissue.12,13 The recoil generated by the ejection of photoablated matter creates a wave on the corneal surface. This wave, together with the shock waves created by the laser impacts, accounts for the noise associated with each impact (acoustic shock). The amplitude of the shock wave decreases gradually as it moves away from the center of the impact.14 When these two mechanical waves cross, they create fluid movement (clearly visible during photoablation for strong ametropia). Secondary ultraviolet radiation (fluorescence), with a wavelength above 193 nm, is produced when the pulse impacts the cornea. Only 0.001% of the primary radiation is converted into secondary radiation. It has a wavelength of 460 nm at the epithelium and 310 nm at the stroma and is visible as a discreet bluish light, particularly on the epithelium. During transepithelial photoablation, the change in color (disappearance of blue fluorescence) signals the end of the phase of epithelial ablation.15 The corneal penetration of this secondary irradiation is negligible, as its fluence is low (< 5 mJ/cm2).

Mutagenicity Ultraviolet light with a wavelength between 248 and 358 nm is absorbed by DNA and can cause mutations. Therefore the 193-nm laser beam should not be mutagenic, which has been confirmed by experimental studies. The secondary ultraviolet radiation emitted by fluorescence at the stromal level (310 nm) could theoretically be mutagenic, but its fluence (5 mJ/cm2) is below the mutagenic threshold (10 mJ/cm2).

Tissular Effects about 30% more rapidly than the Bowman layer. Corneal scars ablate less rapidly than healthy tissue. The ablation rate per impact also increases with corneal dehydration, which can lead to under- or overcorrection of 10% to 15%.

Effects of the Excimer Laser on Corneal Tissue Absorption of excimer laser radiation by the cornea mainly produces a photochemical effect (ablative photodecomposition), together with a small photothermal effect. A challenge of using excimer lasers in the human cornea is the biologic interaction. Wound healing responses may limit predictability of laser ablation and may contribute to the development of complications, such as haze formation.

Molecular Effects The 193-nm excimer laser emits very-high-energy photons (6.4 eV) that can break chemical bonds (ablative photode-

These effects, secondary to the photothermal effect, lead to structural modifications of corneal collagen, which can be affected by temperatures above 40°C. These modifications are reversible as long as the temperature remains below a threshold. In clinical practice, temperature increase in the stroma adjacent to the treatment field is no more than 1°C to 10° C. The collagen denaturation induced by this minimal temperature increase leads to the formation of a pseudomembrane, visible under the electron microscope as an electron-dense layer about 0.02 to 0.05 µm thick. Studies based on electron microscopy confirm that the residual tissue is not disrupted.

Eye Tracker All recent laser devices used clinically are equipped with a complex system that detects and compensates for eye movements that inevitably occur during the procedure. These

CHAPTER 7  Excimer Lasers

systems can be passive or active. An eye tracker is said to be active if the direction of the laser beam can follow any eye movements. The beam is generally oriented by mobile mirrors. Passive eye trackers interrupt the laser beam when the eyeball moves beyond certain limits. Some eye trackers combine the two approaches. The current trend toward customized treatments, with increasingly small spots and increasingly high pulse frequencies, requires parallel improvements in eye tracking systems. All eye movements that are not taken into account lead to a loss of treatment efficiency and reduce the final optical quality. The consequences of decentered treatments (leading to an increase in high-order aberrations) are now well quantified by wavefront analyzers.16,17

Eye Movements During Refractive Corneal Photoablation Even when the patient fixes a spot during treatment, involuntary ocular saccades are unavoidable. These movements during treatment can occur not only in the X–Y axis (horizontal plane), but also in the Z axis (vertical plane). For the latter, few effective systems are available, which is especially a concern with small spots. Two types of cyclotorsion must also be taken into account. First, passage from the sitting to the horizontal position frequently causes rotation. Cyclotorsion of 15 degrees leads to a 50% loss of treatment effect. The same problem arises when treating high-order aberrations, as the decentering effect increases with the degree of aberration.18 The best way to overcome this problem is to use a tracking system based on iris recognition; marking the conjunctiva with a felt-tipped pen is also possible. Second, moderate perioperative cyclotorsion has also been described; cyclotorsional eye trackers that can correct for these movements are a standard feature of modern laser platforms.

induced by the change of position from seated to horizontal is also taken into account. This technique offers the added safety of avoiding confusion between two patients, each iris being unique. Modern eye trackers track the cyclotorsion rotations, which can be classified into static (when the patient moves from an upright to a supine position) or dynamic (occurring during the treatment procedure).6 Prickett et al. evaluated the average cyclotorsional and noncyclotorsional components (NCY) of eye rotation from sitting to supine position.19 Most of the rotations were most likely due to NCY, such as postural misalignments. Measured iris rotation (total rotation [TR]) was decomposed into two components: NCY, defined as the common rotation component of each eye of the same patient, and cyclotorsional component (CY), defined as the assumed independent eye rotation for each eye in relation to the face, so that TR = NCY + CY (Fig. 7.5). Cyclotorsion ratio (CR) was calculated as CR = |CY|/|TR| and used to correlate CY with TR for each eye. TR demonstrated that 40.6% and 8.4% of patients presented bilateral excyclotorsion and incyclotorsion, respectively. When excluding NCYs, average CYs demonstrated that 74.2% of patients presented with excyclotorsion and 23.9% presented with incyclotorsion, respectively. CR demonstrated that TR represented from 75% to 125% of

Non-Cyclotorsional Component (NCY)

Total Rotation (TR) +14o

Eye Tracker Function Eye Movement Recording An eye tracker comprises a system that records eye movements, usually with an infrared detector. A charge-coupled device (CCD) camera acquires and digitizes the iris. The center of the pupil serves as a set point against which eye movement can be measured. Detection efficiency improves with the sampling frequency of the infrared camera. The maximum sampling frequency can reach 500 Hz. The most modern systems are based on iris recognition systems. The image of the iris is acquired and digitized during preoperative examinations (wavefront analysis) with the patient seated. The image is transferred to the laser platform. Treatment can then be carried out with the patient horizontal while respecting the position of each impact calculated during the preoperative examination. The change in position of the pupil in the horizontal plane (X, Y) induced by its dilation is measured preoperatively and compensated for during the laser surgery. The cyclotorsion

111

+10o

+6o

A

B NCY Compensation

Average Cyclotorsional Component (CY)

-10o

+4o

C •

-4o

D

Fig. 7.5  Diagram demonstrating average cyclotorsional (CY) and noncyclotorsional (NCY) components of total rotation (TR) measured. (A) TR measured in supine position in relation to seated position. (B) NCYs calculated as mentioned in the text. (C) Graphical representation of NCYs compensation. (D) Final average CY. (From Prickett AL, Bui K, Hallak J, Bakhtiyari P, de la Cruz J, Azar DT, Chamon W. Cyclotorsional and non-cyclotorsional components of eye rotation observed from sitting to supine position. Br J Ophthalmol. 2015;99(1):49–53.)

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average CY in 19.68% of the eyes. TR overestimated and underestimated average CYs above these limits in 52.26% and 28.06% of the eyes, respectively. There was no statistical association between average CYs and the different variables.19

FDA-Approved Excimer Lasers (2006 to Present) Table 7.2 provides a comprehensive list of the lasers that got approved by the FDA after 2006.20 It also lists the indications and the characteristics of each laser system.

Current systems are characterized by technologies such as wavefront-guided ablations, corneal topographers, treatment planning software, and variable spot scanning systems. These technologies have led to significant improvements in clinical outcomes for refractive surgery procedures.

Topography and Wavefront-Based Treatments in Excimer Lasers Topography-Guided Laser Refractive Surgery Topography-guided ablation treats corneal surface irregularities in addition to treating refractive error. Some studies

TABLE List of FDA-Approved Excimer Lasers (2006-Present) 7.2 

Device Name/Company and Approval Date

Indications

Laser System

STAR S4 IR Excimer Laser System and iDesign Advanced WaveScan Studio System – P930016/S044 AMO Manufacturing USA LLC May 6, 2015

The systems are intended for wavefront-guided LASIK treatment of up to −11 diopters of power (D) of nearsightedness and up to −5 D of astigmatism as measured by the iDesign System.

• Eye tracker • iDesign System that includes an aberrometer • Corneal topographer • Treatment-planning software

Nidek EC-5000 Excimer Laser System September 30, 2013

Topography-assisted LASIK treatment using the Final Fit custom ablation treatment planning software for the reduction or elimination of myopic refractive errors from −1.0 D to −4.0 D of sphere with astigmatic refractive errors from > −0.5 to −2.0 at the spectacle plane.

• Corneal topographer • Treatment-planning software

Allegretto Wave Eye-Q Excimer Laser System September 27, 2013

Topography-guided LASIK treatment used in conjunction with the WaveLight Allegro Topolyzer and T-CAT treatment-planning software for reduction or elimination of up to −9.0 D of spherical equivalent myopia with or without astigmatism, of up to −8.0 D of spherical equivalent and up to −3.00 D of astigmatic component at the spectacle plane.

• WaveLight Allegro Topolyzer • Corneal topographer • T-CAT treatment-planning software

Meditec MEL 80 Excimer Laser System March 28, 2011

Primary LASIK treatment using an optical zone of 6.0–6.5 mm diameter and transition zone of 2.0–4.0 mm, for the reduction of elimination of naturally occurring hyperopia of ≤ +5.0 D with or without astigmatism of >+0.5 and ≤ +3.0 D with a maximum MRSE of + 5.0 D.

• Gaussian beam • Laser control software • Eye tracker

STAR S4 IR Excimer Laser System and Wavescan System July 11, 2007

Wavefront-guided LASIK to achieve monovision by the targeted retention of myopia of −1.25 D to −2.00 D in the nondominant eyes of presbyopic myopes, with myopic astigmatism up to −6.00 D MRSE, with cylinder up to −3.00 D, and minimum preoperative myopia in their nondominant eye at least as great as their targeted myopia. Uses variable spot scanning and Wavescan wavefront system.

• Variable spot scanning • Wavescan wavefront system

Nidek EC-5000 Excimer Laser System October 11, 2006

LASIK treatment using a 6.0-mm optical zone and a 9.0-mm treatment zone for the reduction or elimination of hyperopic refractive errors from +0.5 D to +5.0 D of sphere with or without astigmatic refractive errors from +0.5 to +2.0 D at the spectacle plane with MRSE of +5.0 or less.

• Dragon eye software • Eye tracker

CHAPTER 7  Excimer Lasers

113

TABLE List of FDA-Approved Excimer Lasers (2006-Present)—cont’d 7.2 

Device Name/Company and Approval Date

Indications

Laser System

MEL 80 Excimer Laser System August 25, 2006

Primary LASIK treatment using an optical zone of 6.0–7.0 mm diameter and a transition zone of 1.7–1.9 mm diameter for the reduction or elimination of myopia of ≤ −7.0 D, with or without refractive astigmatism of ≤ −3.0 D, with a maximum MRSE of −7.0 D.

• Eye tracker • OPASS Software

WaveLight Allegretto Wave Excimer Laser System August 17, 2006

Wavefront-guided LASIK for the reduction or elimination of up to −7.0 D of spherical equivalent with myopia or myopic astigmatism, with up to −7.0 D of spherical component and up to 3.0 D of astigmatic component at the spectacle plane. Used in conjunction with the WaveLight Allegro analyzer, and using a 6.5-mm optical zone and a 9.0-mm ablation zone.

• Wavelight Allegro Analyzer

WaveLight Allegretto Wave Excimer Laser System May 12, 2006

LASIK treatment using optical zone of 6.0–7.0 mm with an ablation zone of up to 9.0 mm for the reduction or elimination of naturally occurring mixed astigmatism of up to 6.0 D at the spectacle plane.

• WaveLight Allegretto Wave • Wavefront guided • Scanning spot

LASIK, Laser in situ keratomileusis, MRSE, manifest refraction spherical equivalent; T-CAT, topography−computer assisted treatment.

have shown that topography-guided ablation improved outcomes when treating postoperative complications, such as ectasia, decentered ablation, and small optical zones.21,22 In a prospective study, Stulting et al. evaluated the safety and efficacy of topography−computer assisted treatment (T-CAT) to correct myopia and myopic astigmatism with LASIK.23 They found that the T-CAT procedure significantly reduced the manifest refraction spherical equivalent and cylinder, with stability of outcomes from 3 to 12 months after surgery. Postoperative uncorrected distance visual acuity improved by 1 line or more in 30% of eyes, and most visual symptoms improved after T-CAT.23

Wavefront-Based Laser Refractive Surgery Wavefront-based treatments have increased ablation accuracy and predictability. They have been shown to decrease induced higher-order aberrations and can be divided into two categories: wavefront-optimized and wavefront-guided algorithms.8 In wavefront-optimized systems, additional laser pulses are delivered to the periphery of the cornea in order to maintain the natural corneal shape; this, in turn, helps preserve the original spherical aberration. Wavefront-optimized treatments apply an additional precalculated ablation depending on the patient’s refractive error and keratometry, without addressing individual preexisting higher-order aberrations.8 They do not require wavefront imaging. Wavefront-guided treatments require preoperative wavefront measurements of the eye to develop customized ablations to reduce preoperative higher-order aberrations. The customized ablation profile then guides the laser in reshap-

ing the corneal surface. Two popular laser platforms are the WaveLight Allegretto and the VISX custom Vue Star S4 IR. Most studies found no significant differences between these two main laser platforms. Two globally popular excimer laser platforms that offer wavefront-optimized ablation algorithms are the Schwind Amaris 750S and the MEL 90. According to a prospective, comparative study done by Khalifa et  al., wavefront-guided LASIK provided a more effective correction of myopic astigmatism than wavefront-optimized LASIK in 221 myopic eyes.24 In both low and moderate astigmatism eyes, the wavefrontguided group showed significantly better postoperative uncorrected visual acuity (UCVA) and efficacy (P ≤ .041). The wavefront-guided treatment group also showed that 90.6% of eyes had a postoperative cylinder less than or equal to 0.25 D compared to 65.5% of eyes for the wavefront-optimized treatment group for moderately myopic eyes (P = .002). Further, for both low and moderate myopia, wavefront-guided ablations induced significantly less higher-order aberrations (P ≤ .006).24 Wavefront-guided LASIK has also been reported to offer significantly better results than wavefront-optimized LASIK in terms of contrast sensitivity, uncorrected distance acuity, and residual refractive error.25 He et al., in a prospective, randomized, fellow-eye-controlled study of 110 eyes with myopia with or without astigmatism, compared the clinical outcomes of wavefront-guided and wavefront-optimized LASIK. They reported that both treatments are safe and effective; however, wavefront-guided treatments appear to be better in terms of residual refractive error, uncorrected distance acuity, and contrast sensitivity.25 In the wavefrontguided group, 56% eyes achieved visual acuity of 20/12.5 or

114 114 se c t i o n III

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better compared to 41% of eyes in the wavefront-optimized group. Better-corrected visual acuity was achieved for the wavefront-guided group at both 5% and 25% contrast sensitivities.25 According to another prospective, randomized, comparative study done on the effect of wavefront-guided versus wavefront-optimized LASIK on subjective quality of vision by Kung and Manche,26 the self-reported patient visual outcomes were similar for both groups. Of the 55 patients, 45% had no preference between the treatments, 36% preferred wavefront-guided, and 19% preferred wavefrontoptimized treatments. In patients who had higher-order aberrations less than 0.3 µm in both eyes, wavefrontoptimized treatment trended toward worse fluctuating vision, daytime clarity, and nighttime clarity.26 In terms of wavefront-optimized versus wavefront-guided photorefractive keratectomy (PRK), wavefront-guided treatment has been shown to offer a small advantage in photopic low-contrast visual acuity. In a study by Sia et al., both groups were comparable in terms of coma, trefoil, spherical aberration, and total higher order aberrations.27

Topography-Guided Ablation Profiles Compared to Wavefront-Based Treatments Studies directly comparing topography-guided versus wavefront-based treatment have been performed. In a contralateral eye study, Falavarjani et al. demonstrated similar visual outcomes and contrast sensitivity after PRK with topography-guided ablation in one eye and wavefrontoptimized in the other eye.28 Reinstein et al. demonstrated that, in cases of a large-angle kappa, topography-guided ablations better approximate the visual axis than wavefrontguided ablations centered on the pupil.29 Comparing the visual outcomes of T-CAT and wavefront-optimized ablation profiles in myopic eyes, Shetty et al. performed a prospective interventional study in 60 eyes of 30 patients.30 For each patient, T-CAT was performed in one eye and wavefront-optimized treatment in the other eye. Although there was a greater decrease in individual higher-order aberrations, along with a better root mean square of lower-order aberrations in eyes treated with T-CAT (P < .05), essentially similar accuracy, safety, and efficacy were seen in both treatment groups. Recently, there has been interest in combining the advantages of topographyguided and wavefront-laser systems into a phenomenon called ray tracing. This method would be helpful in cases in which a decision tree needs to be employed to choose which ablation profile to use, especially in cases in which wavefront maps cannot be validated and there is a need to drive ablation profiles based on corneal topography.

Conclusions Excimer laser platforms have improved significantly over the years. These platforms have not only improved the safety and efficacy of refractive surgery procedures, but have

also allowed the development of new techniques, such as wavefront-based and topography-guided treatments. Future developments will further tailor treatments for patients with spherocylindrical errors, higher-order aberrations, and induced aberrations, improving refractive surgery outcomes.

References 1. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery of the cornea. Am J Ophthalmol. 1983;96(6):710–715. 2. Marshall J, Trokel S, Rothery S. Photoablation reprofiling of the cornea using an excimer laser photorefractive keratectomy. Lasers Ophthalmol. 1986;1:21–48. 3. Munnerlyn C, Koons SJ, Marshall J. Photorefractive keratectomy: a technique for laser refractive surgery. J Cataract Refract Surg. 1988;14(1):46–52. 4. McDonald MB, Frantz JM, Klyce SD, et al. One-year refractive results of central photorefractive keratectomy for myopia in the nonhuman primate cornea. Arch Ophthalmol. 1990;108(1): 40–47. 5. McDonald MB, Kaufman HE, Frantz JM, et al. Excimer laser ablation in a human eye. Arch Ophthalmol. 1989;107(5): 641–642. 6. El Bahrawy M, Alio JL. Excimer laser 6th generation: state of the art and refractive surgical outcomes. Eye Vis (Lond). 2015;2:6. 7. Kohnen T. Classification of excimer laser profiles. J Cataract Refract Surg. 2006;32(4):543–544. 8. Chen LY, Manche EE. Comparison of femtosecond and excimer laser platforms available for corneal refractive surgery. Curr Opin Ophthalmol. 2016;27(4):316–322. 9. Assouline M, Moossavi J, Muller-Steinwachs M, et al. PMMA model of steep central islands induced by excimer laser photorefractive keratectomy. Surv Ophthalmol. 1997;42(suppl 1):S35–S51. 10. Lubatschowski H, Kermani O, Welling H, et al. A scanning and rotating slit ArF excimer laser delivery system for refractive surgery. J Refract Surg. 1998;14(suppl):S186–S191. 11. Huang D, Arif M. Spot size and quality of scanning laser correction of higher-order wavefront aberrations. J Cataract Refract Surg. 2002;28(3):407–416. 12. Puliafito CA, Stern D, Krueger RR, et  al. High-speed photography of excimer laser ablation of the cornea. Arch Ophthalmol. 1987; 105(9):1255–1259. 13. Srinivasan R, Dyer P, Braren B. Far-ultraviolet laser ablation of the cornea: photoacoustic studies. Lasers Surg Med. 1987;6(6): 514–519. 14. Krueger RR, Seiler T, Gruchman T, et al. Stress wave amplitudes during laser surgery of the cornea. Ophthalmology. 2001; 108(6):1070–1074. 15. Phillips AF, McDonnell PJ. Laser-induced fluorescence during photorefractive keratectomy: a method for controlling epithelial removal. Am J Ophthalmol. 1997;123(1):42–47. 16. Mrochen M, Kaemmerer M, Mierdel P, et al. Increased higherorder optical aberrations after laser refractive surgery: a problem of subclinical decentration. J Cataract Refract Surg. 2001;27(3): 362–369. 17. Marcos S, Barbero S, Llorente L, et  al. Optical response to LASIK surgery for myopia from total and corneal aberration measurements. Invest Ophthalmol Vis Sci. 2001;42(13):3349–3356. 18. Chernyak DA. Cyclotorsional eye motion occurring between wavefront measurement and refractive surgery. J Cataract Refract Surg. 2004;30(3):633–638.

CHAPTER 7  Excimer Lasers

19. Prickett AL, Bui K, Hallak J, et al. Cyclotorsional and noncyclotorsional components of eye rotation observed from sitting to supine position. Br J Ophthalmol. 2015;99(1):49–53. 20. U.S. Food & Drug Administration. List of FDA-Approved Lasers for LASIK. https://www.fda.gov/MedicalDevices/Productsand MedicalProcedures/SurgeryandLifeSupport/LASIK/ucm192109 .htm. Accessed August 29, 2017. 21. Lin DT, Holland S, Tan JC, Moloney G. Clinical results of topography-based customized ablations in highly aberrated eyes and keratoconus/ectasia with cross-linking. J Refract Surg. 2012;28(11 suppl):S841–S848. 22. Chen X, Stojanovic A, Zhou W, Utheim TP, Stojanovic F, Wang Q. Transepithelial, topography-guided ablation in the treatment of visual disturbances in LASIK flap or interface complications. J Refract Surg. 2012;28(2):120–126. 23. Stulting RD, Fant BS, T-CAT Study Group, et al. Results of topography-guided laser in situ keratomileusis custom ablation treatment with a refractive excimer laser. J Cataract Refract Surg. 2016;42(1):11–18. 24. Khalifa MA, Alsahn MF, Shaheen MS, Pinero DP. Comparative analysis of the efficacy of astigmatic correction after wavefrontguided and wavefront-optimized LASIK in low and moderate myopic eyes. Int J Ophthalmol. 2017;10(2):285–292.

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25. He L, Liu A, Manche EE. Wavefront-guided versus wavefrontoptimized laser in situ keratomileusis for patients with myopia: a prospective randomized contralateral eye study. Am J Ophthalmol. 2014;157(6):1170–1178. 26. Kung JS, Manche EE. Quality of vision after wavefront-guided or wavefront-optimized LASIK: a prospective randomized contralateral eye study. J Refract Surg. 2016;32(4):230–236. 27. Sia RK, Ryan DS, Stutzman RD, et al. Wavefront-guided versus wavefront-optimized photorefractive keratectomy: clinical outcomes and patient satisfaction. J Cataract Refract Surg. 2015; 41(10):2152–2164. 28. Falavarjani KG, Hashemi M, Modarres M, Sanjari MS, Darvish N, Gordiz A. Topography-guided vs wavefront-optimized surface ablation for myopia using the WaveLight platform: a contralateral eye study. J Refract Surg. 2011;27(1):13–17. 29. Reinstein DZ, Archer TJ, Gobbe M. Is topography-guided ablation profile centered on the corneal vertex better than wavefrontguided ablation profile centered on the entrance pupil? J Refract Surg. 2012;28(2):139–143. 30. Shetty R, Shroff R, Deshpande K, Lahane S, Jaydeva C. A prospective study to compare visual outcomes between wavefront-optimized and topography-guided ablation profiles in contralateral eyes with myopia. J Refract Surg. 2017;33(1):6–10.

8 

Laser and Mechanical Microkeratomes JOELLE HALLAK, FRÉDÉRIC VAYR, PHILIPPE CHASTANG, AND THANH HOANG-XUAN

Introduction Unlike methods of surface photoablation, the laser in situ keratomileusis (LASIK) technique requires a superficial corneal flap to be created prior to photoablation with an excimer laser. Mechanical microkeratomes and femtosecond lasers have been the two methods for LASIK flap creation. Safety is excellent with both methods, although the risk of complications cannot be eliminated. Femtosecond technol­ ogy has allowed greater safety and studies have shown that compared with mechanical microkeratomes, femtosecond lasers provide more predictable flap dimensions. In theory, femtosecond lasers are advantageous because they can create precise cutting to allow variation of flap width, depth, hinge, and side cuts.1 However, femtosecond lasers can also lead to unforeseen complications. In this chapter, we provide a general description of mechanical microkeratomes, followed by a detailed descrip­ tion of femtosecond lasers. Studies comparing the femto­ second lasers and mechanical microkeratome are discussed. Additionally, newer applications for the femtosecond laser, such as small incision lenticule extraction (SMILE) will be described.

Mechanical Microkeratomes In 1958, José Ignacio Barraquer, the father of modern corneal refractive surgery, unveiled his first manual microkeratome, which he had designed for keratophakia and freeze keratomi­ leusis. Until 1984, the microkeratome was used to cut a free corneal flap, which was frozen, cryolathed on its posterior surface, thawed, and then sutured back in place.2,3 1985 saw the introduction of the nonfreeze kerato­ mileusis technique by Krumeich and Swinger. The len­ ticule was processed unfrozen on its stromal side with a Barraquer-­Krumeich-Swinger (BKS) refractive system 1000 refractive set.4,5 In 1986, Ruiz introduced the in situ keratomileusis tech­ nique, in which a microkeratome was used to make two consecutive cuts with a diameter and depth that varied according to the degree of ametropia, using a set of suction 116

rings of different sizes, calibrated applanation lenses, and various plates. Motorized microkeratomes, of which the Castroviejo electrokeratome (unveiled in 1963) was the pre­ cursor, became practical in 1991 with Ruiz and Lenchig’s automated corneal shaper (ACS; Chiron; Fig. 8.1), which made more reproducible cuts. The ACS was equipped with a system of gears to ensure a constant rate of movement on the suction ring to create a corneal flap with a nasal hinge. The height of the suction ring could be adjusted to vary the diameter of the second cut, avoiding the need to change rings. However, this automated lamellar keratoplasty (ALK) technique6 was imperfect and poorly reproducible. It was abandoned in 1995 in favor of LASIK, in which photoabla­ tion with a 193-nm excimer laser replaces the second refrac­ tive mechanical cut. The first human LASIK treatment was done in 1990.7 In 1996, the Carriazo–Barraquer pivoted rotating micro­ keratome (CB) appeared on the market, with the theoretical advantage of allowing the hinge to be placed wherever desired. The use of an upper hinge limited the risk of flap displacement during blinking. Moria, the company that manufactured the device, also marketed the first disposable adaptable microkeratome heads. In 1997, Chiron released the Hansatome automated microkeratome, which allowed a corneal flap with an upper hinge. In 2001, Carriazo unveiled the first generation of pendular microkeratomes (Carriazo Pendular, Schwind). The cutting head moves ver­ tically rather than horizontally, and the pendular motion requires a slightly lower cutting pressure than do conven­ tional microkeratomes, leading to less mechanical friction and smaller size. Perhaps the most important advance in corneal flap creation technology is the introduction of the femtosecond laser microkeratome (Fig. 8.2). Pallikaris developed an alternative modality of epithelial separation with a blunt oscillating separator similar to a mechanical microkeratome used for LASIK flaps, which he called Epi-LASIK–Centurion.8 In contrast to laser-assisted subepithelial keratectomy (LASEK), this surgical approach does not require the use of alcohol for epithelial loosening.9 Mechanical microkeratomes consist of the following basic components: (1) a peripheral part (Fig. 8.3) that

CHAPTER 8  Laser and Mechanical Microkeratomes

• Fig. 8.1

 

Automated corneal shaper (Chiron) microkeratome.

117

includes the suction ring, the microkeratome head, and the drive unit; (2) a central unit, which delivers the calibrated energy necessary to power the motors; and (3) connections/ accessories that include two pedals, one to start and stop the vacuum and the other to control blade oscillation. Most microkeratomes are fully reusable after dismantling, cleaning, and sterilization, apart from the blade, which is always single use. The single-use components can include all the peripheral components (suction ring, preassembled head and blade, and handpiece; Steritome); the head alone, equipped with a preassembled blade (CBSU and M2SU); and both the head (with the preassembled blade) and the suction ring (LSK One Use and One Use-plus). Most mechanical microkeratomes require the use of both hands, one holding the suction ring and the other the microkeratome. Additionally, all mechanical microkera­ tomes have some safety devices, for example, a manually adjustable hinge stop (LSK One, M2, and M2SU), and a tunnel-shaped ring protecting the cutting head progression against mechanical obstruction.

Laser Microkeratomes: The Femtosecond Lasers The safety of mechanical microkeratomes has improved markedly over the years but complications still occur, espe­ cially in patients with thin, flat, or steep corneas. In addi­ tion, the mechanical nature of the cut can be off-putting for the patient. Preparation of the corneal flap with a fem­ tosecond laser appears to overcome these problems (Fig. 8.3). Flap size, flap thickness, edge angle, hinge width, and hinge location are more controlled with the computerguided femtosecond laser platforms. A

B •

Fig. 8.2  Femtosecond laser microkeratome. (A) IntraLase FS2 (Abbott Medical Optics, Inc.) femtosecond laser unit. (B) Screenshot during flap creation. A raster scan pattern is used to create the flap for a LASIK procedure (Video 8.1).

Physical Principles of the Femtosecond Laser The femtosecond laser delivers ultrashort pulses lasting about 10−15 s. Its wavelength is situated in the infrared (about 1000–1053 nm). As the cornea is infrared transpar­ ent, femtosecond laser energy is not absorbed by the cornea, contrary to the excimer laser beam. The main feature of femtosecond lasers is that high powers can be obtained with low-energy pulses. Higher energies would immediately destroy the laser components. Several femtosecond laser systems are available today, including the IntraLase (Abbott Medical Optics, Inc.), the Wavelight (Alcon Surgical, Inc.), the Visumax (Carl Zeiss Meditec AG), the Victus (Bausch & Lomb Technolas GmbH), and the Femto LDV (Ziemer Ophthalmic Systems AG) (Video 8.2). Newer-generation femtosecond plat­ forms with higher frequency (60 kHz, 150 kHz, 500 kHz) produce more predictable LASIK flaps with a more uniform flap interface and less inflammation.10 The IntraLase was the first commercially available platform.10 The system has

118 se c t i o n III 118

LASIK Techniques and Complications

A

B

C

E

F

G

D

H

• Fig. 8.3

  Suction ring. (A) Suction ring (sr) (LSK One [Moria]) with two parallel dove-tail grooves (arrows) for rectilinear translation; h, head; s, stop; and du, drive unit. (B) Different angle view of suction ring. (C) suction ring (CB [Moria]) with single arciform rail. (D) linear microkeratome head (LSK One [Moria]) (left). (E) pivoted rotating microkeratome head (CB [Moria]) (right). (F) 130-mikron microkeratome head (CB [Moria]): it creates a 160-mikron flap. (G) cavities of a microkeratome head (LSK One [Moria]): (a) for the blade/folder unit; (b) for the flap. (H) the drive unit (du) is screwed to the microkeratome head (h) in order to ensure that the drive axis fits the blade holder properly and oscillates correctly; (c) connections between gas turbine drive unit and central unit (Video 8.3).

been continuously updated with changes in the laser pulse rate (from 15–30 to 60–150 kHz). Laser energy is created through Nd:glass (amplification glass matrix mixed with neodymium). Emission of low-energy pulses necessitates a pulse amplifier placed downstream of the generator (chirped pulse amplification [CPA] system). The delivery system, composed of two perpendicular galvanometers (rotary mirrors), allows 3-dimensional scanning of the laser. The beam is focused to the desired corneal depth by an aspheric convergent lens. The Visumax is another widely used system. Multiple studies have compared the IntraLase to the Visumax. No significant differences were found in safety, efficacy, and pre­ dictability.11,12 The efficiency of an eye tracker after LASIK flap creation among the two systems was also evaluated with no significant differences.13 Using higher-frequency lasers, Yu and Manche in two prospective studies compared the morphologic features of LASIK flaps created with the FS 60 kHz and the iFS 150 kHz,14 and the visual outcomes.15 With regard to morphology, both lasers produced uniform planar flaps, but mean thickness was greater with the Intra­ Lase 60 kHz.14 With regards to visual outcomes, while both systems produced excellent visual results, a higher intraoperative patient preference and a trend toward faster visual recovery was observed with the IntraLase 150-kHz platform.15

Corneal Interactions With the Femtosecond Laser The femtosecond laser causes molecular disruption within the cornea owing to atomic ionization. The beam must be focused on a spot small enough to reach the required fluence threshold (energy per unit surface area). Ionization during ultra-brief pulses is provoked by multiphotonic absorption, that is, simultaneous absorption of several photons by a single electron of a given atom, which confers enough energy to liberate the electron. The phenomenon is nonlinear,16 varying exponentially with the number of photons absorbed. The free electron then generates other free electrons by collision in a process known as avalanche ionization. With ultra-brief pulses, the energy remains concentrated close to the impact, and the laser–matter interaction is very short lived. The free electrons are extremely energetic and their energy is trans­ ferred very rapidly to the surrounding medium. The target tissue is vaporized directly and the resulting vapor has very high kinetic energy. This results in the characteristic acoustic shock, which dissipates most of the energy. The volume of vaporized matter (cavitation bubble) is small and very precise. The shorter the pulse, the lower the fluence threshold neces­ sary to vaporize the target tissue. This reduces the required pulse energy and the size of the cavitation bubble. For a spot diameter of 5 to 10 µm, a pulse lasting 450 femtoseconds

CHAPTER 8  Laser and Mechanical Microkeratomes

A

B

• Fig. 8.4

  Central units: (A) MK-2000 (Nidek). (B) Evolution 3 (Moria). (Courtesy Prof. Jean-Marc Legeais, Laboratoire Biotechnologie et Oeil, Hôtel-Dieu Paris). [Figure 10-5, 2nd ed.]

with an energy of 7.5 µJ produces cavitation bubbles 10 µm in diameter. The cavitation bubble can be smaller than the spot itself (down to 2 µm). Scanning electronic microscopy of the surface of corneal stroma after lamellar dissection of a corneal flap with the femtosecond laser shows a regular surface and precise dis­ section (Fig. 8.4A). The collateral thermal effects of fem­ tosecond pulses are minimal. The zone of thermal damage extends very little beyond the cavitation bubble.17

Corneal Flap Preparation With the Femtosecond Laser With the IntraLase laser, a suction ring is used but the increase in intraocular pressure (IOP) is small (about 30 mmHg). A cone incorporating a glass applanation lens is crucial to obtain a cut with parallel faces (Fig. 8.4B). Cut depth range is 90 to 400 µm. The largest flap diameter is 9 mm. Lamellar dissection is achieved by juxtaposing very small impacts, about 3 µm in diameter. The impacts are delivered in raster mode (consecutive lines of impacts paral­ lel to the hinge; Fig. 8.4C). The first pulses are delivered along the hinge. A pocket is first created to receive the gases generated during treatment. The edges of the flap are pre­ pared last with a variable angle chosen by the operator. This ensures excellent stability when the flap is put back in place. The many thousands of impacts required to cut the flap are delivered in less than 45 s. The flap is raised with a blunt spatula, starting next to the hinge.

Advantages and Disadvantages of the Femtosecond Laser Femtosecond lasers have numerous theoretical advantages. All intraoperative mechanical microkeratome-induced flap complications—such as free and incomplete flaps, button­ holes, or epithelial erosions—are markedly reduced. The reduction in IOP increase during flap creation improves patient comfort and limits the risk of optic nerve damage. The flap geometry, especially its depth, is far better con­ trolled. Thin flaps (< 100 µm) can be prepared, if necessary (high myopia; thin corneas). The hinge can be placed in any

119

direction and its size can be adjusted (the larger the hinge, the lower the degree of postoperative dry eye). The angu­ lated cut edges improve the stability of the flap when it is put back in place. This should reduce the astigmatism and high-order aberrations induced by the cut, together with the risk of postoperative flap dislocation, folds, and epithe­ lial ingrowth. The absence of metallic debris should also reduce the risk of diffuse lamellar keratitis. Femtosecond lasers also have other applications, such as for lamellar kera­ toplasty and intrastromal tunnel creation before intracor­ neal ring segment insertion.18 Drawbacks of the femtosecond laser for LASIK flap cre­ ation include the need to switch the patient to the excimer laser during the procedure (this can be overcome with a pivotable excimer laser bed, the moderately (few minutes) increased procedure duration, and mainly the current cost of the device.

Comparison Between Mechanical Microkeratome and Femtosecond Laser The major advantage of femtosecond lasers has been the accuracy of flap creation and reduced complications, with the majority of studies showing improved uniformity and predictability with femtosecond laser-created flaps when compared to mechanical microkeratomes.1,18 With regard to complications, LASIK flap complications were reported to be as high as 5% with mechanical microkeratomes1 versus femtosecond lasers, which ranged from 0.33% to 0.92%.19–21 Femtosecond lasers had lower rates of epithelial defects,22,23 flap displacement,24 and epithelial ingrowth25 when com­ pared to mechanical microkeratomes. Dry eyes have also been the most common side effect of LASIK. Femtosecond laser flaps may induce less dry eyes.26 However, early femto­ second lasers have been shown to have a higher incidence of diffuse lamellar keratitis than microkeratomes.27,28 A systematic review and meta-analysis evaluated the safety, efficacy, and predictability of the IntraLase femtosec­ ond laser assisted compared to the microkeratome assisted for myopic LASIK.29 A total of 3679 eyes were identified. No significant differences were identified between the two groups with regard to safety and efficacy as defined by loss of greater than or equal to two lines of corrected distance visual acuity, patients achieving uncorrected distance visual acuity 20/20 or better, final uncorrected visual acuity, final mean refractive spherical equivalent, final astigmatism, or changes in higher-order aberrations. However, the Intra­ Lase group had advantages in predictability: more patients were within ±0.50 diopters of target refraction compared to the microkeratome group, and flap thickness was more predictable in the IntraLase group. Additionally, the micro­ keratome group had more epithelial defects, whereas the IntraLase group had more cases of diffuse lamellar kera­ titis.29 In another meta-analysis of randomized controlled trials, Zhang et al. reported that femtosecond LASIK did not have an advantage in efficacy, accuracy, and safety

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measures over mechanical microkeratome LASIK in the early and midterm follow-up, although femtosecond LASIK may induce fewer aberrations.30 Observational studies comparing the femtosecond laser and mechanical microkeratome included prospective studies and retrospective case series. Pajic et al., in a prospective randomized, paired-eye study in which the femtosecond was applied in one eye and the microkeratome in the other eye for each patient, evaluated the visual outcomes and the deviation of flap thickness.31 An efficiency index, defined as the visual outcome differences between the corrected dis­ tance visual acuity at baseline and the uncorrected distance visual acuity on the first day postoperatively, showed that the femtosecond laser was superior to the microkeratomeassisted LASIK in the speed of visual acuity recovery. Six months after surgery, improvement in the uncorrected dis­ tance visual acuity was significant in both groups. Flap thickness deviation in the microkeratome eyes was higher.31 In another prospective nonrandomized study, Xia et al. reported that both the microkeratome and femtosecond laser for flap creation are safe and effective to correct myopia. However, the femtosecond laser may have advantages in flap thickness predictability, fewer induced higher-order aberra­ tions, better contrast sensitivity, and longer tear breakup time.32 In a retrospective case series, Antonios et al. evalu­ ated predictability and safety of LASIK flap creation with a femtosecond laser and a mechanical microkeratome for mild to moderate hyperopia.33 They reported that the shortterm outcomes were comparable; however, the femtosecond laser group showed significantly better stability over the 6-month follow-up and better predictability.

Conclusions Although LASIK techniques have significantly evolved with advancements in flap creation methods, from conventional LASIK flaps to thin and sub-Bowman keratomileusis, further investigation into improving platforms to provide the safest and most precise treatments are needed. Future studies will allow the development of newer platforms to further improve outcomes of LASIK.

References 1. Farjo AA, Sugar A, Schallhorn SC, et al. Femtosecond lasers for LASIK flap creation: a report by the American Academy of Ophthalmology. Ophthalmology. 2013;120(3):e5–e20. 2. Barraquer JI. The history and evolution of keratomileusis. Int Ophthalmol Clin. 1996;36(4):1–7. 3. Krumeich JH. Indications, techniques, and complications of myopic keratomileusis. Int Ophthalmol Clin. 1983;23(3):75–92. 4. Krumeich JH, Swinger CA. Nonfreeze epikeratophakia for the correction of myopia. Am J Ophthalmol. 1987;103(3 Pt II): 397–403. 5. Laroche L, Gauthier L, Thenot JC, et al. Nonfreeze myopic keratomileusis for myopia in 158 eyes. J Refract Corneal Surg. 1994;10(4):400–412.

6. Lyle WA, Jin GJ. Initial results of automated lamellar kerato­ plasty for correction of myopia: one year follow-up. J Cataract Refract Surg. 1996;22(1):31–43. 7. Pallikaris IG, Papatzanaki ME, Stathi EZ, et al. Laser in situ keratomileusis. Lasers Surg Med. 1990;10(5):463–468. 8. Pallikaris IG, Katsanevaki VJ, Kalyvianaki MI, et al. Advances in subepithelial excimer refractive surgery techniques: Epi-LASIK. Curr Opin Ophthalmol. 2003;14(4):207–212. 9. Pallikaris IG, Naoumidi II, Kalyvianaki MI, et al. Epi-LASIK: comparative histological evaluation of mechanical and alcoholassisted epithelial separation. J Cataract Refract Surg. 2003;29(8): 1496–1501. 10. Chen LY, Manche EE. Comparison of femtosecond and excimer laser platforms available for corneal refractive surgery. Curr Opin Ophthalmol. 2016;27(4):316–322. 11. Ang M, Mehta JS, Rosman M, et al. Visual outcomes compari­ son of 2 femtosecond laser platforms for laser in situ keratomi­ leusis. J Cataract Refract Surg. 2013;39(11):1647–1652. 12. Rosman M, Hall RC, Chan C, et al. Comparison of efficacy and safety of laser in situ keratomileusis using 2 femtosecond laser plat­ forms in contralateral eyes. J Cataract Refract Surg. 2013;39(7): 1066–1073. 13. Luengo Gimeno F, Chan CM, Li L, Tan DT, Mehta JS. Com­ parison of eye-tracking success in laser in situ keratomileusis after flap creation with 2 femtosecond laser models. J Cataract Refract Surg. 2011;37(3):538–543. 14. Yu CQ, Manche EE. A comparison of LASIK flap thickness and morphology between the IntraLase 60- and 150-kHz femtosec­ ond lasers. J Refract Surg. 2014;30(12):827–830. 15. Yu CQ, Manche EE. Comparison of 2 femtosecond lasers for flap creation in myopic laser in situ keratomileusis: one-year results. J Cataract Refract Surg. 2015;41(4):740–748. 16. Kurtz RM, Liu X, Elner VM, et al. Photodisruption in the human cornea as a function of laser pulse width. J Refract Surg. 1997;13(7):653–658. 17. Kurtz RM, Horvath C, Liu HH, et al. Lamellar refractive surgery with scanned intrastromal picosecond and femtosecond laser pulses in animal eyes. J Refract Surg. 1998;14(5):541–548. 18. Murakami Y, Manche EE. Comparison of intraoperative sub­ traction pachymetry and postoperative anterior segment optical coherence tomography of laser in situ keratomileusis flaps. J Cataract Refract Surg. 2011;37(10):1879–1883. 19. Davison JA, Johnson SC. Intraoperative complications of LASIK flaps using the IntraLase femtosecond laser in 3009 cases. J Refract Surg. 2010;26(11):851–857. 20. Chang JS. Complications of sub-Bowman’s keratomileusis with a femtosecond laser in 3009 eyes. J Refract Surg. 2008;24(1):S97–S101. 21. Haft P, Yoo SH, Kymionis GD, Ide T, O’Brien TP, Culbertson WW. Complications of LASIK flaps made by the IntraLase 15and 30-kHz femtosecond lasers. J Refract Surg. 2009;25(11): 979–984. 22. Kezirian GM, Stonecipher KG. Comparison of the IntraLase femtosecond laser and mechanical keratomes for laser in situ keratomileusis. J Cataract Refract Surg. 2004;30(4):804–811. 23. Moshirfar M, Smedley JG, Muthappan V, Jarsted A, Ostler EM. Rate of ectasia and incidence of irregular topography in patients with unidentified preoperative risk factors undergoing femtosec­ ond laser-assisted LASIK. Clin Ophthalmol. 2014;8:35–42. 24. Clare G, Moore TC, Grills C, Leccisotti A, Moore JE, Schallhorn S. Early flap displacement after LASIK. Ophthalmology. 2011;118(9):1760–1765.

CHAPTER 8  Laser and Mechanical Microkeratomes

25. Letko E, Price MO, Price FW Jr. Influence of original flap cre­ ation method on incidence of epithelial ingrowth after LASIK retreatment. J Refract Surg. 2009;25(11):1039–1041. 26. Sun CC, Chang CK, Ma DH, et al. Dry eye after LASIK with a femtosecond laser or a mechanical microkeratome. Optom Vis Sci. 2013;90(10):1048–1056. 27. Gil-Cazorla R, Teus MA, de Benito-Llopis L, Fuentes I. Inci­ dence of diffuse lamellar keratitis after laser in situ keratomileusis associated with the IntraLase 15 kHz femtosecond laser and Moria M2 microkeratome. J Cataract Refract Surg. 2008;34(1): 28–31. 28. Chan A, Ou J, Manche EE. Comparison of the femtosecond laser and mechanical keratome for laser in situ keratomileusis. Arch Ophthalmol. 2008;126(11):1484–1490. 29. Chen S, Feng Y, Stojanovic A, Jankov MR 2nd, Wang Q. Intra­ Lase femtosecond laser vs mechanical microkeratomes in LASIK for myopia: a systematic review and meta-analysis. J Refract Surg. 2012;28(1):15–24.

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30. Zhang ZH, Jin HY, Suo Y, et al. Femtosecond laser versus mechanical microkeratome laser in situ keratomileusis for myopia: metaanalysis of randomized controlled trials. J Cataract Refract Surg. 2011;37(12):2151–2159. 31. Pajic B, Vastardis I, Pajic-Eggspuehler B, Gatzioufas Z, Hafezi F. Femtosecond laser versus mechanical microkeratome-assisted flap creation for LASIK: a prospective, randomized, paired-eye study. Clin Ophthalmol. 2014;8:1883–1889. 32. Xia LK, Yu J, Chai GR, Wang D, Li Y. Comparison of the fem­ tosecond laser and mechanical microkeratome for flap cutting in LASIK. Int J Ophthalmol. 2015;8(4):784–790. 33. Antonios R, Arba Mosquera S, Awwad ST. Hyperopic laser in situ keratomileusis: comparison of femtosecond laser and mechanical microkeratome flap creation. J Cataract Refract Surg. 2015;41(8):1602–1609.

9 

Crosslinking Instrumentation RENAN RODRIGUES, MARIO ANTONIO STEFANI, AND WALLACE CHAMON

Introduction The clinical success of crosslinking was made possible by the development of ultraviolet (UV)-light emitting diodes (LEDs) that allowed for a reasonable balance of cost and performance with reliable control and dependable performance, which are essential for the scientifically verifiable results. Crosslinking technology has experienced fast growth and improvement since its introduction in the beginning of the 21st century, mainly owing to the development of lowcost, highly efficient and reliable UV-light sources.

Crosslinking Equipment: Common Architecture and Internal Parts It is important to understand that the internal architecture of the crosslinking platforms must present similar components and system-level internal blocks, mainly due to safety regulations, as will be discussed later. Crosslinking equipment based on the current technology consists of the following main parts: • UV source and its electronic control system • Optical beam delivery system • Main system electronics and human interface

UV-Light Source There are several UV-light sources, such as xenon discharge lamps, deuterium lamps, fluorescent mercury arc lamps, and high-temperature halogen lamps. Although these technologies can deliver considerable amounts of UV light, the light spectrum emitted is broad, and the spectral power density is very low in the UV region of interest for riboflavin-based crosslinking. Initially, very-narrow-band interference light filters had been employed to allow only the UV region of interest to be delivered onto the corneal tissue. Therefore very-highpower sources and high-power electronics were needed at that time. The development of moderate-power LEDs in the UV spectral region changed this scenario in the beginning of the 21st century. Light emitting diodes had been established since the semiconductor revolution at the beginning of the 1960s. Initially, only infrared, red, and green 122

emitting diodes were feasible, with progressively higher output power and broader visible spectral coverage. In the late1990s, consequent to new dopants and semiconductor structures, the development of LEDs composed of indium gallium nitride semiconductors allowed emission in the UVA spectrum (315–400 nm). An interesting history of the development and principles of operation of such blue and UV devices can be found elsewhere.1 Briefly put, an LED emits photons in a predetermined spectral region owing its material constituents and the existence of enough density of charge carriers, electrons, by means of carefully controlled voltage and current applied. Medical use of LEDs is based on specific behavior and performance characteristics. Some of the most important subjects in this field will be discussed.

Wavelength Selection Owing to its internal tolerances and material variations, a typical UV LED does not present a precisely tuned wavelength and viable devices must be selected in each production batch.2 For instance, a typical 365-nm device production batch shows around ±10 nm peak position distribution. Therefore when selecting the device, it is necessary to specify the tolerance of the desired wavelength. Factory standard selection classifies devices on ±3 nm peak position range bands. This tolerance centered on 365 nm is well inside the riboflavin/tissue crosslinking reaction confidence area.

Temperature Influence on Wavelength As with any semiconductor, the peak wavelength varies with temperature. Typical variation values are about 0.02 nm/C° in LED UV devices, which is considered a very stable emission. Under the recommended operational range of temperature for clinical use and the assistance of a closed-loop power control, there is very low risk of wavelength slippage that could compromise its performance. Aging also influences semiconductor devices, and some wavelength deviation is possible, but all LED UV devices present on the market remain inside ± 2 nm through their entire lifetime.

Temperature Influence on Power Output Power output is strongly dependent on semiconductor temperature. The performance of the LED decreases with

CHAPTER 9  Crosslinking Instrumentation

123

increasing temperature. This dependency makes it impossible to control the device’s UV emission based only on a constant voltage or current. A closed-loop control must continuously sample the UV output power and modulate the current applied to reach the desired value at a certain time.

These techniques are very effective, as one can see in beam profile power density measurements (Figs. 9.2 and 9.3). “Top hat” profiles with planar power distribution with lower than 3% fluctuations can be found.3

The UV Light Optical Beam Delivery System

As crosslinking is highly dependent on the power density of an irradiated invisible light, special strategies to center the treatment on the patient’s cornea are required. A viable approach is to install a coincident visible aiming beam to guide the treatment. To minimize the patient’s discomfort, a deep red wavelength may be employed. The red beam is produced either by a red LED or by a low-power laser line or crosshair generator (Figs. 9.4 and 9.5). Owing to the necessary optical beam shaping and homogeneity control, the output beam reaching the cornea should have a subtle converging conical format (Fig. 9.6) to allow a closeto-perpendicular incidence on the convex corneal surface. Gaussian-shaped beams are not recommended because they increase the heterogeneity of the energy delivered to the cornea.

Key factors of crosslinking equipment are optical beam output shaping and control.3

Optical Output Power Density Distribution Many of the UV LED sources employed in crosslinking procedures are selected owing to their power output requirements. Unfortunately, in the required power range, all devices are composed of a group or an array of very small emitters tied together, assembled and electrically connected on the same thermal substrate. Consequently, the lightemitting surface is not homogeneous and shows very strong power variation and power density fluctuation. This characteristic imposes a critical constraint as the riboflavin/tissue interaction is highly dependent on power density. Therefore the optical system must employ techniques to create a virtual source with a homogeneous profile. Otherwise, a heterogeneous power distribution on the corneal surface may cause differential deformation, called hot spots. Hot spots may cause nonuniform results and localized endothelium cell damage and haze, especially in thin corneas. Fortunately, there are several optical design methods that can be employed that are similar to techniques employed in movie and television projectors or in laser beam shaping. An optical design for beam homogeneity control employing a mix of such techniques is shown in Fig. 9.1.

Optical Beam Aiming and Positioning, Auxiliary Aiming Beam

Optical Beam Spot Size Several UV sources on the market are equipped with a spot size selector, ranging from 5 mm to 25 mm. As power density should be maintained constant, an electronic control system must automatically correct the power emission to keep power density at the desired value (Fig. 9.7).

The Main Electronic Control System Crosslinking demands a very tight control of its parameters, especially regarding the nature of UV light and power density. In Fig. 9.8, a common control diagram block of a

Focal Plane

Surface 1 (Diaphragm)

LED

Y X

• Fig. 9.1

Z

  Typical optical layout of the beam output delivery system. (From Pereira FRA, Stefani MA, Otoboni JA, Richter EH, Ventura L. Homogeneous UVA system for corneal cross-linking treatment. SPIE Proceedings Volume 7556, Design and Quality for Biomedical Technologies III; 75560Z. February 2010. https://doi.org/10.1117/12.842260.)

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LASIK Techniques and Complications

• Fig. 9.2  Output power density distribution of OPTO XLINK. (From Pereira FRA, Stefani MA, Otoboni JA, Richter EH, Ventura L. Homogeneous UVA system for corneal cross-linking treatment. SPIE Proceedings Volume 7556, Design and Quality for Biomedical Technologies III; 75560Z. February 2010. https://doi .org/10.1117/12.842260.)

•

Fig. 9.3  Output power density distribution of the AVEDRO-KXL System. (From Avedro. The Cross-Linking Solution for Your Keratoconus & Lasik Xtra®Patients. http://www.avedro.com/medicalprofessionals/products/kxl/.)

• Fig. 9.4  Visible aiming beam spots to help positioning the patient eye in the correct position; crosshair red laser beam (left), red light-emitting diode spot on same size and position as ultraviolet beam (right). (From Opto. Opto XLink – Corneal Crosslinking System. http://www.opto .com.br/xlink/.)

• Fig. 9.5  Auxiliary aiming beam profiles of the AVEDRO KXL system. (From Avedro. The Cross-Linking Solution for Your Keratoconus & Lasik Xtra®Patients. http://www.avedro.com/medical-professionals/ products/kxl/.)

crosslinking system is presented. It is based on the functional flow required to fulfill all clinical and safety regulatory standards.

Main Processor, Display, and Keyboard Powerful microprocessors available on the market are used to control and continuously check power delivery, exposure

time, energy density, and dose calculation with low cost and high reliability. The display and keyboard section allow users to select desired parameters and command operations. Although touchscreen input devices are commonly used at present, they are inherently very sensitive to static discharges. Therefore medical-grade devices, which can sustain correct

CHAPTER 9  Crosslinking Instrumentation

operation even when submitted to high static electrical discharges caused by cloth friction or gloves, must be employed. After selection of desired clinical parameters, power density, spot size, energy dose, and exposure time, the software calculates all remaining parameters. Messages and values are presented on the display for a clearance to start the operation.

45 mm

Heat sink

Reference surface Output beam profile Ø 10 mm

Treatment region

• Fig. 9.6

  Optical head general geometry. Treatment region is formed by the selected power density at beam focus, in a subtle convergent conic shape, located between 45 to 50 mm from a reference surface. This design enables a perpendicular incidence of light. (From Opto. Opto XLink – Corneal Crosslinking System. http://www.opto.com.br/ xlink/.)

The emergency switch is a regulatory requirement, as in other medical devices. It allows one to immediately stop treatment in case of any device malfunction.

Watchdog Circuit All microprocessor-controlled devices need software that may malfunction owing to external or internal disturbances or failures. Every medical-grade device must have some way to avoid damage in these cases. The conventional approach is to use a “watchdog” circuit. These circuits generate a periodic signal to check the microprocessor. If the microprocessor response does not match in time or in value, the watchdog circuit “resets” the microprocessor to a safe state. In addition, a direct link to the power control block halts all power delivered to the LED, emission is interrupted, and an error message issued to the operator. In more sophisticated architectures, a secondary redundant processor can take control of the action and recover the mission, mainly in case of minor errors and small disturbances, without any user intervention.

The Power Control Block, Current Sensor, Main Photodiode Led Control Loop The main control block is the circuit that ensures that LED UV emission remains within a very small error margin and

• Fig. 9.7  Optical spot size selector. The control system corrects the power of the LED to keep power density at the selected desired value. (From Opto. Opto XLink – Corneal Crosslinking System. http://www .opto.com.br/xlink/.)

Watchdog circuit

Power control circuit

Emergency switch Display keyboard

Power driver

LED UV

Main processor Current sensor

Spot selection Main photodiode

Safety photodiode

• Fig. 9.8

125

  Main electronic control block diagram. (From Opto. Opto XLink – Corneal Crosslinking System. http://www.opto.com.br/xlink/.)

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will be kept constant independent of temperature variation and aging. After starting the procedure, the current/voltage applied to the LED device is continuously monitored and LED performance is compensated in real time. LED emission is sampled by optical means using a specific photodiode placed over the output optical system. The photodiode is a device that creates a current directly proportional to the direct light incident on it. A spectral filter above the photodiode ensures that only the wavelength corresponding to the LED UV emission is sampled to avoid any ambient or environmental interference on power delivery. If the energy measured is above or below the safe operating range of the LED device, an error message is issued. This can occur owing to overheating.

Continuous and Pulsed Power Control Oxygen availability is a limiting factor during riboflavin UV crosslinking treatment because it is one source of free radicals, which enable covalent collagen bridge formation. In the Dresden protocol, with its relatively low power density and long exposure time, this is not an issue because of the natural diffusion of oxygen into the cornea. However, with higher power density, the use of continuous energy delivery can deplete the oxygen available for crosslinking.4 In higher-power density treatments, pulsed UV-light application was introduced as a new strategy to avoid this problem. Several studies report long biomechanical stability with this modified treatment. Evaluation of patients submitted to continuous (30 mW/cm2 for 4 minutes) or pulsed fast crosslinking (30 mW/cm2, 1 second on, 1 second off, for 8 minutes) demonstrated a mean depth of the demarcation line of 149.32 ± 36.03 µm and 213 ± 47.38 µm, respectively, which suggests a benefit of the pulsed delivery technique.5 Another study,6 using similar parameters of pulsed and continuous energy delivery, evaluated stromal alterations regarding keratocyte apoptosis by confocal microscopy after crosslinking with both strategies. It found that, with pulsed energy, there was a deeper apoptotic effect around 200 µm (range, 190–240 µm), while with continuous energy delivery, the apoptotic effect was detected around 160 µm (range, 150–200 µm). Although promising, this strategy needs to be studied further.4

Auxiliary Devices Interlock Device

One regulatory requirement is the interlock device. This interlock can be tied in a door switch to avoid nonauthorized entrance into the procedure room, a remnant of safety regulations originally intended for very-high-power invisible laser systems. This same device can be used to interrupt emission when attached to a patient head belt, ensuring that patient head movement is inside the beam alignment margin. Sound Emission

Sound emission may indicate the presence of invisible light.

Aiming Beam, or Alignment Auxiliary System Control

As described earlier, there is an auxiliary device to allow correct beam placement over the cornea. There are several methods on the market, as described before. A visible LED source is used in most crosslinking devices. Its light intensity is selectable and closed loop controlled. During treatment, or during UV LED exposure, normally its light intensity is reduced to increase patient comfort. Eye Tracker

As some crosslinking procedures take a long time to perform (30 minutes is a standard protocol), patients may move their heads, causing misalignment of the system. Some misalignment can decrease the effectiveness of the procedure and potentially cause damage to limbus stem cells. Therefore some manufacturers offer optional video eye trackers to check alignment in real time.

Regulatory and Normative Requirements All crosslinking equipment must be compliant with normative regulatory technical requirements. LED UV emitters are included in specific chapters in several regulations, such as the CFR 1040 as required by CFR 510K in the United States.7 In 2001, the standards regarding the safety of laser products in Europe through the European Committee of Standardization (CEN) and internationally through the International Electrotechnical Commission (IEC) were condensed in the regulation IE 60825-1. These standards apply equally to lasers and LED emission products.8 Depending on the emission wavelength, source type, output beam geometry, and irradiation power levels, several safety procedures, devices, and controls must be employed. As the radiofrequency spectrum is becoming increasingly more crowded, the electromagnetic compatibility of the medical device is mandatory. For instance, a nearby cellphone can emit enough power to jam any nonprotected electronic device. In this way, all medical appliances must be prepared to sustain perfect functionality under several interference scenarios. IEC 61000 is a common electromagnetic interference (EMI) and electromagnetic compatibility (EMC) normative regulation being used by several countries.9 As a general requirement, any medical device must comply with electrical safety regulations related to maximum current leakage, minimum isolation, electrical discharge resistance, power supply performance, grounding, and shielding. The most common regulations adopted by several countries are described in IEC 60601-1-11:2015.10 For the physician in charge of crosslinking procedure application, it is recommended to select properly certified products based on local or international regulations. Use of a device that does not comply with local technical safety regulations may cause legal issues in the case of unexpected behavior or induced patient damage.

CHAPTER 9  Crosslinking Instrumentation

A Survey of Crosslinking Platforms on the Market There are several products available on the market. Some representative models are listed in Table 9.1.

Nonphotoactivated Crosslinking Agents The most common photoactivated crosslinking agent is riboflavin, which has been extensively studied, is in widespread use, and is highly effective in preventing progression of corneal ectasia. Nevertheless, it is not free of potential complications, such as endothelial decompensation, corneal edema, bullous keratopathy, recurrent corneal epithelial

127

defects, infection, haze formation, and others. Alternative methods to achieve corneal crosslinking that could be more effective or have less complications are wanted. Some nonphotoactivated alternatives have been studied, such as genipin, as well as extracts from barbatimão (Stryphnodendron adstringens) and açaí (Euterpe oleracea). Genipin is a natural molecule derived from Gardenia jasminoides. It was previously studied in several applications, such as promoting crosslinking in cardiac valves and as collagen biospheres to prevent posterior capsule opacification in cataract surgery, among other uses. It induces crosslinking by reacting spontaneously, without UV irradiation, releasing free radicals in the corneal stroma, resulting in intra- and intermolecular collagen bonds. It has been shown that genipin may increase Young modulus by 1.88 in porcine corneas depending on its concentration. The

TABLE Crosslinking Systems Available on Market. See References Indicated in Table for Details. 9.1 

Manufacturer/ Model

Wavelength (nm)

Power Density (mW/cm2)

Spot Size (mm)

Focal Distance (mm)

Continuous/ Pulsed

Duration (min)

Eye Tracker

OPTO X-Link (Fig. 9.9)11

365 ± 5

0.18–23.0

6, 8, or 10

45

Both

0.2–30

Video

UV-X iron cross (now AVEDRO) (Fig. 9.10)12

365 ± 10

9–10

7.5 or 9.5

45

Continuous

10

Not available

AVEDRO KXL System (Fig. 9.11)13

365 ± 5

3–45

4–11

50

Both

3–8

Not available

Kestrel–Intacs–XL (Fig. 9.12)14

365 ± 5

3, 9, 18, 30

6–9

50

Continuous

0.1–30

Not available

CSO VEGA (Fig. 9.13)15

370 ± 5

3

4–11

54

Continuous

30

Video

Peschke Trade, Switzerland (Fig. 9.14)16

365

3–30

3–12

45–55

Both, plus LASIK & PRK Xtra mode

3–30

Yes, tracking zone can be adjusted

• Fig. 9.9  OPTO XLINK with optional video eye tracker and static mounting. (From Opto. Opto XLink – Corneal Crosslinking System. http://www.opto.com.br/xlink/.)

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LASIK Techniques and Complications

• Fig. 9.10

 

AVEDRO UV-X. (From http://www.avedro.com/medical-professionals/products/iroc-innocross/.)

• Fig. 9.11  AVEDRO KXL system featuring accelerated crosslinking. (From Avedro. IROC Innocross. http://www.avedro.com/medical -professionals/products/iroc-innocross/.)

• Fig. 9.12

• Fig. 9.13

  CSO VEGA with video eye tracker. (From CSO. VEGA CBM-X-Linker. http://www.csoitalia.it/en/prodotto/info/38-vega-cbm -x-linker.)

  KESTREL INTACS XL system. (From Kestrel Ophthalmics. Intacs XL – Cross Linking System. http://www.kestrelophthalmics.com/intacs-xl-cross-linking-system.)

CHAPTER 9  Crosslinking Instrumentation

•

Fig. 9.14  PXL Platinum 330. (From Peschke Trade Switzerland, http://peschketrade.com/products/peschke-cxl/.)

stress-strain curve demonstrated a 171%, 218%, and 268% increase when using 0.1%, 0.25%, and 1.0% genipin, respectively.17 Genipin also delayed enzymatic digestion by bacterial collagenase-A. While untreated corneas had complete dissolution after 56 hours, treated corneas degraded after 220 hours. Histopathologic analysis showed that treatment with genipin decreased interfibrillar spaces, which was more pronounced at higher concentrations. Although results are promising, clinical effects regarding toxicity must be better investigated considering that the treatment cannot be precisely limited to the anterior portion of the cornea. It has been demonstrated that corneas submitted to 4% S. adstringens extract for 2 hours had higher denaturation temperature than untreated controls.18 In another study, an extract of 4% açaí berry (Euterpe oleracea) was used for 0.5 to 2 hours in rabbit corneas.19 This extract contains several polyphenolic compounds (mainly proanthocyanidins) that have the potential to promote stable hydrogen-bonded structures, thus increasing the cohesion of collagen fibrils. Results showed that in the 2-hour group there was an increase in resistance to thermal heating and an increase in elastic modulus (10.6 times) compared with a control group. On the other hand, the main disadvantage of treatment with açaí extract is the purple pigmentation acquired by treated corneas. Fractionating the plant extract may help to solve this problem.

References 1. Nakamura S, Gerhard Fasol G. The Blue Laser Diode: GaN Based Light Emitters and Lasers. New York: Springer Verlag; 1997. 2. NICHIA UV LED Catalog; 2017. NICHIA Corp. http://www .nichia.co.jp/specification/products/led/NVSU233B.pdf. Accessed May 17, 2018.

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3. Pereira FRA, Stefani MA, Otoboni JA, Richter EH, Ventura L. Homogeneous UVA system for corneal cross-linking treatment. SPIE Proceedings Volume 7556, Design and Quality for Biomedical Technologies III; 75560Z. February 2010. https://doi. org/10.1117/12.842260. 4. Kling S, Hafezi F. An algorithm to predict the biomechanical stiffening effect in corneal cross-linking. J Refract Surg. 2017;33(2): 128–136. 5. Moramarco A, Iovieno A, Sartori A, Fontana L. Corneal stromal demarcation line after accelerated crosslinking using continuous and pulsed light. J Cataract Refract Surg. 2015;41:2546–2551. 6. Mazzotta C, Traversi C, Caragiuli S, Rechichi M. Pulsed vs continuous light accelerated corneal collagen crosslinking: in vivo qualitative investigation by confocal microscopy and corneal OCT. Eye (Lond). 2014;28(10):1179–1183. 7. U.S. Government Publishing Office. 21 CFR 1040.10 LASER PRODUCTS. https://www.gpo.gov/fdsys/granule/CFR2000-title21-vol8/CFR-2000-title21-vol8-sec1040-10. Accessed May 17, 2018. 8. IEC Web Store. IEC 60825-1:2014 Safety of laser products: Part 1: Equipment Classification and Requirements. https:// webstore.iec.ch/publication/3587. Accessed May 17, 2018. 9. IEC. Structure of IEC 61000. http://www.iec.ch/emc/basic_emc/ basic_61000.htm. Accessed May 17, 2018. 10. IEC. IEC 60601-1-11:2015 Medical Electrical Equipment Part 1: General Requirements for Safety. https://www.iso.org/standard/ 65529.html. Accessed May 17, 2018. 11. Opto. Opto XLink – Corneal Crosslinking System. http://www.opto .com.br/xlink/. Accessed May 17, 2018. 12. Avedro. IROC Innocross. http://www.avedro.com/medical -professionals/products/iroc-innocross/. Accessed May 17, 2018. 13. Avedro. The Cross-Linking Solution for Your Keratoconus & Lasik Xtra®Patients. http://www.avedro.com/medical-professionals/ products/kxl/. Accessed May 17, 2018. 14. Kestrel Ophthalmics. Intacs XL – Cross Linking System. http:// www.kestrelophthalmics.com/intacs-xl-cross-linking-system. Accessed May 17, 2018. 15. CSO. VEGA CBM-X-Linker. http://www.csoitalia.it/en/prodotto/ info/38-vega-cbm-x-linker. Accessed May 17, 2018. 16. Swissmed. PESCHKE Trade CCL-VARIO Cross-linking. http:// www.swissmed.asia/shop/refractive-corneal-therapies/peschketrade-ccl-vario-cross-linking/. Accessed May 17, 2018. 17. Avila MY, Navia JL. Effect of genipin collagen crosslinking on porcine corneas. J Cataract Refract Surg. 2010;36(4):659–664. 18. da Cruz LGI, Moraes GA, Nogueira RF, Araujo AMG, Bersanetti PA. DSC characterization of rabbit corneas treated with Stryphnodendron adstringens (Mart.) Coville extracts. J Therm Anal Calorim. 2017. doi:10.1007/s10973-017-6096-8. 19. Bersanetti PA, Bueno TL, Morandim-Giannetti AA, Nogueira RF, Matos JR, Schor P. Characterization of rabbit corneas subjected to stromal stiffening by the açaí extract (Euterpe oleracea). Curr Eye Res. 2017;42(4):528–533.

10 

Ocular Diseases of Importance to the Refractive Surgeon ELENA ALBÉ, JANINE AUSTIN CLAYTON, DIMITRI T. AZAR, AND JEFFREY C. LAMKIN

Introduction

Anterior Blepharitis

This chapter discusses the pathogenesis and management of ocular diseases that are frequently encountered in the preoperative evaluation and course of management of the refractive surgery patient. Many of these conditions should be identified and treated preoperatively, while others are contraindications for refractive surgery. The chapter reviews these conditions, beginning with ocular surface diseases: inflammatory eyelid disease followed by conjunctivitis and keratitis, tear film abnormalities, atopic and allergic diseases, peripheral corneal ulceration, keratoconus, and corneal dystrophies and degenerations. This is followed by a brief review of those disorders, both systemic and ocular, that have been clearly associated with either myopia or hyperopia and that are of day-to-day relevance to the practicing ophthalmologist. The relationship of these conditions to keratorefractive surgical procedures will be emphasized.

Staphylococcal blepharitis can be manifested as acute blepharitis or, more commonly, as chronic blepharitis or blepharoconjunctivitis. In acute ulcerative blepharitis, there is evidence of erythema and ulceration of the anterior lid margin. These findings can be unilateral or bilateral. Generally, conjunctival involvement is not prominent. All corneal refractive procedures should be postponed to avoid transmitting the infection to the cornea. The entity that general ophthalmologists confront frequently is chronic staphylococcal blepharitis; it may be associated at various degrees with meibomitis. The patients often report symptoms of burning, foreign-body sensation, and crusting of the eyelashes, especially in the morning. On examination, there is evidence of debris adhering to the eyelashes (classic sign of the fibrin collarette1) and anterior lid margin; there also may be some thickening of the lid margin itself. There may be evidence of hyperemia of palpebral and bulbar conjunctiva, and papillae involving the limbus. Phlyctenulosis can also accompany this condition as a type IV hypersensitivity reaction to microbial antigens.2 Chronic staphylococcal blepharitis can involve the cornea with a superficial coarse epitheliopathy and punctate corneal erosions. More serious corneal involvement, such as acute marginal infiltration and ulceration, is less common. Proper management of staphylococcal blepharitis and associated corneal conditions should increase the likelihood of successful refractive surgery.

Blepharitis and Meibomitis An examination of the skin of the eyelid as part of the external ophthalmologic examination should include a search for any signs of active inflammation or infection. Acute infectious blepharitis—such as staphylococcal blepharitis, herpes simplex, or zoster virus blepharitis—represents an absolute contraindication for keratorefractive surgery as long as the infection has not been eradicated. One must probe carefully and specifically for any history of herpetic dermatoblepharitis because recurrent corneal or conjunctival disease, or associated corneal hypesthesia, are factors that would impact adversely the suitability of these patients for refractive surgical procedures (Fig. 10.1). Chronic eyelid inflammation is frequently underestimated and could alter the visual and refractive outcome of patients undergoing corneal refractive surgery. Careful examination of the eyelid margins is therefore essential in evaluating keratorefractive surgery patients. 132

Meibomitis and Meibomian Gland Dysfunction Dysfunction of the meibomian glands is thought to result in a form of blepharitis that has a wide range of severity. The symptoms are burning, foreign-body sensation, and fluctuation of vision that changes with blinking. These patients often give a history of recurrent chalazion. The

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133

A • Fig. 10.2

  Rosacea blepharoconjunctivitis. Note extensive telangectasia of the nose.

B • Fig. 10.1

  (A) Patient with herpes zoster dermatoblepharitis localized to the left side of the face. (B) Associated corneal subepithelial scarring is a relative contraindication for laser refractive surgery.

classic signs of meibomian gland dysfunction are inspissated meibomian glands, lipid or foam in the tear film, thickening of the lid margin, and hyperemia of the lid margin and conjunctiva. The cornea may be secondarily involved with epithelial erosion, pannus formation, peripheral neovascularization, marginal catarrhal infiltration or ulceration, or phlyctenular disease. Sebaceous gland dysfunction may accompany meibomian gland dysfunction with associated acne vulgaris, acne rosacea, and seborrheic dermatitis. Acne rosacea is a chronic condition that is characterized by facial flushes, telangiectasias, and pustules along the nose and cheeks (Fig. 10.2).3 An eyelid hygiene regimen that includes warm compresses is valuable in keratorefractive surgery patients preoperatively but should be avoided postoperatively. A course of preoperative systemic tetracycline, doxycycline, or erythromycin also can be useful postoperatively because of the possible association of meibomian secretions and diffuse lamellar keratitis following laser in situ keratomileusis (LASIK).4

Bacterial Conjunctivitis and Keratitis

by infection with Staphylococcus aureus.5–7 The eyelids are often involved as well, a condition thought to be related to the toxins and lipases elaborated by this class of bacteria. This entity is discussed in full in the earlier section on blepharitis and meibomitis. Other causes of chronic bacterial conjunctivitis are the Gram-negative bacteria, such as Moraxella lacunata, Serratia marcescens, Escherichia coli, Klebsiella pneumoniae, and Proteus species. Appropriate cultures should be obtained and directed antimicrobial therapy with erythromycin and bacitracin ointments should be administered in order to minimize the morbidity of this condition. Adult inclusion conjunctivitis is secondary to infection with Chlamydia trachomatis immunotypes D, E, F, G, H, I, J, and K and is an important cause of chronic conjunctivitis in the adult, an entity distinct from trachoma. Transmission is through contact of the eye with infected secretions. The history is often one of chronic ocular limitation and redness, which may be accompanied by mucopurulent discharge. The most helpful sign in diagnosis is a prominent lymphoid reaction, that is, conjunctival follicles that may involve the bulbar or limbal conjunctiva and preauricular lymphadenopathy. There may be micropannus formation in the cornea, superficial epitheliopathy on the superior cornea, and even subepithelial infiltrate formation. Patients with chronic follicular conjunctivitis seeking keratorefractive surgical procedures complain of chronic redness and ocular irritation with or without contact lenses. Treatment can ameliorate symptoms and increase their contact lens tolerance. It is advisable to treat these patients preoperatively with oral tetracycline 1.0 to 1.5 g daily or oral doxycycline 100 mg b.i.d for 2 weeks, or a single 1-g dose of azithromycin.8,9 If untreated, this infection can lead to persistent keratitis and/or conjunctivitis, resulting in corneal and conjunctival scarring.

Chronic Bacterial Conjunctivitis and Keratitis

Viral Conjunctivitis and Keratitis

Chronic bacterial conjunctivitis, which is defined by a duration of longer than 3 weeks, is most commonly caused

The major etiologic agents of acute viral conjunctivitis are herpes simplex, adenovirus, and varicella zoster. There are

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• Fig. 10.3  Classic subepithelial infiltrates that persist for several months following the initial epidemic keratoconjunctivitis episode.

• Fig. 10.4

41 antigenically distinct serotypes of adenovirus, a nonenveloped DNA virus that is probably the most common cause of viral conjunctivitis in the adult. There are three clinical presentations of infection with adenovirus: pharyngoconjunctival fever (PCF), epidemic keratoconjunctivitis (EKC), and acute nonspecific follicular conjunctivitis (NFC). PCF is most commonly caused by adenovirus serotypes 3, 4, and 7, but it can also be caused by other serotypes. In this instance, the follicular conjunctivitis is accompanied by fever, pharyngitis, and regional lymphadenopathy. Constitutional symptoms frequently are encountered. The conjunctivitis is generally bilateral but not severe, and secondary corneal involvement is usually restricted to mild epithelial keratitis. In contrast, EKC is more serious and can have significant ocular morbidity. EKC is caused most commonly by adenovirus serotypes 8, 19, and 37. This highly contagious condition produces symptoms of watery discharge, redness, irritation, and itching. The corneal signs, which occur in 80% of patients, consist of diffuse punctate epithelial keratitis for 2 to 5 days and the formation of classic subepithelial infiltrates (Fig. 10.3) as a late complication.10 The use of topical corticosteroids is not recommended, even for severe conjunctival or corneal involvement, because it prolongs viral shedding and may worsen the final visual outcome. A history of acute adenoviral infection should not be a contraindication for keratorefractive surgery except in some cases when chronic subepithelial infiltrates are noted. Herpes simplex keratitis can accompany both primary and recurrent infections. It may range in severity from a diffuse punctate epithelial keratitis to typical dendritic keratitis. It can be associated with preauricular adenopathy, a mild follicular or papillary conjunctivitis. Recurrent ocular herpes can present as isolated conjunctivitis, epithelial and stromal keratitis, or uveitis. Dendritic epithelial keratitis is a sign of active viral replication (Fig. 10.4). Punctate keratitis can accompany the conjunctivitis seen with primary herpes simplex infection or can occur without the conjunctivitis before dendrite formation or as a manifestation of drug

toxicity. Geographic epithelial keratitis should be distinguished from trophic ulceration caused by chronic disease. Most keratorefractive surgeons believe that patients with past history of herpetic keratitis should not undergo corneal laser surgery because dormant viral disease may be reactivated. However, perioperative prophylactic treatment with oral 400 mg acyclovir twice daily could prevent the onset of herpetic recurrence following refractive photoablation.11 The varicella zoster virus causes two clinically distinct entities: chickenpox and herpes zoster (shingles). Herpes zoster keratitis (HZK) can be associated with severe late corneal complications, such as recurrent stromal keratitis, scarring, neovascularization, lipidic infiltrates, and neurotrophic keratitis, all of which are absolute contraindications for keratorefractive surgery. When HZK during the acute phase is limited to punctate superficial keratitis and microdendrites that resolve and leave a clear and compact cornea with no corneal hypesthesia, keratorefractive surgery can be considered. Chronic follicular conjunctivitis can occur as a toxic response secondary to infection with the poxvirus, molluscum contagiosum. A pearly white, umbilicated lesion may hide among cilia along the lid margin and elaborate toxins onto the conjunctival surface, leading to chronic follicular conjunctivitis. A superficial epitheliopathy may also be seen in addition to micropannus formation. These lesions respond to excision and cryotherapy, which should be performed before surgery. Patients should be educated about the risks of combining keratorefractive surgery with the excision of molluscum lesions.

  Epithelial keratitis, as evidenced by rose bengal staining, is a sign of active herpes simplex viral replication.

Tear Abnormalities and Exposure Keratitis Tear Film Abnormalities Because dry-eye symptoms are the most frequent complaints of patients following LASIK, it is fundamental to assess the tear film function of all candidates for this surgery. Performing a flap with a mechanical microkeratome or with

CHAPTER 10  Ocular Diseases of Importance to the Refractive Surgeon

a femtosecond (FS) laser cuts the corneal nerves that all penetrate into the cornea from the periphery to the center. It is well known that corneal nerves play a significant role in tear film homeostasis. Aqueous tear deficiency may be caused by inadequate tear production or excessive tear evaporation.12 Many tests exist to assess tear film function. The most frequently utilized measure of tear production is the Schirmer test. In 83% of patients with dry eyes, the Schirmer test without topical anesthetic will be positive, showing a value of paper strip wetting over 5 minutes of less than 5.5  mm (vs. 15  mm or more in normal individuals).13 The marginal tear film strip or tear meniscus present on the lower eyelid can also be an indicator of the amount of tear produced. The height of the tear meniscus should be 0.5 to 1.0 mm. The most specific diagnostic tests for keratoconjunctivitis sicca (KCS) are the rose bengal staining and Schirmer test with topical anesthetic. The detection of increased tear lactoferrin concentration and tear osmolarity are the most sensitive indicators of dry-eye syndrome. The recovery time following refractive surgery may be prolonged in patients with dry eyes, generally because of superficial epithelial keratitis and persistent epithelial defects (Fig. 10.5). All diseases that are associated with severe tear production deficiency are contraindications for LASIK surgery. A nonexhaustive list of these diseases includes multiple congenital ocular diseases, such as Riley–Day (familial dysautonomia), anhidrotic ectodermal dysplasia, multiple endocrine neoplasia, and congenital hypoplasia or aplasia of the lacrimal gland. Idiopathic aqueous deficiency frequently develops in middle-aged women but can also occur secondary to systemic autoimmune diseases, infiltrative disorders, and neurologic conditions that affect the autonomic nervous system and thereby lacrimal gland innervation. Conditions that are characterized by infiltration of the lacrimal gland itself—such as lymphoma, amyloidosis, pulmonary fibrosis, graft-versus-host-disease, hemochromatosis, and some hematopoietic disorders—can result in replacement of normal gland tissue, thereby causing dry eyes. Disorders more likely to be encountered in the relatively healthy

• Fig. 10.5

135

potential refractive surgery patient include autoimmune thyroiditis, sarcoidosis, and systemic lupus erythematosus (SLE). There are several infectious causes of dry eye, including hepatitis B and C, syphilis, trachoma, tuberculosis, and human immunodeficiency virus (HIV)–related diffuse infiltrative lymphadenopathy syndrome, in which CD+ cells infiltrate the lacrimal gland and lymphatic tissues. Keratoconjunctivitis sicca in conjunction with xerostomia comprises Sjögren syndrome. This is characterized by focal lymphoid infiltrates in the lacrimal and salivary gland and circulating autoantibodies (ANA, SS-A, and SS-B).14 Primary Sjögren syndrome is characterized by the absence of associated autoimmune diseases, such as rheumatoid arthritis, progressive systemic sclerosis, primary biliary cirrhosis, dermatomyositis, and SLE. Mucus deficiency occurs whenever the conjunctival goblet cells are affected and can result in inadequate wetting of the ocular surface.15 As a result, tear film stability is compromised, with a decreased tear break-up time (TBUT; less than 10 seconds’ duration between the blink and the appearance of the first dry area after instillation of 2% fluorescein solution and examination with oblique illumination using a cobalt blue filter). Diseases associated with inadequate mucus production include chemical burn, ocular cicatricial pemphigoid, Stevens–Johnson syndrome, and vitamin A deficiency. Complete lipid deficiency is primarily seen in ectodermal dysplasia, which is a rare disease secondary to the congenital absence of meibomian glands. Defective tear film lipid secretion also is a permanent finding in conditions such as meibomitis and blepharitis. It results in meibomian gland inspissation and increased tear evaporation.16 Many medications can decrease tear production; these often can be obtained over the counter and are not even considered to be medicine by patients. Antihistamines are probably most commonly taken by young patients, and they clearly reduce tear production, as do nasal decongestants, antitussives, and some analgesics that contain antimuscarinic compounds. Any agent with anticholinergic properties—such as antidepressants, antihypertensives, antiulcer medications, and some antiarrhythmics—will inhibit tear production. Some of the beta-adrenergic antagonists, specifically timolol, have been shown to decrease tear production as measured by the Schirmer test. A careful history searching specifically for symptoms of dry eye is indicated in the evaluation of the refractive surgery patient. These symptoms include foreign-body sensation, burning, and heaviness of the eyelids. They typically are exacerbated by activities in which the frequency of blinking is reduced because of the effort required to concentrate, such as with reading. Severe dryness can manifest as photophobia, whereas minimal dryness may be asymptomatic.

Neurotrophic Keratitis

Dry-eye syndrome. The recovery time following refractive surgery is prolonged in patients with dry eyes, generally because of superficial epithelial keratitis.  

Lesions of the fifth cranial nerve from the trigeminal nucleus to the cornea may lead to interruption of the normal

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A

A

B

B

• Fig. 10.6

  (A) Epithelial defect with heaped-up edges in a patient with neurotrophic keratitis. (B) Vascularization of the cornea can follow repeated episodes of neurotrophic epithelial defects.

• Fig. 10.7  The inferior one-third of the cornea undergoes epithelial breakdown when there is significant lagophthalmos (A). Lateral tarsorrhaphy is used to limit the ocular surface exposure (B).

sensation and trophic stimulation of the cornea and result in neurotrophic ulceration. Corneal anesthesia results, leading to decreased tear production. The blink rate can also be decreased while the tear film osmolarity is increased. The trigeminal nerve provides trophic factors that are necessary for the maintenance of healthy corneal epithelium. The trophic ulceration results from abnormal repair of the corneal epithelium secondary to abnormal epithelial cell turnover and reduced reflex tearing. In addition, corneal epithelial mitosis appears to be damaged when corneal innervation is disrupted, reportedly secondary to reduction in glycolytic and respiratory cell activity. An epithelial defect with heaped-up edges is a characteristic finding (Fig. 10.6A). This can occur either in varicella zoster and herpetic viral infections, in which the virus travels via retrograde axoplasmic flow to the trigeminal ganglion, where it can become dormant, or in response to space-occupying lesions, such as aneurysms or tumors, which compromise trigeminal nerve function. Vascularization of the cornea can follow repeated episodes of epithelial defects (Fig. 10.6B). Clearly, these patients should not undergo keratorefractive surgery.

disease, and cicatricial ocular diseases. Any exposed corneal epithelium quickly becomes desiccated, causing cell membrane damage and death. There is loss of corneal epithelial cells and thinning of the entire corneal epithelium (Fig. 10.7).

Exposure Keratopathy Exposure keratopathy may result from a variety of causes: thyroid disease, lagophthalmos secondary to neuroparalytic

Immunologic Diseases of the Conjunctiva and Cornea Ocular Allergic Diseases Allergic Conjunctivitis The most common ocular allergic disease is allergic conjunctivitis, the result of a type I hypersensitivity response to seasonal or perennial allergens such as pollen, molds, mite dust, and cat danders. The allergens crosslink immunoglobulin E (IgE) molecules fixated on mast cells, which then degranulate and release vasoactive amines such as histamine, eosinophil chemotactic factor (ECF), and platelet-activating factor (PAF); eosinophil granule major basic protein (EMBP); and prostaglandin D2.17 Histamine results in conjunctival hyperemia, via H2 receptors,18 and itching, via H1 receptors, quite characteristic of this condition. Ocular signs include various degrees of conjunctival redness, chemosis, and tarsal conjunctival papillae. Patients

CHAPTER 10  Ocular Diseases of Importance to the Refractive Surgeon

with seasonal or perennial allergic conjunctivitis are good candidates for keratorefractive surgery, but they should be instructed to refrain from eye rubbing during the early postoperative period following LASIK.

Atopic Keratoconjunctivitis Atopic keratoconjunctivitis (AKC) is the most severe ocular allergic disease. It involves young adults and is associated with atopic dermatitis. Other atopic manifestations, including bronchial asthma and hay fever, can be present. Itching, burning, photophobia, and blurred vision are frequent complaints. This may be one reason to discourage atopic patients from undergoing keratorefractive surgery. Atopic blepharitis is typically characterized by tylosis, a thickening of the eyelid margins, and eyelid swelling associated with a scaly, indurated, and wrinkled appearance of the periocular skin (Fig. 10.8A).19 Marginal blepharitis caused by staphylococcal infection, maceration of the canthal skin, and excoriation of the periorbital region are common and are exacerbated by scratching (Fig. 10.8B). A hallmark of AKC is chronic ocular surface inflammation. The conjunctiva becomes hyperemic and edematous. Tarsal conjunctival papillary hypertrophy is a common finding. This

A

chronic condition can result in conjunctival cicatrization and symblepharon. Corneal involvement may include punctuate erosions and keratitis. Patients with AKC are at risk for developing infectious and noninfectious corneal ulcers. Peripheral micropannus is common in chronic AKC. Neovascularization and scarring can extend to the central cornea. A subcapsular anterior cataract and posterior subcapsular opacity can develop, mainly due to long-term corticosteroid use.20 As a result, many patients with atopic disease may seek refractive surgery procedures. A strong relation between atopy and keratoconus has been described; 25% of patients with atopic dermatitis and 16% of patients with AKC demonstrate classic signs of keratoconus.21 Accordingly, atopic patients are not good candidates for refractive surgery.

Giant Papillary Conjunctivitis Because many refractive surgery prospective patients are long-term contact lens wearers, a thorough examination of the palpebral conjunctiva is indicated. Giant papillary conjunctivitis (GPC) has been found in conjunction with contact lens wear, protruding suture material, presence of irregularities in the ocular surface, and the use of ocular prostheses22 (Fig. 10.9). Investigators have estimated that between 1% and 5% of wearers of rigid gas permeable contact lenses and between 10% and 15% of those wearing hydrogel contact lenses have GPC.23 The origin of GPC appears to be a combination of mechanical irritation and allergic factors. It has been postulated that mechanical trauma induced by contact lenses on the conjunctiva, intolerance to accumulated lens deposits, hypoxia, and bacterial colonization of the lenses are all involved in the pathogenesis of this condition. Keratorefractive surgery is thus a viable alternative for many patients with GPC. GPC is characterized by the presence of abnormally large papillae on the upper tarsal conjunctiva, conjunctival hyperemia and thickening, excess mucus secretion, foreignbody sensation, or pruritus and intolerance to contact lens wearing.

B • Fig. 10.8

  (A) Atopic keratoconjunctivitis associated with atopic dermatitits of the eyelids. (B) Mild atopic disease. Maceration of the canthal skin and excoriation of the periorbital region is exacerbated by scratching.

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•

Fig. 10.9  Giant papillary conjunctivitis of the upper palpebral conjunctiva.

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Ocular Mucous Membrane Pemphigoid The ocular surface may be the site of autoimmune mucocutaneous blistering diseases, such as ocular mucous membrane pemphigoid. It is important to diagnose these conditions in order to avoid exacerbation of the disease process following ocular surgery. Mucous membrane pemphigoid,24 previously known as cicatricial pemphigoid, is an immune-mediated disease characterized by autoantibodies to the basement membrane zone at the epithelial–subepithelial junction of mucous membranes and occasionally skin. Mucosal surfaces affected include eyes, nose, mouth, respiratory tract, and gastrointestinal tract. Ocular mucous membrane pemphigoid is seen as a progressive cicatrizing conjunctivitis, which, if left untreated, results in scarring and obliteration of the conjunctival fornices (symblepharon).25 Additionally, the goblet cells are affected and lacrimal gland ducts sclerosed, resulting in both mucus and aqueous tear deficiency. These each can cause devastating effects on the cornea, which may be further compromised by trichiatic lashes, exposure, and secondary conjunctival cicatrization.

Connective Tissue Disease and Systemic Vasculitides Systemic rheumatologic disease can be manifest initially in the eye, which makes the ophthalmologist very important in the evaluation of these patients. The systemic vasculitis most likely to involve the eye is rheumatoid arthritis. In this condition, the diagnosis is usually made before the ocular manifestations occur, of which keratoconjunctivitis sicca is the most common. Sjögren syndrome in 24% to 31% of rheumatoid arthritis patients has been demonstrated by lacrimal gland biopsy.25 This syndrome can cause corneal disease, which may be a mild epitheliopathy or may progress to furrowing, peripheral ulcerative keratitis, keratolysis, and perforation (Fig. 10.10).26 Some 15% of patients with rheumatoid arthritis show corneal involvement. It is very often accompanied by episcleritis and/or scleritis, which can be necrotizing with or without inflammation (scleromalacia

• Fig. 10.10

 

Rheumatoid melting of the corneal periphery.

perforans). One of the severe manifestations is sclerosing keratitis, in which peripheral stromal opacification progresses accompanied by stromal vascularization and associated scleritis. The proposed etiology of these findings is type III (immune complex) hypersensitivity; circulating immune complexes have been isolated from the serum and synovial fluid of these patients. With appropriate treatment, including immunosuppressive therapy, the disease process may be halted. Significant astigmatism and surface irregularity may bring the patient to the attention of the refractive surgeon. Keratorefractive surgery may worsen the ocular condition and is contraindicated. Keratorefractive surgery also is contraindicated in SLE. In particular, LASIK worsens the dry-eye syndrome that is a consistent feature of SLE and that can be associated with a superficial epitheliopathy and, rarely, peripheral ulcerative keratitis. Systemic vasculitides, which can potentially be associated with corneal complications, also are contraindications for keratorefractive surgery. Corneal thinning may rarely occur centrally, requiring patch grafting. The corneal manifestations of polyarteritis nodosa tend to be severe, consisting of peripheral ulceration that can accelerate to involve the entire limbal region. There is loss of tissue secondary to the enzymes produced by the phagocytic white blood cells attracted to the region by immune complex formation. Peripheral ulcerative keratitis can also be seen in Wegener granulomatosis, even as the presenting sign of disease. The lesion starts at one region of the limbus and can progress to involve the entire limbus, even moving centrally. Relapsing polychondritis is characterized by inflammation of the cartilage of the ears, nose, and trachea. This serious disorder can be accompanied by peripheral ulcerative keratitis thought to be secondary to the formation of antibodies against type II collagen. Progressive systemic sclerosis can have the following ocular manifestations: keratoconjunctivitis sicca, foreshortening of the inferior fornix, and blepharophimosis.

Developmental Abnormalities of the Cornea Although rarely encountered routinely, developmental corneal abnormalities are important to recognize in the newborn or during early childhood. Recognition can inform the clinician concerning the natural history of the condition, indicate the necessary medical or surgical treatment, and alert the physician to the various ocular and systemic complications that may accompany the disorder and warrant additional investigation. In addition, accurate identification and analysis of the disease help parents deal with the prognosis and guide them in seeking the proper genetic counseling when indicated. Anomalies of corneal size include megalocornea and microcornea, whereas anomalies of corneal shape include oval cornea (horizontal or vertical cornea), sclerocornea, posterior keratoconus, and keratoglobus.

CHAPTER 10  Ocular Diseases of Importance to the Refractive Surgeon

Megalocornea The normal newborn cornea measures approximately 10 mm horizontally, reaching the adult size by 2 years of age when the horizontal diameter is approximately 12 mm. The measured horizontal diameter usually exceeds the vertical diameter by 1 mm. Megalocornea refers to an enlarged cornea with a horizontal diameter greater than or equal to 13 mm. It is a nonprogressive, bilateral, and symmetrical condition. Because of its predominant transmission as an X-linked recessive trait, 90% of cases are found in the male population.27 Clinically, it is an enlarged but clear cornea of normal thickness and curvature, with normal endothelial cell density. The steeper cornea usually results in a myopic eye with with-the-rule astigmatism. Ocular associated findings include phacodonesis, iridodonesis, and ectopia lentis owing to zonular stretching caused by the widened ciliary ring and enlarged anterior segment (anterior megalophthalmos). The differential diagnosis is mainly buphthalmos from congenital glaucoma.

Microcornea Microcornea is defined as a cornea having a horizontal diameter less than or equal to 10 mm in an otherwise normal-sized globe. Not to be confused with microphthalmos (the entire eye is small and disorganized) or nanophthalmos (the entire eye is small but otherwise normal),28 it is a nonprogressive condition and may be unilateral or bilateral. The small cornea is clear, with normal thickness, but usually flatter than the normal cornea, giving rise to hyperopia, although any refractive error can exist depending on axial length.17 Unlike megalocornea, microcornea is rarely an isolated condition and can have many ocular and systemic anomalies associated with it. The crowded anterior chamber contributes to the development of glaucoma.

Oval Cornea Although the normal cornea is horizontally oval, the term horizontal oval cornea is reserved for extreme cases of this proportion and indicates some degree of sclerocornea. Vertical oval cornea exists when the vertical diameter exceeds the horizontal diameter. When associated with other ocular abnormalities, oval cornea can present some ametropia.

Sclerocornea In sclerocornea, the cornea is flat with a curvature commonly ranging from 30 to 35 diopters (D) (in some cases, as low as 20 D).18 This ocular abnormality is usually associated with cornea plana and hyperopia (Fig. 10.11). It is a nonprogressive, bilateral, and asymmetric condition. Most cases are sporadic; the autosomal-recessive cases exhibit a more severe manifestation of total sclerocornea and autosomal-dominant cases present with a more benign form of peripheral sclerocornea.29 Similarly, autosomal-dominant

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transmission in cornea plana is related to less corneal flattening, compared to autosomal-recessive transmission.

Posterior Keratoconus Posterior keratoconus is considered to be a rare developmental condition that bears no relationship to anterior keratoconus. It is usually unilateral, nonprogressive, noninflammatory, and it rarely affects visual acuity. However, it may cause a myopic astigmatism that should be corrected with spectacles to prevent amblyopia. The condition may occur in a generalized or circumscribed form. Generalized posterior keratoconus exists when the entire posterior corneal surface has an increased curvature with a shorter radius of curvature and a normal anterior corneal surface. This pattern of posterior keratoconus is less common. The more common circumscribed form of posterior keratoconus is characterized by one or more localized, crater-like lesions in the central or eccentric posterior cornea. Corneal clouding with variable corneal thinning is frequently encountered overlying the posterior corneal defect. The majority of cases are sporadic. It is also thought to be a mild variant of Peters anomaly, thereby implying intrauterine inflammation or some other anterior segment dysgenesis as an etiologic factor.30

Keratoglobus Keratoglobus is more frequently present at birth and is considered to be a developmental anomaly. It is a bilateral, noninflammatory, ectatic disorder in which the entire cornea becomes thinned (to approximately one-third to one-fifth of the normal corneal thickness) and takes on a globular shape, with keratometry readings as high as 50 to 60 D, generating high myopia. The anterior chamber is very deep with otherwise normal anterior segment structures and a normal-sized globe (Fig. 10.12).31 Corneal hydrops can occur from spontaneous breaks in the Desçemet membrane. Corneal rupture is a potential complication and may occur spontaneously or following minimal trauma.32 The differential diagnosis includes keratoconus, pellucid marginal degeneration, megalocornea, and buphthalmos. Treatment is centered on correcting the accompanying high myopia with spectacles to prevent amblyopia. Lamellar/penetrating keratoplasty and epikeratoplasty are technically challenging procedures in this setting and should be attempted only when absolutely necessary.

Keratoconus Keratoconus was first described in 1854, when it was called conical cornea. This condition is usually bilateral and is characterized by progressive corneal steepening, most typically inferior to the center of the cornea, with corneal apex thinning, induced myopia, both regular and irregular astigmatism (Figs. 10.13A and 10.13B) and lack of active inflammation.

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C

A

B • Fig. 10.11

  (A) A 22-year-old woman with sclerocornea and cornea plana. (B) Corneal topography showing severe corneal flattening under 30 D in both eyes. (C) Ultrasound biomicroscopy showing shallowing of the anterior chamber with 0.995 mm of depth.

• Fig. 10.12  Side view of keratoglobus revealing the globular shape of the cornea and deep anterior chamber. (Courtesy of Lincoln Freitas, MD, Federal University of Sao Paulo, Paulista School of Medicine, Sao Paulo, Brazil.)

Vogt striae can be often seen in the stroma as deep stress lines that clear when the lids are pressed upon during slit lamp examination. A ring of iron deposition accumulates in the epithelium at the base of the cone (Fleisher ring). In advanced stages, scarring at the level of the Bowman layer also is visible. Steepening of the cornea leads to clinical signs, which include protrusion of the lower eyelid on downgaze (Munson sign), focusing of a light beam shown from temporally across the cornea in an arrowhead pattern at the nasal limbus (Rizutti sign), and a dark reflex in the area of the cone on observation of the cornea with the pupil dilated using a direct ophthalmoscope set on plano (Charleaux sign). In some patients, acute rupture of the Desçemet membrane may occur and result in acute hydrops.33 Computer-assisted analysis of the complex corneal topographic findings of keratoconus was first reported by Klyce

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spectacle-corrected acuity becomes inadequate. When contact lenses no longer provide adequate acuity, contact lens comfort becomes inadequate, or the steepness of the cornea is such that lenses cannot be maintained in position, surgical treatment is indicated. Standard surgical treatment consists of keratoplasty; lamellar keratoplasty is effective, and intracorneal ring segments have achieved some success in patients without corneal scarring in reducing the myopia and astigmatism and improving spectacle-corrected visual acuity.37 A

B • Fig.

10.13  (A) Slit lamp appearance of cornea in keratoconus showing apical thinning and scarring as well as forward bulging of the lower lid (Munson sign). (B) Videokeratographic appearance of patient with keratoconus, showing high myopia and irregular astigmatism.

in 1984.34 Several authors further characterized two corneal topographic patterns typical of keratoconus: inferotemporal steepening and central steepening with an associated asymmetric astigmatic pattern.35 In addition, there was a statistically significant difference in the following parameters in eyes with keratoconus compared with normal eyes36: • central corneal power > 47.20 D • difference in corneal power between fellow eyes > 1 D • steepening of the inferior compared with the superior cornea > 1.4 D • skewing of the radial axis of astigmatism > 21° These findings have a sensitivity of 98% and a specificity of 99.5% for the diagnosis of keratoconus. Keratoconus has been found to be clearly associated with atopy, Down syndrome, Ehlers–Danlos syndrome, and osteogenesis imperfecta. Many other connective tissue diseases have been linked to keratoconus, including neurofibromatosis, pseudoxanthoma elasticum, ichthyosis, and Marfan syndrome.33 The incidence of keratoconus has also been found to be increased in retinitis pigmentosa (RP), Leber congenital amaurosis, retinal aplasia and coloboma, aniridia, and vernal keratoconjunctivitis. Treatment consists of spectacles for astigmatism and myopia initially, followed by rigid contact lenses once

Other Noninflammatory Corneal Thinning Disorders Other noninflammatory corneal thinning disorders include keratoglobus, Terrien and pellucid marginal degenerations, and posterior keratoconus. Patients with these conditions are not good candidates for refractive surgery. A nonprogressive, diffuse corneal thinning and resultant globular corneal protrusion occurs in keratoglobus, in which there is no evidence of the iron deposition or corneal scarring of keratoconus. Thinning is maximal at the corneal periphery; in this condition, the cornea is more prone to perforation from minimal trauma.38 Treatment includes protection from trauma and is similar to that of keratoconus. In pellucid marginal degeneration, the corneal thinning is inferior and peripherally located; the resultant corneal protrusion is above the zone of thinning. The central cornea is regular but usually with marked against-the-rule astigmatism. Hydrops may occur. There are no corneal blood vessels associated with the thinning, which helps to distinguish this condition from Terrien marginal degeneration. In the latter, the thinned cornea is vascularized and frequently lipid is deposited at the junction of normal and diseased cornea. It is believed that conventional keratorefractive procedures are unpredictable, risky, and unstable in patients with corneal thinning disorders. Corneal reinforcement surgery has been advocated for several of these conditions whenever impending perforation, as sometimes occurs in Terrien marginal degeneration and in keratoglobus, is encountered.

Epithelial Corneal Dystrophies A corneal dystrophy is a hereditary, bilateral corneal disease that is only rarely associated with systemic disease. Most disorders are inherited, characteristically in a dominant fashion, and often appear clinically to involve only one layer of the cornea. Only epithelial dystrophies will be considered in this chapter, because they can be treated by laser refractive surgery, in contrast to stromal dystrophies and endothelial dystrophies, which are associated with loss of corneal transparency. Treatment of these latter dystrophies involves penetrating or lamellar keratoplasties, which are not addressed in this book. Epithelial dystrophies have in common a predisposition for the spontaneous development of recurrent erosions and

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persistent epithelial defects. They represent absolute contraindications for LASIK because they can be a source of intraoperative corneal erosions as well as postoperative persistent epithelial defects and epithelial ingrowth. Surface photoablation is the treatment of choice for patients with epithelial dystrophies who are candidates for laser refractive surgery.39

Map-Dot Fingerprint Dystrophy Both Cogan and Guerry described a syndrome of visible, aberrant epithelial formations, later termed map-dot-fingerprint dystrophy. Thickened multilaminar, subepithelial basement membrane material forms areas of thin lines and thicker irregular geographic areas. Intraepithelial microcysts of epithelial cell debris form dots. These lesions are best visualized with sclerotic scatter or retroillumination. Although they are probably autosomal dominant in inheritance, many show no apparent familial pattern. Irregular astigmatism from these superficial lesions sometimes can lead to decreased visual acuity. Painful, recurrent corneal erosions are more common after the third decade of life and usually are self-limited, with spontaneous resolution after several years. The etiology of this common dystrophy appears to be related to abnormal basement membrane production, which fails to adhere properly to the overlying epithelium and predisposes to the development of recurrent erosions (Fig. 10.14). The cycle of abnormal basement membrane adhesion and impaired epithelial maturation can be broken in some patients with a variety of treatment modalities, such as anterior stromal micropuncture, superficial keratectomy, and excimer laser phototherapeutic keratectomy.40

A

B • Fig. 10.14  (A) Basement membrane dystrophy. (B) Abnormal basement membrane production prevents proper adhesion of the overlying epithelium and predisposes to the development of recurrent erosions.

Meesmann dystrophy is an autosomal-dominant, inherited, bilateral disorder usually seen as early as the first year of life as multiple tiny intraepithelial cysts. No systemic associations occur. The patient remains asymptomatic until middle age, at which time diffusely distributed intraepithelial vesicles break through the anterior epithelial surface and cause punctual staining, intermittent irritation, and irregular astigmatism. These vesicles stain with fluorescein and rose bengal stains. Histopathology of these lesions shows a periodic acid–Schiff (PAS)-positive materia.41 Symptoms are generally mild and related to mild ocular irritation and foreign-body sensation.

specific defect in the keratoepithelin gene on chromosome 5q.42 No systemic associations are known. Histopathology reveals destruction of the Bowman layer and the accumulation of an indistinct fibrillar material in its place. The histopathologic features are characteristic and unfortunately result in frequent, recurrent erosions that typically begin in the first 1 to 2 years of life. By the second or third decade of life, the painful erosions diminish as corneal sensitivity decreases, but the increasing fibrosis results in visual dysfunction. Anterior membrane dystrophy of Grayson and Wilbrandt and honeycomb dystrophy of Thiel and Behnke appear to be variants of Reis–Bückler dystrophy (Fig. 10.15). The anterior location of the lesions in these conditions causes them to respond well to excimer laser phototherapeutic keratectomy.40

Reis–Bückler Dystrophy

Band Keratopathy

In Reis–Bückler dystrophy, diffuse, irregular opacities at the level of the Bowman membrane take on a characteristic reticular appearance. The gradual development of intervening anterior stromal haze between these lesions causes decreased visual acuity. This condition also shows autosomaldominant inheritance and recently has been linked to a

Band keratopathy can be inherited as a primary disorder whose characteristic histopathologic finding of calcium deposition within the epithelium and Bowman layer is identical to that seen in the more common condition resulting from chronic ocular irritation or systemic disease (Fig. 10.16). It can be treated by laser phototherapeutic

Meesmann Dystrophy

CHAPTER 10  Ocular Diseases of Importance to the Refractive Surgeon

• Fig. 10.15  Reis–Bückler dystrophy with “honeycomb” appearance at the level of the Bowman layer. (Courtesy of Walter J. Stark, MD.)

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• Fig. 10.17  Optic nerve of axial myope. Note the vertical elongation, peripapillary atrophy, and relatively large cup.

had LASIK because there is no correlation between PDCT and central corneal thickness.45

Ocular Hypertension and Primary Open-Angle Glaucoma

• Fig. 10.16  Band keratopathy showing calcium deposition within the epithelium and Bowman layer in the inferior cornea.

keratectomy, but chelation with ethylenediaminetetraacetic acid (EDTA) is the preferred method of treatment.40

Glaucoma After central photoablation for myopic patients, intraocular pressure (IOP) measurements can be underestimated.43 No precise conversion between the amount of ablated tissue and IOP changes after refractive surgery is available. Therefore refractive surgery in glaucoma-suspect patients or in patients with controlled glaucoma under topical medication may be considered a relative contraindication due to difficulty in detecting changes in IOP, concealing its progression, and compromising its early detection and treatment. The Ocular Hypertension Treatment Study (OHTS), which evaluated 1301 subjects, also concluded that central corneal thickness may influence the accuracy of applanation tonometry in patients with glaucoma.44 Pascal dynamic contour tonometry (PDCT) may be more reliable than Goldmann applanation tonometry for monitoring IOP in unoperated eyes and in eyes that have

Myopia is one of several ocular risk factors for the development of ocular hypertension and subsequent glaucomatous optic nerve damage. Myopes seem more likely to develop visual field loss at IOP less than 21 mm Hg (normal tension glaucoma).46 Estimates of the frequency of myopia among patients with glaucoma range from 6.6% to 37.8% (compared with 3% to 25% of the general population).47 Mastropasqua and associates47 found a significantly higher frequency of high myopia in patients with primary openangle glaucoma (POAG). Approximately 9% to 28% of myopic patients also carry the diagnosis of POAG. Wilson et al.,48 using multiple logistic regression for simultaneous evaluation of numerous factors, found that myopia was a “suggestive association” both for patients with overt POAG and for individuals suspected of having glaucoma. In myopes, early glaucomatous changes can be difficult to recognize.49 Myopic tilting of optic discs and peripapillary atrophy can further obscure analysis of optic nerve topography (Fig. 10.17). Furthermore, myopes are significantly more likely to develop nonglaucomatous atypical nerve fiber bundle defects on the perimetry, complicating the interpretation of serial visual fields.

Pigment Dispersion Syndrome and Pigmentary Glaucoma The majority of patients with pigmentary dispersion, with or without glaucoma, are young myopic men with particularly deep anterior chambers (ACs).50 Based on the classic pattern of radial midperipheral transillumination defects of the iris, the excessive pigment is felt to be liberated by abnormal contact between the pigment epithelium of the concave iris and the zonules of the lens (reverse pupillary block).51

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Pigmentary dispersion syndrome includes a pigment spindle on the corneal endothelium, radial midperipheral transillumination defects of the iris, pigment on the anterior lens capsule, and heavy pigment in the trabecular meshwork and on the Schwalbe line. Once IOP is found to be elevated, or glaucomatous optic nerve or visual field changes are noted, the diagnosis of pigmentary glaucoma is generally made. Wide fluctuations in IOP are another hallmark of the syndrome. Management of patients with pigmentary glaucoma is not unlike that for patients with POAG, except that the patients are typically younger and tolerate miotic therapy poorly. Laser trabeculoplasty often lowers IOP temporarily (weeks or months), typically for a shorter period than in POAG. Standard filtration surgery is successful.

Steroid-Induced Glaucoma It is well established that approximately one-third of the general (nonglaucomatous) population will develop a moderate rise in IOP after 4 to 6 weeks of topical corticosteroid administration. The pressure response is significant or marked (> 31 mm Hg) in only 5% to 6% of the population, however.52 Older patients, as well as those with previously diagnosed POAG, are particularly susceptible. Patients with a family history of glaucoma are also at very high risk for this so-called steroid response. Over 85% of high myopes also will suffer a significant increase in response to a topical steroid challenge.53 Pathogenesis is believed to be related to abnormal accumulation of glycosaminoglycans within the trabecular meshwork in susceptible individuals. Following cessation of exposure, IOP tends to return to normal within days to weeks, although rare cases take significantly longer. In very rare cases, the glaucoma may be permanent, although many of these cases may be previously undiagnosed or latent POAG. Some myopes at higher risk of developing POAG may fall into this category, as mentioned before. If topical steroids are clearly indicated, fluorometholone and rimexolone are known to elicit the least effect. This issue becomes more important when photorefractive keratectomy (PRK) is performed because longer use of topical corticosteroids is necessary to avoid haze formation.

Chorioretinal Disorders Myopic Macular Degeneration Myopic macular degeneration generally occurs in high myopes (> 6 D), who have an abnormally elongated globe. This category of patients represents approximately 1.7% to 2.1% of the general population.54 This prevalence of high myopia depends strongly on ethnic origin. Women are more frequently affected and seem more susceptible to developing associated macular degeneration. The clinical findings of myopic macular degeneration are probably a direct result of axial elongation with progressive distension of the posterior globe leading to thinning of the sclera, choroid, and retina. The optic nerve is usually elongated vertically and may appear tilted. The sclera adjacent to the optic nerve may become visible as a temporal myopic conus (Fig. 10.18) or an annular atrophy. A staphyloma develops in very high myopia and can affect central acuity if the fovea is involved. Profound atrophy of the retinal pigment epithelium (RPE) and choroid can occur, resulting in the so-called tigroid fundus (Fig. 10.19) in focal patches resembling the geographic atrophy seen in age-related macular degeneration. The finding considered pathognomonic of myopic macular degeneration is the lacquer crack (see Fig. 10.19) due to ruptures in the Bruch membrane and the RPE. Subretinal hemorrhage is frequently associated with new or enlarging lacquer cracks. Thus their presence does not necessarily indicate concomitant choroidal neovascularization. They typically reabsorb completely over weeks to months, with little long-term impact on vision. The most feared complication of myopic macular degeneration is choroidal neovascularization (CNV). Some 5% to 10% of the myopic population will develop CNV, with a prevalence of up to 40% in high myopia.55 In a study, the rate of bilaterality was 41%.56 Clinically, the development of CNV is heralded by painless loss of vision or metamorphopsia. Myopic membranes

Congenital Glaucoma B-scan ultrasonography of an eye with congenital glaucoma will typically show significant globe lengthening. The more severe the glaucoma, the greater the degree of enlargement. Eyes with significant secondary axial myopia will probably have suffered optic nerve damage from the glaucoma. This, plus secondary amblyopia, renders the myopia more an epiphenomenon than a management issue. Eyes with useful vision should receive full correction, if possible, to minimize ongoing amblyopia. Congenital glaucoma is an absolute contraindication for refractive surgery.

• Fig. 10.18

  Myopic conus. Note the tilted optic nerve and peripapillary atrophy extending into the macula.

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A

A

B

B

• Fig. 10.19  Myopic fundus. Diffuse atrophy of the retinal pigment epithelium renders the larger choroidal vessels easily visible against the sclera. (A) The vessels stand out on color photography. The linear hypopigmented streaks inferior and temporal to the macula are lacquer cracks, a form of dry macular degeneration. (B) On fluorescein angiography, the choroidal vessels are even more striking. The lacquer cracks appear as window defects (early hyperfluorescence that fades in late views).

are distinguished by a tendency to become hyperpigmented (Fuchs spot) and to be clinically indolent, with scanty hemorrhage and fluid leakage (Fig. 10.20). Fluorescein angiography confirms early hyperfluorescence, which increases in size and intensity in late views, but the leakage is not pronounced. CNV often develops in direct continuity with lacquer cracks.57 The membranes are usually quite close to the center of the fovea, with the majority involving the fovea center at the time of examination. Because of the controversy regarding the natural history of the disorder, the role of laser photocoagulation in treatment has been uncertain as well. Laser treatment for CNV outside the fovea center is probably justified if the patient understands most of the important issues. Recently, photodynamic therapy using verteporfin has been used for treatment of subfoveal CNV in highly myopic patients. Verteporfin seems to improve visual prognosis in these patients.58

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• Fig. 10.20  Myopic choroidal neovascularization (CNV). This 32-yearold woman presented with a 1-week history of decreased reading vision and purple chromatopsia. Visual acuity is 20/100. (A) Note the classic hyperpigmented plaque just superior to the foveal center with a rim of surrounding atrophy of the retinal pigment epithelium. The lesion in the superior macula probably represents scarring from previous CNV that spontaneously involuted. (B) Angiography discloses a classic membrane with surrounding blocked fluorescence, mostly due to hyperpigmentation. Note the relative lack of fluorescein leakage. This lesion was also left untreated owing to its proximity to the fovea. Acuity subsequently dropped to 20/200 after 3 months of observation.

Lattice Degeneration of the Retina Lattice degeneration, along with peripheral cystoid and cobblestone degeneration, is one of the three most common degenerations of the peripheral retina. Like cobblestone degeneration, lattice degeneration bears a clear association with increased axial length. Lattice degeneration is the only one of the three to be associated with primary retinal detachment. Histologic hallmarks of lattice degeneration include localized retinal thinning, overlying vitreous liquefaction, and enhanced vitreoretinal adhesion at the lesions’ borders. Of eyes with lattice degeneration, 75% are myopic to some degree.59 With myopia of 1 D or greater, the incidence of lattice degeneration is 15%, twice that of the general population,60 and it increases with increasing axial length.61

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The primary clinical features of lattice degeneration are well described, including lattice-like sclerotic vascular changes, multiple tiny yellow–white flecks on the inner retinal surface, hyperplasia or atrophy of the RPE, and oval or linear erosions of the retinal surface. When the yellowish flecks are extensive and coalescent, the retina appears shiny and wet, in which case the term snailtrack degeneration is applied. The clinical importance of lattice degeneration is its clear association with rhegmatogenous retinal detachment. Because of the abnormally strong vitreoretinal adhesion at the borders of lattice lesions, there is significant risk of retinal break formation at the time of acute posterior vitreous separation. Byer62 followed 204 eyes with lattice degeneration over 3 to 10 years and found that 1.5% developed tears at the margin of lattice lesions. The risk of detachment in all patients with lattice degeneration is estimated at 0.3% to 0.5%, while 20% to 32% of all rhegmatogenous retinal detachments are associated with lattice degeneration.60,61 If no lattice degeneration is discovered by the end of the third decade, it is unlikely to develop subsequently. If there is active lattice degeneration, the patient should undergo routine dilated examination, perhaps every 1 to 2 years. Prophylactic retinopexy (laser or cryotherapy) of lattice degeneration may be of value in the following cases: when symptoms of vitreoretinal traction (flashes and floaters), are associated with a history of detachment in the fellow eye; on the fellow eye when the contralateral eye had a poor functional outcome after repair of a retinal detachment; patients less able to detect or attend to acute posterior vitreous separation (patients with intellectual disabilities or who are homebound); patients with new symptomatic retinal breaks. However, Wilkinson63 reviewed the literature on this topic and concluded that there is not sufficient information to support strongly prophylactic treatment of lesions other than symptomatic flap tears.

Retinal Detachment The risk of rhegmatogenous retinal detachment clearly increases with increasing axial length. Depending on the series, between 40% and 80% of retinal detachments occur in eyes with axial myopia. Vitreous liquefaction, together with the increased incidence of lattice degeneration, increases the incidence of retinal detachment. These factors also increase the risk of retinal detachment after cataract extraction and laser capsulotomy.64 Moreover, cataract surgery is associated with higher incidence of posterior capsule opacification (PCO) in these myopic eyes, requiring posterior capsulotomy.65 Repair of myopic retinal detachment is not significantly different than for other eyes, except that intraoperative and postoperative complications are more frequent. These include inadvertent perforation due to a thin sclera, excessive fluid drainage with hypotony, retinal incarceration,

choroidal effusion and hemorrhage, or postoperative glaucoma (including steroid induced). Highly myopic eyes are also at risk for progressive retinal detachment after idiopathic macular hole formation. This is distinctly uncommon in emmetropic or hyperopic eyes. Pars plana vitrectomy with gas–fluid exchange and prone positioning is necessary for repair.

Other Peripheral Retinal Degenerations White Without Pressure This not uncommon but poorly understood peripheral retinal change occurs most commonly in the young black myopic eye. Thirty-five percent of myopic eyes under 40 years of age show some white without pressure, but this rate falls to 9.5% of patients over 40 years old. The changes appear as an unusual whitish sheen to the inner retinal surface. If the change is seen only on depressed examination, it is referred to as white with pressure. The cause of the appearance is not known but is believed to be due to an abnormality in the vitreoretinal interface. The condition does not seem to constitute any risk for primary retinal detachment but it does carry an important implication for patients with a history of a giant tear in the fellow eye. In some of these patients, the white without pressure progresses with subsequent formation of retinal breaks, often giant tears.

Cobblestone Degeneration Cobblestone degeneration (also known as pavingstone degeneration) is a common peripheral retinal disorder characterized by round or oval punched-out regions of peripheral chorioretinal atrophy. The disorder is probably secondary to choroidal vascular insufficiency, affecting localized areas of the choriocapillaries. Local ischemia leads to focal atrophy of the RPE and outer retina. The incidence increases with age and axial length, occurring in over 50% of myopes. The disorder is not associated with the formation of primary retinal breaks but can be the source of secondary breaks in an eye with a progressive retinal detachment.

Peripheral Pigmentary Degeneration The peripheral retina of axially elongated eyes often shows significant variation in outer retinal and subretinal pigmentation. It may be diffusely darkened and show discrete focal hyperpigmentation or even a pseudo–RP appearance. The pigmentary “degeneration” is strongly associated with increasing axial length and age. It does not constitute any independent risk for retinal breaks or detachments beyond that of the myopia itself.

Idiopathic Multifocal Choroiditis In 1973, Nozik and Dorsch described a “new chorioretinopathy” characterized by multiple, small, yellow– white lesions of the RPE and inner choroid that appeared similar to those seen in the presumed ocular histoplasmosis

CHAPTER 10  Ocular Diseases of Importance to the Refractive Surgeon

syndrome (POHS).66 Two features have come to distinguish the syndrome from POHS. First, there is usually little or no peripapillary scarring; more important, there is often AC or vitreous inflammation, which is not seen in POHS. Some authors have noted that many affected patients were mildly myopic, but the reason is unknown.67 The disorder tends to affect otherwise healthy younger people (generally < 45 years of age), with a female-to-male ratio of up to 3 : 1. The majority of cases will become bilateral. Recurrent episodes of choroiditis and panuveitis occur, which are often asymptomatic. Any initial symptoms relate to vitreous floaters, since most involved eyes are white and quiet. The choroiditis typically involves the postequatorial fundus, with numerous 100- to 300-µm lesions. Occasionally, active choroiditis near the center of the macula can result in a scotoma or metamorphopsia. Many patients (between 25% and 50%) will develop CNV with loss of central acuity. A smaller subset develops progressive subretinal fibrosis, with no angiographic evidence of CNV. Treatment of active choroiditis is generally reserved for lesions threatening the center of the macula. Oral corticosteroids are sometimes successful in this situation. Any patient with active CNV is generally treated promptly, most often with laser photocoagulation. It is important to note that the term multifocal choroiditis is purely descriptive and can apply to a variety of etiologies and syndromes with systemic manifestations (sarcoidosis, tuberculosis, syphilis, Pneumocystis carinii, herpes zoster, atypical mycobacteria, and fungi).68 The association with mild to moderate myopia has only been demonstrated in idiopathic cases.

Choroidal Hemorrhages/Effusions Axial myopia has been associated with both choroidal effusions and hemorrhages. Effusions are more common among high myopes and the elderly. Risk factors in suprachoroidal expulsive hemorrhage include increased axial length.69 Choroidal hemorrhages are also associated with short eyes, such as in nanophthalmos, when undergoing an intraocular procedure.70 Most effusions and delayed hemorrhages can be observed for spontaneous resolution. Indications for intervention include significant AC shallowing, severe secondary glaucoma, or prolonged contact of extremely large bullous detachments. Surgical drainage is the definitive treatment.71 Recognition of risk factors is important for prevention. In eyes with axial myopia, a Flieringa ring can reduce the amount of mechanical distortion that the globe undergoes during anterior segment procedures.

Choroidal Folds Choroidal folds are a direct manifestation of mechanical distortion of the choroid and overlie a Bruch membrane– RPE complex. They can arise from a variety of conditions,

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such as postoperative or posttraumatic hypotony, posterior scleritis, and tumors of the choroid or orbit, and do not represent a specific disorder. They appear as alternating dark and light striae seen clinically and angiographically. Most cases are asymptomatic. Kalina and Mills72 described a syndrome of acquired hyperopia associated with choroidal folds and no other discernible ocular abnormality. Dailey et al.73 subsequently reported seven healthy adults with hyperopic shifts in refraction associated with new choroidal folds. Computed tomography scanning or B-scan ultrasound testing documented flattening of the posterior sclera, thickening of the choroid, mild to moderate optic nerve enlargement, and a visible space between the optic nerve and its sheath. Refractive correction restored excellent acuity that tended to remain stable over time.

Acquired Retinoschisis This degeneration of the peripheral retina has been reported to affect 7% of patients aged over 40 years. Its incidence and severity increase with age. It consists of a splitting of the sensory or neural retina at the outer plexiform layer. In the reticular form, distinguished clinically (in some cases) by fine white lines corresponding to retinal blood vessels and by a particularly transparent inner layer, the schisis cavity is within the nerve fiber layer, similar to juvenile schisis. Most experts agree that the reticular form is more frequently associated with retinal detachment. Both forms are closely associated with peripheral cystoid degeneration of the retina and probably represent the severe end of a common disease spectrum. Retinoschisis manifests itself clinically as retinal elevation, similar to true retinal detachment. Unlike retinal detachment, the inner layer of a schisis cavity is quite transparent and immobile. There are two important complications of retinoschisis. The first is posterior progression of the schisis cavity with a symptomatic visual field defect. The second, and more important, complication of retinoschisis is true retinal detachment. Unlike true retinal detachment, these breaks are not full thickness but rather are limited to either the outer (3.7%) or inner (1.6%) layer.74 Rarely (0.8% of affected patients), breaks develop in both outer and inner layers. Many investigators have confirmed that retinoschisis is more common in hyperopes.75,76 On the other hand, when considering the foveal region, schisis has been very common in high myopia.77 Because the risk of visual loss due to posterior progression is small, treatment is generally reserved for cases of true retinal detachment. Laser barriers may also be used in the setting of combined inner and outer layer breaks without subretinal fluid. In the setting of a small detachment, laser retinopexy circumscribing the entire area of schisis can prevent the spread of subretinal fluid and visual loss. Scleral buckling surgery is required if the area of schisis or detachment is extensive.

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Nanophthalmos and Uveal Effusions Eyes that are 21 mm or shorter are generally considered nanophthalmic.78 Nanophthalmos is a rare condition consequent upon arrest in the development of the globe. The condition may be sporadic or familial. There is no sex predilection (unlike the idiopathic uveal effusion syndrome, which is more common in men). Because of short axial length, these eyes are always highly hyperopic (at least +8 D). Every feature of the eye is smaller than normal, with the notable exception of the lens, which is of normal size and much too large for the small AC. In nanophthalmos, the lens may represent 11% to 32% of the space,79 with a significant incidence of pupillary block and angle-closure glaucoma. It has long been recognized that cataract and filtration procedures on nanophthalmic eyes result in a significant rate of vision-threatening choroidal (uveal) effusions. Effusions can also develop spontaneously. This is because the sclera in patients with this condition is markedly thickened and disorganized histologically. These changes result in significantly increased resistance to vascular flow through the vortex venous system. Treatment of uveal effusion associated with nanophthalmos consists of decompression of the vortex veins along with drainage sclerotomies.80

sions, including axial length. Thus axial hyperopes may be at increased risk for two important disorders of small optic nerve heads.

Optic Disc Drusen Optic disc drusen are hyaline, calcific deposits within the prelaminar portion of the optic nerve head and occur in 3.4 to 24 per 1000 of the population; they are bilateral in approximately 75%.86 Like astrocytic hamartomas of the optic nerve head, optic disc drusen may autofluoresce (Fig. 10.21). They may be inherited in a dominant fashion. They are also associated with RP. They commonly cause asymptomatic visual field loss, indicating an insidious course, but unless they are associated with vascular occlusion (usually venous) or choroidal neovascularization, they do not threaten central acuity. It is accepted that optic disc drusen are more common in small crowded optic nerve heads; they have also been associated with nanophthalmos, which is believed to be due to relative impairment of axoplasmic transport by congestion

Inherited Retinal Degenerations Myopia is far more commonly associated with inherited retinal degenerations than hyperopia. Conversely, virtually every class of retinal degeneration has been reported in association with myopia, including congenital achromatopsia, congenital stationary night blindness, classic RP, choroideremia, and gyrate atrophy (discussed later). In Sieving and Fishman’s review81 of 268 eyes with inherited retinal degenerations, 201 were myopic (75%). The association with myopia may be strongest for congenital stationary night blindness.82 The two main exceptions to this rule are Leber congenital amaurosis and so-called preserved para-arteriolar RPE. Both are autosomal recessive forms of RP and are characterized by moderate to high hyperopia.83,84 Isolated pedigrees of early-onset autosomal-dominant RP and X-linked congenital stationary night blindness,85 each associated with hyperopia, have been reported as new exceptions to the myopia–RP association.

A

Optic Nerve Disorders The nerve fiber layer exits the eye through the lamina cribrosa at the optic nerve head. In eyes with abnormally small lamina, the normal complement of nerve fibers will be crowded. The physical crowding of the small optic nerve head predisposes it to a variety of alterations in normal axonal function. These so-called discs at risk are more likely to be found in eyes with other abnormally small dimen-

B • Fig. 10.21  Optic disc drusen. (A) The “rock-candy” appearance of the optic disc makes the presence of disc drusen obvious. (B) Optic disc drusen may autofluoresce if they are not buried deep within the nerve head. That is, they will “light up” with both barrier and exciter filters in place before fluorescein injection.

CHAPTER 10  Ocular Diseases of Importance to the Refractive Surgeon

of the crowded nerve head. The connection between hyperopia and disc drusen is disputed, however.

Nonarteritic Anterior Ischemic Optic Neuropathy As with optic disc drusen, patients with a small crowded optic nerve head seem to be at risk for developing a common cause of significant visual loss, nonarteritic anterior ischemic optic neuropathy (AION). This syndrome is well recognized as a leading cause of sudden, painless, monocular visual loss in older adults. The sine qua non is disc edema (at least for the nonarteritic type); the classic visual field defect is altitudinal. Same-eye recurrences are rare, but 40% of cases become bilateral with time. The pathogenesis is believed to be related to insufficiency of the posterior ciliary supply to the prelaminar portion of the optic nerve. Systemic associations with AION— including diabetes, hypertension, and atherosclerotic vascular disease—may merely represent the co-incidence of various disorders of aging. On the other hand, they may provide important pathogenetic clues. Giant cell arteritis must still be aggressively ruled out. Small optic nerve size has come to be accepted as important in the pathogenesis of this disorder.87 Katz and Spencer88 showed that eyes with nonarteritic AION tended to be slightly hyperopic.

Systemic Associations Marr et al89 have reported that, among highly myopic infants, only 8% had no associated ocular or systemic disorders. In 54%, there was an underlying systemic association with or without further ocular problems (e.g., developmental delay; prematurity; or Marfan, Stickler, Noonan, or Down syndrome). In the remaining 38%, there were further ocular problems associated with the high myopia (e.g., lens subluxation, coloboma, retinal dystrophy, anisometropic amblyopia).

Diabetes Mellitus Patients with both newly diagnosed and chronic diabetes are subject to unpredictable refractive changes with fluctuations in blood sugar levels. Myopic shift with acute hyperglycemia is seen only in phakic eyes, and it has become widely accepted that the site of diabetic refractive shifts is in the lens rather than the cornea or axial length. Most reports have dealt with the short-term variations in poorly controlled or recently diagnosed diabetes. More recently, interest has been dedicated to chronic diabetes and permanent refractive changes.

Transient Refractive Shifts Myopic Shifts

Conventional teaching holds that acute elevation in blood sugar causes a myopic shift with a gradual hyperopic shift

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back toward the baseline refraction as blood sugar comes under control. This is what Elschnig originally reported and Duke-Elder and Abrams90 undertook to explain. DukeElder and Abrams hypothesized an osmotic imbalance between the lens and aqueous humor, with hyperglycemia leading to lens hydration, decreased radius of curvature, and increased lenticular power. In hyperglycemia, lens fibers take on more glucose than is required metabolically, leading to intracellular accumulation of glucose and its metabolic by-products, sorbitol and fructose. Lens fiber membranes are far less permeable to these latter two than glucose, making them more important osmotically. Most reports of refractive shifts in humans deal with myopic shifts in hyperglycemia.91 Hyperopic Shifts

Although clinical experience has emphasized this tendency for a myopic shift with hyperglycemia, there are several reports of hyperopic shifts that regressed gradually in association with the achievement of long-term euglycemia.92,93 Obviously, inhibition of water by the crystalline lens will lead to a reduction in its refractive index. This will decrease the lens power, resulting in a hyperopic shift. If the curvature change associated with osmotic swelling outweighs the drop in refractive index, the net result will be a hyperglycemic myopic shift. Prescription for refractive correction or refractive surgery is clearly unwise during a period of known or anticipated blood sugar swings. It is important to suspect new-onset diabetes in any patient suffering an abrupt change in refractive error, regardless of its direction. One less common mechanism for a hyperopic shift in newly diagnosed diabetics is accommodative paresis. This has been reported to affect as many as 19% of all new diabetics and 77% of diabetic patients less than 30 years of age with refractive changes.94 The change usually occurs when insulin therapy is started and disappears over 2 to 6 weeks.

Permanent Myopia Fledelius95 demonstrated that diabetics were significantly more likely to have a myopic refractive error than nondiabetics (37.9% vs. 27.5%). The myopia was nearly always mild (less than −2.0 D) and occurred later (after 20 years of age) than in nondiabetics. With subsequent ultrasound information, Fledelius and Miyamoto showed that, when compared with nondiabetics with similar refractive errors, the lenses of diabetics were significantly thicker.96 Lens thickness correlated positively with duration of diabetes.

Myopia and Diabetic Retinopathy In 1967, Jain and associates97 were the first to suggest that myopia may be associated with less progressive diabetic retinopathy. In their study, myopes of greater than −5 D were less likely to develop retinopathy. In 1985, Rand et al.98 demonstrated an increased risk of proliferative retinopathy in association with HLA-DR phenotypes 3/0, 4/0, and x/s (non-3 or non-4). Interestingly, the risk was

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negated by myopia as low as −2 D.98 A second study also showed this relationship to be important for nonproliferative disease.99 Of further interest, myopia did not lessen the severity of retinopathy among patients with the nonsusceptible HLA phenotype. The authors invoked possible ocular (reduced retinal perfusion in myopes) and nonocular causes for myopia’s effect on the natural history of diabetic retinopathy in genetically susceptible individuals.

Acquired Immunodeficiency Syndrome New-onset and rapidly progressive myopia have been reported in patients with human immunodeficiency virus (HIV) infection.100 However, the exact incidence and etiology of the myopia seen in patients with autoimmune deficiency syndrome (AIDS) is unclear.

• Fig. 10.22

  Marfan syndrome. The lens in this high myope (axial length 27 mm) dislocated temporally and posteriorly. Acuity with an aphakic contact lens is 20/20.

Albinism Albinism is an inherited disorder of melanin synthesis that causes hypopigmentation systemically. When eyes, skin, and hair seem equally affected, the disorder is referred to as oculocutaneous albinism. When the eyes are significantly more affected than skin and hair (which may appear normal), it is referred to as ocular albinism. Both disorders are usually inherited on an autosomal recessive basis. Ocular findings include moderately or severely reduced vision, nystagmus, hypopigmented irides with prominent transillumination, and sometimes foveal hypoplasia. The fundus is usually strikingly blond, with visible choroidal vessels and sclera. Visual pathway alterations are frequent. In one review, 5 of 16 albino patients were myopic (31%), 2 of whom were highly myopic (> −12 D).101

Wagner and Stickler Syndromes Historically, these entities have generally been considered as part of the same disease spectrum.102 However, although ocular findings in each may be quite similar, the risk of retinal detachment for patients with Wagner syndrome is much lower than for patients with Stickler syndrome. Also, the findings are limited to the eye in Wagner syndrome, whereas in Stickler syndrome there are prominent abnormalities of the musculoskeletal system. The features common to the two disorders include a high incidence of progressive myopia (> 50%), posterior subcapsular cataract, and the hallmark of the disorders: so-called optically empty vitreous degeneration with epiretinal membranes and lattice-like changes. The retina undergoes progressive pigmentary degeneration, with loss of ERG waveforms and vascular sheathing, while there is also progressive choroidal atrophy. The myopia of these disorders is often severe (> −6 D). Both are inherited in an autosomaldominant pattern. Stickler syndrome has been associated with congenital glaucoma, which may explain in part the high myopia found in this condition.103

Marfan Syndrome Marfan syndrome is another autosomal-dominant disorder of the eyes and musculoskeletal system associated with myopia and retinal detachment. Patients are tall, with long limbs and arachnodactyly, and can have serious, often fatal, cardiovascular problems (aortic valvular insufficiency, dissecting thoracic aortic aneurysm, mitral valve disease). Ectopia lentis is one of the hallmarks of Marfan syndrome (Fig. 10.22). Axial myopia is very common in patients with Marfan syndrome, often apparent by age 5 years. Over 20% of patients are highly myopic. The findings of ectopia lentis and retinal detachment are positively correlated with increasing axial length.104

Weill–Marchesani Syndrome Patients with Weill–Marchesani syndrome, another inherited cause of ectopia lentis, are usually short, with abnormally stiff limbs. The inheritance is autosomal recessive. The myopia in this condition is purely refractive, due to microspherophakia and increased lenticular refractive power.85 The severity of myopia varies from moderate to extremely high (around −20 D). Microspherophakia should be suspected if the equator of the lens can be seen through a dilated pupil (Fig. 10.23). With ectopia lentis, the risk of retinal detachment and acute angle-closure glaucoma (favored by pupil dilation) rises.

Down Syndrome This well-known inherited complex is the most common chromosomal syndrome. With advancing age, nondisjunction of chromosome 21 becomes more likely, resulting in Down syndrome. The systemic findings are well recognized. They include short stature, flattened occiput with low-set ears, and a small nose. The tongue is large and fissured, with

CHAPTER 10  Ocular Diseases of Importance to the Refractive Surgeon

• Fig. 10.23

  Weill–Marchesani syndrome. A 51-year-old man with an anterior inferonasally subluxated lens in the right eye. Note the lens equator characteristic of microspherophakia. The lens is located at the anterior chamber, causing endothelial touch and requiring surgical intervention.

glossoptosis. Feet are short and the hands show an exaggerated simian crease. Ocular findings include epicanthal folds, “mongoloid” slant (upwardly displaced lateral canthi) and hypertelorism. Keratoconus is also frequent. Myopia is significantly more common (> 25%) in patients with Down syndrome.105,106

Gyrate Atrophy Although this disorder is caused by a systemic deficiency of a mitochondrial enzyme (ornithine-oxalate aminotransferase), the ocular findings greatly overshadow the impact of the systemic findings (alopecia and muscle weakness). The autosomal recessive inborn error of metabolism leads to hyperornithinemia. The ocular manifestations consist of a relentlessly progressive tapetoretinal degeneration and cataract. The geographic areas of progressive retinal pigment epithelium (RPE) atrophy are strikingly characteristic of the disorder. Myopia, usually moderate or high, is seen in the majority of affected patients.

Cerebral Palsy This is a heterogeneous group of disorders characterized by motor and cognitive impairment that can be congenital or acquired early in childhood. Cycloplegic refractions on 417 affected children found that higher degrees of hyperopia were more common in children with the dyskinetic type of cerebral palsy than in healthy children.107

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51. Farrar SM, Shields MB. Current concepts in pigmentary glaucoma. Surv Ophthalmol. 1993;37(4):233–252. 52. Arrigg CA. Corticosteroid-induced glaucoma. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia, PA: WB Saunders; 1993:1462–1467. 53. Wang RF, Guo BK. Steroid-induced ocular hypertension in high myopia. Chin Med J. 1984;97(1):24–28. 54. Soubrane G, Coscas G. Choroidal neovascular membrane in degenerative myopia. In: Ryan SJ, ed. Retina. St Louis, MO: Mosby; 1989:201–217. 55. Hotchkiss ML, Fine SL. Pathologic myopia and choroidal neovascularization. Am J Ophthalmol. 1981;91(2):177–183. 56. Fried M, Siebert A, Meyer-Schwickerath G, Wessing A. Natural history of Fuchs’ spot: a long-term follow-up study. Doc Ophthalmol Proc Ser. 1981;28:215. 57. Avila MP, Weiter JJ, Jalkh AE, et al. Natural history of choroidal neovascularization in degenerative myopia. Ophthalmology. 1984;91(12):1573–1581. 58. Blinder KJ, Blumenkranz MS, Bressler NM, et al. Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial—VIP report no. 3. Ophthalmology. 2003;110(4):667–673. 59. Byer NE. Clinical study of lattice degeneration of the retina. Trans Am Acad Ophthalmol Otolaryngol. 1965;69(6):1065–1081. 60. Hyams SW, Neumann E. Peripheral retina in myopia. With particular reference to retinal breaks. Br J Ophthalmol. 1969;53(5): 300–306. 61. Byer NE. Lattice degeneration of the retina. Surv Ophthalmol. 1979;23(4):213–248. 62. Byer NE. Changes in and prognosis of lattice degeneration of the retina. Trans Am Acad Ophthalmol Otolaryngol. 1974;78(2): OP114–OP125. 63. Wilkinson CP. Evidence-based analysis of prophylactic treatment of asymptomatic retinal breaks and lattice degeneration. Ophthalmology. 2000;107(1):12–15, discussion, 15–18. 64. Koch DD, Liu JF, Gill EP, Parke DW 2nd. Axial myopia increases the risk of retinal complications after neodymium-YAG laser posterior capsulotomy. Arch Ophthalmol. 1989;107(7): 986–990. 65. Colin J, Robinet A, Cochener B. Retinal detachment after clear lens extraction for high myopia: seven-year follow-up. Ophthalmology. 1999;106(12):2281–2284, discussion, 2285. 66. Nozik RA, Dorsch W. A new chorioretinopathy associated with anterior uveitis. Am J Ophthalmol. 1973;76(5):758–762. 67. Morgan CM, Schatz H. Recurrent multifocal choroiditis. Ophthalmology. 1986;93(9):1138–1147. 68. Deutsch TA, Tessler HH. Inflammatory pseudohistoplasmosis. Ann Ophthalmol. 1985;17(8):461–465. 69. Speaker MG, Guerriero PN, Met JA, et al. A case-control study of risk factors for intraoperative suprachoroidal expulsive hemorrhage. Ophthalmology. 1991;98(2):202–209, discussion, 210. 70. Wu W, Dawson DG, Sugar A, et al. Cataract surgery in patients with nanophthalmos: results and complications. J Cataract Refract Surg. 2004;30(3):584–590. 71. Wirostko WJ, Han DP, Mieler WF, et al. Suprachoroidal hemorrhage: outcome of surgical management according to hemorrhage severity. Ophthalmology. 1998;105(12):2271–2275. 72. Kalina RE, Mills RP. Acquired hyperopia with choroidal folds. Ophthalmology. 1980;87(1):44–50. 73. Dailey RA, Mills RP, Stimac GK, et al. The natural history and CT appearance of acquired hyperopia with choroidal folds. Ophthalmology. 1986;93(10):1336–1342.

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74. Hirose T, Marcil G, Schepens CL, Freeman HM. Acquired retinoschisis: observations and treatment. In: Pruett RC, Regan CDJ, eds. Retina Congress. New York, NY: Appleton-CenturyCrofts; 1974:489. 75. Hagler WS, Woldoff HS. Retinal detachment in relation to senile retinoschisis. Trans Am Acad Ophthalmol Otolaryngol. 1973;77(2):OP99–OP113. 76. Byer NE. Clinical study of senile retinoschisis. Arch Ophthalmol. 1968;79(1):36–44. 77. Panozzo G, Mercanti A. Optical coherence tomography findings in myopic traction maculopathy. Arch Ophthalmol. 2004; 122(10):1455–1460. 78. Brockhurst RJ. Uveal effusion. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia, PA: WB Saunders; 1993:548–559. 79. Kimbrough RL, Trempe CS, Brockhurst RJ, Simmons RJ. Angle-closure glaucoma in nanophthalmos. Am J Ophthalmol. 1979;88(3 Pt 2):572–579. 80. Brockhurst RJ. Vortex vein decompression for nanophthalmic uveal effusion. Arch Ophthalmol. 1980;98(11):1987–1990. 81. Sieving PA, Fishman GA. Refractive errors of retinitis pigmentosa patients. Br J Ophthalmol. 1978;62(3):163–167. 82. Khouri G, Mets MB, Smith VC, et al. X-linked congenital stationary night blindness. Review and report of a family with hyperopia. Arch Ophthalmol. 1988;106(10):1417–1422. 83. Wagner RS, Caputo AR, Nelson LB, Zanoni D. High hyperopia in Leber’s congenital amaurosis. Arch Ophthalmol. 1985;103(10): 1507–1509. 84. Heckenlively JR. Preserved para-arteriole retinal pigment epithelium (PPRPE) in retinitis pigmentosa. Br J Ophthalmol. 1982; 66(1):26–30. 85. Fong DS, Pruett RC. Systemic associations with myopia. In: Albert DM, Jakobiec FA, eds. Principles and Practice of Ophthalmology. Philadelphia, PA: WB Saunders; 1993:3142–3151. 86. Auw-Haedrich C, Staubach F, Witschel H. Optic disk drusen. Surv Ophthalmol. 2002;47(6):515–532. 87. Mansour AM, Shoch D, Logani S. Optic disk size in ischemic optic neuropathy. Am J Ophthalmol. 1988;106(5):587–589. 88. Katz B, Spencer WH. Hyperopia as a risk factor for nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol. 1993;116(6):754–758. 89. Marr JE, Halliwell-Ewen J, Fisher B, et al. Associations of high myopia in childhood. Eye. 2001;15(Pt 1):70–74. 90. Duke-Elder S, Abrams D. Ophthalmic optics and refraction. In: Duke-Elder S, ed. System of Ophthalmology. London, UK: Henry Kimpton; 1970:368–370.

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11 

Patient Evaluation for Refractive Surgery JAYNE S. WEISS, JONATHAN CARR, PETER HERSH, ASHISH G. SHARMA, AND KAZUO TSUBOTA

Introduction As refractive surgery has evolved from the controversial to the routine, more patients want to decrease their dependence on glasses. Laser in situ keratomileusis (LASIK) is a very common refractive procedure; approximately 596,000 LASIK surgeries were done in the United States in 2015, and the number is expected to increase to almost 720,000 by the year 2020.1 Ophthalmologists are increasingly confronted with refractive surgical candidates who also have ocular or systemic disease. In such cases, the ophthalmologist must determine whether refractive surgery poses an unacceptable risk. However, the evaluation of patients for corneal refractive surgery has changed considerably in recent years. We have a better understanding of new refractive surgery technologies, such as the wavefront sensor, as well as greater experience with the intricacies of the excimer laser. This has allowed us to clarify issues of patient candidacy as well as to measure and subsequently treat subtle imperfections of vision. Two aspects of refractive surgery make it a unique surgical procedure necessitating a novel approach to patient selection and preoperative evaluation. First, the eye to be operated on is generally healthy. Second, success is ultimately defined by patient satisfaction, an outcome comprising both objective and subjective patient perceptions.

Philosophical Issues Increased patient interest and evolving attitudes toward refractive surgery within the profession now make it important that all ophthalmologists be conversant with the complete menu of surgical and nonsurgical options for the ametropic patient so that they can properly counsel their patients regarding the advisability and the risks and benefits of each of these procedures. Although some surgeons may philosophically advise against any type of surgical intervention in an otherwise healthy eye, it remains the ophthalmologist’s responsibility to afford considered information and advice to potential refractive surgery patients. 154

Motivations for surgery are largely unchanged, with independence from spectacles and contact lenses during leisure time being the most common reason for consultation. Law enforcement, emergency services employees, and military recruits are undergoing refractive surgery procedures in increasing numbers to avoid the limitations of wearing spectacles or contact lenses in emergency situations. Although all forms of refractive surgery pose inherent risks to the healthy eye, other traditional forms of optical correction are not without potential problems. Contact lens wear is a source of morbidity, with problems ranging from minimal discomfort to sight-threatening infections. Giant papillary conjunctivitis, sequelae of corneal hypoxia, sterile infiltration, and microbial keratitis may all complicate contact lens wear, precluding their use in many patients. Several extensive and comprehensive studies have been conducted on the complications caused by contact lens wear. In one well-controlled study, users of extended-wear lenses had a 10- to 15-fold greater risk of ulcerative keratitis than did users of daily-wear soft lenses.2 In another study, the risk of keratitis was reported to increase fourfold when daily disposable contact lens use was extended to occasional overnight (less often than one night per week) use.3 Stapleton et al. also reported that the wearing of disposable contact lenses appeared to be associated with the lowest risk of microbial keratitis, adding that age is not associated with the severity of the keratitis (age 15–24 vs. 25–54 vs. 55–64).4,5 However, younger age (50 years) were reported to be at significantly greater risk of developing corneal infiltrates in a 1-year prospective study of 6245 wearers of overnight silicone hydrogel lenses.6 It was even reported that there was a 5% greater risk of developing contact lens–related complications for every additional year of a patient’s age.7 In this study of overnight silicone hydrogel lenses, 2.5% of the infiltrates were observed to be lens-related.8 In a related article, the annual incidence of ulcerative keratitis was described as 20.9 per 10,000 wearers when using extended-wear soft contact lenses and 4.1 per 10,000 wearers when using daily-wear soft contact

CHAPTER 11  Patient Evaluation for Refractive Surgery

lenses.9 Some cases of hospital-based microbial keratitis have also been reported in pediatric patients in Hong-Kong and Taiwan, although reports of these kinds of adverse events are rare in the United States and Europe.10,11 Clearly refractive surgical procedures are not without risk, but patients who are using contact lenses are also ultimately accepting a degree of risk. Thus the philosophical debate regarding refractive surgery is not simply one of whether it is appropriate to operate on an otherwise healthy eye. Rather, specific patient circumstances must be carefully considered in order for both the ophthalmologist and the patient to arrive at an appropriate informed decision based on the risks and benefits of the available treatment options.

Guidelines for Patient Selection As experience with refractive surgery has improved, insight has been gained into the absolute and relative contraindications associated with these procedures. Ideally a prospective patient should have an entirely normal eye with an appropriate refractive error. However, patients often request treatment of eyes having problems for which surgery might be contraindicated.

Absolute Contraindications Although advice regarding the propriety of refractive surgery must always be individualized to each patient’s risk-benefit ratio, the following situations include those in which refractive surgery is best avoided. Patients with poorly controlled systemic immunologic disorders such as rheumatoid arthritis, systemic lupus erythematosus, polyarteritis nodosa, and other collagen vascular diseases are at risk of inflammatory and wound-healing sequelae that may cause severe corneal complications. Refractive surgery in such patients is not advised. Contraindications may also derive from the health of the eye itself. Patients with severe dry eye syndromes― including those with conjunctival cicatrizing disorders like Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and a chemically burned ocular surface―are poor candidates because of wound-healing problems that may supervene following surgery. Patients with keratoconus and other ectatic corneal dystrophies should be identified preoperatively. Such patients may frequently present to the refractive surgical practice because of their poor vision with optical correction. Because the optical and physical effects of refractive procedures and the long-term prognoses are unclear in these patients, most refractive surgery is contraindicated in such situations. One exception to this rule might be consideration of insertion of intracorneal ring segments in patients with keratoconus who suffer contact lens intolerance or where a corneal transplant is inevitable; intracorneal ring segments in this situation have delayed but not prevented progression to corneal transplant.12–15 Patients with irregular astigmatism in the absence of keratoconus or ectasia should be managed with caution. The advent of wavefront sensors and the ability to

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custom reshape the cornea with the excimer laser has allowed some of these patients to achieve improved uncorrected and spectacle-corrected vision.16,17 Outside the United States, some surgeons18 have performed topographyguided partial transepithelial photorefractive keratectomy (PRK) and collagen cross linking to treat post-LASIK corneal ectasia. Patient selection is very important, given the tissue removal at the time of cross linking. An alternative approach is delaying the consideration of excimer laser surface ablation until several months after cross linking is performed. Within the United States, keratoconus, forme fruste keratoconus, or other corneal ectasias are typically considered contraindications to excimer laser ablation. The American Academy of Ophthalmology (AAO) Preferred Practice Pattern for Refractive Errors & Refractive Surgery lists the following conditions as contraindications for refractive surgery19: • Unstable refraction • Active or recently active uveitis or uveitis that requires ongoing treatment or is recurrent in nature • Corneal endothelial disease including Fuchs dystrophy • Visually significant cataract in the case of phakic intraocular lenses (IOLs) • Shallow anterior chamber in the case of phakic IOLs • Uncontrolled autoimmune or other immune-mediated disease • Uncontrolled glaucoma • Uncontrolled external disease • Unrealistic patient expectations

Ocular Hypertension and Glaucoma Between 9% and 28% of myopic patients have primary open-angle glaucoma (POAG). The frequency of myopia in the glaucomatous population ranges from 6.6% to 37.8%, compared to 3% to 25% in the normal population. The risk of glaucoma development in low myopia (≤3.00 diopters [D]) is 1.65, whereas it is 2.46 for moderate to high myopia (>3.00 D) based on the pooled odds ratio of 48,161 individuals.20 Worldwide, the number of people with glaucoma in the population aged 40 to 80 years was estimated to be 64.3 million in 2012, and the number is estimated to increase to 76.0 million in 2020 and 111.8 million in 2040.21 The ophthalmic surgeon will encounter glaucoma in some candidates for prospective refractive surgery. Of particular concern in the patient with ocular hypertension (OHT) or POAG undergoing LASIK is the effect of an acute intraocular pressure (IOP) rise to greater than 65 mm Hg when suction is applied during flap creation. Although the normal optic nerve seems to tolerate this IOP elevation, we do not yet fully know the resultant effect on the compromised optic nerve. There have been few reports of new visual field defects immediately after LASIK that have been attributed to mechanical compression or ischemia of the optic nerve head from the increase of IOP. Evaluation of the patient with OHT or POAG includes a complete history and ocular examination with peripheral visual field and corneal pachymetry. Ocular computed

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30

B

A

C • Fig. 11.1

  Glaucomatous optic nerve atrophy in a patient with “normal intraocular pressure (IOP)” after laser in situ keratomileusis (LASIK). (A) Increased cup/disc ratio in a patient diagnosed with glaucoma 1 year after LASIK. Patient had decreased vision with best-corrected visual acuity of 20/40 and IOP of 21 mm Hg. (B) 24-2 visual field with extensive inferior arcuate visual field loss corresponds to thinning of the superior optic nerve rim. (C) Ocular computed tomography demonstrates marked optic nerve cupping. (Courtesy Jayne S. Weiss, MD.).

tomography (OCT) may also assist the assessment of optic nerve cupping. A history of poor IOP control, noncompliance with treatment, maximal medical therapy, or prior surgical interventions may suggest progressive disease, which may contraindicate refractive surgery. As part of the complete dilated examination, the surgeon should note the status of the angle, presence and amount of optic nerve cupping, and degree of visual field loss. Central corneal thickness must be considered in the evaluation of applanation IOP. The principle of applanation tonometry assumes a corneal thickness of 0.52 mm. The IOP is underestimated by 5.2 mm in corneas of 0.45-mm thickness. Corneal curvature can also influence IOP readings with an estimated 1 mm Hg of IOP increase for every 3-D increase in corneal curvature. Many articles document the inaccuracy of IOP measurements after PRK or LASIK because of apparent lowering of the reading. These inaccurately low central applanation tonometry measurements have been reported to obscure the

diagnosis of steroid-induced glaucoma after PRK or LASIK, resulting in optic nerve cupping, visual field loss, and decreased visual acuity (Fig. 11.1).22,23 Because of the difficulty of interpreting IOP measurements after PRK or LASIK, these procedures should not be considered when the IOP is poorly controlled. Glaucoma referral should be obtained when indicated. Patients with OHT can often have refractive surgery. They must be counseled preoperatively that the LASIK treats only the refractive error and not the natural history of the OHT, which can sometimes progress to glaucoma with optic nerve cupping and visual field loss. Particular attention should be paid to risk factors for progression to glaucoma including age, corneal thickness, cup/ disc ratio, and IOP. Patients should also understand that refractive surgery will make it more difficult to accurately assess their IOP after excimer laser ablation. The refractive surgeon may want the patient to sign ancillary consent documenting their understanding that POAG

CHAPTER 11  Patient Evaluation for Refractive Surgery

may result in progressive visual loss independent of any refractive surgery.24,25 Whether to perform refractive surgery in the patient with glaucoma is a controversial issue.26 LASIK is contraindicated in any patient with marked optic nerve cupping, visual field loss, or loss of visual acuity. Although most studies have not found a change in the optic disc or nerve fiber layer thickness after LASIK, there are no long-term studies on refractive surgery in the glaucoma population. A series of patients with pigment dispersion syndrome and glaucoma who are using an IOP-lowering agent concluded that they may have slower healing with decreased predictability of their visual outcome.27 The surgeon should be aware that placement of a suction ring may not be possible if there is a functioning filtering bleb. Typically the glaucoma should be well controlled before refractive surgery is even considered. In the rare case where filtering surgery and LASIK are planned, it is preferable to perform the LASIK before the filter. Suction time should be minimized to decrease the chance of optic nerve damage from the transient increase of IOP. Alternatively, surface ablation might be preferable because it eliminates the IOP rise associated with use of the microkeratome. The surgeon must be careful with the use of postoperative steroids because of the potential elevation of IOP that may result. Postoperatively, the patient should be informed when to resume postoperative topical medications for glaucoma. To avoid trauma to the flap, the IOP should not be checked for at least 72 hours. Both the ophthalmologist and the glaucoma patient must be aware that refractive surgery may change interpretation of diagnostic tests.28 Patients should be told that they must inform subsequent ophthalmologists of a prior excimer laser vision correction procedure as well as of the preoperative refractive error in order to assess the postoperative IOP more accurately. LASIK can also affect measurements of the thickness of the nerve fiber layer performed by scanning laser polarimetry because of the change in the corneal architecture.

Connective Tissue Disease Most surgeons consider active uncontrolled connective tissue diseases―such as systemic lupus erythematosus and polyarteritis nodosa―to be contraindications to surface laser ablation because of reports of postoperative corneal melt and perforation. Late corneal scarring has been reported after PRK in a patient with systemic lupus erythematosus.29–31 Peripheral keratitis with infiltrates was reported to occur after LASIK in a patient with rheumatoid arthritis.

Corneal Dystrophies Granular corneal dystrophy 2 (Avellino dystrophy) is an absolute contraindication to the performance of LASIK. LASIK and PRK result in marked progression of the dystrophy because of rapid accumulation of the Transforming growth factor-beta-induced protein (TGFBIp), which leads to a visual decrease.32 LASIK should also be avoided in Fuchs dystrophy.33

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Patient Expectations The patient with unrealistic expectations is at high risk for being unhappy with the most successful result of refractive surgery. Consequently a patient with unrealistic expectations should be considered an absolute contraindication to performing the procedure.

Relative Contraindications Patients with glaucoma should be treated with caution, especially if postoperative corticosteroid use may exacerbate IOP problems. Patients with incipient cataracts should also be avoided because refractive errors can be corrected during subsequent cataract surgery. Monocularity is a potential contraindication for refractive surgery. Surgery in an amblyopic eye may be undertaken in selected cases. Finally, prospective patients between the ages of 18 and 21 years should be considered only if their refraction is stable. Immunodeficiency of any cause is a relative contraindication to refractive surgical procedures on the basis both of possible aberrant wound healing and of predisposition to infection in such patients. One might be less likely to perform PRK on a diabetic patient, for instance, for fear of a persistent epithelial defect following surgery. Preexisting corneal disease may lead to advice against any form of refractive surgery. Patients with a history of herpetic keratitis, for example, may be at risk for recrudescence of the disease following excimer laser surgery.34–37 Some studies have reported good results after LASIK in patients with well-controlled collagen vascular disease. Alio et al. reported the results of LASIK in 42 eyes of 22 patients with controlled autoimmune disease including rheumatoid arthritis, systemic lupus erythematosus, dermatomyositis, scleroderma, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel disease, arthritis, and Behçet disease. There were no reports of corneal haze, melting, flap, or interface complications. These findings were confirmed by Schallhorn et al.38 in their retrospective review of 622 patients with well-controlled collagen vascular and other immune-mediated inflammatory disease. The postoperative complications were those expected after laser surgery with the exception of one peripheral flap melt that did respond to topical steroid treatment. The authors concluded that “Excimer laser surgery can be safely performed in patients with well-controlled collagen vascular or other immune-mediated inflammatory diseases.” However, performing LASIK in patients with these diseases, even when inactive, may still be controversial, as necrotizing keratitis after LASIK has been reported in patients with inactive colitis.39 The response of patients with some of the corneal dystrophies, degenerations, and dysgeneses remains unclear; for example, patients with epithelial basement membrane degeneration have been reported to achieve safe, effective outcomes after surface laser ablation, avoiding the risk for significant epithelial abrasion during LASIK.40,41

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The potential for dry eye after corneal excimer laser surgery, though recognized, might be underestimated. Albeitz and colleagues reported that 38% of 450 consecutive patients undergoing LASIK for myopia exhibited dry-eye symptoms.42 Patients with dry-eye problems require careful evaluation. A patient with a mildly dry eye may be intolerant of contact lens wear and may reasonably be considered for a refractive procedure, although the added risk should be considered in deciding to perform such a procedure rather than correcting with spectacles.43 More significant problems with dry eyes require even more careful patient selection. Tsubota and colleagues have shown that patients with poor basal tear production but preserved reflex tearing can heal adequately after refractive surgery, achieving satisfactory outcomes. The decision to perform LASIK or laser-assisted subepithelial keratectomy (LASEK) on such dry-eye patients should take place on a per patient basis; it is helpful to ask the patient what he or she would consider a tolerable use of topical lubricant eye drops in the postoperative period. Use of topical agents such as cyclosporine or even topical autologous serum have both been shown to improve the ocular surface in dry eye and might be used in the postoperative period in extreme circumstances.44 Not all patients will elect to proceed with surgery if they are apprised of the likely burden of frequent topical medications in the postoperative period. More generally, it has been suggested that dry-eye problems after LASIK can affect the refractive accuracy of the procedure; however, prospective data from Toda and colleagues showed that there were no significant differences in procedure efficacy among those with dry eye, borderline dry eye, and those with normal tear function.45 The AAO Preferred Practice Pattern for Refractive Errors & Refractive Surgery lists the following conditions as contraindications for refractive surgery19: • Significant eyelid, tear film, or ocular surface abnormalities related to keratoconjunctivitis sicca, blepharoconjunctivitis, acne rosacea, conjunctival cicatrization, corneal exposure, neurotrophic keratitis, or other corneal abnormalities • History of uveitis • Inflammation of the anterior segment • Functional monocularity • Presence of a filtering bleb • Pseudoexfoliation • Diabetes mellitus • Autoimmune or other immune-mediated disease

Dry Eye Many patients seek refractive surgery because underlying dry eye has resulted in contact lens intolerance. Any refractive surgery candidate with signs or symptoms of dry eyes should be thoroughly evaluated. Patient history should include questions about connective tissue diseases and conjunctival cicatrizing disorders, as these are relative contraindications to any refractive procedure and would have to be addressed prior to any surgical consideration. Patients are often satisfied by the outcomes of a LASIK procedure, but

side effects such as dryness, burning, and discomfort are reported, which can range in severity and may significantly affect quality of life.46–48 LASIK is considered to lead to corneal nerve damage of the subbasilar plexus, which is permanent, and may cause some changes in the mechanism of corneal neurotransmission postsurgery.48–54 External examination should include evaluation of the blink for such conditions as incomplete blink or lagophthalmos. On slit-lamp examination, the quantity and quality of the tear film are assessed, as is the presence of blepharitis, meibomitis, or keratitis. Ancillary testing for dry eyes―such as Schirmer testing and tear breakup time― can be performed. If connective tissue diseases or cicatrizing diseases are suspected, appropriate referral or laboratory testing should be performed to rule out these conditions prior to consideration of refractive surgery. Preexisting abnormalities should be treated. Topical tear replacement and/or punctal occlusion can be performed. In appropriate cases, a preoperative course of topical anti-inflammatories such as topical steroid or cyclosporine may be indicated. Blepharitis and/ or meibomitis should be treated. Adverse outcomes from refractive surgery can be minimized with proper management of the ocular surface before, during, and after LASIK.55 A normal tear film layer is important for wound healing of the corneal stroma and epithelium. Epidermal growth factor, vitamin A, and IgA in the tears help to prevent postoperative infection and potentiate wound healing. Consequently severe dry eye has previously been thought to be a relative contraindication to refractive surgery. In addition, LASIK may result in a temporary dry eye postoperatively because corneal nerves are severed when the flap is made. Proper management of the ocular surface through topical tear replacement therapy and/or punctal occlusion must be provided in the perioperative period.

Diabetes Mellitus Diabetes mellitus affects 4% to 8% of Americans. Diabetic patients considering refractive surgery should undergo a thorough preoperative history and examination. The diabetes must be under good control to ensure an accurate refraction. A history of laser treatment for proliferative diabetic retinopathy or cystoid macular edema suggests visually significant diabetic complications that typically contraindicate refractive surgery. Any patient who has preexisting visually significant diabetic ocular complications is not a good candidate for refractive surgery. Such a patient’s ocular examination should include examination of the corneal epithelium to detect the health of the ocular surface and evaluate cataract formation and should also undergo a detailed retinal examination. There are few long-term studies of refractive surgery in the diabetic patient. A retrospective review of 30 eyes from diabetic patients who had LASIK 6 months earlier revealed a complication rate of 47% compared with a control population’s complication rate of 6.9%. The most common problems were related to epithelial healing and included epithelial

CHAPTER 11  Patient Evaluation for Refractive Surgery

defects and erosions. Although the uncorrected visual acuity (UCVA) was worse in the diabetic group than in the controls, this was not statistically significant. There was a loss of two or more lines of best-corrected visual acuity (BCVA) in less than 1% in both the diabetic and the control groups. However, six diabetic eyes (6/30) required a mean time of 4.3 months to heal because of persistent epithelial defects. The authors concluded that the high complication rate in diabetic patients was explained by the unmasking of subclinical diabetic keratopathy.56 Another report described the progression and worsening of diabetic retinopathy occurring after LASIK.57 The refractive surgeon should exercise caution in the selection of diabetic patients for refractive surgery. Intraoperative technique should be adjusted to ensure maximal epithelial health. In order to minimize corneal toxicity, the surgeon should use the minimal amount of topical anesthetic immediately before the procedure. Tears, not anesthetics, are used during the microkeratome pass. Diabetic patients should be counseled preoperatively that there is an increased risk of postoperative complications and there may be prolonged healing time after LASIK. It has been well established that there is an increased association between surgical site infection and diabetes.58 In addition, such patients should understand that the procedure treats only the refractive error and not the natural history of the diabetes, which could lead to future diabetic ocular complications and associated visual loss. However, overall, if glycemic control is tight, with no presence of other ocular or systemic complications, LASIK in diabetic patients can be considered to be safe.59

Human Immunodeficiency Virus Little has been written on the performance of refractive surgery in patients with known HIV infection. Some surgeons counsel these patients against refractive surgery because of concerns for postoperative complications, including increased risk for infection associated with their immunosuppression. If the patient has progressed to AIDS, the underlying severe immunosuppression must be the paramount consideration. More importantly, these patients should be monitored for vision-threatening diseases such as cytomegalovirus retinitis. Most ophthalmologists consider AIDS to be an absolute contraindication to refractive surgery. The US Food and Drug Administration (FDA) lists immunodeficiency in patients as absolute contraindications to all excimer laser devices and warns patients that certain conditions such as HIV may prevent proper closure of the wound during wound healing.60 The AAO Preferred Practice Pattern for Refractive Management & Intervention also lists autoimmune or other immune-related disease as relative contraindications, and uncontrolled autoimmune or immune-related disease as absolute contraindications.19 Because HIV-infected patients now live productive lives for longer periods before the onset of AIDS, the question of the appropriateness of refractive surgery in this “healthier” population will be asked more often. Uniform precautions

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must always be applied because the refractive surgeon may operate on patients who do not know they have been infected with viruses such as HIV or hepatitis. One concern is the vaporization of corneal tissue and potential for aerosolizing live virus during laser ablation, which could pose a risk to laser suite personnel. In one study, excimer ablation of pseudorabies virus, a porcine enveloped herpes virus similar to HIV and HSV, did not appear capable of causing infection by transmission through the air.61 The authors concluded that excimer laser ablation of the cornea in a patient infected with HIV is unlikely to pose a health hazard to the surgeon. In another study, after excimer laser ablation of infected corneal stroma, polymerase chain reaction (PCR) did not detect viable varicella virus (200  nm) but did detect viable polio particles (70 nm).62 Although inhaled particles greater or equal to 5 µm are deposited in the bronchial, tracheal, nasopharyngeal, or nasal walls, those smaller than 2 µm are deposited in the bronchioles and alveoli. Even if viral particles are not viable, the excimer laser plume produces particles of a mean diameter of 0.22 µm, which can be inhaled.63 The health effects of inhaled particles from the plume have not yet been determined. There are anecdotal reports of respiratory ailments, such as chronic bronchitis, in laser surgeons. Canister filter masks can filter particles down to 0.1 µm and may be more protective than conventional surgical masks. In addition, evacuation of the laser plume may potentially decrease the amount of breathable debris. Because of the many remaining questions, some surgeons consider patients with known HIV to be poor candidates for refractive surgery. In a 2010 survey study evaluating the preferences of 1123 surgeons in performing elective refractive surgery with patients with HIV positivity or AIDS,64 25.4% responded, and about half of those who responded (50.2%) said that they considered HIV-positive persons acceptable candidates for refractive surgery, whereas only 12.5% said that they considered AIDS patients acceptable candidates. If a surgeon considers performing excimer laser ablation in the “healthy” HIV-infected patient with normal eye examination and excellent best-corrected vision, extra precautions should be taken. Among surgeons who said that they performed elective surgery in patients with AIDS or HIV positivity, 72.7% added that they take extra precautions when performing such surgery.64 The patient should be extensively counseled preoperatively concerning the visual risks of HIV and the lack of long-term follow-up of refractive surgery in this population. The surgeon should consider additional precautions such as wearing a filter mask during the procedure, evacuation of the laser plume, wearing a double layer of gloves, performing unilateral surgery, and scheduling the patient last on any given surgery day.

Previous Ocular Surgery After Retinal Detachment Surgery

Retinal detachment surgery can result in myopic shift because of axial elongation of the eye from indentation

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of the scleral buckle. Refractive surgery can be considered when there is anisometropia with good BCVA. Although a study reported LASIK to be safe in eyes after retinal detachment surgery, the risk of vision regression is always higher in such eyes compared with eyes with no such previous surgery.65 The retina should be extensively evaluated preoperatively. Referral to a retinal specialist should be made when indicated. The surgeon should determine whether conjunctival scarring or the scleral buckle will interfere with placement of the suction ring during the microkeratome pass. If so, PRK may be considered. The patient must be informed that the role of the surgery is solely to treat the refractive error to correct anisometropia or to decrease dependency on corrective eye wear. Preoperative pathology including preexisting macular pathology will continue to limit their UCVA and BCVA after refractive surgery. Successful LASIK after retinal detachment surgery has been reported (Fig. 11.2).66 In one series, 10 eyes of 9 patients who had LASIK for myopia after prior retinal detachment surgery were followed for 6 months. LASIK was successfully completed in eight eyes but aborted intraoperatively in two eyes because scarred conjunctiva prevented adequate suction. No eyes had retinal complications and all eyes had improvement in UCVA with no loss of BCVA.67 Patients who have had prior retinal detachment surgery may have less predictable results after LASIK. Unexpected corneal steepening has been reported in patients undergoing LASIK with previously placed scleral buckles.

After Cataract Surgery

Cataract surgery requires careful preoperative measurements in order to ensure the accuracy of the IOL calculation. Nevertheless, unintentional clinically significant ametropia in the form of myopia, hyperopia, and/or astigmatism may occur after cataract surgery. A retrospective review of 11 consecutive cases of pseudophakic ametropia reported that 45% were due to error in axial length determination and 55% to surgeon or surgical team error.68 Refractive error after cataract surgery may result from preexisting astigmatism that was not addressed by implantation of an IOL to correct spherical refractive error. Sometimes removal of the natural lens can unmask corneal astigmatism that was previously balanced by the lenticular astigmatism. In addition, inaccuracies in IOL calculations may result in unexpected postoperative refractive errors. Finally, in some cases, the surgeon may plan a two-staged procedure called bioptics, with initial cataract surgery and IOL implantation followed by LASIK. LASIK can be considered after there has been sufficient wound healing of the cataract surgery incision to avoid wound rupture (Fig. 11.3). One study examined 22 eyes of 22 patients who underwent LASIK for the correction of residual myopia at least 1 year after the prior cataract surgery and IOL. At 12 months after LASIK, the spherical equivalent refraction was within ±1.00 D of emmetropia in 18 eyes (81.8%) and within ±0.50 D in 11 eyes (50%). No patients had any wound complications. Another study examined 20 eyes of 20 patients with refractive myopic or mixed astigmatism from 3.00 to 6.00 D following cataract extraction with IOL. LASIK was performed at least 3 months after prior surgery. At 6 months after LASIK, mean refractive cylinder decreased from 4.64 ± 0.63 D to 0.44 ± 0.24 D (P < .001) and mean spherical equivalent refraction decreased from −2.19 ± 0.88 D (range −1.00 to −3.88 D) to −0.32 ± 0.34 D (range −1.25 to +0.38 D). No IOL or cataract incisions were related complications and no eyes lost any lines of BCVA.69

• Fig. 11.2

  Microfolds in flap in a patient who underwent laser in situ keratomileusis (LASIK) after prior scleral buckle for retinal detachment. Before LASIK, preoperative uncorrected visual acuity (UCVA) was counting fingers, and best-corrected visual acuity (BCVA) was 20/25 with manifest refraction of −11.25 +1.00 × 70. Two weeks later, UCVA was 20/25 and BCVA was 20/20−2, with manifest refraction of −0.25 +0.25 × 180.

• Fig. 11.3  Slit-lamp photograph of the cornea in a patient who underwent laser in situ keratomileusis (LASIK) for myopia, the result of cataract extraction and the placement of an intraocular lens.

CHAPTER 11  Patient Evaluation for Refractive Surgery

PRK may be advantageous because it eliminates the IOP rise and wound stress associated with the use of the suction ring during the microkeratome pass. Consequently PRK does not stress the cataract surgery wound. A study carried out in 1999 examined 30 consecutive eyes of 30 patients who had PRK for residual myopia at least 6 months after cataract surgery. Although no patient had UCVA of 20/40 prior to LASIK, 53% achieved UCVA of 20/40 or better after LASIK. At 12 months, the spherical equivalent was within ±1.00 D of emmetropia in 27 eyes (90.0%) with no visionthreatening complications. Another study of 31 eyes in 24 patients demonstrated a decrease in anisometropia from 3.44 ± 1.07 D to 0.58 ± 0.31 D after PRK (P < .01). There were no serious complications during or after the surgery.70 Phakic IOL implantation for anisometropia from myopic astigmatism resulting after cataract extraction and IOL has been reported in 2 patients. One patient had UCVA of 20/400, which improved to 20/30 after phakic IOL, and the preoperative UCVA of another patient improved from 20/200 to 20/40 postoperatively. Neither patient had any complications.71 Bioptics is a term coined by Zaldivar in the late 1990s to describe the combination of two or more refractive procedures. For example, LASIK can be performed after clear or cataract lens extraction with IOL implantation. The results of LASIK performed 1 month or more after lens extraction with IOL implantation were reported in 64 eyes of 55 patients. Preoperative mean spherical equivalent refraction was −2.61 and improved to +0.09 1 month after LASIK. Keratitis sicca occurred in 10%.72 After Penetrating Keratoplasty

Despite successful Penetrating Keratoplasty (PKP), patients may have poor vision because of the high residual refractive error. Anisometropia may result if there is a large change in corneal curvature. High astigmatism may be difficult to correct adequately with spectacles. Irregular astigmatism can only be corrected with gas-permeable contact lenses. Ten percent to 30% of patients require contact lens correction after penetrating keratoplasty. However, contact lens fitting may not be possible because of the abnormal corneal curvature. Refractive surgery can be performed to reduce refractive error after PKP in those patients who cannot tolerate contact lenses (Fig. 11.4). Often the attainment of excellent postoperative UCVA is not a realistic goal. Depending on the original refractive error, refractive surgery may allow the patient to be fitted with a contact lens or may permit the use of spectacles (see Chapter 42).

Guidelines for Preoperative Examination A complete examination should take place prior to surgery (Fig. 11.5). Preferably this would be done on a day other than the day of surgery to allow for a considered analysis of results as well as time for further testing or preoperative therapy if needed.

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The goals of the preoperative examination are twofold. First, it is important to assess prospective patients carefully in order to make sure that only those considered appropriate actually undergo surgery. Second, it is critically important to assess patient expectations before embarking on irreversible surgical procedures. It must always be stressed that the goal of refractive surgery is to reduce the patient’s dependence on glasses and contact lenses—not to make all patients free from all optical appliances for all tasks at all times. Patients with such expectations will often be disappointed. The advance of laser technology has created high expectation among prospective patients; it is important to educate them that not all patients will achieve 20/20 unaided vision after the surgery. The patient has often contemplated the risks and benefits of refractive surgery at great length and has already made the decision to proceed. Nevertheless, a thorough discussion of the data on the various available refractive procedures is important to fully inform the patient.

Assessment of Contraindications and Appropriateness for Surgery The patient’s history should be taken to assess any absolute or relative contraindications to surgery. In addition to the contraindications already cited, there are a number of situations where the surgeon will advise the patient against refractive surgery. Stability of the patient’s refraction over time should be ascertained. Review of old spectacles, prescriptions, or patient charts may give the appropriate assurance of refractive stability. Refractive surgery should only rarely be undertaken on the basis of a single day’s refraction. If corroborating data are not available, the patient should return on another day to verify refractive measurements. Further measurements are typically obtained on the day of surgery to confirm a reproducible refraction.

Assessment of Patient Needs and Expectations One priority during the preoperative examination is careful documentation of the patient’s reason for wanting refractive surgery. The most commonly offered is the desire to be independent of glasses or contact lenses, a wish commonly voiced by patients who are physically intolerant of contact lenses. In such cases, it is important to elicit the actual reason for the patient’s inability to wear contact lenses―for example, a dry eye or severe ocular allergy―because this may have a bearing on whether or not to proceed with surgery. The other main group of factors compelling patients to consider refractive surgery relates to professional or specific leisure activities. Visual requirements of certain occupations―such as in law enforcement, the armed forces, and the aviation industries, and the acceptability of the various refractive surgical procedures by the authorities in these

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B

A

C • Fig. 11.4  Laser in situ keratomileusis (LASIK) performed for myopic astigmatism in a patient who had a prior penetrating keratoplasty for keratoconus. Before LASIK, uncorrected visual acuity (UCVA) was 20/400, with best-corrected visual acuity (BCVA) of 20/25 and manifest refraction of −9.00 + 6.00 × 085. After LASIK, UCVA was 20/25 and BCVA was 20/20, with manifest refraction of −0.50 + 2.25 × 090. (B) Computed corneal topography (CCT) before LASIK with 11.27 D of corneal astigmatism. (C) CCT after LASIK, demonstrating postoperative reduction of astigmatism to 5.42 D.

professions―should be ascertained. The patient with 20/20 postoperative vision will be dissatisfied if the rules of his or her chosen profession preclude refractive surgery. Specific visual tasks should also be explored. For instance, myopic patients in certain professions should be advised against surgery when preserved uncorrected near acuity is just as important as the prospect of surgically created unaided distance acuity. Investigators have explored the demographic characteristics of prospective radial keratotomy (RK) patients and have analyzed their particular motivations for requesting surgery.73,74 Of RK patients in the Prospective Evaluation of Radial Keratotomy (PERK) study, 73% of women and 58% of men wanted surgery to avoid being dependent on glasses. This included a fear of being without corrective lenses in an emergency. Thirteen percent of all PERK patients had previously worn glasses but not contact lenses, 34% wore both glasses and contact lenses, and 53% had tried contact lenses and reverted to wearing glasses alone. Interestingly, only one-third of patients who had stopped wearing contact lenses did so because of physical or physiologic problems. Other

reasons for desiring RK included occupational reasons (6% of cases), participation in sports (5%), and cosmesis (3%). A study of patients undergoing excimer laser PRK similarly showed half of patients citing independence from glasses or contact lenses as the primary reason for undergoing PRK. Only 5% of respondents cited sports or occupational endeavors as the primary motivation.75

Review of Risks and Benefits Those procedures relevant to the patient’s particular refractive error should be clearly explained. This includes the usual indices of success, such as UCVA of 20/20 or 20/40 and estimations of the predictability and stability of the refractive correction. Well-informed patients will often benefit from a review of published studies of the various procedures. The surgeon thus should have knowledge of such publications. When the risks of the procedure are being outlined, it is helpful to stratify them into the optical side effects and the medical-physical risks. Optical risks should include

CHAPTER 11  Patient Evaluation for Refractive Surgery

Full ocular examination

Motility assessment

Normal

Abnormal

Refraction: Dry manifest Cycloplegic

Further assessment required

Keratometry

Do keratometry readings and all refractions agree?

Yes

No

Corneal topography

Return visit to repeat measurements

Abnormal shape

Normal shape

Wavefront aberrometry Pupillometry Pachymetry

List treatment options based on: Wavefront aberrometry Pupillometry Pachymetry Spherical error magnitude Cylindrical error magnitude

With contact lens wear

Without contact lens wear

Stay out of contact lenses 1-6 months Repeat topography

Consider cause, e.g., keratoconus

Discuss risks/benefits/ treatment alternatives of relevant procedures

Schedule surgery

• Fig. 11.5

 

Required preoperative checks before surgery.

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discussion of undercorrection and overcorrection. It is helpful for most patients to have this demonstrated by over- and undercorrecting their myopia using lenses in a trial frame, even though this is only an approximate example. Presbyopia and the immediate or ultimate need for near correction should be addressed in addition to possible refractive changes as the patient ages. Subjective optical problems should also be explained in detail, particularly glare, halos, and the starburst phenomenon. The extent to which these various optical side effects play a role in the different refractive procedures under consideration should also be reviewed. When ultimate visual acuity is being discussed, it is best to inform patients of their relative chances of obtaining both 20/20 and 20/40 unaided vision after a specific procedure in each individual case and considering the patient’s refractive error. The ability to perform reoperations in the event of suboptimal correction and the expectations of such enhancement procedures should be reviewed.75 Specific attention should be paid to calculation of the amount of corneal stromal tissue available for retreatment after completion of the primary surgical procedure. This applies to both LASIK and surface laser treatment (LASEK/PRK). If the surgeon feels that insufficient tissue for subsequent retreatments may remain after primary surgery, the patient should be made aware of this. Patients who have reached the age of presbyopia should understand that obtaining emmetropia would necessitate the use of reading glasses postoperatively. Many patients will not find this a problem because they prefer to have unaided distance acuity rather than reading acuity. Some older patients will elect to avoid surgery upon discovering that they will still need presbyopic correction. Some patients may be candidates for monovision, with full refractive surgical correction of the dominant eye, leaving the nondominant eye slightly myopic for near vision. A preoperative trial of monovision contact lens correction may predict which patients will be satisfied with this option. More general ocular risks include corneal scarring or infection, which potentially could limit the BCVA and ultimately require penetrating keratoplasty. LASIK is the most frequently performed procedure at the time of writing; the majority of complications are related to improper creation of the corneal flap. The surgeon should report his or her flap complication rate candidly to the patient. In cases where preoperative visual acuity is less than 20/20 secondary to other pathologies, it must be understood that the refractive procedure will not improve this baseline best-corrected vision. Discussion of the potential benefits of the planned refractive procedure requires that the surgeon impart honest, realistic information to patients so that they can decide in an informed manner. Unfortunately the many advertisements testifying to the fact that you “will throw away your glasses” encourage patients to think that these are risk-free procedures. If the surgeon does nothing to correct this misimpression, there is a real risk that, in the event of a legitimate complication, a fully informed consent might not

have been obtained. Often, giving the patient time to review educational materials in advance of the preoperative examination allows for a more productive preoperative examination and a more knowledgeable patient with appropriate expectation of the procedure’s outcomes.

Reading Materials The majority of patients will wish to think about their options after the preoperative examination. It is helpful to offer appropriate reading materials for further patient education. Patient education materials have developed in recent years as a response to legal and patient-related issues. Such materials should address the main issues and go some way to impart enough information for the patient to be able to give an informed consent. The educational materials may contain the following: • Review of ocular anatomy and a discussion of refractive error and astigmatism • Outline of the preoperative visit and what should be expected by the patient before, during, and after surgery • Outline of the particular surgical procedures available and their indications • Outline of the likely postoperative course • List of benefits to expect as a result of the procedure, including the published success of the procedure or procedures • Description of the risks and complications of the procedure(s) and perhaps a sample of the informed consent form • Suggestions for treatment alternatives, including glasses and contact lenses

Questionnaire Preoperative patient questionnaires are an easy way for the surgeon to obtain information about his or her refractive surgery population. Questionnaires to assess the level of patient education and awareness can be used before surgery, which can lead the surgeon to present a more or less complex explanation during the preoperative visit or visits.76,77 Questionnaires given during the postoperative course can help alter the surgeon’s usual postoperative management.

Time Interval Between Eyes The majority of patients elect to have either LASIK or surface excimer treatment (LASEK/PRK) in both eyes on the same day. Studies exist that demonstrate that treating both eyes on the same day is both safe and effective.78 However, there are reasons for treating the eyes of a given patient on different days, the obvious one being a desire on either the surgeon or patient’s part to be as conservative as possible.78 In this situation, the time interval between surgery on the first and second eyes varies for the different types of procedure. It is important to apprise the patient of

CHAPTER 11  Patient Evaluation for Refractive Surgery

this interval because of the optical consequences of uniocular treatment such as short-term anisometropia.

Preoperative Examination During the preoperative examination, it is important to meticulously examine the anterior segment, looking for preexisting corneal diseases that might contraindicate a refractive procedure.

Discontinuance of Contact Lens Wear It is common practice for prospective refractive surgery patients to discontinue lens wear before the preoperative examination to ensure that refractive measurements are taken of a cornea whose topography has not been perturbed by the contact lens soft lenses (spherical and toric) about 1 week and rigid lenses 1 month preoperatively. A proportion of contact lens wearers will have abnormal corneal topography preoperatively, and some of these will be considered to have contact-lens–induced corneal warpage.79 A patient with a topographic pattern suggestive of keratoconus who also wears contact lenses should be invited back for repeat topography after an additional period without contact lens wear. This would also apply to patients who have irregular astigmatism in the presence of contact lens wear. How long should we routinely expect contact lens wearers who have these problems with corneal warpage to discontinue their use of contact lenses preoperatively? Wilson suggests that for persons wearing soft contact lenses whose topographies suggest corneal warpage, a period of 1 to 1.5 months would probably be sufficient, although if such patients still have an abnormal topographic pattern after that period, further time without the lenses should be allowed before any decisions are made.79 In practice, the gas-permeable contact lens wearer is faced with the decision to stay out of contact lenses for an additional month beyond the preoperative eye examination to determine whether the abnormal topography will normalize; such patients will seldom allow more than an additional 1 month out of their lenses, because it is inconvenient for them to continue to wear glasses that are typically several years old. In such cases, interim soft lenses can be suggested. These have the advantage of being able to be worn until corneal warpage is resolved and need to be discontinued only 1 week prior to refractive surgery. An additional contact lens–related issue to consider is their use during the time interval before treatment of the second eye in patients electing to have sequential eye surgery. During this time there will be a problem with anisometropia and aniseikonia. The patient who has less than a 3-D difference between the two eyes may not require any correction in the fellow eye between surgeries. For some patients, this monovision is the end point in their management, and they will not want surgery to correct their refractive error in the second eye. Significant anisometropia requires contact lens correction, and for motivated patients who have been contact lens intolerant, further contact lens

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wear can usually be tolerated in the short term. Other patients in this situation will simply leave their second eye uncorrected while waiting for surgery. The patient who wears a contact lens in the second eye is usually asked to stop using the lens at least 1 week prior to surgery. Clearly, for a patient in whom one has suspected contact-lensinduced corneal warpage, no contact lens wear should be allowed between surgery on the two eyes.

Refraction Refraction is the most important part of the examination and is best carried out by two separate observers to assure accurate and consistent measurements. A cycloplegic refraction should also be obtained for further confirmation and to assure that the patient was not accommodating during the dry refraction. All refractions should be compared and any discrepancies resolved. If refractions are not consistent and reproducible, the patient must be reexamined on another occasion.

Keratometry Keratometry readings and refractive astigmatism should typically agree, and any irregularities of keratometer mires evaluated to expose ocular surface disorders or incipient keratoconus. However, some patients will have lenticular as well as corneal astigmatism. Surgeons will typically treat the refractive astigmatism that exists in such eyes provided that the ophthalmic examination is otherwise unremarkable.

Computer-Assisted Videokeratography Corneal topography has become a standard in the assessment of prospective refractive surgery patients. Investigators have demonstrated situations where a topographic map of the cornea may change a decision about a refractive procedure.80 For example, computed topography may reveal a heretofore undiagnosed case of keratoconus, a contraindication for refractive surgery.81,82 Topography can identify patients with forme fruste keratoconus, avoiding the chance that these seemingly normal patients might undergo refractive surgery and achieve poor outcomes (Fig. 11.6).83,84 Topography has also been used to assess the severity of other ectatic corneal diseases.85,86 Even though these diseases should be revealed with a good clinical examination, routine preoperative corneal topography can aid in identifying mild cases of such pathologies. The corneal topographic map is being increasingly incorporated into the surgical planning of the patient’s treatment along with the preoperative wavefront error of the eye.

Wavefront Aberrometry Measurement Preoperative measurement of the wavefront error of the eye is being increasingly performed to better understand the preoperative quality of vision and to plan custom laser ablation.

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observing the eye used is one clue to the preferred eye. In addition, the patient may be instructed to hold a finger in front of the two eyes and gaze at a distant object. The patient should see two images of the finger, with the denser image contralateral to the dominant eye. Assessment of ocular dominance is of particular importance for prospective monovision patients. Most such patients are already successful monovision contact lens wearers, but some patients will benefit from a short-term contact lens trial to help them decide.

Ocular Motility Issues • Fig. 11.6

  The Azar-Lu Keratoconus Classification System combines elements of the clinical and topographic examinations.

Several laser manufacturers have developed the ability to perform custom LASIK or surface laser treatment based on wavefront data. In the United States, Alcon, Visx, and Bausch and Lomb have obtained approval from the FDA for use of their respective custom excimer laser platforms. The surgeon’s enthusiasm for performing custom wavefront-guided laser treatment is influenced by the size of the mesopic pupil and the magnitude of the refractive error on the one hand and tempered on the other hand by the availability of corneal tissue for custom ablations, which remove more tissue than traditional, spectacle-based ablations.

Contrast Sensitivity and Glare Testing A baseline contrast sensitivity test may be helpful for comparison when there are postoperative complaints of foggy vision, dull vision, and glare, cases in which an abnormal contrast sensitivity or glare test may be found.

Pupillary Size Measurement of the diameter of the entrance pupil in both light and dark conditions may identify patients who have very large pupils, which may exacerbate edge effects of the optical zone following refractive procedures (for example, glare, halo, and the starburst phenomenon). Any of several commercially available infrared pupillometers should be routinely used in preoperative assessment. With the wide ablation zones of the lasers of today, it is now unusual for a patient with large mesopic pupil size to be excluded from surgery. Patients with large mesopic pupil diameters would be expected to obtain the most additional benefit from customized laser treatment in comparison with traditional, spectacle-based corrections.

Ocular Dominance Ocular dominance should be ascertained preoperatively. Asking the patient to look through a hole in a card and

Accurate examination of the patient for heterophoria and heterotropia is required. Patients with a heterotropia may suffer from either diplopia or amblyopia, both of which might contraindicate refractive surgery. The patient with a phoria may well have problems after refractive surgery if not recognized and appropriately counseled. For example, consider the young myopic patient with an exophoria who has worn spectacles that are slightly decentered so that the patient is looking through the spectacle lens nasal to the optical center. This patient will have spent considerable time looking through a base-in prism. Postoperatively, the exophoria will become more difficult to control because the patient will no longer be wearing myopic spectacles, especially as he or she approaches the age of presbyopia. Similarly, some young hyperopes with small esotropias have more difficulty maintaining reasonable ocular alignment when wearing contact lenses in comparison to spectacles. The performance of corneal laser surgery can produce increased postoperative difficulties in such patients once the prismatic benefit of spectacles is gone.

Pachymetry and Specular Microscopy Pachymetry is necessary to ascertain corneal thickness to assure its adequacy for LASIK. If there is a question about possible corneal edema or endothelial cell dysfunction, specular microscopy should be performed to document the endothelial cell density and morphology. Corneal thickness measurements will indicate the functional capacity of the endothelium. Patients with compromised endothelial cell function should not undergo refractive surgery. There is good evidence that excimer laser ablation in the LASIK procedure has no deleterious effects on the normal corneal endothelium.87

Informed Consent Appropriate and complete informed consent is essential in the refractive surgery practice. The main points that should be covered during the consent process are as follows: • The nature of the proposed treatment. • An outline of the risks and benefits of the proposed treatment. These may be divided into the optical and physical risks for easier understanding. One must inform the

CHAPTER 11  Patient Evaluation for Refractive Surgery

patient of all risks (even rare risks) associated with the procedure in question because only then will the patient be able to decide in an informed manner whether to have surgery performed on the normal eye. • Explanation of alternatives to the proposed treatment. In the context of refractive surgery, this must include a comment about possibly doing nothing―an important option in these elective procedures. Appropriate selection, education, and evaluation of the prospective patient for refractive surgery is essential to obtaining satisfactory outcomes. Attention to the details of patient expectations, preoperative examination, and appropriate surgical strategies will help to ensure that patients are ultimately satisfied with their preoperative and postoperative management and their visual outcome.

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32. Poulsen ET, Nielsen NS, Jensen MM, et al. LASIK surgery of granular corneal dystrophy type 2 patients leads to accumulation and differential proteolytic processing of transforming growth factor beta-induce protein (TGFBIp). Proteomics. 2016;16(3):539–543. 33. Woreta FA, Davis GW, Bower KS. LASIK and surface ablation in corneal dystrophies. Surv Ophthalmol. 2015;60(2):115–122. 34. Perry HD, Doshi SJ, Donnenfeld ED, Levinson DH, Cameron CD. Herpes simplex reactivation following laser in situ keratomileusis and subsequent corneal perforation. CLAO J. 2002;28(2): 69–71. 35. Jarade EF, Tabbara KF. Laser in situ keratomileusis in eyes with inactive herpetic keratitis. Am J Ophthalmol. 2001;132(5):779–780. 36. Vrabec MP, Durrie DS, Chase DS. Recurrence of herpes simplex after excimer laser keratectomy. Am J Ophthalmol. 1992;114(1): 96–97. 37. Pepose JS, Laycock KA, Miller JK, et al. Reactivation of latent herpes simplex virus by excimer laser photokeratectomy. Am J Ophthalmol. 1992;114(1):45–50. 38. Schallhorn JM, Schallhorm SC, Hettinger KA, et al. Outcomes and complications of excimer laser surgery in patients with collagen vascular and other immune-mediated inflammatory diseases. J Cataract Refract Surg. 2016;42(12):1742–1752. 39. Aman-Ullah M, Gimbel HV, Purba MK, van Westenbrugge JA. Necrotizing keratitis after laser refractive surgery in patients with inactive inflammatory bowel disease. Case Rep Ophthalmol. 2012;3(1):54–60. 40. Dastgheib KA, Clinch TE, Manche EE, Hersh P, Ramsey J. Sloughing of corneal epithelium and wound healing complications associated with laser in situ keratomileusis in patients with epithelial basement membrane dystrophy. Am J Ophthalmol. 2000;130(3):297–303. 41. Carr JD, Patel KH. PRK instead of LASIK for myopia correction in eyes with epithelial basement membrane degeneration using a Visx laser. Presented at Annual Meeting of American Society of Cataract and Refractive Surgery; 2002. 42. Albeitz JM, Lenton LM, McLennan SG. The effect of ocular surface management of myopic LASIK outcomes. Adv Exp Med Biol. 2002;506(Pt A):711–717. 43. Toda I, Yagi Y, Hata S, Itoh S, Tsubota K. Excimer laser photorefractive keratectomy for patients with contact lens intolerance caused by dry eye. Br J Ophthalmol. 1996;80(7):604–609. 44. Pflugfelder SC. Antiinflammatory therapy for dry eye. Am J Ophthalmol. 2004;137(2):337–342. 45. Toda I, Asano-Kato N, Hori-Komai Y, Tsubota K. Laser-assisted in situ keratomileusis for patients with dry eye. Arch Ophthalmol. 2002;120(8):1024–1028. 46. Raoof D, Pineda R. Dry eye after laser-in-situ keratomileusis. Semin Ophthalmol. 2014;29(5–6):358–362. 47. Shtein RM. Post-LASIK dry eye. Expert Rev Ophthalmol. 2011; 6(5):575–582. 48. Nettune GR, Pflugfelder SC. Post-LASIK tear dysfunction and dysthesia. Ocul Surg. 2010;8(3):135–145. 49. Li M, Zhou Z, Shen Y, Knorz MC, Gong L, Zhou X. Comparison of corneal sensation between small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK for myopia. J Refract Surg. 2014;30(2):94–100. 50. Tuisku IS, Lindbohm N, Wilson SE, Tervo TM. Dry eye and corneal sensitivity after high myopic LASIK. J Refract Surg. 2007;23(4):338–342. 51. Denoyer A, Landman E, Trinh L, Faure JF, Auclin F, Baudouin C. Dry eye disease after refractive surgery: comparative outcomes

of small incision lenticule extraction versus LASIK. Ophthalmology. 2015;122(4):669–676. 52. Mian SI, Li AY, Dutta S, Musch DC, Shtein RM. Dry eyes and corneal sensation after laser in situ keratomileusis with femtosecond laser flap creation: effect of hinge position, hinge angle, and flap thickness. J Cataract Refract Surg. 2009;35(12): 2092–2098. 53. Shaheen BS, Bakir M, Jain S. Corneal nerves in health and disease. Surv Ophthalmol. 2014;59(3):263–285. 54. Parra A, Madrid R, Echevarria D, et al. Ocular surface wetness is regulated by TRPM8-dependent cold thermoreceptors of the cornea. Nat Med. 2010;16(12):1396–1399. 55. Albietz JM, Lenton LM. Management of the ocular surface and tear film before, during, and after laser in situ keratomileusis. J Refract Surg. 2004;20(1):62–71. 56. Fraunfelder FW, Rich LF. Laser-assisted in situ keratomileusis complications in diabetes mellitus. Cornea. 2002;21(3):246–248. 57. Ghanbari H, Ahmadieh H. Aggravation of proliferative diabetic retinopathy after laser in situ keratomileusis. J Cataract Refract Surg. 2003;29(11):2232–2233. 58. Ata A, Lee J, Bestle SL, Desemone J, Stain SC. Postoperative hyperglycemia and surgical site infection in general surgery patients. Arch Surg. 2010;145(9):858–864. 59. Simpson RG, Moshirfar M, Edmonds JN, Christiansen SM Laser in-situ keratomileusis in patients in patients with diabetes mellitus: a review of the literature. 2012;6:1665–1674. 60. U.S. Department of Health and Human Services. FDA U.S. Food and Drug Administration. https://www.accessdata.fda.gov/ scripts/cdrh/devicesatfda/index.cfm. Accessed December 22, 2017. 61. Hagen KB, Kettering JD, Apecio RM, Beltran F, Maloney R. Lack of virus transmission by the excimer laser plume. Am J Ophthalmol. 1997;124(2):206–211. 62. Taravella MJ, Weinberg A, May M, Stepp P. Live virus survives excimer laser ablation. Ophthalmology. 1999;106(8):1498–1499. 63. Taravella MJ, Viega J, Luiszer F, et al. Respirable particles in the excimer laser plume. J Cataract Refract Surg. 2001;27(4): 604–607. 64. Aref AA, Scott IU, Zerfoss EL, Kunselman AR. Refractive surgical practices in persons with human immunodeficiency virus positivity or acquired immune deficiency syndrome. J Cataract Refract Surg. 2010;36(1):153–160. 65. Farvardin M, Farvardin M, Hosseini H. LASIK after retinal detachment surgery. Acta Ophthalmol Scand. 2006;84(3):411–414. 66. Sforza PD, Saffra NA. Laser in situ keratomileusis as treatment for anisometropia after scleral buckling surgery. J Cataract Refract Surg. 2003;29(5):1042–1044. 67. Sinha R, Dada T, Verma L, Chaudhury DB, Tandon R, Vajpayee RB. LASIK after retinal detachment surgery. Br J Ophthalmol. 2003;87(5):551–553. 68. Smith LF, Stevens JD, Larkin F, Restori M. Errors leading to unexpected pseudophakic ametropia. Eye (Lond). 2001;15(Pt 6): 728–732. 69. Norouzi H, Rahmati-Kamel M. Laser in situ keratomileusis for correction of induced astigmatism from cataract surgery. J Refract Surg. 2003;19(4):416–424. 70. Li Y, Zhou F, Zhao GQ. Photorefractive keratectomy for correction of anisometropia after cataract surgery. Zhonghua Yan Ke Za Zhi. 2003;39(9):541–544. 71. Chiou AG, Bovet J, de Courten C. Pseudophakic ametropia managed with a phakic posterior chamber intraocular lens. J Cataract Refract Surg. 2001;27(9):1516–1518.

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72. Zaldivar R, Oscherow S, Piezzi V. Bioptics in phakic and pseudophakic intraocular lens with the Nidek EC-5000 excimer laser. J Refract Surg. 2002;18(3 suppl):S336–S339. 73. Bourque LB, Rubenstein R, Cosand B, et al. Psychosocial characteristics of candidates for the prospective evaluation of radial keratotomy (PERK) study. Arch Ophthalmol. 1984;102(8): 1187–1192. 74. Brook RH, Ware JEJ, Avery A. Conceptualization and Measurement of Health for Adults in the Health Insurance Study: Overview. Santa Monica, CA: Rand Corporation; 1976. 75. Hersh PS, Stulting RD, Steinert RF, et al. Results of phase III excimer laser photorefractive keratectomy for myopia. The Summit PRK Study Group. Ophthalmology. 1997;104(10):1535–1553. 76. Vitale S, Schein OD, Meinert CL, Steinberg EP. The refractive status and vision profile: a questionnaire to measure vision-related quality of life in persons with refractive error. Ophthalmology. 2000;107(8):1529–1539. 77. Fraenkel G, Comaish IF, Lawless MA, et al. Development of a questionnaire to assess subjective vision score in myopes seeking refractive surgery. J Refract Surg. 2004;20(1):10–19. 78. Waring GO, Carr JD, Stulting RD, Thompson KP, Wiley W. Prospective randomized comparison of simultaneous and sequential bilateral laser in situ keratomileusis for the correction of myopia. Ophthalmology. 1999;106(4):732–738.

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79. Wilson SE, Lin DT, Klyce SD, Reidy JJ, Insler MS. Topographic changes in contact lens-induced corneal warpage. Ophthalmology. 1990;97(6):734–744. 80. Wilson SE, Klyce SD. Advances in the analysis of corneal topography. Surv Ophthalmol. 1991;35(4):269–277. 81. Maguire LJ, Bourne WM. Corneal topography of early keratoconus. Am J Ophthalmol. 1989;108(2):107–112. 82. Rabinowitz YS, McDonnell PJ. Computer-assisted corneal topography in keratoconus. J Refract Corneal Surg. 1989;5(6): 400–408. 83. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in situ keratomileusis. J Refract Surg. 1998;14(3):312–317. 84. Lafond G, Bazin R, Lajoie C. Bilateral severe keratoconus after laser in situ keratomileusis in a patient with forme fruste keratoconus. J Cataract Refract Surg. 2001;27(7):1115–1118. 85. Maguire LJ, Klyce SD, McDonald MB, Kaufman HE. Corneal topography of pellucid marginal degeneration. Ophthalmology. 1987;94(5):519–524. 86. Wilson SE, Lin DT, Klyce SD, Insler MS. Terrien’s marginal degeneration: corneal topography. Refract Corneal Surg. 1990;6(1):15–20. 87. Collins MJ, Carr JD, Stulting RD, et al. Effects of laser in situ keratomileusis (LASIK) on the corneal endothelium 3 years postoperatively. Am J Ophthalmol. 2001;131(1):1–6.

12 

Preoperative Evaluation of Keratoconus and Ectasia EVERARDO HERNÁNDEZ-QUINTELA, VALERIA SÁNCHEZ-HUERTA, ANA MERCEDES GARCÍA-ALBISUA, AND ROSARIO GULIAS-CAÑIZO

Introduction In the last 2 decades, the clinician’s ability to diagnose keratoconus has increased. This is due to the knowledge and development of diagnostic instruments for keratoconus, from corneal topography to the more recent corneal tomography. The advances in surgical treatments for keratoconus are a logical consequence of this evolution. Several alternative procedures have been proposed to delay or prevent the need for penetrating keratoplasty (PK), such as the use of the intracorneal ring segment (ICRS); corneal cross-linking (CXL); therapeutic excimer laser treatments, including phototherapeutic keratectomy and photorefractive keratectomy (PRK), and phakic intraocular lenses (PIOL) alone or in combination; and small incision lenticle extraction (SMILE).1,2 Other keratoplasty techniques have been developed, such as deep anterior lamellar keratoplasty (DALK) and femtosecond (FS) laser-assisted corneal transplantation.3,4 These latter strategies, as well as PK, have had complications, such as allograft rejection, suture problems, healing disturbances, disease progression in the recipient tissue, and difficulties in visual rehabilitation caused by irregular postoperative astigmatism. All of these factors contribute to choosing keratoplasties as the last resource.3 Decreased spectacle corrected visual acuity and contact lens intolerance are two important elements that must be considered to indicate surgical intervention in a patient with keratoconus.3 The purpose of this chapter is to describe the preoperative evaluation of these different techniques.

Guidelines for Preoperative Examination The preoperative ophthalmologic evaluation of patients with keratoconus shares elements between different surgical techniques. Different patient characteristics need to be analyzed to determine the best surgical choice. General health evaluation is the first step in the preoperative approach since most procedures are performed under local or topical 170

anesthesia. A thorough clinical history is very important, as it may help gather valuable information related to corneal pathology. Specifically, the visual history during the patients’ life can provide information regarding amblyopia, retinal disease, optic neuropathy, or glaucoma. The first steps of preoperative clinical examination include visual acuity and refraction. Contact lens wear is an important factor to consider in order to obtain a reliable measurement of visual acuity, refraction, pachymetry, and topographic evaluation. Patients should be required not to wear them for 1 week in the case of soft contact lenses and at least 3 weeks in the case of hard contact lenses.5 Uncorrected visual acuity (UCVA) and best corrected visual acuity (BCVA) must be recorded. Adnexal evaluation must rule out any eyelid or lacrimal disorders and, if they are present, they must be treated before surgery. A healthy ocular surface is needed for a successful procedure. The evaluation of the tear film includes measurement of the tear meniscus, Schirmer test, and tear film break up time.5 At slit lamp examination, the cornea should be examined to analyze its curvature, transparency, and thickness. If it is too opaque for a good anterior segment exploration, an ultrasound biomicroscopy or ocular coherence tomography must be performed. This is important regarding the outcomes: the better the condition of the anterior segment, the more probability of surgical success. Intraocular pressure should be measured in every patient, either by applanation tonometry or (in very steep corneas with keratoconus) with noncontact tonometry. Due to the frequent association of keratoconus and atopy, steroidinduced glaucoma is not unusual in these patients. Ocular pressure (or glaucoma, if present) must be controlled before surgery. A combined surgery could be performed if needed. Dilated ophthalmoscopy is mandatory; in the case of opaque media, ocular fundus must be evaluated by B-scan ultrasonography. Other tests that help to exclude other retinal or optic nerve diseases include color vision testing, electrophysiologic tests, visual fields, and retinal angiography.

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TABLE Different Definitions of Keratoconus Progression 12.1  Progression Definition

Mastropasqua6

Vazirani et al. Definition7

Keratoconus Global Consensus4

• Kmax increase > 1 D over a year • Change of myopia or astigmatism ≥ 3 D in 6 months • Kmean change ≥ 1.5 D in 3 consecutive topographies over 6 months • Decrease in corneal thickness of ≥ 5% in 6 months

• • • •

Kmax ≥ 1 D increase Kmax− Kmin ≥ 1 D increase Kmean ≥ 0.75 D increase Pachymetry ≥ 2% decrease in central corneal thickness • Corneal apex power > 1 D increase • Spherical equivalent > 0.5 D change

(At least two of the following parameters) • Steepening of the anterior corneal surface • Steepening of the posterior corneal surface • Thinning or an increase of corneal thickness change from the periphery to the thinnest point Documented over time and must be consistent.

TABLE Cross-Linking Indications and 12.2  Contraindications

CXL Indications

CXL Contraindications

• Progressive keratoconus • All ages • Combined procedures

• • • • • • • •

Corneal thickness < 400 µm* Prior herpetic infection Severe corneal scarring History of inadequate wound healing Ocular surface disease Autoimmune disorders Pregnancy Breastfeeding

*Standard Dresden Protocol.9 CXL, Cross-linking.

Corneal Cross-Linking Corneal cross-linking (CXL) is a procedure used to increase the biomechanical rigidity of the corneal tissue. It is a new technique that has been used to halt the progression of ectactic diseases, with low complication rates. It uses riboflavin and ultraviolet A light to enhance the corneal biomechanics through increasing the degree of covalent bonding between collagen fibrils and proteoglycans.6

Definition of Progression CXL has been indicated in keratoconus patients that have had progression; some authors propose treating all patients with keratoconus without documenting progression because the benefits exceed the risks.8 It has been difficult to define progression; therefore we do not have an established value because there are many definitions for it. Different definitions of keratoconus progression are shown in Table 12.1.4,6,7 The indications and contraindications of CXL are shown in Table 12.2.9

Corneal Cross-Linking Techniques Guideline The Dresden protocol consists of epithelial removal with application of 0.1% riboflavin solution for 30 minutes

followed by 30 minutes of UVA irradiation with a power of 3 mW/cm.9 Some authors have reported stabilization or flattening of corneal keratometries and stabilization or improvement of visual acuity after standard CXL.3 Patients with progressive advanced keratoconus will usually present with thin corneas. The Dresden protocol establishes a corneal limit of 400 µm and involves the removal of epithelium followed by the instillation of isoosmolar 0.1% riboflavin solution in 20% dextran. For thinner corneas (< 400 µm after epithelium removal)10 cross-linking can result in significant risk of endothelial cell damage; thus hypo-osmolar riboflavin11 has been proposed as an option for thin corneas, achieving a thickness increase of approximately 70 µm after 1 minute of instillation that remained stable for about 22 minutes. Hypo-osmolar riboflavin 0.1% solution was generated by diluting vitamin B2-riboflavin-5-phosphate 0.5% with physiological salt solution (sodium chloride 0.9% solution). Hypo-osmolar riboflavin solution does not contain dextran. It is known that de-epithelialized corneas can swell up to two times their normal thickness when irrigated with a hypo-osmolar solution; thus this method has been used in CXL. Corneas are irrigated with hypo-osmolar riboflavin until the corneal thickness reaches 400 µm. Another proposed option for thin corneas is to perform CXL with custom pachymetry-guided epithelial debridement, leaving epithelium on the thinnest area, but further research is needed to prove its safety and efficacy. A viable option for thin corneas is the use of a 90-µm soft contact lens immersed in iso-osmolar 0.1% riboflavin in dextran for 30 minutes before applying it on the de-epithelialized cornea.12 The advantage of this method is that it is not dependent on corneal swelling and will not cause endothelial damage; even though surface irradiance is reduced about 40% to 50% and oxygen diffusion may be decreased by the contact lens. Accelerated CXL has been used in thin corneas without endothelial loss;for better results, the use of pulsed CXL has been shown to have a higher effect owing to optimization of oxygen availability.12 Photrexa (Avedro) formulations combined with the KXL device (Avedro) have been approved by the US Food and Drug Administration (FDA). This is an epi-off CXL, and either one of two riboflavin solutions: Photrexa (riboflavin

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5′-phosphate ophthalmic solution 0.146%) and Photrexa Viscous (riboflavin 5′-phosphate in 20% dextran ophthalmic solution 0.146%).13

Clinical Evaluation Preoperative evaluation for CXL patients should include UCVA, biomicroscopy (emphasis on ocular surface integrity and severe corneal scarring), manifest refraction (actual and previous), topography (actual and previous), BCVA, intraocular pressure, and corneal thickness.6

Topography Evaluation One of the most critical preoperative values to measure is corneal thickness, either by corneal tomography or ultrasound pachymetry. This parameter indicates whether CXL is a suitable option. Additionally, keratometric values and different corneal indices will help to assess surgery success during follow-up.

Prognostic Factors It has been demonstrated that eccentric cones are associated with higher keratometric values 1 year after CXL treatment. Patients with lower preoperative visual acuity had a greater improvement in visual acuity after CXL treatment.14 It has been postulated that steeper corneas would be flatter after CXL, rarely exceeding 2 diopters (D), but it is also known that corneas steeper than 58 D would have greater risk of progression especially if the cone is eccentric; and an increased risk of decreased vision with K > 55 D.3 Patients should be advised that the treatment failure rate ranges from 8.1% to 33.3% (continued progression with Kmax readings increasing more than 1 D).6 It is important to explain that, in most cases, CXL by its own is not a refractive procedure. However, the earlier the treatment is done, the better results for the patient because it is a procedure that prevents ectasia complications rather than fixing them.

Intracorneal Ring Segments ICRS implantation is considered a minimally invasive and reversible surgical procedure. Its main goals are to: (1) flatten and (2) regularize the cornea, decreasing low and high order aberrations, (3) improve visual acuity, and (4) delay, or eventually prevent, a corneal keratoplasty.15,16 The Global Consensus on Keratoconus and Ectatic Diseases has recommended that surgical treatment of ectatic disorders should be considered when patients are not fully satisfied with nonsurgical treatments.4 General guidelines that apply to the effect of ICRS implantation were recently reviewed and described by Giacomin et al. The ICRSs effect correlates directly to its thickness and inversely to its distance to the visual axis or optical zone.17

Prognostic Factors In one study patients with poorer preoperative visual acuity achieve the greatest benefit from ICRS implantation.18 An uncorrected distance visual acuity (UDVA) of 20/70 or worse had a better prognosis. Disease severity is an important factor to be considered when contemplating the use of ICRS. Some of the parameters studied as predictors of ICRS’s effect is the preoperative astigmatism in advance keratoconus, as astigmatic magnitude increases predictability of correction decreases.17 On the other hand, a greater reduction in spherical equivalent or keratometry has been described in patients with more advance stages of keratoconus.17 Refraction, corneal topographic pattern, the preoperative aberrometry data, and the preoperative corrected distance visual acuity (CDVA) have shown to be significant predictive factors for planning of a ICRS implantation.17 Patients with keratoconus who must benefit from ICRS implantation have a moderate stage of the ectatic disease. Unpredictability of this procedure remains a concern for low grade of keratoconus.17 Peña-Garcia et al. proposed a nomogram for initial stages of the disease, mainly grade II of keratoconus. It takes into account only the refractive astigmatism, excluding corneal astigmatism and internal astigmatism. Their study demonstrated that a favorable outcome would be reached when the refractive and keratometric axis are perfectly aligned, and the internal astigmatism is low.19 It is clear among experts that ICRS implantation has a lower predictability when compared to photorefractive procedures.19 Different ICRS parameter must be taken into consideration for its selection, longer arc lengths are suitable for nipple or central cones, whereas shorter arc lengths are preferred in astigmatic cones. Thicker rings are indicated when a greater effect is desired. In thinner corneas, thinner segments are required to decrease the risk of extrusion.19 Other studies have analyzed the efficacy of the femtosecond laser to dissect the ring channel; it did not reveal any significant difference when compared with a mechanical spreader regarding uncorrected distance visual acuity, CDVA, SE, maximum keratometry value, surface irregularity, or surface asymmetry indices. These studies have also shown that the femtosecond laser method produces fewer and less severe complications than the mechanical one.19

Refractive Evaluation Preoperative assessment includes uncorrected distance visual acuity (UCDVA), best-corrected distance visual acuity (BCDVA), pupil measurement slit-lamp examination, dilated fundus examination, topography, optical pachymetry, and keratometries.20 A manifest refractive measurement should be done whenever possible, as well as cycloplegic refraction.

CHAPTER 12  Preoperative Evaluation of Keratoconus and Ectasia

TABLE 12.3  Indications for Intracorneal Ring Segment • • • • • • • • • •

Poor preoperative CDVA 20/30 or worse Contact lens intolerance Clear central cornea Corneal thickness ≥ 450 at the site of tunnel formation Steep corneal keratometry < 62 D Patient satisfied with a modest improvement in UDVA or BCVA Poor spectacle-corrected vision Poor contact lens vision Compliance with “pachymetry law,” in which the thickest portion of a pair of segments in the stromal bed cannot exceed half the thickness of the cornea Patient with a good VA potential

BCVA, Best corrected visual acuity; CDVA, corrected distance visual acuity; UDVA, uncorrected visual acuity.

Corneal Tomography/Topography Evaluation Ectasia patterns based on corneal topography and tomography maps, thickness evaluation through a pachymetry map, and ectasia distribution are necessary to determine the ICRS type, number, thickness, asymmetry, arc of length, depth of implantation, and site of incision. Topographic maps will show the steeper half of the cone (frequently temporal-inferior), where the thicker segment is usually placed asymmetrically to achieve a maximum flattening effect. The thinner segment will be placed in the opposite half of the cornea.20

ICRS Indications The primary indications for ICRS implantation include keratoconus in moderate to advanced stages with clear corneas and patients with ectasia after excimer laser treatment with unsatisfactory CDVA or contact lens intolerance.17 ICRS have been also used for visual rehabilitation in patients with corneal irregularities after radial keratotomy, penetrating keratoplasty, pellucid marginal degeneration, or after trauma.17 Table 12.3 shows indications for ICRS. The clinician must take time to explain the following key points to the patient before surgery21: • It is a biomechanical procedure, not a refractive one. • It is an effective technique but satisfactory results are slow, expected between 6 and 12 months postoperatively. • The best UCVA is obtained 1 year after surgery in 70% of cases. All ICRS procedures require a minimum corneal thickness of 400 µ both at the site of the incision and through the corneal tunnels. Those patients with corneal thickness less than 400 µ experience worse visual outcomes and a higher frequency of complications.3 The effect of ICRS on post-LASIK ectasia has not been studied as extensively as in primary ectasia. A study performed by Poulsen and Kang suggested that the best

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indication for ICRS in post-LASIK ectasia is either grade 4 post-LASIK ectasia (visual acuity < 0.5, decimal grading) or loss of two or more lines after the development of ectasia.21

Surgical Plan and Patient Preparation Before surgery, the following points must be determined22: • The incision placement should be at the steep keratometric axis, except for long arc rings (210 degrees and up). • The ICRS segments and symmetry is determined by the nomogram used. The incision depth is determined by the corneal thickness; it should be between 70% and 80% of corneal pachymetry at the thinnest point of the tunnel formation. Patients with severe allergic conjunctivitis must be treated accordingly before surgery to decrease the risk of rubbing and ICRS extrusion. Contact lens wear must be discontinued at least 4 days before surgery.

Nomogram Several nomograms have been designed for ICRS selection. As far as we know, clinical trials evaluating different nomograms have not been performed; thus it is at the discretion of the ophthalmologist that testing and evaluation of available nomograms is done. Ectasia asymmetry is an important factor for considering ICRS implantation (Fig. 12.1). There are several nomograms that help the surgeon to select the segments to be implanted, but there are no studies that address the question regarding whether nomograms provide a benefit. In general, the greater the flattening desired, the thicker the segment used and the closer the ring is placed to the visual axis.18

Penetrating Keratoplasty and Deep Anterior Lamellar Keratoplasty Introduction Over the past century, PK has been the elective technique for keratoconus (Fig. 12.2). New lamellar techniques now offer a series of advantages that we must take into consideration. In fact, recent studies compare PK with lamellar procedures and suggest that DALK should be the first treatment alternative.23 Keratoconus, with progressive thinning and steepening of the cornea, leads in a progressive way to the loss of best spectacle corrected visual acuity. Other ectasias, traumatic or infectious scarring, and stromal dystrophies might also be other optical indications for keratoplasty.24 The severity of the disorder impacts the decision regarding type of surgery to perform. The postoperative care of keratoplasty is long; thus preoperative evaluation is essential. In cases of very thin corneas, the position of the donor and recipient border can result in precarious healing. On the other hand, a thick corneal receptor might generate a

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mismatch between the receptors and donor’s endothelium, generating retrocorneal membranes. This problem can be overcome with a structural suturing technique.24 The grade of transparency of the lens must be evaluated in order to add a cataract extraction or an IOL repositioning, explantation, or exchange. IOL calculation might be unpredictable; thus an accurate measurement with the use of the fellow eye keratometries or with the surgeon’s refractive average outcomes and reasonable IOL formulas may lead to a better result. The integrity of the iridocorneal angle and the capsular bag may determine the type of IOL that will be implanted.5 The preoperative ophthalmologic evaluation must be focused in the location of the pathology within the corneal layers so that the optimal keratoplasty technique can be selected.24 Patient rehabilitation might take 1 year or longer; therefore expectations must be explained to the patient before undergoing penetrating keratoplasty. After surgery, patients

may be in need of spectacles, contact lens correction, or refractive surgery.25

Deep Anterior Lamellar Keratoplasty As mentioned earlier, lamellar transplantation is on the rise and DALK is the surgical option for keratoconus patients and in cases of corneal opacification with intact endothelium.24 DALK is contraindicated in cases with endothelial dysfunction, such as posterior dystrophies, corneal edema, bullous keratopathy, or very low endothelial cell counts. Also, a detailed ocular and systemic assessment is needed. Although almost all the preoperative parameters are somehow similar to the ones used for PK, DALK has some essential differences regarding technique. In slit lamp evaluation, corneal thickness must be analyzed since any space of decreased thickness might lead to corneal perforation. In the case of corneal scars or opacities,

A • Fig. 12.1

  Pentacam maps in patients with keratoconus showing 3 different degrees of asymmetry: (A) very asymmetric, (B) moderately asymmetric, and (C) symmetric.

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B • Fig. 12.1, cont’d

location, size, and depth must be taken into account. In the case of keratoconus, cone size should be measured. The diameter and size of the trephine should be planned by these measurements. Corneal curvature must be measured with computerized videokeratography, orbscan, or Pentacam (Oculus) map. The maximum area of steepening along with the minimum corneal thickness must be identified.23 The examination of the Descemet membrane is the main focus during corneal evaluation since its involvement or scarring may be associated with perforation or a change in surgical technique to PK. Thus it is essential to rule out previous hydrops (Fig. 12.3). The endothelium must be healthy for DALK; specular microscopy is required since perforation of the Descemet membrane and conversion to PK may accelerate endothelial cell loss. Pachymetry is needed to avoid potential sites of perforation and to plan the depth at which the trephine will be placed, which is generally about 60% to 90% of the maximum corneal thickness. The pachymetry desired for

Continued

keratoconus is from 250 to 300 µ. When performing the Anwar technique, pachymetry helps deep lamellar preparation and the successful formation of the big bubble.23

Donor Characteristics for Keratoplasty For penetrating keratoplasty, there are recommendations for minimal endothelial cell counts, donor age limits, and time intervals from death to preservation. Longer death to preservation time has been found to be related to graft epithelial sloughing and stromal edema. Also, age has been found to be related to an inadequate endothelium, although in the Cornea Donor Study, there was a negative correlation (Table 12.4).26,27 Also, endothelial cell density is not significantly associated with DALK results.28

Phakic Intraocular Lens for Corneal Ectasia For patients with corneal ectasia with good to best corrected visual acuity and high residual refractive error, PIOL

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C • Fig. 12.1, cont’d

• Fig. 12.2

  Clinical picture of a patient with keratoconus after penetrating keratoplasty.

• Fig. 12.3

 

Ultrabiomicroscopy of a patient with hydrops.

CHAPTER 12  Preoperative Evaluation of Keratoconus and Ectasia

TABLE EBAA Donor Cornea Standards 12.4  Recommendations

TABLE Ancilliary Test for PIOL 12.6  Preoperative Evaluation

Data Related to Donor Cornea

Ancillary Tests

Age of donor

10–75 years

Death to preservation time

< 12 h if body refrigerated or eyes iced and < 8 h if not

Specular microscopy or confocal microscopy

Preservation to transplantation time (days)

< 5 days

Evaluates endothelial cell count (ECC), polymegathism and pleomorphism, which translate into endothelium health6

2300–3300 cells/mm2

Ultrasound, anterior segment optical coherence tomography (AS-OCT), optical biometry, slit beam topography, or Scheimpflug imaging

Anterior chamber depth

Endothelial cells

High-frequency ultrasound (to select the diameter of the IOL)

White-to-white (WTW) diameter.

AS-OCT; slit-beam topography or Scheimpflug imaging

Estimates sulcus-to-sulcus distance (measuring the WTW diameter and adding 0.5 mm)

None to mild polymorphism/ polymegatism No guttae No endothelial cell damage or dystrophy Donor medical and ocular exclusion

Meets EBAA standards. No prior intraocular surgery (phakic)

Slit lamp examination

≤ 50% epithelium defect None to moderate haze None to moderate exposure None to mild stromal edema > 8 mm clear zone None to few Descemet folds None to mild endothelial stress lines

177

IOL, Intraocular lens; PIOL, phakic intraocular lens.

EBAA, Eye Bank Association of America.

TABLE 30 12.5  Requirements Before PIOL Implantation • • • • • • • • •

Age > 21 years Stable refraction and topographic values Refraction (< 0.5 D change for 1 year) No superficial or intraocular disease Clear lens Unsatisfactory vision with contact lenses or spectacles Pupil size according to the specified PIOL Anterior chamber depth (ACD) from 2.8 to 3.0 mm Corneal endothelial cell count (ECC) according to age, above 2000 cells/mm3 (specified for each PIOL)

PIOL, Phakic intraocular lenses.

implantation has been described in several studies to be effective and has proven to provide adequate correction of myopia and astigmatism.29 The main indication for PIOLs is correction of myopia or myopic astigmatism in patients with nonprogressive keratoconus. However, they can also be an option to correct visual acuity in cases out of the scope of laser correction.31

Location of Phakic Intraocular Lenses There are different types and locations to place a PIOL. The two more frequently used are the anterior chamber irisfixated PIOL and posterior chamber PIOL. Toric PIOLs are also available to correct both myopia and astigmatism, but

they are not approved by the FDA.32 Table 12.5 shows the patient requirements for PIOL implantation. Additional tests are necessary to assess the safety of PIOLs (Table 12.6).31

Lens Size Posterior Chamber Phakic Intraocular Lenses Vault The vault is the central distance between the anterior surface of the crystalline lens and the posterior surface of the Implantable Collamer Lens (ICL, Staar Surgical). The correct lens size is correlated to the amount of vaulting and should be between 0.250 and 0.750 mm (1.0 + 0.5 corneal thickness) to reduce complications. (Fig. 12.4) An undersized pICL (< 0.125 mm vault) may increase the risk of anterior subcapsular opacification, with subsequent visual acuity decrease. An oversized pICL (> 1 mm vault) may push the iris forward and close the angle, leading to intraocular pressure rise and iris malfunction. The white-to-white value provided by the Orbscan (Advanced Vision Care) is reliable if both eyes have the same or a very similar value, while the value provided by the IOL Master (Zeiss) shows values that are too large and may therefore lead to an oversized pICL.

Anterior Chamber Phakic Intraocular Lenses Vault The vaulted configuration artisan lens is designed to ensure a normal aqueous flow, but a peripheral iridectomy is necessary to avoid pupillary block glaucoma, and the distance

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between the endothelium and the periphery should be at least 1.5 mm to avoid cell loss (Fig. 12.5)

Indications for Phakic Intraocular Lens Phakic IOLs should be reserved only for patients with stable keratoconus. Progression is considered when any of the

following occur in a 1-year period: (1) an astigmatism increase of 1.0 D or more; (2) change in the refractive axes orientation; (3) increase of 1.0 D or more of the optical power of the steepest corneal meridian and (4) decrease of 25 µor more in corneal thickness. Characteristics of different PIOLs are shown in Table 12.7.

Implantation Criteria33 Indications Indications for implantation are age above 21 years, stable corneal topography, good spectacle-corrected visual acuity (> 20/30), stable refraction for more than 2 years, spherical equivalent greater than −2.75 D, and absence of clinical irregular astigmatism (> 1 line of correction between spectacle and contact lens vision).

Relative Indications

• Fig. 12.4

  Vault is the central distance between anterior surface of the crystalline lens and posterior surface of the Implantable Collamer Lens (ICL, Staar Surgical). The correct lens size is correlated to the amount of vaulting and should be between 0.250 and 0.750 mm (1.0 + 0.5 corneal thickness) to reduce complications. The arrow points vault between the PIOL and the crystalline lens.

• Fig. 12.5

Relative indications for implantation are stability of the ectasia after corneal collagen cross-linking, following DALK or PK, moderately good vision with poor tolerance to spectacles or contact lens, and anisometropia.

Contraindications Contraindications for implantation are ectasia progression, young patients (< 25 years), and high order aberrations with poor correction.

  Oculus pentacam phakic intraocular lenses (PIOL) fitting map allows to calculate and confirm the security profile of the patient. Anterior chamber depth, angle degree, optic and haptic measurements in anterior chamber PIOL.

CHAPTER 12  Preoperative Evaluation of Keratoconus and Ectasia

179

TABLE 12.7  Different Phakic Intraocular Lens Characteristics

Artisan/Verisyse and Artiflex/Veriflex

Visian Implantable Collamer Lens (ICL) STAAR Surgical

Location

Anterior chamber (iris fixated)

Posterior chamber

Myopia correction

−3.00 D to −23.50 D

−3.0 D to −23.0 D

Hyperopia correction

1.00 D to 12.00 D

+3.00 D to +12.00 D (not FDA approved)

Length and diameter

8.5 mm length, PMMA, 5 or 6 mm optic

11.5–13.0 mm 4.65–5.50 mm

Endothelial cell count

2800 2650 2400 2200 2000

Anterior chamber depth

2.8 mm measured from corneal endothelium to the anterior surface of the crystalline lens. PIOL and the endothelium in the periphery must be at least 1.5 mm

cells/mm2 cells/mm2 cells/mm2 cells/mm2 cells/mm2

(18–25 years of age) (26–30 years of age) (31–35 years of age) (36–45 years of age) (>45 years of age)

3800 3375 2975 2625 2325 2050

cells/mm2 cells/mm2 cells/mm2 cells/mm2 cells/mm2 cells/mm2

(21–25 years of age) (26–30 years of age) (31–35 years of age) (36–40 years of age) (41–45 years of age) (>45 years of age)

3.0 mm measured from corneal endothelium to the anterior surface of the crystalline lens

PIOL, Phakic intraocular lens.

References

•

Fig. 12.6  Anterior segment optical coherence tomography (OCT; Visante, Carl Zeiss Meditec, Inc.) image. Safety measurements of a posterior phakic intraocular lenses (Implantable Collamer Lens [ICL], Staar Surgical) with a good vault and a safe distance between the lens and the corneal endothelium. Allows appreciation of the chamber angle and possible changes in iris configuration.

Anterior Segment Optical Coherence Tomography Safety measurements of a posterior PIOL (ICL) with a good vault and a safe distance between the lens and the corneal endothelium. Allows appreciation of the chamber angle and possible changes in iris configuration (Fig. 12.6). In conclusion, the use of PIOL in patients with corneal ectasia is a good alternative for improving visual acuity and refraction in keratoconus eyes with high myopia and astigmatism. Toric PIOL should be reserved for regular astigmatism; if an irregular astigmatism is present, spherical equivalent should be the target.

1. Sykakis E, Karim R, Evans JR, et al. Corneal collagen crosslinking for treating keratoconus. Cochrane Database Syst Rev. 2015;(3):CD010621, doi:10.1002/14651858.CD010621. 2. Sorkin N, Varssano D. Corneal Collagen Crosslinking: a systematic Review. Ophthalmologica. 2014;232:10–27. doi:10.1159/ 000357979. 3. Parker JS, van Dijk K, Melles GR. Treatment options for advanced keratoconus: a review. Surv Ophthalmol. 2015;60(5):459–480. doi:10.1016/j.survophthal.2015.02.004. 4. Gomes JA, Tan D, Rapuano CJ, et al; Group of Panelists for the Global Delphi Panel of Keratoconus and Ectatic Diseases. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34(4):359–369. doi:10.1097/ICO.0000000000000408. 5. Spaeth G, Danesh-Meyer H, Goldberg I, Kampik A. Ophthalmic Surgery, Principles and Practice. Philadelphia, PA: Elsevier; 2011. 6. Mastropasqua L. Collagen cross-linking: when and how? A review of the state of the art of the technique and new perspectives. Eye Vis. 2015;2:19. doi:10.1186/s40662-015-0030-6. 7. Vazirani J, Basu S. Keratoconus; current perspectives. Clin Ophthalmol. 2013;7:2019–2030. Available from: http://dx.doi.org/ 10.2147/OPTH.S50119. Accessed November 26th, 2018. 8. Gore DM, Shortt AJ, Allan BD. New clinical pathways for keratoconus. Eye. 2013;27:329–339. 9. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet A– induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–627. 10. Oltulu R, Satirtav G, Donbaloglu M, Kerimglu H, Ozkagnici A, Karaibrahimoglu A. Intraoperative corneal thickness monitoring during corneal collagen crosslinking with isotonic riboflavin solution with and without dextran. Cornea. 2014;33:1164–1167. 11. Hafezi F, Mrochen M, Iseli HP, Sieler T. Collagen crosslinking with ultraviolet-A and hypoosmolar riboflavin solution in thin corneas. J Cataract Refract Surg. 2009;35:621–624.

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12. Chen X, Stojanovic A, Eidet JR, Uthein TP. Corneal collagen cross-linking in thin corneas. Eye Vis. 2015;2:15. doi:10.1186/ s40662-015-0025-3. 13. Avedro. Avedro Receives FDA Approval for Photrexa Viscous, Photrexa and the KXL System for Corneal Cross-Linking. Available from: http://avedro.com/press-releases/avedro-receives-fda -approval/. Accessed March 14, 2017. 14. Sarac O, Caglayan M, Cakmak HB, Cagil N. Factors Influencing Progression of Keratoconus 2 Years After Corneal Collagen CrossLinking in Pediatric Patients. Cornea. 2016;35:1503–1507. 15. Avni-Zauberman N, Rootman DS. Cross-linking and intracorneal ring segment—review of the literature. Eye Contact Lens. 2014;40(6):365–370. doi:10.1097/ICL.0000000000000091. 16. Muftuoglu O, Aydin R, Kilic Muftuoglu I. Persistence of the cone on the posterior corneal surface affecting corneal aberration changes after intracorneal ring segment implantation in patients with keratoconus. Cornea. 2018;37(3):347–353. 17. Giacomin NT, Mello GR, Medeiros CS, et al. Intracorneal ring segments implantation for corneal ectasia. J Refract Surg. 2016;32(12):829–839. 18. Park J, Gritz DC. Evolution in the use of intrastromal corneal ring segments for corneal ectasia. Curr Opin Ophthalmol. 2013;24(4):296–301. doi:10.1097/ICU.0b013e3283622a2c. 19. Peña-García P, Alió JL, Vega-Estrada A, Barraquer RI. Internal, corneal, and refractive astigmatism as prognostic factors for intrastromal corneal ring segment implantation in mild to moderate keratoconus. J Cataract Refract Surg. 2014;40(10):1633–1644. doi:10.1016/j.jcrs.2014.01.047. 20. Ziaei M, Barsam A, Shamie N, et al. ASCRS Cornea Clinical Committee. Reshaping procedures for the surgical management of corneal ectasia. J Cataract Refract Surg. 2015;41(4):842–872. doi:10.1016/j.jcrs.2015.03.010. 21. Poulsen DM, Kang JJ. Recent advances in the treatment of corneal ectasia with intrastromal corneal ring segments. Curr Opin Ophthalmol. 2015;26(4):273–277. doi:10.1097/ICU. 0000000000000163.

22. Touboul D, Pinsard L, Mesplier N, Smadja D, Colin J. [Correction of irregular astigmatism with intracorneal ring segments]. J Fr Ophtalmol. 2012;35(3):212–219. doi:10.1016/j.jfo. 2011.08.006. 23. Jhanji V, Sharma N, Vajpayee R. Deep Anterior Lamellar Keratoplasty: Different Strokes. New Delhi, India: Jaypee Brothers Medical Publishers.; 2012. 24. Mannis M, Holland E. Cornea Fundamentals, Diagnosis and Management. 4th ed. Philadelphia, PA: Elsevier; 2016. 25. Al-Mohaimeed M. Penetrating keratoplasty for keratoconus: visual and graft survival outcomes. Int J Health Sci. 2013;7(1): 67–74. 26. Feizi S, Javadi M, Ghasemi H, Javadi F. Effect of donor graft quality on clinical outcomes after penetrating keratoplasty for keratoconus. J Ophthalmic Vis Res. 2015;10(4):364–369. 27. Cornea Donor Study Investigator Group. The effect of donor age on corneal transplantation outcome: results of the cornea donor study. Ophthalmology. 2008;115(4):620–626. 28. Borderie V, Sandali O, Basli E, et al. Donor tissue selection for anterior lamellar keratoplasty. Cornea. 2013;32:1105–1109. 29. Fadlallah A, Dirani A, El Rami H, Cherfane G, Jarade E. Safety and visual outcome of visian toric ICL implantation after corneal collagen cross-linking in keratoconus. J Refract Surg. 2013;29(2): 84–89. 30. Gupta S. Implantable contact lenses in keratoconus. Int J Kerat Ect Cor Dis. 2016;5(1):17–20. 31. Moya T, Javaloy J, Montés-Micó R, Beltrán J, Muñoz G, Montalbán R. Implantable collamer lens for myopia: assessment 12 years after implantation. J Refract Surg. 2015;31:548–556. 32. Pineda IIR, Chauhan T. Phakic Intraocular lenses and their special indications. J Ophthalmic Vis Res. 2016;11(4):422–428. 33. Alio JL, Sanz-Diez P. Phakic Intraocular lenses in keratoconus. Int J Kerat Ect Cor Dis. 2015;4(3):103–106.

13 

LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism DAMIEN GATINEL

Introduction Laser in situ keratomileusis (LASIK) is the most widely used technique to correct for most instances of spherocylindrical ametropia because of its safety and predictability, which lead to satisfactory outcomes for both patients and surgeons.1 Analysis of the US Food and Drug Administration (FDA) and multicenter data shows that modern lasers have significantly improved patient-reported visual outcomes after LASIK.2,3 It has been refined over the years and still undergoes continuous improvements. The LASIK surgical procedure consists of two important steps: the flap cut and the laser delivery.4,5 LASIK aims at reshaping the corneal stroma after cutting and lifting a superficial flap in order to correct the preoperative refractive error. Each optical default has its own consequences in terms of geometrical reshaping, and these features have consequences on surgical parameters, such as flap dimension and thickness and the clinical outcomes. Important specific guidelines can help to optimize the visual outcomes of LASIK patients; these will be emphasized in this chapter. Modern excimer laser programming software enables the surgeon to choose between various strategies of correction. Over time, the laser profiles of ablation, eye-tracking technologies, and delivery systems have been optimized to improve postoperative outcomes. LASIK surgery is based on the subtraction of a tissue lenticule, which is photoablated. Differing from aspheric and customized wavefront-guided treatments, the profiles of ablation for conventional treatments do not take into account the asphericity of the cornea and the higher-order optical aberrations of the human eye. In most clinical situations, the main characteristics of the corneal reshaping are dictated by the correction of low-order (i.e., spectacle correctable) aberrations. Three-dimensional graphic representations of the theoretical characteristics of 182

the corneal reshaping constraints, such as morphology of the lenticules ablated during LASIK for similar amounts of spherical and cylindrical treatment, can be generated using digital modeling software (see Appendix).6,7

Pure Myopia (Video 13.1) The correction of myopic errors requires overall corneal flattening.8 The correction of pure myopia relies on the deliverance of a rotationally symmetric profile of ablation. The initial profile of ablation derived from the subtraction model of Munnerlyn et al. in 1988.9 In this model, the initial (preoperative) and final (postoperative) corneal surfaces are spherical and have different radii of curvature, the final surface being flatter (Fig. 13.1). Conforming to that pioneering work, the change in paraxial corneal power can be predicted by considering the initial unablated and the final ablated corneal surface as two spherical surfaces, with a single but different radius of curvature (Fig. 13.2). The removal of tissue is equivalent to adding a thin lens of equal but opposite power. No transition zone was proposed in this model, the junction between the optical zone and untouched periphery being of null thickness. The maximal depth of ablation is attained in the center of the optical zone (OZ), which is also the location of the minimal corneal pachymetry zone. From that mathematical model, a simple rule of thumb could be formulated: the maximal depth of ablation is roughly equal to the magnitude of treated myopia (in diopters) multiplied by the squared value of the OZ diameter (in millimeters) divided by 3 (Fig. 13.2C). This formula slightly underestimates the real depth of laser ablation, especially for higher magnitudes of treatment.10 While the precise maximal depth of ablation is given by the laser programming software, this simple formula enables the clinician to estimate the maximal depth of ablation from the clinical refraction.

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

BEFORE LASIK

183

AFTER LASIK FOR MYOPIA

PROFILE DIFFERENCE

• Fig. 13.1  Scheimpflug camera cross-section imaging of the same cornea before and after myopic LASIK. The superposition of these images enables depiction of the change caused by lenticule photoablation (myopic correction).

LASIK for Low to Moderate Myopia The LASIK technique for low to moderate myopia is safe and effective, and patient satisfaction is extremely high.11,12 With proper patient selection, the incidence of complication is low and rarely leads to severe visual loss.13,14 Night visual symptoms, reduced contrast sensitivity, and retreatment can lead to a decline in patient satisfaction with LASIK.15 Customized ablation using wavefront aberrometry and its optimized profiles were created to correct higherorder aberrations and give more vision quality to patients. Despite high visual demands, physicians and aviators having LASIK had a high percentage of good visual outcomes, satisfaction, and quality-of-life improvements.16–18 To date, there is no evident difference in both ocular low-order and higher-order aberrations and visual performance between photorefractive keratectomy (PRK) and LASIK.19 These results suggest that surgeons can choose refractive procedures according to corneal conditions or the daily activities of patients. In particular, patients with keratoconus or forme fruste keratoconus should not undergo LASIK. Night visual symptoms, reduced contrast sensitivity, and retreatment could have led to a decline in patient satisfaction with LASIK when it was performed with noncustomized profiles, which were designed on smaller optical zones in the late 1990s and early 2000s.15 Efforts to eliminate these variables have been achieved with wavefront aberrometry and custom ablations since then.

LASIK in High Myopia Underlying keratectasia, less corneal thickness, and greater stromal ablation are the main risk factors of corneal ectasia

after LASIK.20,21 Forme fruste keratoconus, genetic predisposition to keratoconus, low residual stromal bed thickness (through high myopia, thin preoperative cornea, or thick LASIK flap), and irregular corneal topography have been identified as risk factors for keratectasia development after refractive surgical procedures.22 Therefore any patient presenting clinical and/or topographic evidence of corneal abnormalities—such as keratoconus, forme fruste keratoconus, and pellucid marginal degeneration—should be excluded from LASIK surgery. In normal corneas, the depth of ablation is an important factor to consider, especially in patients having initially thin corneas and/or high levels of myopia.23–25 To reduce the risk of excessive corneal biomechanical weakening and to prevent iatrogenic keratectasia, there is consensus for the necessity of preserving a certain minimum thickness of untouched posterior stromal bed. The range of residual corneal thickness that puts the eye at risk for developing keratectasia is not precisely determined,26 but a minimum value between 250 and 300 µm is usually recommended. A residual stromal bed thickness of 250 µm does not preclude the development of keratectasia after LASIK.24 Other factors, such as slight asymmetric astigmatism or an isolated difference in central corneal thickness between eyes, may indicate an increased risk of corneal ectasia.27,28 Some authors have advocated the exclusion from LASIK of patients with thin cornea (< 490 µm) despite normal topography29 and low refractive error. A newly proposed metric, percentage tissue altered (PTA), has been reported to be an indicator for post-LASIK ectasia risk calculation.30 To increase the safety of LASIK for high myopia by maintaining a posterior stromal bed of sufficient thickness, the following strategies should be considered.

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y

E(0)~1/3xDS2

R1 R2

S

X

0 E(0)

A

•

Fig. 13.2  (A) Paraxial model described by Munnerlyn et al. to establish the profile of ablation (Ey) over the optical zone S to correct for a myopic spherical refractive error of magnitude D. R1 and R2 are the paraxial radii of curvature of the preoperative and postoperative corneal surfaces, respectively. R2 is computed from R1 using a paraxial approximation: D = (n−1) × (1/R1 − 1/R2). (B) Three-dimensional representation to the scale of the spherical myopic profile of ablation to correct a spherical myopic error of −4 D. The initial and final corneal surfaces are modeled by spherical surfaces of different radii. The surface corresponding to the optical zone is shaded. The optical profile is outlined in orange over 2 arbitrarily chosen meridians. The dimensions of the modeled elements are corneal diameter, 11.5 mm; initial anterior radius of curvature, 7.8 mm; optical zone diameter, 6 mm; final anterior radius of curvature, 8.5 mm; pupil diameter, 4 mm. (C) Mathematical rule of thumb approximation of the maximal depth of ablation for the treatment of spherical myopia with a Munnerlynbased profile of ablation

B

C

E (y) = R1 2-

S – 2

2

- R2 2-

S – 2

2

+ R12 -y 2 - R2 2 -y 2

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

Reducing the Magnitude of the Treatment (Intended Undercorrection) Significant undercorrection is generally poorly accepted, especially by young (nonpresbyopic) patients, but can be part of a monovision strategy in presbyopic patients.31 Because the difference of refraction must be limited to approximately 1.50 D in monovision strategies, this will have limited effect on the depth of ablation.

Reducing the Programmed Optical Zone Because the depth of the treatment is proportional to the square of the diameter of the OZ, reducing the latter can significantly reduce the depth of ablation. For example, reducing the OZ diameter from 6  mm to 5  mm for the same magnitude of treatment induces a reduction of nearly 30% of the maximal depth of ablation (and would also reduce dramatically the volume of the ablated lenticule).32 Thus reducing the OZ could theoretically result in an important decrease of ablation depth and allow the full correction of high myopic errors (8 D and above) in patients with normal or thin corneas. However, many studies have shown that

A

excessive reduction of the ablation zone diameter can lead to poor optical quality and increased risk of regression of the refractive effect.33–37 Even if there is no abrupt step in the periphery of the treated zone, there is an important gradient of curvature due to the law of curvature conservation. This rapid steepening causes the peripheral rays to bend excessively (spherical aberration).37 Flattening the central corneal area causes an increase of curvature at the junction of the optical and transition zones. This curvature change can be spread further out in the periphery by realizing a transition zone38–40 (Figs. 13.3A and 13.3B). However, the realization of a large transition zone implies an increase in the central depth of ablation. This may be counterintuitive to the clinician because of the usual color scale representation of the corneal curvature with specular topography (Fig. 13.4C). The OZ (flatter area) corresponds postoperatively to a blue zone, whereas the area of progressive steepening corresponds to a reddish zone. Enlarging the OZ (pushing out the red ring) would not be achieved by additional spots on the OZ periphery alone, which would result in a steepening of the central cornea (hyperopic-like ablation). The algorithms that preside for the design of the transition

B pwr :34.12

OD

SIM K’S

pwr :34.12

OD

SIM K’S

Same magnitude of treatment

Small OZ

185

Large OZ

C • Fig. 13.3  (A) Sagittal representation of the effects of a myopic profile of ablation without transition zone. There is no abrupt step at the periphery of the ablation but rather a rapid increase in local curvature. (B) The adjunction of a transition zone with no optical zone reduction imposes an additional central parallel ablation and a peripheral smooth blending. (C) In this example, in which myopia is intended to be treated by stromal ablation using a broad beam laser, the enlargement of the optical zone and the spread of the curvature change can be achieved by additional corneal ablation using parallel large spots of increasing diameters that would cover the optical zone.

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LASIK and SMILE

ZO

Magnitude of correction (diopters)

90 80

O

70 60

C

50 40 30 20 108 0

2

3

4

5

6

7

8 9 10 Diameter of the optical zone (mm)

11

P

12

• Fig. 13.4

  Theoretical relations between the optical zone diameter and the achieved correction with a Munnerlyn-based treatment. For the same depth of ablation (100 µm), increasing or decreasing the optical zone width over a given meridian results in a decrease or increase in the achieved correction, respectively. This property is used in the elliptical strategy for myopic compound astigmatism.

zone are proprietary, and there is a lack of theoretical data in the literature to address the theoretical issues of particular transition zone designs.41,42 Some authors have suggested avoiding abrupt curvature changes at the OZ periphery of the optical zone by using special transition profiles at the price of a slight reduction of the OZ diameter.43 When astigmatism is associated with myopia (compound myopic astigmatism), the reduction of the OZ diameter can be achieved selectively on the steeper initial meridians, with no modification on the flat meridian. This would result in an elliptical OZ whose ablation maximal depth is reduced as compared to a circular one. Using the relation between depth and magnitude of myopic correction, the desired selective correction can be applied over the corneal meridians for a given central depth of ablation (Fig. 13.4).

Use of Multizone/Multipass or Aspheric Profiles of Ablation Theoretical modeling studies10,44–45 show that customizing the myopic profile of ablation to control for the postoperative profile asphericity has significant effects on the maximal depth of ablation. Aiming at increased postoperative prolateness by targeting a more negative asphericity (or reduced postoperative oblateness) incurs an increase in the maximal depth of ablation as compared to that of a spherical Munnerlyn-based treatment (Fig. 13.5). Conversely, aiming at reduced postoperative prolateness (or increased postoperative prolateness) results in reduction of the maximal depth of ablation. Many clinical studies have shown that after conventional myopic LASIK or PRK, the postoperative corneal contour within the OZ conforms to an oblate ellipse.37,46,47 This oblate shift is proportional to the magnitude of treatment and is influenced by neither the initial asphericity nor the apical corneal curvature. We have first demonstrated that this oblate shift is opposite to the theoretical predictions of finite models that predict that the

P=1/3 DS2 + dQS4

• Fig. 13.5

Geometrical depiction of the influence of postoperative corneal asphericity within the optical zone with corneal customized ablations. The theoretical surfaces represented in cross-section have the same apical radius of curvature, but their asphericity differs, being, respectively, oblate for the red surface (O), null for the white surface (C) and prolate for the green surface (P). When encompassing the same optical diameter, additional ablation is required to increase the negative postoperative asphericity. The additional central depth of ablation (P) is proportional to intended variation in asphericity and to the fourth power of the optical zone.  

corneal profile should be more prolate within the OZ for initially prolate corneas.48,49 Explanatory reasons for this discrepancy are numerous (biological remodeling, biomechanical effect, reduced laser ablation due to peripheral corneal obliquity).46,47,50 Thus using an aspheric profile of ablation to reduce the postoperative prolateness (or increase postoperative oblateness) may have unpredictable effects and result in an excessive oblateness with marked reduction of the functional OZ and poor optical quality at large pupil diameters (Fig. 13.6). Similar limitations have applied for the multizone–multipass profiles of ablation that were effective in reducing the depth of ablation but at the price of the reduction of the functional OZ.51–54

Reducing the Thickness of the Corneal Flap Despite dissimilarities between different platforms, all femtosecond (FS) lasers are predictable and safe for making corneal flaps in LASIK.55 By adjusting the depth of the infrared ultrashort pulse focus, the surgeon is offered a wider range of flap thickness, with a better predictability (reduced standard deviation).56–59 The flap obtained with the FS laser is relatively independent of the operated cornea and patient characteristics (Fig. 13.7). This is opposed to microkeratome LASIK surgery, in which there were factors such as preoperative total corneal pachymetry,60–63 age,63 preoperative keratometry,60 and microkeratome suction duration61 correlated to the flap thickness.64–68 With microkeratome flap cuts, significant standard deviation between the predicted and obtained flap thickness is confirmed by several authors64,69,70 and the flap thickness was not uniform over the flap area.71

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

Spherical aberration (SA)

187

Some reports of keratectasia following LASIK, despite safe residual bed thickness calculation, may have resulted from larger variation in flap thickness70,72 (Fig. 13.8). These results emphasized the importance of measuring flap thickness and corneal bed thickness during surgery,73 using contact60,72 or noncontact methods.70,74 Flap-thickness values can be calculated using intraoperative optical pachymetry, but they were significantly lower than programmed values or OCT measurements performed in the postoperative period.75

Normal pre-op

Q =-0.2

Pure Hyperopia (Video 13.1) Scotopic pupil

Increase in positive spherical aberration

After myopic LASIK

Oblate OZ

Q = >0

Scotopic pupil

•

Fig. 13.6  Small optical zone diameter and increased oblateness within the optical zone are incriminated in explaining the increase in positive spherical aberration after myopic excimer ablations.

In comparison to myopic correction, in which the goal is to flatten the central cornea, in hyperopia the central corneal area is to be steepened to increase its optical power (Fig. 13.9). This central steepening makes the planned correction of the hyperopic eye more difficult, because the steepened central corneal portion must join the peripheral unablated area of lower curvature via a transition area. These represent the important special features of the correction of hyperopic errors that we will emphasize in this chapter. The profile of ablation to correct for spherical hyperopia is radially symmetric and predominates in the periphery in an annular fashion. A subtraction shape model based on geometric optics allowed Munnerlyn et al.9 to announce in 1988 the principles of laser-guided photoablation in the central corneal area (effective OZ). Spherical hyperopic ablation results in the ablation of a concave lenticule within the OZ (Fig. 13.10). Its thickness, null in the center, increases progressively toward the periphery where it reaches its maximum at the edge of the OZ. In first-order approximation, the maximum thickness of the edge of the ablated

FS-LASIK FLAP IN CROSS SECTION

EPITHELIUM

FLAP EDGE

• Fig. 13.7  High-resolution optical coherence tomography imaging of the cornea after the realization of a myopic LASIK. The flap was cut with a femtosecond laser. The epithelial and stromal layers of the flap are clearly delineated. Note the vertical abrupt edge and thickness constancy, which are characteristic of femtosecond LASIK flap cuts (arrows).

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B Flap stability Thin flaps

Thick flaps Corneal ectasia

Depth of ablation Small OZ

D

Large OZ Optical aberrations

C • Fig. 13.8

  (A) Determination of the residual stromal thickness (RST) with LASIK. The initial central corneal thickness is 530 µm, while the expected flap thickness and laser stromal ablation depth are equal to 160 µm and 70 µm, respectively. The posterior 250 µm of RST are represented with red shading. (B) When the standard deviation of a given microkeratome is equal to 30 µm, 95% of the flaps will have a thickness comprised of between 100 and 220 µm. The achievement of RST of less than 250 µm is thus theoretically possible. (C) The realization of an ultra-thin flap minimizes the risk of corneal ectasia but may increase the risk of flap cut incident and postoperative flap instability. (D) Consequences of adjusting the surgical parameters with LASIK for high myopia. Red arrow: Increased probability. Green arrow: Reduced probability. OZ, Optical zone.

lenticule over the OZ is proportional to the magnitude of the hyperopic treatment and to the square of the chosen OZ diameter. The volume of tissue ablation needed to steepen the cornea is thus limited by the initial anterior surface and the final postoperative steeper spherical surface over a circular optical zone. For the necessary geometric feature, any cornea that had tissue removed centrally to steepen its curvature (OZ) while leaving the periphery untouched must undergo an additional ablation to sculpt a smooth blending zone. This flatter area, commonly referred to as the transition zone, thus represents a constant feature that ideally would have no undesirable optical effects and would ensure the stability of the induced refractive changes in the OZ by limiting unwanted biologic and biomechanical changes.

When we address theoretical considerations of the different approaches to blending a steepened OZ to the untouched peripheral cornea, some constraints must be taken into consideration76,77 (Fig. 13.11). Because the patterns of ablation for the hyperopic optical and transition zones are proprietary, there are insufficient data to compare one ablation profile with another.78,79 Ideally, these profiles should have characteristics that limit the compensatory epithelial hyperplasia in annular midperipheral ablation.80,81 In LASIK, the corneal flap covering of the ablation zone minimizes the epithelial healing response.5,78,82–84 This might account for the better results reported for this technique over PRK.85,86 The total ablation zone diameter being equal to the outer diameter of the transition zone, obtaining large flap sizes is mandatory for hyperopic LASIK procedures

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

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POST-OP HYPEROPIC LASIK

• Fig. 13.9

  After LASIK for hyperopia. Scheimpflug camera cross section imaging of the cornea before and after LASIK. The superposition of these images enables to depict the change caused by the lenticule photoablation (hyperopic correction).

• Fig. 13.10  Schematic representation of the photoablated lenticule over the optical zone for the treatment of pure spherical hyperopia. Its thickness is null in the center and increases gradually toward the edges of the optical zone, where it reaches its maximum. This characteristic implies the realization of a large blend zone.

Optical zone

Transition zone

O 2 1

• Fig. 13.11

• Fig. 13.12  Schematic representation of a hyperopic spherical stromal ablation in laser in situ keratomileusis. The optical zone area is shaded in pink; the transition zone is shaded in blue. The large dimensions of the ablation zone impose the realization of a large flap.

  Theoretical modalities for the realization of a blend zone in hyperopic ablations. The corneal preoperative and postoperative profiles are represented in blue and red, respectively. Point 1 corresponds to the junction of the optical and transition zones; point 2 corresponds to the junction with the transition and untreated zones, respectively. Dotted lines represent two different possible profiles for the realization of the transition zone.

(Fig. 13.12). Modern FS laser platforms enable the surgeon to program and obtain flaps whose diameter can reach theoretically up to 10 mm (Fig. 13.13). Some publications have emphasized the need for a large transition zone outer diameter in order to improve the biologic tolerance and minimize regression.87,88 Conversely, enlarging the OZ diameter, although desirable to preserve the quality of vision and reduce the risk of decentration, represents a limiting factor because the depth per diopter at the edge of the OZ will increase with the square of the OZ diameter. This could

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FEMTOSECOND LASER LASIK FLAP CUT OUTLINE 10 mm

• Fig. 13.14

• Fig. 13.13  After applanation, the flap cut perimeter and interface is outlined in green within a 10-mm zone within the total applanation window. This flap picture can be automatically or manually translated if necessary before laser firing to achieve optimal centration over the pupil. In addition to the flap, a short canal for evacuating the gas bubbles generated during the laser–tissue interaction extends from the hinge to the superficial conjunctiva.

  Specular corneal axial topography (difference map) with the EyeSys topography system between J and J + 9 months after hyperopic laser in situ keratomileusis for 6 D. Between each postoperative visit, 2 D of regression was noted.

account for the low success rate observed for corrections over 5 D or 6 D of hyperopia.78,79 A large cutting gives an increased risk of some intraoperative complications, such as intraoperative bleeding, intraoperative epithelial defect, and blood in the interface.88

Outcomes of Hyperopic LASIK The factor that negatively influences the outcome of hyperopic LASIK is the degree of hyperopia corrected.78,79,89,90–92 Better outcomes are expected when the magnitude of hyperopia is equal to or less than +4 D. Preoperative keratometry does not seem to significantly influence the postoperative results, and postoperative keratometry (> 48 D) does not result in significant worsening of visual results when the attempted correction is less than +4 D.93 Dry eye is problematic after LASIK for hyperopia and is associated with refractive regression94 (Fig. 13.14). Chronic dry eye is associated with preoperative dry-eye symptoms; female gender94; and a narrow, superiorly placed hinge flap.95,96 Preoperative and postoperative treatments—such as a combination of artificial tears, topical autologous serum, topical cyclosporine A, and punctual occlusion—can help in effectively managing patients with severe dry eye.97,98 The quality of vision after hyperopic LASIK and PRK has been investigated. Clinical studies show that third and higher total and corneal aberrations increase significantly after hyperopic LASIK.99 The largest increase occurs in spherical aberration, which shifts to negative value. This is due to postoperative exaggeration of the negative corneal asphericity (increased postoperative prolateness) after hyper-

• Fig. 13.15  Postoperative axial (top) and tangential specular corneal topography maps 1 months after successful bilateral hyperopic LASIK (+3 D). Note the curvature changes (rapid flattening, increased prolateness) from the center to the periphery.

opic profile delivery (Fig. 13.15).100,101 As for myopia, there are some discrepancies between these findings and the theoretical predictions using aspheric corneal models and Munnerlyn-based treatments.102–104 Reasons to explain those discrepancies are similar to those invoked for myopic profiles.47,50 Wound healing might be an especially important issue due to the characteristics of corneal reshaping after hyperopic LASIK. Optimal centration on the entrance pupil is also critical to avoid the induction of odd higherorder aberrations, such as trefoil, third-order, and fifthorder coma (Fig. 13.16). Many reports suggest that the optimal centration should be directed onto or toward the corneal vertex (first Purkinje reflex or coaxial light reflex; Fig. 13.17).105,106 Efficient eye tracking, aspheric ablation profiles,107 and wavefront-supported customized ablation may improve the results of hyperopic LASIK.108,109 Presbyopia usually has earlier onset in the hyperopic population than in the myopic population. Many hyperopic

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

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B • Fig. 13.16

  (A) Specular corneal topography (top left), optical path difference (top right), higher-order wavefront (bottom left) and total wavefront maps (bottom right) with the ARK 10,000 (NIDEK). This 28-year-old patient complained of monocular diplopia on the left eye 1 month after hyperopic laser in situ keratomileusis for 5 D. Uncorrected visual acuity is 15/20, best corrected visual acuity is 20/20 (+1 D). Slight inferior decentration is noted on the axial map. (B) Decomposition of the wavefront with Zernike polynomials. The increase in third-order aberrations relates to the imperfect centration over the entrance pupil and may account for the visual symptoms. The spherical aberration is negative. This is owing to the postoperative increase in prolateness of the anterior corneal profile.

patients are referred for refractive surgery counseling in their forties or fifties because of the global visual impairment owing to near and distance poor uncorrected visual acuity. Monovision seems to lead to results in hyperopes that are slightly inferior to results in the myopic population.110 The increased corneal multifocality can be used to increase the depth of focus to presbyopic patients.

Simple myopic and hyperopic astigmatic treatments rely on the use of negative and positive cylinder modes, respectively. Compound and mixed astigmatism are treated by the combination of negative and/or positive cylindrical and spherical modes.

Simple, Compound, and Mixed Astigmatic Errors (Video 13.1)

This is optimally treated by using positive cylinder excimer ablation. This mode consists of steepening the flattest meridian to the desired value. Three-dimensional modeling is useful to conceptualize its characteristics and that of the required blend zone along the flat axis (Fig. 13.19). No significant coupling effect on the spherical component has been observed after pure positive cylindrical treatments; this relates essentially to the geometry of this profile that spares the center of the cornea and the steepest initial meridian.7,112 A blend zone is necessary to blend the abrupt ablation created at the periphery of the OZ along the initial flattest meridians. Ideally, this blend zone takes an elliptical perimeter, the longest axis of which has the direction of the initially flat axis.7,112 When dealing with compound hyperopic astigmatism or mixed astigmatism, using the expression of refraction that incurs the maximum magnitude, positive cylinder mode results in the minimum amount of tissue ablation.6,113 Negative cylinder ablation was proposed earlier than positive cylinder mode because of the engineering constraints of the first delivery systems, which used slits and

Myopia is often associated with some degree of astigmatism in the general population. It is estimated that astigmatism of more than 0.50 D is present in 44.4% of the population and that 8.44% of these subjects have astigmatism of 1.50 D or more.111 Regular astigmatism is mainly generated by excessive corneal toricity. Corneal toricity can be suppressed either by flattening the steepest meridians to the curvature of the initially flatter meridian or by steepening the flattest meridians to the curvature of the initially steeper meridian. LASIK for astigmatism aims at reducing this excessive toricity by etching from the corneal surface an adequate toric lenticule of corneal tissue of variable thickness. Pure positive and negative cylindrical excimer laser treatments are based on the combination of three elementary profiles of ablation selectively delivered on the different corneal meridians (Fig. 13.18).

Simple Astigmatism Simple Hyperopic Astigmatism

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TEMPORAL TEMPORAL Visual axis Vertex ++Pupil center (1st Purkinje)

NASAL

E

N Center of curvature (cornea)

A

NASAL

Verte Vertex (1st corneal reflex) Pupil Center

B • Fig. 13.17  (A) The line joining the fixation target (F) to the center of the entrance pupil (E) is called the line of sight. The proximity of the center of curvature of the cornea and the nodal points accounts for the proximity of the corneal intercept of the visual axis and the corneal vertex (first Purkinje reflex). (B) The combined acquisition of the pupil contour and Placido disk corneal reflexion allows measurement of the distance from pupil center to the center of the Placido mires, which is the fixation target of the measured eye. During laser in situ keratomileusis surgery, the laser camera tracks the center of the pupil, from which the center of the photoablation can be offset toward the vertex (sometimes labeled “apex”) by a variable amount (e.g., 50%, 75%, or 100% of the chord joining these points).

diaphragms. The use of negative cylindrical modes to treat for pure or compound hyperopic astigmatism led to initial mitigated reported results because of increased tissue ablation leading to excessive scarring and undesired refractive shifts.

Simple Myopic Astigmatism Pure cylindrical myopic ablation consists of ablating a lenticule with a convex shape along the initial steeper meridian and with constant thickness along the initial flatter meridian in order to preserve its curvature (Fig. 13.20). Because of this latter constraint, the amount of pure cylinder treatment is superior to the amount of spherical treatment for a given degree of negative dioptric treatment. The maximal

thickness of the myopic cylindrical ablated lenticule is located along the flatter meridian and is identical to that of a spherical myopic lenticule for a given magnitude of treatment. This ablation pattern along the flat meridian is equivalent to that of a plano ablation (Fig. 13.21). This plano ablation induces some flattening in the flattest meridian. This explains the frequent unanticipated effects from the optical and engineering perspectives of negative cylindrical treatment, such as undercorrection and hyperopic shift.114 To minimize the intensity of these phenomena, the edges of the ablation over the OZ have to be smoothed out evenly by enlarging the transition along the initially flatter meridian, thus creating an elliptical perimeter for the total ablation zone.

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

OZ

A

Initial curvature

TZ

Final curvature TZ

C

Initial curvature

B OZ

Initial curvature

OZ

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TZ

Final curvature

TZ

Final curvature

• Fig. 13.18  (A) Sagittal representation of the flattening of a corneal meridian over the optical zone. This profile is employed over all the meridians with the exception of the flattest in the treatment of simple myopic astigmatism. (B) Sagittal representation of the steepening of a corneal meridian over the optical zone. This profile is employed over all the meridians with the exception of the steepest in the treatment of simple hyperopic astigmatism. (C) Sagittal representation of the parallel ablation of a corneal meridian over the optical zone. This profile is employed over the flattest meridian in the treatment of simple myopic astigmatism to preserve its curvature.

Relation Between Negative and Positive Cylindrical Ablations Because the initially steeper principal meridian cannot be flattened selectively (this would imply plano ablation on the other principal meridian), the lenticule ablated for cylindrical myopic treatment can be considered as a combination of two successive treatments6: cylindrical positive treatment of equal magnitude on the initially flatter meridian (to steepen its curvature until it equals that of the opposite principal meridian), followed by myopic spherical treatment of

similar magnitude aiming to flatten both meridians (Fig. 13.22). The final surface is spherical and its radius is equal to that of the initially flatter meridian. For example, a cylindrical treatment −1.00 × 180 degrees is equivalent in terms of the optical results and the amount of ablated tissue to the following sequential treatment: +1.00 × 90 degrees and −1. This additive relation is useful to compare strategies employed to treat compound and mixed astigmatism. The photoablated volume according to a particular sequential strategy can be converted in a particular sum of negative or positive spherical lenticules and positive

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B • Fig. 13.19  (A) Schematic representation using three-dimensional computer modeling (Boolean operations) of the ablated lenticules etched for the positive cylinder treatment (optical zone only). The profile of ablation has been outlined over different meridians of the lenticule. The peripheral depth is maximum along the initial flat meridian (FM) and null along the initial steep meridian (SM). The transition zone is thus elliptical, having its widest diameter along the initial flatter meridian. (B) Schematic representation using three-dimensional computer modeling of the ablated lenticules etched for positive cylinder treatment. A transition zone of constant slope has been added wherever an abrupt step is sculpted in the cornea at the outer perimeter of the optical zone. The transition zone is thus elliptical, having its widest diameter along the initial flatter meridian. The profile of ablation has been outlined over the flattest meridian of the lenticule.

A

B • Fig. 13.20  (A) Schematic representation using three-dimensional computer modeling (Boolean operations) of the ablated lenticules etched for negative cylinder treatment (optical zone only). The profile of ablation has been outlined over different meridians of the lenticule. The peripheral depth is maximum and constant along the initial flat meridian (FM) and null along the initial steep meridian (SM). (B) Schematic representation using three-dimensional computer modeling of the ablated lenticules etched for negative cylinder treatment. A transition zone of constant slope has been added wherever an abrupt step is sculpted in the cornea at the outer perimeter of the optical zone. The transition zone is thus elliptical, having its widest diameter along the initial flatter meridian. The profile of ablation has been outlined over the flattest and steepest meridians of the lenticule.

cylindrical lenticules. In the past, before the approval of positive cylinder correction by the FDA in 2000, suboptimal strategies in terms of excessive photoablated volume incur negative cylinders and positive sphere sequential treatments. The negative sphere obtained from the splitting of the negative cylinder would then combine with the part of

the positive spherical treatment to result in an unnecessary plano lenticule. To compensate for the high reported rate of undercorrection of the cylindrical component and overcorrection of the spherical component with simple myopic astigmatic treatments, some strategies have been proposed by laser

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

companies. In the case of sequential ablation, the strategy consists of anticipating both the undercorrection and the hyperopic shift by splitting the cylindrical treatment into two successive cylindrical ablations of opposite signs.150-117 Three-dimensional modeling is useful for understanding this concept (Fig. 13.23). With most of the flying spot lasers, such compensation is integrated in the laser system and thus is not directly visible to the surgeon.

Compound Myopic, Hyperopic, and Mixed Astigmatism Noncustom PRK or LASIK ablation of pure, compound, or mixed astigmatic refractive errors is based on paraxial models first described by Munnerlyn et al.9 They generally SM FM

• Fig. 13.21

  In situ schematic representation in cross section of the different constraints applied at the periphery of the flat and steep meridians for negative cylinder ablation (surface treatment). The volume to photoablate is represented in orange. The abrupt step at the periphery of the flat meridian (FM) requires smooth blending. This is achieved by varying the width of the transition zone to allow progressive junction to the unablated periphery. The epithelial and endothelial layers are shown in green and red, respectively.

A

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employ one or more of four elementary treatments: spherical myopic, spherical hyperopic, cylindrical myopic, and cylindrical hyperopic. Thus to achieve emmetropia, tissue photoablation within the OZ must yield a single final apical corneal curvature. As refraction (as commonly measured in clinical practice) is an arc-based mathematical expression limited to the principal major and minor axes, a compound astigmatic refractive error can be expressed by different equivalent expressions. Sequential treatment strategies for the correction of compound astigmatism were proposed, consisting of a combination of spherical and cylindrical treatments, as follows: • ablating the cylinder along the flattest meridian and then treating the residual spherical component (positive cylinder approach); • ablating the cylinder along the steepest meridian and then treating the residual spherical component (negative cylinder approach); • ablating the total refractive error by two pure cylindrical ablations of opposite signs along the principal meridians without spherical correction (bitoric approach); • ablating half the power of the cylinder along the steepest meridian and the remaining half along the flattest meridian, before treating the residual spherical equivalent (cross-cylinder approach). Azar and Primack113 found that strategies combining hyperopic spherical and myopic cylindrical corrections incur the greatest amount of corneal tissue ablation. To provide a direct estimate of the difference in the amount of tissue ablation, we designed a method to compare and illustrate the amount of tissue ablation incurred by different sequential strategies using Boolean operations.6 This method confirmed the universal utility of combining plus cylindrical and negative or positive spherical ablations when

B • Fig. 13.22  (A) In situ schematic representation (lateral view) of the decomposition of the pure negative cylinder treatment into the pure hyperopic treatment (profile of ablation shown in green) and pure spherical treatment (profile o f a blation s hown i n orange). ( B) D ecomposition o f t he l enticule c orresponding t o t he volume ablated for the negative cylinder treatment (NC) into two lenticules, corresponding to the volume of a negative spherical and positive cylindrical volume, respectively. For example, the negative cylinder treatment (−1 × 0°) results in the same amount of ablated tissue as the following sequence: (−1) (+1 × 90°).

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B • Fig. 13.23

  (A) The delivery of a pure negative cylinder treatment on a plate having null optical power and the same refractive index of the cornea will cause a pure cylindrical variation of the refraction. If the same treatment is delivered on the cornea of a living eye, an additional hyperopic shift is commonly observed owing to the conjunction of physical, biologic, and biomechanical mechanisms. (B) Precompensation of the hyperopic shift caused by a pure negative cylindrical treatment (top). This can be achieved by the modification of the value of the magnitude of the negative cylinder entered in the laser software and the addition of a positive cylindrical ablation according to the magnitude of the coupling effect (bottom). The latter is aimed at canceling the excessive flattening of the flatter meridians due to the negative cylindrical ablation (Chayet nomogram with the excimer NIDEK EC 5000 laser).

treating any compound or mixed astigmatism while theoretically minimizing the volume of ablated corneal tissue. Regardless of the expressions chosen to program the correction (i.e., positive or negative cylinder format), the profile of ablation delivered with modern laser platforms equipped with flying-spot delivery systems is always the one that minimizes the amount of tissue removed. Using this approach, the magnitude of astigmatism to correct is expressed in the positive cylinder format of the refraction. It implies variable steepening of the corneal surface, aimed at reducing or suppressing the toricity of the anterior corneal surface, followed by a pure positive or negative spherical treatment to correct for the remaining defocus.

Hyperopic and Mixed Astigmatism Negative cylindrical approaches to compound hyperopic or mixed astigmatism result in additional tissue ablation, the amount of which results from the combination of the myopic spherical treatment in the flat meridian (which is part of the negative cylindrical treatment) with a positive spherical lenticule (in both meridians; Fig. 13.24). They should not be used. This combination also occurs with the cross-cylindrical ablation strategy when it is used to correct mixed or compound hyperopic astigmatism. This strategy has been proposed to favor postoperative prolate asphericity and to reduce the overcorrection on nonprincipal meridians.5,42 In hyperopic astigmatism correction with broad or

slit scanning laser systems, the cross-cylinder technique may also reduce the increase in corneal eccentricity, leading to a more physiologic corneal shape. For mixed astigmatism, the positive cylindrical approach and bitoric ablation would theoretically incur the same minimum volume of tissue ablation (Fig. 13.25). However, because of the global characteristics of the cylindrical profiles of ablation achieved with the newest delivery systems (wide elliptical transition zones), a bitoric strategy might be more practical to treat mixed astigmatism118,119 and reduce the rate of retreatment.120 The bitoric strategy has also been shown to reduce the hyperopic shift caused by the use of the negative cylindrical treatment by ablating more selectively along the extremities of the flat meridian (positive cylindrical treatment), thus preventing the flattening of the latter and avoiding a shift of refraction toward hyperopia. A significant percentage of eyes (67.8%) gained 1 or more of best corrected visual acuity (BCVA) after bitoric LASIK for mixed astigmatism in a study conducted by Albarran-Diego et al.119 This might be explained by reduction of image distortion. Deliverance of the correction of mixed and hyperopic astigmatism with flying-spot laser obeys several constraints, among which is the necessity of minimizing the spatial density of the ablation pulse.121 This results in a nonsequential photoablation in which the correction of the astigmatism is not performed as the successive deliverance of positive cylinder and a negative sphere or cylindrical

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

A

B

C

D

+1

E • Fig. 13.24  Schematic representation of the different strategies aimed at correcting compound hyperopic astigmatism with laser in situ keratomileusis. The outer perimeter of the optical zone is circular and identical for each of the different treatment modes. The volume required for the transition zone is not represented. The profile of ablation is outlined in green and red along the outer perimeter and principal meridians of the photoablated lenticules corresponding to positive and negative cylinder treatments, respectively. (A) Positive-cylinder strategy. This strategy incurs the minimum volume of ablation and spares the center of the ablation zone as opposed to the negative cylinder and cross-cylinder strategies. (B) Negative cylinder strategy. This strategy incurs the maximum depth and volume ablation owing to the additive properties of the negative cylindrical treatment. (C) Cross-cylinder strategy. This strategy causes more ablation than the positive-cylinder strategy. (D) In situ comparison of the positive and negative strategies to correct for the same magnitude of compound hyperopic astigmatism (top). Effect on the principal foci of the cylindrical and spherical ablations: negative-cylinder ablation causes the refraction to be +3 D before being treated by a pure spherical hyperopic ablation, whereas the negative cylinder ablation causes the refraction to be +1 D before being treated. (E) In situ comparison of the positive and negative strategies to correct for the same magnitude of compound hyperopic astigmatism. The additional volume incurred by the negative-cylinder strategy is shown in brown (right). It corresponds to a lenticule with parallel surfaces, whose thickness is the same as that of a pure positive spherical lenticule that would allow the operator to correct for 2 D over the same optical zone diameter. Because of the increased depth at the periphery, more tissue is also needed to sculpt the transition zone.

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B A

C • Fig. 13.25

  Schematic representation of the different strategies aimed at correcting mixed astigmatism with laser in situ keratomileusis. (A) Positive-cylinder strategy. (B) Bitoric strategy. (C) Negative-cylinder strategy. The hinge of the flap is placed superiorly (90°). The outer perimeter of the optical zone is circular and identical for each of the different treatment modes. The profile of ablation is outlined in green and red along the outer perimeter and principal meridians of the photoablated lenticules corresponding to positive and negative cylinder treatments, respectively. The transition zone has the same slope for each of the depicted strategies. The profile of ablation along the principal meridians over the transition zone is outlined in yellow. The deepest ablation is attained at the periphery of the optical zone along the initially flatter meridian. The transition zone has an elliptical perimeter, the widest diameter of which is located along the flatter meridian. The negative-cylinder strategy (C) incurs the maximum amount of volume of ablated tissue and the deepest ablation. Because of this constraint, the transition zone has to be wider and is necessarily extended along the vertical meridian to blend the abrupt step created by the delivery of the positive spherical treatment. The positive-cylinder and cross-cylinder strategies incur the same amount of tissue ablation: owing to the additive properties of the negative-cylinder treatment, the lenticule corresponding to the negative-cylinder treatment (−1 × 0°) is equal to the sequential delivery: (−1) and (+1 × 90°).

corrections but rather as an integrated “full correction.” However, bitoric mixed astigmatism ablative treatments may display nontrivial coupling effects. A recent study has shown interest in considering historical coupling adjustments when planning mixed astigmatism treatments to improve surgical outcomes.122

Compound Myopic Astigmatism Sequential Strategy

Conventional strategies used to correct compound myopic astigmatism are sequential: the spherical and cylindrical

components of the refractive errors are treated successively, over a circular OZ. For compound myopic astigmatism (e.g., −3.00 [−2.00 × 90 degrees]), all available sequential strategies would theoretically lead to the same amount of tissue ablation because any negative cylindrical treatment (−2.00 × 90 degrees) can be split into a sequence combining a negative sphere (−2.00) and a pure cylindrical treatment (+2.00 × 0 degrees). Recombining the negative spherical components and the pure cylindrical treatment leads to the equivalent following refraction expressed in the positive cylinder format, −5.00 (+2.00 × 0 degrees).

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

Elliptical Strategy

The sequential approach is not the only treatment for compound myopic astigmatism. By using a patented elliptical method, VISX software allows the full myopic and astigmatic correction to be sculpted into the cornea in one smooth ablation. This is made possible by the narrowing of the OZ along the initially steeper meridians (Fig. 13.26). The treatment of compound myopic astigmatism aims both to suppress the toricity and to flatten the corneal anterior surface over the effective optical zone: in the elliptical modality, astigmatic and myopic correction are achieved by varying the diameter in elliptical fashion, the narrowest diameter achieving the greatest flattening effect. The relative size of the major and minor axes of the elliptical cut depends on the ratio between the cylindrical and spherical magnitudes. Comparative clinical studies have shown that the elliptical method leads to a significant improvement in results in patients treated for myopic compound astigmatism, at least for the correction of the cylinder.53,123,124 The elliptical method has several theoretical advantages, such as a reduction in the maximal depth of ablation and the induction of a natural transition zone with no steep edges. It implies, however, a reduction of the OZ diameter along the initially steeper meridian, which could theoretically cause optical aberrations with pupil dilation in low-light conditions. Recently, a simplified formula was proposed to accurately approximate the volume of corneal tissue ablated within the optical zone during pure spherical corrections.32 However,

199

no quantitative computations of the tissue removed during cylindrical corrections have been published. Strategy to Optimize the Clinical Outcomes of Astigmatic Treatments

Because the spherocylindrical expression of astigmatic treatments is relatively more complex than that of pure spherical treatment, the refractive formula entered in laser software should be carefully checked before treatment. Most laser software displays a two-dimensional or three-dimensional representation of the elementary characteristics of the computed profile of ablation, whose elliptical shape must match the orientation expected from the cylinder axis. The longest axis of the ellipse is oriented along the flattest corneal meridian in all cases. The spatial orientation of the toric profiles of ablation requires proper alignment of the corneal surface relative to the delivery system in order to avoid undercorrections (Fig. 13.27). Human eyes often undergo torsional movements about their axes depending on body position.125 Accurate laser delivery can be facilitated by the apposition of horizontal ink marks when the patient is in seated or supine position. The surgeon can then detect and compensate for some cyclotorsion during treatment by appropriate head rotations and repositioning.126 Newer ablation systems are equipped with sophisticated tracking systems127 that can improve the clinical outcomes by reducing the amount of decentration and rotation. Some early laser devices could detect eyeball rotations by recognizing and tracking limbal ink marks.128 Currently, nearly all modern excimer laser platforms are linked to an acquisition system that enables the recognition of fine iris details as seen by the tracking laser camera and the compensation of ocular cyclotorsion.129,130

Deg Dio 180 9

• Fig. 13.26

  Comparison between the elliptical (top) and sequential (bottom) strategies to treat compound myopic astigmatism. In the elliptical strategy, the full correction is achieved by varying the width of the optical zone over the meridians to achieve the desired correction (maximum for the shortest and minimum for the longest, respectively). In this example, it results in the narrowing of the vertical diameter of the optical zone, which provides a reduction in the maximal depth of ablation but may increase the incidence of night vision disturbances. In the elliptical strategy, there is no need of a transition zone, since the edge of the ablated lenticule has null thickness. In the sequential strategy, the realization of a transition zone is mandatory to blend the abrupt edges caused by the negative-cylinder treatment.

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60

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40

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C=4D C=3D C=2D C=1D 0

• Fig. 13.27

10

20

30 40 50 60 Axis error (degree)

70

80

90

  Theoretical consequences on the postoperative axis and magnitude of astigmatism after an axis positioning error. The curves correspond to the expected magnitude after 4 different cylindrical treatments (C = 1 D, 2 D, 3 D, and 4 D, respectively) applied with an axis error plotted on the abscissa. The angle variation from the initial axis is plotted in yellow. There is no reduction of the magnitude of the cylinder from axis malpositioning of 30 degrees. For example, for a 30-degree error, a theoretical postoperative cylinder of the same magnitude but axis-shifted 60 degrees is expected.

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TOPOGRAPH & PUPILLOMETER

DATA TRANSFER LIMBUS DETECTION

PUPIL SHIFT COMPENSATION

CYCLOTORSION COMPENSATION

EXCIMER LASER

• Fig. 13.28

  The acquisition of limbus and pupillometry data can be transferred to the excimer laser to optimize the centration and the compensation of cyclotorsion for astigmatic corrections.

Owing to the desirable oval shape of the ablation in the presence of astigmatism to correct for, the hinge of the flap should be located perpendicular to the shorter diameter of the ablation zone, that is, the steeper meridian, to optimize the spatial concordance between the laser delivery area and the exposed stromal bed. Some FS laser platforms, such as the FS200 (Alcon Wavelight), enable the rotation of the hinge over 360 degrees and the design elliptical flaps (Fig. 13.28).

Topography-Guided Ablations Rationale for Topography-Guided Ablations With LASIK All excimer lasers, although using different algorithms, perform identical ablations in all patients with the same refractive error and OZ. The air/tear film interface contributes to 70% of the refractive power of the eye, and even minor variation in the eye’s shape can produce significant visual deficit.131 Thus the corneal surface of some patients exhibits certain irregularities that may limit visual performance. Theoretically, performing a corrective ablation based on actual elevation maps of the corneal surface may be an appropriate method in patients presenting with significant amounts of corneal irregular astigmatism. Because the ablation must take into account the patient’s true corneal shape and not a mathematical fit of it, each topography-guided excimer platform possesses software that couples the corneal elevation mapping system with a scanning or flying-spot excimer laser. The volume of the ablation is determined from the intersection of a threedimensional shape of the cornea and the best aspheric

• Fig. 13.29  Schematic representation of a decentered myopic ablation. The area of the decentered ablation is outlined in pink. The arrow shows the direction of the decentration.

surface of refraction, that is, the surface with an optical power that both restores emmetropia and cancels the optical aberrations of corneal origin (Figs. 13.29 to 13.33). This surface can correspond to an aconic surface, the apical toricity and asphericity of which are calculated from the values of the patient’s refractive astigmatic error and spherical aberration, respectively. In the presence of an astigmatic error to cancel, the corneal preoperative toricity must be decreased by adequate steepening of the initially flatter meridians. An elegant method to assess and quantify the irregular component of the corneal surface is to perform a decomposition of the corneal data in Zernike terms. The irregularity will then correspond to the odd terms with a radial order superior or equal to 3.132 Hence, theoretically and regardless of

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

• Fig. 13.30  Based on the patient’s refraction, an ideal theoretical corneal surface is generated whose optical properties aim at restoring emmetropia for all corneal meridians within the planned optical zone (OZ).

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•

Fig. 13.33  The ablated lenticule corresponds to the amount of corneal tissue located above the level of the aconic surface in a perimeter encompassing the optical zone (OZ).

the method used to establish the topography-guided ablation pattern, the postoperative computed corneal surface exhibits twofold symmetry (i.e., it has no odd asymmetry) and could be reconstructed by using even-order terms only within the OZ. Topography-guided (TOPOLINK) excimer laser surgery is discussed in Chapter 14. An example of using TOPOLINK to manage LASIK decentration is shown in Figs. 13.34 to 13.38.

Q-Based and Wavefront-Guided Ablations

• Fig. 13.31  Topography-guided ablation of a myopic patient with significant amounts of corneal irregularities on the anterior corneal surface (elevation map, inset).

• Fig. 13.32

  An ideal aconic corneal surface is generated and adjusted over an optical zone (OZ) centered on the corneal apex. The dimensions of the OZ must take into account the depth of ablation.

Surgically induced corneal aberrations have been cited as a contributory factor in reduced contrast sensitivity and complaints of glare, halos, and disturbance of night vision.133 Another legitimate goal of custom ablation is to maintain the high-order aberrations at a physiologic level while neutralizing the spherocylindrical error. Improvement in profiles of ablation have been made from the average response of large groups of operated eyes, and “wavefront optimized” profiles of ablation have been developed to reach that goal. They should not be confused with true customized ablations, which take into consideration the specific corneal asphericity and/or aberration profile of the operated eye. In cases in which the ocular aberration originates predominantly from the corneal surface, Placido-based or direct elevation slitscanning topography may allow mapping of the aberrations with higher accuracy and resolution than wavefront sensors. However, corneal topography can measure only the aberration of the corneal surface and therefore cannot measure or allow the treatment of total ocular aberrations. The latter can be achieved by the use of wavefront measurements.

Rationale for Q-Based and Wavefront-Guided Ablation With LASIK Q-Based Ablations The design of Q-based ablations derives from the consideration that the corneal profile is aspheric and can be

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• Fig. 13.35  Topography-guided retreatment was planned with the NIDEK EC 5000 excimer laser platform. Corneal and refractive data were exported in the laser CATz software. Optical and transition zone dimensions were adjusted by the surgeon.

• Fig. 13.34

  Optical path difference (OPD) scan map of a 28-year-old male referred for post–laser in situ keratomileusis (LASIK) decentration. Bilateral LASIK was performed 3 months before using hansatome (8.5 ring, 160 head) for a myopic error of −3.50 D right eye (RE) and left eye (LE). Immediately following the procedure, the patient reported severe halos and glare with the LE. Uncorrected visual acuity had increased to 20/25; best corrected visual acuity: (−1.50 × 160°): 20/25. The instantaneous map reveals a slight temporal superior decentration. The wavefront error owing to high-order aberration is very large (root mean square [RMS] = 3.818  µm for a 6-mm pupil; see histogram bars).

eyes, regardless of their preoperative refraction. This slight prolateness leaves the eye with a slightly positive spherical aberration. The cornea should be more prolate to correct the spherical aberration of the eye completely. After noncustomized myopic and hyperopic laser refractive surgery, there are important variations in corneal asphericity, which contributes to inducing uncontrolled amounts of positive (myopic corrections) or negative (hyperopic corrections) spherical aberration. Custom-Q ablations take into account the corneal asphericity of the preoperative surface and a “target” asphericity, which is usually intended to maintain the corneal prolateness.134,135 This mode can also be used to conceive “multifocal” ablation patterns for the correction of presbyopia (see Chapter 37)

Wavefront-Guided Ablations mathematically approximated by a portion of an ellipse (Fig. 13.39). Two useful parameters are the apical radius of the ellipse and its eccentricity. The profile of a cornea median can be mathematically defined in Cartesian terms by a second-order equation, where the apical radius is R and the asphericity is Q. The apical radius is that of the circle tangent to the apex of the ellipse and relates to the paraxial optical power of the corneal surface. Q describes the variation of the local radius of curvature with distance from the corneal apex. The human cornea is slightly aspherical prolate (flattening to the edges), and the value of Q is generally slightly negative, close to −0.2. This flattening tends to reduce the optical power of the cornea in its periphery, but it does not cancel the physiologic corneal spherical aberration, which is slightly positive in human

If we ignore the effect of pupil diffraction and adopt a geometrical optic standpoint, a “perfect eye” free of optical aberrations can focus all the light rays emitted by a monochromatic point source located at infinity on the fovea. This perfect eye would remain aberration free, even when the pupil is dilated, so that all the light rays emanating from a point distance source would focus onto the fovea. The translation of this concept in wavefront optics necessitates representing a point source as a source emitting spherical wavefronts; the portion that enters the eye’s entrance pupil can be considered as planar owing to the distance with the eye. To focus on the fovea without phase shift, the envelope of the refracted wavefront must be spherical and centered on the fovea. In a myopic eye, the wavefront will converge in front of the fovea; in a hyperopic eye, the wavefront will converge behind the fovea.

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• Fig. 13.36

  Simulation of the CATz ablation. (Top) Representation of the initial and “simulated” (targeted) corneal topography (refractive power map). (Bottom) Total ablation, which can be decomposed between sphere, cylindrical, and irregular ablation.

However, any so-called emmetropic eye (without spherical and cylindrical refractive error) always exhibits a variable amount of “higher-order” aberrations. Even if the refracted wavefront shape is close to that of a sphere, it locally diverges from the perfect spherical shape. Wavefront analyzers can be used to detect, identify, and classify these optical aberrations; identification and quantification of high-order optical aberrations is a required preliminary step before their treatment. Different solutions can then be considered to cancel the wavefront distortion: • Interposition on the optical path of an adequate device (deformable mirror, contact lens) that will selectively delay the most advanced portion of the wavefront to restore its spherical shape. • To selectively reduce the thickness of the considered optical media proportional to the measured wavefront delay. This latter approach corresponds to the principle of excimer laser photoablation. The corneal thickness is reduced to cancel phase retardation (the wavefront is “accelerated” in the air, replacing the corneal photoablated tissue44,136; Figs. 13.40 and 13.41). Removing 1 µm of corneal tissue causes a wavefront acceleration (reduction of the retardation) equal to the difference between the values of the refractive indexes of stromal tissue and air (this optical path difference relates to the difference of propagation speed of the light in air and cornea) approximately. The wavefront deviation profile is thus translated onto the corneal surface by etching an appropriate lens of corneal tissue (Figs. 13.42 and 13.43). • Fig. 13.37

One-month postoperative map depicting the enlargement of the optical zone on the instantaneous map. The wavefront error owing to high-order aberrations has significantly reduced to 0.568 for a 6-mm pupil. Uncorrected visual acuity is 20/20.  

Characteristics of Custom-Q Profile of Ablation The variations of asphericity imply a slight modification of the depth of ablation along the treated meridians. For myopic corrections, targeting a more negative asphericity

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• Fig. 13.38

  Difference map (Orbscan, Bausch & Lomb) in axial mode, before and after flap lifting and delivery of the topography-guided ablation profile, showing the area of accentuated inferonasal flattening.

• Fig. 13.39

  (Top left) Schematic depiction of a circular flap whose diameter is slightly inferior to the diameter of the ablation zone along the flattest axis (simple myopic astigmatism). While there is a large crescent of unablated stromal zone along the steepest meridians, the corneal epithelium can be exposed to laser spots along the flattest meridians. (Top right) The creation of an elliptical flap results in a better congruence between the exposed stromal zone and the astigmatic profile of ablation. (Bottom left) Juxtaposition of the profile of ablation to correct for mixed astigmatism and the contour of a LASIK elliptical flap. (Bottom right) Snapshot taken during photoablation: all excimer spots are directed onto the corneal stroma.

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

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Propagation +

Aberration

–

Pupil

• Fig. 13.40  The wave aberration root mean square coefficient is defined by the square root of the sum of the squared residuals from the reference pupil plane. • Fig. 13.43  Pictorial three-dimensional representation of the correspondence between the wavefront and the profile of ablation characteristics. The profile of ablation mirrors the shape of the wavefront: the ablation is null with regard to the most advanced point of the wavefront and of maximal depth with regard to the most retarded points.

Most advanced point +

– Most retarded point Pupil

• Fig. 13.41

The profile of ablation aimed at canceling the aberration is defined from the most advanced point plane. It is directly related to the “peak-to-valley” wavefront value.  

Ablation 1

2

3

4

5

Characteristics of Wavefront-Guided Profile of Ablation

Retardation 6

7

n=2

1

n=1

2

3

4

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6

correct for hyperopia and presbyopia via an increase in corneal multifocality, it may be indicated to target a more negative Q-value to induce an increased amount of negative spherical aberration.137 This strategy allows reduction of the amount of paraxial myopic error (necessary to provide the operated eye with satisfactory levels of uncorrected near acuity) toward the periphery in order to improve uncorrected distance acuity.

7

• Fig. 13.42  Canceling the wavefront retardation. In this pictorial representation, the refractive index of the represented transparent media is 2. The wavelength of the propagating wavefront is 1 µm. The wavefront retardation is one wavelength in air (top). One µm of ablation results in an optical path difference of 2 − 1 = 1 µm. In this example, the depth of ablation equals the retardation. It allows the wavefront to exit the material sooner and speed up in air.

(increased prolateness) results in an increase in the maximal depth of ablation.10 For hyperopic corrections, targeting a more negative asphericity results in a decrease in the maximal depth of ablation (which is attained at the junction between the optical and transition zones). In strategies employed to

The aberrometric data are usually presented to the clinician via software that can display the total and high-order-only wavefront separately. The goal of a wavefront-customized profile of ablation is to cancel the phase differences within the wavefront. In other words, corneal ablation must be performed to equalize the optical path of all rays entering the entrance pupil from the object of focus to the fovea. Because photoablation is a subtraction process, it can bring phase modulation only via exerting modulated acceleration of the retarded waves (selective shortening of the corneal optical path). This strategy considers the refractive index of the cornea. The theoretical thickness of corneal tissue to be removed is equal to the product between the length of the optical path difference and the refractive index of the stroma. Additional factors—such as corneal curvature, biomechanics, and adequate OZ blending—must be taken into account to optimize the profile of ablation characteristics. Performing wavefront-guided ablations supposes technical requirements that will be addressed separately in this chapter: • adequate wavefront sampling and reconstruction, • perfect alignment of the treatment and the entrance pupil on which the wavefront is measured, • efficient eye tracking,

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• small-size laser spot (less than 1 mm),138 • adequate residual thickness of the posterior stromal bed in LASIK when the treatment is delivered on a large OZ aimed at matching the pupil size.

devices incorporate some quality indexes to determine the eligibility of a given wavefront acquisition to be transferred into a corneal ablation pattern. Good calibration of these devices is mandatory prior to clinical measurements. Wavefront maps are defined with respect to the line of sight, which corresponds to the line joining the center of the entrance pupil to the object of interest. The head and eye position and centration during wavefront acquisition must be adequate to avoid the artificial induction of compensation wavefront errors, such as tilt and coma. A customized laser vision correction requires a large ablation profile in excess to the scotopic pupil. It is preferable to collect the ocular wavefront through a naturally dilated pupil, as subtle variations in the wavefront pattern have been demonstrated with the use of pharmaceutical agents. It has been reported that cyclopentolate eyedrop wavefront analysis results in a considerable difference in the preoperative refractive error compared to the standard subjective refraction, whereas regarding the average differences in refraction, the aberrometry measurements after NeoSynephrine (phenylephrine hydrochloride)-induced dilation of the pupil usually resemble the subjective refractive error.139 The tear film quality can influence the wavefront error and patients with dry eye can exhibit nonreliable wavefront measurements. Hydration with artificial tears may allow better detection of the single spots imaged during

Prerequisites for Successful Q-Based and Wavefront-Guided Ablations To achieve superior clinical outcomes with customized ablations, that is, controlling or reducing low-order and highorder optical aberrations, many points must be respected. Q-Based Ablations

The corneal asphericity must be measured preoperatively. Corneal topographs provide the user with values of the central keratometry and asphericity of the principal hemimeridians (Fig. 13.44). The acquisition of reliable topography data must be performed and communicated to the programming software of the excimer laser. This usually requires obtaining multiple exams before averaging them. This information can be coupled with pupil, vertex, and iris feature data to enable the deliverance of a customcentered and cyclotorsion-compensated aspheric profile of ablation. Wavefront-Guided Ablations

The acquisition and measurement of the wavefront are crucial preliminary steps. Most wavefront measurement

y

ASPHERIC PHOTOABLATION Q2 Q1 R1

R2

Optical zone X

CUSTOM-Q ablation parameters: y2 = 2R1x − (1+Q1)x2

y2 = 2R2x − (1 + Q2)x2

PREOP SURFACE

POSTOP SURFACE

D = (n − 1).

1 1 R2 R1

R2 > R1

Refractiva 2005

• Fig. 13.44

  Aspheric photoablations aim at controlling the variation in the corneal asphericity. The profile of ablation is constructed from the difference between two aspheric surfaces (represented as ellipses in cross-section, with their equations expressed in a Cartesian domain). The difference between their respective apical radii of curvature is governed by the intended correction (D). The target asphericity value (Q2) can be selected by the surgeon.

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

Tscherning or Hartmann–Schack aberrometry, but could also alter the wavefront measurement accuracy by randomly modifying the tear–film interface geometry. Quality of Wavefront Reconstruction

Due to the wavefront acquisition process (focusing of wavefront portion with lenselets on a charged coupled device [CCD] camera), the first derivative of the wavefront (slope) is determined at the specific location of the pupil. The number of sample points is important for performing an accurate wavefront sensing. Similarly, the type and quality of subsequent mathematical fitting functions used to reconstruct the wavefront envelope (e.g., number of Zernike polynomials) is mandatory to reduce significant underestimation or overestimation of wavefront errors. In general, a sixth-order Zernike polynomial wavefront reconstruction is sufficient. Quality of Ablation Profile Calculation

The wavefront map must be transferred into geometrical shape information. This is performed by considering the wavefront as the optical path difference in the eye that is the product of the physical distance (local deviation from the wavefront to its most advanced point) times the refractive index difference from the air to the corneal stroma. The peak-to-valley value of the wavefront envelope will thus be more directly related to the maximal depth of ablation than the total wavefront root mean square (RMS) error value. The ablation profile design should also take into account the changes in angle of light incidence when moving the laser beam from the corneal central area toward the limbus. Adequate transition zone design will also allow blending of the abrupt edges owing to particular ablation and preventing excessive wound-healing reactions. Theoretical calculation shows that corneal topography information specifying corneal shape has very little effect on the desired ablation depth for an optimal refraction.140

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eye movements or incomplete compensation from the eye-tracking system. The software of the custom laser platform already has the appropriate algorithm in place to allow the surgeon merely to download the wavefront information rather than develop a nomogram based on refraction data. Subtle adjustments, such as sphere magnitude or ablation zone dimensions, can be implemented depending on the surgeon factor and environmental conditions. Quality in Minimizing Excessive Unexpected Corneal Response in Custom Q and Wavefront-Guided Corrections

Controlling and anticipating the unexpected corneal wavefront change from the custom LASIK procedure is a challenging but crucial task. Variables other than the threedimensional wavefront map, such as corneal curvature and biomechanics, must be taken into account in the conversion process from the wavefront to the ablation profile.142–144 Some high-order aberrations, such as coma and trefoil, have been shown to be induced by the cut of the flap in LASIK procedures with different microkeratomes.145,146 This may reflect the effect of the hinge, which may cause an asymmetry in the corneal biomechanical response (Fig. 13.45). However, compensation of the effect of the flap may be challenging, because it might be practically impossible to assess a specific mean response for mechanical flapinduced aberrations given the large variability in response from eye to eye. The FS laser keratomes have allowed better prediction of the mechanical changes within the cornea by enabling more predictable flap architecture.147 The incorporation of asphericity and high-order aberrations in the establishment of the profile of ablation results in an increase in ablation depth.10,45,148,149 Increased ablation may increase the biomechanical response of the cornea and reduce the predictability of the method.144,150 In LASIK, the

Quality of Ablation Profile Delivery

Perfect matching between the wavefront acquisition and ablation center location is required to avoid undercorrection in higher-order aberrations. Ideally, wavefront data must be centered or located with respect to a fixed ocular structure to avoid significant decentration between wavefront capture and laser delivery. The center of the iris pupil does not satisfy this condition because it has been shown to shift with pupil diameter variations.141 Some platforms use limbal recognition software to overcome this problem. Cyclorotation prevention and perfect alignment are also mandatory. The use of iris feature detection or detection of marks recorded during the wavefront capture may allow achievement of registration dynamically. On an immobile eye, a small spot is required to correct for high Zernike modes. The overlapping of a finite number of laser spots with a Gaussianlike profile allows performance of the desired correction without increasing surface roughness. The smaller the spot, the more sensitive it will be to displacements owing to

• Fig. 13.45

  High-order aberration has been shown to be induced by the cut of a hinged flap. The resulting biomechanical response may not be exerted evenly on the whole corneal circumference, leading to the induction of asymmetric corneal changes and subsequent highorder aberration.

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corneal epithelium is disrupted only at the area of the microkeratome cut to create the flap, and the overproliferation of epithelial cells is less likely to be observed in LASIK than in PRK. However, wound-healing alterations, such as epithelial hyperplasia or stromal remodeling, may mask subtle features incorporated in the ablation profile.151–154 For example, epithelial and/or stromal thinning could induce a modification of the local or general features of the postoperative corneal contour, such as corneal asphericity. Despite the relatively small degree of scarring and epithelial hyperplasia after LASIK, the structural and biomechanical changes induced by the flap cut may also mitigate the benefits of customized ablation. Adequate tapering of the ablation may also help to reduce wound healing intensity. With all other parameters being equal (magnitude of correction of spherocylindrical error, optical and transition zone dimensions), wavefront customization of the ablation profile logically increases the treatment depth of ablation, because additional corneal tissue must be photoablated to compensate for the wavefront distortions owing to the highorder aberrations and maintain a prolate corneal contour. Aiming at compensating for positive spherical aberration will increase the maximal ablation depth of customized myopic treatments.149 Increasing the OZ will also increase the depth of ablation in an exponential fashion proportional to the radial order of the low-order and high-order aberrations. Excessive depth of ablation may alter the biomechanical properties of the cornea. In addition to the risk of ectasia, corneal weakening may result in unexpected corneal morphologic changes. As well as the increase in the depth of ablation, controlling the volume of corneal tissue to be photoablated may be an important issue. We have shown that the volume of corneal ablation is proportional to the fourth power of the OZ diameter for conventional spherical corrections.32 Increasing the OZ diameter from 6 mm to 7 mm would then result in doubling the total volume of ablation for conventional corrections. This increase might be even bigger for ablation, including high-order corrections, and trigger important wound healing and biomechanical responses. Thus detailed characterization of the wound-healing cascade that occurs following refractive procedures is fundamental to developing pharmacologic and molecular strategies for controlling or normalizing the response to surgery.155

Results of Q-Based and Wavefront-Guided Lasik Procedures Corneal asphericity has been shown to be impaired by the custom-Q treatment up to −5 D of myopia.156 Custom-Q ablation resulted in a mean postoperative asphericity that was closer to the preoperative one than in nonaspheric customized ablations.135 In addition to less impairment in the corneal asphericity in the custom-Q group, a marginally significant change in BSCVA was reported in a comparative study with wavefront optimized ablation.134 With the use of wavefront sensors, the increase of higherorder aberrations of the eye after conventional PRK and

LASIK has been confirmed.157–160 This increase in higherorder optical aberrations was greater in LASIK compared with PRK. Therefore wavefront-guided ablation that can correct irregular astigmatism or reduce surgically induced aberrations might be an improvement over current LASIK procedures.161,162 The basic concept of wavefront-guided LASIK includes measurement of the wavefront aberrations before creating a flap and mathematical transfer of the measured wavefront aberrations into an ablation pattern under the flap. Seiler and associates163,164 reported the first application of wavefront-guided LASIK using the Wavelight Allegretto excimer laser (WaveLight Laser Technology). Their early results and those of other groups were encouraging but far from optimal, because they were not very predictable in reducing higher-order optical aberrations. In fact, on average, the optical aberrations were increased.149,163–167 The first studies performed to evaluate wavefront-guided LASIK did not result in the removal of high-order aberrations, on average, but reduced the increase in high-order aberrations.166,168,169 In particular, in patients with large amounts of high-order aberrations preoperatively, wavefrontguided LASIK may substantially reduce the increment of high-order aberration compared to conventional ablation.168,170 Both wavefront-guided and wavefront-optimized LASIK have shown excellent efficacy, safety, and predictability. However, wavefront-guided technology may be a more appropriate choice for patients who have preoperative RMS higher-order aberrations (> 0.3 µm).171 From this perspective, using wavefront-guided ablation for retreatments may be an effective method to correct residual refractive error and higher-order aberrations after primary LASIK.172,173 Wavefront-guided LASIK retreatment in postLASIK eyes is a good option for laser vision correction: in such circumstances, operated eyes can show a reduction in preexisting total aberrations.174 However, the correction of high amounts of high-order aberrations requires a lot of tissue removal. Because these treatments have to be delivered on already thinned corneas, it might be difficult to use a large OZ to avoid excessive depth of ablation. Careful calculation of residual bed thickness is mandatory to avoid late keratectasia.172 A clinical example of wavefrontcustomized guided ablation is shown in Figs. 13.46 to 13.49. Wavefront-guided and aspheric ablation profile have been combined and compared with an aspheric ablation profile alone to correct myopia in patients with a low preoperative total higher-order aberration root mean square (HOA RMS). Wavefront-guided LASIK with aspheric ablation profile was associated with better limitation of HOAs and faster recovery of mesopic contrast sensitivity for these patients.175 More recently, the results of wavefront guided LASIK have improved, enabling the reduction of the total RMS of HOA and the level of primary spherical aberration176 and clinically translating into an improvement of vision quality over spectacles and low scores for night-vision phenomena.177

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

• Fig. 13.46  Wavefront error map of the right eye for a 6-mm, naturally dilated pupil of a 34-year-old woman before laser in situ keratomileusis (Wavefront, Customview, VISX). Preoperative subjective refraction was −4 D. Global high-order aberration root mean square error is 0.46 µm.

• Fig. 13.47  The customized ablation profile is established from the wavefront characteristics. The Waveprint software package allows the surgeon to adjust the cylinder and axis values and the optical zone and total ablation zone dimensions. The ablation profile is delivered through a patented Variable Spot Scanning (VSS) sequence.

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• Fig. 13.48

  Postoperative wavefront error map for a 6-mm pupil. The total and high-order-only wavefront are practically identical. This reflects the elimination of low-order (sphere and cylinder). The high-order root mean square has reduced from its preoperative value (0.26 µm). The postoperative uncorrected visual acuity was 20/15.

• Fig. 13.49

  Point spread function (PSF) diagram variation from preoperative (left column) to postoperative (right column). Note the reduction of the width of the high-order-aberration-only PSF (bottom right).

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

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Ablation: The Quest for Supervision. Thorofare, NJ: Slack; 2001: 51–56. 137. Gatinel D, Azar DT, Dumas L, Malet J. Effect of anterior corneal surface asphericity modification on fourth-order Zernike spherical aberrations. J Refract Surg. 2014;30(10):708–715. 138. Huang D, Arif M. Spot size and quality of scanning laser correction of higher-order wavefront aberrations. J Cataract Refract Surg. 2002;28:407–416. 139. Giessler S, Hammer T, Duncker GI. Aberrometry due dilated pupils—which mydriatic should be used? Klin Monatsbl Augenheilkd. 2002;219:655–659. 140. Klein SA. Optimal corneal ablation for eyes with arbitrary Hartmann–Shack aberrations. J Opt Soc Am A. 1998;15: 2580–2588. 141. Mabed IS, Saad A, Guilbert E, Gatinel D. Measurement of pupil center shift in refractive surgery candidates with Caucasian eyes using infrared pupillometry. J Refract Surg. 2014;30(10):694–700. 142. Krueger RR. Technology requirements for customized corneal ablation. In: MacRae SM, Krueger RR, Applegate RA, eds. Customized Corneal Ablation: The Quest for Super Vision. Thorofare, NJ: Slack; 2001:133–147. 143. Mrochen M, Seiler T. Influence of corneal curvature on calculation of ablation patterns used in photorefractive laser surgery. J Refract Surg. 2001;17:S584–S587. 144. Dupps WJ Jr, Roberts C. Effect of acute biomechanical changes on corneal curvature after photokeratectomy. J Refract Surg. 2001;17:658–669. 145. Pallikaris IG, Kymionis GD, Panagopoulou SI, et al. Induced optical aberrations following formation of a laser in situ keratomileusis flap. J Cataract Refract Surg. 2002;28:1737–1741. 146. Porter J, MacRae S, Yoon G, et al. Separate effects of the microkeratome incision and laser ablation on the eye’s wave aberration. Am J Ophthalmol. 2003;136:327–337. 147. Krueger RR, Dupps WJ Jr. Biomechanical effects of femtosecond and microkeratome-based flap creation: prospective contralateral examination of two patients. J Refract Surg. 2007;23(8): 800–807. 148. Mrochen M, Donitzky C, Wüllner C, et al. Wavefrontoptimized ablation profiles: theoretical background. J Cataract Refract Surg. 2004;30:775–785. 149. Waheed S, Krueger RR. Update on customized excimer ablations: recent developments reported in 2002. Curr Opin Ophthalmol. 2003;14:198–202. 150. Roberts C. Biomechanics of the cornea and wavefront-guided laser refractive surgery. J Refract Surg. 2002;18:S589–S592. 151. Reinstein DZ, Srivannaboon S, Silverman RH, et al. The accuracy of routine LASIK: isolation of biomechanical and epithelial factors. Invest Ophthalmol Vis Sci. 2000;2000:S318. 152. Reinstein DZ, Srivannaboon S, Silverman RH, et al. Limits of wavefront-guided customized ablation: biomechanical and epithelial factors. Invest Ophthalmol Vis Sci. 2002;43:E-Abstract 3942. 153. Javier ADJ, Charukamnoetkanok P, Azar DT. Wound healing in customized corneal ablation: effect on predictability, fidelity, and stability of refractive outcomes. In: MacRae SM, Krueger RR, Applegate RA, eds. Wavefront Customized Visual Correction: The Quest for Super Vision II. Thorofare, NJ: Slack; 2001: 203–213. 154. Ivarsen A, Fledelius W, Hjortdal JØ. Three-year changes in epithelial and stromal thickness after PRK or LASIK for high myopia. Invest Ophthalmol Vis Sci. 2009;50(5):2061–2066.

CHAPTER 13  LASIK, Q-Based, and Wavefront-Guided LASIK for Myopia, Hyperopia, and Astigmatism

155. Netto MV, Wilson SE. Corneal wound healing relevance to wavefront guided laser treatments. Ophthalmol Clin North Am. 2004;17:225–231. 156. Koller T, Iseli HP, Hafezi F, Mrochen M, Seiler T. Q-factor customized ablation profile for the correction of myopic astigmatism. J Cataract Refract Surg. 2006;32(4):584–589. 157. Martinez CE, Applegate RA, Klyce SD, et al. Effects of pupillary dilation on corneal optical aberrations after photorefractive keratectomy. Arch Ophthalmol. 1998;116:1053–1062. 158. Oliver KM, Hemenger RP, Corbett MC, et al. Corneal optical aberrations induced by photorefractive keratectomy. J Refract Surg. 1997;13:246–254. 159. Oshika T, Klyce SD, Applegate RA, et  al. Comparison of corneal wavefront aberrations after photorefractive keratectomy and laser in situ keratomileusis. Am J Ophthalmol. 1999;127:1–7. 160. Moreno-Barriuso E, Merayo Lloves J, Marcos S, et al. Ocular aberrations before and after myopic corneal refractive surgery: LASIK induced changes measured with laser ray tracing. Invest Ophthalmol Vis Sci. 2001;42:1396–1403. 161. Thibos LN. The prospects for perfect vision. J Refract Surg. 2000;16:S540–S546. 162. Williams D, Yoon GY, Porter J, et al. Visual benefit of correcting higher order aberrations of the eye. J Refract Surg. 2000;16:S554–S559. 163. Mrochen M, Kaemmerer M, Seiler T. Wavefront-guided laser in situ keratomileusis: early results in three eyes. J Refract Surg. 2000;16:116–121. 164. Seiler T, Mrochen M, Kaemmerer M. Operative correction of ocular aberrations to improve visual acuity. J Refract Surg. 2000;16:S619–S622. 165. Mrochen M, Kaemmerer M, Seiler T. Clinical results of wavefront-guided laser in situ keratomileusis 3 months after surgery. J Cataract Refract Surg. 2001;27:201–207. 166. Panagopoulou SI, Pallikaris IG. Wavefront customized ablations with the WASCA Asclepion workstation. J Refract Surg. 2001;17:S608–S612. 167. Kohnen T, Buhren J, Kuhne C, et al. Wavefront-guided LASIK with the Zyoptix 3.1 system for the correction of myopia and compound myopic astigmatism with 1-year follow-up: clinical

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outcome and change in higher order aberrations. Ophthalmology. 2004;111:2175–2185. 168. Kim TI, Yang SJ, Tchah H. Bilateral comparison of wavefrontguided versus conventional laser in situ keratomileusis with Bausch and Lomb Zyoptix. J Refract Surg. 2004;20:432–438. 169. Scerrati E, Gualdi M, Gualdi L. Correction of myopia and myopic astigmatism with customized ablation using the Nidek NAVEX system. J Refract Surg. 2004;20:S676–S677. 170. MacRae SM, Slade S, Durrie DS, et al. Customized ablation using the Bausch and Lomb Zyoptix system. In: Krueger RR, Applegate RA, MacRae SM, eds. Wavefront Customized Visual Corrections: The Quest for Super Vision II. Thorofare, NJ: Slack; 2004:243–245. 171. Feng Y, Yu J, Wang Q. Meta-analysis of wavefront-guided vs. wavefront-optimized LASIK for myopia. Optom Vis Sci. 2011; 88(12):1463–1469. 172. Castanera J, Serra A, Rios C. Wavefront-guided ablation with Bausch and Lomb Zyoptix for retreatments after laser in situ keratomileusis for myopia. J Refract Surg. 2004;20:439–443. 173. Chalita MR, Roth AS, Krueger RR. Wavefront-guided surface ablation with prophylactic use of mitomycin C after a buttonhole laser in situ keratomileusis flap. J Refract Surg. 2004;20: 176–181. 174. Chalita MR, Xu M, Krueger RR. Alcon CustomCornea wavefront-guided retreatments after laser in situ keratomileusis. J Refract Surg. 2004;20(5):S624–S630. 175. Wu J, Zhong X, Yang B, Wang Z, Yu K. Combined wavefrontguided laser in situ keratomileusis and aspheric ablation profile with iris registration to correct myopia. J Cataract Refract Surg. 2013;39(7):1059–1065. 176. Moussa S, Dexl AK, Krall EM, Arlt EM, Grabner G, Ruckhofer J. Visual, aberrometric, photic phenomena, and patient satisfaction after myopic wavefront-guided LASIK using a high-resolution aberrometer. Clin Ophthalmol. 2016;10: 2489–2496. 177. Schallhorn SC, Venter JA, Hannan SJ, Hettinger KA. Outcomes of wavefront-guided laser in situ keratomileusis using a new-generation Hartmann-Shack aberrometer in patients with high myopia. J Cataract Refract Surg. 2015;41(9):1810–1819.

14 

LASIK and TopoLink for Irregular Astigmatism MICHAEL C. KNORZ

Introduction Decentration of the ablation and other factors have contributed to inducing irregular astigmatism in a certain number of eyes treated with laser refractive surgery.1 Topographyguided ablations present a surgical tool to correct theses errors.2,3 In this chapter, the technique of TopoLink laser in situ keratomileusis (LASIK), based on corneal topography, will be described and illustrated by some examples.

The Technique of TopoLink The TopoLink procedure used the Technolas 217z excimer laser (Bausch & Lomb). Laser ablation was based on the preoperative corneal topographic map obtained with the Orbscan II corneal analysis system (Bausch & Lomb). Three different maps were taken and the one featuring the least eye movement was used. Once the topography was taken, data were copied and the ablation profile was calculated using a special software called TopoLink (Version 2.9992TL; Bausch & Lomb Technolas). Input values were manifest refraction in minus-cylinder format and corneal thickness as measured by the Orbscan II. The target K value was determined by the software by subtracting the manifest sphere from the K value in the steep corneal meridian. The target K value and a preset shape factor of −0.25 defined the target asphere that we planned to achieve after LASIK. The TopoLink software basically compares the shape of the target asphere to the corneal shape actually measured. Simplified, the target shape is fitted from beneath to the actual cornea for a given planned optical zone size. The difference between the two shapes is then ablated. Any overlap between target and actual shape must thus be outside the planned optical zone, as tissue cannot be added but rather only ablated. The TopoLink software therefore represents a new and different approach, which is not based on Munnerlyn’s formula. Rather, it calculates a certain “lenticule” of corneal tissue to be removed; the scanning laser used provides the means to remove this tissue even if its shape is asymmetric 216

or even irregular. The diameter of the planned optical zone was 6 to 7 mm. Only in those cases in which the ablation required to achieve these optical zones would have left a residual corneal stromal bed of less than 250 µm was the diameter of the planned optical zone decreased to maintain a residual stromal bed of at least 250 µm. Based on these data, TopoLink calculated a session file that basically contained information for the scanning laser regarding which ablation pattern to perform. The session file was transferred via disc and loaded into the Technolas 217z excimer laser (Bausch & Lomb) just prior to treatment.

Examples of Topolink (Videos 1 to 3) Patient 1: Irregular Astigmatism After Penetrating Keratoplasty and Astigmatic Keratotomy This patient had a penetrating corneal graft because of recurrent stromal herpetic keratitis in 1992. He was first referred in 1993. Manifest refraction was +0.25 sphere −6 cylinder axis 135°. Corneal astigmatism was −8 diopters (D) axis 135° and slightly asymmetric. Initially, astigmatic keratotomy (AK) was performed in 1994. After AK, manifest refraction was −2.5 sphere −4 cylinder axis 165°. Uncorrected visual acuity (UCVA) was 20/400 and best corrected visual acuity (BCVA) was 20/60. Corneal topography showed marked irregularity and axis shift (Fig. 14.1, upper left). We therefore decided to perform TopoLink LASIK. Average refractive power of the cornea overlaying the entrance pupil was estimated to be 45 D. Spherical equivalent of manifest refraction was −4.5 D. We therefore selected a target K value of 40.5 D. A 5.4-mm optical zone was used, and ablation depth was 150 µm. Corneal thickness was 610 µm centrally and both the internal and external margins of the graft were well aligned with the host cornea. It is very important to check alignment prior to the lamellar cut. When alignment is poor or there is localized ectasia at the edge, corneal thickness might be reduced and the keratome cut may cause further

CHAPTER 14  LASIK and TopoLink for Irregular Astigmatism

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• Fig. 14.1  Preoperative and postoperative topographic maps and differential map of patient 1 (penetrating injury with irregular astigmatism).

• Fig. 14.2  Preoperative topographic maps and differential map of patient 2 (irregular astigmatism after penetrating keratoplasty and astigmatic keratotomy).

weakening of the cornea, inducing more ectasia, or even a penetration of the anterior chamber. In this patient, alignment was perfect and the LASIK procedure performed in July 1997 was uneventful. A 160-µm flap was used. One day after TopoLink LASIK, the UCVA had improved to 20/30, and BCVA was 20/25 (correction: +0.75 sphere). After 4 months, UCVA was 20/30 and BCVA 20/25, but manifest refraction had changed slightly to +1 sphere −2.0 cylinder axis 10°. Corneal topography 4 months after TopoLink LASIK showed marked improvement of the irregularity. Some residual withthe-rule astigmatism was still present, but the irregular astigmatism that was present preoperatively had virtually disappeared, as shown by the differential map (Fig. 14.2).

Patient 2: Irregular Astigmatism This patient had irregular astigmatism owing to a peripheral scar caused by a corneal ulcer in prolonged contact lens wear

in his right eye. The preoperative topographic map (see Fig. 14.2) shows marked asymmetry of the astigmatism. Refraction was −2.5 sphere −0.5 cylinder axis 5°. UCVA was 20/200, and spectacle-corrected visual acuity was 20/25. We performed a TopoLink LASIK. One month after surgery UCVA was 20/20 and refraction was plano. Corneal topography showed no irregularities (Fig. 14.3).

Patient 3: Decentered Ablation This 36-year-old woman had LASIK in both eyes in 1998 and was referred because of a decentered ablation. The right eye was perfect but the patient complained bitterly about permanent monocular diplopia and distorted halos in her left eye. A TopoLink LASIK was planned. The corneal topography taken prior to the TopoLink LASIK is shown in Fig. 14.4, lower left and Fig. 14.5, lower right. A decentered myopic ablation is visible. The ablation is decentered about

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• Fig. 14.3

  Postoperative topographic maps and differential map of patient 2 (irregular astigmatism after penetrating keratoplasty and astigmatic keratotomy).

• Fig. 14.4  Treatment plan in TopoLink LASIK. This plan is shown on the screen of the Keracor 217z excimer laser when the treatment is loaded. It features patient data (upper left), preoperative topography (lower left), the simulated ablation pattern (upper right), and the expected postoperative topography (lower right).

• Fig. 14.5  Orbscan II differential map after treatment. The preoperative map (lower right) shows a decentered ablation. The postoperative map (upper right) shows improved centration. The differential map is shown on the left.

CHAPTER 14  LASIK and TopoLink for Irregular Astigmatism

1.5 mm downwards and 1 mm temporally. We calculated a customized ablation based on the Orbscan II topographic map just described. The planned ablation pattern is shown in Fig. 14.4, upper right; the scale is in microns. The predicted outcome of corneal topography is shown in Fig. 14.4, lower right. The scale is in diopters again. The Hansatome (Bausch & Lomb) was used to create a new flap with a thickness of 160 µm and a diameter of 8.5 mm (8.5-mm suction ring). The ablation was centered on the center of the entrance pupil, and the eye tracker was used. Fig. 14.5 shows the preoperative and postoperative maps as well as the differential map, taken 1 day after surgery. The postoperative map (see Fig. 14.5, upper right) shows significantly improved centration and no residual astigmatism. The differential map (Fig. 14.5, left) shows the asymmetric ablation pattern, customized to this individual eye. Visual acuity improved to 20/25 uncorrected; even more important, monocular double vision and halos were no longer visible.

Results of TopoLink in Repair Procedures In our initial prospective study, we evaluated 29 eyes of 27 patients treated between July 1996 and July 1997.2,3 Inclusion criteria were irregular corneal astigmatism owing to trauma or previous corneal surgery. We considered TopoLink LASIK as their last option prior to performing a corneal graft. Eyes were divided into four groups: • Group 1 (postkeratoplasty group) consisted of six eyes (five patients) with irregular corneal astigmatism after penetrating keratoplasty. All grafts were performed more than 2 years ago. • Group 2 (posttrauma group) consisted of six eyes (six patients) with irregular corneal astigmatism after corneal trauma. The trauma dated back more than 2 years in all eyes. • Group 3 (decentered/small optical zones group) consisted of 11 eyes (10 patients) with irregular corneal

astigmatism after photorefractive keratectomy (PRK; one eye) or LASIK (10 eyes) owing to decentered or small optical zones. All patients complained about halos and image distortion even during the day. • Group 4 (central islands group) consisted of six eyes (six patients) with irregular astigmatism after PRK (two eyes) or LASIK (four eyes) owing to central islands or keyhole patterns. All patients complained about blurred vision or image distortion even during the day. The results of our initial study are shown in part in Table 14.1. In the post-keratoplasty group and in the posttrauma group, corrective cylinder was significantly reduced as compared to the preoperative value. The topographic success rate was defined as either the planned correction fully achieved or the attempted correction partially achieved (decrease of irregularity of more than 1 D on the differential map and/or increase of optical zone size by at least 1 mm). Success rate was highest in the decentered/small optical zones group, being 91%, followed by the posttrauma group with a success rate of 83%. The lowest success rate was observed in the central island group, being only 50%. Overall, 14 of the 29 eyes were reoperated on (48%) owing to regression of effect or undercorrection. The rate of reoperation was lowest in the decentered/small optical zones group, being 36% as compared with 50% in all other groups (see Table 14.1). These results demonstrate that topographically guided LASIK works. We were able to significantly reduce irregularities in these extremely irregular corneas. However, our results also demonstrated that most eyes were undercorrected. Thus we had to adjust the algorithm to take care of the undercorrection. This undercorrection is most likely due to the combined effects of the biomechanical response of the cornea to the ablation, which is not fully understood yet, and because of the wound healing. Finally, the problem of registration, that is, targeting the right spot on the cornea, must be addressed. The results of group 4 (central islands)

TABLE 14.1  Refraction, Visual Acuity, and Corneal Topography 12 Months After TopoLink LASIK

Group 1: Post-Keratoplasty

Group 2: Posttrauma

Group 3: Decentered/Small

Group 4: Central Islands

No. of eyes

n=6

n=6

n = 11

n=6

Cylinder preoperatively

5.83 ± 1.25 D (4.00–8.00 D)

2.21 ± 1.35 D (1.00–5.00 D)

0.73 ± 0.71 D (0–2.00 D)

1.42 ± 1.13D (0–3.50 D)

Cylinder at 12 months

2.96 ± 1.23 D* (1.50–4.50 D)

0.50 ± 0.84 D** (0–2.5 D)

0.36 ± 1.05D (0–3.5 D)

0.50 ± 0.84 D* (0–2.00 D)

Success rate (topography as planned or improved)

66% (n = 4)

83% (n = 5)

91% (n = 10)

50% (n = 3)

Reoperation rate

50% (n = 3)

50% (n = 3)

36% (n = 4)

50% (n = 3)

SCVA, Spectacle-corrected visual acuity; UCVA, uncorrected visual acuity. *P = .01 **P = .001.

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were poor, which suggests that we might not have hit the right target in these eyes, which featured small and circumscribed irregularities.

References 1. Knorz MC, Wiesinger B, Liermann A, et al. LASIK for moderate and high myopia and myopic astigmatism. Ophthalmology. 1998;105:932–940.

2. Wiesinger-Jendritza B, Knorz MC, Hugger P, Liermann A. Laser in situ keratomileusis assisted by corneal topography. J Cataract Refract Surg. 1998;24:166–174. 3. Knorz MC, Jendritza B. Topographically-guided LASIK to treat corneal irregularities. Ophthalmology. 2000;107:1138–1143.

15 

LASIK Complications and Their Management RAMON C. GHANEM, MARCIELLE A. GHANEM, AND DIMITRI T. AZAR

Introduction Laser in situ keratomileusis (LASIK) is the most common surgical method for the management of refractive errors. Flap creation is the first and most important step in the LASIK procedure. Two current techniques used to produce corneal flaps during LASIK surgery are the mechanical microkeratome and the femtosecond laser. Some of the intraoperative complications encountered during LASIK are similar between them, while others are technique specific. This chapter includes a review of the more common complications seen with both methods. The rates of flap-related intraoperative complications in most studies performed with trained LASIK surgeons are about 0.01% to 1%.1–4 An experienced surgeon using the latest technology of microkeratome and/or femtosecond laser may reach a very low incidence of flap-related complications. A comprehensive awareness of the potential complications of LASIK and the numerous strategies to handle them is fundamental for surgeons performing the procedure.

Intraoperative Complications Inadequate Exposure Microkeratome and femtosecond laser head placement is more difficult in sunken globes and in eyes with narrow palpebral fissures and small corneas.5 By turning the patient’s head slightly to the opposite side or exerting a gentle pull and tilt on the eye through the suction ring handle, these cases can usually be operated on easily. Alternatively, it may be possible to operate without using a speculum. If a speculum is not used, one must ensure that the eyelashes and the eyelids do not overlap and cover the ring. The patient with a prominent brow should be positioned with the chin raised slightly, as this will maximize exposure.1 When all these

measures are unsuccessful, conversion to photorefractive keratectomy (PRK) should be considered.

Suction Loss (Videos 4 to 6) Inadequate suction or total loss of suction is a potential source of serious problems during LASIK. Factors that may contribute to lacking or loss of suction include improper technique in applying the suction ring, conjunctival chemosis, flat corneas, narrow palpebral fissures, deep-set eyes, patient movement, eye rotation, and head tilt.6–10 Blockage of a microkeratome head progression by the eyelid speculum is also an important cause of suction loss (Fig. 15.1). Suction loss with mechanical microkeratomes may result in more severe flap complications than with a femtosecond laser. Small, incomplete, or torn flap may result. The management of these cases depends on the available stromal bed for ablation. Usually, however, it is safer to reposition the flap, wait 3 months, on average, and retreat the patient with surface PRK. Loss of vacuum by femtosecond laser is not as serious a problem as with the mechanical microkeratome.11 When using the femtosecond laser, the first sign of suction loss is often the appearance of a peripheral asymmetric and incomplete meniscus (Fig. 15.2). Once detected, it is important to discontinue the laser treatment immediately.6 Loss of suction with the femtosecond laser is resolved by replacing the suction ring and re-docking the same applanation cone to subsequently repeat the treatment at the same depth.7,8,12 The vertical limbal pocket, typically created to absorb cavitation bubbles, can be deactivated if it was already created in the first pass. If the loss of suction occurs during the side cut, the surgeon must ensure that the subsequent side cut is created within the lamellar cut used to fashion the flap by decreasing the subsequent side cut by 0.5 mm or more in diameter.6–8 Surface ablation with mitomycin C (MMC) can also be considered over the incomplete flap after repeated suction attempts prove unsuccessful. 221

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There are many precautions that should be taken in an attempt to decrease the risk of epithelial defects. The use of excessive topical medications, especially frequent anesthetics such as proparacaine, should be avoided before flap creation. Topical anesthetic placement should only occur immediately before initiating the procedure to decrease epithelial irregularity and toxicity.2 One study recommended using hyperosmotic agents preoperatively in order to reduce the risk for epithelial disruptions.14 In the event of detachment, the epithelium is repositioned if possible. A bandage contact lens is placed for 1 or 2 days or until the epithelium is completely healed (Fig. 15.3).15-18 Patients with a history of recurrent erosions19,20 and/or anterior basement membrane dystrophy (ABMD) are at higher risk of developing epithelial erosions with LASIK and would be better PRK candidates.21–25 Other risk factors for epithelial disturbances are increasing age, diabetes, dry eye, and a long history of contact lens wear.26–29 When severely injured, the epithelium produces high amounts of cytokines, such as interleukin-1α, that stimulate keratocytes to produce chemokines that attract inflammatory cells, leading to diffuse lamellar keratitis (DLK).6,30 Epithelial defects have also been associated with postoperative complications, including epithelial ingrowth,31,32 recurrent corneal epithelial erosion,33 and flap melt.

Corneal Epithelial Defect This uncommon LASIK complication has been shown to be lower with the use of a femtosecond laser than with a microkeratome because there is no microkeratome movement across the epithelium.13

• Fig. 15.1

  Blockage of a microkeratome head progression by the eyelid speculum (arrow) caused suction loss with consequent free and incomplete flap (arrow head).

A

B

• Fig. 15.2  (A) Complete applanation during femtosecond laser flap creation. (B) Peripheral asymmetric and incomplete meniscus (arrows) typical of suction loss.

A • Fig. 15.3

B

  (A) Loose epithelium in the central corneal just after microkeratome-assisted LASIK (arrowheads). (B) Flap borders (white arrows) and bandage contact lens (black arrows) can also be observed.

CHAPTER 15  LASIK Complications and Their Management

A

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B

• Fig. 15.4  (A) Torn and irregular flap after microkeratome-assisted LASIK. (B) A fragment of cilia beneath the blade was the cause of the tear (arrow).

Incomplete or Irregular Cut (Video 7) Method of flap creation and surgeon experience have both been shown to be the primary reasons for this disparity in complication rates. Of the different types of abnormal flaps, incomplete or short flaps are the most common. Incomplete flaps may be a result of the microkeratome prematurely stopping its course, which may be attributed to a pathway obstruction (e.g., blockage of microkeratome head progression by the speculum) or device malfunction.2 In addition, it may occur if suction is lost during the flap cut. Irregular cuts are more rare and may be related to defective blades and foreign bodies in the interface (Fig. 15.4). Femtosecond lasers can also result in incomplete treatments. Impediments to treatment or flap creation include corneal scars, loss of ring suction, irregular corneas, and low intraocular pressure (IOP). Once a flap defect has occurred, the procedure should be immediately halted. If the exposed stromal bed is not large enough to allow adequate laser ablation, the flap should be repositioned and the laser procedure postponed. With irregular cuts, the surgeon should not proceed with the ablation, but the flap or fragments should be carefully replaced and realigned to their original position using the gutter width as a landmark. The pieces should fit together like a jigsaw puzzle. Additional waiting/drying time is scheduled, and an overnight bandage contact lens is placed. There is no consensus for a waiting period. Usually, 3 months is enough before reattempting a new procedure.34 A no-touch transepithelial PRK (or a phototherapeutic keratectomy [PTK] + PRK) has been our preferred technique. If the created hinge is beyond the visual axis, some surgeons used to manually extend the dissection with a blade. This maneuver is not advised because of the risks of uneven bed creation and flap buttonhole formation.1 If there is sufficient stroma for laser ablation, the diameter of the available stroma should be measured to allow an adjustment in the optical/ablation zone and the flap should be protected from laser exposure. Placement of a surgical sponge over the flap may prevent inadvertent laser ablation on the hinge and flap (Fig. 15.5). If the flap hinge is beyond the visual axis, laser ablation may be performed.

• Fig. 15.5

  Surgical sponge placed over the flap hinge to prevent inadvertent laser ablation in an incomplete flap.

In regard to prevention, surgeons should ensure a properly functioning and clean device and careful ocular examination to identify a safe path for the microkeratome or femtosecond laser.6

Decentered Flaps If the flap is decentered and the area for ablation is adequate, the surgeon may proceed with laser treatment, possibly with a slight reduction in the optical zone. If this is not possible, the flap is repositioned and the operation repeated in 3 to 4 months with the creation of a new flap in a different depth or by using surface ablation, usually transepithelial PRK. This is particularly important in hyperopic or astigmatic treatments and when a large ablation zone is needed.35,36

Free Cap (Video 1) A free flap or cap, an uncommon but well recognized complication, occurs when the flap hinge is inadvertently severed during the LASIK procedure. The reported incidence ranges

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from 0.01% to 1.0% in large sample studies.1 Common causes of microkeratome-created free flaps include small (typically < 11.5 mm) and flat corneas (typically 46 D) have been compared with tennis balls that buckle centrally under applanating pressure, resulting in a central dimple missed by the blade, leading to a buttonhole (Fig. 15.8). Blunted blades, poor oscillation, and microflaws of blades have also been described as mechanical microkeratome problems that may lead to buttonholes.47–49

• Fig. 15.7

• Fig. 15.6  Same patient from Fig. 15.1. Free cap is observed over the microkeratome head (arrow). Despite a decreased stromal bed diameter due to the incomplete flap (arrowhead), a myopic ablation could be performed.

 

Subepithelial scar formation after buttonhole flap.

• Fig. 15.8

 

Theory of buttonhole formation.

CHAPTER 15  LASIK Complications and Their Management

Buttonholes can also occur with the femtosecond laser, specifically during dissection of tissue bridges in the interface. These bridges can be seen after complications such as vertical gas breakthrough (described later) and after femtosecond laser calibration problems (Fig. 15.9). The therapeutic management of buttonholes is challenging. When a buttonholed flap is encountered, the safest way to proceed is to carefully clean the stromal bed and ensure good alignment between flap buttonhole and the uncut tissue to prevent epithelial ingrowth. Reposition the flap immediately and abort the procedure (Fig. 15.10). Epithelial debris should be gently irrigated out with balanced salt solution (BSS) irrigating solution. Most patients with buttonholes end up with no significant loss of vision after adequate healing has occurred, especially if uncomplicated by epithelial ingrowth. The most adopted method is waiting 3 to 4 months, followed by transepithelial PRK with adjunctive MMC (Fig. 15.11).

A

Pizza Slicing This complication may occur when a flap is cut in an eye that had radial keratotomy (RK) with the incisions extending beyond the 8- to 9-mm central area. Inadequate healing of the RK incisions causes a part of the flap to separate in a triangular shape. An epithelial plug in the incision almost always precipitates this complication.50 Refractive errors after RK (usually hyperopia) in most cases are better managed by surface ablation with MMC, usually topography guided.51

Limbal Hemorrhage Bleeding at the corneal limbus is a relatively common complication that may occur when the microkeratome blade or femtosecond laser passes over conjunctival or limbal vessels (Fig. 15.12). The predisposing factors to intraoperative

B • Fig. 15.9  (A) Thin and irregular flap with tissue bridges (arrows) after femtosecond laser flap creation. (B) Small central buttonhole after forceful dissection of tissue bridges (arrow).

A

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B • Fig. 15.10  Buttonhole flap. (A) Intraoperative view (see also video). (B) A geographic area corresponding to the buttonhole can be seen on biomicroscopy 1 month after conservative management.

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A

B

C

D • Fig. 15.11

  Transepithelial photorefractive keratectomy (PRK) with adjunctive mitomycin C (MMC) for buttonhole flap 1 year after the primary surgery (see also video). (A) Transepithelial PRK. (B) Geographic area corresponding to the buttonhole can be seen intraoperatively. (C) Application of MMC 0.02% for 20 seconds. (D) After the MMC is washed away, a contact lens is placed.

A

B • Fig. 15.12

  Corneal bleed after Intra-LASIK with the femtosecond laser. (A) A decentered flap is created. (B) Bleeding from the limbal vessels is observed after the flap is lifted.

CHAPTER 15  LASIK Complications and Their Management

hemorrhages are large diameter flaps, hyperopia, or the use of suction rings that are inappropriately sized or improperly positioned. Eyes with a corneal pannus, such as can be found in chronic contact lens wearers or patients with ocular surface disease, are also more likely to experience hemorrhage during flap creation.39 Bleeding can be minimized in the following ways: • Leave the flap in position, apply a dry sponge to the bleeding area, and exert slight pressure for 1 to 2 minutes or until the bleeding has reduced significantly, allowing lifting of the flap and ablation. This is preferred in cases of hyperopia when the ablation is peripheral. • The blood can be wicked away while simultaneously performing the ablation. • A sponge soaked with 2.5% phenylephrine can be applied on the limbal vessels next to the bleeding area. Usually, this acts quickly, but the surgeon should be aware of the rapidity of concomitant segmental pupillary dilation beneath the area that may have a detrimental effect on eye-tracker and treatment centration. Continuous oozing at the end of the procedure is stopped by flap replacement, irrigation, and smoothing, which closes the interface and tamponades the vessels.

Intraoperative Complications Specific to Femtosecond Laser LASIK Vertical Gas Breakthrough Cavitation bubbles created by the femtosecond (FS) laser can dissect upwards toward the epithelium and are called vertical bubble breaks. The bubbles may either stay below the Bowman membrane or break through the epithelium. When the bubbles stay under the Bowman layer, a focal thinning in the flap is noted.42 The gas breakthrough can mislead the surgeon into leaving a piece of stroma intact when creating the flap. As the flap is lifted, the intact stroma will tear, causing a hole.52 If the break is through the

A • Fig. 15.13

227

epithelium, this is considered a buttonhole. The bubble that escapes to the surface may prevent additional bubbles from forming, resulting in a focal area that cannot be separated during flap reflection. Risk factors include previous RK surgery, corneal scars, microscopic breaks in the Bowman membrane, and thin flaps (programmed at 90 µm).7,8 The morbidity associated with this complication varies and may range from minimal corneal damage to significant corneal tearing, requiring abortion of the LASIK procedure.53 Vertical gas breakthrough (VGB) is an intraoperative complication that may not permit same-day flap creation because a second attempt will likely result in repeat breakthrough.53 Once VGB occurs, the surgeon should stop immediately and assess the situation. The vertical cut should not be performed to provide extra support that prevents flap mobility.53 If a significant VGB is seen between the glass cone and the epithelium, then the surgeon must stop the procedure and not wait for the side cut to finish (Fig. 15.13). Focal thinning in the flap may be lifted without complications. A true buttonholed flap should not be lifted because it can lead to scarring or epithelial ingrowth.8 If the side cut is completed, then it is recommended that the flap not be lifted and that the surgeon treat the patient several months later either with PRK with MMC, mechanical microkeratome, or cut with the FS laser at least 40 µm deeper than the original flap intended depth. It will also be prudent to save the cone used and return to the manufacturer as well as have the FS laser system serviced to check the z-calibration. This comprises a complete investigation of the probable cause of the incident.

Anterior Chamber Bubbles (Video 3) Presence of gas bubbles in the anterior chamber (AC) is another complication specific to the FS laser, with an incidence of 1%54 (Fig. 15.14).

B

  Vertical gas breakthrough (VGB) during femtosecond laser flap creation. (A) Small bubble-like VGB spot (arrowhead) close to an area of opaque bubble layer (arrow). B. Large VGB (arrowhead) that occurred after the pocket was created. (Images courtesy of John S. M. Chang, MD.)

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A

B

• Fig. 15.14

  (A) Gas bubbles in the anterior chamber after femtosecond laser flap creation (arrow). (B) Bubbles may impair pupil recognition for eye tracking.

Postulated risk factors for the development of AC bubbles include the use of large-diameter flaps and the treatment of smaller-diameter corneas. Both of these factors lead to FS dissection and gas formation closer to the limbus, thus facilitating migration of bubbles to the trabecular meshwork via the Schlemm canal.55 The bubbles accumulate centrally over the pupil and, although self-limiting, they can interfere with pupillary tracking. In this situation, the surgeon may delay excimer laser application for a few hours or longer until the bubbles are reabsorbed or perform ablation with manual centration.53,56

Opaque Bubble Layer An opaque bubble layer (OBL) is produced by gas bubbles that accumulate in the superficial layers of the stromal bed during FS laser flap creation, producing a diffuse tissue opacity (Fig. 15.15).57,58 The buildup of trapped microplasma gas bubbles that are unable to vent through the pocket, under high vacuum and corneal compression, travel in errant directions and push apart collagen fibrils to infiltrate the stroma.59,60 It was most commonly seen on earlier FS laser platforms, when higher energies and lower frequencies were used. Excessive OBL may interfere with flap creation and separation and with excimer laser tracking systems, which can delay the surgical procedure.61 Identified risk factors include thick corneas58,62–64 hard-docking technique,64 steep corneal curvature, and small flap diameter.62 When the OBL is not intense, the usual approach is to ignore it and immediately proceed with excimer laser ablation. Another option is to wait (typically 30–45 minutes) for the OBL to spontaneously dissipate within the stroma prior to lifting the flap and applying excimer laser ablation.61 Two distinct types of OBL were already reported: the hard OBLs that look denser and the soft ones that are more transparent.61

Early or Hard Opaque Bubble Layer This occurs when bubbles spread into the stromal tissue anterior and posterior to the plane at which the laser

• Fig. 15.15  Gas bubbles accumulate in the superficial layers of the stroma during femtosecond laser flap creation, producing a diffuse tissue opacity (arrows) called opaque bubble layer. This is a very mild case.

pulses are applied.59 Early or hard OBL can block subsequent pulses and lead to uncut or poorly cut tissue, making flap lifts more difficult and increasing the risk for flap tears.

Late or Soft Opaque Bubble Layer The produced gases can also travel into the intralamellar spaces after laser dissection has passed through an area of the stroma. The main cause of this type of OBL is poor separation of the corneal tissue, which appears more transparent and patchy. Again, lifts can be more difficult with late OBL. Also, eye trackers and iris recognition may be temporarily impaired with thick and central OBL.

CHAPTER 15  LASIK Complications and Their Management

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Once decentration has occurred, it may be difficult to treat. The most adopted method is topography-guided ablation, with variable results (Fig. 15.16).67

General Photoablation-Related Complications Decentration Accurate centration during the excimer laser procedure is critical in optimizing visual results. Centration is even more crucial for hyperopic than myopic treatments.13 A decentered ablation zone may go unrecognized during surgery and result in irregular astigmatism. A decentered ablation may occur if the patient’s eye slowly begins to drift and loses fixation or if the surgeon initially positions the patient’s head improperly; if the patient’s eye is not perpendicular to the laser treatment, parallax can result. This decentration may cause visual symptoms such as halo, glare, and monocular diplopia as well as a decrease in distance-corrected visual acuity.65,66 Decentration can be characterized as mild (0–0.5 mm), moderate (0.5–1.0 mm), or severe (> 1 mm). With modern excimer lasers that incorporate ultrafast real-time tracking systems, this complication is very rare. These systems detect changes in fixation and respond by moving the laser beam to the new location. When fixation changes excessively, the system stops. Decentration may be reduced by ensuring that the patient’s head remains in the correct plane throughout the treatment—that is, perpendicular to the laser (parallel to the ground)—and that there is no head tilt.13

A

Overcorrection and Undercorrection Overcorrection may occur if substantial stromal dehydration develops before the laser treatment is initiated because more stromal tissue will be ablated per pulse. A long delay before beginning ablation after lifting the flap in LASIK allows for excessive dehydration of the stroma and increases the risk of overcorrection. Controlling the humidity and temperature in the laser suite within the recommended guidelines should standardize the surgery and ideally improve refractive outcomes. Overcorrection tends to occur more often in older individuals with moderate to high myopia. A laser retreatment is usually performed after 3 to 6 months in LASIK-treated eyes and after 1 year in PRK. Undercorrection is also a frequent complication of primary LASIK.68–70 It is usually diagnosed in the first few weeks postoperatively, and the refractive error stabilizes early thereafter. Undercorrection after LASIK typically requires flap lift and laser treatment of the residual refractive error after the refraction has remained stable for at least 3 months. Undercorrection and overcorrection are related to the ablation algorithm, no accurate nomograms, age, and the amount of myopia, astigmatism, or hyperopia to be corrected.

B

C

• Fig. 15.16  Severe decentration with irregular astigmatism after LASIK treated with intrastromal topographic-guided ablation. (A) Preoperative corneal topography. (B) One-year postoperative topography. (C) Topographic-guided ablation profile. (Courtesy of Emir Amin Ghanem, MD.)

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Early Postoperative Complications Interface Debris Interface debris may arise from conjunctival or skin epithelial cells swept onto the interface by excessive irrigation or excessive tearing. The debris can also be caused by meibomian secretions, powder from the gloves or swabs used to clean the interface, metal fragments from the microkeratome blade, mucus from the ocular surface, or blood from cut pannus71,72 (Fig. 15.17). It is important to distinguish debris from an inflammatory or infectious reaction. Whereas most substances are biodegradable and cause no lasting harm to the patient, metallic or plastic material in the interface may induce an inflammatory reaction consistent with a corneal foreign body and ultimately has the ability to produce permanent corneal scarring. DLK is another possible postoperative sequela that has been observed with retention of interface debris.2 Keeping the flap environment free of debris is challenging. Several methods can be employed to minimize lint and debris that may contribute to interface debris. Scrub suits for the surgeon, cover over patients’ clothes, use of polyvinyl alcohol sponge (PVA) or cellulose sponge and powder-free

gloves are all useful measures.2 Care should be taken to carefully clean thoroughly around the skin, eyelids, and eyelashes. In general, the operative room should be examined, cleaned, and steps taken to ensure that the room air is purified, filtered, and circulating horizontally.2 If the debris is outside the visual axis and not visually significant, it can be left intact. However, debris observed in the visual axis should be removed if deemed visually significant.7,73 If it is noted during or immediately after the procedure, flap elevation and repositioning after irrigation are helpful, and perhaps both surfaces should be wiped with a moist LASIK sponge. If the debris is thought to be contributing to a significant inflammatory reaction, it is best to lift the flap and irrigate copiously. Generous irrigation is the most effective approach to prevent debris in the flap interface. An examination at the slit lamp afterwards to ensure interface clarity should be done as well.7

Flap Displacement and Flap Folds (Video 2) Flap displacement occurs most commonly in the first 24 hours after LASIK, before the epithelium has had time to heal over the lamellar entry site (Fig. 15.18). In contrast with traumatic dislocation, which can be caused by an

A

B

C

D • Fig. 15.17  Interface debris. (A) Meibomian secretions. (B) Foreign body associated with interface inflammation. (C) Cotton fiber (arrow). (D) Incomplete flap cut with metal fragment from the blade in the interface.

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231

B

A • Fig. 15.18

  Flap displacement and severe flap folds occurring in the first 24 hours after LASIK with nasal hinged flaps. (A) Upward displacement. (B) Downward displacement.

injury many years after LASIK,35,74 displacements occurring early on in the postoperative course usually have no obvious precipitating event.36,75,76 It may also follow lid action, eyelid rubbing, or squeezing. Usual symptoms include acute pain and decreased vision. Studies have shown a significant lower incidence of flap displacements in LASIK flaps created with FS lasers when compared to mechanical microkeratome, probably due to better flap stability associated with the angulation of the side cut, resulting in increased flap adhesion strength.6–8,77 Some risk factors have been related to the presence of folds in the flap, including initial intraoperative misalignment, deep ablations with flap–bed mismatch, persistent interface fluid, excessive flap dehydration, trauma while removing the eyelid speculum, eye rubbing, and early alteration of lubrication, which can cause adherence of the flap to the tarsal conjunctiva. Larger diameter and thinner flaps may be more prone to be displaced, especially if the hinge is small. A dislodged flap is an emergency. It should be repositioned as soon as possible to prevent fixed folds and epithelial ingrowth. Failure to act promptly increases the likelihood of permanent fold formation with decreased visual quality (Fig. 15.19). The flap should first be reflected and the interface (stromal bed and stromal aspect of the flap) carefully examined for epithelial cells or other debris. They should be scraped prior to repositioning the flap. Additional time should be taken in smoothing and drying the flap. A contact lens can be applied to provide added protection from further displacement.17 Recalcitrant folds may require removal of the central epithelium as it may prevent flattening of the folds owing to epithelial hyperplasia in the crevices formed by the folds.7 An eye shield may be suggested for an extended period of time. The surgeon should be aware that striae initially remain visible but disappear over 24 to 48 hours if the flap has been fully distended.

• Fig. 15.19

 

Permanent folds after late flap repositioning.

Flap Striae and Folds (Video 13) Striae and folds on the flap can lead to symptoms such as halos, diplopia, glare, and starbursts.6 Folds, often called macrostriae, represent full-thickness, undulating stromal folds and occur because of initial flap malposition or postoperative flap slippage.13 Folds can resemble fingerprint lines on biomicroscopy (see Fig. 15.19). Early intervention is often crucial as they induce irregular astigmatism with optical aberrations and loss of best-corrected visual acuity (BCVA), especially if they involve the visual axis.78 Striae or microstriae are fine, hair-like optical irregularities that are best viewed on red reflex illumination or by light reflected off the iris, often have normal fluorescein patterns, and do not interfere with BCVA (Fig. 15.20).13 They result from the adaptation of the original posterior curvature of the flap to the modified curvature of the ablated stroma. Microstriae are more likely to be seen in patients undergoing higher myopic LASIK treatments. This is due

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A

B • Fig. 15.20

 

Striae (or microstriae) after LASIK for high myopia. (A) Mild. (B) Intense.

ment procedures may be evaluated after refractive stability is achieved.81 If the flap is found, it typically has been detached for a number of hours and has become very edematous, making it very difficult to distinguish the stromal face from the epithelial surface. Both surfaces must be carefully cleaned to remove debris or epithelial growth; the flap may then be repositioned to its original location. This is not simple, as there are no marks and potentially no landmarks. If the flap is irreparably damaged, it must be discarded.

Diffuse Lamellar Keratitis

• Fig. 15.21

  Cap loss due to trauma (dog’s nail) 10 years after LASIK. Note the exposed stroma just a few hours after the injury.

to the reduced central convexity and stromal support, resulting in flap redundancy that may be quite difficult to flatten. The latter is referred to as the tenting effect.79 Monitoring is usually the treatment of choice.6

Loss of the Flap/Cap Cap loss may occur intraoperatively or during the early or late postoperative period. Factors that may lead to loss of the corneal cap include free cap, eye rubbing, and trauma. Most patients recover well, with no significant visual problems or significant induction of refractive error. The eye has a greater risk of developing significant haze than with primary PRK. This also holds true for cases in which flap removal is indicated because of scarring, infection, or other damage to the flap.80 MMC can be applied to the surface, a bandage contact lens is placed, and the patient is evaluated until the cornea is fully reepithelialized (Fig. 15.21). Secondary enhance-

DLK (or “the shifting sands of the Sahara”) is one of the most common postoperative complications of LASIK and seems to be slightly more common with the use of the FS laser compared to the microkeratome. The condition is a nonspecific sterile inflammatory response to a variety of mechanical and toxic insults. The interface under the flap is a potential space; any cause of anterior stromal inflammation may trigger the accumulation of white blood cells therein. This sterile inflammation typically appears within 24 hours but may rarely be delayed until a few days after surgery.82,83 The course of this disorder can be highly variable, gradually disappearing, persisting, or increasing. There have been several suggestions for the etiology of DLK. Any debris left on the lamellar interface may initiate an allergic or toxic reaction. Tear fluid, mucus, epithelial cells shed from the cornea, conjunctiva, or skin; meibomian secretions; powder from gloves; metal particles from the blade; instrument cleaning solutions; endotoxins released from sterilizer reservoir biofilms; leukocytes; and blood from a pannus are potential triggers for this inflammatory condition. DLK has also been associated with epithelial defects. It seems that several causative agents may lead to a final common inflammatory pathway, which results in the clinical picture of DLK. Finally, DLK is probably the result

CHAPTER 15  LASIK Complications and Their Management

of endogenous risk factors of the patient in response to exogenous exposure.84,85 The effects of DLK can range from asymptomatic interface haze near the edge of the flap to marked diffuse haze under the center of the flap with diminished correcteddistance visual acuity (CDVA).7 Eye pain, photophobia, and foreign-body sensation also can be manifested.84 A typical lamellar infiltrate has the following characteristics: • It is composed of white, granular opacities. • It is confined to the plane of the lamellar cut; there is no anterior or posterior extension. • There is no anterior chamber reaction. • There is no overlying epithelial defect. • The conjunctiva may be inflamed. DLK has been staged for the purpose of treatment and prognosis.85 The patient can progress from one stage to another quite rapidly. Slit lamp examination on a more or less daily basis is recommended for at least the first week. The most commonly used classification system grades DLK in four stages: • Stage 1: White granular cells in the periphery of the flap, sparing the visual axis (Fig. 15.22A). Usually seen on day 1 postoperatively.

• Stage 2: Progression of white granular cells onto the visual axis (Fig. 15.22B). Typically seen on days 1 to 3. • Stage 3: Condensation of denser clumping of granular cells in the central visual axis, with haze and reduced vision (Fig. 15.22 C). • Stage 4: Severe lamellar keratitis with stromal melting and scarring, often leading to secondary hyperopia and irregular astigmatism (Fig. 15.22D). Topical steroids are the mainstay of treatment. They should be potent drops of dexamethasone or prednisolone administered with high frequency in addition to a prophylactic antibiotic cover. The response to steroids is extremely rapid: there may be a worsening of the clinical picture on day 2, usually stabilization by day 3, and start of improvement by day 4 or 5. Generally, if treatment is rapid and massive, there is a complete resolution in 1 to 2 weeks to 1 month at most. Improvement normally starts peripherally and progresses toward the center. Recovery of vision in DLK is usually excellent if the condition is detected and treated promptly. Although stages 1 and 2 usually respond to frequent topical corticosteroid application, stages 3 and 4 usually require lifting the flap and irrigating, followed by intensive topical corticosteroid treatment. Some surgeons use topical

A

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D • Fig. 15.22

 

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(A) Stage 1 diffuse lamellar keratitis. (B) Stage 2. (C) Stage 3. (D) Stage 4 with central folds.

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and systemic corticosteroids in stage 3 DLK instead of, or in addition to, lifting the flap. Lifting the flap usually results in rapid improvement, as it allows removal of inflammatory mediators from the interface and direct placement of corticosteroids to suppress inflammation and collagen necrosis.7 Some surgeons advocate cautious raising of the flap and irrigation to remove toxins in stage 4 but such action should be performed extremely carefully and measures should be taken to prevent the loss of tissue, which is why some authors defend not elevating the flap at this stage.84,85 If there is any suspicion that the inflammation is due to infection, lifting the flap and obtaining samples for corneal cultures of the interface should be considered. Topical antibiotics can also be placed in the flap interface at the same time. In cases of suspected DLK not responsive to steroids within 7 to 10 days of initiation, the diagnosis should be reconsidered, as infectious keratitis or pressure-induced stromal keratopathy (PISK, discussed later) can mimic DLK and requires steroid cessation for resolution. Minimizing the risk factors and investigating and addressing other potential exogenous factors may help prevent DLK. Powderless gloves, proper draping, preoperative removal of the tear fluid in the fornices by surgical sponge, proper cleaning of irrigating cannulas and speculum, washing and sterilizing the instruments immediately after surgery, and periodic microbiologic control of the sterilizer water reservoir may contribute to a decreased incidence of DLK.

Pressure-Induced Stromal Keratopathy A diffuse stromal and interface opacity, termed pressureinduced stromal keratopathy, is caused by acute corticosteroid responsiveness, leading to increased IOP and subsequent presence of fluid in the interface.6,86–88 Regarding the nomenclature, several names have been given to the many manifestations of this entity, resulting in confusion in the diagnostic criteria, making them incorrect several times.

A

Among the most common terms are pressure-induced stromal keratitis,88 pressure-induced interface keratitis,89 and interface fluid syndrome.90 Keratitis is a misnomer in the definition of such an entity, since during the evaluations with confocal microscopy it has been demonstrated that there was no inflammation of the keratocytes present in such a complication.91 The term interface fluid syndrome is technically correct; however, an interface fluid syndrome can occur from a variety of mechanisms independent of acute response to steroids in the early postoperative period. It is often misdiagnosed as DLK or flap edema. Presence of fluid in the interface can falsely lead to an underestimate of the IOP, which can delay diagnosis and treatment. Management is directed at lowering IOP and cessation of corticosteroids.

Infectious Keratitis Bacterial infection under a LASIK flap is rarely reported but remains one of the most vision-threatening complications. LASIK carries a significant risk of infection because the corneal stroma can be exposed to infective agents during lamellar surgery. Eyelashes, conjunctiva, drapes, speculum, microkeratome, and surrounding atmosphere are all sources of infection92,93 The incidence of post-LASIK infectious keratitis among published reports is variable, with estimates ranging from 0% to 1.5%.94–97 In recent years, the incidence of infections has declined with the routine use of fourth-generation fluoroquinolone prophylaxis. Increased pain and decreased vision are the primary indicators of infection. Infection after LASIK is usually associated with redness, photophobia, and decreased vision.7 Slit lamp examination may reveal ciliary injection, epithelial defect, anterior chamber reaction, and hypopyon. Stromal infiltrate usually involves the LASIK interface in one or more loci. In advanced cases, the flap may become necrotic and slough off (Fig. 15.23). Precise diagnosis of DLK vs

B • Fig. 15.23  Infectious keratits after LASIK. (A) Diffuse stromal infiltrate with flap necrosis. (B) Intraoperative view showing that part of the flap was melted and had sloughed off.

CHAPTER 15  LASIK Complications and Their Management

infectious keratitis is of paramount importance to provide appropriate and timely treatment. In general, the timing of the onset of symptoms provides a clue as to the etiology of the infection. Infections occurring within 10 days of surgery are typically bacterial, with the preponderance being from gram-positive organisms. Suggested empirical treatment for broad coverage may include fortified vancomycin (10–50 mg/mL) and tobramycin (14 mg/mL) or a fourth-generation fluoroquinolone and cefazolin (50 mg/mL). Infections presenting more than 10 days after surgery are more likely caused by atypical mycobacteria and fungi. Topical clarithromycin (10 mg/ mL), oral clarithromycin (500 mg b.i.d.), and topical amikacin (8 mg/mL) are recommended for treatment of mycobacterial infections. If a filamentous fungus is identified, natamycin (50 mg/mL) is recommended; amphotericin (1.5 mg/mL) is recommended for yeast infections. Voriconazole (10 mg/mL) may be used for both yeasts and filamentous fungi and is often supplemented with voriconazole tablets (400 mg b.i.d.).7 Other recently reported infection types include viral (e.g., adenovirus and herpes simplex virus) and, of particular importance, Acanthamoeba infections.86,98–103 All eyes suspected of infectious keratitis following LASIK should undergo immediate flap lift to facilitate culture and irrigation of both the flap interface and underlying stromal bed with fortified antibiotics. However, culture results are highly variable, with reported rates of positivity ranging from 36% to 66%.94–97,104,105 The fourth-generation fluoroquinolones gatifloxacin and moxifloxacin have excellent efficacy against the more common bacteria that cause post-LASIK infections, including some atypical mycobacteria. However, monotherapy

A

235

with these drugs may not be sufficient. In cases refractory to treatment or where flap necrosis is present, flap amputation or therapeutic keratoplasty may be indicated.98 Most reported cases have a final BCVA of 20/40 or better. However, infection within the interface can lead to flap melting, severe irregular astigmatism, and corneal scarring that may require corneal transplantation.7

Epithelial Ingrowth (Videos 10 to 12) Epithelialization of the interface, which can occur after flap creation using a mechanical microkeratome or FS laser, is caused by the proliferation of epithelial cells between the stromal bed and the lenticule.106 Epithelial ingrowth is one of the most common complications following LASIK, usually detected within 1 month postoperatively, with large clinical studies demonstrating an incidence between 0.03% and 9.1%.107 The majority of epithelial ingrowth cases are not progressive, are asymptomatic, and do not cause adverse effects. Some cases, however, can be progressive and affect the visual axis, inducing irregular astigmatism. Advanced cases can develop flap melt, which can induce even more irregular astigmatism and corneal scarring.108 Photophobia, glare, decreased vision, and foreign body sensation can be symptoms of epithelial ingrowth. There are two main mechanisms of epithelial ingrowth: (1) deposition of small clumps of epithelial cells by the keratome or other instruments during flap creation/lift (Fig. 15.24) or (2) postoperative migration of surface epithelial cells from the periphery into the flap gutter and across the flap interface (Fig. 15.25).109–111

B

• Fig. 15.24  Central island of epithelial cells in the interface after femtosecond laser LASIK (arrows). (A) Direct tangential illumination. (B) Slit-view illumination.

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A

B

• Fig. 15.25

  Epithelial ingrowth starting from an inferior flap border irregularity (arrows) observed on direct (A) and retroillumination (B).

A

B • Fig. 15.26

  Epithelial ingrowth after LASIK in a patient with previous astigmatic arcuate keratotomy. (A) Note the flap border (short arrow) and the arcuate incision (long arrow) with epithelial cysts and translucent ingrowth along the borders. (B) Corneal optical coherence tomography (OCT) reveals the arcuate incision with epithelial cysts (long arrow) and the epithelium in the interface (short arrow).

Risk factors include those that contribute to an epithelial defect preoperatively (epithelial basement membrane dystrophy; history of recurrent erosions; older age; diabetes mellitus; and previous corneal surgeries, such as LASIK, transplants, and radial and astigmatic keratotomy [Fig. 15.26]) or perioperatively (intraoperative epithelial defect, ablation to the flap border, irregular flaps and flap borders, thinner flaps, buttonholes, free cap, postoperative lamellar keratitis, flap relift, enhancement procedure, flap misalignment or shift).6 Patients undergoing hyperopic LASIK have a greater incidence of epithelial ingrowth than those under-

going myopic treatment. In addition, enhancement procedures have a higher incidence than primary procedures.112 Because of the precise dimensions of the flap creation and flap edge angle, the FS laser induces less epithelial ingrowth than the mechanical microkeratome.113,114 All possible efforts must be made to prevent epithelial ingrowth. The bed should be irrigated and sponged before closing the flap. One should avoid excessive irrigation that might swell the stroma and contribute to poor flap adhesion. When lifting a flap in enhancement LASIK, it is preferable to first identify and lift the flap border with a

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• Fig. 15.27  Technique of flap lift for LASIK retreatments. (A) The inferior cornea periphery is indented, the edge of the flap is visualized, and one tip of the forceps is placed on the groove. (B) The tip of the forceps is placed perpendicular to the corneal surface at the edge of the flap and used to break the adhesion between the LASIK flap and the stromal bed. (C, D) The flap is progressively lifted with the forceps.

Sinskey hook on the slit lamp and later to use a nontoothed forceps to completely lift the flap (Fig. 15.27). A spatula should not be used, as it may carry epithelial cells onto the stroma. A bandage contact lens should be considered in the event of an intraoperative epithelial defect 6,31,115–116 Epithelial ingrowth can be graded using the Probst/ Machat classification115,117: Grade 1: Thin ingrowth, one to two cells thick, limited to within 2 mm of flap edge, transparent, difficult to detect, well-delineated white line along advancing edge, no associated flap changes, nonprogressive. No treatment required. Grade 2: Thicker ingrowth, discrete cells evident within nest, at least 2 mm from flap edge, individual cells translucent, easily seen on slit lamp, no demarcation line along nest, corneal flap edge rolled or gray, no flap edge melting or erosion. Requires reevaluation within 2 weeks and removal if progressive (Fig. 15.28A) Grade 3: Pronounced ingrowth, several cells thick, greater than 2  mm from flap edge, ingrowth areas appear opaque,

obvious on slit lamp, white geographic areas of necrotic epithelial cells without a demarcation line, corneal flap margins rolled with thickened white-grayish appearance. Progression results in large areas of flap melting from collagenase release from necrotic epithelium. Confluent haze develops peripheral to the flap edge as flap pulls away, leaving exposed stromal bed in contact with surface epithelium. Urgent treatment required with close follow-up owing to frequent recurrences (Fig. 15.28B).85 Overall, treatment is generally indicated when the epithelial ingrowth exceeds 2.0 mm from the flap edge, if progression is observed, if melting occurs, and it affects visual acuity or induces astigmatism (Fig. 15.29). Treatment involves removing the invading epithelial cells from the interface by lifting the flap and scraping the epithelial cells from the stromal bed and undersurface of the flap with a PRK spatula, irrigation of the interface with BSS, and placement of a bandage contact lens to achieve closure of the flap edge. To aid the removal process and further

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B • Fig. 15.28

  Epithelial ingrowth contiguous with the flap border, affecting the paracentral cornea and consequently visual acuity. (A) Translucent ingrowth, Machat grade 2. (B) Thicker ingrowth, opaque, with white geographic areas, Machat grade 3.

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C • Fig. 15.29

  (A) More advanced epithelial ingrowth (3–4 mm) coming from the inferotemporal flap margin. (B) Schematic representation showing the extension of the epithelium from the periphery. (C) When the epithelium approaches the pupillary area (arrow) or invades 3 mm or more from the periphery, it is better to lift the flap and scrape the epithelium.

loosen epithelial attachment, dilute ethanol (usually 20% for 20 seconds) can also be applied to the stromal bed and flap underside.118–120 For recurrent cases, fibrin glue, a twopart tissue adhesive containing fibrinogen and thrombin, in conjunction with manual epithelial removal can be used as

an effective means of decreasing clinically significant recurrence of epithelial ingrowth.108 Adjuvant treatments—such as mitomycin, PTK, or Nd:YAG laser—have been described for recurrent epithelial ingrowth. However, these measures may cause adverse

CHAPTER 15  LASIK Complications and Their Management

effects and are rarely necessary. Suturing the flap can also be considered in recurrent cases.6,31,114–116,121–122

Central Toxic Keratopathy Central toxic keratopathy (CTK) syndrome describes a rare, acute, self-limited, noninflammatory process that results in a central or paracentral dense focal opacification of the corneal stroma, usually starting in 3 to 9 days after laser keratorefractive surgery.123 CTK is usually preceded by a brief episode of DLK on postoperative days 1 to 2, then giving place to the central corneal opacity, which is typically associated with loss of overlying tissue, stromal thinning, striae, “lacquer” or “mud crack” appearance and focal scarring leading to anterior curvature flattening and significant hyperopic refractive shift (Fig. 15.30).6 CTK has an acute and usually painless onset,84 but symptoms may include pain, photophobia, decreased vision, halos, and redness.124 The underlying pathophysiology is unknown, although possible precipitating factors include photoactivation of povidone-iodine; laser-induced keratocyte apoptosis; intraoperative exposure to meibomian gland

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secretions, marking pen ink, and talcum from latex surgical gloves; and postsurgical debris from the microkeratome blade.124 CTK has been observed both after LASIK and PRK, suggesting that it may not be appropriate to classify it solely as a flap complication.52 CTK does not worsen over time, unlike most other entities.84 CTK is often misdiagnosed as stage 4 DLK owing to its similar appearance and hyperopic shift, but CTK occurs early in the postoperative period and is noninflammatory, thus showing no response to steroids. Other differential diagnoses include several inflammatory and infectious conditions, such as contact lens–induced keratitis, infectious keratitis, post-PRK haze, and corneal haze secondary to increased IOP. Close monitoring with regularly scheduled follow-up remains the primary management strategy since the central stromal haze in CTK6 usually is self-limited and the treatment may not be enough to solve the clinical condition.123 Although some authors defend the aggressive use of topical steroids125 or the elevation and irrigation of the flap,126 most believe that a surgical intervention does not contribute to the improvement of the condition and may even worsen the final results.123 The recovery in most

B

C • Fig. 15.30  Central toxic keratopathy (CTK) syndrome. Central or paracentral dense focal opacification of the corneal stroma. (A) Direct illumination. (B) Slit-view illumination showing central flattening and stromal thinning. (C) Another case with “mud crack” appearance, paracentral striae, and opacification.

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• Fig. 15.31  Corneal ectasia after LASIK. (A) Corneal tomography in the right eye reveals normal oblate cornea after myopic LASIK. (B) Left eye shows progressive severe central steepening characteristic of corneal ectasia. (C, D) Pachymetric maps shows progressive thinning in the left eye.

• Fig. 15.32  Corneal optical coherence tomography (OCT) of the same patient showing very thick LASIK flap with epithelial cysts on the flap border.

patients is good, but the corneal opacity and significant changes of visual acuity and refraction can remain.127

Late Postoperative Complications Induced or Iatrogenic Keratectasia Corneal ectasia is a vision-threatening complication characterized by progressive corneal steepening, with an increase in myopia and astigmatism, loss of uncorrected visual acuity, and often loss of BCVA (Figs. 15.31 and 15.32).128 The condition can present days to years after LASIK.128–130 The corneal flap does not contribute to the biomechanics of the cornea. Postoperative corneal ectasia most likely represents a reduction in biomechanical integrity below the

threshold required to maintain corneal shape and curvature. This could theoretically occur when a cornea already destined to manifest ectasia has surgery, when a preoperatively weak but clinically stable cornea has surgery, or when a relatively normal cornea is weakened below a safe threshold.131 The majority of ectasia cases after refractive surgery occur after LASIK and not PRK.132 There is an integrated relationship between preoperative corneal thickness, ablation depth, and flap thickness in determining the relative amount of biomechanical change that has occurred after LASIK.131,133,134 A new metric to evaluate ectasia risk factor after LASIK was recently introduced: Percentage of Tissue Altered (PTA) determines the integrated relationship between central corneal thickness (CCT), flap thickness (FT), ablation depth (AD), and the residual stromal bed. It is calculated by the formula PTA = (FT + AD)/CCT; recent studies have shown that a PTA of 40% or more is significantly associated with ectasia in eyes with normal preoperative topography.6 The changes induced by the combination of FT and AD have a significant impact on corneal biomechanical properties.131,133 Abnormal corneal topography has been shown to be the most important risk factor for postoperative ectasia134–138 (Fig. 15.33). Others risk factors include young age, low residual stromal bed thickness, and thin preoperative CCT. Previous incisional surgery, especially radial and astigmatic keratotomy, is also considered an important risk factor.125,139–141 However, cases of ectasia without any demonstrable risk factors have also been reported.7

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• Fig. 15.33

  Frequent abnormal corneal topography patterns. (A) Superior-inferior asymmetry suggestive of initial keratoconus (apical keratometry of 45.6 D). (B) Central steepening with “baby bowtie” aspect. (C) Skewed radial axis with against-the-rule astigmatism suggestive of initial pellucid marginal degeneration. (D) Horizontal asymmetry with “vertical D” pattern, present in some keratoconus suspects.

Early clinical detection of ectasia after LASIK requires high clinical suspicion. Topographic changes are initially subtle, and fluctuating or decreased vision is frequent. There can be a mild increase in irregular astigmatism. This may be accompanied by focal steepening, often inferiorly. These changes progress and become better defined over time. In advanced cases, the changes can be indistinguishable from keratoconus or pellucid marginal degeneration.132 For postoperative ectasia, corneal collagen crosslinking (CXL) is becoming the first-line treatment worldwide.7 The procedure represents a landmark in the treatment of corneal ectasia because, for the first time, it directly targets the underlying pathology (stromal instability stemming from collagen abnormalities) rather than only addressing the refractive consequences of the disorder.142 By inducing additional bonds between and within collagen fibers using

ultraviolet A (UVA) light and riboflavin as photomediators, it increases corneal biomechanical stability and stiffness, thus delaying or avoiding the disease progression.143 Before CXL emerged, treatment options for iatrogenic ectasia were limited to intracorneal ring segments (ICRS)144–147 and to lamellar or penetrating keratoplasty.148 Implantation of ICRS is an effective option to reduce corneal aberrations and improve visual acuity in patients who are contact-lens intolerant (Fig. 15.34). It usually also decreases refractive error, especially astigmatism, and central keratometry. In extreme cases, however, corneal transplantation may be required. Deep anterior lamellar keratoplasty (DALK), a partial-thickness graft that preserves the host endothelium and Descemet membrane, has been used successfully and is the technique of choice for ectatic disorders and anterior corneal opacities.149–152

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tion specific to FS laser technology and was most commonly seen when higher energies were used in earlier FS laser platforms. The incidence significantly decreased after the introduction of newer lasers with lower raster bed and sidecut energies.6 Although the etiology remains unknown and specific objective findings are absent, confocal microscopy analysis of affected patients’ corneas has shown increased keratocytic activity. It is thought that the laser energy may affect keratocytes or corneal nerve endings.7 It has also been speculated that expelled gases traumatize the ciliary body and trigger localized inflammation.156 As the name implies, it is transient and resolves with aggressive corticosteroid therapy over a short course of 2 to 3 weeks. • Fig. 15.34  Intracorneal rings implantation (Ferrara rings) and corneal crosslinking for corneal ectasia after LASIK. Note the flap border (arrows).

Night Vision Problems and Glare Distortion of vision in the form of glare and halos may interfere with an otherwise excellent refractive surgical result. Glare and halo symptoms typically become worse at night when the pupil dilates and more peripheral light rays enter the eye from the untreated zone. The major contributor to glare and halo symptoms is the effective spherical aberration of the centrally treated cornea.153 Decentered ablations, small treatment zones, newly formed cataracts, and induced astigmatism are other important causes of night glare after LASIK. A number of previous studies found a strong correlation between the level of attempted correction and visual symptoms, particularly glare, after refractive surgery. These patients should be warned of this potential complication. Fortunately, most disturbances decrease with time and, at 1-year follow-up, only a low percentage of patients are actually prevented from driving at night. At this time, it can only be speculated regarding how much of this improvement is due to a subjective acceptance of the disturbances (by neural adaptation) or an actual physical–optical improvement (e.g., decreased corneal scarring or corneal remodeling).154 Probably, both factors are important. The newer lasers not only attempt to maximize the optical zone but also produce a transition zone to blend the curvature of the optical zone smoothly into the curvature of the peripheral cornea. As a result, it is quite possible that the former importance of pupil size no longer obtains.155

Transient Light Sensitivity Syndrome Several weeks to months after LASIK with FS laser flaps, some patients experience acute onset of pain, photophobia, and intense light sensitivity in an otherwise white and quiet eye with excellent uncorrected distance visual acuity. Transient light sensitivity syndrome (TLSS) is a rare complica-

Rainbow Glare Rainbow glare is an optical side effect in which patients describe seeing a spectrum of colored bands radiating from a white light source when viewed in a dark environment, such as a nighttime setting.157 The cause of rainbow glare is thought to be the diffraction of light from the grating pattern created on the back surface of an FS laser-created LASIK flap.6,157 Initial management consists of observation and monitoring these patients since the symptom eventually resolves with time. A course of topical steroid administration should be considered.53 In eyes presenting with persistent and visually impairing rainbow glare symptoms, PTK on the stromal side of the LASIK flap can eliminate the condition.158,159

LASIK-Associated Dry Eye and Neurotrophic Epitheliopathy Dry eye is one of the most common complications and a primary reason for patient dissatisfaction after LASIK surgery.160 Post-LASIK dry eye usually peaks in the first few months after surgery and typically begins to improve approximately 6 to 12 months after surgery.161 The level of severity of dry-eye symptoms depends on many factors. For the vast majority of refractive surgery patients, the degree of dry-eye symptoms is not significant enough to cause difficulties. Symptoms of dry-eye disease can significantly affect a patient’s quality of life and include sensations of discomfort, such as irritation, burning sensation, and foreign body sensation, as well as complaints of fluctuations in vision. Chronic dry eye has also been associated with refractive regression.162,163 Clinical signs of dry-eye disease have also been well documented after LASIK, with multiple studies demonstrating increased fluorescein staining (Fig. 15.35) and decreased tear production and stability.162,164–166 It is not uncommon to note symptoms that are out of proportion to signs identified on examination.161 Multiple etiologies have been proposed to explain the causes of dry-eye syndrome after LASIK: decreased tear

CHAPTER 15  LASIK Complications and Their Management

production, damaged afferent sensory nerves, decreased blink reflex, increased tear evaporation, and injured goblet cells and microvilli at the limbus.167 The leading proposed cause is iatrogenic damage to the corneal nerves. During LASIK, there is disruption to both the dense sub-basal nerve plexus and the stromal corneal nerves in the creation of the anterior stromal flap and excimer laser ablation of the cornea.168 As the main cause of superficial punctate keratopathy following LASIK is neurotrophic, the term LASIKinduced neurotrophic epitheliopathy (LINE) was coined.167,169 By definition, it is a transient post-LASIK dry-eye sensation associated with fluctuating vison (if central corneal) and punctate epithelial staining with normal tear production (Fig. 15.36). The lack of sensitivity may cause a patient to blink less. It is vital to identify those patients at risk of severe post-LASIK dry eye to optimize the patient experience and to enhance visual outcomes.161 The major risk factor

• Fig. 15.35

  Superficial corneal punctate epithelial keratopathy within the flap area detected with fluorescein staining in dry eye after LASIK.

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for the development of dry eye after LASIK is preexisting dry-eye symptoms and has been shown to be associated with post-LASIK ocular surface staining and delayed recovery of corneal sensation.170,171 Other factors that have been associated with increased risk of dryness include increasing age,172 contact lens use,166 Asian race,163 and female sex.163,173 Other ocular disorders, such as ocular allergy, may predispose patients to the development of postrefractive dry eye. Collagen vascular diseases—including Sjögren syndrome, rheumatoid arthritis, systemic lupus erythematosus, and the seronegative spondyloarthropathies—have known ophthalmic complications, including dry eye and corneal ulceration.174 Although these conditions are generally considered to be contraindications to refractive surgery, some studies have shown good postoperative results in patients with well-controlled disease and minimal ocular involvement.174 The status of the ocular surface and tear film before LASIK can impact surgical outcomes in terms of potential complications during and after surgery. Before LASIK, the health of the ocular surface should be optimized and patients selected appropriately. As part of the preoperative evaluation, patients should have a detailed slit lamp examination that entails assessment of the ocular surface. Special attention must be directed to evaluation of tear break-up time, tear quality, eyelid margin disease, tear volume, and staining of the cornea or conjunctiva.161 A variety of treatments may be used both preoperatively to optimize conditions and postoperatively to treat symptoms and signs. In general, therapy is based on the severity of the dry-eye disease and the patient response to each added therapy. The patients should be oriented about their environment and activities of daily living. Avoiding systemic medications that can reduce tear secretion, such as systemic antihistamines and tranquilizers with anticholinergic effects, can help maintain adequate tear secretion.

B • Fig. 15.36  Neurotrophic epitheliopathy after LASIK. (A) Confluent central epitheliopathy staining with fluorescein. (B) Diffuse epitheliopathy, punctate epithelial erosions, and microcystic lesions confined to the flap 4 months after LASIK. In both cases, Schirmer tests were normal and distance-corrected visual acuity was decreased.

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Avoiding smoking and maintaining a healthy diet with supplemental omega 3 essential fatty acids may reduce the severity of dry eye. Avoiding, when possible, very dry or windy environments is helpful. Last, practicing completed blinking throughout the day and especially during periods of computer use, reading, and other activities involving high cognitive demand should be encouraged. However, when such preventive measures are inadequate to control episodic or chronic dry eye, there is a logical sequence of therapies that can be used.175 The initial treatment typically begins with the use of preservative-free artificial tears. When signs and symptoms of dry eye persist with artificial tears alone, the addition of punctal plugs may be beneficial, either with temporary collagen or permanent silicone plugs.176 Numerous antiinflammatory agents are being developed as treatments for dry-eye disease to reduce the amount of inflammation on the ocular surface and in the lacrimal unit. The most commonly prescribed short-term treatment for this purpose, however, is still low-dose topical corticosteroids.177 The treatment can be tapered over 2 to 3 months while other agents, such as cyclosporine and tacrolimus, may take up. Topical cyclosporine A 0.05% is a therapeutic agent that is associated with an improvement in tear production, presumably due to a reduction of the inflammatory effect on the lacrimal glands in dry-eye patients. However, the relief of symptoms may take up to 3 months; such a long lag time can result in poor compliance in clinical practice.178–180 Tacrolimus 0.03% is another immunomodulatory and antiinflammatory agent with activity up to 100 times greater than cyclosporine that has been shown to be effective and safe in the treatment of dry eye.181 No studies, however, have evaluated its efficacy in dry eye after LASIK. When there is coexisting meibomian gland dysfunction, treatment should be supplemented with warm compresses and lid hygiene for mild disease and topical azithromycin or oral doxycycline for more severe disease. For patients with dry-eye disease refractory to traditional treatments, as described earlier, autologous serum tears may be considered. Therapeutic silicone-hydrogel contact lenses may also be used in severe dry-eye disease to help retain the tear film and/or promote ocular surface healing.182,183 With proper screening of candidates, pretreatment of risk factors, and postoperative dry-eye management, excellent outcomes can be achieved after refractive surgery with high patient satisfaction.

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performed by ophthalmology residents. J Ophthalmic Vis Res. 2016;11(3):263–267. 4. Estopinal CB, Mian SI. LASIK flap: postoperative complications [review]. Int Ophthalmol Clin. 2016;56(2):67–81. 5. Gimbel HV, Basti S, Kaye GB, et al. Experience during the learning curve of laser in situ keratomileusis. J Cataract Refract Surg. 1996;22:542–550. 6. Oliveira RF, Stonecipher KG, Ignacio TS, et al. Complications related to femtosecond laser-assisted LASIK. In: Alio JL, Azar DT, eds. Management of Complications in Refractive Surgery. 2nd ed. Cham: Springer; 2018. 7. Shah DN, Melki S. Complications of femtosecond-assisted laser in-situ keratomileusis flaps. Semin Ophthalmol. 2014;29: 363–375. 8. dos Santos AM, Torricelli AA, Marino GK, et al. Femtosecondlaser assisted LASIK flap complications. J Refract Surg. 2016; 32(1):52–59. 9. Farjo AA, Sugar A, Schallhorn SC, et al. Femtosecond lasers for LASIK flap creation: a report by the American Academy of Ophthalmology. Ophthalmol. 2013;120(3):e5–e20. 10. Santhiago MR, Kara-Junior N, Waring GO 4th. Microkeratome versus femtosecond flaps: accuracy and complications. Curr Opin Ophthalmol. 2014;25(4):270–274. 11. Cosar CB, Gonen T, Moray M, Sener AB. Comparison of visual acuity, refractive results and complications of femtosecond laser with mechanical microkeratome in LASIK. Int J Ophthalmol. 2013;6(3):350–355. 12. Stonecipher K, Ignacio TS, Stonecipher M. Advances in refractive surgery: microkeratome and femtosecond laser flap creation in relation to safety, efficacy, predictability, and biomechanical stability. Curr Opin Ophthalmol. 2006;17:368–372. 13. Hamill MB. 2017–2018 Basic and Clinical Science Course, Section 13: Refractive Surgery. San Francisco, CA: American Academy of Ophthalmology; 2017. 14. Holzman JCRS. Effect of a hyperosmotic agent on epithelial disruptions during laser in situ keratomileusis. J Cataract Refract Surg. 2015;41(5):1044–1049. 15. Oliva MS, Ambrósio R Jr, Wilson SE. Influence of intraoperative epithelial defects on outcomes in LASIK for myopia. Am J Ophthalmol. 2004;137:244–249. 16. Azar DT, Scally A, Hannush SB, et al. Epithelial-defect-masquerade syndrome after laser in situ keratomileusis: Characteristic clinical findings and visual outcomes. J Cataract Refract Surg. 2003;29:2358–2365. 17. Montes M, Chayet AS, Castellanos A, Robledo N. Use of bandage contact lenses after laser in situ keratomileusis. J Refract Surg. 1997;13(suppl):S430–S431. 18. Salz JJ, Reader AL III, Schwartz LJ, et al. Treatment of corneal abrasions with soft contact lenses and topical diclofenac. J Refract Corneal Surg. 1994;10:640–646. 19. Heyworth P, Morlet N, Rayner S, et al. Natural history of recurrent erosion syndrome—a 4 year review of 117 patients. Br J Ophthalmol. 1998;82:26–28. 20. Puk DE, Probst LE, Holland EJ. Recurrent erosion after photorefractive keratectomy. Cornea. 1996;15:541–542. 21. Azar DT, Stark WJ, Steinert RE. PTK in the management of PRK complications. In: Azar DT, Steinert RF, Stark WJ, eds. Excimer laser phototherapeutic keratectomy. Baltimore, MD: Williams & Wilkins; 1997:175–190. 22. Kozobolis VP, Siganos DS, Meladakis GS, et al. Excimer laser phototherapeutic keratectomy for corneal opacities and recurrent erosion. J Refract Surg. 1996;12:S288–S290.

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CHAPTER 15  LASIK Complications and Their Management

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143. Marino GK, Torricelli AA, Giacomin N, Santhiago MR, Espindola R, Netto MV. Accelerated corneal collagen cross-linking for postoperative LASIK ectasia: two-year outcomes. J Refract Surg. 2015;31(6):380–384. 144. Richoz O, Mavrakanas N, Pajic B, Hafezi F. Corneal collagen cross-linking for ectasia after LASIK and photorefractive keratectomy: long-term results. Ophthalmology. 2013;120(7): 1354–1359. 145. Kymionis GD, Siganos CS, Kounis G, et al. Management of post-LASIK corneal ectasia with Intacs inserts: one-year results. Arch Ophthalmol. 2003;121:322–326. 146. Siganos CS, Kymionis GD, Astyrakakis N, Pallikaris IG. Management of corneal ectasia after laser in situ keratomileusis with INTACS. J Refract Surg. 2002;18:43–46. 147. Lovisolo CF, Fleming JF. Intracorneal ring segments for iatrogenic keratectasia after laser in situ keratomileusis or photorefractive keratectomy. J Refract Surg. 2002;18:535–541. 148. Seitz B, Rozsival P, Feuermannova A, et al. Penetrating keratoplasty for iatrogenic keratoconus after repeat myopic laser in situ keratomileusis: histologic findings and literature review. J Cataract Refract Surg. 2003;29:2217–2224. 149. Ghanem RC, Ghanem MA. Pachymetry-guided intrastromal air injection (“pachy-bubble”) for deep anterior lamellar keratoplasty. Cornea. 2012;31(9):1087–1091. 150. Salouti R, Nowroozzadeh MH, Makateb P, Zamani M, Ghoreyshi M, Melles GR. Deep anterior lamellar keratoplasty for keratectasia after laser in situ keratomileusis. J Cataract Refract Surg. 2014;40(12):2011–2018. 151. Watson SL, Ramsay A, Dart JKG, Bunce C, Craig E. Comparison of deep lamellar keratoplasty and penetrating keratoplasty in patients with keratoconus. Ophthalmology. 2004;111: 1676–1682. 152. Panda A, Bageshwar LM, Ray M, Singh JP, Kumar A. Deep lamellar keratoplasty versus penetrating keratoplasty for corneal lesions. Cornea. 1999;18:172–175. 153. Pop M, Payette Y. Risk factors for night vision complaints after LASIK for myopia. Ophthalmology. 2004;111:3–10. 154. Fan-Paul NI, Li J, Miller JS, Florakis GJ. Night vision disturbances after corneal refractive surgery. Surv Ophthalmol. 2002; 47(6):533–546. 155. Klyce SD. Night vision after LASIK: the pupil proclaims innocence. Ophthalmology. 2004;111(1):1–2. 156. Stonecipher KG, Dishler JG, Ignacio TS, Binder PS. Transient light sensitivity after femtosecond laser flap creation: clinical findings and management. J Cataract Refract Surg. 2006;32: 91–94. 157. Krueger RR, Thornton IL, Xu M, Bor Z, van den Berg TJ. Rainbow glare as an optical side effect of Intra LASIK. Ophthalmology. 2008;115(7):1187–1195.e1. 158. Gatinel D, Saad A, Guilbert E, Rouger H. Unilateral rainbow glare after uncomplicated femto-LASIK using the FS-200 femtosecond laser. J Refract Surg. 2013;29(7):498–501. 159. Gatinel D, Saad A, Guilbert E, Rouger H. Simultaneous correction of unilateral rainbow glare and residual astigmatism by undersurface flap photoablation after femtosecond laser-assisted LASIK. J Refract Surg. 2015;31:406–410. 160. Levinson BA, Rapuano CJ, Cohen EJ, et al. Referrals to the Wills Eye Institute Cornea Service after laser in situ keratomileusis: reasons for patient dissatisfaction. J Cataract Refract Surg. 2008;34:32–39. 161. Raoof D, Pineda R. Dry eye after laser in-situ keratomileusis. Semin Ophthalmol. 2014;29(5–6):358–362. 162. Dohlman TH, Lai EC, Ciralsky JB. Dry eye disease after refractive surgery. Int Ophthalmol Clin. 2016;56(2):101–110.

163. Albietz JM, Lenton LM, McLennan SG. Chronic dry eye and regression after laser in situ keratomileusis for myopia. J Cataract Refract Surg. 2004;30:675–684. 164. Yu EY, Leung A, Rao S, et al. Effect of laser in situ keratomileusis on tear stability. Ophthalmology. 2000;107:2131–2135. 165. Battat L, Macri A, Dursun D, et al. Effects of laser in situ keratomileusis on tear production, clearance, and the ocular surface. Ophthalmology. 2001;108:1230–1235. 166. Benitez-del-Castillo JM, del Rio T, Iradier T, et al. Decrease in tear secretion and corneal sensitivity after laser in situ keratomileusis. Cornea. 2001;20:30–32. 167. Ambrosio R, Tervo T, Wilson S. LASIK-associated dry eye and neurotrophic epitheliopathy: pathophysiology and strategies for prevention and treatment. J Refract Surg. 2008;24(4): 396–407. 168. Salomao MQ, Ambrósio R, Wilson SE. Dry eye associated with laser in situ keratomileusis: mechanical microkeratome versus femtosecond laser. J Cataract Refract Surg. 2009;35(10): 1756–1760. 169. Wilson SE. Laser in situ keratomileusis-induced (presumed) neurotrophic epitheliopathy. Ophthalmology. 2001;108(6): 1082–1087. 170. Toda I, Asano-Kato N, Hori-Komai Y, Tsubota K. Laser assisted in situ keratomileusis for patients with dry eye. Arch Ophthalmology. 2002;120(8):1024–1028. 171. Toda I, Kato-Asano N, Hori-Komai Y, Tsubota K. Dry eye after LASIK enhancement by flap lifting. J Refract Surg. 2006; 22(4):358–362. 172. Azuma M, Yabuta C, Fraunfelder FW, Shearer TR. Dry eye in LASIK patients. BMC Res Notes. 2014;7:420. 173. Shoja MR, Besharati MR. Dry eye after LASIK for myopia: incidence and risk factors. Eur J Ophthalmol. 2007;17(1): 1–6. 174. Simpson RG, Moshirfar M, Edmonds JN, et al. Laser in situ keratomileusis in patients with collagen vascular disease: a review of the literature. Clin Ophthalmol. 2012;6: 1827–1837. 175. Jackson WB. Management of dysfunctional tear syndrome: a Canadian consensus. Can J Ophthalmol. 2009;44:385–394. 176. Alfawaz AM, Algehedan S, Jastaneiah SS, Al-Mansouri S, Mousa A, Al-Assiri A. Efficacy of punctal occlusion in management of dry eyes after laser in situ keratomileusis for myopia. Curr Eye Res. 2014;39(3):257–262. 177. Baudouin C, Irkeç M, Messmer EM, et al. Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting. Acta Ophthalmol. 2018;96(2):111–119. 178. Wilson SE, Perry HD. Long-term resolution of chronic dry eye symptoms and signs after topical cyclosporine treatment. Ophthalmology. 2007;114:76–79. 179. Barber LD, Pflugfelder SC, Tauber J, et al. Phase III safety evaluation of cyclosporine 0.1% ophthalmic emulsion administered twice daily to dry eye disease patients for up to 3 years. Ophthalmology. 2005;112:1790–1794. 180. Torricelli AA, Santhiago MR, Wilson SE. Topical cyclosporine: a treatment in corneal refractive surgery and patients with dry eye. J Refract Surg. 2014;30(8):558–564. 181. Moscovici BK, Holzchuh R, Chiacchio BB, Santo RM, Shimazaki J, Hida RY. Clinical treatment of dry eye using 0.03% tacrolimus eye drops. Cornea. 2012;31(8):945–949. 182. Lemp MA. Management of dry eye disease. Am J Manag Care. 2008;14(3 suppl):S88–S101. 183. Lindsay RG. Therapeutic use of silicone hydrogel lenses for the management of dry eye. Practice. 2007. http://www.siliconehydrogels.org/in_the_practice/mar_07.asp.

16 

Small-Incision Lenticule Extraction (SMILE) PUSHPANJALI GIRI, DIMITRI T. AZAR, AND SUPHI TANERI

Introduction Small-incision lenticule extraction (SMILE) is a refractive surgery procedure currently used to correct refractive errors in patients with myopia with or without astigmatism while the correction of presbyopia and hyperopia is still in development. It involves the creation of a corneal tissue disk called a lenticule and its extraction through a minimally invasive incision, utilizing only a femtosecond (FS) laser. This enables rapid visual recovery with very little discomfort to the patient. Therefore one can consider SMILE as laser in situ keratomileusis (LASIK) without flap, and photorefractive keratectomy (PRK) without pain. The history of SMILE as a refractive procedure began in 1996, when a picosecond laser–based system was first used to generate an intrastromal lenticule that was manually removed after lifting a superficial flap similar to LASIK. At this early stage, significant manual dissection of stromal tissue bridges generated an irregular surface.1,2 In 1998, the FS laser replaced the early picosecond laser–based system to perform lenticule extraction in rabbit corneas.3 FS laser– based lenticule extraction was taken further to perform extractions in partially sighted eyes in 20034; however, these preliminary studies were not followed up by clinical trials. Four years later, in early 2007, femtosecond lenticule extraction (FLEx) was presented in sighted patients that can be thought of as the prototype of the current SMILE procedure as an alternative to LASIK to correct high myopia.5 The refractive outcomes of FLEx were similar to that of LASIK.6 Further refinements led to the development of a procedure to extract a corneal lenticule involving only a small incision of 2 to 4 mm, without creating a flap. September 2011 saw the commercial launch of this SMILE procedure.5

Principles Behind SMILE Unlike an excimer laser used in LASIK to remove corneal tissue by a process called photoablation, the principle by which

an FS laser works to create a corneal lenticule and incision in SMILE is a process called photodisruption. Photodisruption involves vaporizing a small volume of tissue by creating plasma (free electrons and ions), carbon dioxide, an acoustic shockwave, thermal energy, and a cavitation bubble.7 The millions of plasma bubbles created through photodisruption are aligned in a laminar manner at the target location, where they expand and subsequently stretch and separate the surrounding tissues.8 The mechanical separation occurring along the laminar structures of the tissue results in the effect of tissue cleaving (Fig. 16.1). The amount of tissue cleaving depends on the amount of laser pulse energy: the higher the pulse energy, the greater the effect. Often, cleaving occurs owing to the concerted effects of about 10,000 to 100,000 pulses/mm2.9 The laser that is used for SMILE is a neodymium:yttrium aluminum garnet (Nd:YAG) solid-state laser that emits energy into a focal point with a wavelength of 1043 nm. In the United States, the US Food and Drug Administration (FDA) has approved the VisuMax Femtosecond Laser (Carl Zeiss Meditec Inc.) for the reduction or elimination of nearsightedness using SMILE.10 The limit values as approved by the FDA for the correction of myopia with SMILE are presented in Table 16.1.11

Surgical Techniques for SMILE (Video 16.1) Preoperative Considerations Patient Selection In selecting patients for SMILE, the surgeon must screen surgical candidates for myopia and myopic astigmatism. Currently, in the United States, the FDA has approved SMILE for the treatment of myopia of −1.00 diopter (D) to −8.00 D, and astigmatism of less than or equal to −0.50 D.12 Outside the United States, SMILE can be used to treat myopia of up to −10.00 D combined with astigmatism of up to −5.00 D.13 SMILE can be harder to perform for very low myopia chiefly owing to difficulty in managing such a thin lenticule. The difficulty can be overcome by 249

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• Fig. 16.1  Process of photodisruption in the corneal stroma with femtosecond laser. (Modified from Riau A, Mehta JS. Current progress in femtosecond laser-assisted endothelial keratoplasty. In: Zhang Y, ed. Femtosecond Lasers: New Research. Hauppauge, NY: Nova Science Publishers; 2013:297–312). TABLE Limit Values of Adjustment Ranges for 16.1  VisuMax Femtosecond Laser for the

Treatment of Myopia

Parameter

Unit

Range

Laser energy

nJ

125–170

Track distance

µm

2.0–3.0

Spot distance

µm

2.0–3.0

Cap diameter

mm

7.0 or 7.5

Cap thickness

µm

120

Lenticule diameter

mm

6.0 or 6.5

Lenticule edge minimum thickness

µm

15

Residual bed minimum thickness

µm

250

Incision position: opening position

deg

90

Incision angle: cap opening size

deg

90

Side cut angle: opening cut

deg

90

Side cut angle: lenticule cut

deg

90

Intended spherical corrections

D

-100 to -8.00*

Intended cylindrical corrections

D

—

Intended cylindrical axis

deg

—

Laser Parameter

Surgical

Refractive

*Treatment of −8.01 to −10.00 D will present a flagged warning to the users so that the user understands that correction of these powers has not been substantiated by an adequate data set. Data from Zeiss. VisuMax Femtosecond Laser: Small Incision Lenticule Extraction (SMILE) procedure for the correction of myopia. https://www .accessdata.fda.gov/cdrh_docs/pdf15/P150040D.pdf.

making the lenticule thicker using a wider optical zone. The FDA has experimented with a minimum peripheral lenticule thickness of 15 µm in all lenticules, and surgeons have observed good results.14,15 However, with increasing surgeon experience, we recommend a minimum thickness of only 10 µm to reduce the refractively neutral removal of precious stromal tissue (only outside the United States). SMILE for hyperopia is not in routine use yet, but some studies have

been published of its initial success in monkey corneas and small-diopter correction in hyperopic patients.16–20 A prospective multicenter trial is underway.

Centration Unlike in other refractive laser procedures, currently, no eye tracking system is used in SMILE; this is perceived as a major drawback by some colleagues. However, the patient is instructed to fixate coaxially on a fixation light before the application of suction (Fig. 16.2A). This coaxial fixation causes the refractive lenticule to be auto-centered on the corneal vertex of the eye. The surgeon confirms the correct centration by comparing the relative positions of the pupil center and the corneal reflex (which may not coincide) to the Placido eye image obtained from the Atlas topography scan. The coaxial fixation on the fixation light follows a number of steps in SMILE. First, the patient is raised to appropriate height to make contact with the contact glass of the FS laser. The contact glass is curved, allowing for comfortable docking. When contact is made between the cornea and the contact glass, a tear film meniscus appears; simultaneously, the patient is able to see the fixation target clearly. This happens because the vergence of the fixation beam is adjusted according to the individual refraction of the patient’s eye. The surgeon instructs the patient to focus directly on the target green light. Once the patient is focusing on the green light, the surgeon activates the corneal suction ports to fixate the eye in this position in order to align the visual axis. The surgeon can release suction and repeat the docking procedure if the centration of docking is not satisfactory. The physiologic location of the visual axis is only approximated, however, through the corneal light reflex method because a coaxially aligned light reflex corresponds to the center of the optical system as opposed to the true visual axis. The lack of an eye tracking system to compensate for alignment and cyclotorsional errors in SMILE is a weakness of this procedure.21

Incision Technique Incision technique comprises the use of the appropriate laser pulse parameters, the shape of the incision, and the centering accuracy of the incision.

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

A

B

C

D

E

F

G

H

I

251

• Fig. 16.2  Small-incision lenticule extraction (SMILE) surgery on a right eye. (A) Patient is asked to fixate on green light. Note that this may not coincide with the center of the entrance pupil. Patient interface is aligned and suction started. (B) Refractive posterior surface of lenticule is created by spiraling-in application of femto-laser spots. (C) Anterior surface of lenticule is created parallel to anterior surface of the cornea (spiraling-out). (D) Complete laser application with superotemporal incision. (E) Side cut is opened with a semi-sharp tip. First, the upper lenticular surface is entered. (F) Upper interface is separated using a blunt spoon-shaped SMILE spatula (custom-made). (G) Lower interface is separated. (H) Lenticule is extracted with micro-forceps. (I) Finished SMILE procedure.

Appropriate Laser Pulse The FDA-approved laser pulse energy for SMILE is between 125 to 170 nJ (see Table 16.1).11 However, even lower energy settings may be preferable because they have been shown to produce smoother interfaces. The energy settings of 140 and 170 nJ have been reported to be effective for the correction of myopia and myopic astigmatism, respectively.22 No significant differences have been observed in the optical quality, including the corneal light scattering in eyes undergoing SMILE procedure with the laser settings of 140 nJ, spot distance 3.0 µm vs 170 nJ, and spot distance of 4.5 µm.22 The tissue cutting precision results from the average of the axial precisions of a large number of laser pulses. The optimization of laser settings for SMILE depends on 2 factors: (1) the level of energy per area and (2) optimized distances between adjacent spots and adjacent spiral tracks to reduce the roughness of the stromal surfaces after the lenticule is removed. These 2 factors can be responsible for delayed visual recovery. Spiraling-in application of the femto-laser spots is used to create the refractive posterior surface of the lenticule (Fig. 16.2B), while the spiraling-out technique is used to create the anterior surface of the lenticule that is parallel to the anterior surface of the cornea

(Fig. 16.2C). A complete laser application with superotemporal incision is shown in Fig. 16.2D.

Shape of the Incision The current conventional design of the incision technique for lenticule preparation involves cap cutting that is parallel to the corneal surface and a lenticule cut connected to the cap cut by a side cut on the edge of the lenticule (side cut is approximately 10–15 µm in height typically; Fig. 16.3).23 The side cut (Fig. 16.2E) is refractively neutral and is required to give the surgeon some tissue to grasp and manipulate. After opening the side cut with a semi-sharp tip, the upper lenticular surface is entered first (Fig. 16.2F) and then separated using a blunt spoon-shaped SMILE spatula (Fig. 16.2F). The lower interface is separated following the upper interface separation (Fig. 16.2G), and lenticule is extracted with micro-forceps (Fig. 16.2H). A finished SMILE procedure is shown in Fig. 16.2I. The incision shape can be spherical or ellipsoidal depending on whether there is need for astigmatism correction along with spherical correction. The thickness of the lenticule to be extracted during SMILE depends on the degree of the required refractive error based on the theoretical limit

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A

B • Fig.

C

16.3  Incision geometry of small-incision lenticule-extraction surgery. (A) Refractive cut (1), lenticule side cut (2), cap (3), and side cut (4). Ranges for surgical parameters (B) and edges of the cap and lenticule (C).

value according to Munnerlyn. The usual rule of thumb for 1 D correction using a 6-mm correction zone is 13 µm lenticule thickness corresponding to the equivalent ablation depth in excimer laser surgery. This maximum lenticule thickness is central lenticule thickness in cases of myopia correction and the thickness at the optical zone edge in cases of hyperopia correction, respectively. Note that the refractively neutral lenticule side cut adds to lenticule thickness.

• Fig. 16.4

  The optical effect of a rotational decentration of the lenticule inside the stroma with good centration. The optical zone (violet) and the corneal volume (light blue) are shown in the preoperative state (top), with lenticule cut (middle) and with lenticule extracted (bottom). (Modified from Bischoff M, Strobrawa G. Femtosecond laser keratocomes for small incision lenticule extraction. In: Sekundo W, ed. SMILE Principles, Techniques, Complication Management and Future Concepts. Switzerland: Springer; 2015:3–12.]

Centering Accuracy of the Incision The centration of the lenticule cut is important to achieve accurate refractive correction in SMILE. However, the issue is not as serious for lenticule preparation as it is for ablative surgery because, comparatively, lenticule decentration induces a smaller amount of higher-order aberrations owing to the use of an FS laser (Fig. 16.4). The excimer laser used in LASIK is more sensitive, as it typically causes ablation errors around the edge of the working area owing to projection errors and thus a variation of ablation efficiency.9 For SMILE, the visual outcomes can still be good if the lenticule diameter is sufficiently large. Better refractive outcome is reported for lenticules centered near the corneal vertex normal.24–26 Incidentally, eyes that undergo the SMILE procedure have been reported to show less mean centration offset compared to eyes that undergo LASIK.27

acuity (UDVA), corrected distance visual acuity (CDVA), and objective scattering index (OSI) between the four different scenarios. El-Massry et al.29 conducted a prospective comparative interventional clinical trial in patients who underwent SMILE with lenticule creation at two different depths, 100 µm in the right eye and 160 µm in the left eye. They evaluated the manifest refraction, UCVA, total higherorder aberrations (HOAs), and corneal biomechanical properties in both eyes at 1 month postoperatively. Although no statistically significant differences were found between the former three parameters in the two eyes, the left eye with 160 µm–deep lenticule creation displayed less damage to the corneal biomechanics. The predictability of the cap thickness in SMILE is reported to be consistent with the flap thickness in femtosecond-LASIK (FS-LASIK) with the use of same FS laser platform.30

Other Important Considerations Thickness of Lenticule Cap

Corneal Wound Healing After SMILE

The cap thickness of the lenticule appears to have no effect on visual acuity or refractive outcomes after the SMILE procedure.28,29 Guell et al.28 conducted a retrospective, comparative, nonrandomized clinical study in which they performed myopic SMILE with four different cap thicknesses: 130, 140, 150, and 160 µm. They found no statistically significant differences between uncorrected distance visual

The way a cornea heals has a major effect on visual outcomes after refractive surgery. Corneal haze, myopia regression, and epithelial ingrowth after FS-LASIK have been associated with less than ideal corneal wound healing. Complex cascades of molecular and cellular pathways involving cytokines, growth factors, and tumor necrosis factors are involved in corneal wound healing. After an insult to the

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

cornea, cytokines and growth factors are released from the injured epithelium and mediate apoptosis of the stromal keratocytes. Subsequently, proliferation and migration of the remaining keratocytes occur within a few hours in order to restore the cellularity of the stroma.31,32 Simultaneously, inflammatory cells migrate to phagocytize the apoptotic cells and to enhance the transformation of keratocytes to fibroblasts within 24 hours of the injury.33 A good balance between the development of myofibroblasts and the apoptosis of myofibroblast precursors is decisive in determining whether the cornea heals ideally or develops haze after wound healing.34 SMILE appears to induce minimal corneal wound healing responses after the surgery.35 A study of early corneal wound healing responses after SMILE in rabbit eye models showed that significantly fewer terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)–positive stromal cells, Ki67-positive cells, and CD11b-positive cells were found after SMILE than after FS-LASIK.36 The degree of early corneal wound healing response depends proportionally on the degree of correction of the refractive error. In vivo confocal microscopy immediately after SMILE showed greater corneal reflectivity in corneas after −8.00 D of correction compared to lower myopia corrections.35 The greater corneal reflectivity was observed at all planes of the procedure—the anterior, posterior, and extracted lenticular planes. In lower degrees of refractive corrections, there were no differences in the expression of CD11b, fibronectin, and HSP47 observed.35 If any increased amount of inflammation was observed in lower refraction error correction, it was attributed to less surgical experience of the surgeon. Mixed sensory and autonomic nerves enter the cornea by approaching the corneoscleral limbus radially from all directions.37–39 These arise from two long ciliary nerves that enter the posterior globe adjacent to the optic nerve and course forward in the suprachoroidal space at the nasal and temporal meridians (Fig. 16.5).40 The central corneal nerve fiber density is reduced after SMILE owing to the transection of the nerve fibers that intersect the lenticule-cap plane by the FS laser cut. However, the damage is significantly less compared to the flap-based and surface ablation techniques in which almost total fiber resection takes place.41 Surgical denervation is also significantly less in SMILE compared to other refractive procedures, along with faster nerve regeneration, based on in vivo studies. Therefore in theory, there should be less severe and less frequent postoperative dry eye after SMILE compared to other corneal refractive procedures. Only mild to moderate keratocyte apoptosis, secondary keratocyte activation, and stromal inflammation occur in any intrastromal technique. At times, microdistortions can be observed in the Bowman layer after SMILE, especially for high myopia owing to the longer arc length of the cap than the stromal bed after removing the lenticule. Quantitative evaluation of the microdistortions on optical coherence tomography (OCT) has found that there is a positive correlation between the magnitude of the refractive error corrected and the

A • Fig. 16.5

253

B

(A) Stromal nerve fiber bundles run centripetally and toward the surface perforating the Bowman layer (BL; spots indicated by blue circles). Once the fibers penetrate the BL, the subbasal nerve plexus is originated. Different colors illustrate the subbasal fibers originating from central (green), paracentral (light blue), and peripheral (purple) perforating stromal fibers, respectively. (B) With the SMILE procedure, in the absence of a full flap side cut, peripheral nerve fibers are resected only where the 50-degree arc of the incision is placed (thick orange line). Moreover, fibers are resected if rising superficially to perforate the BL within the area of the created and extracted refractive lenticule. The other fibers that had penetrated the BL outside the lenticule area may run undisturbed as subbasal nerve plexus (for simplicity, central subbasal surviving fibers are not depicted in the central zone). (Modified from Mastropasqua L, Nubile. Corneal nerve and keratocyte response to ReLEx surgery. In: Sekundo W, ed. SMILE Principles, Techniques, Complication Management and Future Concepts. Switzerland: Springer; 2015:27–43.)  

Bowman Roughness Index (BRI). The BRI is defined as the enclosed area between the actual and ideal smooth layer to quantify microdistortions.42 The microdistortions, however, are reported to remain stable after a week, with no impact on long-term visual performance.43 The postoperative BRI in SMILE eyes is also reported to be similar to the preoperative BRI in comparison to LASIK eyes,44 indicating earlier wound healing after SMILE. A study has reported milder ocular surface changes after SMILE compared to LASIK, especially pertaining to the tear inflammatory mediators, such as interleukin 6 (IL-6) and nerve growth factor (NGF), which are thought to play important roles in the healing of the ocular surface.45 The authors measured IL-6, NGF, tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (CAM-1) in the tears of myopic patients. Although TNF-α and CAM-1 concentrations were similar between both groups at any follow-up time (1 day, 1 week, 1 month, and 3 months postoperatively), IL-6 and NGF levels were observed to be lower in the SMILE group. The levels of IL-6 and NGF were seen to correlate with the changes of the ocular surface after SMILE or LASIK, and the SMILE group showed faster recovery of IL-6 and NGF levels.

Corneal Biomechanics Corneal shape determines the refraction of the eye, which, in turn, depends on its inherent biomechanical properties. Corneal biomechanics is dependent on several factors, such

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as extracellular matrix components, collagen lamellae organization, osmotic pressure, corneal layers, systemic diseases (e.g., diabetes mellitus), hormonal fluctuations, and to some extent environmental factors (although only little is known). Stable corneal biomechanics after refractive surgery is important in order to maintain satisfactory visual recovery and to avoid any postoperative complications. Corneal biomechanics is typically thought not to be compromised too badly after SMILE because of the minimally invasive nature of the procedure and the absence of the flap cut. Although some studies46–49 have shown the differences in biomechanical properties between flap-based and flapless procedures to be insignificant and inconsistent, other studies have shown some differences in biomechanical strength of the cornea between flap-based and flapless procedures. Based on the tomographic data of 10 eyes, Seven et al.50 reported a mean reduction of 49% in the effective stiffness of the collagen fiber of the corneal stroma in the eyes that underwent the flap-based procedure (FLEx) compared to eyes that underwent the flapless procedure (SMILE). The mean reduction ranged from 2% to 87%, and the eyes that underwent the flap-based FLEx procedure also showed higher stresses and deformations within the residual stromal bed than the eyes that underwent SMILE. Knox Cartwright et al.51 reported that corneal strain after delamination only is lower than the strain after LASIK flap and side cut; they also reported that corneal strain tends to increase with a thicker flap cut. Randleman et al.52 reported that stromal cohesive tensile strength is strongest in the anterior 40% of the central cornea and at least 50% weaker in the posterior 60% of the corneal stroma. The tangential tensile strength also has been reported to be greater for the anterior than the posterior stroma using different methodologies.53,54 Therefore theoretically, the absence of the anterior flap cut in SMILE would not compromise the integrity of the cornea as much as flap cut procedures would. Additionally, in contrast to LASIK, in which deeper ablations contribute to lower tensile strength postoperatively (because of the minimal contribution of the flap to the corneal biomechanics after wound healing), performing SMILE at greater stromal depth (of the weaker posterior stroma) would also leave the cornea with greater tensile strength. A paper by Shih et al.55 compared the hoop stresses of the cornea under tension and bending for patients who undergo radial keratotomy (RK), PRK, LASIK, and SMILE, and mapped the stress concentration, potential creak zones, and potential errors in intraocular pressure (IOP) measurements for all four surgical procedures. The stress and potential creak zones were mapped based on finite element analysis (FEA), in which the roles of the stroma, Bowman membrane, and Desçemet membrane under physiologic tension and nonphysiologic bending of the cornea were determined. The authors did the first principle stress (FPS) analysis of the cornea under four surgical models (FPS is defined as the component of stress tensors when the shear stress component is reduced to zero by rotating the basis56). Based

on the FPS analysis, both SMILE and LASIK appeared to have potential creak zones near the edge of ablation with cracks at 45 degrees spreading radially, but SMILE appeared to have less maximum stress than LASIK (Fig. 16.6). Study of the FPS upon eye rubbing applied to the 4 surgical models showed that SMILE, LASIK, and PRK caused stress concentrations around the Bowman membrane near the ablation zone, whereas the RK incisions caused stress concentrations around the Desçemet membrane (Fig. 16.7). A mathematical model developed by Reinstein et al.57 also predicted considerably greater stromal tensile strength after SMILE compared to LASIK.

Literature Review Several clinical studies have recognized the success and effectiveness of SMILE. However, there have been reports of several complications during and after SMILE. As it is a relatively new procedure, we want to know how it compares to the standard LASIK procedure in terms of the visual and refractive outcomes. We also want to know how SMILE compares to LASIK in terms of the onset of the commonly reported postoperative complications after LASIK, such as dry eye, ectasia, and others. In this chapter, we have systematically compiled a list of papers published on SMILE in PubMed using the search words small incision lenticule extraction from the beginning of time until October 23, 2017. The search yielded 305 papers, which were divided into English and foreign language. Only the papers published in English or with an English abstract were used. The selection included 280 papers.

Inclusion Criteria The relevant papers on SMILE were selected with the following inclusion criteria in mind: (1) retrospective case series, prospective randomized controlled trials, and nonrandomized comparative trials; (2) studies that compared the preoperative and postoperative visual outcomes and reported either spherical equivalent (SE) within ± 0.5 D, SE within ± 1.0 D, or safety and efficacy indices; (3) the follow-up period could be as short as 1 month for visual and refractive outcomes, and as short as 1 week for the dry-eye outcome measurements; (4) patients aged 18 to 60 years with any degree of myopia and myopic astigmatism; (4) patients treated with SMILE alone or in combination with another method and, for comparison studies, patients treated with FS-LASIK; and (5) studies reporting intraoperative or postoperative complications.

Results Predictability, Safety, and Efficacy The abstract of each of the 280 papers was read and categorized into multiple categories, such as “visual and refractive outcomes after SMILE,” “intraoperative SMILE complications,” and “postoperative complications after SMILE.” The

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

A

B

C

D

255

• Fig. 16.6

  High first principle stress (FPS) areas (top view showing FPS >30 kPa) of the four models without (left) and with (right) applanation conditions. (A) Radial keratotomy: the zones with the highest stress are associated with the directions of fibers and incisions. (B) Photorefractive keratectomy: the potential creak zone is near the edges of ablation. (C) Laser in situ keratomileusis (LASIK): the potential creak zone is near the edge of ablation and 45-degree cracks in radial directions. (D) Small-incision lenticule extraction: the potential creak zone is the same as that of LASIK but the maximum stress is less than that in LASIK (unit: kPa). (Permission obtained from Shih P-J, Wang I-J, Cai W-F, Yen J-Y. Biomechanical simulation of stress concentration and intraocular pressure in corneas subjected to myopic refractive surgical procedures. Sci Rep. 2017;7(1):13906. doi:10.1038/s41598-017-14293-0.)

“postoperative complications” category was further divided into “dry eye,” “ectasia,” and “other complications.” In the “visual and refractive outcomes” category, only the papers that reported either the SE within ± 0.50 D, SE within ± 1.00 D, safety index, or the efficacy index were chosen. This inclusion criteria yielded 31 papers. Four of these papers were separated from the primary “visual and refractive outcomes” group because these papers reported predictability and/or safety and efficacy indexes based on the comparison between the traditional SMILE technique and variations of the traditional SMILE technique. Of the 27 papers included in the primary “visual and refractive outcome” group, one paper was entered twice because it reported predictability, safety, and efficacy indices separately for low myopia (< −6.00 D), and high myopia (≥ −6.00 D). The weighted averages of SE with ± 0.50 D, within ± 1.00 D, and weighted averages of safety and efficacy indices were calculated for both “visual and refractive outcome” tables (Table 16.2 and Table 16.3).

Intraoperative Complications Among the 305 SMILE papers, there were 16 that reported some form of intraoperative complications. The reported

intraoperative complications were opaque bubble layer, suction loss, incision bleeding, incision tear, incision abrasion, epithelial defect, difficult lenticule extraction, subconjunctival hemorrhage, lenticule tear, unintended posterior plane dissection, inaccurate laser placement, and cap perforation. Of these reported intraoperative complications, cap perforation was excluded from Table 16.4 because this complication was rare and no paper reported its occurrence in percentage. Of the 16 papers, 10 were included to calculate the weighted average of each of these 11 complications and six were excluded because they reported complications either as case reports or were in a different language. Of the 10 included papers, Ivarsen et al. reported some intraoperative complications, such as cap perforations (four eyes) and lenticule tear (one eye) instead of percentages because these complications were so rare (out of 1800 eyes). Thus only the intraoperative complications that were reported in percentages were included in Table 16.4 and in calculating weighted average percentages. We also could not find any other paper reporting the complication of cap perforation. We also identified five case reports of ectasia, one report of diffuse lamellar keratitis and one report of interface fluid

LASIK and SMILE

256 se c t i o n V 256

A

B

C

D

• Fig. 16.7  First principle stress (FPS) on seven slices of the four models subjected to a certain rubbing force. (A) FPS in the radial keratotomy model, showing the potential fractures occurring at the bottom of the incision with a tensional concentration. (B) FPS in the photorefractive keratectomy model, showing the zone of the potentially tensional tear surrounding the ablation. (C) FPS in the laser in situ keratomileusis model and (D) FPS in the small-incision lenticule extraction model. (C) and (D) indicate the high stresses found around the midperipheral cornea and potentially opening creak zones surrounding the ablation. (Permission obtained from Shih P-J, Wang I-J, Cai W-F, Yen J-Y. Biomechanical simulation of stress concentration and intraocular pressure in corneas subjected to myopic refractive surgical procedures. Sci Rep. 2017;7(1):13906. doi:10.1038/s41598-017-14293-0.)

TABLE Predictability and Safety and Efficacy Index of SMILE Procedure in Eyes With Myopia or 16.2  Myopic Astigmatism

Study Kanellopoulous et al.58 59

Khalifa et al.

60

Zhang et al.

61

Pedersen et al.

62

Kobashi et al.

63

Burazovitch et al. Ganesh et al.

64

65

Hyun et al.

66

Chan TC et al. 67

Wong et al.

68

Hansen et al.

Year

Country

2017

Greece

2017

No. of Eyes

SE Within ± 0.50 D (%)

44

77.3

Egypt

110

81.54

2017

China

9

2017

Denmark

2017

48

1.16 ± 0.14

1.07 ± 0.16

12

1.17 ± 0.17

0.98 ± 0.20

3

1.13 ± 0.19

0.91 ± 0.21

2017

France

496

87

48

2017

India

120

97

3

2017

Korea

69

84

6

2017

China

66

100

6

2017

Singapore

164

83.8

97.2

3

722

88

98

3

89

2016

Singapore

50

2015

Singapore

172

2015

Japan

52

100

2015

Denmark

87

78

Pedersen et al.

1.08 ± 0.16

24

47

61

1.10 ± 0.24

1

100

China

Kamiya et al.

0.92 ± 0.11

30

2016

72

0.98 ± 0.08

Japan

70

Ang et al.

Efficacy Index

74

Denmark

71

Safety Index

101

2016

Ang et al.

Follow-up (mo) 3

88.9

69

Han et al.

SE Within ± 1.00 D (%)

93

94 82.5

12

12 90

36

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

257

TABLE Predictability and Safety and Efficacy Index of SMILE Procedure in Eyes With Myopia or 16.2  Myopic Astigmatism—cont’d

Study Kim et al.*74 74

Kim et al.**

75

Xu Y et al.

No. of Eyes

Year

Country

2015

Korea

58

2015

Korea

125

2015 76

Kamiya et al.

52

SE Within ± 0.50 D (%)

SE Within ± 1.00 D (%)

Follow-up (mo)

87.9

96.6

88

97.6

90.4

Safety Index

Efficacy Index

12

1.27 ± 0.17

1.04 ± 0.19

12

1.24 ± 0.17

0.99 ± 0.19

12

2014

Japan

26

100

2014

Denmark

35

88

Agca et al.

2014

Turkey

20

95

79

2014

Singapore

88

78.4

95.5

3

80

2014

Korea

447

86.1

97.9

6

77

Vestergaard et al. 78

Ang et al. Kim et al.

81

Miao et al.

2014 82

Vestergaard et al. 83

Hjortdal et al.

84

Sekundoet al.

6 97

6 6

66

3

2012

Denmark

144

77

95

3

2012

Denmark

670

80

94

3

2011

Germany

91

80.2

95.6

6

SE Within ± 0.50 D (%)

SE Within ± 1.00 D (%)

1.12 ± 0.17

Weighted average of SE within ± 0.50 D = 85.1% Weighted average of SE within ± 1.00 D = 96.1% Weighted average of safety index = 1.17 Weighted average of efficacy index = 0.93

Study Kanellopoulous et al.58 59

Khalifa et al.

60

Zhang et al.

61

Pedersen et al.

62

Kobashi et al.

63

Burazovitch et al. Ganesh et al.

64

Year

Country

2017

Greece

2017

No. of Eyes 44

77.3

Egypt

110

81.54

2017

China

9

2017

Denmark

2017

Follow-up (mo)

Safety Index

Efficacy Index

0.98 ± 0.08

0.92 ± 0.11

1.10 ± 0.24

1.08 ± 0.16

48

1.16 ± 0.14

1.07 ± 0.16

12

1.17 ± 0.17

0.98 ± 0.20

3

1.13 ± 0.19

0.91 ± 0.21

3

88.9

1

101

74

93

12

Japan

30

100

24

2017

France

496

87

48

2017

India

120

97

3

65

2017

Korea

69

84

6

66

2017

China

66

100

6

2017

Singapore

164

83.8

97.2

3

722

88

98

3

89

Hyun et al.

Chan et al.

67

Wong et al.

68

Hansen et al.

2016

Denmark

69

2016

China

47

70

2016

Singapore

50

2015

Singapore

172

2015

Japan

52

100

2015

Denmark

87

78

90

36

2015

Korea

58

87.9

96.6

12

1.27 ± 0.17

1.04 ± 0.19

2015

Korea

125

88

97.6

12

1.24 ± 0.17

0.99 ± 0.19

Han et al. Ang et al.

71

Ang et al.

72

Kamiya et al.

61

Pedersen et al. 74

Kim et al.*

74

Kim et al.** 75

Xu et al.

2015 76

Kamiya et al.

2014

52 Japan

26

94 82.5

90.4 100

12

12 6 Continued

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258 se c t i o n V 258

TABLE Predictability and Safety and Efficacy Index of SMILE Procedure in Eyes With Myopia or 16.2  Myopic Astigmatism—cont’d

Study

No. of Eyes

SE Within ± 0.50 D (%)

SE Within ± 1.00 D (%)

Follow-up (mo)

Year

Country

2014

Denmark

35

88

Agca et al.

2014

Turkey

20

95

79

2014

Singapore

88

78.4

95.5

3

80

2014

Korea

447

86.1

97.9

6

Vestergaard et al.77 78

Ang et al. Kim et al.

81

Miao et al.

2014 82

Vestergaard et al. 83

Hjortdal et al.

84

Sekundo et al.

97

Safety Index

Efficacy Index

6 6

66

3

2012

Denmark

144

77

95

3

2012

Denmark

670

80

94

3

2011

Germany

91

80.2

95.6

6

1.12 ± 0.17

Weighted average of SE within ± 0.50 D = 85.1% Weighted average of SE within ±1.00 D = 96.1% Weighted average of safety index = 1.17 Weighted average of efficacy index = 0.93 *Denotes mild to moderate myopia; **denotes high myopia, ≥ −6.0 D. SE, Standard error.

TABLE Predictability and Safety and Efficacy Index of SMILE Procedure in Eyes With Myopia or Myopic 16.3  Astigmatism Using Traditional SMILE Technique Vs Custom SMILE Technique

SE Within ± 0.50 D (%)

SE Within ± 1.00 D (%)

Follow-up (mo)

Year

Country

No. of Eyes

85

2017

Germany

100

0.87 ± 0.23

85

100

0.87 ± 0.23

Study Taneri et al. Taneri et al.

Safety Index

Efficacy Index

2017

Germany

86

2016

Korea

52

1

1.12 ± 0.14

1.09 ± 0.17

86

2016

Korea

60

1

1.09 ± 0.15

1.02 ± 0.11

2016

China

32

94

6

1.00 ± 0.00

0.97 ± 0.06

2016

China

21

89

6

0.96 ± 0.06

0.88 ± 0.13

Kim et al. Kim et al.

87

Ng et al.

87

Ng et al.

88

2015

16

1.12

1.06

88

2015

15

1.09

1.09

Zhao et al. Zhao et al.

SMILE, Small-incision lenticule extraction. Taneri et al.85: 200 eyes with myopia and myopic astigmatism, divided into phase I (100 treatments with large variation of laser and surgical parameters) and phase II (100 treatments with mostly constant laser parameters and identical surgical treatments). Kim et al.86: 112 myopic eyes treated, 52 with traditional SMILE technique, and 60 with Chung’s swing technique. Ng et al.87: 51 myopic eyes treated, 32 with traditional SMILE technique and 21 with SMILE in combination with collagen crosslinking. Zhao et al.88: 31 myopic eyes treated, 16 with continuous curvilinear lenticulerrhexis technique for SMILE, and 15 with traditional SMILE technique.

collection.102–108 All reported intraoperative complications in the literature are shown in Fig. 16.8.

Postoperative Complications Among the 305 SMILE papers, SMILE complications papers were categorized separately into several groups, such as dry eye, ectasia, diffuse lamellar keratitis, interface lamellar fluid, and others. This categorization included 21

papers. Among 21 papers, 14 were sorted into the dry-eye category. The papers dealing with meta-analysis of dry eye were excluded, and only the papers that reported original studies on dry eye were included. These inclusion criteria yielded nine papers. From these papers, dry-eye indicators— such as Ocular Surface Disease Index (OSDI) score, tear breakup time (TBUT), Schirmer test values, corneal sensitivity values, and tear osmolarity values—were collected

91

0.65

0.8

4.4

3.13

2.1

0.41

2.7

0.2

0.93

2

0.83

4.38

51.82

0.73

19

Opaque Bubble Layer (%)

4.49

6

3.75

0.33

11

Black Spots (%)

6.23

1.9

9

Difficult Lenticule Extraction

2.27

1.8

0.93

Incisional Bleeding

1.26

0.67

Subconjunctival Hemorrhage

*Son et al.93 included eyes from a retrospective case series, but the incidence of opague bubble layer is 51.82%, which is quite high.

Weighted average of each complication (%)

Ivarsen et al.

1800

183

98

Wong et al.97

3376

8490

160

95

208

12

Ramirez-Miranda et al.96

Osman et al.

Liu et al.

94

93

Son et al. >*

Gab-alla

92

Park and Koo

11,762

3004

Wang et al.

100

90

Eyes

Tityal et al.89

Study

Suction Loss (%)

TABLE 16.4  Reported Occurrence of Intraoperative Complications During SMILE Procedure

0.67

0.33

Unintended Posterior Plane Dissection

0.33

3.84

0.27

Lenticule Tear

0.50

3.13

0.17

Incision Abrasion

0.32

0.1

Inaccurate Laser Pulse Placement

0.10

6

11.3

2

Epithelial Defect

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

259

LASIK and SMILE

260 se c t i o n V 260

TABLE 16.4A  Weighted Average of the Reported OSDI Scores (0–100) After SMILE Procedure

Study 99

Xia et al.

100

Denoyer et al. 101

Li et al.

Year

Eyes

Preop

2016

69

10.7

2015

30

2013

38

Weighted average OSDI

1 wk

1 mo

3 mo

6 mo

20.34

14.91

12.11

19.7±12.7 12.26±12.45

23.95±13.54

11.25

23.95

7.5±4.5

16.72±10.96

12.05±9.38

8.47±7.89

13.89

10.09

19.2

OSDI, Ocular Surface Disease Index; SMILE, small-incision lenticule extraction.

TABLE 16.4B  Weighted Average of the Reported OSDI Scores (0–100) After FS-LASIK Procedure

Study 99

Xia et al.

100

Denoyer et al. 101

Li et al.

Weighted average OSDI

Year

Eyes

Preop

2016

59

10.40 ± 2.87

2015

30

2013

33

1 week

1 mon

3 mon

6 mon

26.03 ± 4.01

20.63 ± 3.66

16.00 ± 2.82

23.9 ± 14.8

20.6 ± 20.8

11.59 ± 16.92

18.78 ± 19.01

17.77 ± 16.64

16.22 ± 15.29

15.50 ± 14.00

10.83

18.78

23.27

19.05

17

FS-LASIK, Femtosecond laser in situ keratomileusis; OSDI, Ocular Surface Disease Index.

• Fig. 16.8  Weighted percentage of various intraoperative complications during small-incision lenticule extraction.

preoperatively and postoperatively at 1 week, 1 month, 3 months, 6 months, and 12 months when reported. These values are organized in Tables 16.5 through 16.8 and weighted average of each of these dry-eye test values are calculated. The weighted average of each of these test values is shown in linear graphs to give a visual representation of the dry-eye parameters after SMILE vs after FS-LASIK.

Explanation of the Graphs (Dry Eye) OSDI is a series of questionnaires designed to evaluate the reported severity of dry eye by the patient. The OSDI score ranges from 0 to 100, with score of 13 to 22 categorized as mild, 22 to 33 categorized as moderate, and greater than 33 categorized as severe. The weighted OSDI scores after

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

261

TABLE 16.5A  Weighted Average of the Reported TBUT (in Seconds) After SMILE Procedure

Study

Year

Eyes

2016

69

Denoyer et al.

2015

30

109

2015

47

9.87 ± 1.57

6.28 ± 1.35

8.21 ± 0.95

9.57 ± 0.93

2014

81

10.35 ± 3.28

6.79 ± 2.25

5.79 ± 2.38

7.39 ±2.36

2013

38

8.58 ± 4.42

4.32 ± 3.57

5.68 ± 4.84

5.03 ± 3.83

7.06 ± 3.85

2013

28

9.0±1.2

9.9 ± 4-14

10.9 ± 2.8

11.6 ± 2.8

11.1 ± 2.7

99

Xia et al.

100

Wang et al.

110

Xu and Yang 101

Li et al.

111

Demirok et al.

Preop 6.8 ± 3.0

1 wk

1 mo

3 mo

6 mo

6.4 ± 3.1

9.7 ± 6.5

6.0 ± 2.2

6.3 ± 2.1

5.9±1.7

Weighted average TBUT

8.93

6.54

7.74

12 mo

7±1.8

6.7

9.83 ± 0.99

7.75

9.83

12 mo

SMILE, Small-incision lenticule extraction; TBUT, tear breakup time

TABLE 16.5B  Weighted Average of the Reported TBUT (in Seconds) After FS-LASIK Procedure

Study

Year

Eyes

2016

59

Denoyer et al.

2015

30

109

2015

43

9.56 ± 1.35

6.53 ± 1.24

7.42 ± 0.96

8.19 ± 1.45

2014

97

11.09 ± 3.15

6.41 ± 2.96

5.67 ± 2.14

7.13 ± 2.56

2013

33

7.88 ± 5.57

4.70 ± 3.65

3.77 ± 2.91

4.43 ± 4.22

4.97 ± 3.57

2013

38

9.1 ± 1.0

10.1 ± 2.3

10.7 ± 2.4

10.9 ± 2.8

10.4 ± 2.5

99

Xia et al.

100

Wang et al.

110

Xu and Yang 101

Li et al.

111

Demirok et al.

Preop

1 wk

1 mo

3 mo

6 mo

7.8 ± 3.3

4.5 ± 3.2

4.2 ± 3.4

5.1 ± 2.2

6.6 ± 1.6

5.1 ± 1.9

Weighted average TBUT

9.46

6.19

6.11

5.2 ± 1.8

6.41

9.30 ± 0.89

7.16

9.3

FS-LASIK, Femtosecond laser in situ keratomileusis; TBUT, tear breakup time.

TABLE Weighted Average of the Reported Schirmer Test Values (in Millimeters Per 5 Minutes) After 16.6A  SMILE Procedure

Study

Year

Eyes

Preop

1 wk

1 mo

3 mo

6 mo

Xia et al.99

2016

69

11.8 ± 5.5

9.1 ± 3.9

9.7 ± 6.1

12.6 ± 5.5

9.5 ± 4.1

Denoyer et al.100

2015

30

Xu and Yang110

2014

81

17.49 ± 7.48

Li et al.101

2013

38

14.63 ± 7.51

Demirok et al.111

2013

28

Weighted average Schirmer Test

13.2 ± 6.1

17.3 ± 8.2

16.98 ± 6.43

17.46 ± 9.25

17.13 ± 6.73

13.51 ± 10.96

12.11 ± 7.58

14.14 ± 9.38

13.28 ± 8.72

17.5 ± 6.5

17.3 ± 4.8

15.8 ± 5.9

16.6 ± 4.0

17.3 ± 4.4

15.17

12.04

13.6

15.21

14.44

SMILE, Small-incision lenticule extraction.

both SMILE and FS-LASIK were comparatively similar, with SMILE showing a higher OSDI score at 1 week than FS-LASIK (23.95 vs 18.78). Over the follow-up period of 1 month, 3 months, and 6 months, however, SMILE showed slightly better dry-eye outcome in the OSDI score index than FS-LASIK (10.09 for SMILE at 6 months vs 17 for FS-LASIK; Fig. 16.9). Considering the weighted OSDI

scores, SMILE does not exacerbate any dry-eye problem, but FS-LASIK does at least in the relatively short follow-up period of 6 months. Further studies with a longer follow-up time are warranted. Both SMILE and FS-LASIK showed comparable outcomes in TBUT assessment. Remarkably, initial TBUT was in both groups slightly shorter than 10 seconds, indicating

LASIK and SMILE

262 se c t i o n V 262

TABLE Weighted Average of the Reported Schirmer Test Values (in Millimeters Per 5 Minutes) After 16.6B  FS-LASIK Procedure

Study 99

Xia et al.

100

Denoyer et al.

110

Xu and Yang 101

Li et al.

111

Demirok et al.

Year

Eyes

Preop

2016

59

2015

30

2014

97

18.55 ± 7.75

2013

33

15.36 ± 9.47

2013

28

18.5 ± 5.5

11.8 ± 5.5

1 wk

1 mo

3 mo

6 mo

5.6 ± 3.5

7.6 ± 3.8

10.4 ± 5.5

9.3 ± 2.6

19.9 ± 10.5

Weighted average Schirmer Test

10.00 ± 8.28 17.93 ± 6

14.25

14.01

16.9 ± 7.8

17.35 ± 7.72

18.22 ± 9.82

17.00 ± 7.20

10.90 ± 7.99

13.73 ± 9.54

13.17 ± 9.32

17.5 ± 5.1

16.5 ± 4.4

16.9 ± 3.9

14.53

15.19

14.63

FS-LASIK, Femtosecond laser in situ keratomileusis.

TABLE 16.7A  Weighted Average of the Reported Corneal Sensitivity Values (in Millimeters) After SMILE Procedure

Study 99

Xia et al.

101

Li et al.

111

Demirok et al. 112

Li et al.

113

Wei and Wang

Year

Eyes

Preop

1 wk

1 mo

3 mo

6 mo

2016

69

59.5 ± 1.7

57.2 ± 6.4

58.7 ± 4.1

59.6 ± 1.6

59.8 ± 0.8

2013

38

58.16 ± 3.37

29.59 ± 17.73

30.00 ± 16.37

37.92 ± 15.42

46.94 ± 11.73

2013

28

56.8 ± 4.7

45.6 ± 11.5

45.3 ± 10.5

49.3 ± 9.9

55.9 ± 4.9

2013

32

58.2 ± 4.5

23.2 ± 14.6

28.4 ± 13.9

34.2 ± 15.7

43.7 ± 11.7

2013

61

56.6 ± 4.5

47.5 ± 12.1

51.1 ± 10.5

57.3 ± 5.1

57.98

44.5

45.99

50.54

Weighted average corneal sensitivity

53.13

SMILE, Small-incision lenticule extraction.

TABLE 16.7B  Weighted Average of the Reported Corneal Sensitivity Values (in Millimeters) After FS-LASIK Procedure

Study 99

Xia et al.

101

Li et al.

111

Demirok et al. 112

Li et al.

113

Wei and Wang

Year

Eyes

Preop

1 wk

1 mo

3 mo

6 mo

2016

59

58.7 ± 2.6

21.0 ± 11.1

27.8 ± 13.6

36.1 ± 10.7

46.9 ± 8.9

2013

33

57.27 ± 6.26

20.61 ± 15.50

21.45 ± 15.34

27.50 ± 17.46

39.17 ± 16.09

2013

28

56.2 ± 5.0

30.3 ± 15.3

31.2 ± 14

37.5 ± 14.8

53.7 ± 5

2013

42

58.0 ± 3.8

15.4 ± 7.9

15.8 ± 9.5

25.6 ± 15.1

36.4 ± 16.1

2013

54

58.1 ± 4.3

22.1 ± 12.8

26.2 ± 17.2

37.9 ± 14.4

57.87

21.33

24.54

28.55

Weighted average corneal sensitivity

43.78

FS-LASIK, Femtosecond laser in situ keratomileusis.

mild dry-eye syndrome before surgery. Both procedures shortened TBUT in the postoperative period but values returned to baseline after 12 months with both procedures (Fig. 16.10). The Schirmer test uses a paper strip to measure the ability of the eyes to produce tears typically in 5 minutes, whereby moisturing of the strip of greater than or equal to 15 mm is considered normal, 14 to 9 mm is considered

mild dry eye, 8 to 4 mm is considered moderate dry eye, and less than 4 mm is considered severe dry eye. According to the weighted Schirmer test values, both SMILE and FS-LASIK had little effect on tear secretion during the postoperative period (14.44 for SMILE vs 14.63 for FS-LASIK; Fig. 16.11). The corneal sensitivity test uses an aesthesiometer (typically Cochet-Bonnet) to measure the degree of tactile

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

263

TABLE 16.8A  Weighted Average of the Reported Tear Osmolarity Values (in Milliosmoles) After SMILE Procedure

Study

Year

Eyes

100

2015

60

111

2013

28

Denoyer et al. Demirok et al.

Weighted average tear osmolarity

Preop

1 wk

1 mo

3 mo

305.1 ± 12.5

6 mo 300.3 ± 11.4

303 ± 10

304 ± 11

303 ± 10

302 ± 6

303

304

304.36

302

306 ± 9 301.91

SMILE, Small-incision lenticule extraction.

TABLE 16.8B  Weighted Average of the Reported Tear Osmolarity Values (in Milliosmoles) After FS-LASIK Procedure

Study

Year

Eyes

100

2015

30

111

2013

38

Denoyer et al. Demirok et al.

Weighted average tear osmolarity

Preop

1 wk

1 mo

3 mo

316.3 ± 11.6

6 mo 315.0 ± 11.9

298 ± 11

300 ± 8

302 ± 10

303 ± 6

298

300

308.31

303

304 ± 8 308.85

FS-LASIK, Femtosecond laser in situ keratomileusis.

• Fig. 16.9  Weighted Ocular Surface Disease Index (OSDI) score in eyes after small-incision lenticule extraction (SMILE) vs after femtosecond laser in situ keratomileusis (FS-LASIK).

• Fig. 16.10

  Weighted Schirmer test values in eyes after small-incision lenticule extraction (SMILE) vs after femtosecond laser in situ keratomileusis (FS-LASIK). TBUT, Tear breakup time.

corneal sensation by retracting the metal filament in an increment of 0.5 cm (full extension length is 6 cm) until the patient is able to feel it contact the cornea. As the length of the filament extension decreases from 6 cm to 0.5 cm, the pressure changes from 11 mm/g to 200 mm/g. Patients seem to have lower corneal sensitivity values after

• Fig. 16.11  Weighted corneal sensitivity in eyes after small-incision lenticule extraction (SMILE) vs after femtosecond laser in situ keratomileusis (FS-LASIK).

• Fig. 16.12  Weighted tear osmolarity values in eyes after small-incision lenticule extraction (SMILE) vs after femtosecond laser in situ keratomileusis (FS-LASIK).

FS-LASIK than after SMILE at all postoperative follow-up periods, which may be explained with the lesser trauma to the innervation associated with SMILE (as described earlier; Fig. 16.12). Tear film osmolarity testing is meant to be used in conjunction with other dry-eye signs and symptoms to

264 se c t i o n V 264

LASIK and SMILE

• Fig. 16.13

  Weighted percentage of various intraoperative complications during small-incision lenticule extraction (SMILE). FS-LASIK, femtosecond laser in situ keratomileusis.

provide quantitative information mainly on the inflammatory component of dry-eye suspects. Abnormality in tear film is indicated either by an elevated reading of greater than 300 mOsm/L (indicating loss of homeostasis) or an intereye difference of greater than 8 mOsm/L (indicating tear film instability). Only two studies were found to report tear film osmolarity measurements after SMILE and FSLASIK; thus the results may not be as valid. However, tear film osmolarity appears to show greater loss of homeostasis after FS-LASIK procedure than after SMILE (301.91 at 6 months for SMILE vs 308.85 at 6 months after FS-LASIK; Fig. 16.13). Overall, looking at the various indicators for dry eye and comparing the preoperative and postoperative values at 6 months, except for the Schirmer test values, SMILE does not appear to exacerbate dry eye, whereas FS-LASIK appears to do so to some extent at least up to 6 months. Discrepancies in different studies in dry-eye evaluation after corneal refractive surgery may partially be explained with the different parameters used to evaluate dry-eye severity.

Corneal Biomechanics Corneal hysteresis (CH) and corneal resistance factor (CRF) are two important measures used to understand the biomechanics of the cornea. CH and CRF both are measurements of the flexibility of the cornea. CH is defined as the difference in the applanation pressures measured (P1 − P2) as a result of the viscous damping in the corneal tissue. Viscous properties of the cornea help maintain the ability of the cornea to absorb and dissipate energy.114 CRF is defined as P1 − K × P2, where K = 0.7, and is determined based on the clinical studies and statistical correlation models. CRF gives more weight to P1 compared to P2 and is thought to be a better indicator of total viscoelastic response of the cornea in response to the air pulse. Two devices are currently used to measure CH and CRF: the Reichert Ocular Response Analyzer (ORA) and Corvis ST (Oculus). Although some authors report a slight increase in CH and CRF values at 3 months postoperatively,115 others report CH and CRF values to be significantly lower (P < .05) after all keratorefractive procedures, such as LASIK, refractive lenticule extraction (ReLEx) flex, and ReLEx SMILE.117 CH and CRF values are also reported to be lower

•

Fig. 16.14  Weighted average of corneal resistance factor (CRF) values after small-incision lenticule extraction (SMILE) vs after femtosecond laser in situ keratomileusis (FS-LASIK).

• Fig. 16.15

  Weighted average of corneal resistance factor values after small-incision lenticule extraction (SMILE) vs after femtosecond laser in situ keratomileusis (FS-LASIK).

in keratoconic corneas in comparison to normal eyes,118 which suggests that biomechanically weaker corneas tend to have lower CH and CRF values. We included seven studies to find the weighted average of CH and CRF values after SMILE (Table 16.9). A study by El-Massry et al.29 was included twice because they reported CH and CRF values separately for the right and left eyes, in which the incision depths were 100  µm and 160  µm, respectively. We included 5 studies to find the weighted average of CH and CRF values after FS-LASIK (Table 16.10). At 1 month postoperatively, there appears to be greater change in CH values after SMILE (1.80) than after LASIK (1.53); however, at 3 months postoperatively, there appears to be greater change in CH values after LASIK (2.35) than after SMILE (2.22). Regarding CRF values, at both 1 month and 3 months postoperatively, there appears to be greater change after FSLASIK than after SMILE. The weighted averages of the CH and CRF values after SMILE vs after FS-LASIK are shown graphically in Figs. 16.14 and 16.15.

Further Areas of SMILE Applicability SMILE has been reported to be applicable for other kinds of treatment besides refractive correction. Park et al122 reported a case of a man with posterior polymorphic corneal dystrophy successfully undergoing a SMILE procedure. The corneal dystrophy was revealed through a band-like lesion in the corneal endothelium of

2015

2015

119

2016

China

Egypt

China

Egypt

Egypt

China

Turkey

Egypt

Country

SMILE, Small-incision lenticule extraction.

Weighted average

Zhang et al.

121

Osman et al.

120

Wu and Wang

El-Massry et al.

2016

2015

El-Massry et al.

29

2015

Dou et al.

29

2013

Agca et al.

115

2017

Hosny et al.118

46

Year

Study

80

25

75

30

30

36

60

30

No. of Eyes

10.46

10.67

12.03

10.16

10.64

10.76

10

10.7

8.9

Preop CH (mm Hg)

8.66

8.03

9.99

9.97

9.71

8.23

8.5

7.7

Postop (1 mo) CH (mm Hg)

8.24

8.06

8.3

8.51

Postop (3 mo) CH (mm Hg)

8.6

8.6

Postop (6 mo) CH (mm Hg)

TABLE 16.9  Corneal Hysteresis (CH) and Corneal Resistance Factors (CRF) Values After SMILE

9.68

10.65

11.42

10.39

10.06

10.2

10.1

10.9

8.7 (6.7–10.6)

CRF (µm)

Preop

7.23

7.13

9.43

9.31

9.13

7.65

8

5.8 (4.9–6.8)

CRF (µm)

Postop (1 mo)

7.26

7.11

7.25

7.61

CRF (µm)

Postop (3 mo)

7.3

7.3

Postop (6 mo) CRF (µm)

CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

265

266 se c t i o n V 266

LASIK and SMILE

TABLE 16.10  Corneal Hysteresis (CH) and Corneal Resistance Factors (CRF) Values After LASIK

No. of Eyes

Preop CH (mm Hg)

Postop (1 mo) CH (mm Hg)

Postop (3 mo) CH (mm Hg)

Study

Year

Country

Agca et al.46

2013

Turkey

60

Dou et al.115

2015

China

36

9.99

Wu and Wang119

2015

China

75

10.09

Osman et al.120

2016

Egypt

25

11.59

8.46

Zhang et al.121

2016

China

80

10.83

8.19

7.93

10.5

8.97

8.15

Weighted average

10.7 8.15

8.6

Postop (6 mo) CH (mm Hg) 8.7

Preop CRF (µm)

Postop (1 mo) CR (µm)

Postop (3 mo) CRF (µm)

10.9

7.9

7.7

8.47

10.21

7.52

7.53

7.86

10.57

6.77 11

8.7

Postop (6 mo) CRF (µm)

7.45

10.69

6.91

6.85

10.6

7.82

7.16

LASIK, Laser in situ keratomileusis.

the right eye on slit-lamp examination. The patient underwent SMILE and obtained 20/20 vision in both eyes with no further progression of his corneal dystrophy 12 months after SMILE. Additionally, the SMILE-derived stromal lenticules have been reported to be used as lenticule patch grafts to treat microperforations and partial-thickness corneal defects, such as corneal tears. Bhandari et al.123 reported the use of fibrin glue to patch SMILE-derived lenticules in the eyes of seven patients who presented with microperforations who were followed up at 1, 7, and 15 days, and at 1 and 3 months postoperatively. The lenticule grafts were reported to have become well attached and clear until the last followup of 3 months in all eyes, with no complications. Abd Elaziz et al.124 also used SMILE-derived lenticules to seal the corneal perforations in the eyes of seven patients. The authors laid the lenticules over the perforations and stitched them in place with interrupted 10-0 nylon sutures. A single layer of amniotic membrane was then laid on top. During the follow-up period of 1 year, all patients showed smooth sealing of the corneal perforations, with three patients exhibiting improved postoperative best corrected visual acuity (BCVA). The SMILE-derived lenticules for use in treating corneal complications can either be fresh or can be used after cryopreservation of the lenticule. Liu et al.125 first showed the viability of the transplanted lenticule in rabbit eyes, in which the lenticules were transplanted from the right eyes into the FS laser–created corneal stromal pockets of the left eyes. During the study, corneal inflammation and edema were observed at day 10; however, the edema had dissolved and nerve regeneration had begun by 1 month.

By 3 months, the lenticule had integrated into the recipient cornea. By 6 months, the morphology and distribution of the corneal stromal fibers and nerve fibers had returned to normal. In patients, Ganesh et al.126 used cryopreserved lenticules to treat eight hyperopic and one aphakic eyes of seven patients, in which the cryopreserved lenticules were implanted in the FS laser–created corneal pockets. The lenticules had been previously collected from patients undergoing SMILE for the correction of myopia and preserved for a range of 19 to 178 days. None of the allogeneic subjects was reported to reject the lenticules or show loss of BCVA at the end of the follow-up period (range, 38–210 days).

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CHAPTER 16  Small-Incision Lenticule Extraction (SMILE)

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44. Shetty R, Francis M, Shroff R, et al. Corneal biomechanical changes and tissue remodeling after SMILE and LASIK. Invest Ophthalmol Vis Sci. 2017;58(13):5703. doi:10.1167/iovs. 17-22864. 45. Gao S, Li S, Liu L, et al. Early changes in ocular surface and tear inflammatory mediators after small-incision lenticule extraction and femtosecond laser-assisted laser in situ keratomileusis. PLoS ONE. 2014;9(9):e107370. 46. Agca A, Ozgurhan EB, Demirok A, et al. Comparison of corneal hysteresis and corneal resistance factor after small incision lenticule extraction and femtosecond laser-assisted LASIK: a prospective fellow eye study. Cont Lens Anterior Eye. 2014;37: 77–80. 47. Pedersen IB, Bak-Nielsen S, Vestergaard AH, Ivarsen A, Hjortdal J. Corneal biomechanical properties after LASIK, ReLEx flex, and ReLEx smile by scheimpflug-based dynamic tonometry. Graefes Arch Clin Exp Ophthalmol. 2014;252: 1329–1335. 48. Wang D, Liu M, Chen Y, et al. Differences in the corneal biomechanical changes after SMILE and LASIK. J Refract Surg. 2014;30(10):702–707. 49. Shen Y, Chen Z, Knorz MC, Li M, Zhao J, Zhou X. Comparison of corneal deformation parameters after SMILE, LASEK, and femtosecond laser-assisted LASIK. J Refract Surg. 2014;30(5):310–318. 50. Seven I, Vahdati A, Pedersen IB, et al. Contralateral eye comparison of SMILE and flap-based corneal refractive surgery: computational analysis of biomechanical impact. J Refract Surg. 2017;33(7):444–453. doi:10.3928/1081597X-20170504-01. 51. Knox Cartwright NE, Tryer JR, Jaycock PD, Marshall J. Effects of variation in depth and side cut angulations in LASIK and thin-flap LASIK using femtosecond laser: a biomechanical study. J Refract Surg. 2012;28:419–425. 52. Randleman JB, Dawson DG, Grossniklaus HE, McCarey BE, Edelhauser HF. Depth-dependent cohesive tensile strength in human donor corneas: implications for refractive surgery. J Refract Surg. 2008;24:S85–S89. 53. Scarcelli G, Pineda R, Yun SH. Brillouin optical microscopy for corneal biomechanics. Invest Ophthalmol Vis Sci. 2012;53: 185–190. 54. Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin and ultraviolet a light. J Cataract Refract Surg. 2006;32:279–283. 55. Shih P-J, Wang I-J, Cai W-F, Yen J-Y. Biomechanical simulation of stress concentration and intraocular pressure in corneas subjected to myopic refractive surgical procedures. Sci Rep. 2017;7(1):13906. doi:10.1038/s41598-017-14293-0. 56. Delalleau A, Josse G, Lagarde JM, Zahouani H, Bergheau JM. Characterization of the mechanical properties of skin by inverse analysis combined with the indentation test. J Biomech. 2006;39:1603–1610. 57. Reinstein DZ, Archer TJ, Randleman JB. Mathematical model to compare the relative tensile strength of the cornea after PRK, LASIK, and small incision lenticule extraction. J Refract Surg. 2013;29(7):454–460. doi:10.3928/1081597X-20130617-03. 58. Kanellopoulos AJ. Topography-guided LASIK versus small incision lenticule extraction (SMILE) for myopia and myopic astigmatism: a randomized, prospective, contralateral eye study. J Refract Surg. 2017;33(5):306–312. 59. Kahlifa MA, Ghoneim A, Shafik Shaheen M, Aly MG, Pinero DP. Comparative analysis of the clinical outcomes of SMILE

and wavefront-guided LASIK in low and moderate myopia. J Refract Surg. 2017;33(5):298–304. 60. Zhang S, Xu H, Zheng K, et al. The observation during small incision lenticule extraction for myopia with corneal opacity. BMC Ophthalmol. 2017;17(1):80. 61. Pedersen IB, Ivarsen A, Hjortdal J. Three-year results of small incision lenticule extraction for high myopia: refractive outcomes and aberrations. J Refract Surg. 2015;31(11): 719–724. 62. Kobashi H, Kamiya K, Igarashi A, Takahashi M, Shimizu K. Two-years results of small-incision lenticule extraction and wavefront-guided laser in situ keratomileusis for myopia. Acta Ophthalmol. 2017. 63. Burazovitch J, Naguzeswski D, Beuste T, Guillard M. Predictability of SMILE over four years in high myopes. J Fr Ophtalmol. 2017;40(6):e201–e209. 64. Ganesh S, Brar S, Patel U. Comparison of ReLEx SMILE and PRK in terms of visual and refractive outcomes for correction of low myopia. Int Ophthalmol. 2017. 65. Hyun S, Lee S, Kim JH. Visual outcomes after SMILE, LASEK, and LASEK combined with corneal collagen cross-linking for high myopic correction. Cornea. 2017;36(4):399–405. 66. Chan TC, Yu MC, Ng A, Wang Z, Cheng GP, Jhanji V. Early outcomes after small incision lenticule extraction and photorefractive keratectomy for correction of high myopia. Sci Rep. 2016;32(90):644–647. 67. Wong JX, Wong EP, Htoon HM, Mehta JS. Intraoperative centration during small incision lenticule extraction (SMILE). Medicine (Baltimore). 2017;96(16):e6076. 68. Hansen RS, Lynche N, Grauslund J, Vestergaard AH. Smallincision lenticule extraction (SMILE): outcomes of 722 eyes treated for myopia and myopic astigmatism. Graefes Arch Clin Exp Ophthalmol. 2016;254(2):399–405. 69. Han T, Zheng K, Chen Y, Gao Y, He L, Zhou X. Four-year observation of predictability and stability of small incision lenticule extraction. BMC Ophthalmol. 2016;16(1):149. 70. Ang M, Farook M, Htoon HM, Tan D, Mehta JS. Simulated night vision after small-incision lenticule extraction. J Cataract Refract Surg. 2016;42(8):1173–1180. 71. Ang M, Ho H, Fenwick E, et al. Vision-related quality of life and visual outcomes after small-incision lenticule extraction and laser in situ keratomileusis. J Cataract Refract Surg. 2015;41(10):2136–2144. 72. Kamiya K, Shimizu K, Igarashi A, Kobashi H. Visual and refractive outcomes of small incision lenticule extraction for the correction of myopia: 1-year follow-up. BMJ Open. 2015;5(11): e008268. 73. Agca A, Demirok A, Cankaya KI, et al. Comparison of visual acuity and higher-order aberrations after femtosecond lenticule extraction and small-incision lenticule extraction. Cont Lens Anterior Eye. 2014;37(4):292–296. 74. Kim JR, Kim BK, Mun SJ, Chung YT, Kim HS. One-year outcomes of small-incision lenticule extraction (SMILE): mild to moderate myopia vs. high myopia. BMC Ophthalmol. 2015; 15:59. 75. Xu Y, Yang Y. Small-incision lenticule extraction for myopia: results of a 12-month prospective study. Optom Vis Sci. 2015; 92(1):123–131. 76. Kamiya K, Shimizu K, Igarashi A, Kobashi H. Visual and refractive outcomes of femtosecond lenticule extraction and small-incision lenticule extraction for myopia. Am J Ophthalmol. 2014;157(1):128–134.

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77. Vestergaard AH. Past and present corneal refractive surgery: a retrospective study of long-term results after photorefractive keratectomy and prospective study of refractive lenticule extraction. Acta Ophthalmol. 2014;92. Thesis 2:1–21. 78. Agca A, Demirok A, Cankaya KI, et al. Comparison of visual acuity and higher-order aberrations after femtosecond lenticule extraction and small-incision lenticule extraction. Cont Lens Anterior Eye. 2014;37(4):292–296. 79. Ang M, Ho H, Fenwick E, et al. Vision-related quality of life and visual outcomes after small-incision lenticule extraction and laser in situ keratomileusis. J Cataract Refract Surg. 2015;41(10):2136–2144. 80. Kim JR, Kim BK, Mun SJ, Chung YT, Kim HS. Oneyear outcomes of small-incision lenticule extraction (SMILE): mild to moderate myopia vs. high myopia. BMC Ophthalmol. 2015;15:59. 81. Miao H, He L, Shen Y, Li M, Yu Y, Zhou X. Optical quality and intraocular scattering after femtosecond laser small incision lenticule extraction. J Refract Surg. 2014;30(5):296–302. 82. Vestergaard A, Ivarsen AR, Asp S, Hjortdal JØ. Small-incision lenticule extraction for moderate to high myopia: predictability, safety and patient satisfaction. J Cataract Refract Surg. 2012;38(11):2003–2010. 83. Hjortdal JO, Vestergaard AH, Ivarsen A, Ragunathan S, Asp S. Predictors for the outcome of small-incision lenticule extraction for myopia. J Refract Surg. 2012;28(12):865–871. 84. Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95(3):335–339. 85. Taneri S, Kießler S, Rost A, Dick B. Experience with introduction of SMILE: learning phase of our first 200 treatments. Klin Monbl Augenheilkd. 2017;234(1):70–76. 86. Kim BK, Mun SJ, Lee DG, Choi HT, Chung YT. Chung’s wing technique: a new technique for small-incision lenticule extraction. BMC Ophthalmol. 2016;16(1):154. 87. Ng AL, Chan TC, Cheng GP, et al. Comparison of the early clinical outcomes between combined small-incision lenticule extraction and collagen cross-linking versus SMILE for myopia. J Ophthalmol. 2016;2016:2672980. 88. Zhao Y, Li M, Yao P, Shah R, Knorz MC, Zhou X. Development of the continuous curvilinear lenticulerrhexis technique for small incision lenticular extraction. J Refract Surg. 2015;31(1):16–21. 89. Tityal JS, Kaur M, Rathi A, Falera R, Chaniyara M, Sharma N. Learning curve of small incision lenticule extraction: challenges and complications. Cornea. 2017;36(11):1377–1382. 90. Wang Y, Ma J, Zhang J, et  al. Incidence and management of intraoperative complications during small-incision lenticule extraction in 3004 cases. J Cataract Refract Surg. 2017;43(6):796–802. 91. Park JH, Koo HJ. Comparison of immediate small-incision lenticule extraction after suction loss with uneventful smallincision lenticule extraction. J Cataract Refract Surg. 2017;43(4): 466–472. 92. Gab-Alla AA. Refraction outcomes after suction loss during small-incision lenticule extraction (SMILE). Clin Ophthalmol. 2017;11:511–515. 93. Son G, Lee J, Jang C, Choi KY, Cho BJ, Lim TH. Possible risk factors and clinical effects of opaque bubble layer in small incision lenticule extraction (SMILE). J Refract Surg. 2017;33(1): 24–29.

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94. Liu M, Wang J, Zhong W, Wang D, Zhou Y, Liu Q. Impact of suction loss during small incision lenticule extraction (SMILE). J Refract Surg. 2016;32(10):686–692. 95. Osman IM, Awad R, Shi W, Abou Shousha M. Suction loss during femtosecond laser-assisted small-incision lenticule extraction: incidence and analysis of risk factors. J Cataract Refract Surg. 2016;42(2):246–250. 96. Ramirez-Miranda A, Ramirez-Luquin T, Navas A, GraueHernandez EO. Refractive lenticule extraction complications. Cornea. 2015;34(suppl 10):S65–S67. 97. Wong CW, Chan C, Tan D, Mehta JS. Incidence and management of suction loss in refractive lenticule extraction. J Cataract Refract Surg. 2014;40(12):2002–2010. 98. Ivarsen A, Asp S, Hjortdal J. Safety and complications of more than 1500 small-incision lenticule extraction procedures. Ophthalmology. 2014;121(4):822–828. 99. Xia L, Zhang J, Wu J, Yu K. Comparison of corneal biological healing after femtosecond LASIK and small incision lenticule extraction procedure. Curr Eye Res. 2016;41(9):1202–1208. 100. Denoyer A, Landman E, Trinh L, Faure JF, Auclin F, Baudouin C. Dry eye disease after refractive surgery: comparative outcomes of small incision lenticule extraction versus LASIK. Ophthalmology. 2015;122(4):669–676. 101. Li M, Zhao J, Shen Y, et al. Comparison of dry eye and corneal sensitivity between small incision lenticule extraction and femtosecond LASIK for myopia. PLoS ONE. 2013;8(10):e77797. 102. Mattila JS, Holopainen JM. Bilateral ectasia after femtosecond laser-assisted small incision lenticule extraction. J Refract Surg. 2016;32(7):497–500. 103. Sachdev G, Sachdev MS, Sachdev R, Gupta H. Unilateral corneal ectasia following small-incision lenticule extraction. J Cataract Refract Surg. 2015;41(9):2014–2018. 104. Mastropasqua L. Bilateral ectasia after femtosecond laserassisted small-incision lenticule extraction. J Cataract Refract Surg. 2015;41(6):1338–1339. 105. Wang Y, Cui C, Li Z, et al. Corneal ectasia 6.5 months after small incision lenticule extraction. J Cataract Refract Surg. 2015;41(5):1100–1106. 106. El-Naggar MT. Bilateral ectasia femtosecond laser assisted small-incision lenticule extraction. J Cataract Refract Surg. 2015;41(4):884–888. 107. Zhao J, He L, Yao P, et al. Diffuse lamellar keratitis after smallincision lenticule extraction. J Cataract Refract Surg. 2015;41(2): 400–407. 108. Bansal AK, Murthy SI, Maaz SM, Sachdev MS. Shifting “ectasia”: interface fluid collection after small incision lenticule extraction (SMILE). J Refract Surg. 2016;32(11):773–775. 109. Wang B, Naidu RK, Chu R, Dai J, Qu X, Zhou H. Dry eye disease following refractive surgery: a 12-month follow-up of SMILE versus FS-LASIK in high myopia. J Ophthalmol. 2015; 2015:132417. 110. Xu Y, Yang Y. Dry eye after small incision lenticule extraction and LASIK for myopia. J Refract Surg. 2014;30(3):186–190. 111. Demirok A, Ozgurhan EB, Agca A, et al. Corneal sensation after corneal refractive surgery with small incision lenticule extraction. Optom Vis Sci. 2013;90(10):1040–1047. 112. Li M, Niu L, Qin B, et al. Confocal comparison of corneal reinnervation after small incision lenticule extraction (SMILE) and femtosecond laser in situ keratomileusis (FS-LASIK). PLoS ONE. 2013;8(12):e81435. 113. Wei S, Wang Y. Comparison of corneal sensitivity between FSLASIK and femtosecond lenticule extraction (ReLEx flex) or

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small-incision lenticule extraction (ReLEx smile) for myopic eyes. Graefes Arch Clin Exp Ophthalmol. 2013;251(6):1645–1654. 114. Luce DA. Determining in vivo biomechanical properties of the cornea with an ocular response analyzer. J Cataract Refract Surg. 2005;31:156–162. 115. Dou R, Wang Y, Xu L, Wu D, Wu W, Li X. Comparison of corneal biomechanical characteristics after surface ablation refractive surgery and novel lamellar refractive surgery. Cornea. 2015;34(11):1441–1446. 116. Pedersen IB, Bak-Nielsen S, Vestergaard AH, Ivarsen A, Hjortdal J. Corneal biomechanical properties after LASIK, ReLEx flex, and ReLEx smile by scheimpflug-based dynamic tonometry. Graefes Arch Clin Exp Ophthalmol. 2014;252(8): 1329–1335. 117. Ortiz D, Pinero D, Shabayek MH, Arnalich-Montiel F, Alio JL. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg. 2007;33:1371–1375. 118. Hosny M, Aboalazayem F, El Shiwy H, Salem M. Comparison of different intraocular pressure measurement techniques in normal eyes and post small incision lenticule extraction. Clin Ophthalmol. 2017;11:1309–1314. 119. Wu W, Wang Y. The correlation analysis between corneal biomechanical properties and the surgically induced corneal high-order aberrations after small incision lenticule extraction and femtosecond laser in situ keratomileusis. J Ophthalmol. 2015;2015:758196.

120. Osman IM, Helaly HA, Abdalla M, Shousha MA. Corneal biomechanical changes in eyes with small incision lenticule extraction and laser assisted in situ keratomileusis. BMC Ophthalmol. 2016;16:123. 121. Zhang J, Zheng L, Zhao X, Xu Y, Chen S. Corneal biomechanics after small-incision lenticule extraction versus Q-valueguided femtosecond laser-assisted in situ keratomileusis. J Curr Ophthalmol. 2016;28(4):181–187. 122. Park JH, Lee JH, Koo HJ. Small-incision lenticule extraction in posterior polymorphic corneal dystrophy. J Cataract Refract Surg. 2016;42(5):795–797. 123. Bhandari V, Ganesh S, Brar S, Pandey R. Application of the SMILE-derived glued lenticule patch graft in microperforations and partial-thickness corneal defects. Cornea. 2016;35(3):408–412. 124. Abd Elaziz MS, Zaky AG, el Saebaysarhan AR. Stromal lenticule transplantation for management of corneal perforations: one year results. Graefes Arch Clin Exp Ophthalmol. 2017;255(6):1179–1184. 125. Liu H, Zhu W, Jiang AC, Sprecher AJ, Zhou X. Femtosecond laser lenticule transplantation in rabbit cornea: experimental study. J Refract Surg. 2012;28:907–911. 126. Ganesh S, Brar S, Rao PA. Cryopreservation of extracted corneal lenticules after small incision lenticule extraction for potential use in human subjects. Cornea. 2014;33(12):1355–1362.

17 

Small-Incision Lenticule Extraction (SMILE) Complications and Their Management SUPHI TANERI

Introduction Small-incision lenticule extraction (SMILE) is highly appealing to patients and surgeons alike because of its minimally invasive and virtually painless nature. However, it is not free from potential complications. In this chapter, we discuss advantages and limitations of SMILE to provide an understanding of the genesis of possible complications. We then propose some strategies to avoid complications in the first place and to manage them if encountered despite due diligence.

Theoretical Advantages and Limitations of SMILE The basic principle of SMILE is to reshape the anterior corneal surface by subtracting (i.e., removing) stromal tissue from the center of the cornea. The same applies to laser in situ keratomileusis (LASIK); therefore most complications of SMILE are similar to those of LASIK in signs, symptoms, and treatment. In SMILE, as opposed to LASIK, a corneal flap is not created. Instead, a small incision is made in the mid-periphery of the cornea with a femtosecond (FS) laser, and the lenticule is removed through this self-sealing incision. This “keyhole procedure” is certainly more demanding in terms of surgical dexterity than performing photorefractive keratectomy (PRK) or LASIK and a steep learning curve is to be expected when starting SMILE.1 Therefore we strongly advise not performing the SMILE procedure before getting enough experience doing LASIK with the VisuMax II laser (Carl Zeiss Meditec). The minimally invasive technique of SMILE makes the treatment of some complications more challenging than after LASIK for the inexperienced surgeon. We therefore also recommend

getting comfortable with the management of LASIK complications first. On the other hand, due to the same minimally invasive technique of SMILE, some of these complications are expected to be less frequent in the hands of an experienced surgeon.

Advantages The most obvious advantage of SMILE compared to LASIK is the absence of a flap. As early as on the first day after uncomplicated SMILE, patients can resume every one of their daily activities, including water sports and putting on make-up, without the risk of traumatic flap dislocation— which may occur even several years after LASIK. When in SMILE a side cut of a few millimeters of length is created, fewer corneal nerves are severed than with a LASIK flap, leading to less impaired corneal sensitivity. This is thought to be the main reason why dry-eye symptoms after SMILE are less pronounced and shorter in duration than after LASIK. The SMILE procedure has additional potential advantages, because no corneal flap is created: SMILE may pose less risk for postsurgical ectasia than refractive lenticule extraction (ReLEx) or LASIK. Several theoretical models postulate a greater tectonic stability after SMILE than after flap procedures.2,3 However, these mathematical models are based on certain assumptions that are difficult to verify at present; the real advantage of SMILE may be smaller than calculated based on these assumptions. Only time will tell the real incidence of ectasia after SMILE. To date, there are few reports of ectasia—all of these cases were also not suitable for LASIK (mostly owing to irregular topography). At present, at least for the novel SMILE surgeon, it seems prudent to apply the same inclusion and exclusion criteria as for LASIK. In the future, these criteria may change once the following question is satisfactorily answered: At what 271

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depth should the lenticule be extracted? It is generally accepted that the anterior stroma is biomechanically stronger than the posterior stroma and that the LASIK flap does not contribute significantly to the tectonic stability, making a thinner flap more desirable than a thicker one. The opposite is being discussed in SMILE: extracting the lenticule at a deeper level may be beneficial in terms of ectasia risk although a thinner residual stromal bed is left behind. In SMILE, the crucial step for the refractive result, the laser application, takes place inside the cornea, that is, in a closed system. Therefore in contrast to excimer-laser ablative surgery, SMILE is not influenced by external factors, such as room temperature and humidity or the water content of the cornea. In other words, in LASIK, dehydration of the flap may lead to striae formation and dehydration of the stroma may cause an inconstant ablation rate in higher corrections or prolonged flap-open time, all affecting the visual outcome. In addition, in LASIK, eye movements may change the angle of incidence of the laser beam on the cornea during laser ablation, also contributing to the induction of higher-order aberrations. In contrast, in SMILE, the eye is fixated and the cornea is normally hydrated during laser application. These principal differences may explain why, according to the published literature, SMILE provides equal or better results compared to excimer-laser ablations for the correction of myopia regarding predictability and long-term stability of the attempted correction and postoperative visual quality. These conceptual benefits and the superior results that we actually yielded in our clinical application have made SMILE our method of choice for the corneal correction of myopia and myopic astigmatism.

Limitations SMILE for hyperopic and mixed astigmatic treatments has been performed in animal models and clinical studies but currently is not routinely available. The geometry of the tissue to be removed in a hyperopic treatment differs substantially from the lenticule extracted in a myopic SMILE. In hyperopia, the subtracted tissue is thinner in the center and the rim but thicker in the mid-periphery, resembling a donut. This requires even more surgical skill than removing a myopic lenticule, which is thickest in the center. Hence, some complications are expected to occur more frequently, including suction loss, tearing of the tissue, dry-eye issues, and more. Furthermore, compared to excimer-laser procedures, which have been refined for almost 3 decades, SMILE is still evolving. At present, there is no iris recognition confirming the correct matching of treatment plan and eye before starting the treatment. Thus the potentially very severe complication of treating an eye with data belonging to another eye, thus aggravating the refractive error beyond the limits that can be corrected with laser surgery, must be ruled out by careful checking. We recommend doing a team time-out. Currently, there is no rotational eye-tracking

compensating for less than optimal cyclotorsional alignment before fixating the eye. Last, it is not possible to adjust centration after docking. However, as these technologies already exist in other lasers, their implementation into a SMILE laser should be possible.

How to Avoid Complications The best complications are those avoided. Therefore the treatment procedure is described step by step, including some pearls to avoid typical caveats. These recommendations are given to the best of our current knowledge and abilities and represent one, but certainly not the only, way to perform SMILE. With ongoing technical improvements and a growing body of scientific evidence, changes in these recommendations seem inevitable. 1. In high astigmatic corrections, you may want to mark the cornea in a sitting position to manually compensate any cyclotorsional eye movements before docking to avoid an astigmatic undercorrection. 2. Make sure to enter the correct treatment data and select the correct patient/eye/procedure (preferably with a team time-out to rule out an inappropriate treatment. 3. Select the desired mode (Standard, Fast, Expert). Choosing Expert mode allows for determining spot and track spacing separately for each cut type (e.g., flap cut, side cut), pulse energy, and more. Another bonus of the Expert mode is that a more detailed report of the procedure is created and saved by the laser. 4. Carefully instruct patients as to what they are going to experience during the procedure and what they are expected to do before actually starting in order to ensure best cooperation: a. “Look at the blinking green light” (allowing us to center on the line of sight). b. “There will be no pain but you will feel some pressure while your eye is fixated and the laser is applied.” c. “Your vision will get foggy starting from the periphery, the green light may appear to move; don’t try to follow it.” d. “Don’t move and don’t speak while suction is on.” 5. Apply anesthetic eye drops right before the next steps. It is imperative that they are unpreserved because preservatives damage the epithelium, thus facilitating abrasions and epithelial nests (Fig. 17.1, Video 17.1) in the interface. 6. We then drape the eye in a sterile fashion; other surgeons prefer not to bother the patient in order not to compromise cooperation. These surgeons often apply the laser in both eyes before draping the eye and removing the lenticule later. 7. We insert a speculum with suction and rinse the ocular surface with a sterile balanced salt solution; others use a wet sponge to clean the cornea. We check through the microscope that the ocular surface is free from eyelashes, other particles, and tear-film residues to avoid problems obtaining and maintaining suction as well as obstruction

CHAPTER 17  Small-Incision Lenticule Extraction (SMILE) Complications and Their Management

of the laser beam, leading to less than optimal tissue separation. 8. The docking procedure should be performed swiftly with the patient fixating on the green target. If centration is not perfect, suction should be released. If need be, the ocular surface may be cleaned or moistened before suction is applied again.

Difficulties in Obtaining Suction In deep-set eyes or patients with a big nose or small palpebral fissure, it may be difficult to sufficiently applanate the cornea with the conical patient interface to build up proper suction. In these cases, the cooperation of the patient is needed to exactly tilt the head to an optimal position while the fixation of the blinking target must not be compromised. It is mandatory to obtain proper centration first before starting the laser to avoid a decentered treatment. It may occur with a patient unable to fixate the green blinking target, usually because of anxiety. It is crucial to make the

• Fig. 17.1

 

Epithelial cell nest within interface (1.5 years postoperatively).

• Fig. 17.3

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patient as comfortable as possible before and during surgery to obtain the patient’s cooperation.

Preparation for Lenticule Extraction Start the laser and observe the progress of the bubble layer formation through the microscope. Very dense (opaque) areas may be due to a pulse energy setting that is too high; “black” areas without noticeable stain may be due to a pulse energy that is too low (Fig. 17.2). Both may be indicative of difficult tissue separation. Therefore these areas should be attacked first during manual separation while the surrounding tissue is still providing stability to avoid lenticule tears and other problems. We prefer to extract the lenticule directly after the laser treatment because the visibility of the cutting planes quickly deteriorates as the gas bubble layers dissolve within minutes, theoretically increasing the risk of a via falsa preparation. Experienced surgeons may be able to perform a lenticule separation with a wide range of spatula-like instruments. However, for the surgeon starting with SMILE, we recommend a dedicated SMILE instrument (Fig. 17.3, Video 17-2; 6-836-1 SMILE Double Ended Dissector with Taneri spoon tip, Duckworth & Kent). This instrument has a

• Fig. 17.2

 

Black spots appearing during lenticule preparation.

  SMILE Instrument with semi-sharp spoon-shaped tip: 6-836-1 SMILE Double Ended Dissector with Taneri spoon tip. (Source: Duckworth & Kent.)

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semi-sharp spoon-shaped tip that facilitates lenticule dissection in every direction, including reverse movements.

Lenticule Dissection and Extraction This part of the procedure may be the most demanding for the surgeon and the least comfortable for the patient. Luckily, there is no need to rush as the cornea may still be considered closed and the refractive result will not be compromised as long as the lenticule is completely extracted in the end. • Open the side cut gently with the blunt rounded tip of the SMILE instrument. Make sure that the opening is long enough to minimize the risk of traumatic enlargements (cap tears). We recommend 5 mm for the first cases. • Identify the anterior and posterior plane of the lenticule with the same tip. We recommend opening the entrance to the anterior plane over the entire length of the side cut. Then, point the tip slightly downward to enter the lower plane about half the size of the side cut. Some resistance together with a visible lenticule edge above the tip are signs that the instrument has entered the posterior plane. This step is easier if the cap diameter exceeds the lenticule diameter by at least 1 mm. • Dissecting the anterior (upper) plane first is much easier than peeling the lenticule from the relatively mobile cap and avoids many complications, such as cap tears, cap perforation, and ruptured lenticules. • Dissect the posterior plane. We prefer to stabilize the globe during dissection using suitable forceps. Some surgeons simply instruct the patient to look into the bright light of the microscope, thus avoiding the discomfort of grasping the eye with forceps. • Extract the lenticule using suitable forceps. Only attempt to extract the lenticule after full separation to avoid a torn lenticule. To this end, it is advisable to make a farreaching circular movement with the dissecting instrument anterior and posterior of the lenticule to ensure complete separation.

Flushing the Interface The interface may be flushed after lenticule extraction to minimize the risk of remaining debris, thus reducing the risk of diffuse lamellar keratitis (DLK) and potentially also that of microdistorsions of the Bowman layer. On the other hand, flushing may lead to more postoperative edema, causing a slower visual recovery. We are currently involved in a multicenter study to better evaluate both options.

Management of Intraoperative Complications Decentration As in other laser procedures, decentration is best avoided because it is difficult to correct. Good centration needs to

be confirmed after applying suction; otherwise, suction must be released and reapplied before starting the laser. A decentered ablation may be corrected with topographyguided excimer ablations.

Suction Loss Intraoperative suction loss occurs in approximately 2%, with a lower incidence as the surgeons gains more experience (Video 17.3).4 It is one of the most dreaded complications because it can permanently preclude a SMILE treatment, necessitating a change to another treatment modality, such as surface ablation, LASIK, or implantation of phakic intraocular lenses (PIOLs). Several issues may contribute to suction loss. Typically, the (anxious) patient squeezes the eye or moves the head forcefully. Immediately after suction loss, the laser automatically stops firing and enters a special mode. Depending on the stage of the procedure at which the suction loss occurred, the user is offered specific options: • If the treatment is interrupted during the first 10% of the lenticule (posterior) cut, a complete restart with the same parameters is recommended. • If the treatment is interrupted between 10% and 100% of the lenticule cut, aborting of SMILE is recommended and the creation of a LASIK-flap is automatically offered. • If the treatment is interrupted during the creation of the lenticule side cut (after completing the lenticule cut), then re-docking and continuing with SMILE is offered. In this case, the side cut will be repeated from the beginning. It may be prudent to decrease the lenticule diameter by 0.2 mm and to increase the lenticule thickness by 10 µm to ensure that the second side cut reaches the posterior cut in its entire circumference in case of slight decentration in relation to the first docking. • If the treatment is interrupted during the cap (anterior) cut, re-docking and resuming the SMILE procedure from the start of the cap cut with the same parameters is recommended. • If the laser treatment is interrupted during the first 80% of the cap side cut creation, the manufacturer recommends repeating the side cut with adjusted parameters, as described earlier. However, we prefer to manually perform the side cut with a blade (Fig. 17.4, Video 17-4) • If re-docking is intended, using the same patient interface may facilitate centering exactly at the first center, as the interface enters the groves it made during the first docking.

Difficult Dissection of the Lenticule After laser application, the presence of an excessive opaque bubble layer may indicate a difficult dissection. Care should be taken to first separate the lenticule from the relatively mobile cap and then from the relatively less mobile stromal bed. If the posterior plane is inadvertently separated first, it

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• Fig. 17.4

  Manually performed side cut with Diamant knife set at a depth of 150 µm after suction loss.

is more demanding to identify and dissect the anterior plane because the cap gives less resistance.

• Fig. 17.5  Incomplete lenticule, visualized with milky solution (prednisolone acetate).

Black Spots Black or uncut spots are rare and may be caused by debris on the applanating glass, especially if several docking maneuvers are attempted. Small uncut zones are difficult to dissect and may cause pain to the patient; however, they are generally not problematic. On the other hand, larger uncut zones can potentially cause lenticule tears and retained fragments, leading to irregular astigmatism. Conjunctiva may get sucked in between the patient interface and the cornea and obstruct the laser beam without causing a suction loss (Video 17.5).

Lenticule Tears and Retained Lenticular Fragments Low dioptric corrections and small lenticule diameters have correspondingly thinner lenticules, which may tear during manipulation. Extra care is required to avoid lenticule tears in these cases. Increasing the diameter of the lenticule not only increases the optical zone but also lenticule thickness. Another way to facilitate dissection in low corrections is to increase the minimum lenticule thickness at its rim by adding a refractive neutral base from the default value of 15 µm to 25 µm. If in doubt as to whether lenticule fragments remain in the interface, the surgeon should uncurl the lenticule on the corneal surface and check its size and shape. Visualization of the lenticule margin may be enhanced by using a milky solution, such as prednisolone acetate (Fig. 17.5). The same solution can be injected into the interface to detect lenticule remnants (Video 17.6).

Cap Tear Sudden patient movement or imperfect surgical technique owing to a difficult and potentially painful lenticule separa-

tion may lead to tear of the cap. Small extensions of the side cut generally heal without sequelae. If a large tear occurs, the margins should be carefully realigned and allowed to adhere well without striae formation, similar to managing a torn LASIK flap. A bandage contact lens may be helpful in these cases (Figs. 17.6A and 17.6.B).

Epithelial Abrasions Epithelial abrasions are most frequently caused by the shaft of the instrument used to separate the lenticule rubbing over the cornea peripheral to the side cut. Small defects heal until the next day. However, larger ones may cause foreign body sensation and tearing, which decrease vision in the early postoperative period (Fig. 17.7, Video 17.7). The real problem is that these tiny and translucent epithelial pieces can be inadvertently inserted with the instrument into the interface without noticing it during surgery.

Management of Postoperative Complications Diffuse Lamellar Keratitis DLK may be caused by epithelial defects, bleeding from cut perilimbal vessels, sebaceous secretions, and other foreign material in the interface and may be managed, like DLK after LASIK, with topical steroids and irrigation.5

Infection A case of bilateral infectious keratitis after SMILE has been reported.6 Management of infection after SMILE is similar to the treatment of infection after LASIK.

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A

B • Fig. 17.6  (A) Cap tear during surgery, visualized with milky solution (prednisolone acetate). (B) Cap tear (3 months postoperatively).

in a LASIK interface and treatment with topical hypertonic saline.7

Ectasia There are several case reports of ectasia after SMILE, suggesting a low incidence.8–10 Corneal cross-linking has been shown to be effective in halting progression of ectatic disease.

Dry-Eye Syndrome Dry-eye syndrome seems to be less frequent and less severe after SMILE than after LASIK and should be managed according to the severity of symptoms and signs.

• Fig. 17.7

 

Abrasion on cap surface (1 day postoperatively).

Epithelium and Other Foreign Bodies in the Interface Epithelium and other foreign bodies in the interface should be removed to avoid irregular astigmatism or DLK.

Interface Fluid Collection Recently, the first case of fluid collection in the interface after SMILE has been reported as a new complication. The hallmark of this new entity is a shifting “ectasia” in corneal topography and optical coherence tomography (OCT) while the intraocular pressure remained normal throughout. The authors suggest a new pathogenesis in contrast to fluid

Undercorrection and Overcorrection and Retreatment Options Undercorrection and overcorrection do occur primarily or due to a myopic shift several years after SMILE. Several enhancement options exist; however, none is perfect as some sacrifice has to be made with each one. We prefer to do a surface ablation using mitomycin C 0.02% for 15 seconds to avoid subsequent haze formation. Obviously, visual recovery will last longer and the postoperative period will be less comfortable than with the initial SMILE surgery. Other surgeons perform femtosecond LASIK (FS-LASIK) as enhancement surgery with either an ultrathin flap created above the SMILE interface (with care taken not to create gas bubble breakthrough or a buttonhole) or a very thick flap below the interface. Another option is to convert the existing cap into a (preferably larger-diameter) flap using dedicated software for the

CHAPTER 17  Small-Incision Lenticule Extraction (SMILE) Complications and Their Management

VisuMax laser, called CIRCLE. This basically converts the original SMILE procedure into an FS-LASIK procedure and the retreatment, performed with an excimer laser, is done on the bed of the original SMILE procedure. Using any of these three comfortable approaches, from the patient’s perspective, the flapless nature of SMILE over LASIK is sacrificed. Last, it has recently been shown that SMILE can be repeated.11 However, this technique is extremely challenging to perform for small amounts of ametropia as typically present in enhancement surgery, because the lenticule would be too thin to manipulate easily.

References 1. Taneri S, Kießler S, Rost A, Dick B. Experience with introduction of SMILE: learning phase of our first 200 treatments. Klin Monbl Augenheilkd. 2016;234(1):70–76. 2. Sinha Roy A, Dupps WJ, Roberts CJ. Comparison of biomechanical effects of small-incision lenticule extraction and laser in situ keratomileusis: finite-element analysis. J Cataract Refract Surg. 2014;40(6):971–980. 3. Reinstein DZ, Archer TJ, Randleman JB. Mathematical model to compare the relative tensile strength of the cornea after PRK, LASIK, and small incision lenticule extraction. J Refract Surg. 2013;29(7):454–460.

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4. Osman IM, Awad R, Shi W, Shousha MA. Suction loss during femtosecond laser-assisted small-incision lenticule extraction: incidence and analysis of risk factors. J Cataract Refract Surg. 2016;42(2):246–250. 5. Zhao J, He L, Yao P, et al. Diffuse lamellar keratitis after smallincision lenticule extraction. J Cataract Refract Surg. 2015;41(2): 400–407. 6. Chehaibou I, Sandali O, Ameline B, Bouheraoua N, Borderie V, Laroche L. Bilateral infectious keratitis after small-incision lenticule extraction. J Cataract Refract Surg. 2016;42(4):626–630. 7. Bansal AK, Murthy SI, Maaz SM, Sachdev MS. Shifting “ectasia”: interface fluid collection after small incision lenticule extraction (SMILE). J Refract Surg. 2016;32(11):773–775. 8. El-Naggar MT. Bilateral ectasia after femtosecond laser-assisted small-incision lenticule extraction. J Cataract Refract Surg. 2015; 41(4):884–888. 9. Wang Y, Cui C, Li Z, et al. Corneal ectasia 6.5 months after small-incision lenticule extraction. J Cataract Refract Surg. 2015; 41(5):1100–1106. 10. Sachdev G, Sachdev MS, Sachdev R, Gupta H. Unilateral corneal ectasia following small-incision lenticule extraction. J Cataract Refract Surg. 2015;41(9):2014–2018. 11. Donate D, Thaëron R. Preliminary evidence of successful enhancement after a primary SMILE procedure with the subcap-lenticule-extraction technique. J Refract Surg. 2015;31(10): 708–710.

18 

Photorefractive Keratectomy VANCE THOMPSON, THEO SEILER, AND DAVID R. HARDTEN

Introduction The excimer laser revolutionized the world of vision correction because of its precision and unique abilities to reshape the corneal surface.1,2 This laser can remove scars and other opacities from the cornea in the procedure termed phototherapeutic keratectomy (PTK).3–8 It can also predictably reshape the anterior surface of the cornea in the procedure termed photorefractive keratectomy (PRK).9–11 The use of PRK as a mainstream refractive modality declined during the late 1990s and early 21st century due to the dramatic increase in laser in-situ keratomileusis (LASIK).12,13 PRK has remained a significant procedure because there is no risk of flap creation and less risk of ectasia.14 PRK has been shown to be safe and effective in long-term studies and is the only corneal refractive procedure that, with proper healing, it is not discernible that a procedure has been performed, even when observing with a slit lamp.15 Early excimer laser experiments were among the first attempts to produce lasers in the visible portion of the electromagnetic spectrum, more specifically the ultraviolet (UV) range. Research in the mid-1970s resulted in excimer lasers consisting of rare gas-halogen mediums, which, upon electrical stimulation, created an unstable fusion of these two molecules (e.g., excited dimer = excimer) followed by immediate dissociation with subsequent fluorescence of UV energy, which, when properly harnessed through sophisticated optical focusing mechanisms, produced a laser beam of considerable energy.16 Different rare gas-halogen excimer laser combinations produced different wavelengths of UV laser light (Table 18.1). Trokel, working with Srinivasan at the IBM Watson Research Center, was the first to suggest that the excimer laser had unique qualities for performing corneal surgery.17,18 In their 1983 paper, they suggested that this laser could be used to remove a lamellar portion of tissue to reshape the corneal curvature and to perform precisely placed incisions in the cornea.18 This early work stimulated considerable interest and research activity in laser corneal surgery with the excimer laser.19 In 1985, Theo Seiler performed the first human corneal excimer laser treatment in the form of an astigmatic kera280

totomy, followed the next year by the first excimer laser PTK.20,21 Marshall’s group first described the technique of anterior surface ablation to reshape the anterior corneal curvature.22 Munnerlyn was the first to describe a computergenerated algorithm relating the treatment zone diameter with the depth of ablation to effect a specific dioptric change.23 Marguerite McDonald performed the first PRK on a sighted, myopic eye.24 An enormous amount of research has followed to make excimer laser PRK a procedure that has changed the face of medicine and eye care.25–28

Excimer Laser Physics and Beam Tissue Interaction The word excimer is a contraction of two words: “excited” and “dimer.” A simplified description of an excimer laser system involves a cavity filled with rare gas and halogen gas molecules. A high-voltage electric discharge is sent across the laser cavity, which causes an unstable bond to be formed between these different types of molecules, resulting in high-energy dimers rare/halogen gas dimers. 29 These dimers then spontaneously dissociate and fall to a lower energy level, releasing a photo of energy at a wavelength of 193 nm that is harnessed through a series of focusing lenses and mirrors, which ultimately reshapes the corneal surface.30 Before exiting the laser, the excimer laser beam can be shaped by various methods. In general, there are two categories of excimer lasers based on the beam size and method of delivery. Broad beam excimer lasers were the most common laser in the beginning of laser vision correction and the main method used to shape the excimer laser beam was an iris diaphragm that gradually opened with every pulse delivered so as to deliver more energy to the central cornea than to the periphery in a myopic correction (Fig. 18.1). Scanning lasers have become the method of choice for excimer laser deliver in a refractive correction for a multitude of reasons. First, it is much more forgiving on the optics of an excimer laser to focus a small beam or slit beam than it is to focus a large beam. Small beams can be also be computer scanned over the corneal surface in many patterns.

CHAPTER 18  Photorefractive Keratectomy

TABLE 18.1  Excimer Laser Wavelengths

Laser Medium

Wavelength (nm)

Argon fluoride

193

Krypton chloride

222

Krypton fluoride

248

Xenon chloride

308

Xenon fluoride

351

• Fig. 18.1

  With every laser pulse, a plume of ablated tissue is released. (From Puliafito CA, Steinert RF, Deutsch TF, et al. Excimer laser ablation of the cornea and lens: experimental studies. Ophthalmology. 1985;92:741–748. Reprinted with permission from Elsevier.)

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Two features of an excimer laser ablation that can create a negative effect if not controlled are the plume that is released during the photoablative process and the heat that is dissipated during the same process. With every laser pulse, a plume of ablated tissue is released.30 With a broad beam laser myopic treatment, every pulse hits the center of the ablation as the iris diaphragm opens. As a result, the plume that is released can block the delivery of the total amount of energy to the central cornea. The end result is that less tissue is removed centrally than predicted, which can cause a central steepening (island) when compared to the rest of the more peripheral ablation (Fig. 18.2). With scanning laser technology, the small laser beam (typically in the 0.9- to 1.0-mm diameter range) is moving constantly. The advantage of this is that by the time a laser pulse is delivered in an area it just treated the plume from the previous pulse should be dissipated. This is why central islands have not been a problem with scanning lasers, as they were with broad beam technology.31,32 In the past, PRK procedures using scanning technology typically took longer than those using the large-area photoablation technique, but with advancements—including increased repetition rates (500–1000 Hz)—the scanning laser time has been greatly reduced.33,34 Also, it has been shown that reduced peripheral ablation can induce high-order aberrations. Scanning laser technology has the ability to address this issue by placing more pulses peripherally and lessening the induction of these unwanted aberrations.35,36 Excimer lasers have several desirable characteristics based on their photon energy. The energy per photon in an excimer laser beam is very high, 6.4 electron volts (ev), which easily overcomes intermolecular bond energies (carbon–carbon bonds equal 3.4 ev and peptide bonds

• Fig. 18.2  Central islands of tissue were more common with broad-beam lasers and could be visually significant.

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equal 3.0 ev) at the corneal surface. This allows for accurate layer-by-layer tissue removal on a molecular level. The penetration depth of each laser pulse is also minimal so that adjacent tissue damage is minimized.37 These unique features provide accuracy on the micron level and control to lamellar cornea surgery never seen previously because a single pulse of the laser removes approximately 0.122 to 0.25 µm of tissue, depending on the laser parameters used.38 This ability to treat in an accurate lamellar fashion allows this laser to be useful in removing scars and opacities from the cornea in addition to its unique ability to reshape the cornea in a refractive procedure.2–11 All patients being considered for PRK need to have a complete examination of their anterior and posterior segments. Excimer laser PRK details, alternatives to the procedure, and informed consent should be discussed. Contact lens status and history, general health history, eye health history, medications review, and allergy history are also documented. Patients with collagen-vascular diseases, such as systemic lupus erythematosus (SLE), are relatively contraindicated from undergoing PRK because of potential problems with delayed epithelial healing and potential corneal melting.39,40 As with any refractive procedure, ocular dominance, manifest refraction, cycloplegic refraction, and measurement of pupil size in dim light should be performed. Patients who cannot be refracted to 20/20 or better need close evaluation. If the cornea, lenses, maculae, and optic nerves appear to be fine, particular attention to computed topographic analysis, which all refractive evaluations should include, is important.41 Because patients with permanent irregular astigmatism, such as clinical keratoconus or pellucid marginal degeneration, often yield poor results after refractive surgery, they are considered contraindicated for refractive surgery42 (Figs. 18.3 and 18.4). Others have found

• Fig. 18.3

 

encouraging results in using PRK to treat preclinical or even clinical keratoconus in an attempt to improve the clinical picture in a topographically guided fashion.43 Caution should be taken in these types of situations, obtaining appropriate informed consent and providing patient education. A different mindset and patient education must be applied to cases such as these, going from a refractive surgery to combination refractive/therapeutic surgery. A thorough slit lamp examination should be performed on all patients undergoing laser vision correction. Blepharitis should be ruled out and, if present, treated aggressively before scheduling PRK. An evaluation for dry eyes is performed, looking for a healthy tear strip and no evidence of any punctate staining of the epithelium with fluorescein. Tear film osmolarity, anesthetized Schirmer test, and analysis of tear film breakup time can all be useful in the preoperative evaluation of the PRK patient.44 Patients with documented dry eye should have aggressive treatment of this condition prior to undergoing PRK. The cornea is evaluated for evidence of keratoconus, such as a Fleischer ring or Vogt lines. Stromal scars are evaluated closely and old herpetic disease is considered. If herpetic disease is felt to be a possibility, refractive surgery is not recommended owing to the risk of recurrence and resultant potential stromal scarring and damage to vision.45 The iris is examined for any evidence of iris transillumination defects since myopes especially are at increased risk for pigment dispersion syndrome. A quiet anterior chamber is expected, and the lens is thoroughly evaluated for any cataractous change. The vitreous and retina are evaluated thoroughly for any evidence of retinal pathology, such as macular disease or peripheral retinal pathology. Intraocular pressure (IOP) is evaluated because myopes are at increased risk for developing glaucoma and because steroids may be used postoperatively. In the event of a steroid-induced

Patients with clinical keratoconus in general make poor refractive surgery candidates.

CHAPTER 18  Photorefractive Keratectomy

• Fig. 18.4

 

283

Patients with pellucid marginal degeneration also make poor refractive surgery candidates.

pressure rise, documentation of a normal IOP preoperatively is important. Other tests we find useful include measurement of the optical scatter index (OSI) with the HD Analyzer. This device measures forward scatter and is a valuable clinical tool to measure objectively what the patient’s image quality is like. Objectively measuring the effects of ocular scatter on total vision can help with early cataract diagnosis, dry-eye diagnosis, early keratoconus detection, and can improve your outcomes with refractive treatment selection. If the OSI is low, we can be confident that the tear film is functioning optically well, the cornea does not have a visually significant irregularity, and the crystalline lens is optically clear46 (Figs. 18.5A and 18.5B). We also find wavefront analysis very helpful in measuring the aberration state of the patient’s eye. We perform conventional (treating just the sphere and cylinder), wavefront-optimized, wavefrontguided, and topographically guided PRK procedures. All of these procedures have their intricacies and preoperative testing that are important to completely understand. All patients in my practice are asked if they are eye rubbers. We know that eye rubbing increases the risk of ectasia. I prefer not to perform PRK, let alone LASIK, on eye rubbers. If they say they can stop, I then consider PRK.47 After the anterior and posterior segment examination and review of the corneal topography and wavefront data, the patients are counseled thoroughly, including, if presbyopic, a discussion on monovision. Pain after the anesthesia wears off is discussed, as are the techniques for treating it, such as nonsteroidal antiinflammatory drugs (NSAIDs), bandage contact lenses, and oral analgesics. Visual return is discussed, including the reduced vision (compared to LASIK) that occurs early on, followed by gradual improvement after reepithelialization (typically within 72 hours), the appearance of functional vision typically 4 to 5 days

postoperatively, and the establishment of best vision 1 to 3 months postoperatively. Patients often have a misperception of the slowness of vision return with PRK. It is common to have 20/40 vision throughout the PRK healing process and, with a properly fit bandage lens, the comfort level can be quite tolerable.48 Risks of infection with the potential for ulceration, scarring, and loss of best corrected vision are reviewed. The rare chance of needing a corneal transplant with a visually significant scar formation is discussed. The normal stromal and subepithelial healing response is reviewed and haze is described. Reducing the risk of haze with mitomycin C use is reviewed. I do not use mitomycin C on all PRK patients. There is an art to using this drug to reduce haze risk but its affect is variable and debated.49 I do use it for all patients with previous corneal surgery history and for all PRKs that will be removing more than 40 µm of tissue. The risks of undercorrection and overcorrection are discussed, as is the potential for glare and halos, especially at night. The risks of topical steroids—including cataracts and IOP elevation, which is rarely permanent—are also discussed. The patients’ questions are then answered and if their goals, expectations, and understanding of the process seem in order, the PRK procedure is scheduled. In general, I prefer scheduling these patients on a Thursday so I can see them day 1 postoperatively on Friday and day 4 postoperatively on Monday. The vast majority of patients are reepithelialized by Monday and the bandage contact lens can be removed. I prefer to limit PRK to low to moderate myopia (< 6.0 diopters [D]), low hyperopia (< 3.0 D), and/or low to moderate astigmatism (< 6.0 d) if possible because of the risk of haze or variabilities in healing for higher, especially hyperopic, corrections. In addition, I have had good results with phakic intraocular lens implants in the high-myopic patients

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A

B • Fig. 18.5

  (A) If the optical scatter index (OSI) is low, we can be confident that the tear film is functioning optically well, the cornea does not have a visually significant irregularity, and the crystalline lens is optically clear. (B) If the OSI is high, we need to be diligent in figuring out if it is a dry eye, the cornea has a visually significant irregularity, and/or the crystalline lens is optically compromised owing to early cataract that is difficult to detect with a slit lamp.

who are not good LASIK candidates because of level of correction or corneal thickness.50 Certain indications, such as thin corneas that are still safe for laser vision correction and preexisting anterior membrane dystrophy with or without recurrent erosion, are natural situations in which PRK can be ideal. Epithelial adherence in these patients can be improved with PRK just as in PTK.51 After laser calibration and ensuring that accurate laser parameters are entered, the patient is brought into the room and positioned under the microscope, reclining on the laser bed. The nonoperative eye is patched to maximize patient fixation with the operative eye. I feel that it is important to ask the patient to close the eye not being treated that is under the patch. When topical anesthetic is in the untreated eye, the cornea can dehydrate and thin rapidly. When that eye is then treated, it can be overcorrected because the laser is removing more microns per pulse.52 A patch can also be placed alongside the operative eye to catch excess fluids, such as tears or topical anesthetic. Topical anesthetic and topical antibiotics are provided preoperatively. I do not use pupil constricting drops because of pupil center shift concerns.53 The light of the surgical

microscope works well to constrict the pupil enough for centration of the PRK procedure. Topical anesthesia may be helpful in the nonoperative eye to relax any reflex tearing or relieve discomfort of the patient. A lid speculum is then placed in the operative eye and topical anesthesia is reapplied. Studies have shown improved PRK centration when the procedure is focused on the center of the pupil rather than on the corneal light reflex.54 For hyperopia treatments, some surgeons advocate centering the procedure on the corneal light reflex, but there is some debate in this arena.55 During this whole beginning process, the physician should explain to the patient in detail what is occurring and also what will be occurring during laser energy delivery. It is important to emphasize to the patient that the eye must be fixated on the fixation light in the laser at all times (Fig. 18.6). Patients should be told that the fixation light may blur during the ablation but that they should be able to see it at all times. Patients should also be told that the laser will produce a certain noise and smell, which they will be introduced to during the preliminary testing before treatment. At this point, the surgeon should check all the parameters that have been entered into the laser computer and

CHAPTER 18  Photorefractive Keratectomy

A

285

B

• Fig. 18.6  It is important to emphasize to the patient that the eye must be fixated on the fixation light in the laser at all times. (A) Orange fixation light of the VISX (Johnson and Johnson) laser. (B) Green fixation light of the Wavelight (Alcon) laser.

compared to the patient’s chart. It is always prudent to document that the laser is armed, tested, and ready to go with the patient’s correction before removing any epithelium. An optical-zone marker 1 mm larger than the desired PRK optical-zone treatment is centered on the epithelial surface (Fig. 18.7A). Alcohol diluted to 18% to 20% with sterile water can be applied to the surface epithelium for 15 seconds to help loosen the attachments of the epithelium to facilitate its removal (Fig. 18.7B). It is important to use a microsurgical sponge to remove the alcohol from the well of the instrument holding it on the epithelium and then rinse with a balanced salt solution prior to lifting the instrument off the cornea in order to minimize the chance of any of the alcohol coming into contact with the limbal epithelial stem cells that are so helpful in promoting rapid reepithelialization (Figs. 18.7C and 18.7D). The epithelium is then removed out to the optical-zone mark with a 64 Beaver blade (Fig. 18.7E). Various methods have been developed to remove the corneal epithelium, including laser epithelial removal (Videos 18.1 to 18.3).56 The epithelial removal time should be less than 30 seconds and at the absolute maximum less than 1 minute because hydration changes in the cornea can occur that can affect the algorithms and increase the chance of a less accurate refractive correction. A microsurgical sponge is used to ensure removal of all of the epithelium, with no loose tags left behind (Fig. 18.7F). Any remnants of epithelium left behind can block the laser beam in that area, promoting the removal of less stromal tissue underneath it, and can result in a small elevation that could affect vision. After ensuring that the Bowman membrane is clean and smooth, the laser procedure is ready to be performed (Fig. 18.7G). The patient is again instructed to look at the fixation light, the tracking device is engaged, the laser foot pedal is depressed, and the laser procedure begins. During the procedure, the patient’s fixation is monitored very closely. If the patient moves, the laser procedure is stopped by lifting the foot off the laser activation pedal, the patient is instructed to refixate, and the laser procedure is then continued because the computer restarts the procedure where it left off.

Postoperative Care After completion of the procedure, antibiotic and steroid drops are instilled, followed by a bandage lens. The bandage lens should be placed without touching it. A blunt conjunctival forceps and moistened microsponge works well for placing the bandage contact lens (Figs. 18.7H and 18.7I). Since there is an increased risk of infection with the use of a contact lens over a healing epithelial defect, I ensure that the bandage lens does not touch the lashes. Topical antibiotics are used six times per day and topical steroids four times per day until the bandage lens is removed. After reepithelialization, the antibiotic and steroid drops are continued at a dose of four times per day, each separated by at least 10 minutes for 5 to 7 more days. The main reason that topical steroids are used are to fight inflammation. The healing epithelial defect and the contact lens can both lead to sterile infiltrates, which can confuse the clinical picture.57 By using topical steroids, this confusing complication should be eliminated. The bandage lens is typically ready to be removed by day 3 or 4. If there is any delay in reepithelialization, a search for the cause is instituted immediately. The most common cause is tear film deficiency. If this is the case, aggressive lubrication with preservative-free drops along with placement of punctual plugs is performed. It may also be necessary to lessen the steroid dose if the epithelium is delayed in its closure. We also ask patients if they use a ceiling fan since this can dry the surface. Finally, we occasionally find benefit in using a shield at night since some patients rub their eyes at night and do not realize it. Postoperative pain usually occurs to some degree. Pain is highly dependent on the fit of the bandage contact lens. With improvements in modern day bandage lenses, I have been amazed at improvements in PRK pain. If there is going to be significant pain, it typically is most prominent the first evening of the PRK treatment, gradually improving over the ensuing 24 hours. Oral pain medications can be helpful in controlling the pain. Topical NSAIDs with or without the use of a bandage lens can be helpful in treatment pain

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A

B

C

D

E

F • Fig. 18.7

  (A) An optical zone marker 1 mm larger than the desired photorefractive keratectomy (PRK) optical-zone treatment is centered on the epithelial surface. (B) 18% alcohol can be applied to the surface epithelium for 15 to 20 seconds to help loosen the attachments of the epithelium to facilitate its removal. (C) It is important to remove the alcohol and then rinse with balanced salt solution prior to lifting the instrument off the cornea. (D) It is important to remove the alcohol to minimize the chance of any alcohol coming into contact with the limbal epithelial stem cells that are so helpful in promoting rapid reepithelialization. (E) The epithelium is then removed out to the optical-zone mark with the instrument of choice. (F) A microsurgical sponge is used to ensure removal of all the epithelium.

CHAPTER 18  Photorefractive Keratectomy

G

287

H

I • Fig. 18.7, cont’d (G) After ensuring that the Bowman membrane is clean and smooth, the laser procedure is ready to be performed. (H, I) After the PRK procedure is complete, a bandage contact lens is put on the cornea.

after PRK.58 Tetracaine used sparingly can also be effective in helping with postoperative pain.59 If I give patients tetracaine, I ask them to not use it more than six times in the first 24 hours and to return it to us the next day so that we can discard it. Used conservatively in this way, tetracaine can be a source of great relief for the patient experiencing significant PRK pain. Some investigators have concluded that steroids are not needed and that they delay the normal healing response and visual recovery.60 Others feel that steroids not only help improve the refractive outcome and lessen haze but also are beneficial to patients with late postoperative regressions that can respond to steroids positively.61 My current impression is that the majority of PRK patients experience benefits with 2 weeks of steroids in comfort, healing, and reducing the change of a confusing sterile infiltrate.

PRK Complications to Consider Complications can occur intraoperatively or postoperatively. Incomplete epithelial removal could be a cause of an irregular refractive result. Because epithelium fluoresces

upon exposure to UV radiation, one can immediately tell if there is any residual epithelium. Delayed removal of the epithelium can lead to hydration changes in the corneal stroma and unpredictable refractive results. Loss of patient fixation can lead to eccentric ablation and can occur in one of two forms.62 The first is a rapid and obvious loss of patient fixation. If the patient briefly loses fixation and refixates immediately, the ablation can continue uninterrupted. But if rapid loss of fixation occurs without an immediate refixation, the laser ablation should be immediately stopped. The laser computer remembers where it left off, so that by simply instructing the patient to be calm and refixate, one can reinstitute the ablation without causing any problems. Problems occur when the ablation is not stopped and is allowed to continue. The second type of loss of fixation is a slow drift, which can be more difficult for the surgeon to recognize. It is helpful for the surgeon to concentrate on the patient’s fixational abilities and try to recognize a slow drift early so that the procedure can stop and then proceed only after patient fixation has been reestablished. An inexperienced excimer laser surgeon sometimes tends to watch the ablation so that

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a slow drift of the HeNe beams from the center of the pupil may not be recognized. However, by concentrating on patient fixation, a slow drift can be easily recognized and corrected. Uncorrected and best corrected vision can be degraded with eccentric ablations that are more than 1 mm decentered.63 Symptoms of blurred vision, glare, ghost images, and poor contrast sensitivity can occur with a decentered ablation.64 Tracking systems, along with concentration on patient fixation, have helped improve the centration of PRK procedures and have lessened the risk of a decentration. Early postoperative complications include delayed reepithelialization. The majority of PRK patients are reepithelialized within 3 to 4 days. During this period, the patient is monitored for any development of infectious infiltrates. Infectious infiltrates after PRK are rare but have been reported.65 Because of the large area of epithelial removal, patients with known epithelial healing disorders should not undergo PRK. Early on, there was concern that ablation of the anterior cornea stroma and Bowman membrane might lead to epithelial disorders, such as recurrent corneal erosion. In fact, the excimer laser has been effective in treating recurrent corneal erosion that has been unresponsive to other treatment modalities.51 It is important to realize that in a patient with recurrent erosion symptoms, sometimes the area of epithelial removal outside of the ablation zone can be a concern for recurrent erosion. For patients with these symptoms, placing them under the surgical microscope and using a surgical microsponge to assess for areas of loose epithelium (we call it the “loose carpet test”) can be helpful. Those areas can be debrided and scraped or a PTK performed to help facilitate quality epithelial adherence. Halos and glare around bright sources of light can occur at night after PRK. Aspheric corrections, including a peripheral blend zone, have helped to create greater effective optical zones and minimize halo effects. Wavefront technology, both guided and optimized, has become a standard in PRK care.66 Wavefront analysis is helpful in understanding the aberration state of the eye both preoperatively and postoperatively. In a patient who does not have significant high-order aberrations, both guided and optimized approaches are equally effective.66 Wavefront data can also be used to construct a treatment that addresses both the low-order and high-order aberrations in patients in whom these aberrations are felt to be visually significant.67 Topographically guided PRK ablations can be helpful in treating refractive error in association with topographic irregularities in both normal and abnormal corneas.67 Comprehensive refractive surgery practices approach PRK with all of these approaches in mind: is this patient best served with a conventional, wavefront-guided, wavefront-optimized, or topographically guided approach? Subepithelial haze formation may also contribute to glare symptoms and to reduction in low light-contrast sensitivity. Haze formation peaks around 3 months postoperatively and returns toward preoperative levels by the 6-month

• Fig. 18.8  Grading of postoperative photorefractive keratectomy haze (moderate haze).

postoperative visit. With the advent of scanning laser technology combined with aggressive preoperative management of the ocular surface and adjuncts such as mitomycin C, corneal haze formation occurs less than it did with broad beam lasers. In addition to topical steroids and mitomycin C, other methods used to lessen the risk of haze formation are the use of sunglasses to lessen ultraviolet exposure and oral vitamin C.68 Intense haze formation to the level that would be considered an anterior stromal scar, with significant regression of effect, occurs rarely after PRK69 (Fig. 18.8). Best corrected vision is reduced in these patients. The treatment of these patients who develop intense haze can be challenging. It is best to approach these patients in a stepwise fashion. We first treat patients with intense haze by placing them on topical steroids. Early on, this haze formation and mild regression can be quite steroid responsive. If no, or minimal, response is noted with topical steroid therapy after approximately 1 month, a corneal scraping with a number 64 Beaver blade can be effective in removing this subepithelial fibrous material. After too long a wait, this material adheres more tightly to the anterior stroma and can be more difficult to remove. In cases in which haze proves unresponsive to steroids and a scraping procedure (too much time may have elapsed since initial therapy), the adherent remaining scar tissue may be removed with repeat excimer laser therapy.70 For instance, an antimetabolite, such as mitomycin C, has been shown to be effective in reducing haze in primary cases and recurrent cases.71,72 PRK has been shown to be an effective technique for treatment of low-order aberrations (myopia, hyperopia, and astigmatism), high-order aberrations, and topographic irregularities. Handled properly, it is one of the safest refractive surgeries available. Scanning laser systems have enabled such smooth ablations that they have improved the accuracy of PRK while lessening the incidence of haze formation. Wavefront technology has helped take PRK to another level of improving low-contrast visual acuity. Topography-guided treatments are helping both regular and irregular corneas

CHAPTER 18  Photorefractive Keratectomy

through normalization of their curvature. The excimer laser has etched its place in history as a mainstream tool to perform exciting procedures such as PRK. PRK remains the only corneal refractive procedure that, once all healing is complete, there is no obvious slit lamp evidence that corneal surgery was performed.

References 1. Seiler T, Wollensak J. In vivo experiments with the excimer laser–technical parameters and healing processes. Ophthalmologica. 1986;192(2):65–70. 2. Flowers CW Jr, McDonnell PJ, McLeod SD. Excimer laser photorefractive keratectomy. Ophthalmol Clin North Am. 2001; 14(2):275–283. Review. 3. Maloney RK, Thompson V, Ghiselli G, Durrie D, Waring GO 3rd, O’Connell M. A prospective multicenter trial of excimer laser phototherapeutic keratectomy for corneal vision loss. The summit phototherapeutic keratectomy study group. Am J Ophthalmol. 1996;122(2):149–160. 4. Thompson VM. Excimer laser phototherapeutic keratectomy: clinical and surgical aspects. Ophthalmic Surg Lasers. 1995;26(5): 461–472. 5. Ward MA, Artunduaga G, Thompson KP, Wilson LA, Stulting RD. Phototherapeutic keratectomy for the treatment of nodular subepithelial corneal scars in patients with keratoconus who are contact lens intolerant. CLAO J. 1995;21(2):130–132. 6. Thompson V, Durrie DS, Cavanaugh TB. Philosophy and technique for excimer laser phototherapeutic keratectomy. Refract Corneal Surg. 1993;9(2 suppl):S81–S85. Review. 7. Wilson SE, Marino GK, Medeiros CS. Santhiago MR. Phototherapeutic keratectomy: science and art. J Refract Surg. 2017;33(3): 203–210. 8. McDonnell PJ, Seiler T. Phototherapeutic keratectomy with excimer laser for Reis-Bückler’s corneal dystrophy. Refract Corneal Surg. 1992;8(4):306–310. 9. Epstein D, Tengroth B, Fagerholm P, Hamberg-Nyström H. Excimer PRK for myopia. Ophthalmology. 1993;100(11):1605–1606. 10. Piebenga LW, Matta CS, Deitz MR, Tauber J, Irvine JW, Sabates FN. Excimer photorefractive keratectomy for myopia. Ophthalmology. 1993;100(9):1335–1345. 11. Salz JJ, Maguen E, Nesburn AB, et al. A two-year experience with excimer laser photorefractive keratectomy for myopia. Ophthalmology. 1993;100(6):873–882. 12. Duffey RJ, Leaming D. US trends in refractive surgery: 2002 ISRS survey. J Refract Surg. 2003;19(3):357–363. 13. Duffey RJ, Leaming D. US trends in refractive surgery: 2003 ISRS/AAO survey. J Refract Surg. 2005;21(1):87–91. 14. Moisseiev E, Sela T, Minkev L, Varssano D. Increased preference of surface ablation over laser in situ keratomileusis between 2008-2011 is correlated to risk of ectasia. Clin Ophthalmol. 2013;7:93–98. 15. O’Brart DP, Shalchi Z, McDonald RJ, Patel P, Archer TJ, Marshall J. Twenty-year follow-up of a randomized prospective clinical trial of excimer laser photorefractive keratectomy. Am J Ophthalmol. 2014;158(4):651–663, e1. doi:10.1016/j. ajo.2014.06.013. 16. Ewing JJ. Laser Pioneer Interviews. Torrance, CA: High Tech Publications; 1985:243–256. 17. Trokel SL. Evolution of excimer laser corneal surgery. J Cataract Refract Surg. 1989;15:373–383.

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18. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery of the cornea. Am J Ophthalmol. 1983;96:710–715. 19. Marshall J, Trokel SL, Rothery S, et al. A comparative study of corneal incisions induced by diamond and steel knives and two ultraviolet radiations from an excimer laser. Br J Ophthalmol. 1986;70:482–501. 20. Seiler T, Wollensak J. In vivo experiments with the excimer laser–technical parameters and healing processes. Ophthalmologica. 1986;192:65–70. 21. Seiler T. Photorefractive keratectomy: European experience. In: Thompson FB, McDonnell PJ, eds. Excimer Laser Surgery: The Cornea. New York, NY: Igaku-Shoin; 1993:53–62. 22. Marshall J, Trokel SL, Rothery S, et al. Photoablative reprofiling of the cornea using an excimer laser: photorefractive keratectomy. Lasers Ophthalmol. 1986;1:21–48. 23. Munnerlyn CR, Koons SJ, Marshall J. Photorefractive keratectomy: a technique for laser refractive surgery. J Cataract Refract Surg. 1988;14:46–52. 24. McDonald MB, Kaufman HE, Frantz JM, et al. Excimer laser ablation in a human eye. Arch Ophthalmol. 1989;107:641–642. 25. Seiler TS, Kahle G, Kriegerowski M. Excimer laser (193 nm) myopic keratomileusis in sighted and blind human eyes. Refract Corneal Surg. 1990;6:165–173. 26. Seiler TS, Wollensak J. Myopic photorefractive keratectomy (PRK) with the excimer laser—one year followup. Ophthalmology. 1991;98:1156–1163. 27. O’Brart DP. Excimer laser surface ablation: a review of recent literature. Clin Exp Optom. 2014;97(1):12–17. 28. Stanley PF, Tanzer DJ, Schallhorn SC. Laser refractive surgery in the United States Navy. Curr Opin Ophthalmol. 2008;19(4):321–324. 29. Waring GO. Development of a system for excimer laser corneal surgery. Trans Am Ophthalmol Soc. 1989;87:854–983. 30. Puliafito CA, Steinert RF, Deutsch TF, et al. Excimer laser ablation of the cornea and lens: experimental studies. Ophthalmology. 1985;92:741–748. 31. Muller B, Boeck T, Hartmann C. Effect of excimer laser beam delivery and beam shaping on corneal sphericity in photorefractive keratectomy. J Cataract Refract Surg. 2004;30(2):464–470. 32. Fiore T, Carones F, Brancato R. Broad beam vs. flying spot excimer laser: refractive and videokeratographic outcomes of two different ablation profiles after photorefractive keratectomy. J Refract Surg. 2001;17(5):534–541. 33. Khoramnia R, Salgado JP, Wuellner C, Donitzky C, Lohmann CP, Winkler von Mohrenfels C. Safety, efficacy, predictability and stability of laser in situ keratomileusis (LASIK) with a 1000-Hz scanning spot excimer laser. Acta Ophthalmol. 2012;90(6):508–513. 34. Khoramnia R, Lohmann CP, Wuellner C, Kobuch KA, Donitzky C, Winkler von Mohrenfels C. Effect of 3 excimer laser ablation frequencies (200 hz, 500 hz, 1000 hz) on the cornea using a 1000 hz scanning-spot excimer laser. J Cataract Refract Surg. 2010;36(8):1385–1391. 35. Lombardo M, Lombardo G, Manzulli M, Palombi M, Serrao S. Relative contribution of central and peripheral aberrations to overall high order corneal wavefront aberration. J Refract Surg. 2006;22(7):656–664. 36. Chung B, Lee H, Choi BJ, et al. Clinical outcomes of an optimized prolate ablation procedure for correcting residual refractive errors following laser surgery. Korean J Ophthalmol. 2017;31(1):16–24. 37. Tuft SJ, Zabel RW, Marshall J. Corneal repair following keratectomy: a comparison between conventional surgery and laser photoablation. Invest Ophthalmol Vis Sci. 1989;30:1769–1777.

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38. Hersh PS, Wagoner MD. Excimer Laser Surgery for Corneal Disorders. New York, NY: Thieme; 1998. 39. Cua IY, Pepose JS. Late corneal scarring after photorefractive keratectomy concurrent with development of systemic lupus erythematosus. J Refract Surg. 2002;18:750–752. 40. Seiler T, Wollensak J. Complications of laser keratomileusis with the excimer laser (193 nm). Klin Monatsbl Augenheilkd. 1992;200:648–653. 41. Ambrosio R Jr, Klyce SD, Wilson SE. Corneal topographic and pachymetric screening of keratorefractive patients. J Refract Surg. 2003;19:24–29. 42. Holland SP, Srivannaboon S, Reinstein DZ. Avoiding serious corneal complications of laser assisted in situ keratomileusis and photorefractive keratectomy. Ophthalmology. 2000;107:640–652. 43. Ziaei M, Barsam A, Shamie N, et al. Reshaping procedures for the surgical management of corneal ectasia. J Cataract Refract Surg. 2015;41(4):842–872. 44. Torricelli AA, Bechara SJ, Wilson SE. Screening of refractive surgery candidates for LASIK and PRK. Cornea. 2014;33(10): 1051–1055. 45. Nagy ZZ, Keleman E, Kovacs A. Herpes simplex keratitis after photorefractive keratectomy. J Cataract Refract Surg. 2003;29: 222–223. 46. Cochener B, Patel SR, Galliot F. Correlational analysis of objective and subjective measures of cataract quantification. J Refract Surg. 2016;32(2):104–109. 47. Galvis V, Tello A, Carreño NI, Berrospi RD, Niño CA. Risk factors for keratoconus: atopy and eye rubbing. Cornea. 2017; 36(1):e1. 48. Taneri S, Oehler S, MacRae S, Dick HB. Influence of a therapeutic soft contact lens on epithelial healing, visual recovery, haze, and pain after photorefractive keratectomy. Eye Contact Lens. 2016. 49. Sy ME, Zhang L, Yeroushalmi A, Huang D, Hamilton DR. Effect of mitomycin-C on the variance in refractive outcomes after photorefractive keratectomy. J Cataract Refract Surg. 2014; 40(12):1980–1984. 50. Maloney RK, Nguyen LH, John ME. Artisan phakic intraocular lens for myopia: short-term results of a prospective, multicenter study. Ophthalmology. 2002;109:1631–1641. 51. Orndahl MJ, Fagerholm PP. Phototherapeutic keratectomy for map-dot-fingerprint corneal dystrophy. Cornea. 1998;17: 595–599. 52. Dougherty PJ, Wellish KL, Maloney RK. Excimer laser ablation rate and corneal hydration. Am J Ophthalmol. 1994;118(2): 169–176. 53. Hoang TA, Macdonnell JE, Mangan MC, et al. Time course of pupil center location after ocular drug application. Optom Vis Sci. 2016;93(6):594–599. 54. Jozato H, Guyton DL. Centering corneal surgical procedures. Am J Ophthalmol. 1987;103:264–275. 55. Reinstein DZ, Gobbe M, Archer TJ. Coaxially sighted corneal light reflex versus entrance pupil center centration of moderate to high hyperopic corneal ablations in eyes with small and large angle kappa. J Refract Surg. 2013;29(8):518–525. 56. Shapira Y, Mimouni M, Levartovsky S, et al. Comparison of three epithelial removal techniques in PRK: mechanical, alcohol-assisted, and transepithelial laser. J Refract Surg. 2015; 31(11):760–766.

57. Baum J, Dabezies OH Jr. Pathogenesis and treatment of “sterile” midperipheral corneal infiltrates associated with soft contact lens use. Cornea. 2000;19:777–781. 58. Solomon KD, Donnenfeld ED, Raizman MR, et al. Safety and efficacy of ketrolac tromethamine 0.4% ophthalmic solution in post-photorefractive keratectomy patients. J Cataract Refract Surg. 2004;30:1653–1660. 59. Brilakis HS, Deutsch TA. Topical tetracaine with bandage soft contact lens pain control after photorefractive keratectomy. J Refract Surg. 2000;16:444–447. 60. Gartry DS, Kerr-Muir MG, Lohman CP, et al. The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy. Arch Ophthalmol. 1992;110: 944–952. 61. Carones F, Brancato R, Venturi E, et al. Efficacy of corticosteroids in reversing regression after photorefractive keratectomy for myopia. Refract Corneal Surg. 1993;10:552–560. 62. Schwartz-Goldstein BH, Hersh PS. Corneal topography of phase III excimer laser photorefractive keratectomy. Optical zone centration analysis. Summit photorefractive keratectomy topography study group. Ophthalmology. 1995;102:951–962. 63. Cavanaugh TB, Durrie DS, Riedel SM, et al. Topographical analysis of the centration of excimer laser photorefractive keratectomy. J Cataract Refract Surg. 1993;19(suppl): 136–143. 64. Mrochen M, Kaemmerer M, Mierdel P, et al. Increased higherorder optical aberrations after laser refractive surgery: a problem of subclinical decentration. J Cataract Refract Surg. 2001;27: 362–369. 65. Forster W, Becker K, Hungermann D, et al. Methicillin-resistant staphylococcus aureus keratitis after excimer laser photorefractive keratectomy. J Cataract Refract Surg. 2002;28:722–724. 66. Ryan DS, Sia RK, Stutzman RD, et al. Wavefront-guided versus wavefront-optimized photorefractive keratectomy: visual and military task performance. Mil Med. 2017;182(1):e1636–e1644. 67. Alió JL, Piñero DP, Plaza Puche AB. Corneal wavefront-guided photorefractive keratectomy in patients with irregular corneas after corneal refractive surgery. J Cataract Refract Surg. 2008; 34(10):1727–1735. 68. Al-Sharif EM, Stone DU. Correlation between practice location as a surrogate for UV exposure and practice patterns to prevent corneal haze after photorefractive keratectomy (PRK). Saudi J Ophthalmol. 2016;30(4):213–216. 69. Kremer I, Kaplan A, Novikov I, et al. Patterns of late corneal scarring after photorefractive keratectomy in high and severe myopia. Ophthalmology. 1999;106:467–473. 70. Spadea L, Bianco G, Balestrazzi E. Four techniques for retreatment after excimer laser photorefractive keratectomy. J Refract Surg. 1996;12:693–696. 71. Carones F, Vigo L, Scandola E, Vacchini L. Evaluation of the prophylactic use of mitomycin-C to inhibit haze formation after photorefractive keratectomy. J Cataract Refract Surg. 2002;28:2088–2095. 72. Vigo L, Scandola E, Carones F. Scraping and mitomycin C to treat haze and regression after photorefractive keratectomy for myopia. J Refract Surg. 2003;19:449–454.

19 

LASEK and Epi-LASIK SUPHI TANERI, DIMITRI T. AZAR, VIKENTIA J. KATSANEVAKI, AND IOANNIS G. PALLIKARIS

Introduction Definition and Terminology Laser subepithelial keratomileusis (LASEK) combines certain elements of both laser in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). In LASEK—instead of completely removing the epithelium, as with PRK—dilute alcohol is used to loosen the epithelial adhesion to the corneal stroma. The loosened epithelium is then moved aside from the treatment zone as a hinged sheet. Laser ablation of the subepithelial stroma is performed before the epithelial sheet is returned to its original position, as with the LASIK flap. The first LASEK procedure was performed at the Massachusetts Eye and Ear Infirmary in 1996 by one of the authors (DTA).1 Camellin popularized the procedure and coined the term LASEK for laser epithelial keratomileusis.2 Alternative expressions include laser subepithelial keratomileusis,1 subepithelial photorefractive keratectomy,3,4 epithelial flap photorefractive keratectomy,5 laser-assisted subepithelial keratectomy,6 excimer laser subepithelial ablation,7 and epi-LASEK.8

Theoretical Advantages of LASEK The main rationale for combining elements of LASIK and PRK to LASEK is to avoid the flap-related LASIK complications and the slow visual recovery and haze risk of PRK. LASEK may avoid several of the inherent complications, including free caps, incomplete flaps, flap wrinkles, epithelial ingrowth, flap melt, interface debris, corneal ectasia, and diffuse lamellar keratitis after LASIK and postoperative pain, subepithelial haze, and slow visual rehabilitation after PRK.

Alcohol-Assisted Epithelial Removal Manual epithelial debridement produced scratches and nicking in the Bowman layer and left variable amounts of epithelium.9,10 Chemical agents such as 0.5% proparacaine, iodine, cocaine, alkali n-heptanol, and ethanol have been used to remove the corneal epithelium in experimental

studies. Today, 18% to 20% ethanol diluted in sterile water or salt solutions is commonly used in LASEK. Early reports revealed that epithelial removal using 18% to 25% alcohol for 20 to 25 seconds was fast, easy, and safe compared to mechanical debridement. They also showed that this concentration can produce sharp wound edges and a clean, smooth Bowman layer and that the central epithelium can be translocated in part or completely.11 Trigo suggested diluting ethanol in artificial tears (polyvinylic alcohol, commercially available as Liquifilm and Allergan) to create a 20% solution that is supposed to cause less epithelial dehydration and trauma.12

Effect of Alcohol on Epithelial Cell Survival In Vitro Our in vitro studies also suggested a dose- and timedependent effect of alcohol on epithelial cells. The 25% concentration of alcohol was the inflection point of epithelial survival. Significant increase in cellular death occurred after 35 seconds of alcohol exposure; 40 seconds of exposure further induced apoptosis after 8 hours incubation. These findings are consistent with clinical observations of variable epithelial attachment to the stromal bed on the first postoperative days after LASEK surgery and also with the use of greater than 50% ethanol in the treatment of progressive or recurrent epithelial ingrowth after LASIK. The in vitro monolayered results may apply to in vivo multilayered epithelium. The critical alcohol concentration and its duration of exposure are thus frequently exceeded during surgery. Increased duration of alcohol application can be used intentionally to weaken the epithelial adhesions, which contributes to the variability in alcohol-induced toxicity that is observed in vivo.

Transmission Electron Microscopy of Corneal Epithelium Specimen To study the effect of alcohol exposure and mechanical manipulation on corneal epithelium, we carried out 291

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A

B

C

D

• Fig. 19.1

  Transmission electron micrographs of freed epithelial sheets after 20% alcohol application for 25 seconds (specimen I: A; II: B; III: C; and IV: D). Variable separation of the basement membrane zone was seen. (A) Specimen I showing a localized area of irregular basement membrane zone (arrow) and basal cell membrane disruption (arrowheads) (original magnification × 17,750). (B) Discontinuous basement membrane zone beneath the basal epithelial cells (arrows), evident at higher magnification, was associated with decreased number of electron-dense hemidesmosomes (arrowheads) (original magnification × 30,000). (C) The basal cell membranes and the basement membrane (arrows) were disrupted in specimen III. Autographic vacuoles formation (arrowheads) was extensive in the cytoplasm (original magnification × 1650). (D) Specimen IV: the freed epithelial sheet retained a duplicated basement membrane zone. Pockets of cross-banded anchoring fibrils were arranged in a network between the layers of basal lamina (arrows). Electron-dense hemidesmosomes (arrowheads) were present along the basal cell membrane (original magnification × 17,750). Bar = 1 µm. (From Chen CC, Chang JH, Lee JB, Javier J, Azar DT. Human corneal epithelial cell viability and morphology after dilute alcohol exposure. Invest Ophthalmol Vis Sci. 2002;43(8):2593–2602, with permission from the Association for Research in Vision & Ophthalmology.)

electron microscopy studies on specimens obtained after conventional alcohol-assisted PRK. The images revealed that the epithelial cell layer is intact and the epithelial cells are still viable immediately after exposure to alcohol and surgical peeling (Fig. 19.1). The presence of the basement membrane attached to the basal epithelial cell layer indicates that the point of separation was likely to be within the basement membrane or between the basement membrane and Bowman layer.13,14

Use of Mitomycin C to Avoid Haze Potential haze formation remains an issue after ablation of the superficial stroma. To date, only topical corticosteroids are widely utilized for modulation of wound healing after refractive surgery. They act by inhibiting activated keratocytes, probably by interfering with DNA synthesis, which decreases cellular activity and reduces collagen synthesis. The use of mitomycin C to modify the wound-healing process was proposed many years ago but is still controversial. The mitomycins are a group of antitumor antibiotics that covalently bind to DNA after reductive activation.15 Mitomycin C inhibits fibroblast function by a dosedependent inhibition of fibroblast proliferation. We believe

that the use of mitomycin C for treating patients with visually significant preexisting corneal scarring may be justified by the excellent data reported by Majmudar et al.,16 Raviv et al.17 and others. Mirza et al. reported successful treatment of a patient with dense subepithelial haze after LASEK with mitomycin C.18 This is in concordance with our own experience using 0.02% mitomycin C applied to the center of the ablation bed for 1 min with a sponge (preferably donut shaped to avoid having the highest concentration in the center, where the cornea is thinnest). Our results suggest that the beneficial effect of mitomycin C may result from inhibition of keratocytes underlying the application zone.19,20 At present, there is a wide range of indications and dosages used.15 We do not use mitomycin C in routine cases. However, if the risk of haze formation seems higher than average owing to previous corneal laser surgery, we use mitomycin C 0.02% for 15 to 30 seconds, as recommended by Virasch et al.21

Surgical Techniques The major surgical techniques are variations of PRK-like ablation under a epithelial sheet created in a different manner.

CHAPTER 19  LASEK and Epi-LASIK

Azar Flap Technique Our LASEK technique (Fig. 19.2) evolved from PRK after alcohol-assisted epithelial removal. After application of topical 0.5% proparacaine (Ophthetic, Allergan, Inc.) and 4% tetracaine (formulated in a pharmacy), a lid speculum is applied. The cornea is then marked with overlapping 3-mm circles around the corneal periphery, simulating a floral pattern. An alcohol dispenser consisting of a customized 7- or 9-mm semi-sharp marker (ASICO) attached to a hollow metal handle serves as the reservoir for 18% alcohol. After 25 to 30 seconds, the ethanol is absorbed using an aspiration hole, followed by dry sponges (Weck-cel or Merocel, BVI). If necessary, the ethanol application may be repeated for an additional 10 to 15 seconds.

We then use ice-chilled, sterile salt solution to wash away any ethanol residues from the ocular surface and cool the cornea. Cooling the cornea to minimize postoperative pain and haze formation was originally described as early as 1994 for PRK.22 Over time, the step of epithelial removal has been modified. Initially, one arm of a jeweler’s forceps was inserted under the epithelium and traced around to delineate the epithelial margin, leaving a hinge of 2 to 3 clock hours of intact margin, preferably at the 12 o’clock position. The loosened epithelium was then peeled back as a single hinged sheet using a dry Merocel sponge. More recently, we have used one arm of a modified Vannas scissors (ASICO) to delineate the epithelial margin and fashion a hinged epithelial flap. The modified Vannas scissors also allows for

A

B

C

D

E

F

G

H

I

• Fig. 19.2

293

  Our current LASEK technique. (A) Multiple marks are applied around the corneal periphery, simulating a floral pattern. (B) An alcohol dispenser consisting of a customized 7- or 9-mm semi-sharp marker attached to a hollow metal handle serves as a reservoir for 18% alcohol. Firm pressure is exerted on the cornea, and alcohol is released into the well of the marker. (C) After 25 to 30 seconds, the ethanol is absorbed using a dry cellulose sponge. (D) One arm of a modified Vannas scissors (note knob at tip of lower arm) is then inserted under the epithelium and traced around the delineated margin of the epithelium, leaving a hinge of 2 to 3 clock hours of intact margin, preferably at the 12 o’clock position. (E) The loosened epithelium is peeled as a single sheet using a Merocel sponge or the edge of a jeweler’s forceps, leaving it attached at its hinge. (F) After laser ablation is performed, an anterior chamber cannula is used to hydrate the stroma and epithelial flap with balanced salt solution. (G) The epithelial flap is replaced on the stroma using the cannula under intermittent irrigation. (H) Care is taken to realign the epithelial flap using the previous marks and to avoid epithelial defects. The flap is allowed to dry for 2 to 5 minutes. Topical steroids and antibiotic medications are applied. (I) A bandage contact lens is placed. (From Taneri S, Zieske JD, Azar DT. Evolution, techniques, clinical outcomes and pathophysiology of LASEK: review of the literature. Surv Ophthalmol. 2004;49:576–602. Reprinted with permission from Elsevier.)

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creative variations of the LASEK incision to be customized for different corneal types (Video 19.1). After pushing aside the epithelial flap, the underlying stromal bed is ablated with an excimer laser. After ablation, an anterior chamber cannula is used to hydrate the stroma and float the epithelial flap over a layer of balanced salt solution. The epithelial flap is then replaced under intermittent irrigation and with careful attention to realignment of the epithelial flap margins using the previous marks. The epithelial flap is then allowed to dry for 2 to 3 minutes. If the epithelium appears healthy and attaches well, we keep it; otherwise, we remove it in light of our newer studies.23 The cornea is cooled with ice-chilled salt solution again for 15 seconds. Topical steroids and antibiotic medications are applied, and a bandage contact lens (Soflens 66, Bausch & Lomb, or Acuvue Oasys, Johnson & Johnson) is placed. We could demonstrate significant benefits of using a bandage contact lens in terms of pain perception, visual recovery, and haze formation in a comparative study.24 The bandage contact lens is removed after complete reepithelialization (generally postoperative day 3 or 4); early removal or manipulation of the contact lens prior to postoperative day 3 risks peeling the epithelial flap with the contact lens. Oral analgesics are prescribed to be taken every 4 hours as needed. From our experience, we have learned that our technique may not require specialized instruments but does necessitate several key steps for consistent epithelial flap creation and replacement. Pretreatment with several drops of 4% tetracaine prior to alcohol exposure helps to loosen the epithelium and reduce intraoperative discomfort. Placement of overlapping corneal marks is crucial to ensuring correct epithelial alignment and avoiding irregular epithelial placement and mismatch. We use an alcohol dispenser, but any optical zone marker with a barrel could be used to expose the epithelium to alcohol and avoid spillage. A modified Vannas scissors or a jeweler’s forceps to delineate the wound edge and locate the dissection plane and a dry, nonfragmenting cellulose sponge to peel the epithelial sheet are easily available instruments for creating the flap. The flap can be repositioned with an irrigating cannula under intermittent hydration, using the preplaced corneal marks as a guide. No overlap of the flap and wound edge has been observed that would have been attributable to stretching of the flap during peeling or overexpansion due to generous hydration. We have described star-shaped, S-shaped, Z-shaped modifications of the epithelial sheet margins as possible variants of our technique.25

Camellin Technique In the Camellin technique26 a sharp, partial-thickness trephination of the epithelium is carried out prior to alcohol application: a preincision of the corneal epithelium is done to circumscribe the flap area and to allow the alcohol solution to penetrate under the flap using a dedicated trephine

(J2900, Janach), which has a blunt section of 90 degrees for the formation of a hinge (Fig. 19.3). A rotation of about 10 degrees is performed, repeating the maneuver two or three times while maintaining a constant pressure. Then 20% alcohol solution (96% pure alcohol in injectable distilled water) is instilled into a small holding well (Janach J2905) on the corneal surface for 30 seconds. The well serves two functions: holding the eye still and avoiding discharge of fluid. The surface is dried and rinsed thoroughly with balanced salt solution (BSS) and a final irrigation with an antihistamine to reduce the amount of histamine induced by the alcohol. Subsequently, the epithelium is detached with the short side of a dedicated epithelial

A

B

C

D

E

F

G

H

• Fig. 19.3

  Camellin’s LASEK technique. (A) A dedicated semi-sharp epithelial trephine is applied after multiple marks are applied around the corneal periphery. (B) Then, 20% alcohol solution (96% pure alcohol in injectable distilled water) is instilled into a small holding well (Janach J2905) on the corneal surface for 30 seconds. The surface is dried and rinsed thoroughly with balanced salt solution. (C, D) The epithelium is then detached with the short side of a dedicated epithelial detaching spatula (Janach J2910A). By making tiny movements almost perpendicular to the margin, the epithelial sheet is folded at the 12 o’clock position. (E) Laser ablation is performed, protecting the epithelial sheet with a sponge. (F) Thorough rinsing with balanced salt solution. (G) The epithelial flap is returned after laser ablation with another spatula (Janach J2920A). (H) A soft contact lens is applied.

CHAPTER 19  LASEK and Epi-LASIK

detaching spatula (Janach J2910A). By making tiny movements almost perpendicular to the margin, the epithelial sheet is folded at the 12 o’clock position to keep it moist during the treatment. Before laser ablation, the longer side of this spatula is passed over the stromal surface to remove any debris. If necessary, the exposed stromal area may be enlarged by slightly stripping the epithelium in the periphery. Camellin has adjusted his PRK nomogram by reducing the preset values by 10% when treating myopia up to 10 D and by 20% for myopias of 10 D to 20 D, thus avoiding overcorrection. He advises protection of the flap with a masking fluid if smoothing is performed. The epithelial flap is returned after laser ablation with another spatula (Janach J2920A) and a soft contact lens is applied. Postoperatively, antibiotic and cortisone eye drops are administered for a few days, and a mild cortisone treatment is continued for up to a month. If complete reepithelialization has not taken place at postoperative day 3 or 4, a new lens is fitted for 3 more days. Camellin strongly points out the importance of a hypotonic solution, obtained by diluting alcohol in distilled water, for facilitating epithelial detachment. The elliptical instruments developed by Lohmann are based on those conceived by Camellin26 and geared toward better accommodation of an elliptical ablation in the treatment of large astigmatism.27

Vinciguerra Butterfly Technique Decreased epithelial viability after alcohol exposure is a postoperative complication of standard LASEK that may prolong visual recovery and cause temporary reduced visual acuity and discomfort. Vinciguerra developed a modification of the standard approach to creating the epithelial flap that, by preserving the limbal connection of epithelial stem cells and limbal vascular connections, aims at increasing epithelial viability, thus reducing the occurrence of these complications. In the Vinciguerra butterfly technique,28–30 a thin paracentral epithelial line, from 8 to 11 o’clock, is abraded with a specially designed spatula, and 20% alcohol in BSS is placed in contact with the cornea for 5 to 30 seconds. With the same spatula, the epithelium is separated from the Bowman layer, proceeding from the center to the periphery on both sides. A special retractor is used to move the two sheets of loose epithelium sideways toward the limbus and hold them in place. After drying the surface, excimer laser ablation is performed. Smoothing of the stromal surface with a hyaluronic acid masking solution (Laservis; Chemedica) is then carried out, followed by repositioning of the stretched epithelial flaps with the margins overlapping.

Alternatives to Alcohol-Assisted Epithelial Removal To avoid the use of alcohol, first, McDonald developed a technique that uses microkeratome suction and a methyl-

295

cellulose gel to create the epithelial sheet.31 Then, Pallikaris developed a mechanical device similar to the microkeratomes used for the flap preparation in LASIK that separates the epithelium from the stroma.32 He called his technique epi-LASIK. More recently, two modifications of surface ablation techniques have been described: transepithelial PRK and epi-Bowman keratectomy. With those latter techniques, the epithelium is destroyed and cannot be replaced, rendering them variants of PRK rather than LASEK. They are nevertheless briefly discussed in this chapter to provide an up-to-date overview of alternative ways to removing the epithelium without alcohol or other chemicals.

Epi-LASIK Introduction Epi-LASIK refers to an alternative surgical approach for epithelial separation by mechanical means. With this technique, the epithelial separation is performed using an instrument initially designed in the University of Crete to operate similarly to a microkeratome.32 The first commercially available device underwent development improvements to achieve epithelial separation by the forward movement of a disposable, oscillating polymethylmethacrylate (PMMA) block (Figs. 19.4 A and B). Histologic studies of specimens obtained with this device have shown that the basement membrane remains intact, whereas the sheet also includes a small portion of the upper part of the Bowman layer with a thickness that ranges between 300 and 1500  nm in different specimens (Fig. 19.4 C). Subsequently, different companies marketed similar devices called epikeratomes (Video 19.2). Although the original idea of epi-LASIK was to avoid the use of alcohol, Camellin has described a modification with an alcohol pretreatment before the use of an epikeratome.33

The Original Surgical Procedure The operative eye is anesthetized with three drops of topical tetracaine hydrochloride 0.5% applied every 5 minutes before the procedure and is prepared with povidone-iodine to be covered with a sterile drape. The epithelial surface may be marked with two concentric circles crossed by eight radial arms with a specially designed marker (epi-LASIK marker, Duckworth & Kent). Before the epithelial separation, the cornea is cooled using drops of prechilled BSS for 30 seconds. A Barraquer tonometer ensures adequate suction before the separation and a few drops of BSS acts as lubricant for the operative cornea. Fig. 19.5 depicts the pass of the separator and the following steps. Once the separator reaches its final position, the suction is released and the device is removed from the eye. With the use of either a moistened Merocel sponge or a metallic spatula (Duckworth & Kent) the epithelial sheet is reflected nasally to reveal the corneal stroma to be ablated.

Advanced Surface Ablation (PRK, LASEK, and Epi-LASIK) and Phototherapeutic Keratectomy

296 se c t i o n V I 296

A

C

B • Fig. 19.4

  Centurion epikeratome. (A) Epikeratome. (B) Central unit and pedals. (C) Transmission electron microscopy of an epithelial sheet harvested immediately after the separation (basal part). The sheet includes intact basement membrane as well as a small portion of the Bowman layer (arrows).

A

B

C

D

E

F

G

H

•

Fig. 19.5  Epi-LASIK procedure: (A–C) Pass of the separator. (D) With the use a metallic spatula (Duckworth & Kent), the epithelial sheet is reflected nasally to reveal the corneal stroma to be ablated. (E) Ablation of the stromal surface. (F) Immediately after the ablation, the procedure of corneal cooling is repeated. (G) The epithelial sheet is replaced with the aid of the metallic spatula. Its replacement is often achieved with a single movement. (H) A therapeutic contact lens is applied on the operative eye.

CHAPTER 19  LASEK and Epi-LASIK

Immediately after the ablation, the procedure of corneal cooling is repeated and the epithelial sheet is replaced with the aid of the metallic spatula. Its replacement is often achieved with a single movement. Any inward or outward folds of its edges are restored with the use of an anterior chamber irrigation cannula under constant irrigation. Once the epithelial sheet is stuck to the underlying stroma, a therapeutic contact lens is applied to the operative eye.

Gel-Assisted Epithelial Removal (McDonald Technique) The alcohol-free McDonald technique31 uses microkeratome suction and a methylcellulose gel to create the epithelial sheet. A dedicated curved cannula (Mastel Precision) is used; it has fine holes along the side through which GenTeal Gel (hydroxypropyl methylcellulose 0.3%; Novartis Ophthalmics) can simultaneously emanate. As methylcellulose gel, unlike alcohol, does not stiffen the epithelial cells, metallic instruments should never touch the epithelium. Instead, the cells are stripped with the assistance of suction and manipulated on a cloud of gel. Generous amounts of GenTeal Gel are applied to the corneal surface to keep the epithelium in good condition. A rounded cataract blade is used to make a small linear abrasion in the far periphery of the cornea. Ten drops of sodium chloride 5% are added for 10 seconds to slightly stiffen the epithelium, which is followed by placement of the suction ring. While the suction is on, a LASEK spatula is slipped through the 1- or 2-mm linear abrasion. Using that hole as a fulcrum, a spatulating motion is made and the epithelium is stripped off. After a maximum of 30 seconds suction time, the dedicated curved cannula is slipped under the epithelium and GenTeal Gel is blown out to dome up the epithelium. Finally, the raised epithelium is bisected with Vannas scissors. After parting the two sides, a wet Weck-cel sponge is used to remove the gel from the Bowman layer. Then, ablation is performed, after which

Postoperative Care All patients are prescribed eye drops of diclofenac sodium for 2 days and combined eye drops of tobramycin– dexamethasone (Tobradex, Alcon Laboratories) q.i.d. until removal of the bandage contact lens, which takes place at postoperative day 4 or 5. Removal of the contact lens before complete epithelial healing may dislocate the epithelial sheet. After removal of the lens, the patients receive fluorometholone eye drops (FML, Allergan) q.i.d. on a tapered dose for 5 weeks. Artificial tears are prescribed as needed.

Epi-LASIK Clinical Results Clinical results of epi-LASIK are excellent in terms of both refractive and visual outcomes and suggest that epiLASIK provides a safe and efficient alternative technique for photorefractive corrections on the stromal surface (Table 19.1).

TABLE 19.1  Epi-LASIK Outcomes

Study Pallikaris et al.50

Number of Eyes 44

Follow-up

UDVA

1 day Day of reepithelialization 1 month

38% 34% 85% 65% 95% 92% 96%

3 months Katsanevaki et al.51

234

1 day Day of reepithelialization 1 month 3 months 1 year

with with with with with with with

297

≥ ≥ ≥ ≥ ≥ ≥ ≥

20/40 20/25 20/40 20/25 20/40 20/25 20/40

28% with ≥ 20/20 53% with ≥ 20/40 34% with ≥ 20/20 78% with ≥ 20/40 54% with ≥ 20/20 95% with ≥ 20/40 81% with ≥ 20/20 99% with ≥ 20/40 86% with ≥ 20/20 100% with ≥ 20/40

CDVA, Corrected distance visual acuity; UDVA, uncorrected distance visual acuity.

Diopters Within Attempted Correction

Loss of CDVA/Rate of Haze formation

48% within ± 0.5 95% within ± 1.0 78% within ± 0.5 100% within ± 1.0

44% haze

60% 86% 78% 95% 80% 97%

within within within within within within

± ± ± ± ± ±

0.5 1.0 0.5 1.0 0.5 1.0

0% lost > 1 line CDVA 41% haze

25% lost > 1 line CDVA 52% with haze 38% haze 0% lost > 1 line 14% haze

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GenTeal Gel is applied again, the epithelial sheet is herded back into position, and a bandage contact lens is placed.

Trans-epithelial Photorefractive Keratectomy In trans-epithelial PRK, only a laser is employed to remove the epithelium by ablation, followed by the ablation of the underlying stroma in a single step. Clinical results indicate equivalent results to alcohol-assisted PRK.34,35

Epi-Bowman Keratectomy Epi-Bowman keratectomy is a novel variant of PRK. Instead of a metallic blade, as in PRK, an instrument with a copolymer tip is used to remove the epithelium layer by layer.36 After a review of the literature, we could not definitely evaluate the potential benefits and drawbacks of this method.37

Clinical Outcomes of LASEK Clinical outcomes of LASEK are summarized in Table 19.2. They indicate excellent safety, efficacy, and stability. Epithelial closure time may serve as an indirect sign of definite return of functional vision and of end of pain perception after LASEK. However, these data are not uniformly reported. Kornilovsky3 gives 4 days, Camellin26 4 to 5 days, Lee38 3.68 ± 0.69 days, and Claringbold39 up to 2 weeks. We observed an epithelial defect in five eyes on day 3 that had no defect on day 1, a closure rate of 78% on day 3 and of 98.8% at 1 week. None of our patients had an epithelial defect after 1 week.

Retreatments The need to retreat because of undercorrection or overcorrection is seeming to be less frequent than reported after LASIK. However, it is comforting for the surgeon and the patient alike that an enhancement can be performed with LASEK after LASEK: Having treated 222 eyes, Claringbold reported no retreatment, whereas we retreated several eyes in the time interval of 6 months to 4 years, all with satisfactory results. Rouweyha et al.40 and Gabler et al.41 also report the safety and efficacy of repeated LASEK for residual myopia. Additionally, LASEK has become our favorite technique for secondary surgical modifications after LASIK, thus avoiding an additional weakening of biomechanical stability by preserving the residual stromal bed. To prevent haze formation in these eyes, we let the wound healing calm down for at least 6 months after LASIK and use MMC for at least 15 seconds. Care must be taken not to dislocate the LASIK flap and not to ablate a hole into the flap. So far, we have had predictable results without visually disturbing haze formation. Recently, we also started using LASEK after small-incision lenticle extraction (SMILE).

Complications Possible complications of LASEK may be classified as sight threatening, non–sight threatening, intraoperative, and early and late postoperative. Possible complications during and immediately after LASEK include free epithelial flap, dissolution, fragments, fold, and slip. Complications in the days following surgery include persistent epithelial defects and subepithelial foreign body. Minor complications are probably not reported in every case. Only a few case reports exist of serious complications, such as infections,42 recurrent erosions, keratoectasia, and severe haze formation.

LASEK vs Photorefractive Keratectomy and Epi-LASIK Clinical studies comparing LASEK to PRK and epi-LASIK are summarized in Table 19.3. The main disadvantages of LASEK remain the unpredictable postoperative pain and epithelial healing. Even after ensuring that no epithelial defects were present at the end of each procedure, deepithelialized areas were observed in more than half the cases 1 day after surgery. There were a similar number of reports of postoperative pain. Since pain is the most compelling drawback of PRK, rapid reepithelialization is paramount to ensuring patient comfort in the immediate postoperative period. LASEK in its numerous variations cannot guarantee that it can achieve this consistently. It can be argued, however, that half of the LASEK patients may not have epithelial defects and postoperative pain on postoperative day 1, which is an improvement over conventional PRK.38 Although controversial,43,44 evidence suggests less wound healing and scarring after LASEK compared to PRK.45,46 This might be related to one or more of the following differences between these surface ablation procedures: (1) the epithelium in LASEK functions as a barrier that reduces the migration of proinflammatory cytokines into the stroma, (2) the viability of basal epithelial cells in LASEK minimizes subsequent epithelial proliferation, and (3) the presence of an intact basement membrane in the epithelial sheet in LASEK may allow epithelial regeneration without scarring.1 The last effect is strongly suggested by preliminary data from experiments that we performed on chick corneas. Haze formation is a major disadvantage of surface ablation procedures. Subepithelial stromal haze appears 2 to 3 weeks after surgery and peaks at 6 to 10 weeks. Problems during the period of reepithelialization may influence stromal regeneration and may result in haze formation. During this period, keratocytes migrate into the wounded area and secrete new extracellular matrix-containing type III collagen and glycosaminoglycans. After 3 months, the number of activated keratocytes declines and the haze subsides to subclinical levels. Variable results after PRK may in part be explained with the change in epithelial thickness and migration of activated

CHAPTER 19  LASEK and Epi-LASIK

299

TABLE 19.2  Laser-Assisted Subepithelial Keratectomy Outcomes

Number of Eyes

Study Azar et al.

1

20

Diopters Within Attempted Correction

Follow-up

UDVA

1 week

64% with ≥ 20/25 100% with ≥ 20/40 92% with ≥ 20/25 100% with ≥ 20/40

1 month Feit et al.52

163

1 year

94% with ≥ 20/40

Taneri et al.53

171

0.5 week

6% with ≥ 20/20 70% with ≥ 20/40

1 week

28% 94% 69% 96% 74% 96% 38% 76%

4 weeks 1 year 2 years Taneri et al.25

Al-Tobaigy54

McAlinden et al.55

173

80

with with with with with with with with

≥ ≥ ≥ ≥ ≥ ≥ ≥ ≥

20/20 20/40 20/20 20/40 20/20 20/40 20/20 20/40

Loss of CDVA/ Rate of Haze Formation

Comments

58% within ± 0.5 75% within ± 0.5 93% within ± 1.0

70% 86% 79% 95% 78% 91% 42% 67%

within within within within within within within within

± 0.5 ± 1.0 ± 0.5 ± 1.0 ± 0.5 ± 1.0 ±0.5 ± 1.0

9.4% lost > 1 line CDVA 33% haze at 3 months 1.2% haze at 1 year 1% lost > 1 line CDVA 20% haze at 13 weeks

6 months

(n = 352) 76% with ≥ 20/20 99% with ≥ 20/40

(n = 152) 83% within ± 0.5 98% within ± 1.0

< 0.1% lost > 1 line 31% haze at 3 months 4% haze at 1 year

3 months

63% with ≥ 20/20 83.2% with ≥ 20/25

94.94% within ± 0.5 100% within ± 1.0

1.32% lost > 1 line CDVA 17.34% haze 1 at 3 months 2.89% haze 2 at 3 months

1 year

95% with ≥ 20/20 100% with ≥ 20/25

98% within ± 0.5 100% within ± 0.5

0% lost > 1 line CDVA no haze at 1

At 1 year, no aberration, including total root mean square HOAs, was statistically significantly different from preoperatively.

CDVA, Corrected distance visual acuity; HOA, higher order aberration; UDVA, uncorrected distance visual acuity.

keratocytes (fibroblasts) in the area of ablation, with synthesis of new collagen. Presumably by maintaining the integrity of the epithelial layers, LASEK reduces the release of proinflammatory cytokines and minimizes the activation of abnormal stromal wound healing. In situations in which the creation of the epithelial sheet in LASEK is complicated, resulting in epithelial defect formation, stromal keratocytes may be activated and extracellular matrix deposition may occur in a PRK-like fashion. Lower levels of apoptosis in the ablated stroma 4 hours after LASEK compared to PRK have been shown by our group.47 However, apoptosis of the epithelial margin and the epithelial sheet itself was also present. Similarly, Lee et al.38

reported that a smaller amount of tear fluid transforming growth factor β1 was released in the early postoperative period following LASEK vs PRK. Managing the corneal epithelium as a hinged flap with 20% ethanol is a safe technique and may offer faster visual rehabilitation and reduced haze compared with debridement of the epithelium with alcohol, as in PRK. However, the influence of alcohol on the clinical outcome remains not fully understood. Experimental studies examining the effect of ethanol in LASEK have focused on three topics: (1) viability of the epithelial cells after alcohol exposure,32,48 (2) electron microscopic studies of the basement membrane,32,48 (3) and postprocedural scar formation. There is

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TABLE 19.3  Outcome Results of Comparative Surface Ablation Studies

Number of Eyes

Study 38

Lee et al.

Pirouzian et al.43

Cui et al.56

Technique

Follow-up

UDVA

27

PRK

27

LASEK

1 3 1 3

week months week months

37% 56% 57% 63%

32

PRK

32

LASEK

1 1 1 1

week month week month

Mean, Mean, Mean, Mean,

140

PRK

1 month 12 months

140

LASEK

1 month 12 months

Teus et al.57

47

LASEK

Epi-LASIK

Hondur et al.58

25

25

LASEK

Epi-LASIK

Diopters Within Attempted Correction

with with with with

≥ ≥ ≥ ≥

20/25 20/25 20/25 20/25

UCVA higher with LASEK; no significant differences in spherical equivalent; more pain and more haze with PRK.

20/27 20/21 20/28 20/20

44%–96% with 20/20 (mean, 73%) 67%–79% with 20/20 (mean, 70%) 52%–82% with 20/20 (mean, 71%) 73%–82% with 20/20 (mean, 75%)

No significant differences in UDVA at any time point. 24%–79%% within ± 0.5 (mean, 43%) 57%–92% within ± 0.5 (mean, 64%)

No between-group differences. 0% lost > 1 line CDVA

≥

29%–71% within ± 0.5 (mean, 47%)

≥

70%–88% within ± 0.5 (mean, 74%)

No between-group differences. 0% lost > line CDVA

≥ ≥

1 1 1 3

day week month months

87% with ≥ 20/40 89% with ≥ 20/40 100% with ≥ 20/40 79% with ≥ 20/20

1 1 1 3

day week month months

64% 87% 96% 66%

with with with with

≥ ≥ ≥ ≥

Comments

20/40 20/40 20/40 20/20

1 month 3 months

72% with ≥ 20/20 80% with ≥ 20/20

6 months

92% with ≥ 20/20

12 months

92% with ≥ 20/20

1 month 3 months

60% with ≥ 20/20 80% with ≥ 20/20

6 months

92% with ≥ 20/20

12 months

92% with ≥ 20/20

89% within ± 0.5 95% within ± 1.0

77% within ± 0.5 93% within ± 1.0

84% 92% 92% 96% 92% 96%

within within within within within within

± ± ± ± ± ±

0.5 1.0 0.5 1.0 0.5 1.0

88% 92% 92% 96% 92% 96%

within within within within within within

± ± ± ± ± ±

0.5 1.0 0.5 1.0 0.5 1.0

UCVA better on day 1 and month 1 only in LASEK group. Greater proportion of LASEK eyes within ± 0.5 D of attempted correction. Safety index better in LASEK. 9% LASEK lost > 1 line CXVA. 15% epi-LASIK lost > 1 line CDVA. Outcomes were similar in all groups.

CHAPTER 19  LASEK and Epi-LASIK

301

TABLE 19.3  Outcome Results of Comparative Surface Ablation Studies—cont’d

Number of Eyes

Study Ghanem et al.

59

51

Technique

Follow-up

UDVA

PRK

2 days 2 weeks

Mean UDVA 20/59 96% with ≥ 20/40 Mean UDVA 20/33 43% with ≥ 20/20 100% with ≥ 20/40 89% with ≥ 20/20 96% with ≥ 20/20 94% with ≥ 20/20

1 month 3 months 6 months 12 months 51

LASEK

2 days 2 weeks

163

361

277

199

Sia et al.61 (contralateral eye study in moderate to high myopia)

84

Epi-LASIK (retained flap) LASEK (retained flap) Epi-LASIK (discarded flap) LASEK (discarded flap)

PRK including use of MMC

PRK without use of MMC

14% haze 16% haze 94% within ± 0.5 100% within ± 1.0 8% haze

No statistically significant differences in outcomes were observed. 2% LASEK eyes lost > 1 line CDVA. 0% PRK lost > 1 line CDVA.

3 months 6 months 12 months

3 months

79% with ≥ 20/20

6 months 12 months 3 months

86% with ≥ 20/20 89% with ≥ 20/20 88% with ≥ 20/20

6 months 12 months 3 months

94% with ≥ 20/20 93% with ≥ 20/20 89% with ≥ 20/20

6 months 12 months 3 months

92% with ≥ 20/20 94% with ≥ 20/20 76% with ≥ 20/20

6 months 12 months

86% with ≥ 20/20 86% with ≥ 20/20

1 month

44% with ≥ 20/20

58.3% within ± 0.5

4.9% MMC-PRK lost > 1 line CDVA.

3 months

76.2% with ≥ 20/20 93.5% with ≥ 20/20 97% with ≥ 20/20 59.5% with ≥ 20/20

63.4% within ± 0.5

1.3% MMC-PRK lost > 1 line CDVA.

6 months 84

8% haze

Comments

Mean UDVA 20/72 92% with ≥ 20/40 Mean UDVA 20/33 43% with ≥ 20/20 100% with ≥ 20/40 89% with ≥ 20/20 96% with ≥ 20/20 94% with ≥ 20/20

1 month

Kulkarni et al.60

Diopters Within Attempted Correction

1 year 1 month 3 months 6 months 1 year

86.6% with ≥ 20/20 89.6% with ≥ 20/20 96.9% with ≥ 20/20

14% haze 24% haze 26% haze 86% within ± 0.5 98% within ± 1.0 8% haze At 1 year, there was no statistically significant difference in visual outcomes between techniques for any degree of myopia. 8% epi-LASIK lost > 1 line CDVA. 3% epi-LASIK (FO) lost > 1 line CDVA. 4% LASEK lost > 1 line CDVA. 7% LASEK (FO) lost > 1 line CDVA.

81.8% within ± 0.5 83.3% within ± 0.5 40.5% within ± 0.5

3.7% PRK lost > 1 line CDVA.

63.4% within ± 0.5 72.7% within ± 0.5 84.6% within ± 0.5

Continued

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TABLE 19.3  Outcome Results of Comparative Surface Ablation Studies—cont’d

Number of Eyes

Study 61

Sia et al. (contralateral eye study in moderate to high myopia)

83

Technique

Follow-up

UDVA

Diopters Within Attempted Correction

LASEK

1 month

63% with ≥ 20/20

48.8% within ± 0.5

2.5% LASEK lost > 1 line CDVA.

3 months

82.1% with 20/20 85.3% with 20/20 90.9% with 20/20 49.4% with 20/20 76.2% with 20/20 85.3% with 20/20 92.4% with 20/20

≥

57.7% within ± 0.5

≥

68% within ± 0.5

1.4% LASEK lost > 1 line CDVA.

≥

78.8% within ± 0.5

≥

42.7% within ± 0.5

≥

55.1% within ± 0.5

≥

62.7% within ± 0.5

≥

75.8% within ± 0.5

6 months 1 year 83

PRK

1 month 3 months 6 months 1 year

Yuksel et al.62 Reilly63

Hansen et al.64

22 20

LASEK Epi-LASIK

1 year 1 year

100

LASEK

100

PRK

6 1 6 1 6 1

Epi-LASIK

46

cPRK

4.6 years (average)

35

LASEK

6 years (average)

4.9% PRK lost > 1 line CDVA. 2.7% lost > 1 line CDVA. 1.5% PRK lost 3 lines due to haze 2.

95% with ≥ 20/25 95% with ≥ 20/25

months year months year months year

97

Comments

Epi-LASIK has a slight advantage over PRK and LASEK early in the post-op course regarding pain. Visual recovery is similar at 1 month; epi-LASIK trends toward less significant haze. 63% within ± 1.0 0 eye cPRK lost > 1 line CDVA. 35% within ± 1.0 1 eye LASEK lost > 1 line CDVA

cPRK was more effective than LASEK in reducing initial significant corneal haze.

CDVA, Corrected distance visual acuity; cPRK, PRK with cooling; epi-LASIK, epithelial laser in situ keratomileusis; LASEK, laser-assisted subepithelial keratectomy; LASIK, laser in situ keratomileusis; MMC, mitomycin C; PRK, photorefractive keratectomy; t-PRK, transepithelial photorefractive keratectomy; UDVA, uncorrected distance visual acuity.

no use of chemical agents, especially alcohol, in epi-LASIK. Comparative clinical studies of LASEK and epi-LASIK allow us to determine the effect of alcohol on the clinical outcome. In the worst-case scenario after LASEK—complete devitalization of the epithelial flap—the patient is assumed to be no worse than having had PRK with alcohol-assisted epithelial removal in the first place. In other words, the in vitro studies, animal studies, and electron microscopic findings result in a simple clinical recommendation: If the surgeon notes that the epithelial sheet is healthy, viable, and adherent at the end of LASEK surgery, it seems wise to allow the epithelial sheet to heal under a bandage

contact lens. However, if the surgeon notes that the epithelium is nonviable or nonadherent to the stromal bed, it may be best to completely debride the epithelium before a contact lens is applied, converting this case to a PRK procedure.

LASEK vs LASIK Clinical studies comparing LASEK to LASIK are summarized in Table 19.4. There are several circumstances in which surface ablation is a better option than LASIK. These may include treatments of patients with relatively large pupils and thin or irregular corneas. Corneal surface irregularities;

CHAPTER 19  LASEK and Epi-LASIK

303

TABLE 19.4  Comparison of Surface Ablation With LASIK

Number of Eyes

Study 65

Randleman et al.

136

Technique

Follow-up

CDVA

ASA

1 day 1 week 2 weeks

54% 71% 29% 88% 82% 99% 90%

with with with with with with with

≥ ≥ ≥ ≥ ≥ ≥ ≥

20/10 20/40 20/20 20/40 20/20 20/40 20/40

58% 96% 71% 97%

with with with with

≥ ≥ ≥ ≥

20/20 20/40 20/20 20/40

3 months 136

LASIK

1 day 1 week 2 weeks 3 months

Ghadhfan et al.66 (low myopia)

Ghadhfan et al.66 (high myopia)

Diopter Within Attempted Correction

Comments

86% within ± 0.5

LASIK had statistically better UDVA until 3 months, when a larger proportion of ASA eyes had ≥ 20/20.

82% within ± 0.5

323

LASIK

< 1 year

55% with ≥ 20/20 98% with ≥ 20/40

91% within ± 0.5

67

LASEK

< 1 year

84% within ± 0.5

49

m-PRK

< 1 year

37

t-PRK

< 1 year

48% with ≥ 20/20 94% with ≥ 20/40 74% with ≥ 20/20 92% with ≥ 20/40 65% with ≥ 20/20 100% with ≥ 20/40

141

LASIK

< 1 year

28% with ≥ 20/20 85% with ≥ 20/40

72% within ± 0.5

37

LASEK

< 1 year

20

m-PRK

< 1 year

22

t-PRK

< 1 year

30% 84% 25% 80% 36% 95%

with with with with with with

≥ ≥ ≥ ≥ ≥ ≥

20/20 20/40 20/20 20/40 20/20 20/40

No between-group differences. 0.3% LASIK lost > 1 line CDVA.

92% within ± 0.5 95% within ± 0.5

76% within ± 0.5

t-PRK more likely to obtain > 20/30 UDVA. t-PRK more likely than LASIK and m-PRK to achieve within ± 0.5 D of attempted correction. 2.7% LASIK lost > 1 line CDVA. 0.7% LASIK lost > 1 line CDVA. 0% m-PRK, t-PRK lost > 1 line CDVA.

70% within ± 0.5 95% within ± 0.5

ASA, Advanced surface ablation; CDVA, corrected distance visual acuity; LASIK, laser in situ keratomileusis; m-PRK, mechanical debridement photorefractive keratectomy; t-PRK, transepithelial photorefractive keratectomy; UDVA, uncorrected distance visual acuity.

hemimeridional asymmetry; very high or very low K readings; low pachymetry; and situations that may predispose to irregular, thin, or buttonholed flaps are better not treated with LASIK and should be treated with LASEK.1 In patients who experience recurrent corneal erosions, LASIK is generally considered a poor option. LASEK may not only correct the refractive error but may also cure the recurrent erosions in this population. In the rare event of intraoperative infections, the process in LASEK starts at the epithelial level, as opposed to the intrastromal level in LASIK, and will therefore theoretically be easier to manage.

From our point of view, LASEK appears to be a safe and effective option when patients request refractive surgery, especially when “saving” approximately 50 to 70 µm of corneal stroma in terms of untouched tissue depth is a decisive factor for the risk of an elective procedure, such as in the presence of thin corneas or wide pupils and comparatively high corrections.

Summary of Clinical Reports Widely accepted relative differences between PRK, LASEK, epi-LASIK, and LASIK are summarized in Table 19.5.

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TABLE 19.5  Widely Accepted Relative Differences Between PRK, LASEK, Epi-LASIK, and LASIK

Factor

PRK

LASEK

EPI-LASIK

Range of correction

Low to moderately high

Postoperative pain

Mild to moderate 24–72 h

Minimum 12 h

Postoperative medications

1–3 months

1 wk

Functional vision recovery

3 d to 1 wk

< 24 h

Refractive stability achieved

3 wk to 3 mo

1 wk to 3 mo

Specific complications

Haze formation, scarring

Dry-eye sensitive

1–6 mo

1–12 mo

Thin corneas

Often not contraindicated

May be contraindicated depending on amount of intended correction

Special (relative) indications

Thin corneal pachymetry, LASIK complications in fellow eye, predisposition of trauma, glaucoma suspect, recurrent erosion syndrome, dry-eye syndrome, basement membrane disease

Concern about postoperative pain, requirement of rapid visual recovery

Special (relative) contraindications

Concern about postoperative pain, requirement of rapid visual recovery

Haze formation, scarring, incomplete epithelial flap, stromal incursions

Concern about postoperative pain, requirement of rapid visual recovery, glaucoma, scleral buckle, deep-set eyes, small palpebral fissure

LASIK

Free caps, incomplete flaps, flap wrinkles, epithelial ingrowth, flap melt, interface debris, corneal ectasia, diffuse lamellar keratitis

Thin corneas, recurrent erosion syndrome, glaucoma, scleral buckle, deep-set eyes, small palpebral fissure

Epi-LASIK, Epithelial laser in situ keratomileusis; LASEK, laser-assisted subepithelial keratectomy; LASIK, laser in situ keratomileusis; PRK, photorefractive keratectomy.

Unfortunately, more than 2 decades after the first LASEK procedure, it remains unclear whether the theoretical, invitro, and in-animal models demonstrated superiority of LASEK over PRK is clinically relevant when treating our patients. This is because prospective comparative trials with a sufficient number of treatments are still missing, as recently stated in a Cochrane library study.49

Summary and Future Applications/ Corneal Cross-Linking Over the last decade, small improvements in the surgical protocols of LASEK and epi-LASIK—such as smoother excimer laser ablations, cooling the cornea, using an appropriate bandage contact lens, and optimized pain medication—have led to a more comfortable postoperative period with quicker recovery of functional vision compared to the initial years of performing these procedures. Additional study of the biochemical and histopathologic causes of the healing response may lead to the development of a flap-making solution superior to the ethyl alcohol now mainly used. A separation below the Bowman layer would be desirable to further minimize haze formation and

accelerate visual recovery. Perhaps a better understanding of how the epithelium adheres to the ablated stroma would enable us to promote the technique and the outcomes. LASEK and other surface ablation procedures have been proposed for improving the corneal surface in keratoconic eyes while adding biomechanical stability by corneal crosslinking. Other rationales for combining LASEK or epiLASIK with corneal cross-linking might be to further minimize the risk of haze formation or keratectasia. Convincing studies to support or refute these combinations are desirable.

References 1. Azar DT, Ang RT, Lee JB, et al. Laser subepithelial keratomileusis: electron microscopy and visual outcomes of flap photorefractive keratectomy. Curr Opin Ophthalmol. 2001;12(4):323–328. 2. Cimberle M, Camellin M. LASEK may offer the advantages of both LASIK and PRK. Ocular Surgery News International, Edition. 1999;10:14–15. 3. Kornilovsky IM. Clinical results after subepithelial photorefractive keratectomy (LASEK). J Refract Surg. 2001;17(suppl):S222–S233. 4. Shah S, Doyle SJ, Chatterjee A, et  al. Comparison of 18% ethanol and mechanical debridement for epithelial removal before photorefractive keratectomy. J Refract Surg. 1998;14(suppl):S212–S214.

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5. Shah S, Sebai Sarhan AR, Doyle SJ, et al. The epithelial flap for photorefractive keratectomy. Br J Ophthalmol. 2001;85(4): 393–396. 6. Shahinian L Jr. Laser-assisted subepithelial keratectomy for low to high myopia and astigmatism. J Cataract Refract Surg. 2002;28(8):1334–1342. 7. Lohmann CP, von Mohrenfels CW, Gabler B, et al. Excimer laser subepithelial ablation (ELSA) or laser epithelial keratomileusis (LASEK) – a new kerato-refractive procedure for myopia; surgical technique and first clinical results on 24 eyes and 3 months follow-up. Klin Monatsbl Augenheilkd. 2002;219(1–2):26–32. 8. Anderson NJ, Beran RF, Schneider TL. Epi-LASEK for the correction of myopia and myopic astigmatism. J Cataract Refract Surg. 2002;28(8):1343–1347. 9. Campos M, Hertzog L, Wang XW, et al. Corneal surface after deepithelialization using a sharp and a dull instrument. Ophthalmic Surg. 1992;23(9):618–621. 10. Griffith M, Jackson WB, Lafontaine MD, et al. Evaluation of current techniques of corneal epithelial removal in hyperopic photorefractive keratectomy. J Cataract Refract Surg. 1998;24(8): 1070–1078. 11. Abad JC, Talamo JH, Vidaurri-Leal J, et al. Dilute ethanol versus mechanical debridement before photorefractive keratectomy. J Cataract Refract Surg. 1996;22(12):1427–1433. 12. Trigo R. Improved alcohol solution for LASEK. [Letter] J Refract Surg. 2004;20(1):86–87. 13. Azar DT, Spurr-Michaud SJ, Tisdale AS, et al. Altered epithelialbasement membrane interactions in diabetic corneas. Arch Ophthalmol. 1992;110(4):537–540. 14. Spurr SJ, Gipson IK. Isolation of corneal epithelium with Dispase II or EDTA: effects on the basement membrane zone. Invest Ophthalmol Vis Sci. 1985;26(6):818–827. 15. Teus MA, de Benito-Llopis L, Alió JL. Mitomycin C in corneal refractive surgery. Surv Ophthalmol. 2009;54(4):487–502. 16. Majmudar PA, Forstot SL, Dennis RF, et al. Topical mitomycinC for subepithelial fibrosis after refractive corneal surgery. Ophthalmology. 2000;107(1):89–94. 17. Raviv T, Majmudar PA, Dennis RF, et al. Mitomycin-C for postPRK corneal haze. [Letter] J Cataract Refract Surg. 2000;26(8): 1105–1106. 18. Mirza MA, Qazi MA, Pepose JS. Treatment of dense subepithelial corneal haze after laser-assisted subepithelial keratectomy. J Cataract Refract Surg. 2004;30(3):709–714. 19. Azar DT, Jain S. Topical MMC for subepithelial fibrosis after refractive corneal surgery. [Letter] Ophthalmology. 2001;108(2): 239–240. 20. Jain S, McCally RL, Connolly PJ, et al. Mitomycin C reduces corneal light scattering after excimer keratectomy. Cornea. 2001; 20(1):45–49. 21. Virasch VV, Majmudar PA, Epstein RJ, Vaidya NS, Dennis RF. Reduced application time for prophylactic mitomycin C in photorefractive keratectomy. Ophthalmology. 2010;117(5): 885–889. 22. Niizuma T, Ito S, Hayashi M, Futemma M, Utsumi T, Ohashi K. Cooling the cornea to prevent side effects of photorefractive keratectomy. J Refract Corneal Surg. 1994;10(2):S262–S266. 23. Taneri S, Oehler S, Koch J, Azar D. Effect of repositioning or discarding the epithelial flap in laser-assisted subepithelial keratectomy and epithelial laser in situ keratomileusis. J Cataract Refract Surg. 2011;37(10):1832–1846. 24. Taneri S, Oehler S, MacRae S, Dick HB. Influence of a therapeutic soft contact lens on epithelial healing, visual recovery, haze,

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and pain after photorefractive keratectomy. Eye Contact Lens. 2016. [Epub ahead of print.] 25. Taneri S, Azar DT, Zieske J Evolution, techniques, clinical outcomes, and pathophysiology of LASEK: review of the literature. Surv Ophthalmol. 2004;49(6):576–602. 26. Camellin M. Laser epithelial keratomileusis for myopia. J Refract Surg. 2003;19(6):666–670. 27. Lohmann CP, von Mohrenfels CW, Herrmann W, et al. Elliptical ELSA (LASEK) instruments for the treatment of astigmatism. J Cataract Refract Surg. 2003;29(11):2174–2180. 28. Vinciguerra P, Camesasca FI. Butterfly laser epithelial keratomileusis for myopia. J Refract Surg. 2002;18(suppl):S371–S373. 29. Vinciguerra P, Camesasca FI, Randazzo A. One-year results of butterfly laser epithelial keratomileusis. J Refract Surg. 2003; 19(suppl):S223–S226. 30. Vinciguerra P, Camesasca FI. Treatment of hyperopia: a new ablation profile to reduce corneal eccentricity. J Refract Surg. 2002; 18(suppl):S315–S317. 31. Piechocki M. Alcohol-free LASEK procedure proves effective in pilot study. Ocular Surgery News, June 1, 2002. 32. Pallikaris IG, Naoumidi II, Kalyvianaki MI, et al. Epi-LASIK: comparative histological evaluation of mechanical and alcoholassisted epithelial separation. J Cataract Refract Surg. 2003;29(8): 1496–1501. 33. Camellin M, Wyler D. Epi-LASIK versus epi-LASEK. J Refract Surg. 2008;24(1):S57–S63. 34. Fadlallah A, Fahed D, Khalil K, et al. Transepithelial photorefractive keratectomy: Clinical results. J Cataract Refract Surg. 2011; 37(10):1852–1857. 35. Antonios R, Abdul Fattah M, Arba Mosquera S, Abiad BH, Sleiman K, Awwad ST. Single-step transepithelial versus alcoholassisted photorefractive keratectomy in the treatment of high myopia: a comparative evaluation over 12 months. Br J Ophthalmol. 2017;101(8):1106–1112. 36. Shetty R, Nagaraja H, Pahuja NK, Jayaram T, Vohra V, Jayadev C. Safety and efficacy of epi-Bowman keratectomy in photorefractive keratectomy and corneal collagen cross-linking: a pilot study. Curr Eye Res. 2016;41(5):623–629. 37. Taneri S, Kießler S, Rost A, Schultz T, Elling M, Dick B. EpiBowman-Keratektomie: klinische Beurteilung einer neuen Variante der Surface Ablation. Klin Monbl Augenheilkd. 2017. 38. Lee JB, Seong GJ, Lee JH, et al. Comparison of laser epithelial keratomileusis and photorefractive keratectomy for low to moderate myopia. J Cataract Refract Surg. 2001;27(4):565–570. 39. Claringbold TV II. Laser-assisted subepithelial keratectomy for the correction of myopia. J Cataract Refract Surg. 2002;28(1):18–22. 40. Rouweyha RM, Chuang AZ, Mitra S, et al. Laser epithelial keratomileusis for myopia with the autonomous laser. J Refract Surg. 2002;18(3):217–224. 41. Gabler B, Winkler von Mohrenfels C, Herrmann W, et al. Laser-assisted subepithelial keratectomy enhancement of residual myopia after primary myopic LASEK: six-month results in 10 eyes. J Cataract Refract Surg. 2003;29(7):1260–1266. 42. Maverick KJ, Conners MS. Aureobasidium pullulans fungal keratitis following LASEK. J Refract Surg. 2007;23(7):727–729. 43. Pirouzian A, Thornton JA, Ngo S. A randomized prospective clinical trial comparing laser subepithelial keratomileusis and photorefractive keratectomy. Arch Ophthalmol. 2004;122(1):11–16. 44. Hashemi H, Fotouhi A, Foudazi H, et al. Prospective, randomized, paired comparison of laser epithelial keratomileusis and photorefractive keratectomy for myopia less than -6.50 diopters. J Refract Surg. 2004;20(3):217–222.

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45. Song IK, Joo CK. Morphological and functional changes in the rat cornea with an ethanol-mediated epithelial flap. Invest Ophthalmol Vis Sci. 2004;45(2):423–428. 46. Autrata R, Rehurek J. Laser-assisted subepithelial keratectomy and photorefractive keratectomy versus conventional treatment of myopic anisometropic amblyopia in children. J Cataract Refract Surg. 2004;30(1):74–84. 47. Lee JB, Javier JA, Chang JH, et al. Confocal and electron microscopic studies of laser subepithelial keratomileusis (LASEK) in the white leghorn chick eye. Arch Ophthalmol. 2002;120(12): 1700–1706. 48. Chen CC, Chang JH, Lee JB, et al. Human corneal epithelial cell viability and morphology after dilute alcohol exposure. Invest Ophthalmol Vis Sci. 2002;43(8):2593–2602. 49. Li S-M, Zhan S, Li S-Y, et al. Laser-assisted subepithelial keratectomy (LASEK) versus photorefractive keratectomy (PRK) for correction of myopia. In: Wang N-L, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2016. 50. Pallikaris IG, Kalyvianaki MI, Katsanevaki VJ, Ginis HS. EpiLASIK: preliminary clinical results of an alternative surface ablation procedure. J Cataract Refract Surg. 2005;31:879–885. 51. Katsanevaki VJ, Kalyvianaki MI, Kavroulaki DS, Pallikaris IG. One-year clinical results after epi-LASIK for myopia. Ophthalmology. 2007;114:1111–1117. 52. Feit R, Taneri S, Azar DT, Chen CC, Ang RT. LASEK results. Ophthalmol Clin North Am. 2003;16:127–135. 53. Taneri S, Feit R, Azar DT. Safety, efficacy, and stability indices of LASEK correction in moderate myopia and astigmatism. J Cataract Refract Surg. 2004;30:2130–2137. 54. Al-Tobaigy FM. Efficacy, predictability, and safety of laserassisted subepithelial keratectomy for the treatment of myopia and myopic astigmatism. Middle East Afr J Ophthalmol. 2012; 19(3):304–308. 55. McAlinden C, Skiadaresi E, Moore JE. Visual and refractive outcomes following myopic laser-assisted subepithelial keratectomy with a flying-spot excimer laser. J Cataract Refract Surg. 2011;37(5):901–906.

56. Cui M, Chen X-M, Lü P. Comparison of laser epithelial keratomileusis and photorefractive keratectomy for the correction of myopia: a meta-analysis. Chin Med J. 2008;121:2331–2335. 57. Teus MA, de Benito-Llopis L, García-González M. Comparison of visual results between laser-assisted subepithelial keratectomy and epipolis laser in situ keratomileusis to correct myopia and myopic astigmatism. Am J Ophthalmol. 2008;146:357–362. 58. Hondur A, Bilgihan K, Hasanreisoglu B. A prospective bilateral comparison of epi-LASIK and LASEK for myopia. J Refract Surg. 2008;24:928–934. 59. Ghanem VC, Kara-José N, Ghanem RC, Coral SA. Photorefractive keratectomy and butterfly laser epithelial keratomileusis: a prospective, contralateral study. J Refract Surg. 2008;24:671–684. 60. Kulkarni SV, AlMahmoud T, Priest D, Taylor SEJ, Mintsioulis G, Jackson WB. Long-term visual and refractive outcomes following surface ablation techniques in a large population for myopia correction. Investig Opthalmology Vis Sci. 2013;54(1):609. 61. Sia RK, Ryan DS, Edwards JD, Stutzman RD, Bower KS, The US. Army Surface Ablation Study: Comparison of PRK, MMCPRK, and LASEK in moderate to high myopia. J Refract Surg. 2014;30(4):256–264. 62. Yuksel N, Bilgihan K, Hondur AM, Yildiz B, Yuksel E. Long term results of Epi-LASIK and LASEK for myopia. Contact Lens Anterior Eye. 2014;37(3):132–135. 63. Reilly C, Panday V, Lazos V, Mittelstaedt B. PRK vs LASEK vs Epi-LASIK: A comparison of corneal haze, postoperative pain and visual recovery in moderate to high myopia. Nepal J Ophthalmol. 2010;2(2):97–104. 64. Hansen RS, Lyhne N, Grauslund J, Grønbech KT, Vestergaard AH. Four-year to seven-year outcomes of advanced surface ablation with excimer laser for high myopia. Graefes Arch Clin Exp Ophthalmol. 2015;253(7):1027–1033. 65. Randleman JB, Loft ES, Banning CS, Lynn MJ, Stulting RD. Outcomes of wavefront-optimized surface ablation. Ophthalmology. 2007;114:983–988. 66. Ghadhfan F, Al-Rajhi A, Wagoner MD. Laser in situ keratomileusis versus surface ablation: visual outcomes and complications. J Cataract Refract Surg. 2007;33:2041–2048.

20 

Phototherapeutic Keratectomy (PTK) and Intralamellar PTK ANTONY M. POOTHULLIL, SANDEEP JAIN, NATHALIE F. AZAR, WALTER STARK, JOSEP TORRAS, MARK ROSENBLATT, AND DIMITRI T. AZAR

Introduction The resurgence of lamellar procedures in corneal surgery over the past several years has come not only in the guise of laser in situ keratomileusis (LASIK) for the correction of refractive error but also as a solution to corneal pathology, such as scarring and ectasia. Theoretical advantages of partial-thickness corneal transplantation (lamellar keratoplasty [LK]) over full-thickness corneal transplantation (penetrating keratoplasty [PK]) include avoiding intraocular surgery and its incumbent risks (including bleeding and infection) and the specter of allograft rejection. With the increased use of lamellar techniques, we have learned much about their limitations, complications, and drawbacks. Although the excimer laser’s primary use has been correction of refractive error using either lamellar (LASIK) or surface ablation (photorefractive keratectomy [PRK]), it may also be used to treat corneal pathology via phototherapeutic keratectomy (PTK).1 First investigated in 1988, this technique has been used to treat a variety of conditions, including to smooth irregularities, treat recurrent erosions, or remove superficial opacities, such as scars and deposits.1–3 PTK can offer an alternative to other surgical techniques, such as superficial keratectomy, lamellar keratoplasty, or penetrating keratoplasty. Advantages of PTK include precise control of corneal ablation, provision of a smooth base for corneal reepithelialization, ease of use, ability to repeat treatment, and relatively fast visual recovery. Disadvantages of PTK include possible hyperopic shift, scarring, and postoperative discomfort. PTK may be contraindicated in patients with deep stromal pathology or active inflammation or infection. This chapter will outline novel applications of PTK in the treatment of interface opacities and irregularities within the cornea following lamellar surgery.

Excimer Laser Advantages and Safety The excimer laser uses a high-energy, ultraviolet, 193-nm argon fluoride beam (ArF) to precisely ablate corneal tissue

with submicron accuracy, without causing significant injury to nonablated tissue.1,4,5 The depth and shape of excimer laser ablative photodecomposition can be accurately controlled,5–8 and ablation of tissue is not affected by corneal opacity.8 Reepithelialization and wound healing begin shortly after surgery and are associated with a small degree of tissue reorganization.8–11 In contrast, incisions made with diamond and steel blades produce relatively irregular and more diffuse tissue damage.9 This is also in contrast to the 248-nm krypton excimer laser, which produces irregular and scattered areas of tissue damage. The far UV laser radiation is thought to be within the limits of safety for the human eye. Adjacent tissues undergo minimal distortion and suffer no apparent thermal damage after 193-nm excimer laser PTK. At a histologic level, there is a clear boundary between the treated and untreated area, and the stromal lamellae show no evidence of distant disorganization.1,5,6,8,9 Endothelial cell loss can occur after PTK when the remaining stromal thickness is 40 µm or less.8 It is not clear, however, whether similar endothelial loss would occur with equally deep mechanical lamellar dissection. In lamellar surgery, the excimer laser has been used to prepare the recipient bed and to create donor tissue of more regular diameter and thickness in order to get more congruent surfaces. The excimer laser has also been used for the treatment of postoperative interface haze and optical irregularity. In this case, the donor graft is reflected away from the host bed, and both the posterior surface of the graft and the anterior surface of the host bed (100 µm residual tissue) are polished using the excimer laser. Only one case has been reported; this patient had an improvement of best corrected visual acuity (BCVA) from 20/100 to 20/22 with no measurable loss of endothelial cells at 9-month follow-up.12 Again, long-term follow-up is not available. Another technique has been reported for thin corneas with irregular astigmatism after repeated unsuccessful LASIK or due to keratoconus in which a donor stromal button graft modulated by excimer laser was positioned inside a host stromal pocket as part of an LK. This “sandwich” technique 307

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allows additional excimer laser ablation. Although there has been visual acuity (VA) improvement after a followup of 14 months, more trials are needed to evaluate this technique.13,14

cantly less than the presumed visual potential and when interface abnormalities are noted after surgery.

Phototherapeutic Keratectomy and Intralamellar PTK Indications

Preoperative Evaluation

PTK is used for the treatment of pathology of the anterior cornea, including diseases that affect corneal transparency and induce corneal surface irregularity. Treatment depth is limited by the thickness of the residual untreated stroma, which should be at least 250 µ. Conditions that have been treated include corneal opacities, corneal dystrophies, and recurrent corneal erosions. Corneal surface irregularities including Salzman nodular dystrophy and irregularities after refractive surgery have also been treated. Of 271 consecutive PTK cases at 17 VISX US centers reviewed by Sanders, 55% of patients had corneal scars or leukomas, 39% had corneal dystrophies, and 5% had corneal surface irregularities.15 In general, eligible patients should be free of active inflammation or infection, including keratoconjunctivitis, uncontrolled uveitis, and severe blepharitis. PTK has been used to treat microbial keratitis, including infectious crystalline keratopathy,16–19 but its use is very limited because of the risk of spreading of micro-organisms during treatment.20 Significant dry eye, lagophthalmos, systemic immunosuppression, and collagen vascular disease are also contraindications under many protocols. A neurotrophic cornea such as that caused by herpes simplex virus (HSV) infection may also be a contraindication to PTK. Corneal surface irregularity resulting from endothelial disease is a contraindication to treatment.21 Hyperopia may be a relative contraindication because PTK causes corneal flattening that may induce a hyperopic shift. For intralamellar PTK (IL-PTK), the decision to perform the procedure should be based on a series of factors. If the primary indication for lamellar surgery is anterior stromal scarring, the ability to complete the initial lamellar dissection at the proper depth is hindered by poor depth determination at the operating scope, technical difficulty of lamellar dissection, or scar depth that varies across the lesion. In such a case, especially when a residual scar is noted intraoperatively, the use of IL-PTK might be warranted. The residual scar could be safely and rapidly removed by laser.22 A second, but related, intraoperative indication for IL-PTK could be a notably irregular dissection and/or a poorly fitting donor lamella. By smoothing the donor and recipient lamellae, problems with interface irregularity could be anticipated and dealt with before they become a problem. If IL-PTK can improve BCVA through its polishing effect, it could become a standard part of LK. Given the additional time and expense required for IL-PTK, it will most likely be used when BCVA following LK is signifi-

Surgical Planning and Technique Preoperative evaluation includes a complete eye examination with dilation. Visual acuity and preoperative refraction should be measured. Visual potential can be assessed using a pinhole, hard contact lens, and potential acuity meter. Pupil size, corneal sensation, and corneal thickness, measured via ultrasound pachymetry, are performed. Corneal topography is a useful means of assessing the contribution of corneal pathology to surface irregularity. Once a patient is recumbent beneath the laser, it may be difficult to accurately assess depth of pathology. Therefore careful preoperative slit lamp biomicroscopy is important to determine the degree of corneal involvement. If extensive corneal deposits make visualization of the corneal slit difficult, other devices can be used to assess corneal involvement. Optical pachymetry (Fig. 20.1) and optical coherence tomography have been used to evaluate patients with corneal scarring and dystrophies.1,23 Rapuano used ultrasound biomicroscopy (UBM) to examine patients with anterior stromal corneal dystrophies before and after PTK treatment. In his study of 20 eyes, he found that UBM was not useful, as it did not measure the depth of pathology accurately.2 Hard contact lens overrefraction is valuable in distinguishing between blurred vision resulting from scarring and opacification vs corneal surface irregularities (Fig. 20.2).

Preoperative Preparation Before each treatment, the laser is calibrated according to the guidelines of each laser manufacturer. A standard treatment is ablated into a calibration plate made of polymethyl methacrylate (PMMA) test block or other material, depending on the laser used. Nitrogen gas flow, previously used during the PMMA calibration in some lasers, is rarely used today.24 The appropriate corneal ablation rate is determined using nomograms and entered into the laser computer

• Fig. 20.1

  Use of optical pachymetry to estimate the depth of an anterior corneal opacity.

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

309

B

A

C • Fig. 20.2

  Corneal opacities often interfere with visual acuity by the associated surface irregularity. The use of a hard contact lens eliminates the influence of the irregularity, allowing the surgeon to determine the impact of the opacity. Three patients shown here (A–C) have varying degrees of corneal opacifications; they were content with their contact lenses.

program. The patient is carefully positioned beneath the laser. Attention is paid to patient comfort, and the head should be stable and level. The skin surface is sterilized, and a lid speculum is placed. Before treatment, the plane of the corneal surface is determined by focusing the microscope at high magnification while the patient looks at the fixation light. If a treatment centered on the entrance pupil is planned, the eye-tracking mechanism of the laser should be engaged.

Laser Treatment and General Surgical Techniques Each PTK treatment must be customized to the individual patient. The duration and pattern of ablation are guided by the depth and location of corneal pathology. Considerations must be made regarding centration and ablation zone size, manual vs laser removal of the epithelium, the use of masking agents, transition zones, and smoothing techniques. The location of corneal pathology guides centration of PTK treatment. Ideally, laser treatments should be centered over the entrance pupil because decentration can lead to the

induction of astigmatism and higher-order aberrations.25–27 Diffuse corneal lesions can be treated with a large-diameter ablation centered over the pupil. Eye-tracking mechanisms can help ensure centration. If the cornea contains only a few lesions, each spot is treated and treatment diameter is adjusted for the size of each lesion. Multiple small lesions pose a greater risk of irregular astigmatism, especially when lesions are paracentral or peripheral. For peripheral or paracentral lesions, irregular astigmatism may be minimized by performing manual superficial keratectomy followed by PTK treatment. Additionally, masking agents, described later, can be used to smooth the ablated surface. Corneal lesions may induce surface irregularity by affecting the corneal epithelium or the underlying stroma. The smoothness of the ablated cornea can be improved by choosing the appropriate technique for removal of the corneal epithelium—either manual debridement or laser ablation. Prior to epithelial removal, it is important to assess the smoothness of the epithelial surface and anterior stromal surface. If the epithelium is a major cause of surface irregularity and the anterior stromal surface is judged to be smooth, the epithelium should be removed manually with a blade. Ablation then proceeds, starting with the smoother

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surface of the anterior stroma. If the anterior stromal surface is thought to be irregular, the epithelium is ablated with the laser. The epithelium helps mask the irregularity of the underlying stromal surface, resulting in a smoother stromal surface contour following PTK. Masking agents or surface modulators are fluids that are applied to the cornea following epithelial removal to help smooth the ocular surface. Agents that have been used include 1% hydroxy-methylcellulose, 0.5% tetracaine, or Tears Naturale II. The viscous fluid is applied to the irregular corneal surface before ablation and fills the valleys, exposing the peaks to the excimer laser (Fig. 20.3). The masking agent can be reapplied as needed between laser pulses. Highly viscous fluids (2% hydroxymethylcellulose or Healon) are not appropriate because they do not mask surface irregularities uniformly, only partially covering the peaks and valleys. Low-viscosity fluids tend to expose both the peaks and valleys. Another surface modulating agent, BioMask, has been studied by Kremer and colleagues. BioMask is a collagen that is applied as a liquid to the surface of the cornea, forms under a rigid gas-permeable contact lens, and then is ablated.28 The corneal epithelium also acts as a masking agent. Preoperative evaluation showing greater smoothness of the epithelium than the epithelial–

Laser beam

stromal interface should alert the surgeon to consider performing transepithelial PTK instead of epithelial scraping. A transition zone is usually created during stromal ablation. It is intended to allow smooth and uniform reepithelialization over the ablation bed. This procedure is referred to as a standard taper ablation and may reduce the induction of halos and hyperopia that can be seen after PTK. Sher et al. used a “smoothing” technique in their early cases, in which the eye was moved in a circular manner under the laser beam.29 A similar “polish technique” was used in the Summit excimer laser clinical trials. The surgeon moved the patient’s head in a controlled circular manner under the laser beam to “polish” the corneal surface.29,30 Stark et al. have described a “modified taper” technique, in which the surgeon attempts to decrease central flattening by moving the eye under the laser in a circular fashion and treating the circumference of the ablation zone with a 20-µm-deep, 2-mm-diameter spot size.1 This edge modification creates a ring-shaped ablation pattern at the periphery of the PTK to reduce the hyperopic shift that is often seen after PTK (Fig. 20.4). Approximation of the amount of final hyperopic error without the circumferential treatment may also

Laser beam

A

Laser beam

A

2mm Laser beam

Before

B • Fig. 20.3

(A) Corneal surface irregularities will be duplicated by treatment with phototherapeutic keratectomy (PTK) alone. (B) A masking agent can be applied to fill valleys on the corneal surface, allowing peaks to be ablated by the excimer laser.  

B •

After

Fig. 20.4  (A) The “modified taper” technique described by Stark et al.1 (B) A 2-mm beam is applied at the perimeter of the ablation zone to smooth the periphery and reduce hyperopic shift.

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

be used to add a hyperopic PRK treatment at the end of the procedure.

IL-PTK: Surgical Technique (Fig. 20.5) The first stage of the IL-PTK should be gaining access to the intracorneal lamellae that require treatment. If the IL-PTK is performed at the time of surgery, access is available following dissection of the donor tissue and recipient bed. If the IL-PTK procedure is performed postoperatively, the donor tissue must be at least partially removed. Residual sutures should be removed, but a single suture may be left in place to serve as a hinge during reflection of the donor tissue away from the stromal bed. The hinge facilitates accurate reapproximation of the lamellae at the end of the procedure. In any event, marking the flap edge is recom-

A

B

C

D

311

mended in case the flap is inadvertently completely displaced. Unless the IL-PTK is to be performed in the immediate postoperative period, gentle, blunt dissection may be necessary at the graft interface in order to adequately reflect the graft away from the recipient bed. Once access to the lamellae has been achieved, the recipient bed and posterior surface of the graft should be carefully dried and inspected for obvious irregularities, fibrosis, or scarring. In our technique, the ablation is done in two phases. First, a limited ablation is performed at the optical center of the cornea. Then, the ablation is slowly moved centrifugally to allow treatment of a larger zone, while minimizing the hyperopic shift. The posterior surface of the graft can be similarly treated by applying the laser first centrally with slow movement to the periphery. Smoothing of both surfaces is likely to result in the best fit. When intraoperative IL-PTK is performed during deep lamellar keratoplasty, more extensive IL-PTK of the posterior surface of the donor tissue can be performed in lieu of true lamellar dissection with a blade. Following the primary IL-PTK treatment, further application of the excimer laser to the residual bed using a masking agent can improve the smoothness of the interface. In this step, balanced salt solution (BSS) is applied to the central corneal bed and laser pulses applied until the bed appears dry. This procedure may be repeated several times. By ablating the cornea with the masking agent in place, slightly elevated regions of the cornea are exposed to the laser energy first, as the fluid is removed by the laser. The “ridges” of tissue are therefore ablated without affecting the “valleys.” Once the lasering is complete, the stroma should be rinsed and dried to remove debris prior to reapproximating the treated lamellae. After proper alignment of the graft and bed, the flap is sutured into place with either interrupted or continuous 10-0 nylon sutures (Fig. 20.6).

Elevated Central Corneal Nodules (Video 20.4) E

F

G

H

• Fig. 20.5  Intralamellar phototherapeutic keratectomy (IL-PTK) surgical technique. In this case, a lamellar keratoplasty was made some months before but a remaining scar was present. We needed to remove sutures (A) to get access to the interface. We left a suture to work as a hinge (B). After lifting the flap (C), a direct view of the recipient bed scar was seen (D). With the excimer laser, we first made a limited central ablation (E) and then we moved the aim in a circular way toward the periphery in order to treat a larger but more superficial zone (F). The stromal side of the flap was also treated. Finally, we applied more central pulses with balanced salt solution as a masking agent to smooth the surface even more (G). After rinsing and reapproximating the treated lamellae, we resutured the flap (H).

Treatment of elevated corneal opacities located in the central optical zone is difficult, even with the use of surface modulators. Some surgeons suggest using a blade to excise the elevated lesion prior to PTK (Figs. 20.7 and 20.8).29,32 We present a case report illustrating a surgical technique utilizing epithelial debridement to create a depression around the lesion, followed by application of surface modulators to fill the annular furrow around the lesion before laser treatment. This technique may result in removal of the elevated central corneal opacity and improve postoperative visual acuity. We used the technique described in Fig. 20.7 to treat an 87-year-old white woman with a central Salzmann nodule and irregular astigmatism in the right eye. She had undergone cataract extraction and posterior chamber lens implantation 9 years earlier and also had received LK for a Salzmann nodular degeneration of the right cornea. At initial presentation, her BCVA was 20/400 (+1.25 +3.00 × 145 correction) in the right eye and 20/20 in the left eye. Hard contact lenses improved her visual acuity to 20/50

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inducing myopic shift.27 Overall, PTK is reported to be safe and effective in treating elevated corneal nodules in pediatric and adult patients alike.33,34

Multiple Surface Irregularities

A

Multiple surface irregularities can be treated with the aid of surface modulators or “masking” agents. The epithelium is first removed either manually or with the laser. A masking fluid is then applied to the ocular surface, followed by laser application. This process is repeated as needed to smooth the ocular surface (Figs. 20.11–20.13). In addition to creating a smooth corneal surface, masking agents may reduce the amount of induced hyperopia.

Corneal Dystrophies (Videos 20.1 and 20.6)

B • Fig. 20.6

  Intralamellar phototherapeutic keratectomy (IL-PTK) outcomes. (A) Residual scarring at 1-month follow-up of a lamellar keratoplasty. (B) No evidence of scarring in the first-day examination after IL-PTK.

OD. On slit lamp examination, the cornea had linear elevated subepithelial opacities 1 to 2 mm from the visual axis (Fig. 20.9). Superficial punctate keratitis was noted around the opacities. Corneal topography showed localized +5 diopters (D) steepening over the opacities. Fundus examination showed age-related macular degeneration and mild epiretinal membrane. Intraocular pressure (IOP) and other ocular findings were within normal limits. PTK was performed as described earlier using ArF excimer (fluence: 160 mJ/cm2; repetition rate: 5 Hz; epithelial ablation rate: 0.24 µm/pulse; stromal ablation rate: 0.27 µm/pulse) followed by photoastigmatic keratectomy (cylindrical correction). After PTK, the corneal surface appeared smooth. The central elevated opacity noted preoperatively disappeared (Fig. 20.10). Anterior stromal haze was barely detectable throughout the 12-month follow-up period. In Salzmann Nodular Degeneration (SND), midperipheral corneal elevations often form an asymmetric pool of tear film, which can lead to optical corneal plana, resulting in a pronounced hyperopic shift and irregular astigmatism. In such scenarios, combination of excimer laser PTK with mechanical pannus removal is reported to give good outcomes by normalizing the corneal curvature and by

Corneal dystrophies have been traditionally treated with lamellar and penetrating keratoplasty. Following grafting, the primary pathology can eventually recur. PTK has become a useful alternative that may help patients delay or avoid keratoplasty. Patients with superficial corneal lesions, as in epithelial (Meesmann; Fig. 20.14) basement membrane dystrophies (Figs. 20.15 and 20.16) rarely require PTK. Patients with Reis-Buckler dystrophy respond well to PTK (Fig. 20.17). Patients with recurrent granular or lattice dystrophy in a graft have relatively superficial lesions. The success rate in these cases is very high and is similar to that for primary Reis-Buckler dystrophy, in which the deposits are limited to the Bowman layer (Fig. 20.18).1 Most patients achieve a relatively smooth ablation bed by treating through the epithelium. For patients with granular dystrophy, the aim is to ablate most of the areas of diffuse haze between the granular deposits and not necessarily all the granular hyaline deposits (Figs. 20.19–20.23). A similar approach is used for the management of lattice dystrophy (Fig. 20.24) and macular dystrophy (Fig. 20.25). The healing of the corneal epithelium is typically delayed after PTK treatment of lattice dystrophy compared to others. Therefore extra care must be taken for these patients by providing adequate counseling and close follow-up until complete wound healing to prevent scarring, ulceration, and infection. Medications (such as autologous serum drops and hyaluronic acid drops), simultaneous lateral tarsorrhaphy, or amniotic membrane patching may be helpful for these cases.35 For patients with granular corneal dystrophy type 2 and cataracts, PTK treatment done in the PRK mode following cataract surgery is reported to be effective.36 If corneal dystrophy recurs following primary treatment, PTK can be repeated (Fig. 20.26).37 Some studies have reported the efficacy of mitomycin C (MMC) in terms of recurrences and visual outcomes when used in conjunction with PTK in treating corneal dystrophies.38,39 However, another recent study reported severe recurrences with the use of MMC over a longer follow-up of at least 3 years.40 Another study reported success in using femtosecond laserassisted anterior lamellar keratoplasty (FALK) postkeratoplasty for four cases of recurrent granular corneal dystrophy.41

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

Localized epithelial debridement

Step 1

313

Surface modulators in annular furrow

Step 2

Laser ablation 30-40 µm

Additional surface modulators to cover peak

• Fig. 20.7 Step 3

  Schematic drawings of the surgical techniques of phototherapeutic keratectomy (PTK) for elevated central corneal nodules.

Step 4

PRK or PAK for residual myopia or astigmatism

PTK laser stromal ablation

Step 5

A

Step 6

B

• Fig. 20.8

  (A) Salzmann nodules interfering with vision can be effectively treated with phototherapeutic keratectomy (PTK) using the technique shown in Fig. 20.7. (B) Clearing of the nodule following PTK.

A

B

• Fig. 20.10  Postoperative appearance of the patient shown in Fig. 20.2. After phototherapeutic keratectomy (PTK), the corneal surface appeared smooth. The linear elevated opacity noted preoperatively had disappeared (A) by direct and by slit lamp biomicroscopy (B).

Corneal grafting can also be performed successfully following PTK.42,43

Recurrent Corneal Erosions (Videos 20.2 and 20.3)

• Fig. 20.9

  The epithelium overlying the elevated corneal nodule is scraped with a blade before applying surface modulators. The postoperative outcome is shown in Fig. 20.8.

Patients with recurrent corneal erosions will often respond to manual epithelial debridement or anterior stromal puncture. PTK is usually reserved for cases that are recalcitrant to more conservative measures or cases in which recurrences involve the central visual axis (see Fig. 20.16). Epithelial debridement is performed prior to laser application with a dry Weck-cell sponge. A wet Weck-cell sponge is used to sweep any residual deposits. Treatment depth with PTK is relatively minimal (5–10 µm) and is usually limited to the Bowman layer. Long-term follow-up (34–68 months) of shallow ablation PTK than typically considered (4.6 µm) is also reported to be successful after single treatment in

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A

B

• Fig. 20.11

  (A) Multiple elevated nodules are often treated using a wide-beam approach after the application of a modulating agent, as illustrated in Fig. 20.3. (B) Postoperative result showing a smooth corneal surface.

A

B • Fig. 20.12

  Climatic keratopathy showing evidence of surface scarring prior to phototherapeutic keratectomy (PTK) (A) and clearance of the central corneal opacities after PTK surgery (B).

A

B

• Fig. 20.13

  (A) Central scarring following radial keratotomy (RK) surgery can be treated with PTK. (B) Short-term follow-up shows substantial reduction of the central opacity, but subepithelial haze persists. The use of adjuvant mitomycin C treatment may help in minimizing postoperative haze and scarring in such patients.

84.6% cases.44 Additionally, PTK with low frequency and low energy of laser pulses ensures fast and durable epithelial closure in most patients with corneal map-dot-fingerprint dystrophy while preventing recurrent cornea erosions and increasing visual acuity.45 Significant postoperative hyperopic shift is not observed, and corneal wound healing is less prolonged. In most cases, the use of surface modulators before laser ablation is not necessary. Combination of PTK with PRK can also prove to be effective in resolution of

symptoms in patients who have symptomatic epithelial basement membrane disorders along with myopia or myopic astigmatism.46

Corneal Scars Treatment of corneal scars limited to the superficial stroma (see Figs. 20.11 and 20.12) can produce significant improvement of visual function.1 Visual improvement with deeper Text continued on p. 320

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

•

Fig. 20.14  Meesmann dystrophy. This condition rarely requires surgery. It may respond well to phototherapeutic keratectomy, but superficial keratectomy or epithelial scraping may be equally effective.

A

• Fig. 20.16

315

  Recalcitrant recurrent erosion syndrome in Cogan dystrophy may require phototherapeutic keratectomy (PTK). This patient did not respond to anterior stromal puncture but responded to subsequent PTK.

B

D C • Fig. 20.15  Cogan anterior basement membrane dystrophy showing fingerprints (A, B) and maps and dots (C, D) rarely requires phototherapeutic keratectomy.

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B

A • Fig. 20.17

  Reis-Buckler dystrophy. (A) Before phototherapeutic keratectomy (PTK). (B) Three months postoperatively. (From Chamon W, Azar DT, Stark WJ, et al. Phototherapeutic keratectomy. Ophthalmol Clin North Am. 1993;6:399–413. Reprinted with permission from Elsevier.)

A

B

• Fig. 20.18

  Recurrent lattice dystrophy in the graft after penetrating keratoplasty (A). The deposits are generally superficial, which can be treated with superficial phototherapeutic keratectomy (B), leaving minimal residual central deposits.

A

B • Fig. 20.19

  A 73-year-old woman with a history of granular dystrophy. The left eye was treated with 40 µm of stromal ablation combined with a modified tapering procedure. (A) Preoperative clinical appearance of granular dystrophy. (B) Nine months postoperatively. (From Azar DT, Jain S, Woods K, et al. Phototherapeutic keratectomy: the VISX experience. In: Salz JJ, McDonnell PJ, McDonald MB, eds. Corneal Laser Surgery. St Louis, MO: Mosby-Year Book; 1995:213–226.)

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

A

B

D C • Fig. 20.20

  (A, B) Corneal deposits are located predominantly in the central cornea. (C) Postoperative appearance of cornea in (A) shows evidence of substantial clearing of granular deposits. (D) Deeper deposits of cornea in (B) persist after phototherapeutic keratectomy with improved vision.

A

B • Fig. 20.21

 

(A, B) Preoperative slit lamp and retroillumination of patient with granular dystrophy. Continued

317

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C

D • Fig. 20.21, cont’d

(C, D) Appearance of cornea after phototherapeutic keratectomy.

A

B

C

D • Fig. 20.22  Preoperative (A, B) and postoperative (C, D) appearance of granular dystrophy treated with phototherapeutic keratectomy.

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

A

B

C

D • Fig. 20.23

  Deposits in granular dystrophy may have distinct borders (A) or more diffuse edges (C). The postoperative appearance of superficial phototherapeutic keratectomy (PTK) of the cornea in (A) is shown in (B), leaving residual, visually insignificant, deposits in the central cornea. This contrasts with the deep PTK of the cornea in (C), which shows subtle subepithelial haze and absence of granular deposits. Significant hyperopic shift accompanies deep PTK. This contrasts with the deep PTK of the cornea in (D), which shows subtle subepithelial haze and absence of granular deposits. Significant hyperopic shift accompanies deep PTK.

B

A • Fig. 20.24

  (A, B) Lattice deposits with predominant localization to the central cornea (A) were treated with phototherapeutic keratectomy (PTK), resulting in central clearing (B). Residual peripheral amyloid deposits are visible. Continued

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C

D • Fig. 20.24, cont’d (C, D) Similar outcome in cornea with central haze in the space between the deposits.

B

A

• Fig. 20.25  Preoperative (A) and postoperative (B) appearance of cornea treated for macular corneal dystrophy.

postinfectious and posttraumatic scars is less likely to occur.29,47 The scar may ablate at a different rate than the adjacent normal stroma, which may not benefit from laser ablation. This and the presence of calcified or cartilaginous tissue may result in postoperative irregular astigmatism (Fig. 20.27). Long-standing posttraumatic superficial stromal scars may be resistant to ablation.48 This can be minimized by using surface modulating agents or a “smoothing” technique. Gentle rotation of the head under the laser beam blends the edges of the irregularities. By maintaining the corneal surface meticulously clear of debris and cellular remnants, further irregularities may be avoided. At times, the scars and keloids on the cornea can be very large such that laser ablation can take too long. In these cases, manual resection prior to excimer laser use for surface smoothening can both eliminate irritation and produce cosmetically a acceptable result. The surface can also be rendered smooth enough for the placement of a prosthesis or contact lens.49 Band keratopathy has also been treated with PTK, although EDTA is still the standard means of treatment.

Infectious Keratitis PTK has been attempted for the treatment of infectious keratitis cases that include fungal, viral, bacterial, and parasitic origins,50–55 but is discouraged because of the possibility of spread of infectious agents during and following treatment. Involvement of the stroma in most microorganism infections extends deeper than the clinically observable lesion. As the tissue penetration depth of 193-nm radiation is no more than 1 mm, deep stromal infiltration may limit the effectiveness of treatment of infectious keratitis with the excimer laser. Reactivation of latent HSV has been reported following excimer PTK.56 Overall, though, early PTK intervention can prove advantageous in treating unresponsive acanthamoeba keratitis because of the direct removal of the amoebic cysts. Sclerotic scatter illumination technique can provide better visualization of the opacity and help prevent excessive ablation in cases of diffuse keratitis.53 PTK combined with other techniques, such as flap amputation and collagen cross-linking, is also reported in

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

A

321

B

D

C • Fig. 20.26

  Preoperative appearance of recurrent lattice dystrophy in a graft by side scatter (A) and retroillumination (C). Superficial phototherapeutic keratectomy was sufficient to clear the recurrence, as evidenced by scatter (B) and retroillumination (D).

A

B

• Fig. 20.27

  Excimer laser phototherapeutic keratectomy may not be necessary to treat band keratopathy (A), which is better treated with ethylenediaminetetraacetic acid (B).

cases of severe intractable post-LASIK mycobacterial infection with corneal melt.57

Refractive Surgery Complications PTK is a valuable tool for the treatment of surface irregularities following refractive surgery (see Figs. 20.13 and 20.28). Ablation of the epithelium with the excimer laser results in fluorescence in the blue wavelength that can be visualized under low illumination. With excimer laser ablation of the corneal stroma, fluorescence is lost.58 This characteristic has been used to help manage patients

with central islands or decentration following PRK and flap striae following LASIK. Rachid et al. have described a technique for the management of central islands and decentrations in which transepithelial PTK is followed by PRK and repeat PTK.58 Transepithelial PTK set at 50 µ is performed first to expose the island or decentered area. PRK is applied to treat the residual refractive error, and PTK is repeated to eliminate any residual epithelium, confirmed by absence of epithelial fluorescence58 (Fig. 20.28). Steinert et al. have described a technique for the treatment of flap striae after LASIK.59 Transepithelial ablation is performed

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images falling on the fovea of one eye and a nonfoveal point in the other eye. The same object is seen at two different locations in subjective space. In physiologic diplopia, objects outside Panum’s area fall on noncorresponding points. The angle of deviation, PD, can be calculated from the equation

until epithelial fluorescence begins to disappear between the striae. A masking agent is then applied with PTK to smooth the surface.59

Prismatic Photokeratectomy We have studied the use of a modified PTK technique, prismatic photokeratectomy (PPK) in patients with smallangle strabismic deviations and diplopia. Diplopia results when the visual axes are misaligned with simultaneous

PD =

360( N − 1) h ⋅ , π OZ

where PD is the angle of deviation (prism diopters), N is the index of refraction, h is the maximal ablation depth, and OZ is the optical zone (diameter of laser ablation) h OZ OZ or h = PD ⋅ . 42

or PD = 42 ⋅

Figs. 20.29 and 20.30 show a schematic of PPK used to correct binocular diplopia. PPK makes the cornea resemble a curved prism with spherical sides. The prismatic correction is proportional to the depth of ablation and inversely proportional to the diameter of the ablation zone. Theoretical analysis has been performed on the optics of prisms with spherical sides and the relationship of the prismatic correction to the diameter and maximal depth of laser

Sites of early loss of fluorescence

• Fig. 20.28

Transepithelial ablation of the central island following phototherapeutic keratectomy (PTK). This is the first step in a sequential treatment of PTK followed by photorefractive keratectomy and repeat PTK. Ablation of the epithelium creates fluorescence in the blue wavelength that can be visualized at low illumination. This helps define the area of the central island.  

Angle of deviation

A

Uncorrected: image falls on extrafoveal location, giving impression of seeing two objects

B

External prism bends rays toward the base and brings image into fovea, avoiding diplopia

Corneal prism bends rays toward the ablated side of the cornea and brings the image into the fovea

C

D • Fig. 20.29  Schematic diagram of (A) binocular diplopia, (B) corrected with external prism, or (C) prismatic photokeratectomy. (D) Clinical appearance of eyes treated with prismatic photokeratectomy.

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

323

Excimer prismatic ablation

R

Non movable diaphragm (PTK)

R Same radius of curvature Corneal prism ablated (removed from cornea) by excimer laser

Shutter

Axis of treatment

B

Equivalent prism ablated from flat surface

A 5

4

5

2

1 Slow shutter movement = deep

D

Tapered edge of treatment zone minimizes epithelial hyperplasia

Fast shutter movement = shallow

C

E • Fig. 20.30  Prismatic photokeratectomy principle (A) and excimer delivery system (B) showing the effect of moving the shutter at various rates (C). The optimal treatment (D) results from decentering the treatment toward the base and oscillating the circular shutter to create smooth edges. (E) Histologic appearance of eyes treated with prismatic photokeratectomy.

ablation.60,61 Variable degrees of small-angle prismatic correction can be obtained. For example, a deep PPK treatment of 240 µm maximal depth and 5 mm diameter ablation would induce 2.5 prism diopters (D). The healing process that follows the stromal prismatic ablation may alter the final effect depending on how well the epithelial surface conforms to the ablation bed.

Postoperative Management Following treatment, a therapeutic contact lens is often placed. Topical antiinflammatory agents are applied frequently in the postoperative period. One percent prednisone acetate or 0.1% fluoromethalone drops are used q.i.d. for 1 week and then tapered to once daily by 1 month. Topical antibiotics are typically applied q.i.d. until the reepithelialization of the cornea is complete, approximately 3

to 7 days. The bandage contact lens is removed once the corneal epithelium is intact. If a bandage contact lens is not used, patients can be managed by application of a topical antibiotic ointment with patching of the eye. Some physicians give sub-Tenon’s injections of gentamicin and dexamethasone immediately postoperatively and/or instill a topical cycloplegic agent, such as homatropine. Patients can experience significant pain during the first 24 to 48 hours following surgery. Oral medications (sedative analgesics) are usually required for pain control. Topical nonsteroidal agents, such as 0.1% diclofenac sodium (Voltaren Ophthalmic, CIBA Vision Ophthalmics) have also been used in the immediate postoperative period to reduce pain. One report suggests caution, however, describing corneal melt and perforation following PRK and prolonged use of topical diclofenac in the setting of diabetes mellitus.62 The report suggests that matrix metalloproteinases, enzymes

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involved in corneal remodeling, might have been involved in delayed corneal healing seen in this patient. Other pain control measures that have been suggested include cycloplegics, ice packs, and peribulbar or retrobulbar anesthesia. Patients are examined 1 day postoperatively, 1 week postoperatively, and then at 1 month, 3 months, 6 months, and 12 months. More frequent visits are scheduled if needed. The postoperative examination at each visit includes symptomatic evaluation, measurement of visual acuity, a detailed anterior segment examination, and slit lamp biomicroscopy.

Corneal Wound Healing Corneal healing after PTK proceeds in two overlapping stages: re-epithelialization and stromal healing. Reepithelialization is usually complete by the first week following surgery.1,4–8,15,63,64 Adhesion of the newly formed epithelium to the underlying stroma occurs between 1 and 3 months as anchoring complexes (hemidesmosomes) are created, binding the epithelium, basal lamina, and anterior stroma.5,65 After PTK, stromal keratocytes of the anterior stroma initially undergo apoptosis.66 New keratocytes establish a hypercellular zone adjacent to the wound margin to replace and remodel the damaged stroma.5,64 The remodeling phase of stromal healing can last years and involves a group of enzymes known as matrix metalloproteinases (MMPs). MMPs are involved in both short-term and longterm healing responses. They are regulated by a group of inhibitors that can bind MMP active sites, the tissue inhibitors of metalloproteinases (TIMPs). Dysregulation of MMPs can lead to complications, such as corneal melting.67,68 The type and extent of wounding affect the corneal healing response. After an epithelial scrape wound, such as a corneal abrasion, a smooth epithelial surface is produced and there is minimal stromal scarring.1,8,69–71 Following a shallow PTK treatment, epithelial hyperplasia and stromal collagen deposition help restore the original corneal surface contour.1,7,63 With deep ablations, some have noted formation of a pseudomembrane after surgery. The pseudomembrane is thought to help hyperplastic migrating epithelial cells fill in the wound and create a smooth epithelial surface.5,63 Generally, hyperplasia takes place in deeper ablations and when there are apparent irregularities in the stromal bed.64,69,71 A residual depression may persist after deep PTK despite the deposition of newly synthesized collagen by the keratocytes.69,71

Complications From PTK and Intralamellar PTK Complications with PTK and intralamellar PTK can be divided into refractive and nonrefractive categories. Refractive complications include hyperopic shift, myopic shift, irregular astigmatism, and glare or halos. Nonrefractive complications can occur in the early postoperative and late postoperative periods. Early postoperative complications

include chronic epithelial defects and infectious keratitis. Late complications include corneal haze formation, recurrence of pathology, endothelial cell loss, graft rejection, and reactivation of disease, such as HSV.

Refractive Complications Refractive shifts of any kind can be seen following PTK, with hyperopic shift being seen most frequently.72 Hyperopic shift results from flattening of the central cornea and has been shown to correlate with ablation depth.72 Four potential mechanisms for hyperopic shift have been hypothesized: (1) greater degrees of epithelial hyperplasia and tear film thickness at the edge of ablation; (2) greater ablation centrally if the corneal pathology thins progressively toward the visual axis; (3) greater shielding of the stroma toward the edge of the ablated zone by the ablation products (plume); and (4) oblique angle of incident radiation falling on the more peripheral cornea, resulting in a decreased peripheral ablation.70,73,74 Strategies to reduce hyperopic shift may include use of a large treatment zone or the use of masking agents during treatment. Careful attention to ablation depth is also important in order to avoid excessive tissue removal. Depth of treatment may be difficult to assess with patients positioned under the laser. In this case, treatment can be stopped, the patient can be brought to the slit lamp for examination of lesion depth, and treatment can resume if necessary. A modified taper technique of Stark and colleagues1 may also minimize hyperopic shift. Combined ablation can also be performed in which PTK is followed by secondary hyperopic correction with PRK.29 When corneal opacities or irregularities are associated with myopic refractive errors, the need for PRK after PTK is reduced by allowing for approximately 1 D of hyperopic shift for every 20 µm of stromal ablation. Myopia and irregular astigmatism are less frequent complications after PTK. Induced myopia can occur with PTK if more tissue is removed peripherally than centrally, and irregular astigmatism occurs with a decentered treatment or an irregular ablation. Glare and halos can result from residual refractive error, a decentered ablation, or irregular astigmatism. With IL-PTK, significant and likely unpredictable refractive change can occur owing to the lack of ready availability of nomograms for refractive change after dual lamellae excimer laser ablation. Significant degrees of astigmatism are likely possible given the mode of treatment.

Early Postoperative Complications Delayed corneal wound healing can follow PTK.1,4 As mentioned, corneal re-epithelialization is usually complete by 1 week. Ocular surface inflammation, toxicity of topical postoperative medications, corneal anesthesia, history of herpetic eye disease, damage to the Bowman membrane, and poor eyelid anatomy may contribute to persistent epithelial defects following PTK.75 Delayed wound healing, in turn,

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

can be associated with corneal haze, recurrent erosions, infections, and corneal ulcers.1,9 Stark et al. reported two patients in whom corneal re-epithelialization took 3 to 4 weeks compared to 1 week or less for other patients.1 Persistent epithelial defects can be managed with treatment of ocular surface disease, lubrication, use of a bandage contact lens or patching, discontinuation of potentially toxic medications, and, ultimately, tarsorrhaphy if needed.75 Damage to the limbal stem cell population has also been described following PTK in a patient with a history of recurrent corneal erosions, diabetes mellitus, and rosacea.76 The incidence of bacterial keratitis following PTK has been reported to be 1.2% in a study by al-Rajhi et al.77 In this series, 258 eyes were treated, and three patients developed bacterial keratitis. Gram-positive organisms were the main species isolated (Streptococcus pneumonia and coagulase-negative Staphylococcus), and final visual outcome was no better than 20/125 in any eye.77 Risk factors for bacterial keratitis may include persistent epithelial defect, disease of the ocular surface adnexa, and the use of bandage contact lenses.75 A Japanese study surveying 22,415 excimer laser cases in a multicenter survey reported an incidence of one infection after PTK (incidence rate of 0.004%).78 The cases were followed up at postoperative 1, 3, 6, and 12 months. This low incidence of keratitis reported could be attributed to greater awareness and better sterile techniques during surgery. It should be noted however, that this study is limited by the retrospective and noncontrolled nature of the study along with other limitations, such as the survey period (2007–2010) being different from the infection outbreak period (2008–2009), and inclusion of responses of only the LASIK Safety Network members. For IL-PTK, the most common complication of surgery is likely to be failure to achieve the desired effect. Following surgery, interface abnormalities may persist. Although masking agents are applied to rid the stromal bed of irregularities, the smoothing may not be adequate. Masking agents have a faster ablation rate than the corneal stroma; thus the surgeon must reapply the agent several times during the procedure. Efforts are being made to get an ideal masking agent with the same ablation rate as the opacities or to customize the ablation according to the surface profile.2,49 When residual scarring is the indication for IL-PTK, it may not be possible to safely carry the ablation to an adequate depth to remove all visually significant posterior stromal opacities. In these cases, the patient may ultimately require a PK for improvement in vision. A second set of complications is caused by application of the excimer laser. One such complication could be the induction of greater interface mismatch and irregularity. The most smoothing is usually applied to the stromal bed, both as a primary treatment and the treatment using a masking agent. Thus one has the potential of reapposing an extremely smooth bed with a less smooth donor tissue with a resultant increase in interface irregularity. Careful laser to the donor and the use of a masking agent to the donor tissue may help obviate this complication.

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Late Postoperative Complications The cornea may remain hazy for several months following PTK. Haze may result from the deposition of new irregular collagen fibers or from light scattering by “activated” keratocytes in the wound.4,7,8,63 The amount of haze appears to be related to the amount of tissue ablation. However, the formation of reticular haze in LASIK patients has been markedly less and is thought to be due at least in part to the intralamellar location of the ablation.79 Since both lamellae are treated in IL-PTK, it is possible that haze could be induced by the procedure instead of reducing opacification. Although not yet clearly limiting the use of PTK, possible solutions to haze may be the application of MMC to the lamellae during the procedure, an adjunct to surgery that has been effective in preventing haze in PRK.80,81 MMC is a topical chemotherapeutic agent that can interfere with fibroblast proliferation. It has been used in combination with PTK to limit potential scar formation and to treat haze after PRK.82,83 Postoperative treatment with steroids may also reduce the thickness of the subepithelial layer of collagen and the density of subepithelial scarring.7 Haze usually decreases after the 3- to 6-month period following surgery.7,64 Other agents under investigation may limit corneal haze formation in PTK. Anderson Penno et al.83a have described the use of topical thiotepa, an alkylating agent, with PTK for the treatment of recurrent haze after PRK in five patients. Uncorrected and best-corrected visual acuities improved in all eyes.49 Subjective and objective methods have been developed for the measurement of corneal haze. Corneal haze can be graded subjectively using slit lamp biomicroscopic examination as follows: 0 = clear; 0.5 = barely detectable; 1.0 = mild, not affecting refraction; 1.5 = mildly affecting refraction; 2.0 = moderate, refraction possible but difficult; 3.0 = opacity preventing refraction, anterior chamber easily viewed; 4.0 = impaired view of anterior chamber; and 5.0 = inability to see the anterior chamber. The cornea is divided into five hypothetical layers (superficial and deep epithelium, anterior and posterior stroma, and endothelium); each layer is graded separately. Subjective methods of grading corneal haze are not accurate and reproducible, and suffer from interobserver variability and bias. Objective methods assess the magnitude of haze by measuring corneal light scattering. The “scatterometer” is a modified slit lamp microscope that measures back-scattered light from a defined region of the cornea under standardized illumination conditions. This device was developed in collaboration with Dr. Russell McCally of the Applied Physics Laboratory at Johns Hopkins University. Corneal light scattering is related to the degree of stromal scarring following excimer laser ablations. This instrument was tested on laboratory animals and humans and was found to yield reproducible results.84 Subjective and objective corneal clarity scores are usually lower following PTK than preoperative scores. In other excimer laser procedures, lasering has reactivated latent herpes virus, leading to HSV keratitis.85 This might

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be more of a problem given the longer-term use of steroids following IL-PTK. In the setting of prior herpetic disease, the surgeon is left with a decision to either avoid IL-PTK altogether or to employ antiviral prophylaxis (i.e., acyclovir). In one study, excimer ablation led to corneal reactivation of HSV in laboratory mice that were latently infected with HSV.20 Fagerholm et al. treated 20 patients with a history of HSV keratitis. During the follow-up period of 16.8 months, recurrences occurred in five patients.56 Prophylactic therapy with oral and possibly topical antivirals may be important in patients with a previous history of HSV blepharoconjunctivitis or keratitis who are undergoing PTK.75 Corneal ectasia following progressive weakening of tectonic corneal stability is possible due to extensive tissue removal within the bed. Corneal ectasia has been noted following LASIK surgery and could be a potential problem in lamellar surgery. This may be particularly true if the indication for the initial LK was an ectatic disorder, such as keratoconus. In LK surgery, additional stability is provided by the suturing of the anterior lamellae and may serve to at least counteract weakening of the cornea by tissue removal. Corneal graft rejection may occur following PTK. In one reported case, rejection occurred in a patient who had PTK for treatment of recurrent lattice dystrophy.86 Another case has been described in a patient with BIGH3-linked corneal dystrophy.42 Rejection episodes were aborted with intensive therapy with topical corticosteroids. Maloney et al. described two episodes of graft rejection in a series of 232 eyes treated with PTK.87 Recurrence of pathology has been demonstrated following PTK for corneal dystrophies. Stewart et al. treated 29 eyes of patients with corneal dystrophies.37 Recurrence occurred between 10 and 35 months in five eyes in patients with diagnoses of Reis-Buckler, granular, and lattice dystrophies. Three eyes developed a second recurrence following retreatment. PTK has also been used to successfully retreat patients with recurrent corneal erosions who failed primary PTK.88 In patients undergoing retreatment, particular attention should be paid to depth of pathology and refraction. A final class of complications is related to lamellar surgery in general. After corneal lamellae are separated, there are potential complications as they are brought back together. Perturbed corneal epithelial cells can enter the intralamellar space and cause significant opacification or corneal melt. Careful suturing techniques and meticulous management of loose epithelium can minimize the occurrence of epithelial ingrowth.89 Attention to wound-edge apposition during the final suturing phase can also abrogate the risks of fluid leak between the lamellae with the concomitant formation of a pseudo-anterior chamber. Suture-related complications— such as induced astigmatism, broken suture, and suture abscess, which are observed for standard LK surgery—may also be found with IL-PTK. Endothelial cell damage is also possible with PTK when ablations are within 40 µm of the Desçemet membrane.8,9 This may be related to acoustic or shock waves and high-pulse energy or resonance in the

posterior cornea.5,9,90 There is no evidence so far of endothelial cell loss or displacement if the ablations stay 40 µm above the Desçemet membrane.8,90,91 DNA damage is yet another potential side effect of PTK that may result from the 193-nm UV radiation or from thermal loading.90–92 The shorter penetration depth of direct 193-nm excimer laser radiation and the minimal fluorescent emission of longer UV wavelengths for energy exposures used in clinical applications make the potential side effects and risks of PTK very limited and remote in subablative laser energy.93 In cases with an impaired limbus, extensive peripheral lasering must be avoided to prevent limbal stem cell deficiency, which could be a first step for a rejection.94,95 As additional patients are treated with IL-PTK, the true risk for potential complications will become better quantified. As the risk–benefit profile of IL-PTK is better defined, surgeons will be able to decide whether IL-PTK should be a standard keratorefractive technique, used to improve the outcomes of LK either intraoperatively or postoperatively. If there are many complications or if the eyes do not improve significantly after PTK, the patient may need to undergo more invasive treatment, such as corneal transplantation.1 Many patients who are currently treated with PTK in order to reduce the chance of needing PK eventually require PK. With further advances in our technique and refinement of PTK indications, the need for PK after PTK can be minimized.

Outcomes of PTK: Major Studies and Specific Diseases The data comparing preoperative to post-BCVA accumulated by Sanders from 271 consecutive PTK cases at 17 VISX US centers show that the average improvement in BCVA was 1.8 lines (P < .001).15 A total of 10% of patients lost 2 or more lines of BCVA, while 45% gained two or more lines. A total of 7% of the patients lost three or more lines, while 36% gained that much. Analysis of the reasons for decreases in BCVA showed corneal surface irregularity induced by PTK accounting for only 3% of cases. Two or more lines of improvement of uncorrected visual acuity (UCVA) were seen in 42% to 44% of patients, as opposed to reduction in 18% to 19%. Based on the dates of treatment, Sanders divided the 271 patients treated at US VISX centers into quartiles.2,15 He found that the first quartile had an average of 5.5 D of hyperopic effect, and the last quartile had less than 2 D of hyperopia. The percentages of patients in Sanders’s review who experienced moderate to severe levels of pain and tearing before treatment were 10% and 8%, respectively. Of these patients, only one experienced postoperative tearing; the rest improved. Similarly, there was no significant worsening of photophobia, redness, or foreign body sensation. The effect of PTK on patients with moderate to severe epithelial corneal opacities shows that 86% to 88% of patients improved following treatment, and

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

in only 1% did the condition worsen. Between 60% and 62% of patients with anterior stromal opacities improved after treatment, and 2% worsened.2 Sher and colleagues reported that 15% of their patients lost 2 or more lines of spectacle-corrected visual acuity following PTK.29 Chamon et al. from the Wilmer Ophthalmological Institute have reported a 3% loss of one line of functional visual acuity, defined as the acuity achieved with the visual aid that a patient is wearing: either contact lenses or spectacles.73 The mean preoperative visual acuity (logarithmic) was 20/92; the mean postoperative visual acuity was 20/47 using manifest refraction. In 80% of patients, spectacle-corrected visual acuity had improved one line or more at the most recent follow-up visit. Four patients became contact lens tolerant after PTK.73 Eyes treated with the standard 0.5-mm taper had an average of 5.11 and 5.28 D of induced hyperopia at 3 and 36 months, respectively. Eyes treated with the modified taper showed a trend toward a decreasing amount of induced hyperopia.73 Chamon et al. observed a positive correlation between depth of stromal ablation and amount of induced hyperopia.73 Campos et al. performed PTK on 18 eyes.47 The follow-up ranged from 2 to 18 months, with a mean of 8 months. Corneal clarity improved in 77.7% of the patients, while 22.2% did not experience any improvement. In 61.1% of the patients, UCVA improved. An induced flattening was observed in all patients, and a hyperopic shift was observed in 55.5%. This induced hyperopia was observed to decrease by the 6-month and 1-year follow-ups. Patients with band keratopathy and corneal calcification who underwent PTK did not experience any visual improvement.47 Durrie et al. have reported 3- to 21-month followup data from 67 procedures performed in phase II and phase III Summit Excimed excimer laser clinical trials for PTK.31 BCVA improved in 67% of eyes, and 20% of eyes lost at least one line of BCVA. Hyperopic shift was noted in 19% of eyes, and there was an average reduction of corneal cylinder postoperatively.31

Corneal Dystrophies Corneal dystrophies and degenerations that have been treated with PTK to improve visual function or comfort include dystrophies of the epithelium and basement membrane (map-dot-fingerprint and Meesmann), dystrophies of the Bowman layer (Reis-Buckler), granular dystrophy, lattice dystrophy, and other stromal dystrophies (gelatinous droplike, macular, Schnyder), endothelial dystrophies (Fuchs), and Salzmann nodular degeneration. Greater success has been achieved in superficial corneal dystrophies such as map-dot-fingerprint (100%), Meesmann (100%), and Reis-Buckler dystrophy (100%) than in stromal dystrophies such as granular (67%), lattice (92%), and Schnyder dystrophy (67%). Patients with granular or lattice dystrophy in a graft have relatively superficial lesions. A study of the distribution of these deposits suggests that patients with granular dystro-

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phy may appreciate better postoperative acuity than those with lattice dystrophy, given the more anterior location of granular deposits.96 The success rate in these cases is very high and is similar to that for primary Reis-Buckler dystrophy, in which the deposits are limited to the Bowman layer.1 Most patients achieve a relatively smooth ablation bed by treating through the epithelium. For patients with granular dystrophy, the aim is to ablate most of the areas of diffuse haze between the granular deposits and not necessarily all the granular hyaline deposits. Patients with superficial corneal lesions, as in epithelial and basement membrane dystrophies, may respond well to PTK, obviating the need for conventional invasive surgery. Dinh et al.97 evaluated the rate of recurrence of various dystrophies following treatment with PTK. After a mean follow-up of 19.5 months, they showed the following recurrence rates: anterior basement membrane dystrophy (42%) within 6 to 9 months after PTK; Reis-Buckler dystrophy (47%), mean 21.6 months; granular dystrophy (23%), mean 40.3 months; lattice dystrophy (14%), mean 6 months.97 If patients fail PTK therapy, PK or LK may be pursued. In those patients who ultimately undergo PK, no difference in outcomes has been demonstrated.43 If disease recurs in a corneal graft, PTK may be employed to treat the graft. Ellies et al. reviewed the cases of 42 eyes and showed that PTK may prevent or delay the need for repeat graft in these patients.42

Recurrent Corneal Erosions Review of major PTK studies shows that functional improvement was achieved in 77% of the 203 eyes after the initial treatment of recurrent epithelial erosions with PTK. In two studies, the success rate improved to 95% (107 of 113) with retreatment. One recent study examined 48 eyes that were treated with PTK for recurrent erosions occurring in anterior basement membrane dystrophy. Data showed no significant change in acuity at 1 month but did show improvements in acuity at 12 months. Symptoms of erosion recurred in 13.8% anterior basement membrane dystrophy (ABMD), and all recurrences occurred within 6 months of PTK. Of those patients surveyed, a high level of satisfaction following PTK was expressed.98

Corneal Scars (Video 20.5) Corneal scars, apical scars in keratoconus (proud nebulae) and band keratopathy (smooth and rough) have been successfully treated with PTK to improve both visual function and the ocular surface. Corneal scars that have been successfully treated with PTK include postinfectious, posttraumatic, herpetic, trachomatous, and pterygium related. The success rate varies from 50% to 80%. Greater success has been achieved in superficial corneal scars following pterygium surgery (80%) than in deeper postinfectious (50%) and posttraumatic scars (61%). One report has shown a high success rate in treating herpetic scars (80%). Despite

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the reported success, several investigators caution against using the excimer laser in herpetic disease because of the risk of recurrence.47,61,99 Treatment of corneal scars limited to the superficial stroma produces significant improvement of visual function.1 Deeper scars have been treated with PTK with some success. Dogru et al. showed improvement in vision in 12 out of 14 eyes treated with PTK for midstromal scars, but hyperopic shift was seen in all eyes.100 A review of outcomes for treatment of apical scars in keratoconus showed that 81% of the 21 eyes improved. Band keratopathy may be treated with PTK; however, EDTA is still the standard treatment for this condition.1,29,47,69–71,84 Of 136 eyes treated for band keratopathy, 91% improved. Most investigators, however, have had limited success with the application of PTK for band keratopathy.29,47

TABLE Causes of Visual Disturbances After 20.1  Lamellar Surgery

Refractive Surgery

follow-up. Although the two treatment groups are not strictly comparable, the differences in postoperative VA are quite marked. There are likely two main reasons for worse outcomes in LK.103,104 • Interface opacification: The clarity of the cornea may be diminished by ingrowth of vessels, epithelial cells, debris, fibrosis after surgery, or failure to completely remove an opacity during surgery. • Interface optical dysfunction: The mere presence of an interface may induce some optical scattering of the light rays, although the phenomenon may not always be observed as a significant VA degradation. For example, following uncomplicated LASIK, in which two lamellae from the same cornea are reapproximated, there is no significant VA loss. However, high-frequency ultrasound corneal analysis has identified irregularities in the interface of LASIK patients with visual complaints but normal clinical and topographic findings.104 In LK, two corneal lamellae, one from a donor and another from the recipient bed, are brought into apposition. In such a case, the ability to achieve a smooth interface is more difficult. The discontinuity between the lamellae may be augmented by redundant folds (such as seen commonly in the posterior lamellae in keratoconus patients), irregular dissection, or leakage between lamellae with or without formation of a pseudochamber. Potential methods for minimizing complications at the lamellar interface include: • Microkeratome-assisted LK, which could reduce the incidence of opacification by making the interface more regular.105 • Deep free-hand dissection106: The deeper the dissection, the better the match between donor lenticule and recipient bed.107

PTK has been performed as a means of treating refractive surgical complications, including central islands and decentration following PRK, flap striae, subepithelial fibrosis and haze, and diffuse lamellar keratitis (DLK). Rachid et al. treated 14 patients with post-PRK central islands or decentration with a sequence of PTK, PRK, and repeat PTK.58 Patients in both groups demonstrated improved visual acuity. Those with central islands improved from 20/100−1 to 20/30−1, and patients with decentration improved from 20/80+1 to 20/30. Steinert et al. described PTK treatment for 23 eyes of patients with flap striae following LASIK.59 These patients had demonstrated improved acuity with contact lens fitting and were treated with transepithelial PTK. Of the 23 treated eyes, 22 had a significant improvement in visual symptoms. Another group has described the combined use of epithelial debridement, PTK, PRK, and amniotic membrane graft for the treatment of severe subepithelial fibrosis following PRK and LASEK.101 Porges et al. have described the use of PTK with MMC for the treatment of patients with severe corneal haze following PRK for high myopia in eight eyes. Visual acuity improved in all eyes and mean haze decreased in all eyes. No adverse effects were reported from the MMC.82 One case report describes PTK treatment of the surfaces of a LASIK flap interface as part of the management of DLK.102

Visual Acuity Outcomes in Lamellar Keratoplasty The main limitation of LKs, even without complication, is less VA improvement compared to PK (Table 20.1). Soong et al.103 reported VA of 20/50 or better in only 38% of eyes in a retrospective review of 37 LK procedures in 52 patients with corneal dystrophies, aniridic keratopathy, corneal scars, or keratoconus at a mean follow-up of 3 years. The same investigators found that patients who underwent PK and sutured posterior chamber intraocular lens implantation had a VA of 20/50 or better in 51% of eyes at a 1-year

Irregularities in the epithelial–stromal interface Discontinuity in the interface (with or without pseudochamber) Remaining scar (in case of scar as a primary diagnosis) Fibrosis or haze formation Vessel ingrowth in the interface Epithelial ingrowth in the interface Debris

Excimer Laser and Lamellar Keratoplasties Excimer laser has been used to prepare the recipient bed and to create donor tissue of more regular diameter and thickness in order to get more congruent surfaces. Eckhardt et al.11 reported the results of three patients who underwent

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

deep LK assisted by the excimer laser. There was good approximation of host and donor tissue without evidence of interface opacification. The long-term outcomes of these patients have not been described. A second application of PTK in lamellar surgery has been the treatment of postoperative interface haze and optical irregularity. In this case, the donor graft was reflected away from the host bed, and both the posterior surface of the graft and the anterior surface of the host bed (100 µm residual tissue) were polished using the excimer laser. Only one case has been reported; this patient had an improvement of BCVA from 20/100 to 20/22 with no measurable loss of endothelial cells at a 9-month follow-up.14 Again, long-term follow-up is not available. Another technique has been reported for thin corneas with irregular astigmatism after repeated unsuccessful LASIK or due to keratoconus in which a donor stromal button graft modulated by excimer laser was positioned inside a host stromal pocket as part of an LK. This “sandwich” technique allows additional excimer laser ablation. Although there has been VA improvement after a followup of 14 months, more trials are needed to evaluate this technique.22,79

References 1. Stark WJ, Chamon W, Kamp MT, et al. Clinical follow-up of 193-nm ArF excimer laser photokeratectomy. Ophthalmology. 1992;99(5):805–812. 2. Rapuano CJ. Excimer laser phototherapeutic keratectomy in eyes with anterior corneal dystrophies: preoperative and postoperative ultrasound biomicroscopic examination and short-term clinical outcomes with and without an antihyperopia treatment. Trans Am Ophthalmol Soc. 2003;101:371–399. 3. Migden M, Elkins BS, Clinch TE. Phototherapeutic keratectomy for corneal scars. Ophthalmic Surg Lasers. 1996;27: S503–S507. 4. Salz JJ, Maquen E, Macy JI, et al. One-year results of excimer laser photorefractive keratectomy for myopia. Refract Corneal Surg. 1992;8(4):269–273. 5. Gaster RN, Binder PS, Coalwel K, et al. Corneal surface ablation by 193 nm excimer laser and wound healing in rabbits. Invest Ophthalmol Vis Sci. 1989;30(1):90–98. 6. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery of the cornea. Am J Ophthalmol. 1983;96(6):710–715. 7. Tuft SJ, Zabel RW, Marshall J. Corneal repair following keratectomy. A comparison between conventional surgery and laser photoablation. Invest Ophthalmol Vis Sci. 1989;30(8): 1769–1777. 8. Marshall J, Trokel S, Rothery S, Kreuger RR. Photoablative reprofiling of the cornea using an excimer laser: photorefractive keratectomy. Lasers Ophthalmol. 1986;1:23–44. 9. Marshall J, Trokel S, Rothery S, et al. A comparative study of corneal incisions induced by diamond and steel knives and two ultraviolet radiations from an excimer laser. Br J Ophthalmol. 1986;70(7):482–501. 10. van Setten GB, Koch JW, Tervo K, et al. Expression of tenascin and fibronectin in the rabbit cornea after excimer laser surgery. Graefes Arch Clin Exp Ophthalmol. 1992;230(2):178–183.

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11. Eckhardt HB, Hütz WW, Heinrich AW, et al. Lamellar keratoplasty with the excimer laser. Initial clinical results. Ophthalmology. 1996;93:242–246. 12. Krumeich JH, Schöner P, Lubatschowski H, et al. Excimer laser treatment in deep lamellar keratoplasty: 100 micrometer over Descemet’s membrane. Ophthalmology. 2002;99:946–948. 13. Alio JL, Shah S, Barraquer C, et al. New techniques in lamellar keratoplasty. Curr Opin Ophthalmol. 2002;13:224–229. 14. Jankov M, Mrochen M, Seiler T. Laser intrastromal keratoplasty – case report. J Refract Surg. 2004;20:79–84. 15. Sanders D. Clinical evaluation of phototherapeutic keratectomy – VISX Twenty/Twenty excimer laser. Submitted to the FDA; written communication 2/7/94. 1994. 16. Keates RH, Drago PC, Rothchild EJ. Effect of excimer laser on microbiological organisms. Ophthalmic Surg. 1988;19(10):715–718. 17. Gottsch JD, Gilbert ML, Goodman DF, et al. Excimer laser ablative treatment of microbial keratitis. Ophthalmology. 1991;98(2):146–149. 18. Serdarevic O, Darrell RW, Krueger RR, et al. Excimer laser therapy for experimental Candida keratitis. Am J Ophthalmol. 1985;99(5):534–538. 19. Eiferman RA, Forgey DR, Cook YD. Excimer laser ablation of infectious crystalline keratopathy. Arch Ophthalmol. 1992; 110(1):18. 20. Pepose JS, Laycock KA, Miller JK, et al. Reactivation of latent herpes simplex virus by excimer laser photokeratectomy. Am J Ophthalmol. 1992;114(1):45–50. 21. Rapuano CJ. Preoperative and postoperative protocols. In: Srinivasan R, Azar DT, Stark WJ, eds. Excimer Laser Phototherapeutic Keratectomy: Management of Scars, Dystrophies, and Prk Complications. Baltimore, MD: Williams & Wilkins; 1997:65–70. 22. Dudenhoefer EJ, Jain S, Azar DT. Treatment of Deep Stromal Haze after Lamellar Keratoplasty with Intrastromal Phototherapeutic Keratectomy. Scientific Poster in American Academy of Ophthalmology 2002 Annual Meeting. Orlando, FL; 2002. 23. Meyer CH, Sekundo W. Evaluation of granular corneal dystrophy with optical coherent tomography. Cornea. 2004;23(3): 270–271. 24. Krueger RR, Campos M, Wang XW, et al. Corneal surface morphology following excimer laser ablation with humidified gases. Arch Ophthalmol. 1993;111(8):1131–1137. 25. Seiler T, Schmidt-Petersen H, Wollensak J. Complications after myopic photorefractive keratectomy, primarily with the Summit excimer laser. In: Salz JJ, McDonnell PJ, McDonald MB, eds. Corneal Laser Surgery. St Louis, MO: Mosby; 1995: 131–142. 26. Mrochen M, Kaemmerer M, Mierdel P, et al. Increased higher-order optical aberrations after laser refractive surgery: a problem of subclinical decentration. J Cataract Refract Surg. 2001;27(3):362–369. 27. Viestenz A, Bischoff-Jung M, Langenbucher A, Eppig T, Seitz B. Phototherapeutic keratectomy in Salzmann Nodular Degeneration with “optical cornea plana. Cornea. 2016;35(6):843–846. 28. Kremer F, Aronsky M, Bowyer B, et al. Treatment of corneal surface irregularities using biomask as an adjunct to excimer laser phototherapeutic keratectomy. Cornea. 2002;21(1):28–32. 29. Sher NA, Bowers RA, Zabel RW, et al. Clinical use of the 193-nm excimer laser in the treatment of corneal scars. Arch Ophthalmol. 1991;109(4):491–498. 30. Thompson V, Durrie DS, Cavanaugh TB. Philosophy and technique for excimer laser phototherapeutic keratectomy. Refract Corneal Surg. 1993;9(2 suppl):S81–S85.

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Advanced Surface Ablation (PRK, LASEK, and Epi-LASIK) and Phototherapeutic Keratectomy

31. Durrie DS, Schumer DJ, Cavanaugh TB. Phototherapeutic keratectomy: the VISX experience. In: Salz JJ, McDonnell PJ, McDonald MB, eds. Corneal Laser Surgery. St Louis, MO: Mosby-Year Book; 1995:227–235. 32. Talamo JH, Steinert RF, Puliafito CA. Clinical strategies for excimer laser therapeutic keratectomy. Refract Corneal Surg. 1992;8(4):319–324. 33. Sharma N, Prakash G, Sinha R, Tandon R, Titiyal JS, Vajpayee RB. Indications and outcomes of phototherapeutic keratectomy in the developing world. Cornea. 2008;27:44–49. 34. Rathi VM, Vyas SP, Vaddavalli PK, Sangwan VS, Murthy SI. Phototherapeutic keratectomy in pediatric patients in India. Cornea. 2010;29:1109–1112. 35. Das S, Langenbucher A, Seitz B. Delayed healing of corneal epithelium after phototherapeutic keratectomy for lattice dystrophy. Cornea. 2005;24(3):283–287. 36. Oya F, Soma T, Oie Y, et al. Outcomes of photorefractive keratectomy instead of phototherapeutic keratectomy for patients with granular corneal dystrophy type 2. Graefes Arch Clin Exp Ophthalmol. 2016;254(10):1999–2004. 37. Stewart OG, Pararajasegaram P, Cazabon J, et al. Visual and symptomatic outcome of excimer phototherapeutic keratectomy (PTK) for corneal dystrophies. Eye. 2002;16(2): 126–131. 38. Kim TI, Pak JH, Chae JB, Kim EK, Tchah H. Mitomycin C inhibits recurrent Avellino dystrophy after phototherapeutic keratectomy. Cornea. 2006;25(2):220–223. 39. Yuksel E, Cubuk MO, Eroglu HY, Bilgihan K. Excimer laser phototherapeutic keratectomy in conjunction with mitomycin in corneal macular and granular dystrophies. Arq Bras Oftalmol. 2016;79(2):69–72. 40. Ha BJ, Kim TI, Choi SI, et al. Mitomycin C does not inhibit exacerbation of granular corneal dystrophy type II induced by refractive surface ablation. Cornea. 2010;29(5):490–496. 41. Taneja M, Rathi VM, Murthy SI, Bagga B, Vadavalli PK. Femtosecond laser-assisted anterior lamellar keratoplasty for recurrence of granular corneal dystrophy in postkeratoplasty eyes. Cornea. 2017;36(3):300–303. 42. Ellies P, Bejjani RA, Bourges JL, et al. Phototherapeutic keratectomy for BIGH3-linked corneal dystrophy recurring after penetrating keratoplasty. Ophthalmology. 2003;110(6):1119–1125. 43. Szentmary N, Langenbucher A, Hafner A, et al. Impact of phototherapeutic keratectomy on the outcome of subsequent penetrating keratoplasty in patients with stromal corneal dystrophies. Am J Ophthalmol. 2004;137(2):301–307. 44. Chow AM, Yiu EP, Hui MK, Ho CK. Shallow ablations in phototherapeutic keratectomy: long-term follow-up. J Cataract Refract Surg. 2005;31(11):2133–2136. 45. Pogorelov P, Langenbucher A, Kruse F, Seitz B. Long-term results of phototherapeutic keratectomy for corneal map-dot-fingerprint dystrophy (Cogan-Guerry). Cornea. 2006;25(7):774–777. 46. Zaidman GW, Hong A. Visual and refractive results of combined PTK/PRK in patients with corneal surface disease and refractive errors. J Cataract Refract Surg. 2006;32(6):958–961. 47. Campos M, Nielsen S, Szerenyi K, et al. Clinical follow-up of phototherapeutic keratectomy for treatment of corneal opacities. Am J Ophthalmol. 1993;115(4):433–440. 48. McDonnell JM, Garbus JJ, McDonnell PJ. Unsuccessful excimer laser phototherapeutic keratectomy. Clinicopathologic correlation. Arch Ophthalmol. 1992;110(7):977–979. 49. Fagerholm P. Phototherapeutic keratectomy: 12 years of experience. Acta Ophthalmol Scand. 2003;81(1):19–32.

50. Kandori M, Inoue T, Shimabukuro M, et al. Four cases of Acanthamoeba keratitis treated with phototherapeutic keratectomy. Cornea. 2010;29:1199–1202. 51. Elsahn AF, Rapuano CJ, Antunes VA, Abdalla YF, Cohen EJ. Excimer laser phototherapeutic keratectomy for keratoconus nodules. Cornea. 2009;28:144–147. 52. Taenaka N, Fukuda M, Hibino T, et al. Surgical therapies for Acanthamoeba keratitis by phototherapeutic keratectomy and deep lamellar keratoplasty. Cornea. 2007;26:876–879. 53. Lin CP, Chang CW, Su CY. Phototherapeutic keratectomy in treating keratomycosis. Cornea. 2005;24:262–268. 54. Lindbohm N, Moilanen JA, Vesaluoma MH, Tervo TM. Acinetobacter and Staphylococcus aureus ulcerative keratitis after laser in situ keratomileusis treated with antibiotics and phototherapeutic keratectomy. J Refract Surg. 2005;21: 404–406. 55. Li LM, Zhao LQ, Qu LH, Li P. Excimer laser phototherapeutic keratectomy for the treatment of clinically presumed fungal keratitis. J Ophthalmol. 2014;2014:963287. 56. Fagerholm P, Ohman L, Orndahl M. Phototherapeutic keratectomy in herpes simplex keratitis. Clinical results in 20 patients. Acta Ophthalmol (Copenh). 1994;72(4):457–460. 57. Kymionis GD, Kankariya VP, Kontadakis GA. Combined treatment with flap amputation, phototherapeutic keratectomy, and collagen crosslinking in severe intractable post-LASIK atypical mycobacterial infection with corneal melt. J Cataract Refract Surg. 2012;38(4):713–715. 58. Rachid MD, Yoo SH, Azar DT. Phototherapeutic keratectomy for decentration and central islands after photorefractive keratectomy. Ophthalmology. 2001;108(3):545–552. 59. Steinert RF, Ashrafzadeh A, Hersh PS. Results of phototherapeutic keratectomy in the management of flap striae after LASIK. Ophthalmology. 2004;111(4):740–746. 60. Azar DT. A new excimer laser technique for the correction of strabismus and diplopia. SPIE Vol. 2126 Ophthal Technol. 1994;IV(4):40–46. 61. Azar DT. ArF excimer prismatic photokeratectomy in the treatment of consecutive small angle prismatic deviations. Ophthalmology. 1993;100(suppl):103. 62. Gabison EE, Chastang P, Menashi S, et al. Late corneal perforation after photorefractive keratectomy associated with topical diclofenac: involvement of matrix metalloproteinases. Ophthalmology. 2003;110(8):1626–1631. 63. Courant D, Fritz P, Azema A, et al. Corneal wound healing after photokeratomileusis treatment on the primate eye. Lasers Light Ophthalmol. 1990;3:189–195. 64. Hanna KD, Pouliguen Y, Waring GO 3rd, et al. Corneal stromal wound healing in rabbits after 193-nm excimer laser surface ablation. Arch Ophthalmol. 1989;107(6):895–901. 65. Fountain TR, de la Cruz Z, Green WR, et al. Reassembly of corneal epithelial adhesion structures after excimer laser keratectomy in humans. Arch Ophthalmol. 1994;112(7):967–972. 66. Gao J, Gelber-Schwalb TA, Addeo JV, et al. Apoptosis in the rabbit cornea after photorefractive keratectomy. Cornea. 1997;16(2):200–208. 67. Zieske JD. Extracellular matrix and wound healing. Curr Opin Ophthalmol. 2001;12(4):237–241. 68. Sivak JM, Fini ME. MMPs in the eye: emerging roles for matrix metalloproteinases in ocular physiology. Prog Retin Eye Res. 2002;21(1):1–14. 69. Azar DT, Jain S, Woods R, et al. Phototherapeutic keratectomy: the VISX experience. In: Salz JJ, McDonnell PJ, McDonald

CHAPTER 20  Phototherapeutic Keratectomy (PTK) and Intralamellar PTK

MB, eds. Corneal Laser Surgery. St Louis, MO: Mosby-Year Book; 1995:213–226. 70. Azar DT, Chamon W, Stark W, et al. Phototherapeutic keratectomy. In: Stenson S, ed. Surgical Management in External Diseases of the Eye. Tokyo: Igaku-Shoin; 1996:303–319. 71. Azar DT. Epithelial and stromal wound healing following excimer laser keratectomy. Semin Ophthalmol. 1994;9:102–105. 72. Amm M, Duncker GI. Refractive changes after phototherapeutic keratectomy. J Cataract Refract Surg. 1997;23(6):839–844. 73. Chamon W, Azar DT, Start WJ, et al. Phototherapeutic keratectomy. Ophthalmol Clin North Am. 1993;6:399–413. 74. Gartry D, Kerr Muir M, Marshall J. Excimer laser treatment of corneal surface pathology: a laboratory and clinical study. Br J Ophthalmol. 1991;75(5):258–269. 75. Azar DT, McCallay RL, Stark W, et al. PTK: indications, surgical techniques, postoperative care, and complications management. In: Talamo JH, Krueger RR, eds. The Excimer Manual: A Clinician’s Guide to Excimer Laser Surgery. Boston, MA: Little, Brown; 1997:173–199. 76. Nghiem-Buffet MH, Gatinel D, Jacquot F, et al. Limbal stem cell deficiency following phototherapeutic keratectomy. Cornea. 2003;22(5):482–484. 77. al-Rajhi AA, Wagoner MD, Badr IA, et al. Bacterial keratitis following phototherapeutic keratectomy. J Refract Surg. 1996;12(1):123–127. 78. Lindbohm N, Moilanen JA, Vesaluoma MH, Tervo TM. Acinetobacter and Staphylococcus aureus ulcerative keratitis after laser in situ keratomileusis treated with antibiotics and phototherapeutic keratectomy. J Refract Surg. 2005;21:404–406. 79. Wilson SE. Analysis of the keratocyte apoptosis, keratocyte proliferation, and myofibroblast transformation responses after photorefractive keratectomy and laser in situ keratomileusis. Trans Am Ophthalmol Soc. 2002;100:411–433. 80. Carones F, Vigo L, Scandola E, et al. Evaluation of the prophylactic use of mitomycin-C to inhibit haze formation after photorefractive keratectomy. J Cataract Refract Surg. 2002;28:2088–2095. 81. Xu H, Liu S, Xia X, et al. Mitomycin C reduces haze formation in rabbits after excimer laser photorefractive keratectomy. J Refract Surg. 2001;17:342–349. 82. Porges Y, Ben-Haim O, Hirsh A, et  al. Phototherapeutic keratectomy with mitomycin C for corneal haze following photorefractive keratectomy for myopia. J Refract Surg. 2003;19(1):40–43. 83. Jain S, McCally RL, Connolly PJ, et al. Mitomycin C reduces corneal light scattering after excimer keratectomy. Cornea. 2001;20(1):45–49. 83a.  Anderson Penno E, Braun DA, Kamal A, et al. Topical thiotepa treatment for recurrent corneal haze after photorefractive keratectomy. J Cataracr Refract Surg. 2003;29(8):1537–1542. 84. McCally RL, Hochheimer BF, Chamon W, et al. A simple device for objective measurement of haze following excimer ablation of cornea. SPIE Proc. 1993;1877:20–25. 85. Dhaliwal DK, Romanowski EG, Yates KA, et al. Experimental laser-assisted in situ keratomileusis induces the reactivation of latent herpes simplex virus. Am J Ophthalmol. 2001;131: 506–507. 86. Hersh PS, Jordan AJ, Mayers M. Corneal graft rejection episode after excimer laser phototherapeutic keratectomy. Arch Ophthalmol. 1993;111(6):735–736. 87. Maloney RK, Thompson V, Ghiselli G, et al. A prospective multicenter trial of excimer laser phototherapeutic keratectomy for corneal vision loss. The Summit Phototherapeutic Keratectomy Study Group. Am J Ophthalmol. 1996;122(2):149–160.

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88. Maini R, Loughnan MS. Phototherapeutic keratectomy retreatment for recurrent corneal erosion syndrome. Br J Ophthalmol. 2002;86(3):270–272. 89. Domniz Y, Comaish IF, Lawless MA, et al. Epithelial ingrowth: causes, prevention, and treatment in 5 cases. J Cataract Refract Surg. 2001;27:1803–1811. 90. Bende T, Seiler T, Wollensak J. Side effects in excimer corneal surgery. Corneal thermal gradients. Graefes Arch Clin Exp Ophthalmol. 1988;226(3):277–280. 91. Ozler SA, Liaw LH, Neev J, et al. Acute ultrastructural changes of cornea after excimer laser ablation. Invest Ophthalmol Vis Sci. 1992;33(3):540–546. 92. Seiler T, Bende T, Winckler K, et al. Side effects in excimer corneal surgery. DNA damage as a result of 193 nm excimer laser radiation. Graefes Arch Clin Exp Ophthalmol. 1988;226(3):273–276. 93. Krueger RR, Sliney DH, Trokel SL. Photokeratitis from subablative 193-nanometer excimer laser radiation. Refract Corneal Surg. 1992;8(4):274–279. 94. Nghiem-Buffet MH, Gatinel D, Jacquot F, et al. Limbal stem cell deficiency following phototherapeutic keratectomy. Cornea. 2003;22:482–484. 95. Cannon TC, Brown MF, Brown HH. Regarding limbal stem cell deficiency following phototherapeutic keratectomy. [Letter]. Cornea. 2004;23:421. 96. Seitz B, Behrens A, Fischer M, et al. Morphometric analysis of deposits in granular and lattice corneal dystrophy: histopathologic implications for phototherapeutic keratectomy. Cornea. 2004;23(4):380–385. 97. Dinh R, Rapuano CJ, Cohen EJ, et al. Recurrence of corneal dystrophy after excimer laser phototherapeutic keratectomy. Ophthalmology. 1999;106(8):1490–1497. 98. Cavanaugh TB, et al. Phototherapeutic keratectomy for recurrent erosion syndrome in anterior basement membrane dystrophy. Ophthalmology. 1999;106(5):971–976. 99. Vrabec MP, Anderson JA, Rock ME, et al. Electron microscopic findings in a cornea with recurrence of herpes simplex keratitis after excimer laser phototherapeutic keratectomy. CLAO J. 1994;20(1):41–44. 100. Dogru M, Katakami C, Yamanaka A. Refractive changes after excimer laser phototherapeutic keratectomy. J Cataract Refract Surg. 2001;27(5):686–692. 101. Lee HK, Kim JK, Kim EK, et al. Phototherapeutic keratectomy with amniotic membrane for severe subepithelial fibrosis following excimer laser refractive surgery. J Cataract Refract Surg. 2003;29(7):1430–1435. 102. Leu G, Hersh PS. Phototherapeutic keratectomy for the treatment of diffuse lamellar keratitis. J Cataract Refract Surg. 2002; 28(8):1471–1474. 103. Soong HK, Katz DG, Farjo AA, et al. Central lamellar keratoplasty for optical indications. Cornea. 1999;18:249–256. 104. Reinstein DZ, Silverman RH, Sutton HF, et al. Very highfrequency ultrasound corneal analysis identifies anatomic correlates of optical complications of lamellar refractive surgery. Ophthalmology. 1999;106:474–482. 105. Jain S, Azar DT. New lamellar keratoplasty techniques: posterior keratoplasty and deep lamellar keratoplasty. Curr Opin Ophthalmol. 2001;12:262–268. 106. Melles GR, Remeijer L, Geerards AJ, et al. The future of lamellar keratoplasty. Curr Opin Ophthalmol. 1999;10:253–259. 107. Krumeich JH, Daniel J, Winter M. Depth of lamellar keratoplasty with the guided trephine system for transplantation of fullthickness donor sections. Ophthalmology. 1998;95(11):748–754.

21 

Principles of Corneal Cross-Linking THEO G. SEI LER AND THEO SEILER

Introduction Originally, corneal cross-linking (CXL) was introduced to prevent the progression of keratoconus.1,2 However, during in vitro and in vivo experiments, in addition to the biomechanical stabilization of the cornea, an increased resistance of tissue against melting enzymes may occur. Consequently, the first publication on clinical application of CXL was about melting disease in the cornea.3 Between 2000 and 2003, our group in Dresden reported on CXL for keratoconus at several meetings and Gregor Wollensak presented the first prospective study on corneal CXL in 23 eyes with a follow-up of 1 year and longer.4 He reported stabilization and even regression of keratoconus as detected by corneal topography in all cases. Based on this publication, the international community took notice of CXL of the cornea and prospective studies were launched in countries such as Italy and Australia. During the following years, the technique was improved: the Dresden Protocol (30 minutes riboflavin/ dextrane application, 30 minutes ultraviolet [UV] light application of 3 mW/cm2, 7 mm in diameter) was established and safety limits defined.5

Basic Principles During the CXL process, hyperactive radicals are generated that produce new chemical bonds within the cornea. Four ingredients are necessary to accomplish corneal CXL: riboflavin, oxygen, UV light, and the extracellular matrix of the cornea. Seconds after switching on the UV light, the pool of oxygen diluted in the cornea is exhausted6; therefore the oxygen-dependent CXL pathway may play only a minor role. The remaining participants in the CXL process (extracellular matrix, riboflavin, and UV light) and their interaction can be modeled7 using a mathematical model that was developed in material science.8 The intensity I of the UV light at a point P inside the cornea is dependent on the depth z = zr•cos α and the local concentration of riboflavin c(z). The Lambert-Beer law leads to I( z ) = I0 iexp( − ε ic( z )iz cos α ), 334

with I0 being the (homogenous and perpendicular to the surface) light intensity in the corneal plane. Owing to the oblique incidence in the periphery of the UV light, a reduced intensity/area Ic follows a simple cosine law: Ic = I0 icos α. For simplification, a linear decrease of the riboflavin concentration from the front to the rear surface of the cornea (thickness d) is assumed: c( z ) = c 0 i(1 − z d ). However, this assumption is not correct: Ehmke et al. measured the riboflavin gradient inside the cornea by means of 2 photon microscopy9 and found a sinusoidal decay toward deeper layers of the stroma that, in first order, may be approximated by a linear function. Following the theory of polymerization,8 the local radical formation rate R(z,α) is proportional to the square root of the product of riboflavin concentration and light intensity: R(z, α ) = k i(c( z )iI(z))1 2 = k i(c0(1 − z d ))1 2 iIc 1 2iexp( − ε ic(z)iz 2icos α ). At the demarcation depth z0, the radical formation rate R(z,α) equals the recombination rate R0, which leads to R 0 k = c 01 2 iIc1 2 i(1 − z 0 d )1/ 2 i exp( −εic 0 i(1 − z 0 d ) z 0 2icos α ).

(1)

For α = 0, c0 = 0.1%, z0 = 0.03 cm, d = 0.04 cm, ε = 500/%•cm, and I0 = 3mW/cm2, the constant R0/k can be determined and consequently the function z0 = f(α) is computed, which is depicted in Fig. 21.1 as theoretical curve th. This theoretical curve fits nicely the clinical demarcation line (seen in anterior segment optical coherence tomography [OCT]), indicating the correctness of the mathematical model described. For a long time, it was not clear where inside the cornea the newly formed cross-links are located. Because the distance between the collagen fibers is approximately 60 nm, it was believed that the cross-links are located merely inside the collagen molecule. However, in 2013, Hayes and the

CHAPTER 21  Principles of Corneal Cross-Linking

100

Relative Depth in %

80 80

th

70 mav 60 50 0

0

1

2

3

Radial Distance/mm

• Fig. 21.1

Depth of demarcation line as a function of the distance from the apex. The theoretical curve is close to the profiles measured with anterior segment optical coherence tomography (n = 10).  

Crosslink locations: Intramolecular Intermolecular Intraproteoglycan Interproteoglycan

Proteoglycan core protein Glycosaminoglycan side chain Collagen fibril Collagen molecule

• Fig. 21.2  Location of the cross-links after ultraviolet A/riboflavin application within the extracellular matrix of the cornea (after Hayes10). In addition to cross-links located in collagen fibers and at their surfaces, x-ray scattering revealed cross-links attached to proteoglycans.

group of Professor Meek in Cardiff, United Kingdom, presented a better understanding of the location of the newly formed chemical bonds inside the extracellular matrix of the cornea.10 Surprisingly it was not the collagen molecule alone that was being cross-linked; Hayes et al. showed that crosslinks occurred at the surface of the collagen macromolecule as well as between the protein cores of the proteoglycans and between the glycans themselves (Fig. 21.2). In essence, all parts of the extracellular matrix become stiffer and better cross-linked. Thus this publication also changed the nomenclature and the term corneal cross-linking (CXL) should be used rather than collagen cross-linking.

335

During the first 10 years, riboflavin was applied exclusively as 0.1% riboflavin diluted in 15% to 20% dextrane solution. These eye drops were instilled for 30 minutes. Using this technique, some corneas dehydrated significantly and after 30 minutes the stromal pachymetry fell short of the 400 µ that are considered the safety limit to avoid endothelium damage.5 In many cases, we had to swell the cornea by means of hypo-osmolar riboflavin drops until a minimal corneal thickness of 400 µ was achieved. As an alternative to dextrane, we are now using 0.1% riboflavin diluted in 1.1% hydroxypropyl methyl cellulose (HPMC) solution. Emke and coworkers9 could demonstrate that the riboflavin gradients inside the cornea after dextrane solution applied for 30 minutes and HPMC solution applied for 10 minutes are very similar (Fig. 21.3). In addition, the HPMC-treated corneas were not dehydrated but showed a slight increase in corneal thickness. This new approach saves time (10 minutes vs 30 minutes) and avoids possible complications related to dehydration of the cornea. The role of oxygen was studied by the group of Marc Friedman measuring the oxygen level inside the cornea 100 µm below the surface.11 Fig. 21.4 shows a UV on-off cycle; it is obvious that it takes only seconds until all intrastromal oxygen is consumed. The problem is the slow diffusion of oxygen into the cornea, which takes minutes to reach acceptable values 100 µ below the surface and even longer in deeper layers. Therefore pulsing the light in onand-off duty cycles of 1 s/2 s does not make sense because the off period is not long enough to let the oxygen diffuse into the stroma. The next parameter to be discussed is irradiation of the riboflavin-saturated cornea. Here we have a full spectrum of irradiances ranging from 3 mW/cm2 to 45 mW/cm2. Technically, irradiances of up to 100 mW/cm2 are feasible using light-emitting diodes (LEDs). Assuming that the creation of radicals is a rate process of first order, a higher irradiance would be reciprocal to a shorter application time (Bunsen-Roscoe law). However, because of the slow diffusion of oxygen involved in radical formation, this law cannot be applied. Therefore using shorter times results in fewer radicals and less CXL. This has been demonstrated by Hafezi and his group in Geneva.12 Currently, we still use an energy dose of 5.4 J/cm2. However, we have increased the irradiance to a range of 10 mW/cm2 to 15 mW/cm2 in our clinical routine. So far, we have not seen a significant negative impact on our clinical success rate or our complication rate, confirming the results of accelerated CXL presented by several groups.13,14 The nomenclature of keratoconus needs to be clarified because, in many publications, the term keratoconus is used as an umbrella term for primary keratectasia and not as a specific differential diagnosis. In contrast, primary keratectasia shows 4 different subforms, depending on the location of the maximum of the posterior float (Table 21.1, Fig. 21.5): central keratoconus, keratoconus, pseudo-pellucid marginal degeneration, and classic pellucid marginal degeneration (PMD). We observed central keratoconus and classic PMD

Collagen Crosslinking and Orthokeratology

336 se c t i o n V II 336

0.10 20% Dextran, t = 30 min 1.1% HPMC, t = 10 min

0.09

0.08

Riboflavin Concentration (%)

0.07

0.06 0.05

0.04 0.03

0.02 0.01 0.00 0

50

100

150

200

250

300

350

Depth (m)

Oxygen Concentration mg/l

• Fig. 21.3  Riboflavin concentration as a function of depth 30 minutes after application of riboflavin/ dextrane solution compared to 10 minutes after riboflavin/hydroxypropyl methyl cellulose solution (after Ehmke9). The gradients are similar within the first 350 µ of depth.

different percentages may apply to secondary keratectasia after laser in situ keratomileusis (LASIK). Other classifications of keratoconus, such as Amsler and Amsler-Krumeich, are clinically outdated; international task forces are currently in the process of obtaining consensus from ophthalmology experts from around the world regarding keratoconus and ectatic diseases.15

UV off

10

5

Cross-Linking for Keratoconus 0 1

2

3

4

Minutes

• Fig. 21.4

Intrastromal oxygen concentration 100 µ below the surface. Within seconds after ultraviolet exposition, all oxygen is consumed and it takes minutes until diffusion has reestablished oxygen concentrations necessary for oxygen-dependent cross-linking.  

in less than 2% of our clinical cases. Keratoconus cases with a prevalence of approximately two-thirds and pseudo-PMD of one-third represent the vast majority of the primary keratectasia cases (these frequencies are based on a review of > 700 keratoconus files at Institut für Refraktive und Ophthalmo-Chirurgie, Zurich). A similar subgrouping but

Since the molecular weight of riboflavin is more than 300 Dalton and the epithelium represents a diffusion barrier for molecules of that size and polarity, the gold standard so far is to enhance the diffusion of riboflavin into the cornea by removing the epithelium. Several attempts have been made in the past to overcome or to trick this epithelium barrier chemically, electrically (iontophoresis), or mechanically. Even intrastromal application of riboflavin has been proposed. In general, transepithelial application of riboflavin leads to a shallower effect, indicating a reduced efficacy.16–18 In one prospective study, 2 years after transepithelial CXL using a commercially available solution, approximately 50% of pediatric patients needed retreatment because of

CHAPTER 21  Principles of Corneal Cross-Linking

337

TABLE Classification of Primary Keratectasia (n = 499) 21.1 

Central keratoconus

Keratoconus

Pseudo-PMD

Classic PMD

Eccentricity of postfloat maximum

< 0.5 mm

0.5–1.5 mm

1.5–2.8 mm

≥ 2.8 mm

Primary optical error

Spherical aberration

Coma

Astigmatism

Astigmatism

Frequency

9/499 = 1.8%

396/499 = 79.4%

57/499 = 11.4%

4/499 = 0.8%

PMD, Pellucid marginal degeneration.

A

B

C

• Fig. 21.5  Axial topographies and posterior elevation maps of 3 special subtypes of keratectasia: central keratoconus (A), pseudo-pellucid marginal degeneration (PMD; B) and classical PMD (C).

insufficient halt of the progression of keratoconus.19 The only really promising transepithelial approach includes iontophoresis: in a prospective study, Vinciguerra et al.20 showed approximate equivalence to epi-off CXL accompanied by faster rehabilitation. This result was confirmed by other independent groups.21 Epithelium can easily be removed using a blunt hockey knife. However, small scratches or ruptures of the Bowman membrane can create significant scarring. Therefore it is recommended to use a harmless epithelial removal tool, such as the ORCA system (Orca Surgical). Deepithelialization using 20% alcohol for 30 seconds, as in photorefractive keratectomy (PRK), is not recommended because residual alcohol may interfere with radicals and may delay epithelial healing. Also, the removal of the epithelium using photo-

therapeutic keratectomy (PTK), as proposed by Kymionis et al.,22 appears to have disadvantages compared to manual removal.23 Owing to the epithelium’s reduced thickness over the cone, a PTK also removes stromal tissue, which results in additional biomechanical weakening at the weakest point of the cornea. The application of 0.1% riboflavin solution is the next step of the procedure. We selected 0.1% riboflavin solution as a best compromise. As stronger solution of riboflavin induces more absorption of UV light in the anterior cornea, however, the CXL depth is smaller, resulting in a more superficial CXL. Concentrations lower than 0.1% result in deeper demarcation lines; however, the risk of endothelial damage may increase and the total CXL effect may be smaller because fewer radicals are produced.

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• Fig. 21.6

  Demarcation line in optical coherence tomography after cross-linking. A standard UV lamp with a standard “homogenous” profile was used. The standard light source shows a significant reduction toward the periphery.

Except for focal applications of CXL—as in localized infections, ulcerations, and customized CXL—generally, the whole cornea with a diameter of 9 mm is irradiated with UV-light sources ranging from mercury gas lamps to LED arrays with a wavelength of 355 to 365 nm. This range of wavelengths is a relatively constant parameter; however, the profile of the UV lamp is different in different approaches. In Fig. 21.6, the two demarcation lines obtained with UV irradiation of the UV X-1000 and the more updated version UV X-2000 are compared. It is obvious that a more uniform depth of CXL is obtained with the UVX-2000 by applying a higher irradiance in the midperiphery than in the center. In contrast, during customized CXL, a bell-shaped CXLprofile is approximated24 in order to produce more CXL at the weakest point of the cornea. After surgery, we apply antibiotic ointment and a bandage lens for up to 3 days. Pain management includes strong painkillers (i.e., tramadol) for the first night as well as topical anesthetics that are diluted 1 : 10 and not used more frequently than once per hour to not slow epithelium healing.25 After epithelial healing, patients receive mild steroids for 2 weeks to reduce the inflammation. Patients are asked not to use hard contact lenses before the one-month follow-up. We see our patients after 1 month, 6 months and 1 year. The 1-month follow-up is especially important, because at that time the demarcation line is easily seen either at the slit lamp or in OCT and one can estimate how deep the cross-linked layer reaches (see Fig. 21.6). Over the past few years, the scientific knowledge about corneal CXL has increased tremendously. A PubMed search for “cross-linking cornea” by May 2016 found more than 1000 items, most of them presenting clinical results. Therefore it was time for a meta-analysis of this huge amount of information. Currently, there are two published metaanalyses of corneal CXL for primary keratectasia: one analyzing only controlled prospective studies26 and the other one analyzing prospective studies without control groups.27 Controlled studies are only necessary if there is a chance that improvement occurs without intervention, which we know is uncommon in keratoconus. Therefore with all due respect, controlled studies (especially if they do not compare partner eyes) are not necessary to prove the therapy effect of corneal CXL. In addition, there were only three controlled prospective studies on corneal CXL included;

• Fig. 21.7

  Ten year-follow-up after cross-linking. The cornea shows flattening continuing more than 10 years. The cornea was clear, without scarring at any time.

therefore a meta-analysis that includes only 119 eyes is neither appropriate nor necessary. In the meta-analysis of Chunyu,27 prospective studies with a 1-year follow-up were included, reflecting results in 487 eyes. The authors found “that corneal cross-linking could effectively stabilize the progression of keratokonus (KC), as assessed by key corneal topographic parameters” such as Kmax and average K-readings. They also concluded that “the effects of CXL on visual acuity (BSCVA [best spectacle-corrected visual acuity]) improvement are also remarkable.” In a 7-year follow-up presented by O’Brart in 2015, the reduction in Kmax continued and none of the 36 eyes progressed, which indicates a failure rate of 0%.28 On the other hand, a failure rate of 3% was reported by Koller and coworkers.29 An even higher failure rate of 11% occurred in a French study with a 6-year follow-up.30 However, “progression” was defined as an increase of 1 diopter (D) in corneal topography, which is plagued with a much higher variance compared to Scheimpflug imaging. Raiskup reported a visual loss of more than 2 Snellen lines 10 years after CXL, which required repeat CXL in one out of 35 eyes. In this study, two eyes required repeat CXL (after 5 years and after 10 years), indicating a failure rate in the order of 5% 10 years after CXL.31 Another problem widely not recognized is the long-term flattening of corneas that have been treated with CXL. In Fig. 21.7, a 10-year follow-up of a patient is depicted showing a continuation of flattening after CXL. The refraction (spherical equivalent) changed from −2.0 D to +1.0 D within those 10 years. Obviously, CXL induces some healing cascades inside the cornea, leading to a regularization of the cornea. This slow, long-term flattening should be distinguished from an early flattening of the cornea owing to stromal scar formation. This early flattening occurs in up to 4% of the cases32 and a flattening of 5 D is not uncommon.

Cross-Linking Beyond Keratoconus Although not within the scope of this chapter, it is worth noting that CXL has two more applications beyond its biomechanical effect. Early on, we realized that CXL may delay or slow down corneal melting, which led to the first clinical application

CHAPTER 21  Principles of Corneal Cross-Linking

of corneal CXL.3 Wollensak demonstrated with digestion experiments that a cross-linked cornea was significantly more resistant against collagenase and pepsin compared to a noncross-linked control.33 This was confirmed by Hayes et al.34 Whether this application will find its way into clinical routine—for example, for the preparation of a graft in high-risk keratoplasties—has not been decided yet. The third and even more important application uses the cytotoxic effect of CXL. The radicals that are created during the CXL process may also hit cell walls and lead to cell death. This effect targets not only keratocytes but also bacteria and fungi. The first clinical report on the antibiotic effect of CXL in therapy-refractory infectious keratitis dates back to 2008.35 In a prospective study, Makdoumi et al. proved the efficacy of CXL to control corneal infections clinically.36 Tabibian and coworkers reviewed the information available in 2016 and coined the new term PACK-CXL.37

References 1. Seiler T, Spoerl E, Huhle M, Kamouna A. Conservative therapy of keratoconus by enhancement of collagen cross-links. Invest Ophthalmol Vis Sci. 1996;37:ARVO Abstract 4671. 2. Spörl E, Huhle M, Kasper M, Seiler T. Erhöhung der Festigkeit der Hornhaut durch Vernetzung. Ophthalmologe. 1997;94:902–906. 3. Schnitzler E, Spörl E, Seiler T. Bestrahlung der Hornhaut mit UV-Licht und Riboflavingabe als neuer Behandlungsversuch bei einschmelzenden Hornhautprozessen, erste Ergebnisse bei vier Patienten. Klin Monbl Augenheilkd. 2000;217:190–193. 4. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135:620–627. 5. Spoerl E, Mrochen M, Sliney D, Trokel S, Seiler T. Safety of UVAriboflavin cross-linking of the cornea. Cornea. 2007;26:385–389. 6. Kamaev P, Friedman MD, Sherr E. Muller DPhotochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci. 2012;53:2360–2367. 7. Koller T, Schumacher S, Fankhauser F 2nd, Seiler T. Riboflavin/ ultraviolet a crosslinking of the paracentral cornea. Cornea. 2013; 32:165–168. 8. Odian GG. Principles of Polymerization. 3rd ed. New York, NY: Wiley; 1991. 9. Ehmke T, Seiler TG, Fischinger I, Ripken T, Heisterkamp A, Frueh BE. Stromal riboflavin gradients prior to CXL with HPMC and dextran solutions. Comparison of Corneal Riboflavin Gradients Using Dextran and HPMC Solutions. J Refract Surg. 2016;32:798–802. 10. Hayes S, Kamma-Lorger CS, Boote C, et al. The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma. PLoS ONE. 2013;8(1):e52860. 11. Kamaev P, Friedman M, Sherr E, Muller D. Photochemical Kinetics of Corneal Cross-Linking with Riboflavin. Invest Ophthalmol Vis Sci. 2012;53:2360–2367. 12. Hammer A, Richoz O, Arba Mosquera S, Tabibian D, Hoogewoud F, Hafezi F. Corneal biomechanical properties at different corneal cross-linking (CXL) irradiances. Invest Ophthalmol Vis Sci. 2014;55:2881–2884. 13. Tomita M, Mita M, Huseynova T. Accelerated versus conventional corneal collagen crosslinking. J Cataract Refract Surg. 2014; 40:1013–1020.

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14. Chow VW, Chan TC, Yu M, Wong VW, Jhanji V. One-year outcomes of conventional and accelerated collagen crosslinking in progressive keratoconus. Sci Rep. 2015;5:14425. 15. Gomes JA, Tan D, Rapuano CJ, et al. Global consensus on keratoconus and ectatic diseases. Cornea. 2015;34:359–369. 16. Gatzioufas Z, Raiskup F, O’Brart D, Spoerl E, Panos GD, Hafezi F. Transepithelial corneal cross-linking using an enhanced riboflavin solution. J Refract Surg. 2016;32:372–377. 17. Al Fayez MF, Alfayez S, Alfayez Y. Transepithelial versus epithelium-off corneal collagen cross-linking for progressive keratoconus: a prospective randomized controlled trial. Cornea. 2015;34(suppl 10):S53–S56. 18. Soeters N, Wisse RP, Godefrooij DA, Imhof SM, Tahzib NG. Transepithelial versus epithelium-off corneal cross-linking for the treatment of progressive keratoconus: a randomized controlled trial. Am J Ophthalmol. 2015;159:821–828. 19. Caporossi A, Mazzotta C, Paradiso AL, Baiocchi S, Marigliani D, Caporossi T. Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg. 2013;39:1157–1163. 20. Vinciguerra P, Romano V, Rosetta P, et  al. Transepithelial iontophoresis versus standard corneal collagen cross-linking: 1-year results of a prospective clinical study. J Refract Surg. 2016;32:672–678. 21. Lombardo M, Giannini D, Lombardo G, Serrao S. Randomized controlled trial comparing transepithelial corneal cross-linking using iontophoresis with the dresden protocol in progressive keratoconus. Ophthalmology. 2017;124:804–812. 22. Kymionis GD, Grentzelos MA, Kankariya VP, et al. Long-term results of combined transepithelial phototherapeutic keratectomy and corneal collagen crosslinking for keratoconus: Cretan protocol. J Cataract Refract Surg. 2014;40:1439–1445. 23. Cagil N, Sarac O, Cakmak H, Can G, Can E. Mechanical epithelial removal followed by corneal collagen crosslinking in progressive keratoconus: short-term complications. J Cataract Refract Surg. 2015;41:1730–1737. 24. Seiler TG, Fischinger I, Koller T, Zapp D, Frueh B, Seiler T. Customized corneal crosslinking—one year results. Am J Ophthlmol. 2016;166:14–21. 25. Maurice DM, Singh T. The absence of corneal toxicity with lowlevel topical anesthesia. Am J Ophthalmol. 1985;99:691–696. 26. Sykakis E, Karim R, Evans JR, et al. Corneal collagen crosslinking for treating keratoconus. Cochrane Database Syst Rev. 2015; (3):CD010621. 27. Chunyu T, Xiujun P, Zhengjun F, Xia Z, Feihu Z. Corneal collagen cross-linking in keratoconus: a systematic review and meta-analysis. Sci Rep. 2014;4:5652. 28. O’Brart DP, Patel P, Lascaratos G, et al. Corneal cross-linking to halt the progression of keratoconus and corneal ectasia: sevenyear follow-up. Am J Ophthalmol. 2015;160:1154–1163. 29. Koller T, Mrochen M, Seiler T. Complication and failure rates after corneal crosslinking. J Cataract Refract Surg. 2009;35: 1358–1362. 30. Poli M, Cornut PL, Balmitgere T, Aptel F, Janin H, Burillon C. Prospective study of corneal collagen cross-linking efficacy and tolerance in the treatment of keratoconus and corneal ectasia: 3-year results. Cornea. 2013;32:583–590. 31. Raiskup F, Theuring A, Pillunat LE, Spoerl E. Corneal collagen crosslinking with riboflavin and ultraviolet—A light in progressive keratoconus: ten-year results. J Cataract Refract Surg. 2015;41:41–46. 32. Hafezi F, Koller T, Vinciguerra P, Seiler T. Marked remodelling of the anterior corneal surface following collagen cross-linking with riboflavin and UVA. Br J Ophthalmol. 2011;95:1171–1172.

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33. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004; 29:35–40. 34. Hayes S, Kamma-Lorger CS, Boote C, et al. The effect of riboflavin/UVA collagen cross-linking therapy on the structure and hydrodynamic behaviour of the ungulate and rabbit corneal stroma. PLoS ONE. 2013;8(1):e52860. 35. Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. Ultraviolet A/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts. Cornea. 2008;27:590–594.

36. Makdoumi K, Mortensen J, Sorkhabi O, Malmvall BE, Crafoord S. UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study. Graefes Arch Clin Exp Ophthalmol. 2012;250:95– 102. 37. Tabibian D, Mazzotta C, Hafezi F. PACK-CXL: Corneal crosslinking in infectious keratitis. Eye Vis (Lond). 2016;3:11.

22 

Epithelium Off and Transepithelial Cross-Linking: Techniques and Outcomes ELENA ALBÉ

Introduction Collagen cross-linking (CXL) was proposed by Wollensak et al. as a new possibility to stabilize progressive keratoconus, preventing some of the underlying pathophysiologic mechanisms of the disease. This shows promise in the attempt to stop progressive visual loss due to the evolution of the pathology and to delay or avoid invasive surgical procedures such as corneal transplantation, which is usually required in advanced cases.1–7 Since this first report by Wollensak et al. in 2003,1 numerous publications have been added to the peerreviewed literature over the last decade addressing safety and efficacy of CXL in treating adult eyes with keratoconus and in other corneal ectatic conditions.2,8,9 These studies have provided sufficient evidence that CXL is successful in slowing or halting keratoconus progression and may even yield visual, topographic, and aberrometric improvement by induced corneal flattening and reduction in irregular astigmatism. It is important to note that medium and long-term studies have validated an excellent safety profile for standard CXL (epi-off Dresden protocol), with respect to the health of the corneal endothelium, lens, and retina despite the potential cytotoxic effect of ultraviolet A (UVA) light. Since no permanent side effects and an acceptable complication rate were observed in adults10–13 when strict inclusion criteria were adhered to, the introduction of corneal collagen cross-linking (CXL) in routine clinical practice has changed the management of keratoconus in both the adult and pediatric populations. Keratoconus is a progressive, frequently asymmetric, noninflammatory corneal dystrophy, characterized by changes in the corneal collagen structure and organization, causing a biomechanical instability that leads to irregular astigmatism, progressive myopia, corneal thinning, and

central corneal scarring, with subsequent mild to marked impairment in visual quality.14–17 Many studies on keratoconus epidemiology from different countries reported an incidence of 1.3 to 22.3 per 100,000 and a prevalence of 0.4 to 86 cases per 100,000.18 The incidence of corneal ectasia after refractive surgery is still unknown, but it has been estimated to be 0.04% to 0.6% after laser in situ keratomileusis (LASIK).19–21 Post-LASIK ectasia represents about 96% of all secondary ectasias after refractive surgery, while 4% are related to photorefractive keratectomy (PRK).22 The disease affects both male and female. However, not all age groups are affected equally, since the onset of the disease is typically during adolescence and puberty.17 Keratoconus etiology is not yet completely understood and includes genetic, biochemical, and physical factors. It usually appears as an isolated condition but has been associated with several ocular and systemic disorders. A reduced number of collagen cross-links and a pepsin digestion higher than normal have been suggested as possible explanations for an overall structural weakness of the corneal tissue in keratoconus, resulting in a stiffness that is only 60% of the normal cornea.17 However, its etiologic basis remains poorly understood: a defective formation of extracellular constituents of corneal tissue, fewer collagen lamellae, less collagen fibrils per lamella, and closer packing of collagen fibrils could all decrease mechanical corneal stability.23 The incidence of keratoconus is higher in relatives of patients with the disorder than in the general population.24 Retinitis pigmentosa, blue sclera, magnesium deficiency, Down syndrome,25 Turner syndrome, Marfan syndrome, Ehlers-Danlos syndrome, mental retardation, Leber congenital amaurosis, osteogenesis imperfecta, and pseudoxanthoma elasticum have been reported to be correlated with keratoconus.17 Approximately 6% to 24% of cases demonstrate clinically recognized familial aggregation.26,27 Both 341

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dominant and recessive models have been observed in individual keratoconus pedigrees.28,29 In addition, segregation analyses,28 twin studies,30 and gene mapping studies31–35 have also indicated the important role of genetic factors.36 In the vast majority of patients (> 90%) keratoconus is bilateral. However, the eyes are affected with different severity. In many cases, the disorder may start unilaterally and involve the other eye over time.37 This bilaterality supports the assumption of a genetic basis for this disease. In addition to genetic factors, many pediatric keratoconus patients show ocular comorbidities, such as surface allergy, atopic dermatitis,24 and especially vernal keratoconjunctivitis (VKC).38 VKC compounds the problems of keratoconus, as continued surface inflammation and the tendency to rub the eyes accelerate keratoconus degeneration.24,29–42 Therefore it is recommended that children with atopy be referred to a comprehensive ophthalmic examination, even in the apparent absence of visual symptoms, to ensure the timely diagnosis and management of any atopyassociated ocular disease. Prompt referral is particularly essential for pediatric corneal ectasia, in which the rapidity of progression may preclude stabilizing treatments and may result in significant childhood visual impairment.43 In addition, VKC should be controlled aggressively prior to CXL and patients and their parents should be counseled about avoiding eye rubbing. Care should be taken to protect limbal stem cells during irradiation with UV-light during CXL. Although keratoconus is frequently diagnosed after adolescence, the corneal ectasia process usually starts at a much younger age.17 Recent studies conducted in Germany suggest that thyroid gland dysfunction due to inflammatory or immunologic causes is associated with keratoconus and might correlate with the onset and progression of the disease. Good medical practice aims to screen patients with hypothyroidism using corneal topography to detect early stage keratoconus. Conversely, serologic tests aimed to identify any malfunctioning thyroid should be recommended to each patient with keratoconus.44 Other reports suggest that hormonal changes occurring regularly during gestation may modify the function of the thyroid gland45 and may affect corneal biomechanics negatively and may have a severe impact on the progression of keratoconus.46–48

Basic Principles of Corneal Cross-Linking The primary aim of corneal CXL is to stop the progression of corneal ectasia. To obtain a strengthening of corneal tissue, the use of riboflavin is combined with UVA irradiation. Riboflavin plays the role of a photosensitizer in the photopolymerization process and, when combined with UVA irradiation, increases the formation of intrafibrillar and interfibrillar carbonyl-based collagen covalent bonds through a molecular process that has still not been completely elucidated.49 It was shown that during the early aerobic phase of the process of CXL, riboflavin molecules are excited to a single or triplet state and stromal proteins

undergo a photosensitized oxidation via interaction with reactive oxygen species.50 During the second anaerobic phase, when oxygen is depleted, corneal stroma interacts with reactive species of radical ions. This photochemical reaction results in an increased corneal rigidity, increased collagen fiber thickness, and increased resistance to enzymatic degradation.51

Basic Research Results Currently, the photochemically induced effect of CXL in the cornea cannot be observed directly by staining methods or microscopic techniques. However, CXL induces several changes to collagen-containing tissue from which indirect signs of the CXL effect can be deduced.52 In fact, stress– strain measurements performed on human and porcine corneas documented an increased corneal rigidity after CXL treatment. The strengthening effect seems to be more evident in corneas with higher collagen content and in older tissue.1,3 Corneal CXL occurs physiologically with aging via natural enzymatic pathways such as transglutaminase and lysyl oxidase.2 Moreover, it has been reported that porcine cross-linked corneas showed a reduced tendency to swelling and hydration when compared to untreated controls.53 Ex vivo studies on corneas of humans and rabbits indicated an increase of collagen fiber thickness after CXL treatment.54,55 Results of basic research studies showed that CXL improves the corneal resistance to degradation processes mediated by pepsin, trypsin, and collagenase with lengthening of the turnover time of collagen.6

Standard Cross-Linking Procedure: Epi-Off Cross-Linking (Video 22.1) Prior to CXL, it is necessary to obtain documented evidence of keratoconus progression. In order to reduce the risk of endothelial damage, it must be ensured that minimum corneal thickness preoperatively is greater than 400 µm. Pediatric keratoconus (keratoconus manifesting in patients younger than 18 years of age) exhibits several unique characteristics. Studies have shown that pediatric keratoconus is often more advanced at diagnosis than in adults, with 27.8% being stage 4 vs 7.8% in adults.56 In addition, pediatric keratoconus demonstrates a higher rate (88% of keratoconic eyes) and speed of progression than adult keratoconus.36,57–59 The biomechanical rigidity of the cornea is related to age60 and children with keratoconus are frequent eye rubbers, especially the subgroup of children with coexisting VKC. Since the progression of the disease can be dramatically fast in children, early detection of the disease and close monitoring are crucial in young patients. CXL is generally performed under topical anesthesia except in noncompliant patients, in whom general anesthesia may be necessary. Thirty minutes before the procedure,

CHAPTER 22  Epithelium Off and Transepithelial Cross-Linking: Techniques and Outcomes

systemic pain medication is administered and pilocarpine 2% drops are instilled in the eye to be treated. After topical anesthesia with two applications of lidocaine 4% and oxybuprocaine hydrochloride 0.2% drops, the eye is draped, the ocular surface is rinsed with balanced salt solution, and a lid speculum is applied. The corneal epithelium is abraded in a central 9-mm-diameter area with the aid of an Amoils brush. A riboflavin 0.1% solution (10 mg riboflavin5-phosphate in 20% dextran-T-500) is applied onto the cornea every minute for 30 minutes to achieve adequate penetration of the solution. Using a slit lamp with blue filter, the surgeon confirms the presence of riboflavin in the anterior chamber. Then, the cornea is exposed to an ultraviolet light emanating from a solid-state device emitting a wavelength of 370.5 nm and an irradiance of 3 mW/cm2. A calibrated UVA meter is used before treatment to check the irradiance. The cropped light beam has a 7.5-mm diameter. Exposure time is 30 minutes. During irradiation, riboflavin solution is applied once every 5 minutes to avoid desiccation of the cornea. Intraoperative pachymetry is performed throughout the procedure. In case corneal thickness goes below 400 µm, hypotonic riboflavin solution can be used to swell the cornea. Fixation is achieved by instructing the patient to focus on the central LED of the probe. During the procedure, the surgeon controls for centration of treatment. Both topical anesthetics are added as needed during irradiation. After surgery, patients receive cyclopentolate and levofloxacin drops. A soft bandage contact lens is applied until reepithelialization is complete. Topical levofloxacin is given 4 times daily for 7 days, dexamethasone 21-phosphate 0.15% drops are administered 3 times daily for 20 days, and sodium hyaluronate 0.15% drops are applied 6 times daily for 45 days. In addition, patients receive oral amino-acid supplements for 7 days. Postoperative CXL follow-up includes daily examinations until reepithelialization occurs (on average, on the third or fourth day). The patient should avoid dusty and windy places to minimize the risk of corneal infection. The use of amino acid supplements and antioxidants in the immediate preoperative and postoperative period is recommended for regular corneal reepithelialization. For the first month after treatment, the patient should avoid saunas, swimming pools and baths, and direct sunlight exposure without appropriate sunglasses. Studies have shown that the corneal epithelium is a significant barrier for penetration of both UVA light and riboflavin, which is a hydrophilic molecule that cannot easily pass the tight junctions of the intact epithelial barrier. A variety of approaches—including transepithelial procedures (using 20% alcohol solutions or tetracaine 1% to loosen epithelial tight junctions), partial epithelial removal, or femtosecond (FS) laser–created intrastromal pockets—have been attempted to improve riboflavin penetration in the presence of intact epithelium, reduce postoperative discomfort, and accelerate visual recovery. Novel formulations of riboflavin (by adding trometamol and sodium ethylene-diaminetetraacetic acid or sodium or benzalkonium chloride) have been developed to facilitate

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transepithelial diffusion. However, to date, none has been close to reaching the efficacy of the epithelium off (epi-off) technique. Raiskup-Wolf et al. reported no changes in the biomechanical properties of corneal tissue after CXL was performed with intact epithelium,9 confirming the need for complete epithelium removal to allow sufficient stromal uptake of riboflavin.

Rapid Accelerated Technique Following the Bunsen-Roscoe law of reciprocity, the same UVA dosage can be administered by increasing the UVA fluence while simultaneously reducing the exposure time, maintaining efficacy and safety of the technique with a substantial reduction of treatment time. Preclinical in vivo studies have been encouraging.61 However, a sudden decrease of efficacy has been observed using UV light with very high intensity (> 45 mW/cm2) probably due to a reduced availability of oxygen, which has been shown to limit the photochemical CXL process.62 So far, few studies with a limited follow-up of 6 months have demonstrated the same efficacy of accelerated CXL to standard protocol of 3 mW/cm2 UVA and 30 minutes of exposure.

Transepithelial Cross-Linking Transepithelial CXL has been adopted in various reports, especially in the pediatric keratoconic population, to reduce postoperative pain and the risk of corneal infections and corneal opacities in addition to reducing potential harmful effects on the endothelium in this young population. The most promising technique is enhanced transepithelial riboflavin absorption using iontophoretic delivery. Riboflavin is a small negatively charged molecule at physiologic pH and is easily soluble in water; therefore it is a suitable molecule for iontophoretic transfer. It has been shown that, using iontophoresis, an imbibition time of only 5 minutes achieves a sufficient riboflavin concentration in the corneal stroma for CXL treatment while preserving epithelial integrity.52 Numerous ex vivo studies confirmed the effectiveness of iontophoresis imbibition in obtaining an adequate riboflavin concentration in the stroma and the induction of important biomolecular and structural modifications of corneal tissue.63–65 Ex vivo biomechanical studies on rabbit and human cadaveric corneas showed that transepithelial CXL with iontophoresis imbibition induced an increase of the biomechanical resistance comparable to that obtained with the standard CXL procedure.66,67 Preliminary clinical results of iontophoresis-assisted corneal CXL are promising. The technique halts keratoconus progression without significant complications.68–70 However, longer follow-up and studies with larger patient populations are needed. Ultrasound, nanoemulsion systems and other epithelial permeation enhancers such as vitamin E-TPGS are currently under preclinical investigation to facilitate transepithelial riboflavin penetration.

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Cross-Linking Results Several published studies present outcomes of CXL treatments (standard epi-off and transepithelial) in adult and pediatric keratoconic patients.38,57,68,71–78 Standard epi-off CXL induces a significant improvement of both uncorrected visual acuity (UCVA) and best spectaclecorrected visual acuity (BSCVA) during the first year after CXL, thereafter remaining unchanged up to 3 years after the procedure. Visual acuity improves due to a progressive topographic flattening of the cornea over time with a reduction of simulated keratometry, minimum keratometry, mean average corneal power, and asymmetry indices. Soeters et al. observed that, before CXL, cones of pediatric keratoconic corneas were located more centrally than in the older age group.71 Significant reductions in mean spherical equivalent were observed, especially during the first year after CXL, with a

reduction in corneal aberrations, including coma. Minimum corneal thickness is typically reduced during the first 6 months after CXL, recovering to preoperative values within 1 year of the procedure. No endothelial cell loss was observed within the first 4 years after the procedure. Abrasion-related discomfort was reported by most patients in the immediate postoperative period. No ocular or systemic adverse events were noted apart from a low incidence of blepharitis and photophobia up to 4 months after the procedure. No significant intraocular pressure change was seen. In most of the eyes, CXL-specific golden striae79 developed and in some eyes a moderate haze was observed, which disappeared after the use of topical steroids. Transient haze appearing at 2 to 6 weeks and clearing at 9 to 12 months is the result of an increased density of extracellular matrix and arises at a depth of 300 to 350 µm. It forms the demarcation line that can be seen at slit lamp examination and with optical coherence tomography (OCT; Figs. 22.1 and 22.2). Persistent

B

A • Fig. 22.1

  (A) Mild stromal opacity 3 months after cross-linking for progressive keratoconus. (B) Optical coherence tomography demonstrating hyperreflectivity in the anterior half of the corneal stroma.

A

B

C

• Fig. 22.2  (A) Moderate stromal opacity seen on direct illumination (arrows) and (B) corneal cross-section (arrowheads). (C) Optical coherence tomography reveals hyperreflectivity and deep demarcation line at about 300 µm.

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haze has been observed in eyes with corneal apex power higher than 72  diopters (D) and central pachymetry thinner than 420 µm (Fig. 22.3). Sterile infiltrates may occur in the early postoperative period and usually resolve with the use of topical steroids (Figs. 22.4 and 22.5).

A

B

• Fig. 22.3

  (A) Intense central stromal opacity seen on direct illumination (arrows) and (B) corneal cross-section (arrowheads).

A

A prospective study report from Caporossi et al.73 (Siena CXL Pediatrics trial) noted that there was a better and faster visual recovery in eyes with less than 450 µm corneal thickness than in eyes with thicker corneas. Vinciguerra et al. performed a comparative analysis, including 400 eyes of 301 patients divided into 4 age groups stratified by age and confirmed the efficacy of corneal CXL in stabilizing the progression of the disease in all age groups, with the best functional and morphologic result in the population between 18 and 39 years of age.80 In contrast to these studies, Buzzonetti et al.,68 despite concluding that transepithelial CXL appears to be a safe treatment in children, demonstrated that K readings and higher-order aberrations significantly worsened during follow-up. Confocal microscopy demonstrated a demarcation line at a depth of only 105 µm in contrast to the demarcation line typically seen at 300 µm in standard CXL treatment. They therefore concluded that transepithelial CXL does not halt keratoconus progression as effectively as standard CXL. The same conclusion was reported by Caporossi et al., showing instability of functional results in pediatric patients after transepithelial CXL. Fifty percent of these patients were retreated after 12 months of follow-up.73 These publications demonstrated that visual, refractive, and topographic stabilization and improvements

B

• Fig. 22.4  (A) Ring-like sterile infiltrates in the peripheral cornea at the 9.0-mm zone 5 days after crosslinking. (B) After 2 weeks, there is complete resolution and only a residual scar.

A

345

B • Fig. 22.5  (A) Isolated peripheral sterile infiltrate 5 days after cross-linking with central residual epithelial defect. (B) After 1 week, there is improvement in the infiltrate and epithelial healing.

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after pediatric CXL are similar to those reported for adult treatments, with stability or improvement maintained for up to 4 years of follow-up when treated with the standard protocol.81 The author suggests following the standard CXL (epi-off Dresden protocol) in pediatric keratoconus, which has been shown to be successful in stabilization in most studies. Nevertheless, Chatzis and Hafezi57 have reported stabilization for 2 years and late regression of the “standard CXL” effect at 3 years follow-up, suggesting that pediatric CXL may not provide long-term stability comparable to adult treatment and may require retreatment, especially in the subset of patients who continue eye rubbing. Since keratoconus may rapidly progress in young patients, it is recommended to evaluate pediatric keratoconus patients every 1 to 3 months (as opposed to 6 months in adults) to identify the earliest signs of progression and offer them CXL. If longer-term follow-up demonstrates continued efficacy and, more important, continued safety of CXL in pediatric age taking into account the very high rate and speed of progression, performing CXL without waiting for definite progression might become the standard of care. However, some authors, such as Chatzis and Hafezi,57 have already suggested performing CXL as soon as diagnosis of pediatric keratoconus is established owing to the safety of the procedure and to the very high rate of keratoconus progression, without awaiting any documentation of progression. They conducted a retrospective analysis of 59 eyes from 42 children and adolescents (aged 9 to 19 years) with confirmed keratoconus with up to 3 years of follow-up demonstrating that 52 of the 59 eyes enrolled in the study showed a progression. Soeters et al. reported rapid progression of keratoconus in the pediatric population, ranging from 2.6 D in 7 weeks to 5.0 D over a year.71 Younger age at diagnosis was associated with topographic progression of keratoconus in a Korean report studying correlation of several topographic indices to keratoconic progression.82

Alternative Uses of Corneal Cross-Linking Infections CXL has an antimicrobial effect inherent to UV light interacting with riboflavin as the chromophore. In fact, UV irradiation is used as an antimicrobial procedure for disinfecting water, surfaces, and air. It damages both the DNA and RNA of pathogens, including bacteria and viruses, and renders them inactive.83 Additionally, photoactivated riboflavin seems to produce an antimicrobial effect. In fact, the use of riboflavin as a photosensitizer to inactivate pathogens in plasma, platelet, and red cell products has been described.84 Owing to its nucleic acid specificity and its limited tendency toward indiscriminate oxidation, riboflavin was hypothesized as a photosensitizer for the inactivation of pathogens in infective keratitis. It was reported that riboflavin activated by UVA showed an antimicrobial effect on

agar plates inoculated with Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, and Candida albicans. The inhibition of microbial growth was significantly higher in plates treated with UVA-activated riboflavin than in those treated with UVA light alone. However, riboflavin alone did not show any significant bactericidal effect.85 The first reported use of CXL in infective keratitis was in 2008, when Iseli at al. reported healing four out of five cases of mycobacterial and fungal corneal melting unresponsive to conventional therapy, using the standard Dresden protocol.86 In 2013, Alio et al. reported similar results in a systematic review and meta-analysis.87 In 2014, Said et al. reported a large prospective clinical trial on infective keratitis comparing 21 eyes treated with CXL in addition to antimicrobial therapy to 19 eyes that received only antimicrobial therapy. They did not find a significant difference between both groups in terms of healing time and final visual acuity. Three patients treated with antimicrobial therapy alone experienced corneal perforation and one an infection relapse; no significant complications occurred in the CXL group. The authors conclude that CXL could serve as a valuable adjuvant therapy and may reduce or avoid severe complications, preventing the need for emergency keratoplasty.88

Pseudophakic Bullous Keratopathy In the case of corneal edema due to endothelial failure, it has been shown that CXL increases corneal resistance to swelling. In fact, CXL increases the interfiber collagen connections, making it difficult for stromal fluid to separate collagen lamellae and create a potential space for edema accumulation. Therefore the use of CXL was proposed as an alternative approach for the management of pseudophakic bullous keratopathy (PBK) to reduce ocular discomfort, improve visual acuity, and delay the need for keratoplasty.89 Clinical studies evaluating the effectiveness of corneal CXL in the treatment of PBK reported a significant improvement in corneal transparency, corneal thickness, and ocular pain 1 month postoperatively. However, CXL did not seem to have a long-lasting effect over 6 months in decreasing pain and maintaining corneal transparency.90,91

References 1. Wollensak G, Spoerl E, Seiler T. Stress-strain measurements of human and porcine corneas after riboflavin-ultraviolet-a induced cross-linking. J Cataract Refract Surg. 2003;29(9):1780–1785. 2. Wollensak G, Spoerl E, Seiler T. Riboflavin/ultraviolet-a-induced collagen crosslinking for the treatment of keratoconus. Am J Ophthalmol. 2003;135(5):620–627. 3. Kohlhaas M, Spoerl E, Schilde T, Unger G, Wittig C, Pillunat LE. Biomechanical evidence of the distribution of cross-links in corneas treated with riboflavin/ultraviolet a light. J Cataract Refract Surg. 2006;32(2):279–283. 4. Spoerl E, Huhle M, Seiler T. Induction of cross-links in corneal tissue. Exp Eye Res. 1998;66(1):97–103.

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5. Spoerl E, Seiler T. Techniques for stiffening the cornea. J Refract Surg. 1999;15(6):711–713. 6. Spoerl E, Wollensak G, Seiler T. Increased resistance of crosslinked cornea against enzymatic digestion. Curr Eye Res. 2004;29(1):35–40. 7. Schilde T, Kohlhaas M, Spoerl E, Pillunat LE. Enzymatic evidence of the depth dependence of stiffening on riboflavin/UVA treated corneas. Ophthalmologe. 2008;105(2):165–169. 8. Wittig-Silva C, Whiting M, Lamoureux E, Lindsay RG, Sullivan LJ, Snibson GR. A randomized controlled trial of corneal collagen cross-linking in progressive keratoconus: preliminary results. J Refract Surg. 2008;24(7):S720–S725. 9. Raiskup-Wolf F, Hoyer A, Spoerl E, Pillunat LE. Collagen crosslinking with riboflavin and ultraviolet-a light in keratoconus: long-term results. J Cataract Refract Surg. 2008;34(5):796–801. 10. Spoerl E, Mrochen M, Sliney D, et al. Safety of UVA–riboflavin cross-linking of the cornea. Cornea. 2007;26(4):385–389. 11. Vinciguerra P, Albè E, Trazza S, Seiler T, Epstein D. Intraoperative and postoperative effects of corneal collagen cross-linking on progressive keratoconus. Arch Ophthalmol. 2009;127(10): 1258–1265. 12. Vinciguerra P, Camesasca FI, Albè E, Trazza S. Corneal collagen cross-linking for ectasia after excimer laser refractive surgery: 1-year results. J Refract Surg. 2010;26(7):486–497. 13. Vinciguerra P, Albè E, Trazza S, et al. Refractive, topographic, tomographic, and aberrometric analysis of keratoconic eyes undergoing corneal cross-linking. Ophthalmology. 2009;116(3): 369–378. 14. Tuori AJ, Virtanen I, Aine E, Kalluri R, Miner JH, Uusitalo HM. The immunohistochemical composition of corneal basement membrane in keratoconus. Curr Eye Res. 1997;16(18):792–801. 15. Cheng EL, Maruyama I, Sundar Raj N, Sugar J, Federer RS, Yue BY. Expression of type XII collagen and hemidesmosomeassociated proteins in keratoconus corneas. Curr Eye Res. 2001; 22(5):333–340. 16. Radner W, Zehemayer M, Skorpik C, Mallinger R. Altered organization of collagen in apex of keratoconus corneas. Ophthalmic Res. 1998;30(5):327–332. 17. Rabinowitz YS. Keratoconus. Surv Ophthalmol. 1998;42(4): 297–319. 18. Gordon-Shaag A, Millodot M, Shneor E, Liu Y. The genetic and environmental factors for keratoconus. Biomed Res Int. 2015; 2015:795738. 19. Binder PS. Analysis of ectasia after laser in situ keratomileusis: risk factors. J Cataract Refract Surg. 2007;33:1530–1538. 20. Chen MC, Lee N, Bourla N, Hamilton DR. Corneal biomechanical measurements before and after laser in situ keratomileusis. J Cataract Refract Surg. 2008;34:1886–1891. 21. Kirwan C, O’Malley D, O’Keefe M. Corneal hysteresis and corneal resistance factor in keratectasia: finding using the reichert ocular response analyzer. Ophtalmologica. 2008;222:334–337. 22. Randleman JB, Woodward M, Lynn MJ, Stulting RD. Risk assessment for ectasia after corneal refractive surgery. Ophthalmology. 2008;115:37–50. 23. Andreassen TT, Simonsen AH, Oxlund H. Biomechanical properties of keratoconus and normal corneas. Exp Eye Res. 1980; 31(4):435–441. 24. Carmi E, Defossez-Tribout C, Ganry O, et al. Ocular complications of atopic dermatitis in children. Acta Derm Venereol. 2006;86(6):515–517. 25. Cullen JF, Butler HG. Mongolism (down’s syndrome) and keratoconus. Br J Ophthalmol. 1963;47:321–330.

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26. Rabinowitz YS. The genetics of keratoconus. Ophthalmol Clin North Am. 2003;16(4):607–620. 27. Edwards M, McGhee CN, Dean S. The genetics of keratoconus. Clin Experiment Ophthalmol. 2001;29(6):345–351. 28. Wang Y, Rabinowitz YS, Rotter JI, Yang H. Genetic epidemiological study of keratoconus: evidence for major gene determination. Am J Med Genet. 2000;93(5):403–409. 29. Falls HF, Allen AW. Dominantly inherited keratoconus. J Genet Hum. 1969;17(3):317–324. 30. Zadnik K, Mannis MJ, Johnson CA. An analysis of contrast sensitivity in identical twins with keratoconus. Cornea. 1984; 3(2):99–103. 31. Tyynismaa H, Sistonen P, Tuupanen S, et al. A locus for autosomal dominant keratoconus: linkage to 16q22.3-q23.1 in Finnish families. Invest Ophthalmol Vis Sci. 2002;43(10): 3160–3164. 32. Brancati F, Valente EM, Sarkozy A, et al. A locus for autosomal dominant keratoconus maps to human chromosome 3p14-q13. J Med Genet. 2004;41(3):188–192. 33. Hutchings H, Ginisty H, Le Gallo M, et al. Identification of a new locus for isolated familial keratoconus at 2p24. J Med Genet. 2005;42(1):88–94. 34. Tang YG, Rabinowitz YS, Taylor KD, et al. Genomewide linkage scan in a multigeneration caucasian pedigree identifies a novel locus for keratoconus on chromosome 5q14.3-q21.1. Genet Med. 2005;7(6):397–405. 35. Li X, Rabinowitz YS, Tang YG, et al. Invest Ophthalmol Vis Sci. 2006;47(9):3791–3795. 36. Li X, Yang H, Rabinowitz YS. Longitudinal study of keratoconus progression. Exp Eye Res. 2007;85:502–507. 37. Holland DR, Maeda N, Hannush SB, et al. Unilateral keratoconus. Incidence and quantitative topographic analysis. Ophthalmology. 1997;104(9):1409–1413. 38. Arora R, Gupta D, Goyal JL, Jain P. Results of corneal collagen cross-linking in pediatric patients. J Refract Surg. 2012;28: 759–762. 39. Gunes A, Tok L, Tok O, Seyrek L. The youngest patient with bilateral keratoconus secondary to chronic persistent eye rubbing. Semin Ophthalmol. 2014. 40. Rahman W, Anwar S. An unusual case of keratoconus. J Pediatr Ophthalmol Strabismus. 2006;43(6):373–375. 41. Panahi-Bazaz MR, Sharifipour F, Moghaddasi A. Bilateral keratoconus and corneal hydrops associated with eye rubbing in a 7-year-old girl. J Ophthalmic Vis Res. 2014;9(1):101–105. 42. Ioannidis AS, Speedwell L, Nischal KK. Unilateral keratoconus in a child with chronic and persistent eye rubbing. Am J Ophthalmol. 2005;139(2):356–357. 43. Downie LE. The necessity for ocular assessment in atopic children: bilateral corneal hydrops in an 8 year old. Pediatrics. 2014; 134(2):e596–e601. 44. Gatzioufas Z, Panos GD, Brugnolli E, Hafezi F. Corneal topographical and biomechanical variations associated with hypothyroidism. J Refract Surg. 2014;30(2):78–79. 45. Gatzioufas Z, Thanos S. Acute keratoconus induced by hypothyroxinemia during pregnancy. J Endocrinol Invest. 2008;31(3): 262–266. 46. Soeters N, Tahzib NG, Bakker L, Van der Lelij A. Two cases of keratoconus diagnosed after pregnancy. Optom Vis Sci. 2012; 89(1):112–116. 47. Hoogewoud F, Gatzioufas Z, Hafezi F. Transitory topographical variations in keratoconus during pregnancy. J Refract Surg. 2013;29(2):144–146.

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48. Bilgihan K, Hondur A, Sul S, Ozturk S. Pregnancy-induced progression of keratoconus. Cornea. 2011;30(9):991–994. 49. ASCRS Cornea Clinical Committee. Reshaping procedures for the surgical management of corneal ectasia. J Cataract Refract Surg. 2015;41:842–872. 50. Kamaev P, Friedman MD, Sherr E, Muller D. Photochemical kinetics of corneal cross-linking with riboflavin. Invest Ophthalmol Vis Sci. 2012;53:2360–2367. 51. Wollensak G. Crosslinking treatment of progressive keratoconus: new hope. Curr Opin Ophthalmol. 2006;17:356–360. 52. Raiskup F, Spoerl E. Corneal crosslinking with riboflavin and ultraviolet a. I. principles. Ocul Surf. 2013;11:65–74. 53. Wollensak G, Aurich H, Pham DT, Wirbelauer C. Hydration behavior of porcine cornea crosslinked with riboflavin and ultraviolet a. J Cataract Refract Surg. 2007;33(3):516–521. 54. Wollensak G, Wilsch M, Spoerl E, Seiler T. Collagen fiber diameter in the rabbit cornea after collagen crosslinking by riboflavin/ UVA. Cornea. 2004;23(5):503–507. 55. Akhtar S, Almubrad T, Paladini I, Mencucci R. Keratoconus corneal architecture after riboflavin/ultraviolet a cross-linking: ultrastructural studies. Mol Vis. 2013;19:1526–1537. 56. Léoni-Mesplié S, Mortemousque B, Mesplié N, et al. Epidemiological aspects of keratoconus in children. J Fr Ophtalmol. 2012;35(10):776–785. 57. Chatzis N, Hafezi F. Progression of keratoconus and efficacy of pediatric [corrected] corneal collagen cross-linking in children and adolescents. J Refract Surg. 2012;28:753–758. 58. Al Suhaibani AH, Al-Rajhi AA, Al-Motowa S, Wagoner MD. Inverse relationship between age and severity and sequelae of acute corneal hydrops associated with keratoconus. Br J Ophthalmol. 2007;91:984–985. 59. Ertan A, Muftuoglu O. Keratoconus clinical findings according to different age and gender groups. Cornea. 2008;27:1109–1113. 60. Kamiya K, Shimizu K, Ohmoto F. Effect of aging on corneal biomechanical parameters using the ocular response analyzer. J Refract Surg. 2009;25:888–893. 61. Beshtawi IM, Akhtar R, Hillarby MC, et  al. Biomechanical properties of human corneas following low- and high-intensity collagen cross-linking determined with scanning acoustic microscopy. Invest Ophthalmol Vis Sci. 2013;54:5273–5280. 62. McCall AS, Kraft S, Edelhauser HF, et al. Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA). Invest Ophthalmol Vis Sci. 2010;51:129–138. 63. Mastropasqua L, Lanzini M, Curcio C, et al. Structural modifications and tissue response after standard epi-off and iontophoretic corneal crosslinking with different irradiation procedures. Invest Ophthalmol Vis Sci. 2014;55:2526–2533. 64. Mastropasqua L, Nubile M, Calienno R, et al. Corneal crosslinking: intrastromal riboflavin concentration in iontophoresisassisted imbibition versus traditional and transepithelial techniques. Am J Ophthalmol. 2014;157:623–630. 65. Mencucci R, Ambrosini S, Paladini I, et al. Early effects of corneal collagen cross-linking by iontophoresis in ex vivo human corneas. Graefes Arch Clin Exp Ophthalmol. 2015;253: 277–286. 66. Cassagne M, Laurent C, Rodrigues M, et al. Iontophoresis transcorneal delivery technique for transepithelial corneal collagen crosslinking with riboflavin in a rabbit model. Invest Ophthalmol Vis Sci. 2016;57(2):594–603. 67. Lombardo M, Serrao S, Rosati M, Ducoli P, Lombardo G. Biomechanical changes in the human cornea after transepithelial

corneal crosslinking using iontophoresis. J Cataract Refract Surg. 2014;40:1706–1715. 68. Buzzonetti L, Petrocelli G, Valente P, Iarossi G, Ardia R, Petroni S. Iontophoretic transepithelial corneal cross-linking to halt keratoconus in pediatric cases: 15-month follow-up. Cornea. 2015;34:512–515. 69. Bikbova G, Bikbov M. Transepithelial corneal collagen crosslinking by iontophoresis of riboflavin. Acta Ophthalmol. 2014; 92:30–34. 70. Vinciguerra P, Randleman JB, Romano V, et al. Transepithelial iontophoresis corneal collagen cross-linking for progressive keratoconus: initial clinical outcomes. J Refract Surg. 2014;30: 746–753. 71. Soeters N, van der Valk R, Tahzib NG. Corneal cross-linking for treatment of progressive keratoconus in various age groups. J Refract Surg. 2014;30(7):454–460. 72. Vinciguerra P, Albé E, Frueh BE, Trazza S, Epstein D. Two-year corneal cross-linking results in patients younger than 18 years with documented progressive keratoconus. Am J Ophthalmol. 2012;154(3):520–526. 73. Caporossi A, Mazzotta C, Paradiso AL, Baiocchi S, Marigliani D, Caporossi T. Transepithelial corneal collagen crosslinking for progressive keratoconus: 24-month clinical results. J Cataract Refract Surg. 2013;39(8):1157–1163. 74. Magli A, Forte R, Tortori A, Capasso L, Marsico G, Piozzi E. Epithelium-off corneal collagen cross-linking versus transepithelial cross-linking for pediatric keratoconus. Cornea. 2013; 32(5):597–601. 75. Zotta PG, Moschou KA, Diakonis VF, et al. Corneal collagen cross-linking for progressive keratoconus in pediatric patients: a feasibility study. J Refract Surg. 2012;28(11):793–799. 76. Kankariya VP, Kymionis GD, Diakonis VF, Yoo SH. Management of pediatric keratoconus — evolving role of corneal collagen cross-linking: an update. Indian J Ophthalmol. 2013;61(8): 435–440. 77. Kumar Kodavoor S, Arsiwala AZ, Ramamurthy D. One-year clinical study on efficacy of corneal cross-linking in Indian children with progressive keratoconus. Cornea. 2014;33(9): 919–922. 78. Sloot F, Soeters N, van der Valk R, Tahzib NG. Effective corneal collagen crosslinking in advanced cases of progressive keratoconus. J Cataract Refract Surg. 2013;39(8):1141–1145. 79. Suri K, Hammersmith KM, Nagra PK. Corneal collagen crosslinking: ectasia and beyond. Curr Opin Ophthalmol. 2012;23(4): 280–287. 80. Vinciguerra R, Romano MR, Camesasca FI, et al. Corneal crosslinking as a treatment for keratoconus: four-year morphologic and clinical outcomes with respect to patient age. Ophthalmology. 2013;120(5):908–916. 81. Salman AG. Transepithelial corneal collagen crosslinking for progressive keratoconus in a pediatric age group. J Cataract Refract Surg. 2013;39(8):1164–1170. 82. Ahn SJ, Kim MK, Wee WR. Topographic progression of keratoconus in the korean population. Korean J Ophthalmol. 2013;27(3):162–166. 83. Tabibian D, Richoz O, Hafezi F. PACK-CXL: corneal crosslinking for treatment of infectious keratitis. J Ophthalmic Vis Res. 2015;10:77–80. 84. Goodrich RP. The use of riboflavin for inactivation of pathogens in blood products. Vox Sang. 2000;78:211–215. 85. Martins SA, Combs JC, Noguera G, et al. Antimicrobial efficacy of riboflavin/UVA combination (365 nm) in vitro for bacterial

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and fungal isolates: a potential new treatment for infectious keratitis. Invest Ophthalmol Vis Sci. 2008;49(8):3402–3408. 86. Iseli HP, Thiel MA, Hafezi F, Kampmeier J, Seiler T. Ultraviolet a/riboflavin corneal cross-linking for infectious keratitis associated with corneal melts. Cornea. 2008;27:590–594. 87. Alio JL, Abbouda A, Valle DD, Del Castillo JM, Fernandez JA. Corneal cross linking and infectious keratitis: a systematic review with a meta-analysis of reported cases. J Ophthalmic Inflamm Infect. 2013;3:47. 88. Said DG, Elalfy MS, Gatzioufas Z, et al. Collagen cross-linking with photoactivated riboflavin (PACK-CXL) for the treatment of

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advanced infectious keratitis with corneal melting. Ophthalmology. 2014;121:1377–1382. 89. Sorkin N, Varssano D. Corneal collagen crosslinking: a systematic review. Ophthalmologica. 2014;232:10–27. 90. Ghanem RC, Santhiago MR, Berti TB, Thomaz S, Netto MV. Collagen crosslinking with riboflavin and ultraviolet-A in eyes with pseudophakic bullous keratopathy. J Cataract Refract Surg. 2010;36:273–276. 91. Sharma N, Roy S, Maharana PK, et al. Outcomes of corneal collagen crosslinking in pseudophakic bullous keratopathy. Cornea. 2014;33:243–246.

23 

Orthokeratology PAULINE CHO

Introduction Orthokeratology is a widely accepted optical treatment for myopia control in children, especially in East Asian countries. However, this treatment has existed for many years, originally having been introduced by Jessen in 1962.1 At that time, the treatment was not well received, but later introduction of reverse geometry designs; sophisticated instruments, such as computerized corneal topography; and super high gas permeable rigid gas permeable (RGP) materials led to a rapid improvement in lens design and fitting. This led to resolution of the majority of problems associated with the older techniques, such as corneal edema, distortion, and poor vision.2–10 Modern orthokeratology allows lenses to be worn on an overnight basis only, with the full refractive change taking place and remaining stable within 2 to 4 weeks after commencing lens wear.3,11–16 It has been shown to be effective in slowing the progression of myopia.9,17–24 Earlier studies showed that one of the main causes of poor post-orthokeratology visual acuity was significant residual refractive error, the major contribution to which was uncorrected corneal astigmatism. Toric design orthokeratology lenses were therefore introduced to correct higher-astigmatic eyes.21,22 For high myopia, a pilot study on high-myopic children has demonstrated a higher level of myopia control using partial correction (PR) orthokeratology while lens designs for full correction are still in the pipeline.23

Changes in Refraction and Visual Acuity With accelerated overnight orthokeratology, refractive change can now be achieved after a short period of lens wear.3,11,16,21,25,26 Studies have shown significant refractive changes to occur after only 1 night of lens wear, with reports ranging from 42% to 69%.16,21,26–28 Most studies aimed for a modest myopia reduction, as recommended by the manufacturers who designed these lenses for myopia up to 4.00 diopters (D) only. In effect, there is a mean decrease in myopia of 3.00 D, associated with improvement of unaided (post-orthokeratology) visual acuity to close to 20/20 Snellen or 0.00 logMAR.3,7,8,20,21,29–32 350

In subjects with no significant residual refractive error after stabilization of treatment, or with residual refractive error corrected, high- and low-contrast logMAR visual acuities have been shown to be comparable to those in spectaclewearing controls.26,30,32 Changes induced by orthokeratology are temporary and questions have been raised as to how fast these changes return to baseline values after overnight lens wear. The retention rate is obviously important, as it reflects the quality and stability of the unaided visual acuity after lens removal. Many researchers have investigated and reported daytime regression to be in the range of 0.25 D to 0.50 D.16,25 Mountford25 suggested that the practitioner should therefore aim for an initial overcorrection of existing myopia by about 0.50 D to minimize the regression effect.

Topographic Corneal Curvature Changes Computerized corneal topography plays an essential role in modern orthokeratology practice. It allows practitioners to assess the prefitting anterior corneal shape and monitor changes to the corneal topography after lens wear. Corneal mapping provides the only reliable means of knowing precisely where the lens is positioned during sleep. This information helps the practitioner determine the appropriate lens modifications necessary to achieve the desired outcome. Most researchers have found no change in the posterior corneal curvatures33–35 and their findings supported the hypothesis that orthokeratology effects refractive changes primarily through remodeling of the anterior corneal curvature and not by overall bending of the cornea.

Anterior Segment Changes Alhabi and Swarbrick16 reported central corneal thinning of 9.3 ± 5.3 µm after one night of orthokeratology lens wear in 18 subjects wearing orthokeratology lenses. At the end of 90 days of lens wear, the central cornea thinned by 19.0 ± 2.6 µm. The corneal changes involved rapid thinning of the central corneal epithelium and thickening of the midperipheral stroma and probably account for the rapid refractive changes induced by orthokeratology lenses. Their results confirmed the findings of an earlier study by Swarbrick

CHAPTER 23  Orthokeratology

et al.,11 which suggested that the refractive changes induced by orthokeratology lens wear were due to the redistribution of corneal tissue and not by overall bending of the cornea. In more recent studies, a smaller amount of central corneal thinning has been reported.20,23 Cho and Cheung20 reported significant reduction of the central corneal thickness in their orthokeratology subjects. The average central corneal thinning was 9 µm after 6 months of lens wear, with no further changes in subsequent visits in their 2-year study. Using four-zone orthokeratology lenses with a target of 4.00 D, Charm and Cho23 partially corrected 12 highmyopic subjects and found no significant central corneal thinning over the course of their study. At the end of 24 months of lens wear, changes in central corneal thickness ranged from –34.5 to +5.3 (median –4.6) µm (negative value indicating thinning) in their PR orthokeratology subjects and from –13.0 to +28.5 (median 3.5) µm in their control subjects. Although the amount of reported corneal thinning varied between studies, it is well documented that central corneal epithelium thinned in orthokeratology. The clinical implication of this thinning may be close and careful monitoring of the central cornea of orthokeratology patients. The nature of changes of thickness in other corneal regions in orthokeratology lens wear is still unclear; thus further investigation is warranted in this area. There were initial concerns that orthokeratology leads to a backward displacement of the cornea, resulting in a decrease in anterior chamber depth (ACD) and giving a false impression of shorter axial length measured during lens wear. However, studies have shown that changes in vitreous chamber depth were consistent with changes observed in axial length in orthokeratology.9,36 Anterior segment length was not altered with orthokeratology lens wear and no significant changes in ACD was reported at the end of 2 years of lens wear in Cheung and Cho’s study.37 Other studies33,35 have also reported no significant changes in ACD, although González-Mesa et al.38 reported significant reduction in ACD with orthokeratology lens wear. Cheung and Cho37,39 concluded that axial length is valid for the determination of axial elongation in orthokeratology.

Orthokeratology for Myopia Control In 2005, Cho et al.9 reported effective myopia reduction (46%) after 2 years of orthokeratology lens wear in children. Their results showed similar control of elongations of the axial length and vitreous chamber depth. Following this report, a number of other clinical studies17–19 were published, all demonstrating effectiveness of orthokeratology for myopia control, although the percentage control varied from 32% to 55%. Variations in the level of myopia control achieved may be attributed to differences in subject criteria and methodology used. In 2012, Cho and Cheung20 published a randomized controlled trial providing further evidence on the effectiveness of orthokeratology for myopia progression in children.

351

Their results showed that axial elongation in 37 children wearing orthokeratology lenses was 43% slower than that of 41 children wearing spectacles. Axial elongations at the end of 2 years were 0.36 ± 0.24 mm and 0.63 ± 0.26 mm in the orthokeratology and control groups, respectively, and were significantly correlated to the initial age of the subjects. Younger myopic children (7–8 years) demonstrated faster progression (increase of myopia > 1.00 D or axial elongation > 0.36 mm per year) compared to older children (9–10 years) in both groups of subjects; 65% and 20% of the younger children in the spectacle-wearing and orthokeratology groups, respectively, and 13% and 9% in the older children, respectively. Charm and Cho23 reported 63% slower axial elongation in 12 high-myopic children using PR orthokeratology and spectacles for residual refraction in the daytime compared to 10 high-myopic children wearing single-vision spectacles. Chen et al.21 reported 52% slower axial elongation in 23 children wearing toric orthokeratology lenses and suggested that the higher level of myopia control demonstrated may be due to better orthokeratology lens centration from the use of toric design orthokeratology lenses. Cho and Cheung40 analyzed the combined data from two studies (72 orthokeratology children and 64 spectaclewearing controls)20,21 to investigate the protective role of orthokeratology in reducing fast progression in children. In children wearing spectacles, younger children (6–8 years old) had the greater and more rapid axial elongation (> 0.36 mm/y) compared to older children (9–12 years old). Moreover, orthokeratology treatment reduced the risk of fast progression in children of this younger age group by 88.8%. The 2-year number needed to treat (NNT) for the younger orthokeratology subgroup was 1.8, which suggests that treating just two younger children with orthokeratology would prevent one from experiencing fast progression.

Other Corneal Changes Corneal Pigmented Arc Brown-pigmented arcs are associated with the use of orthokeratology lenses41–43 and are suggested to be associated with a sudden change in corneal curvature that would allow pooling of the tears in that area. Cho et al.44 reported that the intensity of the pigmented arc, once observed, increased with the period of lens wear. The pre-orthokeratology spherical equivalent refractive error (SERE), the amount of SERE reduction, and changes in corneal curvatures were significantly larger in subjects presenting the pigmented arc than in those without the pigmented arc. In their study of high-myopic children using PR orthokeratology, Charm and Cho23 reported a pigmented arc in 32% of the children at the 1-month visit. The incidence reached 92% and 100% after 6 months and 12 months of lens wear, respectively. Rah and coworkers42 hypothesized that these pigmented arcs would disappear after cessation of lens wear. They suggested that, over time, normal corneal exfoliation would

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slough off the pigments. Cho et al.43 reported the disappearance of the pigmented arc in the corneas of two adult patients when examined 2 months after ceasing orthokeratology lens wear. Our understanding of the formation of the corneal pigmented arc is limited; further studies are certainly needed in this area.

Fibrillary Lines In the early days of orthokeratology using reverse geometry lenses, white fibrillary lines (Fig. 23.1) in the corneas of some orthokeratology patients were reported. When there were many, they appeared in a concentric format in the center of the cornea. As with the pigmented arc, there seems not to be any clinical ramifications. These lines are similar in appearance to fibrillary lines observed in keratoconic corneas.45 The condition is presumed to be pressure related and is reversible after cessation of lens wear. The work of Lum et al.46 confirmed that these fibrillary lines are related to an altered corneal sub-basal nerve plexus associated with orthokeratology lens wear (Fig. 23.2). Lum et al.47 also reported a reduction in corneal sensitivity in 16 adults who had worn orthokeratology lenses for 3 months. Corneal sensitivity recovered quickly, within 1 month, when lens wear was discontinued. However, the recovery of central nerve fiber density change was much slower, with full recovery observed only 3 months after cessation of lens wear.

Corneal Staining With improvements in lens materials, lens designs, and fitting, corneal staining is not as frequently observed as previously reported.10,29 Most studies reported mild central corneal staining, especially at the commencement of lens wear, and the incidence declined with continued lens wear.20-21,23 However, Charm and Cho23 reported that the incidence of corneal staining was generally higher in PR orthokeratology subjects.

Walline et al.10 reported corneal staining in 58.5% of their 23 subjects in the morning visits and in 35.5% of the subjects in the afternoon visits. On average, the staining observed was less than grade 2 and the most common type of staining pattern was the punctate type. Central corneal staining made up 77.8% of the staining recorded in the morning visits and 47.5% of the staining recorded in the afternoon visits. Walline and coworkers10 asserted that, although the incidence of staining was high, the staining was not serious enough to threaten safe contact lens wear. Hiraoka et al.48 reported that only three subjects had moderate superficial punctuate keratopathy and one mild corneal erosion in their orthokeratology subjects in their 5-year study and the staining resolved completely within a week after discontinuation of lens wear. In orthokeratology, the prudent practitioner should monitor corneal staining diligently, especially central corneal staining, in view of evidence of thinning of the central corneal epithelium in orthokeratology and the potential threat to vision should the cornea be infected. The other important factor with respect to the incidence of staining is the level of expertise used in fitting the lens. Staining caused by an incorrect fit should always be corrected. Central corneal staining occurs only when the lens comes into direct contact with the corneal epithelium49 and is therefore indicative of a less than optimal lens/cornea fitting relationship.

• Fig. 23.2

• Fig. 23.1  Example of fibrillary lines observed in the corneas of some orthokeratology patients after formation of the pigmented arc.

  Nerve tracings of the sub-basal nerve plexus superimposed upon computerized corneal topography maps (tangential power) in the same eye of an orthokeratology subject after 3 years of lens wear experience. Note that the areas of reduced nerve fiber density over the central cornea corresponded with the area of relative corneal flattening on the topography maps. The curvilinear nerves in the midperiphery arcing beneath the central corneal zone appear to coincide with the outer edges of the area of relative corneal flattening as well as the midperipheral areas without change and slight steepening in corneal curvature. (Courtesy of Dr Edward Lum.)

CHAPTER 23  Orthokeratology

Lens Binding Lens binding after overnight RGP lens wear is not uncommon50 and has been reported in a number of orthokeratology studies.7,26,51,52 Cheung and Cho29 reported that this was the most common nonvision-related problem (73%) that subjects reported in their study. More recent studies21,23 have reported reduced incidence of lens binding, probably due to improved lens designs and lens fitting. According to Mountford (personal communication), from clinical experience, most bound lenses will automatically free up following active blinking (on awakening) which facilitates tear exchange. However, it is important that practitioners carefully instruct their patients about how to remove a bound lens in the morning. In their study, Cheung and Cho29 reported that over 80% of the subjects who included lens binding as one of their problems did not attempt to loosen their lenses before removal. It is essential that patients do not remove bound lenses forcefully, especially if a suction holder is used to aid removal, as this can lead to significant corneal damage.

Microbial Keratitis in Orthokeratology Several recent reports of corneal ulcers in patients receiving orthokeratology treatment have led to concerns about the use of this procedure.53–56 However, these are case reports, some of which have provided minimal patient or treatment information; as such, they may not reflect the true picture of the potential risk of orthokeratology.57 Nevertheless, there are concerns about the potential risk associated with this treatment, especially since overnight lens wear is required and the level of lens care compliance among child contact lens wearers is uncertain. Boost and Cho58 found no significant change to the ocular microbiota with orthokeratology lens wear over an extended period. However, the majority of their subjects had significant contamination of at least one item, the most frequently contaminated item being the lens case, followed by the lens suction holder. Lens case isolates were significantly associated with those from the lens, suggesting cross-contamination. The majority of subjects who reported good compliance had low or no contamination of their lenses and lens accessories. Their results also showed that the most frequent breaches in the lens care protocol were failure to clean, disinfect, and replace the lens case. Cho et al.59 reported frequent and heavy contamination of the lens suction holders and lens cases, in spite of monthly replacement. They were of the opinion that patients’ (or parents’) attitudes toward the care of accessories (e.g., lens cases) were not satisfactory. It is therefore important that practitioners emphasize proper care and replacement of lens accessories to patients and their parents and avoid prescription of unnecessary accessories, for example, a lens suction holder. To minimize complications in orthokeratology lens wear, it is important that practitioners are diligent in the care of their patients, especially as the treatment involves children and overnight lens wear. During sleep, the cornea becomes

353

hypoxic owing to lid closure; this hypoxia is increased by the presence of the contact lens. The protective mechanisms of the eye, which include intact corneal surface and flushing of tears via blinking, are also absent during sleep. These factors associated with the use of contact lenses contribute to the cause of contact lens–induced complications.

Patient Acceptance The main motivation for children to accept orthokeratology was the convenience of spectacle freedom in the daytime.29 Aversion to lens-handling procedures may be a strong factor reducing the motivation in children. It is important that children should not be forced into orthokeratology; if they are unwilling, the chance of good compliance is likely to be reduced. It is equally important that parents are not only properly educated on lens care procedures but that they closely monitor their children on care procedures. Good and strong parental support is essential and cannot be overemphasized. Safety was the major concern of the parents when considering options for myopia control, but the decision on myopia control treatments was nevertheless affected by a combination of confidence in safety, effectiveness, and any additional benefit(s) provided by the treatment.60

References 1. Jessen GN. Orthofocus techniques. Contacto. 1962;6:200–204. 2. Mountford J, Ruston D, Dave T. Orthokeratology: Principles and Practice. Edinburgh: Butterworth-Heinemann; 2004. 3. Nichols JJ, Marsich MM, Nguyen M, Barr JT, Bullimore MA. Overnight orthokeratology. Optom Vis Sci. 2000;77:252–259. 4. Lui WO, Edwards MH. Orthokeratology in low myopia. Part 1: efficacy and predictability. Cont Lens Anterior Eye. 2000;23:77–89. 5. Lui WO, Edwards MH. Orthokeratology in low myopia. Part 2: corneal topographic changes and safety over 100 days. Cont Lens Anterior Eye. 2000;23:90–99. 6. Cho P, Cheung SW, Edwards MH. Practice of Orthokeratology by a group of contact lens practitioners in Hong Kong. I. General overview. Clin Exp Optom. 2002;85:365–371. 7. Rah MJ, Jackson JM, Jones LA, Marsden HJ, Bailey MD, Barr JT. Overnight orthokeratology: preliminary results of the Lenses and Overnight Orthokeratology (LOOK) study. Optom Vis Sci. 2002;79:598–605. 8. Tahhan N, Du Toit R, Papas E, Chung H, La Hood D, Holden AB. Comparison of reverse-geometry lens designs for overnight orthokeratology. Optom Vis Sci. 2003;80:796–804. 9. Cho P, Cheung SW, Edwards MH. The longitudinal orthokeratology research in children (LORIC) study in Hong Kong. A pilot study on refractive changes and myopic control. Curr Eye Res. 2005;30:71–80. 10. Walline JJ, Rah MJ, Jones LA. The children’s overnight orthokeratology investigation (COOKI) pilot study. Optom Vis Sci. 2004;81:407–413. 11. Swarbrick HA, Wong G, O’Leary DJ. Corneal response to orthokeratology. Optom Vis Sci. 1998;75:791–799. 12. Lu F, Jiang J, Qu J, Jin WQ, Mao XJ, Shen Y. Clinical study of orthokeratology in young myopic adolescents. Int Contact Lens Clin. 1999;26:113–116.

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13. Mountford J. Orthokeratology. In: Phillips AJ, Speedwell L, eds. Contact Lenses. 4th ed. London, UK: Butterworth-Heinemann; 1997:653–692. 14. Caroline PJ. Contemporary orthokeratology. Cont Lens Anterior Eye. 2001;24:41–46. 15. Mountford J. History and general principles. In: Mountford J, Ruston D, Dave T, eds. Orthokeratology Principles and Practice. Edinburgh, UK: Butterworth-Heinemann; 2004:1–16. 16. Alharbi A, Swarbrick HA. The effects of overnight orthokeratology lens wear on corneal thickness. Invest Ophthalmol Vis Sci. 2003;44:2518–2523. 17. Walline JJ, Jones LA, Sinnott LT. Corneal reshaping and myopia progression. Br J Ophthalmol. 2009;93:1181–1185. 18. Santodomingo-Rubido J, Villa-Collar C, Gilmartin B, GutiérrezOrtega R. Myopia control with orthokeratology contact lenses in Spain: refractive and biometric changes. Invest Ophthalmol Vis Sci. 2012;53:5060–5065. 19. Kakita T, Hiraoka T, Oshika T. Influence of overnight orthokeratology on axial elongation in childhood myopia. Invest Ophthalmol Vis Sci. 2011;52:2170–2174. 20. Cho P, Cheung SW. Retardation of myopia in Orthokeratology (ROMIO) study: a 2-year randomized clinical trial. Invest Ophthalmol Vis Sci. 2012;53:7077–7085. 21. Chen C, Cheung SW, Cho P. Myopia control using toric orthokeratology (TO-SEE study). Invest Ophthalmol Vis Sci. 2013;54:6510–6517. 22. Pauné J, Cardona G, Quevedo L. Toric double tear reservoir contact lens in orthokeratology for astigmatism. Eye Contact Lens. 2012;38:245–251. 23. Charm J, Cho P. High myopia-partial reduction ortho-k: a 2-year randomized study. Optom Vis Sci. 2013;90:530–539. 24. Swarbrick HA, Alharbi A, Watt K, Lum E, Kang P. Myopia control during orthokeratology lens wear in children using a novel study design. Ophthalmology. 2015;122:620–630. 25. Mountford J. Retention and regression of orthokeratology with time. Int Contact Lens Clin. 1998;5:59–64. 26. Chan KY, Cheung SW, Cho P. Clinical performance of an orthokeratology lens fitted with the aid of a computer software in Chinese children. Cont Lens Anterior Eye. 2012;35:180–184. 27. El Hage S, Leach NE, Miller W, et al. Empirical advanced orthokeratology through corneal topography: the University of Houston clinical study. Eye Contact Lens. 2007;33:224–235. 28. Chan B, Cho P, Cheung SW. Orthokeratology practice in a University Clinic. Clin Exp Optom. 2008;91:453–460. 29. Cheung SW, Cho P. Subjective and objective assessments of the effect of orthokeratology – a cross-sectional study. Curr Eye Res. 2004;28:121–127. 30. Cheung SW, Cho P, Chui WS, Woo G. Refractive error and visual acuity changes in orthokeratology patients. Optom Vis Sci. 2007;84:410–416. 31. Joslin CE, Wu SM, McMahon TT, Shahidi M. Higher-order wavefront aberrations in corneal refractive therapy. Optom Vis Sci. 2003;80:805–811. 32. Chen CC, Cheung SW, Cho P. Toric orthokeratology for highly astigmatic children. Optom Vis Sci. 2012;89:849–855. 33. Tsukiyama J, Miyamoto Y, Higaki S, Fukuda M, Shimomura Y. Changes in the anterior and posterior radii of the corneal curvature and anterior chamber depth by orthokeratology. Eye Contact Lens. 2008;34:17–20. 34. Chen D, Lam AK, Cho P. Posterior corneal curvature change and recovery after 6 months of overnight orthokeratology treatment. Ophthalmic Physiol Opt. 2010;30:274–280.

35. Yoon JH, Swarbrick HA. Posterior corneal shape changes in myopic overnight orthokeratology. Optom Vis Sci. 2013;90:196–204. 36. Sun Y, Xu F, Zhang T, et al. Orthokeratology to control myopia progression: a meta-analysis. PLoS ONE. 2015;10:e0124535. 37. Cheung SW, Cho P. Validity of axial length measurements for monitoring myopic progression in orthokeratology. Invest Ophthalmol Vis Sci. 2013;54:1613–1615. 38. González-Mesa A, Villa-Collar C, Lorente-Velázquez A, NietoBona A. Anterior segment changes produced in response to longterm overnight orthokeratology. Curr Eye Res. 2013;38:862–870. 39. Cheung SW, Cho P. Long-term effect of orthokeratology on the anterior segment length. Cont Lens Anterior Eye. 2016;39: 262–265. 40. Cho P, Cheung SW. Protective role of orthokeratology in reducing risk of rapid axial elongation: a reanalysis of data from the ROMIO and TO-SEE Studies. Invest Ophthalmol Vis Sci. 2017;58:1411–1416. 41. Cho P, Chui WS, Mountford J, Cheung SW. Corneal iron ring associated with orthokeratology lens wear. A case report. Optom Vis Sci. 2002;79:565–568. 42. Rah MJ, Barr JT, Bailey MD. Corneal pigmentation in overnight orthokeratology: a case series. Optom Vis Sci. 2002;73:425–434. 43. Cho P, Chui WS, Cheung SW. (Case Report) Reversibility of corneal pigmented arc associated with orthokeratology. Optom Vis Sci. 2003;80:791–795. 44. Cho P, Cheung SW, Mountford J, Chui WS. Incidence of corneal pigmented arc associated with orthokeratology. Ophthalmic Physiol Opt. 2005;25:478–484. 45. Bron AJ, Lobascher DJ, Dixon WS, Das SN, Ruben M. Fibrillary lines of the cornea. A clinical sign in keratoconus. Br J Ophthalmol. 1975;59:136–140. 46. Lum E, Golebiowski B, Swarbrick HA. Mapping the corneal sub-basal nerve plexus in orthokeratology lens wear using in vivo laser scanning confocal microscopy. Invest Ophthalmol Vis Sci. 2012;53:1803–1809. 47. Lum E, Golebiowski B, Swarbrick HA. Changes in corneal subbasal nerve morphology and sensitivity during orthokeratology: onset of change. Ocul Surf. 2016 Sep. pii: S1542–0124(16)30144-6. doi:10.1016/j.jtos.2016.07.005. [Epub ahead of print]. 48. Hiraoka T, Kakita T, Okamoto F, Takahashi H, Oshika T. Longterm effect of overnight orthokeratology on axial length elongation in childhood myopia: a 5-year follow-up study. Invest Ophthalmol Vis Sci. 2012;53:3913–3919. 49. Mountford J. Design variables and fitting philosophies of reverse geometry lenses. In: Mountford J, Ruston D, Dave T, eds. Orthokeratology Principles and Practice. Edinburgh, UK: ButterworthHeinemann; 2004:69–107. 50. Swarbrick HA, Holden BA. Ocular characteristics associated with rigid gas-permeable lens adherence. Optom Vis Sci. 1996;73:473–481. 51. Chen JZ, Chen L, Li YY, et al. 423 Cases of orthokeratology treatment. J Int Ophthalmol. 2012;24:130–132. 52. Cho P, Chan B, Cheung SW, Mountford J. Do fenestrations affect the performance of orthokeratology lenses? Optom Vis Sci. 2012;89:401–410. 53. Chen KH, Kuang TM, Hsu WM. Serratia marcescens corneal ulcer as a complication of orthokeratology. Am J Ophthalmol. 2001;132:257–258. 54. Hutchinson K, Apel A. Infectious keratitis in orthokeratology. Clin Exp Ophthalmol. 2002;30:49–51. 55. Lau LI, Wu CC, Lee SM, Hsu WM. Pseudomonas corneal ulcer related to overnight orthokeratology. Cornea. 2003;22:262–264.

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56. Young AL, Leung AT, Cheng LL, Law RWK, Wong AKK, Lam DSC. Orthokeratology lens-related corneal ulcers in children. Ophthalmology. 2004;111:590–595. 57. Cho P, White P, Cheung SW. Letter to the editor. Orthokeratology lens-related corneal ulcers in children. Ophthalmology. 2005;112:167–169. 58. Boost MV, Cho P. Microbial flora of tears of orthokeratology patients, and microbial contamination of contact lenses and contact lens accessories. Optom Vis Sci. 2005;82:451–458.

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59. Cho P, Boost M, Cheng R. Non-compliance and microbial contamination in orthokeratology. Optom Vis Sci. 2009;86: 1227–1234. 60. Cheung SW, Lam C, Cho P. Parents’ knowledge and perspective of optical methods for myopia control in children. Optom Vis Sci. 2014;91:634–641.

24 

Radial and Astigmatic Keratotomy SUPHI TANERI, RICHARD E. BRAUNSTEIN, AND DIMITRI T. AZAR

Introduction The use of radial and astigmatic keratotomy has declined over time as laser vision correction and cataract surgery with the implantation of toric intraocular lenses have gained popularity owing to superior predictability in most cases. Radial keratotomy for myopia correction is an especially abandoned procedure. Nevertheless, it is included in this chapter to illustrate its principles and the reasons for its eventual failure. On the other hand, incisional corneal surgery continues to play a role as a surgical method of correcting high astigmatism that is beyond the range of laser correction, for example, as it may occur iatrogenically after penetrating keratoplasty or for the correction of smaller degrees of astigmatism within the framework of cataract surgery.1 It may be combined with laser ablation or implant surgery in one session or as a staged procedure. This chapter presents the principles and techniques of incisional keratotomy. This knowledge is particularly valuable when working in developing countries with limited access to refractive laser surgery or toric intraocular implants. Likewise, in developed countries, the introduction of femtosecond (FS) lasers into corneal and cataract surgery rekindled interest in this technique assuming more predictable results by eliminating the surgeon factor.2,3 As early as 1885, Schiötz4 described corneal incisions as a means of treating astigmatism after cataract extraction. In 1898, L. J. Lans5 systematically examined the astigmatic effect of incisions in rabbit eyes and described many principles that are still accepted today. In 1981, Luis Ruiz noticed that five transverse incisions bounded by “pseudoradial” incisions on either side of the optical zone (OZ) resulted in an extremely large effect in correcting astigmatism, much larger than could be achieved by either transverse or pseudoradial incisions performed separately. He called this procedure trapezoidal keratotomy for the correction of astigmatism, which was later renamed the Ruiz procedure.6 In performing this correction, the meridian perpendicular to the one in which the Ruiz procedure was performed (the uninvolved meridian) became steeper as the involved meridian became flatter (Fig. 24.1). The degree of steepening of the uninvolved meridian was directly proportional to the length of the transverse elements of the Ruiz procedure. 358

In other words, the total correction of astigmatism was equal to the net sum of the flattening of the meridian in which the Ruiz procedure was performed added to the steepening of the flatter (uninvolved) meridian.

Success and Failure of Radial Keratotomy Radial keratotomy (RK) was the first refractive procedure and thus the beginning of refractive surgery as a subspecialty of ophthalmology (Fig. 24.2, Video 24.1). It was the most common form of surgical correction of myopia from the 1970s through the early 1990s. Important lessons can be learned from its history: Early reports from Fydorov and media coverage were quite enthusiastic.7 However, a multicenter prospective clinical trial with a long-term follow-up, called the Prospective Evaluation of Radial Keratotomy (PERK) study, revealed severe disadvantages of this technique. Although results were acceptable at 1 year and 5 years after RK, there was a significant loss of uncorrected and corrected visual acuity after 10 years, and a continuous hyperopic shift was observed.8–12 This hyperopic shift was also demonstrated in other studies; thus it was established as an inherent side effect of RK. As this side effect has not stopped the use of the procedure, knowing this complication is important to every ophthalmologist. Patients treated many years ago may now present with diurnal fluctuating vision, an irregular and instable hyperopic astigmatism and corresponding loss of visual acuity and changes of the corneal architecture (Figs. 24.3 and 24.4).

Astigmatic Keratotomy Astigmatic keratotomy (AK) when performed correctly is a lot safer and more predictable than RK. Because the spherical equivalent of a patient who undergoes an AK becomes more hyperopic while the spherical component of the refraction becomes more myopic, a solid understanding of these terms is essential to comprehend the mechanics of AK. Hoffmann coined the descriptive term coupling to describe the ratio of the flattening of the principal (steeper) meridian to the steepening of the flatter meridian.13 Fyodorov14,15 developed parallel incisions for the correction of astigmatism, which were unpredictable in the higher

CHAPTER 24  Radial and Astigmatic Keratotomy

359

• Fig. 24.1

  In a Ruiz procedure, the flatter meridian steepens from 40  D to 42 D while the steeper meridian flattens from 46 D to 42 D in this example. The total change in astigmatism is the sum of the flattening plus the steepening: in this case, 4 D + 2 D, for a total of 6 D.

• Fig. 24.2

 

Radial keratotomy in retroillumination

ranges of astigmatism and gave way to “T-cuts,” or flags that were staggered along the radial incisions on one or either side of the OZ. A T-cut had a predictable effect whether it was performed on only one side or on both sides of the visual axis. The Ruiz procedure always had to be performed on both sides of the visual axis. The presence of a transverse incision made AK much more predictable, but the intersection of transverse and radial incisions could lead to delayed corneal healing and epithelial recurrent erosions, especially when metal blades were used. Soon, most surgeons tried to avoid joining transverse and radial incisions. Currently, the most commonly used AK patterns are the arcuate and transverse incisions (T-cut), with or without a peripheral radial incision (Figs. 24.5A–C) and an OZ diameter of 6 to 7 mm. Up to about 4 diopters (D) of

• Fig. 24.3  Radial keratotomy after 20 years with an unremarkable appearance at the slit lamp.

astigmatism can be corrected by a pair of T-cuts, one on either side of the visual axis. The correction of astigmatism by means of wedge resection has been investigated since the 1960s and 1970s by two of the great corneal surgeons, Jose Barraquer16–18 and Richard Troutman.19,20 Lindstrom et al21,22 and Friedlander et al23,24 have investigated the effect of the Ruiz procedure on cadaver eyes. These studies tended to show a 150% to 200% greater effect than the in vivo procedure (common for cadaver eyes following incisional keratotomy); any generalizations from cadaver eyes to live patients were difficult, at best. Merlin25 suggested that better results are possible with arcuate rather than straight astigmatic incisions (see Fig. 24.5C). This idea was repopularized by Lindstrom. Arcuate incisions less than 45 degrees tend to act like straight ones, but the excessive gaping and subsequent unpredictability caused by arcuate incisions in the 75- to 90-degree range are undesirable. Straight transverse incisions appear rectilinear only when viewed perpendicular to the corneal surface (Fig. 24.6A and B). Using a ball as a substitute cornea, it is easy to visualize T-cuts in a three-dimensional view and to understand that these incisions are actually curvilinear because they follow the curved corneal surface. Thus these “straight” T-cuts are really a segment of a great circle around the imaginary corneal sphere, imparting a consistency of action and promoting coupling by gaping less at the end of the incisions. Only when viewed in two dimensions, instead of three, do arcuate incisions appear to be a favorable pattern relative to the center of the cornea, the visual axis. Because all points of an arcuate incision are equidistant from the center of the cornea, an equal amount of wound gape occurs. This equal and large degree of gaping tends to increase irregular astigmatism and makes coupling less predictable.

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Other Refractive Procedures

Limbal Relaxing Incisions Limbal relaxing incisions (LRIs) are a type of arcuate incisions made at the limbus to correct low degrees of astigmatism. These cuts are also called peripheral corneal relaxing incisions (PCRIs). LRIs can be considered safe and effective for correcting astigmatism of up to 2.5 D. A major advantage of LRIs is that night vision problems, which may be associated with incisions in the corneal midperiphery, are avoided. This is because LRIs are made in the periphery near the limbus and most patients’ pupils will not dilate that wide, eliminating night glare. LRIs can be performed with cataract surgery if an astigmatic error was preexisting, allowing the simultaneous correction of a patient’s astigmatism. However, if astigmatism has been induced by cataract or corneal surgery, the incisions can be made months after the

A

B

C • Fig.

D

• Fig. 24.4

  Pentacam 20 years after radial keratotomy, revealing significant corneal distortion. This patient (same eye as in Fig. 24.3) complained about diurnal fluctuating vision and loss of corrected and uncorrected vision. The patient was subsequently treated with corneal cross-linking.

A • Fig. 24.6

B

24.5  The most common astigmatic incisions. (A) Transverse (T-cut); (B) T-cut with radial; (C) arcuate; (D) chevron.

C

  Demonstrating the curvilinear nature of T-cuts, using a ping-pong ball for a cornea. Notice that the T-cuts (red ink lines) appear straight when viewed perpendicular to the incision (A), but are actually curvilinear (B) and a segment of a great circle encompassing the “theoretical corneal sphere” (C), as evidenced when viewed from above the center of the ball (cornea).

CHAPTER 24  Radial and Astigmatic Keratotomy

initial surgery to improve uncorrected visual acuity (UCVA) to acceptable values. Different nomograms for LRIs exist. Although corneal thickness varies by patient, the most preferred incision depth is 600 µm. Nevertheless, taking a pachymeter measurement at the site of the cut is recommended to prevent accidental perforation into the anterior chamber. Table 24.1 shows the nomogram of Wang et al.26–28 Based on a corneal diameter of 11.5 mm, a chord length of 45 degrees equals 4.5 mm and a chord length of 60 degrees equals 6.0 mm. It is applicable for a refractive cylinder equal to 0.75 D stable within plus or minus 0.50 D on manifest refraction (MR) at least 2 weeks apart, and a mean spherical equivalent cycloplegic refraction within plus or minus 0.75D of emmetropia. Corneal disease that might interfere with corneal wound healing should be ruled out. The length and number of LRIs are chosen based on age and refractive astigmatism. TABLE Nomogram of Wang et al.28 for LRI to 24.1  Correct Refractive Astigmatism After

Astigmatism (D)

Number

Length (Degrees)

2 1 2 2 2 2

45 45 60 45 80 60

With-the-Rule 0.75–1.00

< ≥ < ≥ < ≥

65 65 65 65 65 65

Against-the-Rule/Oblique 0.75–1.00

All

1

45

1.25–2.00

< 65 ≥ 65

2 2

50 40

> 2.00

< 65 ≥ 65

2 2

55 45

*Based on a corneal diameter of 11.5 mm; a chord length of 45 degrees = 4.5 mm and 60 degrees = 6.0 mm).

A • Fig. 24.7

Incisions are centered around the plus axis of the cylinder of the manifest refraction. To ensure correct centration of LRIs, two approaches may be used: (1) When available, the meridional location of prominent landmarks on the conjunctiva or limbus can be noted and drawn relative to the 6 o’clock and 12 o’clock positions. (2) If a clear landmark is not evident by slit lamp biomicroscopy, the corneal and conjunctival epithelia at the limbus at the 90 and 270 semimeridians are marked with a Sinskey hook stained with gentian-violet dye. Intraoperatively, a degree gauge is aligned with the 90 and 270 semi-meridians, enabling identification of the surgical meridians. Incisions are placed in the peripheral cornea just inside the anterior insertion of the conjunctival vessels with a guarded diamond knife set at a depth of 600 µm. Care must be taken to avoid the corneal flap in eyes previously treated with laser in situ keratomileusis (LASIK). Patients should be monitored after 1 day; 1 week; and 1, 3, 6, and 12 months.

Mechanism of Action

Refractive Surgery* Age (Years)

Although the Ruiz procedure was too complicated for routine astigmatic cases, it allowed a great deal to be learned about the mechanics of AK. To investigate the mechanism of action of an AK, let us consider a mini-Ruiz procedure performed to correct 6 D of astigmatism. The patient’s refraction is plano −6 × 180 and the K readings are 40 D @ 180 and 46D @ 90 (Fig. 24.7). Remember, even though the Ruiz procedure is highlighted in this example, the corneal mechanics described are valid for any form of AK. The surgeon must confirm that the astigmatism is regular, that is, that the patient does not have irregular astigmatism. Regular astigmatism is an astigmatism that can be corrected by a cylindrical lens, that is, an astigmatism in which the steeper meridian and flatter meridians are perpendicular to each other (Fig. 24.8). The cause of irregular astigmatism may be an abnormal epithelium (with normal stroma), as in punctate keratopathy, or an abnormal stroma (with normal epithelium), as in keratoconus or stromal injury and scarring. AK corrects only regular astigmatism.

B

Astigmatic keratotomy (AK) model. (A) Preoperative refraction: plano −6 × 180. (B) Following AK incisions placed in the vertical meridian, the coupling ratio is 2 : 1. The diagram shows that both meridians following AK now focus light in front of the retinal plane. The spherical equivalent has become more hyperopic (−3 D to −2 D), but the spherical component has become more myopic (plano to −2 D).  

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Because of its high magnification and very thin mire, manual keratometry was the most accurate method of determining keratoconus and irregular astigmatism for a long time. However, manual keratometry requires an experienced observer. Over the past several years, automated topography and tomography examinations have become the standard of care as screening methods for keratoconus because of their ease of use, colorful permanent display, and technician-oriented approach. In addition to a topographic representation of anterior corneal curvature and its deviation from a perfect sphere, these modern devices also provide a map of the posterior corneal surface (endothelium). Subtle changes in this posterior float may precede

B

A

C

• Fig. 24.8

  Depiction of regular and irregular astigmatism. (A) In regular astigmatism (egg), the steeper and flatter meridians are perpendicular to each other. (B) Irregular astigmatism caused by an epithelial (photo) abnormality like punctate keratopathy (orange). (C) Irregular astigmatism caused by stromal pathology (potato chip).

• Fig. 24.9

anterior surface alterations and may be helpful in determining very early stages of keratoconus (Fig. 24.9). The coupling ratio for a specific AK has to be derived empirically through experience. A surgeon cannot calculate or divine a coupling ratio. Also, the coupling ratio is unpredictable when an AK is performed following a corneal transplant because the encircling scar can change corneal dynamics significantly. Let us return to our patient with a refraction of plano −6 × 180. The flatter meridian of the cornea corresponds to the “plano” term of the refraction, and the “6” corresponds to the steeper meridian of the cornea (see Fig. 24.7). This should seem correct to the surgeon because a steeper meridian creates myopia by focusing light in front of the retina. The plano term of the refraction indicates that light passing through this meridian of the cornea is focused in a line (not a point, because this is an astigmatic cornea) on the retina. With a refraction of plano −6 × 180, the spherical equivalent (sph + 1/2 cyl) is −3 D and the spherical component of the refraction is plano. The spherical equivalent represents the single best representation of the patient’s refractive status. A refraction of plano −6 × 180 can be transposed to the plus cylinder form as −6 + 6 × 90. An AK should be performed on the steeper meridian of the cornea, which usually corresponds closely to the plus axis of the refraction. What happens to the cornea and the patient’s refraction? Because there is a coupling ratio of 2 : 1, we know that 6 D of astigmatism will be corrected with two “units” of flattening for every 1 unit of steepening. Consider the original K readings. The steeper meridian started at 46 D and will be flattened by 4 D, ending up at 42 D. The flatter meridian started at 40 D and will be steepened by 2 D, ending up at 42 D (see Fig. 24.7). The patient has no astigmatism. But how has the patient’s refractive status changed?

  A patient with keratoconus that is extremely mild in the right eye and moderate in the left. Manual keratometry and a trained observer are necessary to diagnose keratoconus in the right eye because the automated topography map of the right cornea appears normal in all respects. Automated topography easily alerts the observer to the keratoconus in the left eye that results in severe irregular steepening of the inferior cornea.

CHAPTER 24  Radial and Astigmatic Keratotomy

TABLE a 24.2  Correction of Six Diopters of Astigmatism

Coupling Ratio

Flatter Meridian (D)b

Steeper Meridian (D)

Postoperative Refraction

1 : 1

40 → 43

46 → 43

2 : 1

40 → 42

3 : 1

40 → 41.5

TABLE 24.3  Coupling Ratios

Coupling Ratio

Procedure

Size

Long corneoscleral crescentic resection

−

1 : 1

−3.00 sph

46 → 42

−2.00 sph

Arcuate incisions

60 degrees

1 : 1

46 → 41.5

−1.50 sph

T-cuts

3.5–4.5 mm long

2 : 1

Ruiz procedure

1.5 mm wide

5 : 1

Ruiz procedure

3 mm wide

3 : 1

Ruiz procedure

4.5 mm wide

2 : 1

Refraction: plano 6 × 180; K readings: 40 @ 180; 46 @ 90. The spherical component becomes myopic by the amount of steepening of the flatter meridian.

a

b

Before the surgery, the 40 D (flatter) meridian was focusing light on the retina. Now, it has steepened to 42 D. Therefore the eye must be more myopic by 2 D. Similarly, the steeper meridian of 46 D is now flatter, thereby focusing light closer to the retina by 4 D, the amount it has flattened. The patient’s refraction is −2 sph (see Fig. 24.7B). It may seem enigmatic at first, but it is totally predictable that the patient’s spherical equivalent has become more hyperopic (−3 D to −2 D) following AK. The minus cylinder has been removed by flattening the cornea faster than it could steepen—remember, that is what a 2 : 1 coupling ratio means. The myopic component has become more myopic, even though the spherical equivalent has become more hyperopic. If the coupling ratio were 1 : 1 (which it is not), the principal meridian of the patient’s cornea would flatten at the same rate as the secondary meridian steepened. The K readings would have become 43 D and the postoperative refraction would have ended up −3 sph; that is, the steeper meridian would flatten by 3 D and the flatter meridian would steepen by 3 D in order to correct the 6 D of astigmatism. Postoperatively, the spherical equivalent would remain unchanged from its preoperative value of −3 D. Similarly, a coupling ratio of 3 : 1 should leave this patient with a refraction after AK of −1.50 D. It is interesting that the variation between an assumption of 2 : 1 coupling and 3 : 1 coupling is only 0.50 D, whereas the difference between a coupling ratio assumption of 2 : 1 and 1 : 1 is 1 D, a twofold increase (Table 24.2). In the next section, we will explore the major significance of assuming different coupling ratios (Table 24.3). AK with a transverse length longer than 5 mm can cause a paradoxical flattening of the steeper meridian. That is, coupling is destroyed and the eye becomes wildly hyperopic. Thus one rule for AK should be not to perform any form of AK with a transverse width greater than 5 mm. In the early 1980s, opposing quadratic T-cuts at the 8.5 mm OZ were used to correct astigmatism, often with poor and very unpredictable results (Fig. 24.10). A working knowledge of coupling allows us to predict the patient’s postoperative refraction even before performing an AK. Here is the method:

363

•

Fig. 24.10  Large quadratic astigmatic incisions. Such incisions, greater than 5 mm in length, can cause a paradoxical flattening of the flatter meridian, resulting in significant unexpected hyperopia.

• The refraction is placed in “minus” cylinder form. • Since the coupling ratio is 2 : 1, dividing the astigmatism by 3 will determine the amount that the flatter meridian will steepen (1 unit). Adding this result (astigmatism/3) to the spherical component will predict the patient’s post-AK refraction. For example: • Preoperative: +1.00 −4.00 × 180; AK performed • Postoperative: −0.33 D • Steps: (1) −4.00/3 = −1.33 D (2) +1.00 + (−1.33) = −0.33 D

The ability to predict a patient’s refraction following AK is very powerful knowledge.

Patient Selection It must be remembered that AK corrects regular astigmatism, not irregular astigmatism. Of course, any other factors limiting good vision must be documented and explained to the patient before AK is performed. For example, LRI is a popular method for correcting small amounts of astigmatism during cataract surgery. These patients may have macular degeneration that may limit postoperative improvement. Today, astigmatic incisions are sometimes performed during femto-cataract surgery.

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TABLE 24.4  Transverse and Arcuate Incisions Nomograms

Astigmatism

OZ

Length

Number Transverse

Number Radial

Nordan Nomogram (Transverse T-Cuts) −85% Depth 1.00–1.50 D

7.0 mm 7.0 mm 7.0 mm

4.5 mm 3.5 mm 4.5 mm

1 (single)* 2 2

1* 2 2

Composite Nomogram (Arcuate Incisions) 1.00–1.50 D

7.0 mm

2.5 mm

40 degrees

2

1.75–2.50 D

7.0 mm

3.0 mm

50 degrees

2

2.75–3.50 D

7.0 mm

3.5 mm

57 degrees

2

3.75–4.50 D

7.0 mm

4.0 mm

65 degrees

2

*Refers to single hemi-meridian: combined radial and transverse incision (see Fig. 24.5B).

matter which side of the meridian it is performed on. Nonopposing AK incisions create irregular astigmatism.

Steeper Corneal Meridian

• Fig. 24.11

  Schematic diagram demonstrating “asymmetric astigmatism” and a variation in the “axis” of the steeper meridian. Two possible astigmatic keratotomy (AK) plans may be considered: treatment of the symmetric astigmatism by asymmetric incisions (three incisions on one side of the visual axis and two on the other) and non-opposing AK incisions (left); or a symmetric approach based on the steeper meridian of the central cornea, 110 degrees, as indicated by manual keratometry and central automated topography (right). A symmetric, opposed AK approach is highly recommended.

Astigmatic Power The astigmatic power to be corrected should be based on the patient’s refraction, and the orientation of the AK should be based on the steeper corneal meridian at the visual axis as determined by keratometry and/or automated topography. The concept of asymmetric astigmatism has been created; it is derived from the observation that an automated topography map often displays hemi-meridians of different powers. This concept is mentioned only so that it can be clinically disregarded in routine cases. Astigmatic incisions should be placed opposing each other according to the nomogram (Table 24.4), and the position of these AK incisions should not be changed according to supposed meridional variations in the cornea outside the functional optical surface of the cornea (Fig. 24.11). An AK performed on the proper meridian has the same effect on that meridian, no

The steeper corneal meridian is easily visualized by automated topography (Fig. 24.12). The steeper corneal meridian may not coincide exactly with the steeper axis of the refraction because of lenticular astigmatism. Theoretically, an AK should be centered on the steeper corneal meridian because the function of the AK is to act perpendicularly to the steeper meridian. Astigmatic incisions not perpendicular to the steeper meridian tend to cause irregular astigmatism and are less predictable. Clinically, a difference of 10 to 15 degrees between the steeper meridian and axis is not important because the T-cuts are long enough to extend across the steeper meridian and have a predictable effect. The surgeon must remember to orient the patient’s head and the operating microscope so that slight disparities of K readings, topography, and patient placement become subtractive, not additive. Degree markers are useful but can only be as precise as their orientation. The surgeon should be able to approximate degrees around the limbus to within 10 degrees. This is easily done by first locating 90 degrees and 180 degrees and then subdividing these sectors. For example, if the 75th meridian is desired, the surgeon can easily establish the 90-degree and 45-degree locations and bisect this sector to find 67.5 degrees. Halfway between 67.5 and 90 degrees is 78.75 degrees (Fig. 24.13).

Front-Cutting Blade Unlike RK, AK of all patterns is best performed with a front-cutting (Russian) blade. All blades for incisional keratotomy should end in a sharp point in order to increase consistency of penetration and to avoid macroperforations. This blade configuration allows the surgeon to better

CHAPTER 24  Radial and Astigmatic Keratotomy

365

• Fig. 24.12  An automated topography map highlights the steeper corneal meridian nicely. This information should be correlated with the patient’s refraction, keratometry, and slit lamp examination.

• Fig. 24.13  A process for estimating the 75th meridian of the cornea, using successive bisection of an angle.

visualize the incisions to be made because a back-cutting (American) blade blocks the surgeon’s view of where the incision is to be made. To achieve an incision depth of 85% to 90%, the frontcutting blade is set at 95% to 100% of the corneal pachymetry at the point where the incision is to be made. The blade is changed when more than a 5% (0.03 mm) change in pachymetry is noted.

Mechanized Arcuate Keratomes and Femtosecond Lasers Several mechanized keratomes were designed to increase the reproducibility of arcuate incisions. The one developed by

Hanna29 has many design features in common with the Hanna trephine and is called the arcuate keratome. Several features provide theoretical superiority to manual knives, including the ability to fix the arcuate length and a centering guide that is also aligned with the steep meridian to ensure proper orientation. In addition, a pair of incisions with different radii can be made by independently setting the location of the two diamond blades incorporated. Its use has been described after penetrating keratoplasty.29–31 A similar instrument, called Arcutome (Duckworth & Kent), was developed by Pallikaris.32 This device has an outer ring to determine the cord length and an inner ring to set the optical zone from 5.0 mm to 10.0 mm in 0.5-mm intervals. Another device, called Astigmatome (Oasis Medical, Inc.), was originally conceived by Terry and has modifications by Schanzlin. Arcuate keratotomy using the Terry astigmatome was a safe and reliable treatment for corneal astigmatism up to −6 diopters.33 Today, several FS lasers allow for an even higher reproducibility of incision site, length, and depth than mechanized keratomes.34,35

Surgical Technique The same principles apply, whether the FS laser, mechanized keratome, or surgical blade is used. The steps of the operative procedure for manually performed AK are listed in Table 24.5. A nomogram of T-cuts and arcuate incisions is provided in Table 24.4. Each step is important. The mark of an excellent surgeon is consistency in approach. Note that the blade is set and the speculum is placed in the eye immediately before commencing the procedure. There is a tendency for surgeons who are learning incisional keratotomy to place the speculum in the eye first and then get ready. The cornea thins as a result of evaporation at a rate of about 0.01 mm per minute. OZ markers are placed concentric with the miotic pupil. To obtain a well-placed 7-mm OZ for AK, a 3-, 5-, 7-mm

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TABLE 24.5  Astigmatic Keratotomy Step by Step

Preoperative: Patient 1. Proparacaine drops: i. pilocarpine 0.5% drops ii. antibiotic drops 2. Patient’s name written on headcover: i. Operative eye dot on forehead 3. Valium, 5 mg p.o.

Surgical Preparation 1. Microscope coaxial 2. Position patient properly, iris parallel to floor 3. Verify patient, chart, eye 4. Proparacaine drops, each eye 5. Optical zone and astigmatic axis marked 6. Pachymetry

Values Read Aloud and Charted 7. Determine bias and blade length

Chart Placed on Patient’s Chest 8. Patient’s eye prepped

Surgery 1. Surgeon dons gloves 2. Sterile handle onto microscope 3. Blade depth set 4. Lancaster speculum in place 5. Copious proparacaine drops per minute (10–20) 6. Note optical zone and astigmatism axis 7. Fixation forceps or ring applied 8. Instruct patient not to follow apparent movement of microscope light 9. Astigmatic keratotomy incisions performed 10. Fixation forceps or ring removed 11. Surgeon retracts diamond blade 12. Irrigation with balanced salt solution only if blood is present in incision

No Irrigation for Incision With Microperforation 13. Antibiotic drops/prednisone drops 14. Lid speculum removed 15. Patient taken to recovery area

OZ marker is more precise than simply a 7-mm OZ marker because the 3-mm portion can be positioned accurately on the miotic pupil. The eye is patched for 12 to 24 hours, and antibiotic/ steroid drops are used every 6 hours for 4 days. Artificial tears are used as desired and the patient is seen the day after surgery. The patient is examined within every 48-hour period until reepithelialization is complete. Nonsteroidal antiinflammatory eye drops have a hypesthetic effect on the cornea and can greatly reduce patient discomfort. Such agents may be used every 6 hours for 1 to 2 days but may tend to reduce epithelial healing if used for an extended length of time. The goal of postoperative care is to accomplish reepithelialization quickly so that topical antibiotic and cortisone medications may be stopped. An AK incision must gape in order to be effective in correcting corneal astigmatism. Therefore AK patients tend

• Fig. 24.14  Astigmatic keratotomy–laser in situ keratomileusis: an incision is performed in the stromal bed after a corneal flap is reflected.

to have foreign body sensation for a few days longer than RK patients. Because of the gaping of the cornea, AK incisions may present by slit lamp as wider scars than RK incisions. Whereas RK incisions fade noticeably with time, AK incisions do so to a much lesser extent.

AK-LASIK Gerten et al36 presented a variation of combined incisional and laser ablative surgery for higher degrees of astigmatic correction. Their two-staged procedure is called AKLASIK.37 As a first step, a corneal flap is created and lifted. Arcuate incisions of 80% of the stromal bed thickness are then performed perpendicular to the steep meridian (Fig. 24.14). The flap is repositioned. After achieving refractive stability, 4–12 weeks later, the flap is relifted and a laser ablation of the stromal bed is performed to correct the residual error. Performing the incisions under a flap may avoid epithelial ingrowth into the incisions. The main advantage of this approach, however, seemed to be a reduced ablation depth as the ablated volume is more evenly distributed between the two meridians. This is because the spherical equivalent after performing the incisions remained almost stable in early clinical trials in agreement with the theoretical principles stated above.38

Complications Infection In AK, topical antibiotics are administered preoperatively, intraoperatively, and postoperatively until epithelialization is complete. If a corneal ulcer does occur, aggressive treatment with fortified antibiotic drops is indicated. Medications are then

CHAPTER 24  Radial and Astigmatic Keratotomy

changed according to the Gram stain and culture reports. The onset of flare and cell in the anterior chamber by slit lamp indicates a more serious corneal ulcer.

Perforation Microperforation during AK is more common than during RK because the transverse incision may be moving toward an area of decreasing corneal thickness. Such microperforations should not be irrigated as this increases the chances of endophthalmitis. The second eye of a proposed bilateral case should not be performed because the potential tragedy of a bilateral endophthalmitis must be avoided.

Undercorrection The patient is monitored until a stable postoperative result is known. This usually takes about 4 to 8 weeks, depending upon the severity of the original refraction. There is no known effective medical treatment for an undercorrected AK. The original incisions can be redeepened if they appear to be grossly shallow, but this is often difficult to ascertain accurately by slit lamp. The surgeon must resist the temptation to continually employ merely a smaller OZ, as irregular astigmatism will result. The additional use of laser ablation on the stromal surface may be a viable option. However, LASIK should be avoided after incisional surgery as flap complications and ectasia may occur.39

Overcorrection Overcorrection following AK means that the preoperative flatter meridian has now become steeper than the new flatter meridian, and the axis of the correcting cylinder has usually changed by about 90°. After a stable refraction has been recorded, the residual astigmatism can be treated with a second surgical procedure perpendicular to the first (Fig. 24.15). However, the surgeon must avoid performing the secondprocedure incision too close to the first because a hexagonal keratotomy-type incision can be created inadvertently, leading to increased myopia and irregular astigmatism. The goal of surgery should be reduced by about 1.00D to 1.50D to avoid another overcorrection.

• Fig. 24.15

  One possibility for treating an overcorrected astigmatic keratotomy (AK) patient. Beware that the AK incisions intended to help an overcorrected AK do not inadvertently join to create a weakened central cornea with irregular astigmatism.

367

If the overcorrection has occurred because the OZ used was too small, and irregular astigmatism exists, then suturing the wounds with interrupted 10-0 nylon for 3 to 4 months may be of value. The reduced gaping of the corneal incisions centrally will improve the patient’s quality of vision and may permanently reduce the astigmatism. Again, additional laser surgery may provide the necessary fine-tuning.

Rotation of Axis With Residual Astigmatism The same principles apply to this situation as to the undercorrection and overcorrection of astigmatism. This situation is often more difficult, however, because the original incisions may preclude an easy pattern of AK to be oriented on the steeper meridian as a result of the original AK incisions.

Irregular Astigmatism Most irregular astigmatism following AK is created by an OZ of less than 7 mm; OZs less than 6 mm are contraindicated because the amount of glare and reduction in quality of vision in mydriatic situations will be substantial. These problems are increased significantly with long arcuate incisions because arcuate incisions gape more than T-cuts. The suturing of such incisions is a good initial attempt at treatment. A lamellar or penetrating corneal transplant may be necessary, with subsequent laser ablation, to achieve the goal of improved, high-quality vision. Undoubtedly, prevention is a better course to follow by not employing a small OZ initially and making 7 mm the standard OZ for astigmatism of 5D or less. This covers the vast majority of AK patients. OZs of less than 7 mm require the patient to be well informed about the compromises between effect and reduced quality of vision.

Recurrent Erosions and Superficial Punctate Keratitis Superficial punctate keratitis occurs frequently after incisional keratotomy. Although some short-term recurrent erosions may also bother the patient for up to several months, such long-term problems are very rare following incisional keratotomy using diamond, rather than metal, blades. Classically, the patient complains of foreign body sensation and photophobia upon arising in the morning, but the symptoms subside as the day goes on; the epithelial defect has reepithelialized. Treatment with artificial tears and lubricating ointment before bed and upon arising, plus tincture of time as the epithelium adheres to the Bowman membrane, is usually sufficient to solve the problem. In fact, incisional keratotomy is not contraindicated in patients with anterior basement membrane dystrophy who are plagued by recurrent corneal erosions. Treatment for a recurrent erosion may range from debridement with a cotton tip applicator and the wearing of a therapeutic contact lens for 6 weeks to focal treatment with a 25-gauge needle tip that perforates the Bowman

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membrane to phototherapeutic keratectomy to promote epithelial adhesion.

References 1. Geggel HS. Arcuate relaxing incisions guided by corneal topography for postkeratoplasty astigmatism: vector and topographic analysis. Cornea. 2006;25(5):545–557. doi:10.1097/01. ico.0000214222.13615.b6. 2. Nubile M, Carpineto P, Lanzini M, et al. Femtosecond laser arcuate keratotomy for the correction of high astigmatism after keratoplasty. Ophthalmology. 2009;116(6):1083–1092. doi:10. 1016/j.ophtha.2009.01.013. 3. Rückl T, Dexl AK, Bachernegg A, et al. Femtosecond laserassisted intrastromal arcuate keratotomy to reduce corneal astigmatism. J Cataract Refract Surg. 2013;39(4):528–538. doi:10. 1016/j.jcrs.2012.10.043. 4. Schiötz H. Ein Fall von hochgradigem Hornhautastigmatismus nach Staarextraction: Besserung auf operativem Wege. Arch Augenheilk. 1885;15:178–181. 5. Lans LJ. Experimentelle Untersuchungen über Entstehung von Astigmatismus durch nichtperforirende Corneawunden. Albrecht Von Graefes Arch Ophthalmol. 1898;45:117–152. 6. Villansenor RA, Stimac GR. Clinical results and complications of trapezoidal keratotomy. J Refract Surg. 1988;4(4):125–131. 7. Fyodorov SN, Agranovsky AA. Long-term results of anterior radial keratotomy. J Ocular Therapy Surg. 1982;1:217–223. 8. Waring GO III, Lynn MJ, Gelender H, et al. Results of the prospective evaluation of radial keratotomy (PERK) study one year after surgery. Ophthalmology. 1985;92:177–198, 307. 9. Lynn MJ, Waring GO III, Sperduto RD, the PERK Study Group. Factors affecting outcome and predictability of radial keratotomy in the PERK study. Arch Ophthalmol. 1987;105:42–51. 10. Waring GO III, Lynn MJ, Nizam A, et al. Results of the prospective evaluation of radial keratotomy (PERK) study five years after surgery. Ophthalmology. 1991;98:1164–1176. 11. Sawelson H, Marks RG. Three-year results of radial keratotomy. Arch Ophthalmol. 1987;105:81–85. 12. Waring GO III, Lynn MJ, McDonnell PJ. and the PERK study group. Results of the prospective evaluation of radial keratotomy (PERK) study 10 years after surgery. Arch Ophthalmol. 1994; 112:1298–1308. 13. Hoffmann RF. The surgical correction of idiopathic astigmatism. In: Sanders DR, Hoffmann RF, Salz JJ, eds. Refractive Corneal Surgery. Thorofare, NJ: Slack; 1986:241–290. 14. Fyodorov SN. Surgical correction of myopia and astigmatism. In: Schacher AR, Levi S, Schacher S, eds. Keratorefraction. Denison, TX: LAL Publishing Co; 1980:141–172. 15. Fyodorov SN, Agranovsky AA. Long-term results of anterior radial keratotomy. J Ocul Ther Surg. 1982;1:217–223. 16. Barraquer JI. Keratomileusis and keratophakia. In: Rycroft PV, ed. Corneoplastic Surgery. New York: Pergamon; 1969. Proceedings of the 2nd International Cornea-Plastic Conference. 17. Barraquer JI. Special methods in corneal surgery. In: King JH Jr, McTigue JW, eds. The Cornea World Congress. Washington, DC: Butterworths; 1965:586–604. 18. Barraquer C, Guiterrez A, Espinosa A. Myopic keratomileusis: short term results. Refract Corneal Surg. 1989;5:307–313. 19. Troutman RC. Microsurgical control of corneal astigmatism in cataract and keratoplasty. Trans Am Acad Ophthalmol Otolaryngol. 1973;77:OP563–OP572.

20. Troutman RC, Swinger C. Refractive keratoplasty: keratophakia and keratomileusis. Trans Am Ophthalmol Soc. 1978;LXXVI: 329–339. 21. Lindstrom RL, Lindquist TD. Surgical correction of postoperative astigmatism. Cornea. 1988;7:138–148. 22. Lindstrom RL. The surgical correction of astigmatism: a clinician’s perspective. Refract Corneal Surg. 1990;6:441–454. 23. Friedlander MH, Rich LF, Werblin TP, et al. Keratophakia using preserved lenticules. Ophthalmology. 1980;87:687–692. 24. Friedlander MH, Safir A, McDonald MB, et al. Update on keratophakia. Ophthalmology. 1983;90:365–368. 25. Merlin U. Curved keratotomy procedure for congenital astigmatism. J Refract Surg. 1987;3:92–97. 26. Budak K, Friedman NJ, Koch DD. Limbal relaxing incisions with cataract surgery. J Cataract Refract Surg. 1998;24: 503–508. 27. Wang L, Misra M, Koch DD. Peripheral corneal relaxing incisions combined with cataract surgery. J Cataract Refract Surg. 2003;29:712–722. 28. Wang L, Swami A, Koch DD. Peripheral corneal relaxing incisions after excimer laser refractive surgery. J Cataract Refract Surg. 2004;30:1038–1044. 29. Hanna KD, Hayward JM, Hagen KB, et  al. Keratotomy for astigmatism using an arcuate keratome. Arch Ophthalmol. 1993;111: 998–1004. 30. Chastang P, Borderie V, Carvajal S, et al. [Surgical treatment of postkeratoplasty astigmatism with the arcuate keratome.]. J Fr Ophtalmol. 1997;20:360–365. 31. Hoffart L, Touzeau O, Borderie V, Laroche L. Mechanized astigmatic arcuate keratotomy with the Hanna arcitome for astigmatism after keratoplasty. J Cataract Refract Surg. 2007;33(5): 862–868. doi:10.1016/j.jcrs.2007.01.031. 32. Pallikaris IG, Xirafis ME, Naoumidis LP, et al. Arcuate transverse keratotomy with a mechanical Arcutome based on videokeratography. J Refract Surg. 1996;12(suppl):S296–S299. 33. Baykara M, Dogru M, Özçetin H. Refractive outcomes after arcuate keratotomy using the Terry astigmatome. J Cataract Refract Surg. 2003;29:2397–2400. 34. Chan TCY, Ng ALK, Cheng GPM, Wang Z, Woo VCP, Jhanji V. Corneal astigmatism and aberrations after combined femtosecond-assisted phacoemulsification and arcuate keratotomy: two-year results. Am J Ophthalmol. 2016;170:83–90. doi: 10.1016/j.ajo.2016.07.022. 35. Loriaut P, Borderie VM, Laroche L. Femtosecond-assisted arcuate keratotomy for the correction of postkeratoplasty astigmatism: vector analysis and accuracy of laser incisions. Cornea. 2015;34(9):1063–1066. doi:10.1097/ICO.0000000000000487. 36. Gerten GVP, Schmiedt K, Oberheide U, et al. Die AK-LASIK: eine neue chirurgische Methode zur Korrektur hoher Astigmatismen. In: DOC. Nürnberg, Germany: DIOmed, Ebelsbach, Germany; 2003. 37. Gerten GVP, Schmiedt K, Oberheide U, et al. Die AK-LASIK: Ergebnisse zur Korrektur hoher Astigmatismen. In: DOC. Nürnberg, Germany: DIOmed, Ebelsbach, Germany; 2004. 38. Schraepen P, Vandorselaer T, Trau R, Tassignon MJ. LASIK and arcuate incisions for the treatment of post-penetrating keratoplasty anisometropia and/or astigmatism. Bull Soc Belge Ophtalmol. 2004;292:19–25. 39. Ghanem RC, Ghanem MA, Bogoni A, Ghanem VC. Corneal ectasia secondary to LASIK after arcuate keratotomy. J Refract Surg. 2013;1–4. doi:10.3928/1081597X-20130313-02.

25 

Conductive Keratoplasty and Laser Thermokeratoplasty MARGUERITE B. MCDONALD AND DIMITRI T. AZAR

Introduction Conductive keratoplasty (CK) and laser thermokeratoplasty (LTK) were originally conceived for the treatment of hyperopia by applying energy to the midperipheral cornea, causing the central cornea to become steeper. LTK has been plagued by a history of regression of refractive effect. The regression of the refractive effect after CK is less than that after LTK, allowing CK to be used to treat presbyopia, the gradual decrease in the range of accommodative amplitude resulting from age-related changes in the crystalline lens.1 A better understanding of corneal and collagen response to heat, combined with improved heat delivery systems, may offer new promise for the future of thermal refractive surgery. The cornea responds to increased temperature by flattening in the area of heating owing to corneal collagen contraction. If the cornea is heated centrally, then flattening occurs in the most optically active part of the cornea, and the refractive power of the cornea decreases, with the eye becoming relatively more hyperopic. This central flattening is the optical effect that has been sought in the treatment of centrally steep keratoconus corneas. When the corneal temperature is increased peripherally, the contracting collagen causes peripheral flattening, with a concomitant beltlike effect and resultant central steepening. The peripheral heating may be carried out in an annular pattern or in multiple radials. In general, the greater the number of peripheral burns or radials and the smaller the optical zone, the greater the central steepening. When peripheral heating is brought in centrally to the range of a 4-mm-diameter optical zone, the effect begins to reverse and central flattening begins.2–4 The optical zone diameter at which central flattening occurs seems to be pattern and modality dependent. For example, the noncontact Ho:YAG laser used in a 32-spot ring at a 3-µm optical zone produces significant central steepening on human cadaver eyes, whereas the same laser used with four to eight spots at a

3-µm optical zone causes central flattening on fresh swine eyes. A pulsed CO2 laser used in a continuous ring pattern at a 5.5-µm optical zone causes central flattening in human cadaver eyes.4–6 In vivo human and animal models demonstrate that the effect of the corneal collagen contraction tends to decrease with time.3,7 This regression of effect may be due to the production of new collagen by corneal fibroblasts, although the actual reason for the apparent reversal of collagen contraction is not clear.7

Historical Background Heat has long been known to affect the curvature of the cornea. Cautery was used to treat keratoconus beginning with Gayet in 1879 and continuing until the first penetrating keratoplasty was performed by Castroviejo in 1936.8 In 1898, Lans first reported using cautery to decrease corneal astigmatism.9 In 1900, Terrien reported using cautery to correct severe astigmatism in an eye with Terrien’s marginal degeneration.10 In 1914, Wray also reported a case of astigmatism successfully treated with corneal cautery.11 In 1933, O’Connor reported the successful, but variable, 10-year follow-up results on a patient with high myopic astigmatism whom he had treated with corneal cautery.12 Rowsey and coworkers reported in 1980 their initial work with a 1.6-MHz radiofrequency probe (the Los Alamos Probe).13–15 This probe used a circulating saline electrode to deliver energy 200 to 400 µm below the surface of the probe, allowing the stroma to be heated with relative sparing of the endothelial and epithelial areas. The recurring problem of regression of effect seen with other thermal keratoplasty procedures also plagued the Los Alamos Probe.16,17 In 1981, Fyodorov (in Moscow) began using superficial peripheral corneal thermal treatments for hyperopia, called radial thermokeratoplasty. By 1984, he and the engineers at the Moscow Research Institute for Eye Microsurgery developed a fine-needle probe for deeper thermal keratoplasty.18 369

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Response of Corneal Collagen to High Temperature Human corneal collagen shrinks when its temperature is increased to 55°C to 58°C.12 The covalent bonds of the primary collagen structure are not disturbed, but the high temperature provides the necessary energy to disrupt the hydrogen bonds of the tertiary collagen structure, allowing the collagen triple helix to partially unwind and form new cross-links between amino acid moieties with different collagen hydration levels.19–26 The actual amount of shrinkage depends on the mechanical tensions on the collagen; in the cornea, the shrinkage is approximately 7%.27 If the temperature of collagen is increased past its shrinkage temperature of 65°C to 78°C, then the contracted collagen relaxes as heat-labile cross-links are hydrolyzed. The aging process increases the number of thermally stable cross-links, raising the temperature required for relaxation of the collagen.24 Further elevation of temperatures can cause the collagen fibers to undergo necrosis. Temperature elevation in the cornea varies by proximity to the heating source. Histopathologic evaluation of human corneas treated with a Gasset thermokeratoplasty probe offers some insight into the changes the cornea undergoes with heating from a 100°C to 130°C surface probe. The Bowman layer appears to be more affected by destruction and abnormalities than would be expected with keratoconus alone.22,23 There is also a marked loss of hemidesmosome complexes between the basement membrane and basal cells, which may be the cause of reepithelialization problems in some thermokeratoplasty cases.24 Other changes included corneal vascularization, epithelial thinning and irregularity, and stromal scarring.22,23

Laser Thermokeratoplasty Multiple types of lasers have been investigated for use in LTK, including hydrogen fluoride,25–27 cobalt:magnesium fluoride,28 erbium:glass,29 carbon dioxide,30–33 and the Ho: Yag diode. For each of these lasers, the light energy is absorbed by water in the corneal epithelium and stroma, and the heat is passively transferred to the stromal collagen. The heating allows collagen shrinkage with subsequent topographic and refractive changes in the cornea (Fig. 25.1).

Holmium:YAG Lasers There were two principal Ho:YAG laser delivery systems for LTK. The first is a contact probe type manufactured by Summit; the second is a noncontact type manufactured by Sunrise Technologies.

Contact Holmium:YAG The contact Ho:YAG laser from Summit Technology emitted infrared electromagnetic energy at the wavelength

• Fig. 25.1

  Appearance of cornea 2 years after laser thermokeratoplasty showing barely perceptible haze.

of 2.06 µm and operates with 300-µs pulses at a repetition frequency of 15 Hz and a pulse power of approximately 19 mJ.34 The laser focally raises the stromal collagen temperature to approximately 60°C by delivering 25 pulses at each treatment location. The laser energy reaches the cornea through a fiberoptic handpiece with a sapphire tip that provides a cone angle of 120 degrees. When the tip is applied to the cornea and laser energy is delivered, it creates a coneshaped zone of collagen contraction with a base diameter at the corneal surface of 700 µm and a depth of 450 µm.

Noncontact Holmium:YAG The noncontact Ho:YAG laser from Sunrise Technologies functioned at a 2.13-µm wavelength with a 5-Hz pulse repetition frequency and a 250-µs pulse duration. The system employs a compact, solid-state laser with a fiberoptic noncontact delivery system mounted to a slit lamp to deliver one to eight simultaneous treatment spots, each approximately 600 µm in diameter. Koch’s in vitro studies with fresh swine eyes and this laser looked at corneal topographic changes with varying treatment zones using four to eight spots, 10 pulses per spot, and an energy density of 8 to 11 J/cm.9,34 The topographic changes were measured with the EyeSys Corneal Analysis System (EyeSys Technologies). Treatment zones of 3.0 and 3.5  mm produced central corneal flattening of up to 9  diopters (D). Treatment zones of 4.0 to 4.5 mm produced no effect, and 5.0  mm or greater treatment zones caused central corneal steepening of over 4 D. The central steepening could be increased by using 16 treatment spots instead of 8 and by placing a second ring of 16 spots around the first. Increasing the energy density of the spots also increased the curvature changes. Astigmatic treatments were made with pairs of laser spots along the flat corneal meridian. Moreira and colleagues treated human eye-bank eyes with the Sunrise noncontact Ho:YAG laser using a 300-µm spot size and a 9 J/cm2 laser energy with a 32-spot treatment ring (four sets of eight spots; each set rotated by 11.25 degrees)

CHAPTER 25  Conductive Keratoplasty and Laser Thermokeratoplasty

371

at 3- to 7-mm treatment zones.5 The central cornea steepened at all of these treatment zones; less steepening occurred in a near-linear fashion with enlarging treatment zones. The treatment ring produced a beltlike contraction effect in the cornea. Moreira et al. also conducted rabbit histopathologic studies of the effects of noncontact Ho:YAG laser energy, as described earlier in the section on nonrefractive corneal responses to heat. The difference in refractive results between Koch’s and Moreira’s work indicates that at smaller treatment zones factors such as spot size, spot number, and energy density play a role in the refractive outcome.

Clinical Outcomes of LTK Noncontact LTK treatments for hyperopia have been reported by several groups.34–46 The summary of the results of 612 eyes from 379 patients who participated in both the IIa and III US studies after a 2-year follow-up has been presented by Aker and Brown.43 In this extended trial, no eye lost more than two lines of best spectacle-corrected visual acuity (BSCVA). No laser-related adverse effects were reported; there was a transient increase in intraocular pressure. Corneal edema (0.2%) and pain (0.2%) were also reported, as well as a mild foreign body sensation, requiring artificial tears in a small number of eyes, mostly during the first postoperative month. Astigmatism of less than 2.00 D was induced in 4.2% of individuals in the second year. Regarding efficacy, at the 2-year examination, the mean improvement in distance uncorrected visual acuity (UCVA) was 2.8 lines, with 69% of patients having at least 2 lines of improvement. The attempted correction in this study was emmetropia in the early posttreatment period (third to sixth month). Two years postoperatively, 62.5% of eyes were within 1.00 D of emmetropia, from 11% preoperatively. The remaining 37.5% of eyes not within 1.00 D of emmetropia were all undercorrected, mostly by up to 2.00 D (4% of eyes undercorrected by > 2.00 D). The rate of postoperative refraction change was much higher during the first 3 months, around 0.3 D per month, declining to 0.1 D per month thereafter during the 2-year follow-up period. Regression of the original refractive effect after LTK had led to the development of CK, in which the regression is less severe.

Conductive Keratoplasty The ViewPoint CK System (Fig. 25.2) used to perform the CK procedure consists of a radiofrequency energygenerating console, a handheld, reusable, pen-shaped handpiece attached by a removable cable and connector, a foot pedal that controls release of radiofrequency energy, and a speculum that provides a large surface for an electrical return path. Attached to the probe is a single-use, disposable, stainless-steel, Keratoplast tip, 90 µm in diameter and 450 µm long, that delivered the current directly to the corneal stroma (Fig. 25.3). The tip has a proximal bend of

• Fig. 25.2

  The ViewPoint conductive keratoplasty system consists of a 14-lb portable console, a handpiece that holds the Keratoplast Tip, a corneal marker, a choice of 3 speculae, and a foot pedal. The speculum is a return path for the radiofrequency energy.

• Fig. 25.3

  The single-use Keratoplast Tip, 450 µm long and 90 µm wide, with a cuff that ensured correct depth of penetration.

45 degrees and a distal bend of 90 degrees to allow access to the cornea over the patient’s brow and nasal regions. At the very distal portion of the tip is an insulated stainlesssteel stop (cuff) that ensures correct depth of penetration.

Conductive Keratoplasty Procedure (Video 25.1) The procedure was performed with topical anesthesia. The surgeon places a lid speculum in the eye to be treated to obtain maximal exposure and provide the electrical return path. While the patient fixates on the microscope’s light, the cornea is then marked with a gentian-violet-dampened CK marker. Centration with the marker is very important, as is confirmation of satisfactory sphericity with the ring light. The surgeon then inserts the Keratoplast tip into the stroma at defined spots in a ring pattern around the peripheral cornea according to the supplied nomogram (Fig. 25.4). Placement of the Keratoplast tip perpendicular

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Pre-op N=133 16 spots (1.00 – 1.625 D)

Month 1 N=129

100

90 81

Percent

80

24 spots (1.75 – 2.25 D)

Month 6 N=130

96 98 89

77

56

60

47 37

40 20 1 0

Month 12 N=64

J1 or better

15

7 J2 or better

J3 or better

J5 or better

• Fig. 25.5 Optical zone 6 mm OZ 7 mm OZ 8 mm OZ

• Fig. 25.4

  Sixteen- and 24-spot conductive keratoplasty presbyopia nomograms. Sixteen spots are applied at the 6- and 7-mm optical zones for correction of 1.00 to 1.625 D of correction and 24 spots are applied at the 6-, 7-, and 8-mm optical zones for 1.75 to 2.25 D.

to the corneal surface at the treatment markings is also highly important. The cuff around the probe, which settles perpendicular to the cornea, helps to achieve perpendicular placement. Light pressure must be applied until the tip penetrates the stroma to its insulator stop. Energy is applied by depressing the foot pedal. An increasing number of spots and rings are used for higher amounts of correction. Postoperative care includes application of a topical antibiotic solution, a topical nonsteroidal antiinflammatory agent, and artificial tears, as needed.

Visual Outcomes The FDA clinical study for approval of CK for the correction of presbyopia (NearVision CK) was conducted in five centers in the United States. The treatment goal was to improve near vision in the nondominant eye of hyperopic or emmetropic presbyopes and, if needed, to improve distance vision in the dominant eye. A total of 150 patients (188 eyes) with symptoms of presbyopia were enrolled and treated with CK; 112 eyes were treated for near vision correction and 38 eyes for distance correction as well as near (bilateral correction). The average patient age was 53 years old; 96% of patients were white, and 61% were female. The mean intended correction for eyes treated for near vision was +2.03 D ± 0.63 D. The range of correction was +0.75 D to 3.00 D. Eyes treated for partial near correction (intermediate distance target) were excluded from the analysis (n = 14).

  Binocular uncorrected visual acuity near following conductive keratoplasty presbyopia treatment.

Visual Acuity Of the eyes treated for near vision with an intended correction of +1.25 to 2.25 D (16–24 CK spots), 105 of 130 (81%) and 49 of 64 (77%) had J2 or better binocular for near at 6 months and 12 months, respectively (Fig. 25.5). For UCVA near of J3 or better, the statistics were 117 of 130 (90%) and 57 of 64 (89%), compared with 20 of 133 (15%) that had this uncorrected binocular near acuity preoperatively. Binocular UCVA distance results showed 95% and 97% with 20/20 or better acuity at 6 and 12 months, respectively, 100% and 98% for 20/25 or better at 6 and 12 months, respectively, and 100% with 20/32 or better at 6 and 12 months (Fig. 25.6). The combination of binocular UCVA distance of 20/20 or better with UCVA near of J2 or better was achieved by 100 of 130 (77%) at 6 months and 48 of 64 (75%) at 12 months. For combined binocular UCVA distance of 20/20 or better with UCVA near of J3 or better, the statistics were 110 of 130 (85%) at 6 months and 56 of 64 (87%) at 12 months (Fig. 25.7). The 6-month cohort of patients showed no loss of contrast sensitivity under mesopic conditions. BSNVA before CK compared with BSCVA following CK was unchanged through postoperative month 12. Also, BSCVA before CK compared with UCVA near following CK was unchanged through postoperative month 12.

Safety At 1 month, 2% of the treated eyes showed loss of more than two lines of BSCVA distance; this incidence fell to 0% for all subsequent months. There were no cases of BSCVA worse than 20/40, increases of 2.00 D or > 2.00 D of cylinder, or eyes that had 20/20 or better BSCVA preoperatively that had worse than 20/25 postoperatively. Postoperative increases in absolute cylinder were generally 1.50 D or less and decreased with time. At 1 month,

CHAPTER 25  Conductive Keratoplasty and Laser Thermokeratoplasty

Preop n=147

Month 1 n=142

98

98

Month 12 n=76 100 100

100

100

99 98

97

96 Percent

Month 6 n=144

95

94 92

92

88

20/20 or better

20/25 or better

20/32 or better

• Fig. 25.6  Binocular uncorrected visual acuity distance following conductive keratoplasty presbyopia treatment.

Preop n=133

Month 1 n=128

Month 6 n=130

Month 12 n=64

100 85 87 77 75

96 Percent

Patient Satisfaction A questionnaire following the CK procedure showed that most patients reduced spectacle dependence. After the CK procedure, 90% of patients could see the computer screen without spectacles, 86% could see menus, and 86% could read newspaper-sized print (approximately J5 or 8-point font size). This attained the goal of the CK procedure, which was to allow the patient to perform most daily tasks without spectacles.

References

90

94

51

45

92 90 88

373

1 20/20 & J1 or better

6 20/20 & J2 or better

14 20/20 & J3 or better

• Fig. 25.7  Binocular combined uncorrected visual acuity distance and near following conductive keratoplasty presbyopia treatment.

22 of 74 (30%) showed an increase of cylinder of 1.00 to 1.50 D; this incidence fell to 7 of 77 (9%) at 6 months. At month 6, no eyes showed a cylinder increase of 1.75 D or greater. No intraoperative complications or adverse events occurred during any of the surgeries.

Stability Stability data are shown here from the FDA CK hyperopia study because there was a longer period of follow-up than for the presbyopia study. The mean changes in refraction in diopters per 3-month postoperative interval and the mean changes per month decrease with time. When these data were analyzed by mean change of refraction using paired differences, CK showed a nominal change per month between the 12- and 24-month visits.

1. Glasser A, Campbell MC. Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia. Vision Res. 1999;39:1991–2015. 2. Neumann AC, Sanders DR, Salz JJ, et al. Effect of thermokeratoplasty on corneal curvature. J Cataract Refract Surg. 1990;16: 727–731. 3. Schachar RA. Radial thermokeratoplasty. Int Ophthalmol Clin. 1991;31:47–57. 4. Koch DD, Berry MJ, Vassiliadis A, et  al. Non-contact holmium:YAG laser thermal keratoplasty. In: Salz JJ, McDonnell PJ, McDonald MB, eds. Corneal Laser Surgery. St Louis: MosbyYear Book; 1995:247–254. 5. Moreira H, Campos M, Sawusch MR, et al. Holmium laser thermokeratoplasty. Ophthalmology. 1993;100:752–761. 6. Chandonnet A, Bazin R, Sirois C, et al. CO2 laser annular thermokeratoplasty: a preliminary study. Lasers Surg Med. 1992;12:264–273. 7. Feldman ST, Ellis W, Frucht-Pery J, et al. Regression of effect following radial thermokeratoplasty in humans. Refract Corneal Surg. 1989;5:288–291. 8. Gasset A. Changes in corneal curvature associated with thermokeratoplasty. In: Schachar RA, Levy NS, Schachar L, eds. Keratorefraction. Denison, TX: LAL Publishing; 1980:59–64. 9. Lans LJ. Experimentelle Untersuchungen über die Entstehung von Astigmatismus durch nicht-perforierende Corneawunden. Graefes Arch Klin Exp Ophthalmol. 1898;45:117–152. 10. Terrien F. Dystrophie marginale symétrique des deux cornées avec astigmatisme regulier consécutif et guérison par la cauterisation ignée. Arch Ophthalmol. 1900;20:12. 11. Wray C. Case of 6 D of hypermetropic astigmatism cured by the cautery. Trans Ophthalmol Soc UK. 1914;34:109–110. 12. O’Connor R. Corneal cautery for high myopic astigmatism. Am J Ophthalmol. 1933;16:337. 13. Rowsey JJ. Radiofrequency probe keratoplasty. In: Schachar RA, Levy NS, Schachar L, eds. Keratorefraction. Denison, TX: LAL Publishing; 1980:65–76. 14. Rowsey JJ, Gaylor JR, Dahlstrom R, et al. Los Alamos keratoplasty techniques. Contact Intraocul Lens Med J. 1980;6:1–12. 15. Rowsey JJ, Doss JD. Preliminary report of Los Alamos keratoplasty techniques. Ophthalmology. 1981;88:755–760. 16. McDonnell PJ, Garbus J, Romero JL, et al. Electrosurgical keratoplasty: clinicopathologic correlation. Arch Ophthalmol. 1988; 106:235–238. 17. Rowsey JJ. Electrosurgical keratoplasty: update and retraction. Invest Ophthalmol Vis Sci. 1987;28:224. 18. Caster AI. The Fyodorov technique of hyperopia correction by thermal coagulation: a preliminary report. J Refract Surg. 1988;4: 105–108.

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19. Flory PJ, Garrett RR. Phase transitions in collagen and gelatin systems. J Am Chem Soc. 1958;80:4836–4845. 20. Deak G, Romhanyi G. The thermal shrinkage process of collagen fibres as revealed by polarization optical analysis of topooptical staining reactions. Acta Morphol Acad Sci Hung. 1967;15:195–208. 21. Verzar F, Zs-Nagy I. Electronmicroscopic analysis of thermal collagen denaturation in rat tail tendons. Gerontolgia. 1970;16: 77–82. 22. Allain JC, Le Lous M, Cohen-Solal L, et al. Isometric tensions developed during the hydrothermal swelling of rat skin. Connect Tissue Res. 1980;7:127–133. 23. Aquavella JV, Smith RS, Shaw EL. Alterations in corneal morphology following thermokeratoplasty. Arch Ophthalmol. 1976; 94:2082–2085. 24. Fogle JA, Kenyon KR, Stark WJ. Damage to epithelial basement membrane by thermokeratoplasty. Am J Ophthalmol. 1977;83: 392–401. 25. Choi B, Kim J, Thomsen SL, et al. Impedance studies on dynamics of CK lesion formation. IEEE Trans Biomed Eng. 2002; 49(12):1610–1616. 26. Berry MJ, Fredin LG, Valderrama GL, et al. Temperature distributions in laser-irradiated corneas. Invest Ophthalmol Vis Sci. 1991;32(abstracts):994. 27. Koch DD, Padrick TD, Halligan DT, et al. HF chemical laser photothermal keratoplasty. Invest Ophthalmol Vis Sci. 1991;32(abs tracts):994. 28. Koch DD, Padrick TD, Menefee RF, et al. Laser photothermal keratoplasty: nonhuman primate results. Invest Ophthalmol Vis Sci. 1992;33(abstracts):768. 29. Horn G, Spears KG, Lopez O, et al. New refractive method for laser thermal keratoplasty with the Co:MgF2 laser. J Cataract Refract Surg. 1990;16:611–616. 30. Kanoda AN, Sorokin AS. Laser correction of hypermetropic refraction. In: Fyodorov SN, ed. Microsurgery of the Eye: Main Aspects. Moscow, Russia: MIR Publishers; 1987. 31. Kenyon KR. Histological changes in Bowman’s membrane associated with thermokeratoplasty. In: Schachar RA, Levy NS, Schachar L, eds. Keratorefraction. Denison, TX: LAL Publishing; 1980:51–57.

32. Householder J, Horwitz LS, Murillo A, et al. Laser induced thermal keratoplasty. SPIE Proc. 1994;1066:18–23. 33. Beckman H, Fuller TA, Boyman R, et al. Carbon dioxide laser surgery of the eye and adnexa. Ophthalmology. 1980;87:990–1000. 34. Thompson VM, Seiler T, Durrie DS, et al. Holmium:YAG laser thermokeratoplasty for hyperopia and astigmatism: an overview. Refract Corneal Surg. 1993;9(suppl):S134–S137. 35. Peyman GA, Larson B, Raichand M, et al. Modification of rabbit corneal curvature with use of carbon dioxide laser burns. Ophthalmic Surg. 1980;11:325–329. 36. Durrie DS, Schumer DJ, Cavanaugh TB. Holmium:YAG laser thermokeratoplasty for hyperopia. J Refract Corneal Surg. 1994; 10(suppl):S277–S280. 37. Seiler T, Matallara M, Bende T. Laser thermokeratoplasty by means of a pulsed Holmium: YAG laser for hyperopic correction. Refract Corneal Surg. 1990;6:335–339. 38. Seiler T, Matallana M, Bende T. Laser coagulation of the cornea with a holmium:YAG laser for correction of hyperopia. Fortschr Ophthalmol. 1991;88:121–124. 39. Thompson V. Holmium:YAG laser thermokeratoplasty for correction of astigmatism. J Refract Corneal Surg. 1994;10(suppl):S293. 40. Durrie DS, Schumer DJ, Cavanaugh TB. Holmium:YAG laser thermokeratoplasty for hyperopia. J Refract Corneal Surg. 1994; 10(suppl):S277–S280. 41. Koch DD, Abaica A, Menefee RF, et al. Ho:YAG laser thermal keratoplasty: in vitro experiments. Invest Ophthalmol Vis Sci. 1993; 34(abstracts):1246. 42. Koch DD (personal communication, June 1996). 43. Koch DD, Berry MJ, Vassiliadis A, et al. Laser thermal keratoplasty for correction of astigmatism and myopia. In: Salz JJ, McDonnell PJ, McDonald MB, eds. Corneal Laser Surgery. St Louis, MO: Mosby-Year Book; 1995:274–276. 44. Aker AB, Brown DC. Hyperion laser thermokeratoplasty for hyperopia. Int Ophthalmol Clin. 2000;40(3):165–181. 45. Rocha G, Castillo JM, Sánchez-Thorin JC, et  al. Two-year followup of noncontact holmium laser thermokeratoplasty for the correction of low hyperopia. Can J Ophthalmol. 2003;38:385–392. 46. Alió JL, Ismail MM, Sánchez Pego JL. Correction of hyperopia with non-contact Ho:YAG laser thermal keratoplasty. J Refract Surg. 1997;13:17–22.

26 

The Intrastromal Corneal Ring Segments DAVID J. SCHANZLIN, BAVAND YOUSSEFZADEH, STEVEN M. VERITY, AND EVERARDO HERNÁNDEZ-QUINTELA

Introduction Several methods of altering the anterior corneal curvature to modify the refractive status of the eye have been developed. In 1987, Reynolds began experimenting with implanted rings within the corneal stroma, introducing the concept of an intrastromal corneal ring (ICR) as a refractive device with the potential to correct myopic and hyperopic refractive errors.1 Finite element modeling analysis demonstrated that intrastromal rings induce central corneal flattening by acting as a space-occupying element within the corneal stroma. The spacer effectively produces a shortening of the central corneal arc length.2 Because there is no tissue removal associated with corneal flattening, the normal physiologic prolate shape of the cornea is maintained.3 The ICR’s flattening effect has an important role in the management of keratoconus and has been proved to be a safe and effective technique. The types of ICRs most commonly used are Keraring (Mediphacos; Fig. 26.1) and Intacs (Addition Technologies; Fig. 26.2). Characteristics of these types of ICRs are shown in Table 26.1. The Intacs SK and Myoring (Dioptex), a 360-degree continuous full-ring implant placed into a corneal pocket, are usually indicated in advanced keratoconus when a more prominent effect is desired.

Results of Clinical Trials With the Intrastromal Corneal Ring Nonfunctional Eye Study To evaluate the safety and efficacy of the ICR, a phase I clinical trial was initiated in July 1991.4 In this study, the ICR was well tolerated in all patients with no complications that necessitated its removal. There were no problems with wound healing after implantation of the device. There were

no instances of implant extrusion, undue inflammation, or stromal thinning throughout the 12-month follow-up period. The ICR was noted to induce a mean keratometric flattening and the retinoscopic spherical equivalence was reduced. These parameters appeared stable throughout the follow-up period.

Sighted Eye Studies After phases I, II, and III and development from 360-degree rings to small arcuate segments to correct corneal astigmatism,5–7 a new paired 150-degree arcuate segment device was developed. Titration of the refractive correction was achieved by varying the device thickness. The results of these studies verified the utility of ICRs as a method to alter the anterior corneal curvature and refractive status of the eye. The ICR material is well tolerated and does not produce deleterious alterations in the nutritional or metabolic activity of the cornea when placed at the appropriate depth.8 There have been no significant alterations of intraocular pressure (IOP) associated with the ICR. Experimental studies have shown that placement of the ICR device does not interfere with accurate measurement of IOP. In patients, no differences between Goldman and Tonopen tonometry measurements have been noted.9 The 150-degree paired arcuate device tested in the clinical trials was approved by the US Food and Drug Administration (FDA) in April 1999, at which time the name Intacs (Keravision) was adopted. Ferrara ICR segments or Keraring (Mediphacos) are variants of Intacs, which have a triangular cross-section and work like a prism, reflecting away light that hits the rings (Fig. 26.3).10 The biomechanical corneal effect of ICR implantation has been studied by Piñero et al.11 through the Ocular Response Analyzer (ORA). A case series of 45 consecutive keratoconic eyes were retrospectively analyzed after the 375

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Keraring ICR implantation by femtosecond (FS) laser. Significant changes in ORA parameters were observed 3 months after surgery. Preoperative corneal hysteresis (CH) and corneal resistance factor (CRF) were correlated with postoperative corneal high-order aberration. It was observed that corneal biomechanical changes after ICR implantation are not maintained in all cases in a medium to long-term follow-up. Some corneas may continue to show optical

•

Fig. 26.1  Keraring intracorneal ring segments implanted in the cornea of a patient with keratoconus.

deterioration owing to biomechanical alterations despite ICR implantation. The effect of Keraring ICR mechanical implantation on the quality of life of patients with keratoconus have been studied by de Freitas Santos Paranhos et al.12 through the National Eye Institute Refractive Error Quality of Life (NEI-RQL) instrument. The different items in the NEI-RQL scale that have improved include “clarity of vision,” “far vision,” “near vision,” “activity limitations,” “appearance” and “satisfaction with correction.” This study has shown a positive impact on patients’ quality of life after ICR implantation. There have been some reports of bacterial keratitis after Keraring ICR implantation; some of these patients may require penetrating keratoplasty.13 Viral keratitis have also been reported in a patient with a history of herpetic keratitis 5 years prior to ICR implantation.14 Other complications reported after Intacs implantation include corneal thinning and segment exposure (6/20), anterior chamber perforation (1/10), dense corneal infiltrate (1/20),15 and corneal melting with ICR extrusion.16 Despite these sight-threatening complications that both patients and clinicians must be aware of, they are encountered infrequently. Tognon et al.17 analyzed the visual outcomes of 1222 eyes from 1196 patients that received a Keraring ICR, with either manual (mechanical) implantation or FS laser–assisted implantation, for which only 67 patients experienced surgical complications, including: external environment or anterior chamber perforation, late (≥30 days) or early infection, late or early segment extrusion and malposition/movement of the intrastromal corneal ring segments after the procedure.

• Fig. 26.3 • Fig. 26.2

  Intacs intracorneal ring segments implanted in the cornea of a patient with keratoconus.

  Cross-sectional triangular shape of a Keraring intracorneal ring segment that generates a prismatic effect, reducing the incidence of glare and halos. (Courtesy of Mediphacos, Belo Horizonte, MG, Brazil.)

TABLE 26.1  Intracorneal Ring Features

Designs

Intacs

Intacs SK

Keraring SI5

Keraring SI6

Arc length (degrees)

150–210

90–150

90–355

90–210

Cross-section

Rounded

Rounded

Triangular

Triangular

Thickness (mm)

0.25–0.45

0.25–0.50

0.15–0.35

0.15–0.35

Optical zone (mm)

7

6

5

5.5–6

CHAPTER 26  The Intrastromal Corneal Ring Segments

Studies performed by Piñero et al.18 through multiple regression analysis have suggested that the monograms for selection of the ICR in keratoconus should not only be based on refraction and subjective appearance of the corneal topographic pattern but rather the corneal should also be considered.

Removal and Exchanges (Video 26.5) Intacs is an additive refractive procedure not involving the removal of corneal tissue. Removal of the implanted device has been found to result in a return to the baseline refractive error.19,20 Data from 46 eyes in the clinical trials that underwent explantation of the device were analyzed for visual acuity and refractive status. The main indication for removal was unsatisfactory visual symptoms. Three months after removal of the device, 97% of eyes returned to within 1 diopter of their baseline manifest spherical equivalent refraction and 90% of eyes were within two lines of their preoperative uncorrected visual acuity (UCVA).20 No patient had a loss of more than two lines of best spectacle-corrected visual acuity (CDVA). Topographic change stability induced by an ICR may be partially maintained in some cases after its removal when ICR implantation is combined with same-day corneal collagen cross-linking in keratoconus.21 Alternative refractive procedures may be safely performed on patients after Intacs removal.22 Adjustment of the refractive effects of Intacs placement can be achieved by exchanging devices of greater or smaller thickness, greater or smaller arc length, or even by simply rotating the device.23,24 The potential for visual improvement by replacing the Intacs with the Keraring in patients with keratectasia has been studied by Bali et al.25 in a 10-eye (nine patients) retrospective case series. This exchange procedure appeared to be safe and provided an increase in corrected distance visual acuity (CDVA) in some eyes. The authors believe that this is due to the change in corneal asphericity in their cohort. Another alternative, explored by Chan and Hersh,26 is to remove and reposition the Intacs ICR; the repositioning of ICRs was based on corneal topography maps.

Prognosis Factors The evaluation of functional outcomes after 1 year of Ferrara ICR FS laser–assisted implantation for treatment of keratoconus have shown a greater efficiency for patients with moderately advanced asymmetric keratoconus with an initial visual acuity (VA) of less than 0.4 (decimal scale).27 Vega-Estrada et al. analyzed the outcomes of ICR implantation of 611 eyes of 361 keratoconic patients that were classified according to their preoperative CDVA. Their results support other studies28 in which patients with severe preoperative CDVA alteration showed greater improvement. The depth of tunnel creation has an effect on potential complications, such as corneal thinning and ring extrusion.

377

As reported by Sadigh et al.,29 the depth of Keraring ICR mechanical implantation in patients with keratoconus has no effect on BCVA, UCVA, keratometry, and refractive cylinder as long as the ICR is implanted from 40% to 80% of corneal thickness. These findings are different from a study performed by Hashemi et al.,30 in which patients with post-LASIK ectasia underwent Intacs implantation. Parameters evaluated included CDVA, UCVA, mean refractive spherical equivalent (MRSE), keratometries, and topographic cylinder. Improvement was compromised when the implantation depth was greater than or equal to 80% and less improvement was found when ICRs were implanted between 40% and 59% of stromal thickness. Atopic dermatitis has been associated with an increased ICR extrusion, probably related to increased levels of MMP-9 and MMP-2 in the tear fluid, resulting in corneal melting. Patients with ICRs suffering from atopic dermatitis should be closely followed and given appropriate instructions to seek ophthalmologic treatment for ocular symptoms.16

Surgical Technique (Videos 26.1 to 26.3) There are two different methods for implantation of ICRs into the deep stroma: mechanical and FS laser–assisted. The FS laser was first reported for Intacs ICR implantation in 2006 by Rabinowitz et al.,31 who stated that “Inserting Intacs using the femtosecond laser to create the channels is as effective as using the mechanical spreader” (p. 764). The Intacs and Keraring procedures are performed using topical anesthesia. The eye is prepped and draped in the usual sterile fashion with isolation of the lid margins and lashes from the surgical field. The corneal center is marked by indentation of the epithelium with a Sinskey hook. The peripheral corneal thickness is measured over the incision site by ultrasonic pachymetry. The incision site is usually indicated by the steep keratometric axis. A diamond knife set from 70% to 80% of the thinnest tunnel corneal path is used to create an incision that will allow introduction of the channeling tool. For each of the ICR type, the intrastromal channel is created with a proprietary set of instruments. In the case of Intacs ICR implantation, a vacuum-centering device is applied to the globe; for the Keraring ICR, the tunnel dissection is performed manually. A stromal separator tool is then introduced through the incision in the clockwise direction to produce a 180-degree intrastromal channel in the midperipheral cornea. This step is repeated in the other direction to produce a counterclockwise channel. For Intacs ICR implantation, the vacuum-centering device is then removed and the Intacs segments are dialed into the intrastromal channel. The corneal incision is closed with 10-0 nylon sutures. A bandage soft contact lens may be placed on the eye for comfort and to aid in postoperative healing of the incision site. Keraring ICRs are implanted without the need of a vacuum device; their effect is based on the same principle as Intacs, achieving comparable outcomes on refractive,

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topographic, and optical quality measurements. Based on Kaya et al.32 data, patients who underwent Keraring ICR implantation showed a greater decrease in scotopic contrast sensitivity under glare. This finding was significantly correlated with pupil diameter. Several studies have compared the outcomes of mechanical and FS laser–assisted tunnel creation for ICR implantation in eyes with keratoconus. The visual and refractive outcomes have been reported to be similar between these two procedures.33

Therapeutic Applications (Video 26.4) Since ICRs became available, applications for correction of visual loss associated with keratoconus, pellucid marginal degeneration, post-LASIK ectasia, corneal instability post– radial keratotomy, and residual refractive errors after maximal photorefractive keratectomy (PRK) or LASIK have been explored. The ICR segments appear to reinforce the keratoconic cornea and the space-occupying effect of the device in tissue produces a more regular corneal topography. The regularization of the corneal shape makes the refractive error more amenable to standard spherocylindrical spectacle or contact lens correction, obviating the need for penetrating keratoplasty. Improvements in keratoconus patients have been observed in studies in the United States using the limited selection of available Intacs sizes. Reversibility and adjustability of the refractive effect has been observed in keratoconic corneas, as has been seen in patients with spherical myopia.34 A number of published case reports have demonstrated the ability of Intacs to improve the visual acuity in patients with corneal ectasia associated with pellucid marginal degeneration.35 Corneal ectasia can occur after ablation of the central corneal stroma in LASIK.36 Topographic changes are characterized by marked elevation of the posterior corneal surface. Implantation of Intacs in these eyes has resulted in improved refractive outcomes and improvement in visual acuities without complications.37 ICRs have been used for astigmatic correction after penetrating keratoplasty. Bastos Prazeres et al.38 evaluated the effect of FS laser–assisted ICR implantation for the correction of residual astigmatism after penetrating keratoplasty (PKP) in 14 cases. An improvement in UCVA was observed in 85.7% of cases at 6 months after surgery. This procedure had reduced the refractive astigmatism and maximum corneal curvature. Koppen et al.39 have used ICRs to obtain corneal stabilization after radial keratotomy in a patient with persistent diurnal visual fluctuations. Intacs ICRs were implanted inferiorly in both corneas; stabilization was achieved and the patient was satisfied. Intacs ICRs have also been shown to be very stable over the years. In 2012, Bedi et al. looked at the refractive and

topographic stability of Intacs ICRs in eyes with progressive keratoconus. This study showed that 91.3% of the eyes that had undergone Intacs implantation had no progression between 1-year and 5-year follow-up.40 In 2006, Alio et al. did a retrospective study comprised of 13 eyes showing that Intacs not only increased BSCVA but also decreased the inferior-superior asymmetry with stability up to 3 years. Also, patients noticed a decrease of K values throughout the study.41 Another long-term retrospective study done in 2006 by Kymionis et al. looked at 17 eyes. This study found no late postoperative complications and showed that UCVA, BSCVA, and refraction improved in most of the patients. The implantation of ICRs In young patients with progresive keratoconus may be associated with crosslinking in order to stabilized the cornea, as regression of the effect has been demonstrated after ICRs in young patientes.42,43 Very few publications report on complications induced by ICR implantation. Rare cases of corneal infection44,45 and stromal melting46,47 have been described. Even though Intacs placement is known to be a safe procedure, it does come with certain risks.48–50 Intraoperative complications can start with the placement of Intacs ICRs either too close to each other or too close to the wound. These complications can lead to erosion through the corneal stroma or wound gape, leading to infection.48 Also, intraoperatively, there can be superficial placement of Intacs ICRs or perforation through the anterior chamber. Postoperatively, infection can occur because of a wound gape or loose stitch. In 2010, Mulet et al. evaluated the incidence of acute microbial keratitis after intrastromal corneal ring segment; of the 134 eyes, only 1.4% had acute microbial keratitis.50 Patients with large pupils may complain of halo and glare. Some other postoperative complications include photophobia, vascularization of the wound, inflammation, and loss of CDVA. Even though complications are rare, it is of utmost importance to explain to patients all the risks alongside the benefits of Intacs ICRs.48–50

References 1. Fleming JF, Reynolds AE, Kilmer L, et al. The intrastromal corneal ring: two cases in rabbits. J Refract Surg. 1987;3: 227–232. 2. Pinsky PM, Datye DV, Silvestrini TA. Numerical simulation of topographical alterations in the cornea after intrastromal corneal ring (ICR) placement. Invest Ophthalmol Vis Sci. 1995;36(suppl):308. 3. Holmes-Higgin DK, Baker PC, Burris TE, Silvestrini TA. Characterization of the aspheric corneal surface in ICRS patients. Invest Ophthalmol Vis Sci. 1998;19:S74. 4. Assil KK, Barrett AM, Fouraker BD, et al. One-year results of the intrastromal corneal ring in nonfunctional human eyes. Arch Ophthalmol. 1995;113:159–167. 5. Verity SM, Ito M, Quantock AJ, et al. ICR (intrastromal corneal ring) astigmatism arcs for the correction of corneal astigmatism: an eyebank study. Invest Ophthalmol Vis Sci. 1996;37: S573.

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6. Durrie DS, Asbell PA, Schanzlin DJ. The ICR (intrastromal corneal ring). One-year results of a phase II study in myopic eyes. Ophthalmology. 1995;102:101. 7. Schanzlin DJ, Abbott RL, Asbell PA, et al. Two-year outcomes of intrastromal corneal ring segments for the correction of myopia. Ophthalmology. 2001;108:1688–1694. 8. Silvestrini TA, Pinsky PM, Datye DV. Numerical simulation of glucose diffusion in the cornea with an ICR (intrastromal corneal ring). Invest Ophthalmol Vis Sci. 1996;37:S66. 9. Tran DB, Zadok D, Carpenter M, et al. Intraocular pressure measurement in patients with intracorneal ring segments. J Refract Surg. 1999;15:441–443. 10. Kwitko S, Severo NS. Ferrara intracorneal ring segments for keratoconus. J Cataract Refract Surg. 2004;30(4):812–820. 11. Piñero PD, Alio JL, Barraquer RI, Michael R. Corneal biomechanical changes after intracorneal ring segment implantation in keratoconus. Cornea. 2012;31:491–499. doi:10.1097/ ICO.0b013e31821ee9f4. 12. de Freitas Santos Paranhos J, Ávila MP, Paranhos A Jr, Schor P. Evaluation of the impact of intracorneal ring segments implantation on the quality of life of patients with keratoconus using the NEI-RQL (National Eye Institute Refractive Error Quality of Life) instrument. Br J Ophthalmol. 2010;94:101–105. doi:10.1136/bjo.2009.161562. 13. Chalasani R, Beltz J, Jhanji V, Vajpayee RB. Microbial keratitis following intracorneal ring segment implantation. Br J Ophthalmol. 2010;94:1541e1542. doi:10.1136/bjo.2008.148619. 14. Rayward O, Arriola-Villalobos P, Cuiña-Sardiña R, Diaz-Valle D, Benítez-Del-Castillo JM, García-Feijoo J. Annular herpetic keratitis after intracorneal ring segment implantation. Cornea. 2011;30(11):1286. 15. Kanellopoulos J, Pe LH, Perry HD, Donnenfeld DE. Modified intracorneal ring segment implantations (INTACS) for the management of moderate to advanced keratoconus. Efficacy and complications. Cornea. 2006;25:29–33. 16. Neira W, Krootila K, Holopainen JM. Atopic dermatitis is a risk factor for intracorneal ring segment extrusion. Acta Ophthalmol. 2014;92(6):e491–e492. doi:10.1111/aos.12377. 17. Tognon T, Campos M, Wengrzynovski JP, et al. Indications and visual outcomes of intrastromal corneal ring segment implantation in a large patient series. Clinics. 2017;72(6):370–377. 18. Piñero DP, Alio JL, Teus MA, Barraquer RI, Uceda-Montañés A. Modeling the intracorneal ring segment effect in keratoconus using refractive, keratometric and corneal aberrometric data. Invest Ophthalmol Vis Sci. 2010;51:5583–5591. 19. Asbell PA, Ucakhan OO, Abbott RL, et al. Intrastromal corneal ring segments: reversibility of refractive effect. J Refract Surg. 2001; 17:25–31. 20. Clinch TE, Lemp MA, Foulks GN, Schanzlin DJ. Removal of intacs for myopia. Ophthalmology. 2002;109:1441–1446. 21. Yeung SN, Lichtinger A, Ku JYF, Kim P, Low SAW, Rootman DS. Intracorneal ring segment explantation after intracorneal ring segment implantation combined with same-day corneal collagen crosslinking in keratoconus. Cornea. 2013;32:1617–1620. 22. Gomez L, Chayet A. Laser in-situ keratomileusis after intrastromal corneal ring segments (Intacs). Ophthalmology. 2001;108:1738–1743. 23. Asbell PA, Ucakhan OO, Durrie DS, Lindstrom RL. Adjustability of refractive effect for corneal ring segments. J Refract Surg. 1999;15:627–631. 24. Chan SM, Khan HN. Reversibility and exchangeability of intrastromal corneal ring segments. J Cataract Refract Surg. 2002;4: 676–681.

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25. Bali SJ, Chan C, Hodge C, Sutton G. Intracorneal ring segment reimplantation in keratectasia. Asia Pac J Ophthalmol (Phila). 2012;1(6):327–330. doi:10.1097/APO.0b013e31826e1d30. 26. Chan K, Hersh PS. Removal and repositioning of intracorneal ring segments: improving corneal topography and clinical outcomes in keratoconus and ectasia. Cornea. 2017;36:244–248. 27. Vega-Estrada A, Alio JL, Brenner LF, et al. Outcome analysis of intracorneal ring segments for the treatment of keratoconus based on visual, refractive, and aberrometric impairment. Am J Ophthalmol. 2013;155:575–584. 28. Peña-García P, Vega-Estrada A, Barraquer RI, Burguera-Giménez N, Alio JL. Intracorneal ring segment in keratoconus: a model to predict visual changes induced by the surgery. Invest Ophthalmol Vis Sci. 2012;53:8447–8457. 29. Sadigh AL, Aali TA, Sadeghi A. Outcome of intrastromal corneal ring segment relative to depth of insertion evaluated with Scheimpflug image. J Curr Ophthalmol. 2015;27(1–2):25–31. 30. Hashemi H, Yazdani-Abyaneh A, Beheshtnejad A, Jabbarvand M, Kheirkhah A, Ghaffary SR. Efficacy of intacs intrastromal corneal ring segment relative to depth of insertion evaluated with anterior segment optical coherence tomography. Middle East Afr J Ophthalmol. 2013;20(3):234–238. 31. Rabinowitz YS, Li X, Ignacio TS, Maguen E. INTACS inserts using the femtosecond laser compared to the mechanical spreader in the treatment of keratoconus. J Refract Surg. 2006; 22(8):764–771. 32. Kaya V, Utine CA, Karakus SH, et al. Refractive and visual outcomes after intacs vs ferrara intrastromal corneal ring segment implantation for keratoconus: a comparative study. J Refract Surg. 2011;27(12):907–912. 33. Kubaloglu A, Sari ES, Cinar Y, et al. Comparison of mechanical and femtosecond laser tunnel creation for intrastromal corneal ring segment implantation in keratoconus: prospective randomized clinical trial. J Cataract Refract Surg. 2010;36(9):1556–1561. 34. Alio JL, Artola A, Ruiz-Moreno JM, et al. Changes in keratoconic corneas after intrastromal ring segment explantation and reimplantation. Ophthalmology. 2004;111:747–751. 35. Rodriguez-Prats J, Galel A, Garcia-Lledo M, et al. Intrastromal rings for the correction of pellucid marginal degeneration. J Cataract Refract Surg. 2003;29:1421–1424. 36. Seiler T, Koufala K, Richter G. Iatrogenic keratectasia after laser in-situ keratomileusis. J Refract Surg. 1998;14:312–317. 37. Alio JL, Salem TF, Artola A, Osman AA. Intacs corneal rings to correct corneal ectasia after laser in-situ keratomileusis. J Cataract Refract Surg. 2002;28:1568–1574. 38. Bastos Prazeres TM, da Luz Souza AC, Pereira NC, Ursulino F, Grupenmacher L, Barbosa de Souza L. Intrastromal corneal ring segment implantation by femtosecond laser for the correction of residual astigmatism after penetrating keratoplasty. Cornea. 2011;30:1293–1297. 39. Koppen C, Gobin L, Tassignon MJ. Intacs to stabilize diurnal variation in refraction after radial keratotomy. J Cataract Refract Surg. 2007;33:2138–2141. 40. Bedi R, Touboul D, Pinsard L, Colin J. Refractive and topographic stability of intacs in eyes with progressive keratoconus: five-year follow-up. J Refract Surg. 2012;28(6):392–396. 41. Alio JL, Shabayek MH, Artola A. Intracorneal ring segments for keratoconus correction: long-term follow-up. J Cataract Refract Surg. 2006;32:978–985. 42. Kymionis GD, Siganos CS, Tsiklis NS, et al. Long-term followup of intacs in keratoconus. Am J Ophthalmol. 2007;143(2): 236–244.

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43. Vega-Estrada A, Alió JL, Plaza-Puche AB. Keratoconus progression after intrastromal corneal ring segment implantation in young patients: Five-year follow-up. J Cataract Refract Surg. 2015;41(6):1145–1152. 44. Hofling-Lima AL, Branco BC, Romano AC, et al. Corneal infections after implantation of intracorneal ring segments. Cornea. 2004;23(6):547–549. 45. Bourcier T, Borderie V, Laroche L. Late bacterial keratitis after implantation of intrastromal corneal ring segments. J Cataract Refract Surg. 2003;29(2):407–409. 46. Guell JL, Velasco F, Sanchez SI, et al. Intracorneal ring segments after laser in situ keratomileusis. J Refract Surg. 2004;20:349–355. 47. Bourges JL, Trong TT, Ellies P, et al. Intrastromal corneal ring segments and corneal anterior stromal necrosis. J Cataract Refract Surg. 2003;29(6):1228–1230.

48. Kanellopoulos AJ, Pe LH, Perry HD, Donnenfeld ED. Modified intracorneal ring segment implantations (INTACS) for the management of moderate to advanced keratoconus: efficacy and complications. Cornea. 2006;25(1):29–33. 49. Levy J, Lifshit T. Keratitis after implantation of intrastromal corneal ring segments (Intacs) aided by femtosecond laser for keratoconus correction: case report and description of the literature. Eur J Ophthalmol. 2010;20(4):780–784. 50. Mulet ME, Pérez-Santonja JJ, Ferrer C, Alió JL. Microbial keratitis after intrastromal corneal ring segment implantation. J Refract Surg. 2010;26(5):364–369.

27 

Intraocular Lens Calculations After Keratorefractive Surgery ELIAS F. JARADE, MAZEN AMRO, AND FRANÇOISE C. ABI NADER

Introduction As part of the normal aging process, patients who are undergoing keratorefractive procedures may ultimately develop cataracts and may need cataract extraction with intraocular lens (IOL) implantation. The increasing volume of cataract surgical procedures after corneal refractive surgery is associated with similar expectations of perfect vision without correction after cataract surgery. Early results, however, have shown a hyperopic shift after cataract surgery in eyes that underwent corneal refractive surgery. IOL lens power calculation depends on the axial length (AL), anterior chamber depth (ACD), and keratometry reading (K-reading). With few exceptions, the AL and ACD are not changed following refractive surgery.1–3 Keratometry, on the other hand, may show significant changes. The current methods for measuring keratometry include manual keratometer, automated keratometry and corneal topography. These methods underestimate corneal flattening after myopic radial keratotomy (RK),4–7 photorefractive keratectomy (PRK),8–13 and laser in situ keratomileusis (LASIK)14–17 with an overestimation of the K-reading. Such reading may lead to falsely low IOL power calculation with subsequent hyperopia following cataract surgery.

Source of Error in K-Reading Following Corneal Refractive Surgery Current instruments measure with accuracy the anterior corneal radius of curvature (Ra) by measuring the reflected images of the projected mires; the posterior corneal radius of curvature is not assessed but is compensated for by the use of a modified (effective) index of refraction (Fig. 27.1). For example, the Zeiss ophthalmometer uses an effective index of refraction of 1.3315, whereas EyeSys corneal topography uses an effective index of refraction of 1.3375. The keratometric diopters are derived from the anterior 382

radius of curvature using an effective refractive index (n) in the paraxial formula18: keratometric diopters (D) = (n −1) R a (m ). Because there is a constant ratio between the anterior and posterior surface curvatures in the central optical zone of normal corneas, the use of these indices in the current instruments to compensate for the posterior corneal power is acceptable. However, corneal refractive surgery changes the architecture of the central cornea such that standard methods of measurement overestimate the corneal power. Following RK, both the anterior and posterior corneal surfaces undergo a relatively proportional flattening, and the relationship between them is not disrupted. The central cornea flattens more than the paracentral cornea, and the midperipheral cornea steepens (Fig. 27.2A). The standard keratometer measures close to the paracentral transition (knee) zone after RK, which leads to an overestimate of the curvature of the central flat effective optical zone (Fig. 27.2B). The greater the amount of myopic correction, the smaller the effective central optical zone and the greater the magnitude of error. A temporary hyperopic shift in the early course after cataract surgery in eyes that underwent RK is due to mechanical instability of the cornea, which may flatten almost as if refractive keratotomy had just been done.19 This temporary hyperopic shift may be as high as +4 D to +6 D, giving the false impression of a miscalculated IOL power. Therefore hyperopic shift after RK should not be corrected surgically before corneal stability is ensured after cataract surgery. In contrast, mechanical stability of the cornea is not significantly decreased after PRK and LASIK.4,11,19 Following uncomplicated photorefractive surgery (PRS), the Ra measurement by current instruments is still accurate because the transition area (knee zone) is far outside the 2.6- to 3-mm zone that is measured, and the irregular astigmatism in the central 3-mm zone is usually minimal. In this instance, the lack of accuracy in the K-reading results from

CHAPTER 27  Intraocular Lens Calculations After Keratorefractive Surgery

383

SEQS = sphere + 0.5 (cylinder)

Index of refraction at air-cornea interface, “Nc” = 1.376

SEQC = 1000/ [(1000/SEQS) – V]

•

Fig. 27.3  The spheroequivalent refraction for refractions at the corneal plane (SEQC) is calculated using the spheroequivalent refractions at the spectacle plane (SEQS) at a given vertex distance (V).

+48D

A

-5.6D

B

• Fig. 27.1  (A) Reflected images from the anterior corneal surface of the projected keratometric mires are analyzed to calculate accurately the anterior corneal radius of curvature. (B) Normal cornea with an average anterior corneal power of +48 D and an average posterior corneal power of −5.6 D. Index of refraction at the air–cornea interface (Nc = 1.376) can be used only to assess the anterior corneal power; posterior surface is not measured but compensated for by the use of the modified (effective) index of refraction “n” (e.g., EyeSys videokeratography: 1.3375). Central flattening

Peripheral steepening with transitional (knee) zone

A

normal corneas does not compensate correctly for the posterior corneal surface power, which results in an inaccurate K-reading. Change in corneal thickness following a photoablative procedure has a minimal effect20 (estimated to be < 0.1 D) on the parameters used to calculate IOL power, and posterior corneal curvature changes slightly or remains unchanged following uncomplicated refractive surgery.21

Present Methods for K-Reading After Corneal Refractive Surgery To obtain an accurate IOL power calculation following corneal refractive surgery, several methods have been adopted for assessing the K-reading following refractive surgery.

Clinical History Method The clinical history method (CHM), or calculation method, first published by Holladay21 in 1989 and later by Hoffer19 as the CHM for eyes after RK involves subtracting the change in spherical equivalent (SE) refraction at the corneal plane (ΔSEQC) induced by the refractive procedure from the preoperative K-reading (K-readingpreop): K-reading after surgery = K-reading preop − ∆SEQC

Unmeasured central optical zone

∆SEQC = SEQC postop − SEQC preop. SEQC is the SE refraction at the corneal plane (Fig. 27.3).

Example Measured transitional knee zone

B •

Fig. 27.2  (A) Proportional flattening of the anterior and posterior corneal surfaces after radial keratotomy (RK) associated with peripheral steepening and the formation of a transitional knee zone in an eye that underwent radial keratotomy. (B) Standard keratometer measures close to the paracentral transitional zone (knee) after RK, which is steeper than the central flat effective optical zone.

The patient’s preoperative corneal power was 45.0 D and refractive error (SE) was −6.00 D at the spectacle plane (V = 12 mm). At 1 year postoperatively, the eye had an SE refractive error of −1.00 D at the spectacle plane without cataract: SEQC preop = 1000 [(1000 −6) − 12] = −5.6 D SEQC postop = 1000 [(1000 −1) − 12] = −0.9 D ∆SEQC = ( −0.9) − ( −5.6 ) = 4.7 D K-reading after surgery = 45 D − 4.7 D = 40.3 D SEQS = sphere + 0.5 (cylinder )

the fact that the normal relationship between the anterior and posterior corneal surface curvature is disrupted as a result of anterior corneal surface flattening while the posterior surface curvature remains unchanged. Therefore the use of an effective index of refraction that was generated in

SEQC = 1000 [(1000 SEQS) − V ]. Recommendation to use the SE change at the spectacle plane rather than the corneal plane has been suggested in order to minimize the amount of possible overestimation

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of K-reading.13 The CHM is considered to be accurate and perhaps the most reliable method after RK and photorefractive procedures. It does, however, have limitations because it requires postrefractive surgery refraction before cataract surgery, which may be biased because of lens-induced and AL progression myopia after refractive surgery. Lenticular opacities at the time of cataract surgery may also preclude accurate refraction. Therefore it is important to choose a postoperative refraction at a time point when the cornea is stable and before any myopic shift from nuclear sclerosis. Corneal regression after refractive surgery is not uncommon and may affect the result of K-reading when a “remote” postoperative refraction is used. To avoid the error induced by corneal regression, we suggest comparing the K-reading measured using the conventional methods at the time of cataract surgery to the previous K-reading measured at the same time as the refraction was performed. Any significant change in corneal power should be subtracted from the refraction (at the corneal plane) used to calculate the corneal power.

Same refraction: corneal power = HCL base curve

A

Hyperopic shift: corneal power > HCL base curve

B

Hard Contact Lens Method This method was first described by Soper and Goffman22 and later recommended for determining the corneal power for IOL calculation after RK19,21 and after PRK and LASIK.23 The concept of the hard contact lens (HCL) method (also known as the contact lens overrefraction method) is based on the principle that if an HCL with plano power and a base curve equal to the corneal power is fitted over the cornea, it will not change the refractive error of the eye. This method can be used with no knowledge of pretreatment data. The patient’s manifest refraction is determined without a contact lens and then repeats the manifest refraction after placement of a plano HCL of known base curve. The difference between the HCL overrefraction and the SE refraction without the contact lens is added to the contact lens base curve measured in diopters to obtain the corneal dioptric power. Three results are possible: (1) If the refraction does not change, the central corneal power is equal to the contact lens base curve; (2) if the SE shifts toward hyperopia after fitting the contact lens, the corneal power is more than the HCL base curve; (3) if the SE shifts toward myopia, then the corneal power is less than the HCL base curve (Fig. 27.4).

Example The patient’s refraction (SE) is −1.0 diopter (D). After adding the HCL of base curve 40.0 D, the manifest refraction becomes −2.0 D. This means that the corneal power is less than the HCL base curve and equal to 40.0 D + [( −2.0 D) − ( −1.0 D)] = 39.0 D. This method is widely used after RK but has not been validated for use after photorefractive surgery. Dense cataract may give rise to a false refraction. Thus the accuracy of this method in cataractous eyes is questionable.

Myopic shift: corneal power < HCL base curve

C • Fig. 27.4

  Plano hard contact lens (HCL; pink) of a known base curve is fitted over the cornea (blue). (A) HCL and anterior cornea have the same base curve. In this case, the tear film meniscus formed between the HCL and the cornea (green) has no dioptric power and the refraction does not change after lens fitting. (B) Anterior cornea is steeper than the HCL base curve. In this case, the formed tear film meniscus has a divergent power and the sphere equivalent of refraction shifts toward hyperopia after HCL fitting. (C) The HCL base curve is steeper than the anterior corneal curvature, and the SE shifts toward hyperopia after fitting of the HCL due to the formation of a convergent tear film meniscus between the HCL and the cornea.

Our analysis of this method shows that the difference in SE refraction before and after adding the HCL is the power of the tear film meniscus created between the lens and the anterior corneal surface. Thus adding this power (the difference of SE refraction before and after adding the HCL) to the HCL base curve gives the value of the anterior corneal surface power and not the total corneal power. Many corneas (especially after keratorefractive surgery) have different posterior curvatures and may share the same anterior curvature (with different total corneal power) but give rise to an equal difference in SE refraction after adding the same plano HCL (Fig. 27.5). We conclude that only the anterior corneal power can be assessed by this method, which may be useful after RK surgery in which the current instruments cannot adequately assess the anterior corneal curvature. This measurement must be converted to a total corneal power by appropriate use of the effective index of refraction (e.g., n = 1.3315 if using the Zeiss ophthalmometer, and n =

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385

Dablation = Kpreop – Kpostop Dablation = (Ka-preop + Kp-preop) – (Ka-postop + Kp-postop) = Ka-preop – Ka-postop; (Kp-preop is unchanged following uncomplicated LASIK) = ((Nc – 1) / Ra-preop) – ((Nc – 1) /Ra-postop) = (Nc – 1) × (Ra-postop – Ra-preop) / (Ra-postop × Ra-preop) Kpostop = Kpreop – Dablation = Kpreop – [(Nc – 1) × (Ra-postop – Ra-preop)/(Ra-postop × Ra-preop)]

• Fig. 27.7

A

B

C

• Fig. 27.5

  The same tear film meniscus (green), with equal difference in sphere equivalent refraction after adding the same plano hard contact lens (HCL), is formed between the same HCL (pink) and three different corneas (blue) with the same anterior curvature but different posterior curvature and different total dioptric power. (A) The cornea has the flattest posterior curvature, and (C) the cornea has the steepest posterior curvature. The HCL method would erroneously give an equal value of total dioptric power in these three corneas that have different total dioptric power.

Kpostop = Kpreop –

• Fig. 27.6

(Nc – 1) × (Ra–postop– Ra–preop) Ra–postop × Ra–preop

Jarade’s formula for the calculation of K-reading following LASIK. Kpostop = K-reading following LASIK. Kpreop = K-reading before LASIK. Nc = index of refraction of the cornea (air–cornea interface: 1.376). Ra-postop = radius of curvature of the anterior corneal surface following LASIK. Ra-preop = radius of curvature of the anterior corneal surface before LASIK.  

1.3375 if using EyeSys corneal topography). Since the anterior corneal curvature measurement can still be assessed adequately by current instruments following PRS, use of the HCL method is not meaningful.

Calculation of the Corneal Dioptric Power by Measuring the Anterior Corneal Curvature Jarade and Tabbarra24,25 proposed a new formula (Fig. 27.6) to calculate the K-reading in eyes that underwent myopic LASIK according to the change of Ra induced by LASIK surgery. This formula does not use the assumed index of refraction, which might vary between devices. It can also be applicable for eyes after PRK. The theoretical basis of this formula is the fact that change in corneal power following LASIK is proportional to the amount of corneal ablation measured in diopters. This amount of corneal ablation can be subtracted from the K-reading measured before the photorefractive procedure to obtain the K-reading following surgery (Fig. 27.7).  ( Nc − 1) × (R a − postop − Ra − preop )  K postop = K preop −   R a − postop × R a − preop  

  Derivation of the formula. Dablation = total amount of dioptric ablation induced by LASIK. Kpreop = total corneal dioptric power before LASIK. Kpostop = total corneal dioptric power after LASIK. Ka-preop and Ka-postop are the dioptric power of the anterior corneal surface before and after LASIK, respectively. Kp-preop and Kp-postop are the dioptric power of the posterior corneal surface before and after LASIK, respectively. Nc is the corneal index of refraction at the air–cornea interface (1.376).

Example Before surgery, a patient’s anterior corneal curvature (Ra) is 7.8 mm and the K-reading is 45.0 D. After surgery, Ra is 8.5 mm and the K-reading is 42.0 D. Using this formula, the calculated K-reading after surgery is equal to 45 − [(1.376 − 1) × (0.0085 − 0.0078) (0.0085 × 0.0078) = 41.03 D. Thus the measured K-reading overestimates the corneal power by 0.97 D. This formula has been proven to be simple, objective, nonrefraction dependent, and as accurate as the CHM formula. Also, this formula compensates for corneal regression, which might happen at any time after refractive surgery as a result of the wound-healing process, epithelial hyperplasia, or other factors. This regression will be manifested by a change in the anterior corneal curvature. Axial length progression myopia (not infrequent after refractive surgery, especially in relatively young patients who undergo refractive surgery) and lenticular myopia will not affect the K-reading result obtained by this formula since it is independent of the refractive error of the eye at the time of cataract surgery. The only prerequisite of this formula is to have records of K-reading and anterior radius of curvature before refractive surgery. Dablation = K preop − K postop Dablation = (K a-preop + K p-preop ) − (K a-postop + K p-postop ) = K a − preop − K a − postop ; (K p-preop is unchanged following uncomplicated LASIK ) = ( Nc − 1) × (R a-postop − R a-preop ) (R a-postop × R a-preop ) K postop = K preop − Dablation = K preop − [( Nc − 1) × (R a-postop − R a-preop ) (R a-postop × R a-preop )] These two prerequisites can be retrieved easily from the patient’s record in addition to the anterior radius of curvature (Ra) measured at the time of cataract surgery following PRS. Following uncomplicated LASIK and other refractive surgery procedures, the measurement of Ra using the conventional methods (auto-K, corneal topography) is still accurate because

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the flattening of the anterior surface is often fairly uniform over the entire ablation zone and the irregular astigmatism in the central 3-mm zone is usually minimal. However, corneal topography analysis to assess the average Ra in the central optical zone is important in complicated cases with irregular astigmatism following refractive surgery. The limitations of this formula include the inability to compensate for the posterior curvature change that might happen after refractive surgery, and a possible change in the internal corneal optical behavior induced by the creation of intracorneal interfaces with possible changes in the corneal index of refraction. Also, measurement error of the anterior radius of curvature after refractive surgery due to the change of asphericity from a prolate to an oblate shape in the ablation zone after myopic refractive surgery—especially after procedures involving small ablation zones, inadvertent multifocal power distribution (central island), or decentered treatment zone—may result in an additional limitation. Similar to the LASIK procedure, myopic correction by PRK is manifested by a change of the anterior corneal curvature. Therefore use of this formula after PRK is expected to be accurate. However, the mechanism of misreading the K-reading after RK, in which a peripheral bulging and central flattening of the cornea occur but the relationship between the anterior and posterior corneal surface is unchanged, differs from that of PRS. Therefore application of our formula is not justified for post-RK patients.

Direct Measurement of the Total Corneal Power Using Modified Effective Index of Refraction

ACD (mm)

Patients may ask for cataract surgery in centers other than those where the refractive procedure has been performed; neither the preoperative K-reading (and/or Ra) nor the exact amount of refractive correction may be available. After PRS, the conventional methods (automated K-reading and corneal topography) accurately measure the front radius of the cornea (Ra). In this instance, derivation of corneal power from the radius of curvature has to be refined following PRS by developing a new effective index of refraction (rN) to compensate for the corneal change and allow simple predictive K-reading following refractive surgery. Jarade et al.25,26 included in their study a total of 332 eyes that underwent 1.345 1.34 1.335 1.33 1.325 1.32 1.315 1.31 1.305 1.3 1.295 -20

• Fig. 27.8

-18

-16

-14

-12

myopic LASIK in order to find the new corneal relative indices of refraction (rN) following LASIK to be used for accurate K-reading by appropriate conversion of the measured Ra to total corneal dioptric power. Patients were divided into four subgroups according to the amount of SE of myopic LASIK ablation: subgroup I (< −4 D), subgroup II (−4 D to −8 D), subgroup III (−8 D to −12 D) and subgroup IV (> −12 D). The CHM was used to determine the actual K-reading, and rN was derived using the paraxial formula: K-reading = (rN − 1) R a (m). The new indices were 1.3355 (SD ± 0.0027), 1.3286 (SD ± 0.0042), 1.3237 (SD ± 0.0066), and 1.3172 (SD ± 0.0065) in subgroups I, II, III, and IV, respectively. The rN decreased as the amount of myopic ablation (D) increased (Fig. 27.8); the least squares linear regression analysis of their data is shown in Eq. (1) (R2 = 0.703; standard error of estimate (SEE) ± 0.004635; P < .0001). rN = 0.0014 × D + 1.3375

(1)

Example The measured Ra in a patient who underwent −7.5 D SE of myopic ablation is 8.5 mm. rN = 0.0014 × (−7.5) + 1.3375 = 1.327. The actual K-reading after LASIK using the new determined rN in paraxial formula is (1.327 − 1)/0.0085 = 38.41 D. This study shows that the use of the new determined corneal effective indexes of refraction (rN) following LASIK in each subgroup (according to the amount of ablation) gives an accurate K-reading when compared to the K-reading values obtained by the CHM. Cataract surgery may be performed at a different surgical center from where the refractive surgical procedure was performed. However, in most cases, the patients can still remember the exact or the approximate amount of the photoablation correction performed, which will allow for the appropriate selection of the new effective index value to be used for the derivation of the keratometric power from Ra. If the exact amount of correction is known, Eq. (1) can be used to determine the exact value of the new effective index to be used. If only the approximate amount of correction is known, the average value of the new effective index of refraction determined

-10

-8

-6

-4

-2

0

  Relationship between the amount of spherical equivalent of myopic LASIK ablation “D” (x axis), and the new effective index of refraction “rN” (y axis). The rN decreased as the amount of myopic ablation increased (rN = 0.0014*D +1.3375; R2 = 0.703; standard error of estimate (SEE) ± 0.004635; P < .001).

CHAPTER 27  Intraocular Lens Calculations After Keratorefractive Surgery

in each subgroup can be used. Determination of the new effective index of refraction after LASIK may allow a direct compensation for the optical sequences of the benign anterior shift of the posterior radius of curvature that may accompany most uncomplicated LASIK surgeries. It may also allow compensation for the possible change in the internal corneal optical behavior induced by the creation of intracorneal interfaces and new stromal tissue deposition secondary to wound healing. Although central corneal thickness change after LASIK has little effect on the total corneal keratometric power, it can also be compensated for. However, myopic regression after LASIK might affect the results; therefore it is suggested that the new effective index of refraction be chosen after subtracting the estimated amount of the myopic regression from the initial amount of the ablation at the time of LASIK surgery. Also, it is suggested to use corneal topography to assess the average Ra in the central optical zone in complicated cases with irregular astigmatism following refractive surgery. These rN values derived in this study have to be refined after clinical experience during cataract surgery after LASIK. Furthermore, the validity of these numbers (rN values) after PRK has to be tested despite the fact that both PRK and LASIK procedures have a similar optical effect on the cornea. These new effective indices of refraction may be obtained by automatically changing the index value in the equipment algorithm for keratometry and videokeratography according to the amount of LASIK ablation.

Posterior Corneal Curvature Method The principle of this method is to derive the anterior corneal power of the cornea from the measured anterior corneal curvature using the corneal index of refraction at the aircornea interface (Nc = 1.376) and subtract from it the estimated posterior corneal power to obtain the total corneal power. The value given for the dioptric power of the posterior surface can either be measured or fixed theoretical values. The Orbscan corneal topography system (Bausch & Lomb) allows for individual measurement of the posterior corneal curvature. The unit’s central opening misses the important central zone and there is always a blind spot in the center. It has been impossible to validate the accuracy of this measurement, which has been questionable, especially in eyes that underwent refractive surgery. Giving a predetermined value for the posterior corneal power (Gullstrand’s model eye gives a theoretical value for the posterior cornea of −5.9 D) may lead to a significant error, since posterior corneal power varies considerably (−2.1 D to −8.5 D) between individuals.27,28

Discussion Patients who have undergone refractive surgery are highly motivated to have perfect vision without correction after cataract surgery. Accurate IOL power calculation is highly dependent on accurate K-reading, especially after refractive

387

surgery. Thus keratometric power measurement is an essential step in meeting the requirement of these patients. Several methods are recommended to determine the effective corneal power as accurately as possible. Therefore it is very important for cataract surgeons to be familiar with the current methods. Table 27.1 summarizes the previously discussed and other different formulas that were published on the topic of IOL power calculation post keratorefractive procedures. With the exception of the previously mentioned fourth method, which modified the effective index of refraction,25,26 most current methods of measuring the K-reading following refractive surgery are dependent on many preoperative data. Therefore all candidates for refractive surgery should be given wallet cards containing their preoperative data (pretreatment average keratometric power, proposed treatment, preoperative refraction, and refraction at a suitable postoperative time when the cornea has stabilized and before the development of lens opacity). Also, AL measurement should be included to easily differentiate in the future between corneal regression and AL progression. If enough data are available, it is recommended to use many methods to calculate the corneal power and to choose the lowest value in order to avoid a hyperopic shift after cataract surgery. Once the corneal power is determined, it is recommended that a third-generation theoretical formula is used for IOL power calculation (e.g., Hoffer Q, Holladay 2, SRK-T, Haigis). Since these eyes never fall into the category of average eyes despite being emmetropic, the assumptions made by the empirical formula (e.g., SRK I and SRK II) make them unreliable in these patients. Moreover, it is recommended that more than one third-generation formula should be applied, and the highest resulting IOL power should be used. Irregular astigmatism after refractive surgery is not uncommon, and it is mandatory to perform corneal topography before cataract surgery on all patients. Although many studies have shown that the automated keratometer is superior to topography in eyes after refractive surgery,27–31 the average corneal power in the central optical zone provided by corneal topography is more valuable to determine the corneal parameters if irregular astigmatism is present.30–35 Furthermore, the average central corneal power can be used in eyes after RK if there are not enough preoperative and postoperative data to allow accurate calculation of corneal power. Patients who are going to have cataract surgery after corneal refractive surgery should be informed that the accuracy of these methods to calculate the IOL power after refractive surgery has not yet been validated and that an exchange of the IOL or other interventions may be necessary to achieve emmetropia. Special attention should be paid to eyes that are post–hyperopic refractive surgery since all the current methods are directed mainly to solve the problem in eyes post–myopic refractive surgery. Hyperopic PRS is similar in principle to myopic PRS. The relationship between the anterior and posterior surfaces of the cornea is disrupted. Regarding the theoretical basis of the previously mentioned first, third, and fourth methods (CHM,19,21 calculation of the corneal dioptric power by measuring the

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TABLE Summary of the Published Equations for Keratometric Estimation and Intraocular 27.1  Lens Power Calculation A. Methods Based on the Knowledge of the Patient Clinical History Required Parameters: Preoperative Keratometry, Preoperative Surgery Refraction, Postoperative Surgery Refraction 1. Clinical History Method: K eff = K pre – ΔRef (Holladay,21 Hoffer19) Keff = corneal power included in the formulas Kpre = Preoperative mean corneal power ΔRef = change of refraction measured as spherical equivalent Required Parameters: Preoperative Surgery Refraction, Postoperative Surgery Refraction ( rN − 1) 1. K-readings = (Jarade et al.25,26) Ra Ra = radius of anterior corneal curvature in meters rN = 0.0014 ∗Δ + 1.3375, Δ = amount of myopic ablation 1336 ( 4Radj − L ) 2. P = (Camellin and Calosi36) (L − ACDpost )( 4Radj − ACDpost ) Radj =

0.3319 × R 0.3319 × R = , if incisional surgery nadj − 1 0.00096 × SIRC + 0.3319

Radj =

0.3316 × R 0.3319 × R = , if photorefractive surgery nrel − 1 0.0013 × SIRC + 0.3319

P = power of IOL to be implanted L= axial length ACDpost = actual position of IOL Radj = radius of curvature after refractive surgery SIRC = refractive changes induced by surgery 3. Single K SRK /T formula: adjusted central K method (Chen and Hu37) ΔAuto K = 0.7397 × ΔES + 0.3778, using Topcon CR 3000 autokeratometer ΔAuto K = change in corneal power after corneal refractive surgery ΔES = preoperative and postoperative refractive change ΔK Central = 0.9183 × ΔES − 0.0204, using TMS1 Corneal topographer ΔK Central = change in central keratometry ΔES = change in preoperative and postoperative refraction 4. Target postoperative refractive error (D) to achieve emmetropia during IOP power calculation = −0.018 ∗ (MRSE Change) ∗ (MRSE Change) + 0.192 ∗ (MRSE Change) − 0.062 (Diehl et al.38) MRSE change = manifest refraction spherical equivalent change in diopters 5. Feiz-Mannis method (Feiz et al.15) Myopic LASIK: IOLimp = IOLcalc − 0.231 + (0.595 × ΔES) Hyperopic LASIK: IOLimp = IOLcalc + 0.751 − (0.862 × ΔES) IOLimp = Power of IOL to be implanted IOLcalc = Power of IOL calculated by the traditional method ΔES = difference in refraction before and after refractive surgery 6. K post − adj = K post − 0.24 × ( ∆Rif ) + 0.15 , using Bausch & Lomb keratometer Adjusted effective refractive power: EffRPpost − adj = EffRPpost − 0.15 ( ∆Rif ) − 0.05 , using EyeSys Topographer (Hamed et al.16) Kpost-adj = corneal power to be included in calculation formulas Kpost = average postoperative corneal power obtained by keratometry ΔRif = preoperative and postoperative refractive change measured as spherical equivalent EffRPpost-adj = corneal power included in calculation formulas EffRPpost = average postoperative corneal power, using the parameter EffRP from EyeSys Topographer 7. Masket Method: IOL power add = ((LSE ∗ (−0.326)) + 0.101 (Masket and Masket39) IOL power add = power of IOL to be added LSE=effective treatment at the corneal apex 8. Modified Masket formula: IOLpost + (RC x 0.4385) + 0.0295 = IOLadj (Hill40) IOLpost = the calculated IOL power following ablative corneal refractive surgery RC = the refractive change after corneal refractive surgery at the corneal plane, IOLadj = the adjusted power of the IOL to be implanted 9. Adjusted Atlas 9000 (4-mm zone) formula: Atlas 9000 4-mm zone − (RC × 0.2) = Post-LASIK/PRK adjusted corneal power (Wang et al.41) The Atlas 9000 4-mm zone value is obtained from the Zeiss Humphrey Atlas 9000 topographer. This value is then modified according to the amount of refractive correction induced by the surgery. RC = amount of refractive correction induced by the LASIK/PRK at the corneal plane Shammas-PL formula (no-history method) then used to calculate the IOP power.

CHAPTER 27  Intraocular Lens Calculations After Keratorefractive Surgery

389

TABLE Summary of the Published Equations for Keratometric Estimation and Intraocular 27.1  Lens Power Calculation—cont’d 10. Adjusted Atlas Ring Values: Atlas Ring Values − (Rc × 0.2) = Post-LASIK/PRK adjusted corneal power (Wang et al.41) The average corneal power is obtained by averaging the 0-mm, 1-mm, 2-mm, and 3-mm ring values on the Atlas 9000 or the Numerical View from the Atlas 992–995 series. This value is then modified according to the amount of refractive correction induced by the surgery. RC = the amount of refractive correction induced by the LASIK/PRK at the corneal plane The double-K Holladay 1 IOL calculation formula is used. 11. Adjusted ACCP/ACP/APP: ACCP − (Rc × 0.16) = Post-LASIK/PRK adjusted corneal power (Awwad et al.42) The average central corneal power (ACCP) is the average of the mean powers of the central Placido rings over the central 3.0 mm of the cornea, as displayed by the Tomey Topography Modeling System. With the adjusted ACCP method, the ACCP is modified according to the amount of refractive correction induced by the surgery. Rc = the amount of refractive correction induced by the LASIK/PRK at the corneal plane 12. y = 0.7615x − 0.6773 (Rosa et al.43), x = difference in refraction at the corneal plane, y = keratometric difference evaluated with IOL Master, Corrected K = (measured postoperative K − (difference between x and y)) 13. Y= aX −b (Stakheev and Balashevich44), Y = corneal power correcting factor, X = effective treatment, a and b = constants, depending on type of refractive surgery and equipment used to measure the corneal power 14. Barrett True-K formula (Barrett45): Universal II formula used, modified from a universal theoretical formula for IOL calculation. Uses (ΔMR) change in refraction induced by the corneal refractive surgery. Required Parameters: Preoperative Keratometry  (Nc − 1) ∗ (Ra-postop − Ra-preop )  25,26 1. K postop = K preop −  )  (Jarade et al. (Ra-postop ∗ Ra-preop )   Kpostop = corneal power to be included in the formula to calculate the IOL Kpreop = corneal power before corneal refractive surgery Nc = cornea’s index of refraction (1.376) Ra-postop = radius of curvature of the anterior surface of the cornea after refractive surgery Ra-preop = radius of curvature of the anterior surface of the cornea before refractive surgery [1000 ∗ na ∗ (na ∗ rpost − 0.333 ∗ LOPT )] 2. Double-K SRK-T method (Aramberri46): IOL emme = [(LOPT − ACDest ) ∗ (na ∗ rpost − 0.333 ∗ ACDest )] na =1.336, rpost= radius of curvature after refractive surgery LOPT = L + (0.65696 − 0.02029 ∗ L), L = axial length ACDest = estimated anterior chamber depth, it requires knowledge of preoperative radius of curvature   0.376 0.376 11 − 3. K calc-ex = K pre −   (Seitz et al. ) K K ∗ ∗ ( 0 . 3313 ) ( 0 . 3313 ) pre post   Kcalc-ex = keratometric value to be included in the formula Kpre = keratometric value prior to corneal refractive surgery Kpost = keratometric value after corneal refractive surgery Available Parameters: Preoperative Keratometry, Preoperative Refraction 1. Corneal bypass method (Walter et al.47): RPRE = patient refraction before surgery is considered as RXTARG (target refraction), calculated using AL (axial length) and KPRE (keratometry before surgery) Available Parameters: Prerefractive Surgery Refraction 1. IOL implanted = IOL calc − (0.47x + 0.85) (Latkany et al.48) IOL implanted = IOL calc − (0.47x + 0.85) IOL calc = IOL calculated using SRK-T formula x = preoperative refractive error B. Methods That Do Not Require the Knowledge of the Patient’s Clinical History 1 1 1  1  1. BESSt K =  ∗ (nadj − nair ) +  ∗ (nacq − nadj ) − d ∗ ∗ (n nadj − nair ) ∗ ∗ (nacq − nadj ) ∗ 1000 (Borasio et al.49) rB r  rF   rB    rF = anterior radius of curvature, nadj = refractive index modified according to corneal thickness, nair = refractive index of air (1), nacq = aqueous index of refraction (1.336), rB = posterior radius of curvature, d = dcct/1.3265, dcct = CCT/1,000,000, CCT=central corneal thickness Calculated K value is used with SRK-T or Hoffer Q, depending on the axial length. 2. IR = −0.0006 ∗ (AL ∗AL) + 0.0213 ∗ AL +1.1572 (Ferrara et al.50) IR= new index of refraction after cornea refractive surgery, used to calculate the new K-readings 331.5 3. rcorr = (Haigis51) ( −5.1625 × rmeas + 82.2603 − 0.35 ) rcorr = corrected radius of curvature (mm), rmeas = radius of curvature (mm) after corneal refractive surgery measured with IOL Master, the rcorr is then used in the Haigis formula to calculate the IOL power. 4. KM = 0.715 ∗ KC + 11.998 (Kim et al.52) KM = average corneal power after refractive surgery KC = average corneal power

{

}

Continued

390 se c t i o n I X 390

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TABLE Summary of the Published Equations for Keratometric Estimation and Intraocular 27.1  Lens Power Calculation—cont’d 337.5 ( 0.0276 ∗ AL + 0.3635 ) (Rosa et al.53) Rmis Keff = corneal power to be included in calculations formulas Rmis = mean radius of curvature measured with a common keratometer, AL= axial length SRK-T formula with AL < 30 mm, average result of SRK-T and SRKᴨ with AL over 30 mm A recent modification of the above formula was proposed as follows: If AL ∗ Kmis (corneal power measured with a common keratometer) > 1060, the IOL power should be reduced using the formula: Y = − (−0.0157 ∗ AL ∗ Kmis + 16.437), where Y = refractive error to insert in SRK-T formula to obtain emmetropia. 6. Modified Double K method or anterior posterior (A-P) method after LASIK (Saiki et al.54): linear regression formula, using the postoperative posterior corneal power to calculate the preoperative Km, which is used to calculate ELP (effective lens position) y = −4.907x + 12.371 y = preoperative Km evaluated with Pentacam x = posterior postoperative Km evaluated with Pentacam (npost − 1) 7. Ppost = (Savini at al.55) r P post = corneal power after corneal refractive surgery n post = postoperative index of refraction=1.338 + 0.0009856 ∗ attempted correction r = radius of curvature 8. Wang-Koch-Maloney method: (Atlas 4-mm zone x 1.114) − 5.59 D = Post-LASIK/PRK adjusted corneal power (Wang et al.41) The Atlas 4-mm zone value is obtained from the Zeiss Humphrey Atlas topographer. This value is then converted back to the anterior corneal power by multiplying this value by 376.0/337.5, or 1.114. An assumed posterior corneal power of 5.59 D is then subtracted from this product. Shammas-PL formula is then used to calculate the IOL power. 9. Barrett true K no history (Barrett45): Universal II formula used, modified from a universal theoretical formula for IOL calculation. Does not use any historical data. 10. Shammas formula (Shammas et al.56,57): Kc.cd = 1.14 ∗ Kpost − 6.8 Kc.cd = mean corneal power recalculated by the formula Kpost = mean corneal power after refractive surgery The corrected Kpost is used in the double-k Holladay 1 formula to calculate the IOL power. Calculations for an emmetropic IOL using the Shammas-PL formula (no-history method): 1336 1 IOLemm = − L − 0.1(L − 23 ) − (C + 0.05 ) 1.0125 − C + 0.05 Kc 1336 Where L = axial length (mm), C =pACD (estimated postoperative anterior chamber depth) in mm, the corrected K-readings Kc = 1.14 Kpost − 6.8, with Kpost being the post-LASIK K-readings in diopters For converting the A-constant of a specific IOL to the Shammas pACD: C = pACD = (0.5835 ∗ A) − 64.4 Where A is the A-constant of the IOL being used. This conversion equation is different from the equation used to calculate other pACDs in other formulas. Calculations for an ametropic IOL: 1336 1 IOLemm = − L − 0.1(L − 23 ) − ( C + 0.05 ) 1.0125 C + 0.05 − 1336 Kc + R R = desired refraction at the corneal plane 11. OCT-based formula (Huang et al.58): Effective corneal power in post-myopic LASIK/PRK = 1.0208 * net corneal power − 1.6622 IOL depth = 0.711∗ ACD + 0.623 ∗ AL − 0.25 ∗ Pp + ( pACD − 8.11) , if AL ≤ 24.4 mm 5. K eff =

IOL depth = 0.711∗ ACD + 0.623 ∗ [ AL + 0.8 ∗ ( AL − 24.4 )] − 0.25 ∗ Pp + ( pACD − 8.11) , if AL > 24.4 mm pACD is the ACD-constant, PP is the posterior corneal power by OCT. The ACD-constants are personalized constants for the clinical investigators based on their clinical series with the IOLMaster partial-coherence interferometer in routine cataract surgery. Overall, the OCT-based IOL formula took as input five preoperative biometric measurements: The partial coherence interferometer provided AL and ACD. OCT provided NCP (net corneal power), PP , and CCT(central corneal thickness).

CHAPTER 27  Intraocular Lens Calculations After Keratorefractive Surgery

391

TABLE Summary of the Published Equations for Keratometric Estimation and Intraocular 27.1  Lens Power Calculation—cont’d 12. Ray tracing technique (Preussner et al.59) : The assumed postoperative IOL position is calculated: 0.7  a Aa = cm ∗   + Am − cm − 0.5 ∗ ( d − dm )  am  Aa = anterior chamber depth with the IOL in the eye of interest cm = distance between the posterior cornea and center of a 21.00-D IOL in a mean-sized eye (4.6 mm) a, am = axial length of the eye of interest and a mean-sized eye (23.6 mm) Am = anterior chamber depth with the IOL model of interest in a mean-sized eye d, dm = thickness of the IOL of interest and 21.00-D IOL of the same model AL = Ap + 0.574 ∗ tL − 0.632 − 0.5 ∗ d AL = anterior chamber depth with the IOL in the eye of interest Ap = preoperative anterior chamber depth tL = thickness of the crystalline lensD = thickness of the IOL

anterior corneal curvature,25,26 and direct measurement of the total corneal power using modified effective index of refraction,25,26 respectively), their use in such an instance can be justified and expected to be accurate. The newly approved techniques for the treatment of low to moderate hyperopia, conductive keratoplasty (CK) and laser thermokeratoplasty (LTK) have a postulated effect similar to the RK procedure, in which both surfaces of the cornea are shifted together in the same direction. The anterior– posterior corneal surfaces relationship is not disrupted, the effective optical zone is relatively large, and the transitional zone (knee zone) is far outside the measured area. Thus accurate K-reading using the current instruments might be anticipated after CK and LTK.

References 1. Hoffer KJ. Calculating intraocular lens power after refractive corneal surgery. Arch Ophthalmol. 2002;120:500–501. [Editorial]. 2. Hoffer KJ, Darin JJ, Pettit TH, et al. UCLA clinical trial of radial keratotomy: preliminary report. Ophthalmology. 1981;88: 729–736. 3. Seitz B, Langenbucher A. Intraocular lens power calculation in eyes after corneal refractive surgery. J Refract Surg. 2000;16: 349–361. 4. Koch DD, Liu JF, Hyde LL, et al. Refractive complications of cataract surgery after radial keratotomy. Am J Ophthalmol. 1989; 108:676–682. 5. Celikkol L, Pavlopoulos G, Weinstein B, et al. Calculation of intraocular lens power after radial keratotomy with computerized videokeratography. Am J Ophthalmol. 1995;120:739–750. 6. Lyle WA, Jin GJ. Intraocular lens power prediction in patients who undergo cataract surgery following previous radial keratotomy. Arch Ophthalmol. 1997;115:457–461. 7. Gimbel H, Sun R, Kaye GB. Refractive error in cataract surgery after previous refractive surgery. J Cataract Refract Surg. 2000;26:142–144. 8. Lesher MP, Schumer J, Hunkeler JD, et al. Phacoemulsification with intraocular lens implantation after excimer photorefractive keratectomy: a case report. J Cataract Refract Surg. 1994; 20(suppl):265–267.

9. Siganos DS, Pallikaris IG, Lambropoulos JE, Koufala CJ. Keratometric readings after photorefractive keratectomy are unreliable for calculating IOL power. J Refract Surg. 1996;12: S278–S279. 10. Kalski RS, Danjoux JP, Fraenkel GE, et al. Intraocular lens power calculation for cataract surgery after photorefractive keratectomy for high myopia. J Refract Surg. 1997;13:362–366. 11. Seitz B, Langenbucher A, Nguyen NX, et al. Underestimation of intraocular lens power for cataract surgery after myopic photorefractive keratectomy. Ophthalmology. 1999;106:693–702. 12. Gimbel HV, Sun R, Furlong MT, et al. Accuracy and predictability of intraocular lens power calculations after photorefractive keratectomy. J Cataract Refract Surg. 2000;26:1147–1151. 13. Odenthal MT, Eggink CA, Melles G, et al. Clinical and theoretical results of intraocular lens power calculations for cataract surgery after photorefractive keratectomy for myopia. Arch Ophthalmol. 2002;120:431–438. 14. Gimbel HV, Sun R. Accuracy and predictability of intraocular lens power calculation after laser in situ keratomileusis. J Cataract Refract Surg. 2001;27:571–576. 15. Feiz V, Mannis MJ, Garcia-Ferrer F, et al. Intraocular lens power calculation after laser in situ keratomileusis for myopia and hyperopia: a standardized approach. Cornea. 2001;20:792–797. 16. Hamed AM, Wang L, Misra M, et al. A comparative analysis of five methods of determining corneal refractive power in eyes that have undergone myopic laser in situ keratomileusis. Ophthalmology. 2002;109:651–658. 17. Randleman JB, Loupe DN, Song CD, et al. Intraocular lens power calculations after laser in situ keratomileusis. Cornea. 2002;21:751–755. 18. Olsen T. On the calculation of power from curvature of the cornea. Br J Ophthalmol. 1986;70:152–154. 19. Hoffer KJ. Intraocular lens power calculation for eyes after refractive keratotomy. J Refract Surg. 1995;11:490–493. 20. Langenbucher A, Seitz B, Kus MM, et al. Berechnung der Kunstlinsenstärke nach photorefraktiver Keratektomie. In: Duncker G, et al, eds. Kongress der Deutschsprachigen Gesellschaft für Intraokularlinsen-implantation und Refraktive Chirurgie. Berlin: Springer; 1998:441–446. 21. Holladay JT. IOL calculations following radial keratotomy surgery. Refract Corneal Surg. 1989;5:36A. 22. Soper JW, Goffman J. Contact lens fitting by retinoscopy. In: Soper JW, ed. Contact Lenses: Advances in Design, Fitting, Application. New York: Stratton; 1974.

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23. Holladay JT. Cataract surgery in patients with previous refractive corneal surgery (RK, PRK, and LASIK). Ophthalmic Prac. 1997;15:238–244. 24. Jarade EF, Tabbara F. New formula for calculating intraocular lens power after laser in situ keratomileusis. J Cataract Refract Surg. 2004;30:1711–1715. 25. Jarade EF, Tabbara KF. Intraocular lens calculations after corneal refractive surgery. Middle East J Opththalmol. 2002;10:107–112. 26. Jarade E, Abinader F, Tabbara F Intraocular lens (IOL) power calculation following LASIK: change of the effective index of refraction. ARVO meeting Poster 4141; 2002. 27. Seitz B, Langenbucher A, Hofman B, et al. Refractive power of the human posterior corneal surface in vivo in relation to gender and age. Ophthalmologe. 1998;95(suppl 1):S50. 28. Langenbucher A, Seitz B, Kus MM, et  al. Regularität der Hornhauttopographie nach perforierender keratoplastik-Vergleich zwischen nichtmechanischer (Excimer-Laser-193 nm) und mechanischer Trepanation. [Eng. Abstr] Klin Monatsbl Augenheilkd. 1996; 208:450–458. 29. Langenbucher A, Seitz B, Kus MM, et al. Fourieranalyse als mathematisches Modell zur Auswertung und Darstellung von postoperativen Hornhauttopographiedaten nach nichtmechanischer perforierender Keratoplastik. [Eng. Abstr] Klin Monatsbl Augenheilkd. 1997;210:197–206. 30. Seitz B, Langenbucher A, Fischer S, et al. The regularity of laser keratectomy depth in nonmechanical trephination for penetrating keratoplasty. Ophthalmic Surg Lasers. 1998;29:33–42. 31. Tsilimbaris MK, Vlachonikolis IG, Siganos D, et al. Comparison of keratometric readings as obtained by Javal Ophthalmometer and Corneal Analysis System (EyeSys). Refract Corneal Surg. 1991; 7:368–373. 32. Alimisi S, Miltsakakis D, Klyce S. Corneal topography for intraocular lens power calculations. J Refract Surg. 1996;12:S309–S311. 33. Celikkol L, Ahn D, Celikkol G, et al. Calculating intraocular lens power in eyes with keratoconus using videokeratography. J Cataract Refract Surg. 1996;22:497–500. 34. Cuaycong MJ, Gay CA, Emery J, et al. Comparison of the accuracy of computerized videokeratography and keratometry for use in intraocular lens calculations. J Cataract Refract Surg. 1993;19(suppl):178–181. 35. Husain SE, Kohnen T, Maturi R, et al. Computerized videokeratography and keratometry in determining intraocular lens calculations. J Cataract Refract Surg. 1996;22:362–366. 36. Camellin M, Calossi A. A new formula for intraocular lens power calculation after refractive corneal surgery. J Refract Surg. 2006;22(2):187–199. 37. Chen S, Hu FR. Correlation between refractive and measured corneal power changes after myopic excimer laser photorefractive surgery. J Cataract Refract Surg. 2002;28(4):603–610. 38. Diehl JW, Yu F, Olson MD, et al. Intraocular lens power adjustment nomogram after laser in situ keratomileusis. J Cataract Refract Surg. 2009;35(9):1587–1590. 39. Masket S, Masket SE. Simple regression formula for intraocular lens power adjustment in eyes requiring cataract surgery after excimer laser photoablation. J Cataract Refract Surg. 2006;32(3):430–434. 40. Hill WE. IOL power calculations following keratorefractive surgery. Presented at Cornea Day of the Annual Meeting of the American Society of Cataract and Refractive Surgery Symposium on Cataract, IOL and Refractive Surgery; March 2006; San Francisco, CA.

41. Wang L, Booth MA, Koch DD. Comparison of intraocular lens power calculation methods in eyes that have undergone LASIK. Ophthalmology. 2004;111(10):1825–1831. 42. Awwad ST, Manasseh C, Bowman RW, et al. Intraocular lens power calculation after myopic laser in situ keratomileusis: estimating the corneal refractive power. J Cataract Refract Surg. 2008;34(7):1070–1076. 43. Rosa N, Capasso L, Lanza M, et al. Reliability of the IOLMaster in measuring corneal power changes after photorefractive keratectomy. J Cataract Refract Surg. 2004;30(2):409–413. 44. Stakheev AA, Balashevich LJ. Corneal power determination after previous corneal refractive surgery for intraocular lens calculation. Cornea. 2003;22(3):214–220. 45. Barrett GD. An improved universal theoretical formula for intraocular lens power prediction. J Cataract Refract Surg. 1993;19(6):713–720. 46. Aramberri J. Intraocular lens power calculation after corneal refractive surgery: double-K method. J Cataract Refract Surg. 2003;29(11):2063–2068. 47. Walter KA, Gagnon MR, Hoopes PC, et al. Accurate intraocular lens power calculation after myopic laser in situ keratomileusis, bypassing corneal power. J Cataract Refract Surg. 2006;32(3):425–429. 48. Latkany RA, Chokshi AR, Speaker MG, et al. Intraocular lens calculations after refractive surgery. J Cataract Refract Surg. 2005;31(3):562–570. 49. Borasio E, Stevens J, Smith GT. Estimation of true corneal power after keratorefractive surgery in eyes requiring cataract surgery: BESSt formula. J Cataract Refract Surg. 2006;32(12):2004–2014. 50. Ferrara G, Cennamo G, Marotta G, et al. New formula to calculate corneal power after refractive surgery. J Refract Surg. 2004;20(5):465–471. 51. Haigis W. Intraocular lens calculation after refractive surgery for myopia: Haigis-L formula. J Cataract Refract Surg. 2008;34(10): 1658–1663. 52. Kim JH, Lee DH, Joo CK. Measuring corneal power for intraocular lens power calculation after refractive surgery: comparison of methods. J Cataract Refract Surg. 2002;28(11):1932–1938. 53. Rosa N, Capasso L, Romano A. A new method of calculating intraocular lens power after photorefractive keratectomy. J Refract Surg. 2002;18(6):720–724. 54. Saiki M, Negishi K, Kato N, et al. Modified double-K method for intraocular lens power calculation after excimer laser corneal refractive surgery. J Cataract Refract Surg. 2013;39(4):556–562. 55. Savini G, Barboni P, Zanini M. Correlation between attempted correction and keratometric refractive index of the cornea after myopic excimer laser surgery. J Refract Surg. 2007;23(5):461–466. 56. Shammas HJ, Shammas MC, Garabet A, et al. Correcting the corneal power measurements for intraocular lens power calculations after myopic laser in situ keratomileusis. Am J Ophthalmol. 2003;136(3):426–432. 57. Shammas HJ, Shammas MC. No-history method of intraocular lens power calculation for cataract surgery after myopic laser in situ keratomileusis. J Cataract Refract Surg. 2007;33(1):31–36. 58. Huang D, Tang M, Wang L, et al. Optical coherence tomography–based corneal power measurement and intraocular lens power calculation following laser vision correction (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2013;111:34. 59. Preussner PR, Wahl J, Lahdo H, et al. Ray tracing for intraocular lens calculation. J Cataract Refract Surg. 2002;28(8):1412–1419.

28 

Phakic Intraocular Lens Power Calculations ALBERT CHAK MING WONG AND DIMITRI T. AZAR

Introduction Phakic intraocular lenses (PIOLs) are implanted in phakic eyes. Piggyback IOL implantation involves the placement of two IOLs in the eye.1 Piggyback IOL implantation can be primary, by putting in both lenses at the same stage, or secondary, by putting the second lens in at a second stage. Formulae for PIOLs and secondary piggyback IOLs are essentially the same, as they share the same principle for calculating IOL powers. Several formulae have been developed for phakic IOL and secondary piggyback IOL calculations; the most established one is van der Heijde’s equation.2 Published in 1988, the equation determined the IOL power needed for phakic myopia and aphakia (hyperopia). Van der Heijde’s formula, which assumed postoperative emmetropia, was modified by Holladay, who took into account the desired postoperative refraction and published his equation in 1993.3 Thereafter, other formulae, such as the matrix formula and the Olsen– Feingold formula, were developed. Most are derived from the vergence formula; a few of the formulae use regression analysis. All of these formulae have good clinical predictability but most are complex, such that the IOL powers could be calculated only with the use of computers. Tables and graphs have been used to approximate the desired IOL powers. The authors have designed a simplified formula that enables surgeons to double-check the desired powers of lenses without using computers and tables. In this chapter, we will review how the vergence formula was converted to formulae for PIOLs and secondary piggyback IOLs. We will also compare the parameters that require greatest accuracy to avoid IOL power calculation errors.

Van der Heijde’s Equation and Holladay’s Equation The two equations are based on the vergence formula. The (reduced) vergence of light (L, in diopters) is defined by the

refractive index of the medium (n) divided by the vergence distance (1, in meters): n L = . 1

(1)

Using the lens-maker equation, the image vergence (L′) can be calculated by adding the object vergence and the power of the lens (F): L + F = L ′.

(2)

In the vertex formula, the object vergence (Li) of the refracting surface, i, can be deduced from the previous image vergence (Li-1′) and the distance (di) between them: Li =

ni ⋅ Li −1 ′ , ni − d i ⋅ Li −1 ′

(3)

where ni is the refractive index of the corresponding refracting surface. This equation is usually applied for the prescription of a contact lens when n is equal to the refractive index of air (n = 1): Ps ′ =

PS , 1 − t ⋅ PS

(4)

where PS is the power of the spectacles or Brechkraft der Brille (in diopters),2,4 PS′ is the spectacle correction at the corneal vertex (in diopters), and t is the back vertex distance (in meters). The image vergence of the lens after operation (without spectacles) will be the same as the one of the corresponding site before operation (with spectacles; Fig. 28.1).5 Preoperatively, the image vergence, L2′ (preop), at the imaginary principal plane of the PIOL is presented as follows (Fig. 28.2): FIOL =

n

n −d K + Ps ′

−

n

n −d K

,

(5)

where n is the refractive index of aqueous (n = 1.336), d is the effective lens position (ELP), K is the corneal power, 393

Refractive Intraocular Lenses and Phakic Intraocular Lenses

394 se c t i o n I X 394

Spectacle

IOL Cornea

Lens

Retina

The predicted postoperative refraction can be calculated using the following formula: PPostRx =

A Same image vergence

B

L0

L1

L2

• Fig. 28.1  (A) This figure illustrates the pathway of the light (blue solid line) to the retina using a correcting spectacle, before the insertion of a phakic intraocular lens (PIOL). (B) This figure illustrates the pathway of the light (red dotted line) after the insertion of a PIOL, without the need of a spectacle.

Spectacle FS

n0

Cornea

Phakic IOL/

FC

2o piggyback IOL FIOL

n1

n2

d

t 0,

Vertex

L0 ′

formula:

L0= n0 = r0 (Lens-maker formula:) Vergence formula:

• Fig. 28.2

 

L0′= FS

1 ∞

=0

L1, L1 ′

L2, L2′

L1= Fs′ = n1. L0′ n1-t. L0′

L2= n2. L1′ n2-d. L1′

L1′ = FS′+ FC

L2′ = L2+ FIOL

The method to calculate the vergences of corresponding

planes.

and PS′ is the spectacle correction at the corneal vertex and is equal to Eq. (4): Ps ′ = Ps (1 − t ⋅ Ps ), where t is the back vertex distance and PS is the spectacle power.

1000 . 1000 +V 1336 −K 1336 + ELP 1336 − IOL 1336 − ELP 1000 +K 1000 −V Pr eR x (6)

The power calculation of the secondary piggyback IOL shares the same concept as PIOLs; thus the formula can also be applied for it. Before the vergence formula was widely used, some surgeons used their own nomograms based on empirical data. In Gills’s nomogram,6 the power of the IOL is determined by multiplying the spherical equivalent with 1.5× to 1.3×, depending on the axial lengths. The results were added by 1 for hyperopia but subtracted by 1 for myopia. In contrast to this nomogram and the formulae for pseudophakic eyes, the vergence formula tells us that axial length measurement is not required in the power calculation of PIOLs and secondary IOLs. Ocular parameters that are included are preoperative and desired postoperative refraction in the spectacle plane, vertex distance, corneal power (keratometry), and anterior chamber depth (ACD) for calculation of the ELP. 1.336 rather than 1.3375 is used as the refractive index because it is more physiologic to take the refraction index of the tear film into account; the resultant power is 44.8 D. Despite the differences in concepts between the nomogram and the vergence formula, Fenzl et al. found that both show 90% predictability within ±1 D, but fewer outliers were found from the vergence formula.7 The advantages of using van der Heijde’s or Holladay’s formula are simple and straightforward. By assuming that the cornea and the implantation lens behave as thin lenses, the power can be calculated using a minimal number of parameters. Thus the power calculations can be simplified in graphic or table form. Power calculation for toric PIOL is essentially the same by considering the power of each axis separately. However, the wound may contribute to some reduction of the power along its meridian.

Azar/Wong Simplified Phakic IOL Formula Although the van der Heijde equation and the Holladay equation are comparatively simpler than others, the IOL power PIOL must be calculated using a computer. Surgeons usually supply the parameters to the company and the company works out the powers for them; surgeons may have no ideas on the correct PIOL. For that reason, we have developed a new formula by making assumptions of some variables. The new formula can approximate PIOL in patients

CHAPTER 28  Phakic Intraocular Lens Power Calculations

with a corneal spherical equivalent from +10 to −20. For the Azar/Wong simplified or KLM formula, PIOL = 1.06L + KLM ,

Cornea

nair

ncor

Lens

First principal plane

of cornea Pcor′

(7)

where K is the keratometry reading, L is the preoperative spherical equivalent power corrected at the corneal plane, M is the IOL position or ELP in meters, which is equal to ACD minus the surgical factor or the surgeon factor (SF). This approximation formula works best for an ELP of 2.5–3.5 mm and myopic eyes with a steep cornea ranging from 41 D to 49 D and hyperopic eyes with a flat cornea from 39 D to 45 D. Thus this formula is good for the power calculation of PIOL. It can also be considered if a posterior chamber lens is replaced by an AC lens in a pseudophakic eye. However, it may not fit for the power calculation of secondary piggyback IOL, as the placement of the second lens is usually situated at the sulcus or in the bag. The ELP, M, is much deeper than those phakic eyes owing to the loss of bulk effect after removal of the crystalline lens, and the formula may need an adjustment factor for M > 4 × 10−3 m.

IOL

Second principal plane

395

of IOL PIOL PIOL′

naq

R1 P1 P

ELP

ng

R2 P′

x

n aq

P2

F’

Optic-lens

• Fig. 28.3  The effective lens position measured with respect to the two principal planes (red lines). The dotted line shows the pathway of a parallel light pass at the first principal plane, leave at the second principal plane, and fall on the optical axis at the back focal point (dotted line). The optic-lens distance is illustrated by the planes of two surfaces (dotted green lines). ELP is the effective lens position; n is the corresponding refractive index of the medium; Pcor′ and PIOL′ are the second principal planes of cornea and IOL; PIOL is the first principal plane of IOL; R1 and R2 are the anterior and posterior curvatures of the lens; x is the “optic constant” measured from the posterior surface of the lens to the first principal plane of IOL.

Effective Lens Position The ELP was previously calculated by subtracting a fixed anterior chamber depth (AA) with a variable SF (ELP = AA − SF).3 However, from the ultrasonic examinations of PIOLs, the lens–optic distance shows less variability compared with the endothelium–optic distance.8–16 There was a statistically significant annual reduction of about 24.7 µm in endothelium–optic distance over a 3-year follow-up period.17 Currently, it is preferable to use the measured ACD and subtract it with an “optic-lens” constant to obtain the value of the ELP. Thus accurate ACD measurement is important in determining the IOL power of the lens as it determines the lens position. Take an example using a phakic 6 lens; the ELP is determined by subtracting the ACD by 1 mm. Thus for an eye with an ACD of 3.30 mm, the ELP is 2.30 mm (i.e., 3.30 mm − 1.0 mm = 2.30 mm). This example is simplified to a thin-lens model in which the first and the second principal planes lie exactly at the vertex of the lens. Thus principal planes of the two refracting surfaces—the cornea and the IOL—change the vergences at the vertices of cornea and IOL, respectively. Anatomically, the positions of the lens have been studied vigorously by Olsen18,19 and Holladay7,20–22 on pseudophakic eyes, for the last decade. These data are useful as the three types of PIOLs—anterior supported PIOL (AS PIOL), iris-fixated PIOL (IF PIOL), posterior chamber PIOL (PC PIOL)—are situated at the same positions where pseudophakic AC IOL, iris-clip IOL, and sulcus IOL are placed. The optic-lens distances of the PIOLs have been studied as well.9–16 However, in reality, the thickness of the cornea and the IOL should be taken into account. Thus ELP is affected not only by the anatomic position of an IOL, but also by the locations of the principal planes of that IOL. The ELP should be measured from the second principal

plane of cornea to the first principal plane of the lens (Fig. 28.3). When a parallel light enters at the first principal plane of the lens, it will exit at the second principal plane and meet the optical axis at the back focal point (dotted line). The location of the principal planes with respect to the vertice distance depends on the powers of the two surfaces and the thickness and refractive index of the lens. They can be calculated using the Gaussian reduction.

Anterior Chamber Depth ACD measurement is required for the power calculations of phakic and secondary piggyback IOLs.20 Axial length (AL) measurement is not required. ACD measurements should be performed by a noncontact method, such as immersion ultrasound. Other noncontact instruments, such as Orbscan topography and IOL Master, can be used. Readings measured by contact methods can be more operator dependent and may be affected by the physical conditions in which the measurements are taken.23 In addition, repeated contact measurements may induce corneal abrasions or infections.

Keratometry and Refractive Index The keratometry readings can be measured by computerized corneal topography,24,25 autokeratometer, or Javal keratometer. The keratometer uses the tear film on the anterior corneal surface as a convex mirror.26,27 At a fixed working distance, the object size is adjusted to form the first Purkinje image of a constant size; object size is inversely proportional to curvature. For an average eye, only the central 3.2 mm

396 se c t i o n I X 396

Refractive Intraocular Lenses and Phakic Intraocular Lenses

of the cornea contributes to the reading. Owing to the small difference in refractive indices between the cornea and the aqueous, the image from the posterior cornea is too faint to allow measurement of curvature. For the interpretation of the keratometric results, certain things should be considered optically. The surgeon should be aware of what value of the refractive index of the cornea is used and whether the operated eye has a history of previous refractive surgery. In patients with previous photorefractive keratectomy, corneal topography to determine corneal power may result in unpredictable IOL power calculations.28 Overestimation of true corneal power may occur as the ratio of anterior to posterior corneal curvature has been altered by previous refractive surgery. Thus preoperative data, clinical history, and refraction should be considered in IOL calculations before cataract surgery. The present assumption of keratometry reading is a refractive index of the cornea of 1.3375. Some authors suggest using a value of 1.3315 to give a more appropriate measurement in the optical system.29,30

White-to-White Distance White-to-white distance is an important parameter for sizing PIOLs, especially for AS PIOLs and PC PIOLs. The parameter is not required for the calculation of PIOL using the van der Heijde equation. Different types of instruments can be used to measure corneal diameter or white-to-white distance.31 The most common manual device is the measuring caliper. It has a scale from 0 to 20.0 mm in 1.0-mm steps. Another manual device is the Holladay–Godwin cornea gauge, which is a hexagonal plate with a half-circle scale from 9.0 to 14.0 mm in 0.5-mm increments; it is held 1.0 mm from the cornea on measurement. Automated optical methods using Orbscan II and IOL Master can detect the border between white sclera and darker iris image. Measurement of white-to-white diameter with an Orbscan is more accurate than a caliper clinically32 but it has a mean of 0.24 mm lower than IOL Master. IOL Master showed a better correlation with the measurements of the video images and had the highest reliability.31 Pentacam measured significantly shorter white-to-white of about 0.05 mm than the IOL Master.33

Preoperative Refraction If the preoperative refraction has an error of 1.0 diopter (D) at the spectacle plane, the error of the postoperative refraction will be affected more in the hyperopic eye. If an error of 1 D higher is measured in the preoperative refraction (error +), the postoperative refraction will be more myopic compared with an eye that was aimed at postoperative emmetropia. Larger deviations of refractive errors found in hyperopic eyes are due mainly to the effect of the vertex distance.

Vertex Distance If a vertex distance of 13 mm is used but it was actually measured at 12 mm (error +), the postoperative refraction is estimated to be more myopic. Thus practically, if an eye was refracted at 11 mm but assumed to be measured at 12 mm (error +), the resultant refraction will be more myopic. This deviation can be approached to an error of 0.5 D in IOL power for an eye with extreme power. The effect will occur similarly in the PC IOLs and the AS PIOLs (within 0.02 D even in extreme powers).

Effective Lens Position and Anterior Chamber Depth For a lens situated at 2.1 mm with an error of 0.3 mm, the error can approach 0.4 D in −30.0 D. A more profound error can be seen in hyperopic eyes, which approaches 0.5 D in +15.0 D. Thus accurate determination of the ELP is necessary to produce high predictability. Although Pentacam measured significantly longer ACD measurement of about 0.14 mm than the IOL Master,33 the error should be within 0.2 D based on the PIOL power calculations; thus it is clinically not significant. If an incorrect ACD (from inner surface of cornea to anterior surface of the lens) is used, an error of 0.8 D in IOL power can be found in a +15.0 D eye (Fig. 28.4).

Mathematical Analysis of the Predictability of Different Types of PIOL Some parameters may be rounded to the nearest whole number for calculations. In addition, there may have been some measurement errors in different parameters. Thus using the van der Heijde formula, a number of mathematical models were made to estimate the predictability of outcome by assuming some errors in the parameters. The following parameters were considered: preoperative refraction, vertex distance, effective lens position, keratometry, and astigmatism.

• Fig. 28.4  The expected postoperative error in spectacle refraction if anterior chamber depth (ACD; endo) instead of ACD (epith) is taken into calculation.

CHAPTER 28  Phakic Intraocular Lens Power Calculations

Keratometry and Refractive Index Similar mathematical models were applied to keratometry and refractive index. Errors of ±3 D and ±0.04 were proposed for keratometry and refractive index. respectively. Despite proposing such high errors, the postoperative refractive errors are not high. At this juncture, we concluded that the keratometry readings measured by any instruments are good enough for power calculations of PIOLs. Any manipulations of keratometry readings using refractive index could not increase the predictability significantly. Other parameters are less important in causing errors in the final outcome.

Bioptics and Piggyback IOL Bioptics Bioptics, named by Zaldivar, is the correction of refractive error at both the corneal plane and the plane of the lens implant. The possible indication of bioptics should be at least −15.0 D or higher.34 Alternatively, it can be used for the correction of residual refractive error after implantation of the PIOL. The correction by laser in situ keratomileusis (LASIK) should be no sooner than 4 weeks after implantation. If planned bioptics was performed, Guell et al. suggested the adjustable refractive surgery (ARS) approach,34 in which a LASIK flap was performed immediately before the IOL implantation on the same setting as the cataract operation. The flap is lifted approximately 3 to 5 months after the first procedure and then stromal ablation with the excimer laser is performed. This procedure has an advantage in avoiding endothelium–IOL contact of the keratome procedure and lens position owing to sudden iris dilatation. However, this approach may increase intraoperative risks, as two procedures are involved at the same time. Also, a change of physiologic aberrations may occur and the risk of epithelial ingrowth may be greater. Studies on both Artisan and STAAR ICL showed high precision, predictability, and stability.34–39 When comparing with eyes undergoing PRK or LASIK, Sánchez-Galeana et al. preferred PRK over LASIK when the residual refractive error is lower than 6.00 D, corneal thickness is less than 500 µm, or nonorthogonal nonsymmetric astigmatism is present.39 The value of bioptics has been studied using our mathematical models, which show that bioptics may be indicated for extreme myopia or hyperopia, as predictability may decrease in these eyes.

Piggyback IOL The power calculation of primary piggyback IOLs requires axial length measurement. It is relatively unreliable, mainly because the back IOL in the bag can be displaced posteriorly by the front IOL. The power calculation will be different if the front IOL is put in the sulcus. Also, the principal planes of the two IOLs are somewhere between the princi-

397

pal planes of the individual IOLs and are related to their individual powers; and it will be difficult to determine the ELP and the cardinal planes.6 In addition, astigmatism induced by tilting may occur. Furthermore, the development of interlenticular opacification can induce a late hyperopic shift in refraction.40–44 Secondary piggyback IOL implantation can be considered in correcting refractive surprises in pseudophakic patients. The secondary lens can be put either into the bag with the first one or in the sulcus. The principle of IOL calculation for secondary piggyback IOL is similar to that for phakic IOL. Unlike primary piggyback IOLs, secondary piggyback IOLs do not require axial length for the calculation of IOL power. As a rule of thumb, for myopic cases, the IOL power chosen is approximately the power of the refractive surprise,45,46 which means that if a patient had a −3.00 D refractive surprise, the patient would most probably need a −3 D of IOL to neutralize the refraction. As for hyeropic cases, the power of the lens needed is about 1.5× the refractive power. This approximation is true only for low-power lenses and not for higher-power lenses.

IOL Calculations After PIOL Implantation Calculation of the correct IOL power for emmetropia will be difficult in patients with a history of PIOL.46 The presence of the posterior chamber IOL leads to a decrease in ultrasound velocity. This results in a longer axis measurement of the globe than normal. Wiechens et al.46 suggested that subsequent correction for velocity effects would be needed. Intraoperative retinoscopy of aphakic refraction and IOL calculation would be recommended. In addition, selection of a stronger power obtained in the IOL calculations (not SRK II) may be needed. Hoffer suggested a method of calculating the axial lengths in biphakic eyes47: if the eye is measured at an average velocity of 1555 m/s, the following calculation can be used, depending on the material of the phakic IOL: AL(corrected) = AL1555 + X*T, where T is the central thickness of the phakic IOL and X = + 0.42 (0.41–0.42) for PMMA, −0.59 (0.56–0.59) for silicone, +0.11 (0.10–0.12) for Collamer, and +0.23 (0.23–0.24) for acrylic. After the AL has been approximated by this formula, the author recommended that the Hoffer Q formula should be used for eyes < 22.0 mm, the Holladay 1 formula (not Holladay 2) for eyes between 24.5 and 26.0 mm, and the SRK/T formula for those longer than 26.0 mm.

Summary Accurate power calculations of phakic IOLs and piggyback IOLs and the correct choice of lenses are important in providing better quality of vision for patients requiring these procedures. The parameters required in the power calculation of these lenses differ from the calculation of a pseudophakic lens or a primary piggyback IOL in that they do not require axial length measurements. Our analysis confirms that the vertex distance, ELP (ACD), and preoperative

398 se c t i o n I X 398

Refractive Intraocular Lenses and Phakic Intraocular Lenses

TABLE 28.1  Effective Lens Position (ELP), 2.4 mm—Spherical Equivalent Measured at Vertex Distance of 12 mm SE (spec)

Rx pre ± 1 D

Vertex Distance ± 1 mm

ELP/M ± 0.3 mm

Keratometry ± 3 D

Refractive Index ± 0.04

IOL diff (D)

Rx post (D)

IOL diff (D)

Rx post (D)

IOL diff (D)

Rx post (D)

IOL diff (D)

Rx post (D)

IOL diff (D)

Rx post (D)

−25

0.65

0.55

0.41

0.34

0.36

0.31

0.25

0.21

0.09

0.07

−20

0.72

0.61

0.29

0.24

0.32

0.27

0.21

0.18

0.08

0.06

−15

0.81

0.68

0.18

0.15

0.27

0.23

0.17

0.14

0.06

0.05

−5

1.03

0.87

0.03

0.02

0.11

0.09

0.06

0.05

0.03

0.02

5

1.36

1.16

0.03

0.03

0.15

0.12

0.07

0.06

0.03

0.03

10

1.59

1.35

0.16

0.14

0.34

0.29

0.16

0.14

0.08

0.07

15

1.89

1.60

0.42

0.36

0.59

0.50

0.27

0.23

0.14

0.12

IOL diff, Difference of intraocular lens power; Rx, Refractive index

refraction are the most important parameters needed for ensuring high predictability of PIOLs. Other parameters are less important in causing errors in the final outcome. The mathematical models are consistent with previous clinical studies showing that PIOLs are highly predictable. These lenses can be considered in patients with moderate or high refractive errors. The approximation equation of residual astigmatism provides the general idea of how the lenticular astigmatism affects the astigmatism in an eye with a spherical lens implanted. The estimated difference of intraocular lens power in diopters (IOL diff [D]) and the postoperative refractive error (Rx post [D]) in different scenarios where errors of preoperative refractive error (Rx pre ± 1 D), vertex distance ± 1 mm, effective lens position (ELP/M ± 0.3 mm), keratometry ± 3 D, and refractive index ± 0.04 were summarized in Table 28.1.

References 1. Gayton JL, Sanders VN. Implanting two posterior chamber intraocular lenses in a case of microphthalmos. J Cataract Refract Surg. 1993;19:776–777. 2. van der Heijde GL, Fechner PU, Worst JG. Optical consequences of implantation of a negative intraocular lens in myopic patients. Klin Monatsbl Augenheilkd. 1988;193:99–102. 3. Holladay JT. Refractive power calculations for intraocular lenses in the phakic eye. Am J Ophthalmol. 1993;116:63–66. 4. van der Heijde GL. Some optical aspects of implantation of an IOL in a myopic Eye. Eur J Ophthalmol. 1989;1:245–248. 5. van der Heijde RGL, Budo CJ. Power calculation of phakic IOLs. In: Alió JL, Perez-Santonja JJ, eds. Refractive Surgery With Phakic IOLs. El Dorado, Panama: Highlights of Ophthalmology; 2004:64 (chap 5). 6. Holladay JT, Gills JP, Grabow JP, et al. Piggyback intraocular lenses. Ann Ophthalmol. 1998;30:203–206. 7. Fenzl RE, Gills JP, Cherchio M. Refractive and visual outcome of hyperopic cataract cases operated on before and after imple-

mentation of the Holladay II formula. Ophthalmology. 1998;105: 1759–1764. 8. Saragoussi JJ, Priech M, Assouline M, et al. Ultrasound biomicroscopy of Baikoff anterior chamber phakic intraocular lenses. J Refract Surg. 1997;13:135–141. 9. de Souza RF, Allemann N, Forseto A, et al. Ultrasound biomicroscopy and Scheimpflug photography of angle-supported phakic intraocular lens for high myopia. J Cataract Refract Surg. 2003;29:1159–1166. 10. Pop M, Payette Y, Mansour M. Ultrasound biomicroscopy of the Artisan phakic intraocular lens in hyperopic eyes. J Cataract Refract Surg. 2002;28:1799–1803. 11. Jiménez-Alfaro I, García-Feijoó J, Pérez-Santonja JJ, et al. Ultrasound biomicroscopy of ZSAL-4 anterior chamber phakic intraocular lens for high myopia. J Cataract Refract Surg. 2001;27: 1567–1573. 12. Muñoz G, Monté-Micó R, Belda JI, et al. Cataract after minor trauma in a young patient with an iris-fixated intraocular lens for high myopia. Am J Ophthalmol. 2003;135:890–891. 13. Trindade F, Pereira F, Cronemberger S. Ultrasound biomicroscopic imaging of posterior chamber phakic intraocular lens. J Refract Surg. 1998;14:497–503. 14. García-Feijoó J, Alfaro IJ, Cuiña-Sardiña R, et al. Ultrasound biomicroscopy examination of posterior chamber phakic intraocular lens position. Ophthalmology. 2003;110:163–172. 15. García-Feijoó J, Hernández-Matamoros JL, Castillo-Gómez A, et al. High-frequency ultrasound biomicroscopy of silicone posterior chamber phakic intraocular lens for hyperopia. J Cataract Refract Surg. 2003;29:1940–1946. 16. García-Feijoó J, Hernández-Matamoros JL, Méndez-Hernández C, et al. Ultrasound biomicroscopy of silicone posterior chamber phakic intraocular lens for myopia. J Cataract Refract Surg. 2003;29:1932–1939. 17. Ferreira TB, Portelinha J. Endothelial distance after phakic irisfixated intraocular lens implantation: a new safety reference. Clin Ophthalmol. 2014;8:255–261. 18. Olsen T, Olesen H, Thim K, et al. Prediction of pseudophakic anterior chamber depth with the newer IOL calculation formulas. J Cataract Refract Surg. 1992;18:280–285.

CHAPTER 28  Phakic Intraocular Lens Power Calculations

19. Olsen T, Corydon L, Gimbel H. Intraocular lens power calculation with an improved anterior chamber depth prediction algorithm. J Cataract Refract Surg. 1995;21:313–319. 20. Holladay JT. Standardizing constants for ultrasonic biometry, keratometry, and intraocular lens power calculations. J Cataract Refract Surg. 1997;23:1356–1370. 21. Holladay JT, Long SA, Lewis JA, et al. Determining intraocular lens power within the eye. J Am Intraocul Implant Soc. 1985;11:353–363. 22. Holladay JT, Maverick KJ. Relationship of the actual thick intraocular lens optic to the thin lens equivalent. Am J Ophthalmol. 1998;126:339–347. 23. Vetrugno M, Cardascia N, Cardia L. Anterior chamber depth measured by two methods in myopic and hyperopic phakic IOL implant. Br J Ophthalmol. 2000;84:1113–1116. 24. Cuaycong MJ, Gay CA, Emery J, et al. Comparison of the accuracy of computerized videokeratography and keratometry for use in intraocular lens calculations. J Cataract Refract Surg. 1993;19(suppl):178–181. 25. Husain SE, Kohnen T, Maturi R, et al. Computerized videokeratography and keratometry in determining intraocular lens calculations. J Cataract Refract Surg. 1996;22:362–366. 26. Elkington F. Clinical Optics. 2nd ed. Oxford, UK: Blackwell Scientific Publications; 1991. 27. Leyland M. Validation of Orbscan II posterior corneal curvature measurement for intraocular lens power calculation. Eye (Lond). 2004;18:357–360. 28. Ladas JG, Boxer Wachler BS, Hunkeler JD, et al. Intraocular lens power calculations using corneal topography after photorefractive keratectomy. Am J Ophthalmol. 2001;132:254–255. 29. Olsen T. On the calculation of power from curvature of the cornea. Br J Ophthalmol. 1998;24:152–154. 30. Gobbi PG, Carones F, Brancato R. Keratometric index, videokeratography, and refractive surgery. J Cataract Refract Surg. 1998;24:202–211. 31. Baumeister M, Terzi E, Erici Y, et al. Comparison of manual and automated methods to determine horizontal corneal diameter. J Cataract Refract Surg. 2004;30:374–380. 32. Thompson HW, Romero C, Kaufman HE. Reproducibility and agreement of caliper, ultrasound and Orbscan measurement of anterior chamber width. In: International Society of Refractive Surgery Meeting. New Orleans, LA: 2001. 33. Sayed KM, Alsamman AH. Interchangeability between Pentacam and IOLMaster in phakic intraocular lens calculation. Eur J Ophthalmol. 2015;25(3):202–207.

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34. Güell J, Vázquez M. Bioptics. Int Ophthalmol Clin. 2000;40(3): 133–143. 35. O’Brien TP, Awwad ST. Phakic intraocular lenses and refractory lensectomy for myopia. Curr Opin Ophthalmol. 2002;13:264–270. 36. Zaldivar R, Davidorf JM, Oscherow S, et al. Combined posterior chamber phakic intraocular lens and laser in situ keratomileusis: bioptics for extreme myopia. J Refract Surg. 1999;15:299–308. 37. Zaldivar R, Oscherow S, Piezzi V. Bioptics in phakic and pseudophakic intraocular lens with the Nidek EC-5000 excimer laser. J Refract Surg. 2002;18(suppl):S336–S339. 38. Güell JL, Vázquez M, Gris O. Adjustable refractive surgery: 6-mm Artisan lens plus laser in situ keratomileusis for the correction of high myopia. Ophthalmology. 2001;108:945–952. 39. Sánchez-Galeana CA, Smith RJ, Rodriguez X, et al. Laser in situ keratomileusis and photorefractive keratectomy for residual refractive error after phakic intraocular lens implantation. J Refract Surg. 2001;17:299–304. 40. Findl O, Menapace R, Rainer G, et al. Contact zone of piggyback acrylic intraocular lenses. J Cataract Refract Surg. 1999;25: 860–862. 41. Shugar JK, Keeler S. Interpseudophakos intraocular lens surface opacification as a late complication of piggyback acrylic posterior chamber lens implantation. J Cataract Refract Surg. 2000;26: 448–455. 42. Shugar JK, Schwartz T. Interpseudophakos Elschnig pearls associated with late hyperopic shift: a complication of piggyback posterior chamber intraocular lens implantation. J Cataract Refract Surg. 1999;25:863–867. 43. Gayton JL, Apple DJ, Peng Q, et al. Interlenticular opacification: clinicopathological correlation of a complication of posterior chamber piggyback intraocular lenses. J Cataract Refract Surg. 2000;26:330–336. 44. Mejía LF. Piggyback posterior chamber multifocal intraocular lenses in anisometropia. J Cataract Refract Surg. 1999;25: 1682–1684. 45. Milauskas AT, Marnay S. Pseudo axial length increase after silicone lens implantation as determined by ultrasonic scans. J Cataract Refract Surg. 1988;14:400–402. 46. Wiechens B, Winter M, Haigis W, et al. Bilateral cataract after phakic posterior chamber top hat-style silicone intraocular lens. J Refract Surg. 1997;13:392–397. 47. Hoffer KJ. Ultrasound axial length measurement in biphakic eyes. J Cataract Refract Surg. 2003;29:961–965.

29 

Refractive Lens Exchange JORGE L. ALIÓ, ANDRZEJ GRZYBOWSKI, AND PIOTR KANCLERZ

Introduction The idea of removing the lens for refractive purposes dates back the 18th century. Abbé Desmonceaux was probably the first to propose such a surgery in France in 1776 for a patient with high myopia. In the last decades of the 19th century, the first systematically conducted operations of clear lens exchange were carried out by a Polish ophthalmologist named Vincenz Fukala in Vienna. Fukala’s indications for surgery included poor vision, inability to work, and myopia of −13 diopters (D) or higher. He operated on children with progressive myopia or young adults; the upper age limit was 40 years. The first step of Fukala’s procedure was the dissection of the clear lens in order to observe a clear pupil at the end of surgery. Postoperatively, the eye was treated with atropine; then, several days were to elapse after washing out the swollen lens fragments. If symptoms of intraocular inflammation, pain, or photophobia arose, the remaining lens material was removed by needle. Following this procedure, most patients for the first time in their lives achieved robust visual acuity. Fukala recommended this surgery for both eyes to establish binocular vision. Despite many opponents, this operation was widespread among ophthalmologists in Europe. As a result of high rates of postoperative retinal detachment and other complication—such as ocular infection, retinal hemorrhages, and glaucoma—the procedure was gradually abandoned at the beginning of the 20th century.1 Currently, as a result of advances in small-incision technique, cataract surgery has evolved from being primarily considered as a method of opaque lens removal to a procedure yielding the best postoperative refractive result. As the incidence of complications has significantly decreased, the use of lens removal as a refractive procedure has emerged. A significant advantage of lens refractive surgery compared to corneal surgery is that it covers a wider range of refractive errors. In high refractive errors both phakic intraocular lens (IOL) and refractive lens exchange (RLE) might be considered. According to the European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO), 400

RLE is the second most frequently performed noncorneal refractive procedure. Furthermore, there has been a significant increase in number of RLE cases over time. The age of patients undergoing this procedure is older than patients having other refractive procedures; one of the reasons might be early cataract formation but also the possibility to correct presbyopia. This group of patients is socially better situated, thus able to afford this costly treatment.2 With increasing numbers of performed RLE procedures and overrepresentation of myopic patients, in certain western countries the population of phakic myopes reaching “cataract age” will likely be lower in future.3

Pearls in Surgical Technique The surgical technique for RLE is a modification of standard cataract surgery. The main differentiating elements are transparency and softness of the crystalline lens, absence of cataract, and presence of an abnormal ocular anatomy because of high refractive error. The best approach to RLE includes a minimally invasive surgery, either with coaxial or biaxial methods, through the smallest possible incision. Micro-incisional cataract surgery (MICS), with the final incision of 1.6 to 1.8 mm for IOL implantation, improves the visual and surgical outcomes while also reducing the risk of complications.4 The procedure is typically performed under topical anesthesia. RLE can be conducted more conveniently and safely using a bimanual technique. In a biaxial procedure surgery, the steepest corneal meridian is marked, and two incisions are performed 90 degrees apart from each other. Currently, 19 G (1/1.1 mm) and 21 G (0.7 mm) instrumentation is employed for MICS. Thus a relatively wider incision should be made to enable unhampered manipulations within the anterior chamber (AC): 1.2 mm internally and 1.4 mm externally for 19 G tools and 1 mm for 21 G. One of the incisions should be located in the positive meridian of the cornea—it will be enlarged for IOL implantation. Another approach is to create a third incision for IOL implantation in the positive meridian shortly before IOL introduction into the eye. Likewise, with femtosecond laser-assisted cataract surgery (FLACS), the multiplanar clear corneal incision

CHAPTER 29  Refractive Lens Exchange

for IOL implantation is performed as a separate incision at the beginning of the procedure subsequent to the docking of the laser. It is believed that femtosecond (FS) corneal incisions exhibit less damage to the cornea and allow faster healing. Moreover, femtoincisions prove to be stable, more resistant to deformation and leakage, and reproducible at various intraocular pressures. Another advantage is that they do not change corneal high-order aberration significantly, featuring favorable results in triplanar configuration.5 After the incision, a 1% preservative-free lidocaine solution diluted 1:1 with balanced salt solution4 or pure 1% lidocaine7 is injected into the AC. As a result of small incision size, the continuous curvilinear capsulorhexis (CCC) has to be carried out with a bent capsulotomy needle or 23-gauge vitrectomy-style micro-incisional capsulorhexis forceps. The capsulotomy construction is significant for the final position of the IOL. An inaccurate prediction of the effective lens position (ELP) has been identified as the biggest source of error in IOL power calculations. Hence, performing an FS laser capsulotomy might enhance the degree of circularity and improve IOL centration. Moreover, FS laser capsulotomies compared to manual CCC manifest less distortions over time. This is believed to provide a more stable refractive result, although no significant differences were observed for the ELP, corrected distance visual acuity, or refractive error.6 Cortical cleaving hydrodissection should be performed in two distal quadrants. Although in RLE the nucleus is soft, the use of specially designed symmetric prechoppers, such as Alió-Scimitar MICS (Katena Inc.) might yield cutting the nucleus in half without placing any asymmetric pressure on the zonules.7 For RLE during phacoemulsification, high values of fluidics are recommended, though with low phaco power. Further, short power modulation techniques, such as hyperpulse or ultrapulse, may decrease the risk of corneal wound burn, as the off-time cycle permits cooling of the phaco-tip and cornea. The use of femtolaserassisted lens fragmentation might be beneficial, as it decreases the energy required to emulsify the lens, ensuring that endothelial cells have less exposure to phaco-energy.5 Following emulsification of the nuclear segments, the cortical material remaining in the capsular bag is removed with irrigation/aspiration. Separation of irrigation and aspiration in two independent handpieces prevents generating vortex currents at the end of the phaco-tip. Another advantage of the bimanual technique is the feasibility to remove the subincisional cortex without switching handpieces. It is worth highlighting that MICS enables outstanding AC stability, as the irrigation handpiece is constantly within the AC. As well, the impermeability of two smaller incisions is greater than with a larger incision. Thus the incidence of intraocular hypotony and the risk of AC collapse declines considerably, resulting in decreased risk of posterior vitreous detachment during surgery. This is likely quite beneficial, particularly in myopes. The value of MICS is that it can be performed with most phacoemulsification platforms. The parameters favor

401

fluidics with high levels of irrigation/aspiration pressure, rather than phaco power. A Venturi pump system may be recommended, as it provides fast reaction and great flexibility. Standard infusion tools could be insufficient regarding hydrodynamics; hence, particular MICS high-inflow tools should be employed. The major disadvantage of bimanual phacoemulsification lies in the current limitations of IOL technology.

IOL Power Calculation The calculation of IOL power does not differ from those calculations made when a cataract is present. Yet, based on the absence of other ocular pathologies and long life expectancy, the patient may be more demanding. Furthermore, the loss of accommodation, particularly in prepresbyopic patients, should be discussed meticulously. An alternative might be the use of multifocal or accommodative lenses. Optical coherence-based biometry with integrated keratometry has become a gold standard in IOL power calculations. The actual desired postoperative refraction should also be discussed since a small degree of myopia (−0.5 D) may be desirable in the case of monofocal IOL use. The parameters taken into consideration for IOL calculations are the axial length of the eye, corneal curvature, and AC depth. The Haigis formula utilizes the formerly mentioned measurements and can be treated as the first choice for use (Table 29.1).8 It has a rather small postoperative median absolute error and can be used with eyes of all axial lengths. Westin et al.3 claim that the use of Haigis’s formula resulted in better biometry prediction in the RLE cohort compared to patients undergoing cataract surgery. For eyes under 22 mm in axial length, the Hoffer Q formula should be applied for comparative assessment. The SRK-T formula manifests a lower predictive accuracy in short eyes. For that reason, it should be used for comparative purposes only in eyes over 22 mm of axial length. The Holladay 1 formula might be the second choice for eyes with an axial length of 22 to 26 mm. The Holladay 2 is a 4th-generation formula that takes into account the disparities in the anterior segment by adding the corneal white-to-white diameter and lens thickness. This might facilitate estimating the exact position of the IOL and shows benefits in eyes under 22 mm of axial length. With most of the currently used devices for IOL calculation, the ability to determine true corneal power is limited. The relationship between the anterior and posterior corneal surfaces is fixed and estimated based on an empiric “keratometric index.” Such evaluation leads to overestimation of astigmatism in with-the-rule astigmatism, whereas in eyes with against-the-rule astigmatism it could be underestimated. Therefore assessing the optical power of the posterior corneal surface—specifically, its astigmatism— with a Scheimpflug analyzer could potentially increase the refractive outcome in RLE.9 This issue was known to be important in IOL calculations in eyes that underwent

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TABLE 29.1  Criteria for IOL Calculation Formula Selection Depending on Axial Length of the Eye

Criteria

Axial Length < 22 mm

Axial Length 22 mm

Axial Length 24.5 mm

Axial Length > 26 mm

1st choice formula

Hoffer Q, Haigis

SRK-T, Haigis

SRK-T, Haigis

SRK-T, Haigis

2nd choice formula

Holladay 2

Holladay

Holladay

−

Adapted from Alió JL, Grzybowski A, Romaniuk D. Refractive lens exchange in modern practice: when and when not to do it? Eye Vis (Lond). 2014;1:10

1st possibility

2nd possibility

Kpre, Rpre, Kpost, Rpost

Rpre, Rpost, Kpost

Holladay 2 formula

Clinical history method

Holladay 2 formula

Refraction method

IOL calculation

Corrected Kpost

Holladay 2 formula

IOL calculation

• Fig. 29.1

  Methods to calculate intraocular lens (IOL) power following keratorefractive surgery. Kpost, Postoperative keratometry; Kpre, preoperative keratometry; Rpost, postoperative refraction; Rpre, preoperative refraction. (Adapted from Alio JL, Grzybowski A, El Aswad A, Romaniuk D. Refractive lens exchange. Surv Ophthalmol. 2014;59:579–598.)

a corneal refractive surgery, as it removes corneal tissue. Subsequently, the relationship between the front and back surfaces of the cornea is altered, invalidating the use of this standardized index of refraction. Another important issue after a corneal refractive procedure and in irregular corneas is the inaccuracy of keratometry—it performs the measurements from small regions or paracentral points of the cornea. This might be insufficient for a postsurgical cornea, that has a wide range of curvature, even in the central 3-mm region. The strategy for calculating IOL power following keratorefractive surgery depends on the preoperative data that can be obtained—in particular, preoperative keratometry and refractive error. These data should be employed for assessing the corrected postoperative keratometric values. The clinical history method is the most reliable to evaluate the corneal power after the refractive procedure. In this method, the spherical equivalent change is subtracted from the original lens power.

Finally, the Holladay 2 formula is used for IOL calculation. Many strategies exist, and the recommended practice pattern is presented in Fig. 29.1. It should also be noted that newer formulas—such as Camellin-Calossi, ShammasPL, Haigis-L, and Barrett True-K—might provide a low prediction error. However, to date, a clear advantage of applying these formulas has not been proven. Another fascinating idea for improving IOL calculation is the application of ray-tracing analysis. Ray tracing is defined as a calculation method for a single ray passing through the optical system. Specifically, the refraction of rays at each optical surface is calculated using Snell’s law. A map of corneal power achieved in topography or with the Scheimpflug camera can be transformed into an array of individual measurements representing a polygonal shape. With ray tracing, optical properties of each structure of the eye is analyzed in order to evaluate the performance of the entire optical system. This software used for calculation of

CHAPTER 29  Refractive Lens Exchange

IOL power might provide the best performance for these demanding cases. Particularly in eyes after refractive surgery, it might help to solve the issue of higher-order aberrations (HOA) of the cornea by selecting a particular design of an IOL.

Main Indications and Outcome Patients with high-myopia are often willing to undergo refractive procedure in order to become spectacle or contact lens independent. In these cases, RLE or AC phakic IOL can be considered, particularly when corneal surgery is not possible. The EUREQUO database analysis revealed that the mean preoperative corrections with RLE, phakic IOL, PRK, and laser in situ keratomileusis (LASIK) were −5.8 D, −8.5 D, −3.2 D and −3.5 D, respectively.2 Moreover, the mean patient age was significantly higher for RLE: 54.2 years compared to 38.0 years for phakic IOL. In a study conducted on a Swedish cohort, 47.6% undergoing refractive lens surgery were myopic.3 In contrast, just 18.2% of patients undergoing cataract surgery were myopic, with a statistically significant difference. The refractive outcome of RLE is similar or better than that of cataract surgery. In a study by Westin et al. the mean postoperative refractive error for cataract surgery was significantly greater than for RLE; 0.17 ± 0.27 D and 0.4 ± 0.58 D, respectively.3 One possible explanation for higher accuracy in the RLE cohort was the use of the Haigis formula. However, it must be taken into account that abnormal ocular anatomy might lead to difficulties in accurate IOL power prediction. Fink et al.13 reported good refractive predictability in hyperopic RLE only up to +4.0 D. In patients with high myopia, the postoperative refractive goal of a mild residual myopia can be helpful to avoid a hyperopic surprise. In some studies, the target refraction for patients with high myopia has been determined to be −1 D to −3 D.11 The outcome of RLE is summarized in Table 29.2. Considering RLE as a refractive procedure, safety should be treated as a priority. Although the incidence of complications is similar to that of cataract surgery, the abnormal ocular anatomy must be taken into account. The most vision-threatening complication of RLE, especially in myopic eyes, is retinal detachment (RD). The reported incidence ranges from 8.1%18 to 0.37%.3 Being under 50 years of age is associated with the risk of RD. Furthermore, the peril of cystoid macular edema might be higher in eyes with posterior vitreous adherence, particularly in younger patients. On the other hand, the EUREQUO database analysis presented that intraoperative complications were reported in only 1.1% of surgery, while postoperative complications in 2.6% of cases. The most commonly reported problem in this cohort was a postoperative refractive error. The most common postoperative complication in this cohort was incidence of a refractive error.2 A long-term complication of RLE is posterior capsule opacity, which can take place from months to years after

403

surgery. Incidence rates reach up to 77.89% in a 4.78 years follow-up.10 No preoperative prophylaxis can be made. Neodymium:yttrium-aluminum-garnet (Nd:YAG) capsulotomy is the optimal treatment, though capsulotomy should be avoided as much as possible.7 In small hyperopic eyes with shallow AC, the risk of angle-closure glaucoma could be higher than in other eyes. This could be an indication for RLE, offering a favorable risk:benefit ratio. The incidence of complications such as retinal detachment and cystoid macular edema is lower than in RLE treatment for myopia. Despite typical cataract surgery complications, the risk for complications in short hyperopic eyes with axial lengths < 21 mm is related to their anatomy.12 Less space in the anterior segment and shallower AC may predispose patients to pupillary block or fluid misdirection syndrome. Furthermore, uveal effusions are also seen more often in hyperopic eyes. The introduction of toric IOLs has become a milestone in pseudophakic astigmatism treatment. The use of these lenses might be beneficial specifically in patients with a high refractive error.14 For smaller refractive errors, RLE with IOL implantation could have more sight-threatening complications than corneal refractive surgery. A potential complication of RLE for astigmatism is toric IOL misalignment, which might significantly influence the visual outcome. Furthermore, RLE with toric IOL implantation was reported to predictably correct myopia in eyes with keratoconus.15 It should be emphasized that for eyes with a smaller degree of astigmatism, limbal relaxing incisions might be an attractive alternative to toric IOL implantation. The use of FS laser might enhance the reliability and preciseness of the limbal relaxing incision (LRI).19 Additionally, nonpenetrating FS intrastromal keratotomy might decrease the postoperative pain and risk for infection, as the corneal epithelium and stroma are not opened up to the ocular surface.20 RLE provides several alternatives for correcting presbyopia, including monovision, multifocal, and accommodating IOLs.21 Currently micro- and minimonovision are most commonly applied, and they can be combined with monofocal and multifocal IOLs. Multifocal IOL optical designs aim to provide patients with spectacle independence for both distance and near visual conditions by generating several foci at various distances. Accommodative IOLs take advantage of ciliary muscle residual activity, supplying, during its contraction, an anterior movement of the IOL optical plate within the posterior chamber. A recent study presented that sulcus placed accommodative IOLs might provide an amplitude of accommodation reaching 1.27 D for a 4 D stimulus.22 RLE is absolutely necessary in particular subpopulations of children. The vast majority of anisometropic children do well with glasses and some can be managed with contact lenses. Many with neurobehavioral disorders or who are neurologically normal children, but cannot tolerate standard correction might require refractive surgery. The most common neurobehavioral indications are cerebral palsy,

388/273 (RLE/ cataract extraction)

20/12

50/29 Group A Preop SE ≤ 4 D Group B Preop SE > 4 D

30/19

34/20

26/13

7/7

Ravalico et al., 200311

Preetha et al., 200312

Fink et al., 200013

Ruiz et al., 200914

Leccisotti, 200615

Tychsen et al., 200616

Ali et al., 200717

0.45 ± 0.25 Group A: 0.81 ± 0.30 Group B: 0.58 ± 0.33 0.89 ± 0.09

0.48 ± 0.25

0.53 ± 0.29 Group A: 1.13 Group B: 1.04

0.87 ± 0.10

0.55 ± 0.23

+0.68 Group A: −0.18 ± 0.73 Group B: −0.19 ± 1.28 -0.007 ± 0.61 (mean refractive cylinder: −0.53 ± 0.30) −1.31 ± 1.08 (mean refractive cylinder 1.22 ± 1.37) 73% within ±1 D of goal refraction (+1.0 D) 86% within the goal refraction of 0 to +3 D

Group A: +2.26 ± 0.94 Group B: +6.32 ± 1.32 -0.70 ± 5.32 (mean refractive cylinder −2.46 ± 0.99) −11.0 ± 4.65 (mean refractive cylinder 1.86 ± 1.39) −19.1 −16.7

20/2550 (UDVA)

0.26

0.15

N/A

N/A

+6.66 ± 2.17

0.2

-2.0 ± 1.62 (goal refraction between −1.0 D to −3.0 D)

N/A

−15.95

0.37

−1,22 41% within ±1 D of emmetropia 79% within ±2 D of emmetropia

Mean Postoperative UDVA

−17.84

Mean Postoperative SE (D)

Mean Preoperative CDVA

N/A

0.52

0.76 ± 0.23

Myopic regression 0,43 D/y 2 eyes PCO

Myopic regression 0.16 D/y

9% PVD 15% dysphotopsia phenomena

Not reported

3.8 y

4.5 y

12 mo

6 mo

10 mo

1 eye CME 1 eye CSR Group A: 1.10 ± 0.17 Group B: 1.02 ± 0.16 0.95 ± 0.09

16.96 mo

47.16 mo

4.78 y

Mean Follow-up Time

6 patients PCO

32.73% risk of PCO 0.26% risk of RD

77.89% risk of PCO 2.1% risk of RD

Postoperative Complications

0.63 ± 0.30

0.58 ± 0.32

Comparing to preoperative: 83.7% better 12.6% equal 3.7% worse

Mean Postoperative CDVA

Visual acuities presented in decimal scale. a For comparative purposes, two studies were chosen for all of the following indications: myopia, hyperopia, RLE with toric intraocular lens implantation, and RLE in children. CDVA, Corrected distance visual acuity; CME, cystoid macular edema; CSR, central serous chorioretinopathy; N/A, not available; PCO, posterior capsule opacification; PVD, posterior vitreous detachment; RD, retinal detachment; RLE, refractive lens exchange; SE, spherical equivalent; UDVA, uncorrected distance visual acuity. Adapted from Alió JL, Grzybowski A, Romaniuk D. Refractive lens exchange in modern practice: when and when not to do it? Eye Vis (Lond). 2014;1:10.

190/107

No. of Eyes/ Patients

FernándezVega et al., 200310

Author, Year

Mean Preoperative SE (D)

TABLE a 29.2  Outcome of Refractive Lens Exchange in Selected Studies

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autism, Angelman syndrome, more severe Down syndrome, suboptimally controlled seizure disorders or idiopathic developmental delay.23 Neurologically normal children might not accept a standard correction because of aniseikonia and anisovergence, with chronic asthenopia or diplopia. As well, wearing glasses may be stigmatizing for a child, and contact lenses might be difficult to insert or remove. Another group of indications in children is severe ametropia.17 While the range of excimer laser correction is limited to eyes between −12 D and +6 D, for children with a refractive error beyond this, other methods are required. Implanting a phakic IOL is likely the most frequently employed method in these patients. There is concern surrounding safe lens insertion and endothelial cell loss in eyes with ACs shallower than 3.2 mm. In such patients, RLE should be considered. In addition, the upper limit of ametropia that can be corrected with phakic IOLs is 20 D, and with higher refractive errors, RLE might be necessary. RLE can be beneficial for children with particular congenital lens abnormalities (i.e., microspherophakia), secondary glaucoma, or other congenital disorders disabling proper binocular vision.8 In children, all RLE procedures are performed under general anesthesia. A primary capsulectomy with anterior vitrectomy is recommended, as there is a high rate of formation of a dense, posterior capsule fibrosis if the capsule is preserved. In children, because of an increase in axial length of the eye, the final refractive outcome might be difficult to estimate. Thus in certain cases, clear lens extraction (CLE) may be performed, with postponing the decision for IOL implantation. Importantly, removing the lens abolishes the ability to accommodate. This disadvantage can be partly resolved by multifocal IOL implantation. Moreover, there is a risk in approximately 3% of patients of developing retinal detachment. If axial length exceeds approximately 29 mm, barrier diode laser therapy might be applied. In children, the results of RLE are satisfactory, as the improvement in uncorrected visual acuity might be strongly relevant. Furthermore, the correction of the refractive error might prevent development of amblyopia. The refractive accuracy of RLE in children is estimated as 81% of eyes reaching ±2 D of target refraction.16 Another issue is the unpredictability of the increase in eye size during childhood, which is actually concomitant with overall growth. This leads to a myopic regression of 0.16 to 0.43 D annually, which has to be taken into account during preoperative IOL calculation.16,17

Conclusions In patients with high degrees of myopia, hyperopia, and astigmatism, RLE might be an appealing alternative to corneal refractive surgery. However, for every patient, a scrupulous risk–benefit analysis should be performed. The possibility for a potential postopreative refractive error should be taken into consideration. The most adequate surgical technique should be chosen, including an FS

405

laser–assisted procedure, if possible. Proper patient selection and education and thorough follow-up are the most important factors leading to success, particularly for multifocal lenses.

References 1. Schmidt D, Grzybowski A. Vincenz Fukala (1847-1911) and the early history of clear-lens operations in high myopia. Saudi J Ophthalmol. 2013;27:41–46. 2. Lundström M, Manning S, Barry P, Stenevi U, Henry Y, Rosen P. The European Registry of Quality Outcomes for Cataract and Refractive Surgery (EUREQUO): a database study of trends in volumes, surgical techniques and outcomes of refractive surgery. Eye Vis (Lond). 2015;2:8. 3. Westin O, Koskela T, Behndig A. Epidemiology and outcomes in refractive lens exchange surgery. Acta Ophthalmol. 2015;93: 41–45. 4. Alió JL, Klonowski P, El Kady B. Microincisional lens surgery. In: Kohnen T, Koch DD, eds. Cataract and Refractive Surgery. Berlin, Heidelberg: Springer-Verlag; 2009:11–26. 5. Alio JL, Soria F, Abdou AA. Femtosecond laser assisted cataract surgery followed by coaxial phacoemulsification or microincisional cataract surgery: differences and advantages. Curr Opin Ophthalmol. 2014;25:81–88. 6. Panthier C, Costantini F, Rigal-Sastourné JC, et al. Change of capsulotomy over 1 year in femtosecond laser-assisted cataract surgery and its impact on visual quality. J Refract Surg. 2017;33: 44–49. 7. Alio JL, Grzybowski A, El Aswad A, Romaniuk D. Refractive lens exchange. Surv Ophthalmol. 2014;59:579–598. 8. Alió JL, Grzybowski A, Romaniuk D. Refractive lens exchange in modern practice: when and when not to do it? Eye Vis (Lond). 2014;1:10. 9. Rydström E, Westin O, Koskela T, Behndig A. Posterior corneal astigmatism in refractive lens exchange surgery. Acta Ophthalmol. 2016;94:295–300. 10. Fernández-Vega L, Alfonso JF, Villacampa T. Clear lens extraction for the correction of high myopia. Ophthalmology. 2003;110: 2349–2354. 11. Ravalico G, Michieli C, Vattovani O, Tognetto D. Retinal detachment after cataract extraction and refractive lens exchange in highly myopic patients. J Cataract Refract Surg. 2003;29:39–44. 12. Preetha R, Goel P, Patel N, et al. Clear lens extraction with intraocular lens implantation for hyperopia. J Cataract Refract Surg. 2003;29:895–899. 13. Fink AM, Gore C, Rosen ES. Refractive lensectomy for hyperopia. Ophthalmology. 2000;107:1540–1548. 14. Ruíz-Mesa R, Carrasco-Sánchez D, Díaz-Alvarez SB, Ruíz-Mateos MA, Ferrer-Blasco T, Montés-Micó R. Refractive lens exchange with foldable toric intraocular lens. Am J Ophthalmol. 2009;147: 990–996, 996.e1. 15. Leccisotti A. Refractive lens exchange in keratoconus. J Cataract Refract Surg. 2006;32:742–746. 16. Tychsen L, Packwood E, Hoekel J, Lueder G. Refractive surgery for high bilateral myopia in children with neurobehavioral disorders: 1. Clear lens extraction and refractive lens exchange. J AAPOS. 2006;10:357–363. 17. Ali A, Packwood E, Lueder G, Tychsen L. Unilateral lens extraction for high anisometropic myopia in children and adolescents. J AAPOS. 2007;11:153–158.

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18. Colin J, Robinet A, Cochener B. Retinal detachment after clear lens extraction for high myopia: seven-year follow-up. Ophthalmology. 1999;106:2281–2284, discussion 2285. 19. Hatch KM, Talamo JH. Laser-assisted cataract surgery: benefits and barriers. Curr Opin Ophthalmol. 2014;25:54–61. 20. Day AC, Stevens JD. Stability of keratometric astigmatism after non-penetrating femtosecond laser intrastromal astigmatic keratotomy performed during laser cataract surgery. J Refract Surg. 2016;32:152–155.

21. Finkelman YM, Ng JQ, Barrett GD. Patient satisfaction and visual function after pseudophakic monovision. J Cataract Refract Surg. 2009;35:998–1002. 22. Alio JL, Simonov A, Plaza-Puche AB, et al. Visual outcomes and accommodative response of the lumina accommodative intraocular lens. Am J Ophthalmol. 2016;164:37–48. 23. Tychsen L. Refractive surgery for children: excimer laser, phakic intraocular lens, and clear lens extraction. Curr Opin Ophthalmol. 2008;19:342–348.

30 

Iris-Fixated Phakic Intraocular Lenses KÉVIN PIERNÉ AND FRANÇOIS MALECAZE

Introduction In the 1950s, the pioneers Strampelli, Barraquer, and Choyce introduced the concept of intraocular lens (IOL) implantation in phakic eyes to correct high myopia. Since the 1980s, phakic IOL (PIOL) quality has improved and several PIOLs have been developed, either angle-supported or located in the posterior chamber. A completely different concept based on stabilization of the lens by an iris fixation was adopted by Worst. This approach was initially developed for pseudophakic patients1; in 1986, the concept of the claw lens was applied to correct myopia in phakic patients.2,3

Lens Designs Jan Worst developed the lens in 1978 under the name Iris Claw. Now built by Ophtec, it is available under four names: Artisan and Artiflex (distributed by Cristallens) and Verisyse and Veriflex (distributed by AMO). This lens has a convex–concave design to increase the distance between the PIOL and the corneal endothelium. Suppression of the prominent optical rim also reduced the prismatic effect possibly responsible for halos or glare. The vaulted design (0.5 mm) of the posterior face of the IOL allows it to ensure optimal space in front of the natural lens (about 0.8 mm) and prevents aqueous flow blockage. It also accounts for the forward displacement of the human lens during accommodation, which is at maximum about 0.6 mm.4 The optical part of the Verisyse myopic PIOL comes in two diameters: 5.0 mm and 6.0 mm (developed in 1997 to reduce phenomena such as glare and halos), with a power range of −5 to −20 diopters (D) for the 5-mm-diameter lens and 5 D to −15 D for the 6-mm-diameter lens, the power range increasing in 1.0 increments. It is a single-piece lens manufactured from ultraviolet light absorbing polymethylmethacrylate (PMMA). In 1993, an iris-claw lens specially designed for the correction of hyperopia was introduced (5-mm diameter, power range of +1.0 D to +12.0 D). Toric Verisyse IOL for the correction of astigmatism, which combines spherical anterior and spherocylindrical posterior surfaces, has been available since 2001.

To reduce surgically induced astigmatism, a foldable Verisyse IOL, Artiflex IOL, with a polysiloxane optic and PMMA haptics, has been developed. This is a lens with a polynomial design able to be injected in a 3.2-mm incision.

Indications and Contraindications The following conditions must be fulfilled for phakic irisclaw lens implantation: • Stable refraction. • Periphery of the retina is healthy or adequately treated. • No history of ocular disease, including glaucoma, cataract, uveitis, and macular disease. • Endothelial cell density superior to 2000 cells/mm (specular microscopic examination of the cornea should be performed preoperatively). • A pupil smaller than 8.0 mm in scotopic luminance (but the reactivity of the pupil seems to be as important as pupil size). • A deep anterior chamber: the minimal central depth of the anterior chamber as measured by ultrasound should not be less than 3.2 mm. • Lifelong close ophthalmologic follow-up will be possible.

Surgical Procedure Preparation IOL Power Calculation The power of the IOL is calculated on the basis of the curvature of the cornea (K), the anterior chamber depth measured by ultrasonography and the spectacle correction, by applying a special mathematical formula (van der Heijde’s tables).5 Roughly, it will be about the same as the power of the spectacles at a vertex distance of 12 mm.

Preoperative Miosis Preoperative application of topical myotics such as pilocarpine the day of the surgery is important. Miosis forms a protective shield for the natural lens during the insertion and fixation of the iris-claw lens. 407

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Operative Technique (Videos 30.1 and 30.3) Incision Techniques Various incision techniques can be used: clear corneal or scleral tunnel incision superiorly, or clear corneal incision temporally.

Incision Size The incision should be 5.2 mm for the 5-mm lens and 6.2 mm for the 6-mm lens to avoid difficulties of IOL insertion. It could be 3.2 mm for the Artiflex and Veriflex.

Paracenteses Two paracenteses are used for the introduction of the enclavation needles. These two small incisions of approximately 1 mm are located at 10 o’clock and 2 o’clock, when the main incision is superior.

Viscoelastic Material The viscoelastic substance is injected through one of the puncture incisions to create a deep anterior chamber. It is mandatory to use high-viscosity sodium hyaluronate; material with lower viscosity (e.g., methylcellulose, hydroxypropylmethylcellulose) should be avoided. Before the entrapment of the haptics, some viscoelastic should be injected on top of the implant to protect the endothelium.

Introduction of the Phakic IOL Into the Anterior Chamber The PIOL is introduced with the Verisyse fixation forceps into the anterior chamber by its smaller diameter (Fig. 30.1). Then, the PIOL is rotated 90 degrees.

Guaranteeing Pupillary Miosis Pupillary miosis should be guaranteed during the inserting and fixation procedure. The use of an intraocular myotic reduces the risk of lens touch.

• Fig. 30.1 diameter.

 

Implantation of a Verisyse intraocular lens by its smaller

Centration and Fixation of the IOL Centration and fixation of the IOL is probably the most critical step of the procedure; its accuracy influences the postoperative results. The pupil is used as a reference for centration of the implant. Correct axial centration of the operating microscope will prevent postoperative parallactic errors. Fixation of the IOL is performed by gently creating an iris fold under the claw and, consequently, entrapping the iris fold into the claw. Specially designed iris entrapment needles are used. They are blunt and can create a fold of midperipheral iris tissue. The IOL claws are then pressed over the fold (Fig. 30.2).

Iridectomy/Iridotomy Although a prophylactic iridectomy or iridotomy as a standard procedure is theoretically unnecessary (the Verisyse lens is vaulted to encourage natural fluid flow), experience has shown that it can prevent pupil block glaucoma in certain cases. A slit iridotomy, which is more elegant, is usually used.

Wound Closure Watertight wound closure is of paramount importance to prevent a shallow anterior chamber leading to IOL endothelial contact in the immediate postoperative period.

Particularities of the Toric and Foldable Models The Toric Lens

In this case, it is particularly important to position the lens accurately in the correct axis. A careful preoperative biomicroscopic examination of the iris with the patient sitting up (to avoid rotation of the globe) is necessary. The Artiflex Lens (Video 30.2)

The Artiflex foldable lens is inserted using a spatula through a small (3.2-mm) incision (Fig. 30.3). For the enclavation,

• Fig. 30.2

  Enclavation of a Verisyse intraocular lens using specially designed iris entrapment needles.

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a similar predictability while the quality of vision seemed better with Verisyse.

Results for Hyperopia Güell and al.9 report accurate refractive results for the 41 hyperopic patients implanted with satisfying spherical equivalent at 5-year follow-up (+4.92 ± 1.7 before surgery and +0.02 ± 0.51 D at 5-year follow-up) with no significant loss of vision.

Results for Astigmatism

• Fig. 30.3  Implantation of an Artiflex through a small (3.2-mm) incision. Specially designed curved forceps in order to facilitate the enclavation of the Artiflex haptic.

A prospective European multicenter study led by Doors and al.10 followed 115 eyes of 73 patients who were implanted with an Artiflex Toric PIOL. At 6 months, 81.8% of eyes were ±0.5 D of the intended refraction; in 74.5% postoperative uncorrected visual acuity (UCVA) was equal to or better than preoperative best corrected visual acuity (BCVA).

Optical Quality After Artisan Implantation special curved forceps are used, which hold the base of the PMMA haptic. The incision is usually watertight and suturing is not necessary.

Removal of the Viscoelastic Material Once the wound has been closed almost completely, the viscoelastic material should be entirely removed to prevent a shallow anterior chamber and a touch between the IOL and the cornea.

Postoperative Management Nonsteroidal and/or steroidal antiinflammatory drugs are usually prescribed for 2 to 4 weeks after surgery. Glaucoma drugs are not used on a regular basis. It is crucial to inform the patient of the necessity for a regular follow-up. In particular, long-term evaluation of the corneal endothelium density using specular microscopy is recommended. Patients also must be instructed not to rub their eyes the week following the surgery.

The Hartmann-Shack wavefront sensor did not reveal a tendency toward deterioration of the optical performance after the insertion of an Artisan lens for the treatment of high myopia.11 Both postoperative internal and ocular spherical aberrations (Z4(0)) were significantly lower in the Artiflex group than in the Artisan group with small pupil diameters (< 5 mm)12 and the postoperative 6 months of total root main square and trefoil aberration change may deteriorate the visual quality after Artisan PIOL implantation.13 However, at 1 year, both rigid PIOL and flexible PIOL bring similar CDVA and contrast sensitivity function values, suggesting that other optical or neural factors compensate for differences in optic quality.14

Complications Anterior Chamber Inflammation Early postoperative moderate iridocyclitis—quickly cleared with a local antiinflammatory therapy—is occasionally observed in cases when the surgery was a bit difficult.

Outcome and Complications

Glaucoma

Functional Outcome Results for Myopia

Postoperative glaucoma can be corticosteroid induced and usually resolves after discontinuation of steroid therapy. Pupil block glaucoma is a complication of nonfunctional peripheral iridectomy (Fig. 30.4). Transient ocular hypertension can also occur if the viscoelastic material has been inadequately removed.

Several studies have shown that, concerning high myopia, the refractive outcomes are satisfying: Malecaze et al.,6 in a series of 25 eyes (mean SE −13.08 D) implanted with the 6-mm Verisyse PIOL, found an 81.8 predictability value for 1.0 D or less of the desired refraction. Miraftab and al.7 report on 3-year results that PIOL implantation is a better choice than photorefractive keratectomy mitomycin C (PRK-MMC) for treating patients with > 8.0 D myopia with less spherical aberrations. A prospective randomized clinical trial conducted by Malecaze et al.8 comparing Verisyse and laser in situ keratomileusis (LASIK) for moderately high myopia has shown that both techniques produced

Impact on the Crystalline Lens Cataracts have been observed in patients with Verisyse™ PIOLs.15 Delayed cataract development and cataract type indicate that age and myopia are the determinant factors.

Endothelium Tolerance It is commonly noticed that most of endothelial cell count decrease occurs in the immediate postoperative period.

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Reduction in pupil size diameter is usually observed and may contribute to the maintenance of the quality of vision in scotopic conditions.19,20

Miscellaneous Endophthalmitis, although rarely reported, can occur, as in any anterior segment surgery. Intraoperative hyphema owing to excessive manipulation of the iris during entrapment can occur but usually clears completely. Urrets–Zavalia syndrome owing to insufficient removal of the viscoelastic material associated with a frail iris was reported.21 Viscoelastic injection associated with prolonged iris prolapse may damage the iris sphincter. • Fig. 30.4

  Nonreflective semi-mydriatic pupil associated with pupil block glaucoma owing to nonfunctional iridectomy.

Conclusions The advantages of the iris-claw lens are multiple: predictable postoperative refraction thanks to the van der Heijde’s table, excellent quality of vision, stable surgical results, reversible surgery, and a low complication rate. The main disadvantages are the necessary training, which may be improved with wet lab courses before implanting patients, and the endothelial cell loss particularly noticeable just after surgery is performed.

References

• Fig. 30.5

 

Posttraumatic Verisyse intraocular lens dislocation.

Bouheraoua and al.16 proposed a predictive model considering that, for patients with preoperative endothelial cell counts of 3000, 2500, and 2000 cells/mm2, a critical threshold of 1500 cells/mm2 will be reached at 39, 28, and 15 years after implantation, respectively. Yaşa and al.17 consider that Artisan PIOL implantation is a safe and highly effective procedure; their 42 patients included in their study encountered endothelial cell loss only in the early postoperative period, which stabilized by then. Morral and al.18 followed 29 eyes with iris-claw PIOL implantation that did not produce significant corneal endothelial cell loss up to 10 years after surgery compared with corneal refractive surgery and unoperated eyes. However, unexplained endothelial cell loss is still observed with some patients, whether with a deep anterior chamber or not, even with new anterior segment imaging techniques.

Iris Changes IOL dislocation is usually due to an insufficient amount of iris tissue fold through the claw and is usually provoked by an ocular trauma (Fig. 30.5).

1. Fechner PU. [Iris claw lens]. Klin Monatsbl Augenheilkd. 1987; 191(1):26–29. 2. Fechner PU, Heijde GL, van der Worst JGF. Intraokulare Linse zur Myopiekorrektion des phaken Auges. Klin Monatsblätter Für Augenheilkd. 1988;193(07):29–34. 3. Fechner PU, Worst JGF. A new concave intraocular lens for the correction of myopia. Eur J Implant Refract Surg. 1989;1(1): 41–43. 4. de Vries FR, van der Heijde GL, Goovaerts HG. System for continuous high-resolution measurement of distances in the eye. J Biomed Eng. 1987;9(1):32–37. 5. Heijde GLVD. Some optical aspects of implantation of an IOL in a myopic eye. J Cataract Refract Surg. 1989;1(4):245–248. 6. Malecaze F, Hulin H, Bierer P. [Iris-claw phakic (Artisan) lens to correct high myopia]. J Fr Ophtalmol. 2000;23(9):879–883. 7. Miraftab M, Hashemi H, Asgari S. Matched optical quality comparison of 3-year results of PRK-MMC and phakic IOL implantation in the correction of high myopia. Eye. 2015;29(7):926–931. 8. Malecaze FJ, Hulin H, Bierer P, et al. A randomized paired eye comparison of two techniques for treating moderately high myopia: LASIK and artisan phakic lens. Ophthalmology. 2002; 109(9):1622–1630. 9. Güell JL, Morral M, Gris O, Gaytan J, Sisquella M, Manero F. Five-year follow-up of 399 phakic Artisan-Verisyse implantation for myopia, hyperopia, and/or astigmatism. Ophthalmology. 2008;115(6):1002–1012. 10. Doors M, Budo CJ, Christiaans BJ, et al. Artiflex Toric foldable phakic intraocular lens: short-term results of a prospective European multicenter study. Am J Ophthalmol. 2012;154(4): 730–739.e2. 11. Brunette I, Bueno JM, Harissi-Dagher M, Parent M, Podtetenev M, Hamam H. Optical quality of the eye with the Artisan

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phakic lens for the correction of high myopia. Optom Vis Sci. 2003;80(2):167–174. 12. Torii H, Negishi K, Watanabe K, Saiki M, Kato N, Tsubota K. Changes in higher-order aberrations after iris-fixated phakic intraocular lens implantation. J Refract Surg. 2013;29(10):693–700. 13. Park YM, Choi BJ, Lee JS. Effect of incision types for Artisan phakic intraocular lens implantation on ocular higher order aberrations. Int J Ophthalmol. 2016;9(12):1785–1789. 14. Peris-Martínez C, Artigas JM, Sánchez-Cortina I, Felipe A, DíezAjenjo A, Menezo JL. Influence of optic quality on contrast sensitivity and visual acuity in eyes with a rigid or flexible phakic intraocular lens. J Cataract Refract Surg. 2009;35(11):1911–1917. 15. Moshirfar M, Imbornoni LM, Ostler EM, Muthappan V. Incidence rate and occurrence of visually significant cataract formation and corneal decompensation after implantation of Verisyse/Artisan phakic intraocular lens. Clin Ophthalmol. 2014; 8:711–716. 16. Bouheraoua N, Bonnet C, Labbé A, et al. Iris-fixated phakic intraocular lens implantation to correct myopia and a pre-

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dictive model of endothelial cell loss. J Cataract Refract Surg. 2015;41(11):2450–2457. 17. Yaşa D, Ağca A, Alkın Z, et al. Two-year follow-up of Artisan iris-supported phakic anterior chamber intraocular lens for correction of high myopia. Semin Ophthalmol. 2016;31(3):280–284. 18. Morral M, Güell JL, El Husseiny MA, Elies D, Gris O, Manero F. Paired-eye comparison of corneal endothelial cell counts after unilateral iris-claw phakic intraocular lens implantation. J Cataract Refract Surg. 2016;42(1):117–126. 19. Lemarinel B, Racine L, Rohart C, Hoang-Xuan T, Gatinel D. [Long-term changes in pupil size after implantation of an Artisan phakic intraocular lens for correction of high myopia]. J Fr Ophtalmol. 2007;30(1):11–16. 20. Bootsma SJ, Tahzib NG, Eggink FA, de Brabander J, Nuijts RM. Evaluation of pupil dynamics after implantation of artisan phakic intraocular lenses. J Refract Surg. 2006;22(4):367–371. 21. Arendt P, Gerding H. Urrets-Zavalia syndrome after iris-clawlens implantation, inadequate iridectomy and acute glaucoma. Klin Monatsbl Augenheilkd. 2016;233(4):373–374.

31 

Posterior Chamber Phakic Intraocular Lens JEAN-LOUIS ARNÉ

Introduction In 1986, Fyodorov1 originated the first plate posterior chamber phakic intraocular lens (PIOL). He used a onepiece silicone collar button PIOL with a Teflon coat. Encouraging initial results were achieved but problems with cataract formation,2,3 uveitis, glaucoma, and decentration led to changes in lens design and type of material to improve biocompatibility. Currently, there are three phakic posterior chamber lenses. Two are available: the implantable contact lens (ICL; manufactured by STAAR Surgical) and the phakic refractive lens (PRL; manufactured by CIBA). One is under evaluation: the Sticklens, developed by IOLTECH.

Lens Design The STAAR surgical ICL is made of a collagen copolymer, a compound combining acrylic and porcine collagen (less than 0.1% collagen). Its refractive index is 1.45 at 35°C. The polymer material is soft, elastic, and hydrophilic. The optical zone of myopic lenses is 60 µm thick; the diameter varies between 4.5 and 5.5 mm according to the power required. The optical zone diameter of hyperopic lenses is 5.5 mm. Available powers are −3 to −23 diopters (D) for myopic lenses, and +3 D to +21.5 D for hyperopic lenses. Several lengths are manufactured: 11 to 13.0 mm for hyperopic lenses, and 11.5 to 13.5 mm for myopic lenses. An astigmatic ICL is also available, but it was marketed too recently to appear in articles in peer-reviewed journals. This implant is placed in the ciliary sulcus. The posterior surface is concave in order to vault over the anterior capsule. The CIBA PRL is made from an ultra-thin silicon polymer; its refractive index is 1.46. The material is soft, elastic, and hydrophobic. The width is 6.0 mm; two lengths are available for myopic lenses: 10.8 or 11.3 mm, and one for hyperopic lenses: 10.6 mm. Available powers are −3 to −20 for myopic lenses, and +3 to +15 for hyperopic lenses. 412

The lens has no anatomic fixation sites; it is supposed to move unaided into a centered position inside the posterior chamber spaces, without exerting pressure on the ciliary structures, the zonule in particular; it does not come into contact with the anterior capsule of the crystalline lens: it “floats.” The Sticklens, developed by IOLTECH, is made of a high-hydrophilic material in order to allow metabolic exchanges through the implant; it is “stuck” on the anterior capsule of the crystalline lens.

Preoperative Evaluation Exclusion criteria include previous intraocular surgery, endothelial dystrophy, opacities of the crystalline lens, glaucoma, pigment dispersion syndrome, diabetic retinopathy and systemic disease, nonstable ametropia, and an anterior chamber depth less than 2.8 mm in myopic eyes and 3.00 mm in hyperopic eyes. Lens power calculation is performed with formulae that take several variables into account: manifest and cycloplegic refraction, keratometric power, anterior chamber depth, and corneal thickness. The length of the lens is determined based on the horizontal corneal diameter. White-to-white measurement can be made by several methods: caliper, gauge, videokeratoscope, photographic devices, and ultrasound biometry (UBM). However, only very expensive devices, such as high-frequency UBM, could give an accurate measurement of the sulcus diameter. The size of the PIOL chosen is, in most cases, white-to-white length plus 0.5 mm, rounded to the nearest 0.5 mm increment for myopic eyes, and whiteto-white length for hyperopic eyes.

Surgical Technique (Video 31.1) Two weeks before surgery, laser iridotomies are performed. Two peripheral superior iridotomies are placed 80 degrees

CHAPTER 31  Posterior Chamber Phakic Intraocular Lens

apart in order to avoid the possibility of iridotomy occlusion by the haptics of the implant. Otherwise, a surgical iridectomy will be performed at the time of implantation.

Preparation and Anesthesia A combination of mydriatic topical medications is applied serially, beginning 1 hour before surgery. The anesthesia methods—general anesthesia, peribulbar injection, or topical anesthesia—are based on patient and surgeon preference.

Surgical Procedure A puncture is performed and aqueous humor is replaced by a viscoelastic gel. A temporal corneal tunnel (width 3.2 mm, length 1.75–2 mm) is created. A narrow diamond blade allows progressive opening of the anterior chamber. Viscoelastic (ideally, methylcellulose) is injected into the anterior chamber. The implant can be inserted by different techniques.

Inserting the Implant With an Injector (Fig. 31.1) The IOL is positioned in the lens insertion cartridge under direct vision through the operating microscope. In the absence of a soft-tip injector, a small silicon sponge can be placed to protect the IOL from the hard injector arm.

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Because IOL insertion into the cartridge is complicated and time-consuming, it must be done before the incision is made. The injector tip is placed in the tunnel and the lens is injected into the anterior chamber. As the IOL unfolds slowly, its progression can be controlled, to ensure proper orientation.

Inserting the Implant With Forceps (Fig. 31.2) The IOL is easy to fold between the jaws of a MacPherson forceps. The tip of the forceps is introduced in the entrance of the tunnel. Then, another MacPherson forceps, held in the operator’s other hand, is used to grasp the sides of the implant. The first forceps is opened, regrasps the IOL a little further, and pushes it slowly. By repeating these maneuvers with the forceps, the operator moves the IOL into the tunnel, and the IOL unfolds in a controlled manner. The tip of the forceps must never enter into the anterior chamber to avoid contact with the crystalline lens. As the IOL unfolds, its proper orientation must be checked. Then, each foot plate is placed one after the other beneath the iris with a specially designed, flat, nonpolished manipulator, without pressure being placed on the crystalline lens. It is important to avoid touching the optic of a myopic lens in the middle, as it is the thinnest part. Then, the viscoelastic is removed with gentle irrigation–aspiration and acetylcholine chloride is injected. A Dementiev forceps can be used to implant a PRL; the implant is grasped by the special forceps designed to prevent damages on the optical zone (only the haptic area of the implant is in contact with the forceps). The forceps is pushed into the middle part of the anterior chamber. The forceps is opened gently to release the lens; care must be taken because the lens can be damaged when withdrawing the forceps.

Functional Results Most of the published results concern series of patients implanted with an ICL. Only two publications present results obtained by PRL implantation.4,5

Predictability

• Fig. 31.1

 

Injectors for the STAAR surgical implantable contact lens.

Predictability was good and results were relatively similar in all studies, as shown in the following publications. Assetto et  al.6 implanted 15 lenses in 14 patients. Average follow-up was 7 ± 1.95 months. Mean spherical equivalent was −15.3 D ± 3.1 D preoperatively, −2 D ± 1.5 D postoperatively. Only 31% of eyes had less than 1 D of residual myopia. However, an old model of lenses was used. Rosen and Gore7 operated on 16 myopic eyes (−5.25 D to −14.50 D). At 3 months after surgery, refraction ranged from −1.25 D to +1 D; 56.2% of eyes were within 0.50 D from emmetropia. Zaldivar et al.8 analyzed a cohort of 124 eyes; the mean follow-up period was 11 months (range, 1–36 months). The

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B A

D C

E • Fig. 31.2  Intraoperative sequential views of implantation of the STAAR surgical implantable contact lens using the forceps technique. (A) Lens folding. (B) Lens insertion. (C) Trailing haptic insertion. (D) Positioning of distal haptic. (E) Positioning of proximal haptic.

CHAPTER 31  Posterior Chamber Phakic Intraocular Lens

mean preoperative spherical equivalent was −13.38 ± 2.23 D (range, −8.50 D to −18.63 D). The target was emmetropia. The postoperative mean spherical equivalent was −0.78 D ± 0.87 D (range, +1.63 D to −3.50 D); 69% of the eyes were within 1 D and 44% within 0.50 D from emmetropia. Arné and Lesueur9 implanted 58 eyes of 46 myopic patients. Follow-up ranged from 9 months to 2 years. Spherical equivalent was −13.85 D ± 4.61 D (range, −8 D to −19.21 D) preoperatively and −1.22 D ± 0.58 D postoperatively; 56.9 % of the eyes were within 1 D of emmetropia. Residual myopia was more than 2 D in 15.5% of the eyes. Uusitalo et al.10 reported the results of ICL implantation in 38 eyes of 22 patients. The mean preoperative myopia was −15.10 D (range, −7.75 D to 29 D); the mean followup was 13.6 months (range, 6–24 months). Postoperatively, the mean spherical equivalent refraction was −2 D ± 2.48  D (range, +0.13 D to −13 D); 96.4% of the eyes were within 1 D and 85.7% within 0.5 D of emmetropia. Pallikaris et al.4 evaluated the 1-year results of PRL implantation in 34 myopic eyes. They found a statistically significant reduction in the manifest refraction in spherical equivalent (preoperative: −14.70 D, range, −10.5 D to −20.75 D; postoperative: −0.61 D, range, −2.25 D to +1 D); 79% and 44% of the eyes were within 1 D and 0.5 D of target refraction, respectively. Sanders et al.11 reported on 526 eyes with between 3.0 D and 20.0 D of myopia participating in the US Food and Drug Administration clinical trial of the ICL for myopia: 67.5% of patients were within 0.5 D and 88.2% were within 1.0 D of predicted refraction. There were few studies on results of hyperopic ICL7,12–15: Rosen and Gore7 operated on 9 hyperopic eyes (preoperative spherical equivalent [SE] range, +2.25 D to +5.62 D); 3 months postoperatively, refraction ranged from −0.12 D to +1 D. Davidorf et al.12 implanted a collamer PIOL into 24 eyes with hyperopia greater than 3.50 D. The mean preoperative SE was +6.51 D ± 2.08 D (range, +3.75 D to +10.50 D). The mean postoperative SE was −0.39 D ± 1.29 D (range, +1.25 D to −3.88 D). Postoperatively, 79% of the eyes were within +1 D and 58% within +0.50 D from emmetropia. These results compare favorably with predicted results of the authors’ series of highly myopic eyes.8 Gimbel and Ziémba16 reported one case of an astigmatic eye implanted with a posterior chamber PIOL. Manifest preoperative refraction was −9.25 (−2.25 × 98 degrees); 5 months after surgery, manifest refraction was +0.25 (−0.25 × 60 degrees). Hoyos et al.5 presented the results of implantation of a PRL in 31 eyes (17 myopic, 14 hyperopic). The mean preoperative spherical equivalent was −18.46 D (range, −11.85 D to −26 D) for myopia, +7.77 D (range, +5.25 D to 11 D) for hyperopia. At 1 year, the mean postoperative spherical equivalent in the myopic group was −0.22 D (range, +1.50 to −2  D) and −0.38 (range +1.50 to −1.75 D).

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Visual Acuity In the series of phakic implantation in myopic eyes by Zaldivar et al.,8 the preoperative best-corrected visual acuity (BCVA) was 20/40 or better in 80% and 20/20 or better in 5% of the eyes. Postoperatively, uncorrected visual acuity (UCVA) was 20/40 or better in 93% and 20/20 or better in 19% of the eyes. Again, two or more lines of corrected visual acuity was attained in 36% of the cases; 7% of the eyes lost one line, 0.8% lost 2 lines. In the series reported by Arné and Lesueur,9 the mean preoperative BCVA was 0.57 and the mean postoperative UCVA and BCVA were 0.40 and 0.71, respectively. The postoperative UCVA was better than the preoperative BCVA in 15.5% of the cases, unchanged in 15.5%, and worse in 68.9% of the eyes. The mean efficacy index (ratio of postoperative UCVA to preoperative BCVA) was 0.84. A total of 20.6% of the eyes retained the same BCVA, 77% gained one or more lines, and 3.4% lost two lines. Safety, calculated as the ratio between postoperative and preoperative BCVA, was 1.46. In the series reported by Uusitalo et al.,10 the BCVA improved by one or more lines in 71.9% of the eyes; 6.3% of the eyes lost one line of BCVA. Pallikaris et al.,4 after implantation of PRLs in myopic eyes, noted an improvement of BCVA from 0.70 ± 0.24 to 0.85 ± 0.24. In the series of myopic and hyperopic patients implanted with PRL by Hoyos et al.,5 lines of BCVA were gained in 65% of the myopic eyes, with eight eyes gaining one line and three eyes gaining two lines. No eye lost one line of BCVA. In the hyperopic group, one eye gained one line of BCVA and one eye lost one line. Good efficacy and predictability have been demonstrated in all studies on posterior chamber phakic lenses for treatment of high myopias. The marked gains in postoperative BCVA compared with the preoperative spectacle BCVA in high myopes are largely due to elimination of the spectacleinduced image reduction. Conversely, only 8% of the hyperopic eyes operated on by Davidorf et al.12 demonstrated a gain in postoperative BCVA compared to the preoperative spectacle BCVA. In this series, 7 of 24 eyes (29%) lost one or more lines of postoperative spectacle BCVA. This is explained by the loss of magnification induced by the surgery. Also, 4% of the eyes lost two or more lines of spectacle BCVA due to postoperative glaucoma.

Stability Excellent stability has been demonstrated in all series. For 51 eyes followed by Zaldivar et al.,8 refraction was −0.90 D at 1 month, −0.91 D at 6 months, and −0.83 D at 12 months postoperatively. In all reported series, the refraction remained stable at each interval during the follow-up.

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Quality of Vision

Anatomic Outcome

The level of patient satisfaction is very high. In the study by Arné and Lesueur,9 55.7% of the patients were very satisfied, 36.2% were satisfied, and 6.9% moderately satisfied. No patient was dissatisfied.

Early Postoperative Complications Decentration of the Implant

Halos The rate of subjective complaints, including glare and halos, varied from 2.4% for Zaldivar et al.,8 55% for Arné and Lesueur,9 and 25.8% for Hoyos.5 The rate of halos was higher when the size of the optical zone of the ICL was small. Arné and Lesueur9 tested contrast sensitivity preoperatively with contact lenses and 6 months after surgery (Fig. 31.3). The mean postoperative level without correction was higher than the mean preoperative level with correction; the difference was statistically significant for each level of luminance. Jiménez-Alfaro et al.17 evaluated contrast sensitivity in 20 eyes operated on for the correction of high myopia; they reported that contrast sensitivity increased after implantation of an ICL in all spatial frequencies when compared to preoperative contrast sensitivity with best spectacle correction. Pallikaris et al.4 found no statistically significant difference in higher-order aberrations after PRL implantation. 8b 7b

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Early Postoperative Intraocular Pressure Rise High intraocular pressure (IOP) is not rare during the early postoperative period, and usually resolves rapidly, spontaneously, or with a short antiglaucoma therapy. However, high IOP can be severe in some cases owing to the following causes. Incomplete viscoelastic substance removal resulting in trabecular blockage is the most common mechanism: there can be an epithelial edema associated with a deep anterior chamber. IOP levels usually return rapidly to normal with antiglaucoma therapy, and sometimes a slight instrumental decompression at one side port incision can relieve the patient’s pain immediately by removing excess viscoelastic substance. Malignant glaucoma is a dramatic complication characterized by very high IOP associated with a shallow anterior chamber.18 Its exact mechanism must be recognized. • Pupillary block glaucoma after posterior chamber phakic lens implantation occurs when peripheral iridectomy is absent or not functional. The iris bows forward and the anterior chamber is often shallow in the center; a surgical or laser iridectomy must be performed. • Ciliary block is another mechanism, which can occur even in a case of functional iridectomy: the primum movens is an aqueous humor misdirected posteriorly into the vitreous cavity, usually due to congestion of the ciliary body, which is irritated by the implant haptics. Another hypothesis is that some viscoelastic substance, “trapped” in the posterior chamber when the pupil is constricted, misdirects the aqueous humor to the vitreous cavity. If medical treatment consisting of atropine cycloplegia fails, the ICL must be removed, the anterior chamber filled with a bubble of air, and the aqueous humor aspirated in the vitreous through a posterior sclerotomy.

2t

Long-Term Postoperative Outcome

1t

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Posterior chamber PIOL implantation between the iris and crystalline lens is an original surgical procedure; it is important to assess possible modifications of the anatomic structures of the eye induced by the presence of the implant.

18

Endothelial Cell Damage

Spatial frequency (cycles per degree)

• Fig. 31.3

This can occur when the implant is too small. The functional disturbance depends on the importance of the decentration and on pupil diameter. However, it leads to a high risk of contact between the implant and the crystalline lens, and in most cases the implant must be changed.

Contrast sensitivity before and after implantation.

This is a major concern with anterior chamber IOLs. Fyodorov et al.1 reported a mean decrease in endothelial cell

CHAPTER 31  Posterior Chamber Phakic Intraocular Lens

density of 5% with their silicone posterior chamber PIOL; Assetto et al.6 found a mean endothelial loss of 4% with the Staar IOL. Arné and Lesueur,9 using the same PIOL, noted a mean endothelial cell loss of 2.1% 3 months after surgery, 2.3% at 6 months, 2% at 1 year, and 2% at 2 years. In no case did endothelial cell loss exceed 3.8% at 1 year. DejacoRuhswurm et al.19 evaluated the long-term endothelial cell change in phakic eyes after implantation of the Staar IOL; they noted a rapid loss until 1 year postoperatively, after which the rate of loss was no longer statistically significant. This absence of chronic ongoing endothelial loss has also been confirmed by more recent studies.11,20

Subclinical Inflammation This has been reported as a frequent complication of the first model of silicone posterior chamber phakic lenses. Jiménez-Alfaro et al.21 noted that increase in aqueous flare levels was 49.19% compared to preoperative levels during the first month following ICL implantation. These values then decreased but remained above the preoperative ones. Uusalito et al.10 found normal aqueous flare values in 12 eyes measured at least 6 months after ICL implantation. Sanders also found no long-term (2–3 years) ocular inflammation following ICL implantation22 (Fig. 31.4).

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PRL, Krukenberg spindles, and dense pigmentation of the trabecular meshwork. In two cases,9 pigmentary deposits that were not present preoperatively were seen in the angle in association with elevated IOP (Fig. 31.5B). Zaldivar et al. also noted pigmentary deposits associated with elevated IOP in 14 of 124 eyes.8 Sanchez-Galeana et al.24 reported an intractable case of pigmentary glaucoma secondary to an ICL implantation requiring filtering surgery. Pineda-Fernandez et al. reported a 22.2% incidence of moderate pigmentary dispersion in their series of 18 eyes.25 Some of the pigment dispersion may be partly surgically induced, by yttrium-aluminum-garnet (Nd:YAG) iridotomies and trauma to the iris during implantation. However, contact of the optic–haptic junction with the posterior pigmented epithelium of the iris is the major cause

Pigmentary Dispersion A pigmentary dispersion was first reported by Assetto et al.6 Pigment deposits on the periphery of the ICL optic are constant 1 year after surgery (Fig. 31.5A) but they have no visual consequence. Brandt et al.23 reported a case of bilateral pigmentary dispersion induced by the implantation of a PRL. They noted transillumination defects of the iris in areas that were in contact with the anterior surface of the

A

• Fig. 31.4

  Inflammatory deposits on the optic of a STAAR surgical implantable contact lens.

B • Fig. 31.5

  (A) Pigmentary deposits on the optic of a STAAR surgical implantable contact lens (ICL). (B) Pigmentary deposits in the angle associated with the ICL.

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of pigmentary dispersion. Trindade et al.,26 using UBM, showed that there was more contact between the ICL and the iris than between the crystalline lens and the iris in the same patients before surgery.

Elevated Intraocular Pressure This can result from several mechanisms: transient iritis, corticosteroid-induced glaucoma, and angle narrowing has been observed with UBM.26 Careful follow-up is mandatory for hyperopes, since their anterior chamber depth can be reduced by 9% to 12.5% following ICL implantation.17 Also, pigmentary deposits were found in the angle. This is a concern in high myopes, who already are at increased risk of developing glaucoma.

Cataractogenesis Cataract formation is one of the most crucial concerns for the future of posterior chamber PIOLs. There is an incidence of lens opacities from 1.5% to 33%. This large rate range may be due to the definition of cataract or opacities, the duration of the follow-up period, the surgical technique, and the model of implant. Fechner et al.2 implanted silicone posterior chamber IOLs in 45 myopic eyes with clear crystalline lenses and found central subcapsular opacities in 8 eyes (17.8%) after 1 to 2 years. Zaldivar et al.8 found 1.5% anterior subcapsular opacity incidence. Trindade and Pereira27 reported a

A

case of visually significant cataract formation 6 months after uneventful ICL implantation. Fink et al.28 reported on the occurrence of lens opacification in three eyes of two patients. Arné and Lesueur9 observed 2 cases (3.4%) of anterior subcapsular opacities; one required removal of the ICL followed by phacoemulsification and posterior chamber IOL implantation. Jiménez-Alfaro et al.17 found a progressive decrease in lens transmittance from 0.72% at 1 month to 2.24% at 24 months after ICL implantation; they were not able to find lens opacities by biomicroscopy after 24 months. Lackner et al.15 reported on subcapsular anterior opacifications of the crystalline lens in 25 eyes (33.3%) of 75 eyes that received an ICL. Conversely, in the US Food and Drug Administration (FDA) clinical trial of the ICL for myopia, studying 526 eyes in a 3-year period, Sanders et al. reported only presumably surgically induced anterior subcapsular opacities in 14 eyes (2.7%).11 Sanchez-Galeana et al.24 classified lens opacities secondary to posterior chamber PIOL implantation into three categories: • Focal dot-like anterior subcapsular opacities (Fig. 31.6A): punctate opacities located on the center or on paracentral or superior quadrants nasally and temporally. They are asymptomatic and tend to be nonprogressive; they are the most common type of opacities after implantation of posterior chamber PIOLs.

B

C • Fig. 31.6  (A) Focal dot-like anterior subcapsular opacities. (B) Diffuse anterior subcapsular opacities. (C) Contact between implant and center part of the crystalline lens.

CHAPTER 31  Posterior Chamber Phakic Intraocular Lens

• Diffuse anterior subcapsular opacities (Fig. 31.6B), located either centrally or paracentrally, causing nocturnal glare; they tend to progress slowly. • Nuclear sclerotic cataracts, combined with diffuse anterior opacities, cause decreasing of BCVA; they progress over the course of several months. Several mechanisms have been put forth to explain cataractogenesis: • Trauma of the crystalline lens during the implantation procedure is possible. • Contact between the ICL and the central area of the crystalline lens is considered as the cause of cataract formation (Fig. 31.6C). Examination by UBM and Scheimpflug camera can demonstrate this contact in the case of insufficient vault. The incidence of cataract appears high with some models of ICL with insufficient vaulting. Petternel et al.29 used partial coherence interferometry biometry technology to study the changes in distance between ICLs and the crystalline lens under various conditions. They found no significant changes during subjective accommodation and after instillation of pilocarpine but did find a significant decrease in distance between the natural and artificial lens under photopic conditions, with constriction of the pupil. They also observed no central contact between the ICL and the crystalline lens, but did find a direct contact in the midperiphery. Metabolic disturbances induced by the material of the implant may also play a role, although biocompatibility of hydroxyethyl methacrylate (HEMA) collagen copolymers has proven to be excellent. • High myopic eyes have a natural tendency to develop cataracts earlier than normal eyes. This explains why cataract surgery is often required earlier in high myopes than in emmetropic patients. One can postulate that phakic lens implantation may promote the progression of early changes in the crystalline lens into the development of cataract. • Cataract surgery in patients implanted with posterior chamber PIOLs is not difficult. Explantation of the IOL is performed easily through the same-sized primary clear corneal incision. Phacoemulsification and posterior chamber IOL implantation can be done in routine fashion.

Advantages and Disadvantages Implantation of posterior chamber PIOLs is an effective method for correcting high refractive errors. This site of implantation of phakic implants presents the following advantages: The safe distance between the anterior surface of the implant and the corneal endothelium allows secondary LASIK to be performed as early as 2 months after PIOL implantation. This bioptic treatment is used to treat extreme spherical ametropias or spherical ametropias combined with astigmatism.30–32

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The lack of harm to the cornea and pupil has permitted the implantation of these IOLs in children to correct refractive amblyopia. Lesueur and Arné33 evaluated the anatomic and functional outcomes of 12 eyes of children 3 to 16 years old with high myopic amblyopia following ICL implantation. They noted good tolerance of the ICLs without inflammatory reactions or opacification of the crystalline lens, and with stable IOP. The main disadvantage of posterior PIOLs is the choice of size, since only very sophisticated and expensive devices can determine with accuracy the sulcus-to-sulcus distance, which is different depending on the meridian. This issue is critical, since it depends on the vaulting of the IOL, which is associated with the risk of contact between the IOL and the crystalline lens and/or the posterior face of the iris. Also, the crystalline lens thickness (and its distance with the IOL) varies with accommodation and age; therefore its opacification remains the principal concern of posterior chamber IOL implantation surgery.

References 1. Fyodorov SN, Zuev VK, Aznabayev BM. Intraocular correction of high myopia with negative posterior chamber lens. Ophthalmosurgery (Moscow). 1991;3:57–58. 2. Fechner PU, Haigis W, Wichmann W. Posterior chamber myopia lenses in phakic eyes. J Cataract Refract Surg. 1996;22:178–182. 3. Wiechens B, Winter M, Haigis W, et al. Bilateral cataract after phakic posterior chamber top hat-style silicone intraocular lens. J Refract Surg. 1997;13:392–397. 4. Pallikaris IG, Kalyvianaki MI, Kymionis GD, et al. Phakic refractive lens implantation in high myopic patients: one-year results. J Cataract Refract Surg. 2004;30:1190–1197. 5. Hoyos JE, Dementiev DD, Cigales M, et al. Phakic refractive lens experience in Spain. J Cataract Refract Surg. 2002;28: 1939–1946. 6. Assetto V, Benedetti S, Pesando P. Collamer intraocular contact lens to correct high myopia. J Cataract Refract Surg. 1996;22: 551–556. 7. Rosen E, Gore C. Staar collamer posterior chamber phakic intraocular lens to correct myopia and hyperopia. J Cataract Refract Surg. 1998;24:596–606. 8. Zaldivar R, Davidorf JM, Oscherow S. Posterior chamber phakic intraocular lens for myopia of -8 to -19 diopters. J Refract Surg. 1998;14:294–305. 9. Arné JL, Lesueur LC. Phakic posterior chamber lenses for high myopia: functional results and anatomical outcomes. J Cataract Refract Surg. 2000;26:369–374. 10. Uusitalo RJ, Aine E, Sen NH, et al. Implantable contact lens for high myopia. J Cataract Refract Surg. 2002;28:29–36. 11. Sanders DR, Doney K, Poco M. United States Food and Drug Administration clinical trial of the Implantable Collamer Lens (ICL) for moderate to high myopia: three-year follow-up. Ophthalmology. 2004;111(9):1683–1692. 12. Davidorf JM, Zaldivar R, Oscherow S. Posterior chamber phakic intraocular lens for hyperopia of +4 to +11 diopters. J Refract Surg. 1998;14:306–311. 13. Pesando PM, Ghiringhello MP, Tagliavacche P. Posterior chamber Collamer phakic intraocular lens for myopia and hyperopia. J Refract Surg. 1999;15:415–423.

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14. Sanders DR, Martin RG, Brown DC, et al. Posterior chamber phakic intraocular lens for hyperopia. J Refract Surg. 1999;15: 309–315. 15. Lackner B, Pieh S, Schmidinger G, et al. Outcome after treatment of ametropia with implantable contact lenses. Ophthalmology. 2003;110(11):2153–2161. 16. Gimbel HV, Ziémba SL. Management of myopic astigmatism with phakic intraocular lens implantation. J Cataract Refract Surg. 2002;28:883–886. 17. Jiménez-Alfaro I, Benítez del Castillo JM, García-Feijoó J, et al. Safety of posterior chamber phakic intraocular lenses for the correction of high myopia: anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2001;108:90–99. 18. Kodjikian L, Gain P, Donate D, et al. Malignant glaucoma induced by a phakic posterior chamber intraocular lens for myopia. J Cataract Refract Surg. 2002;28:2217–2221. 19. Dejaco-Ruhswurm I, Scholz U, Pieh S, et al. Long-term endothelial changes in phakic eyes with posterior chamber intraocular lenses. J Cataract Refract Surg. 2002;28:1589–1593. 20. Edelhauser HF, Sanders DR, Azar R, et al. Corneal endothelial assessment after ICL implantation. J Cataract Refract Surg. 2004;30(3):576–583. 21. Jiménez-Alfaro I, Gómez-Tellería G, Bueno JL, et al. Contrast sensitivity after posterior chamber phakic intraocular lens implantation for high myopia. J Refract Surg. 2001;17(6):641–645. 22. ICL in treatment of myopia (ITM) Study Group. Postoperative inflammation after implantation of the implantable contact lens. Ophthalmology. 2003;110(12):2335–2341. 23. Brandt JD, Mockovak ME, Chayet A. Pigmentary dispersion syndrome induced by a posterior chamber phakic refractive lens. Am J Ophthalmol. 2001;131:260–263.

24. Sanchez-Galeana CA, Zadok D, Montes M, et al. Refractory intraocular pressure increase after phakic posterior chamber intraocular lens implantation. Am J Ophthalmol. 2002;134: 121–123. 25. Pineda-Fernandez A, Jaramillo J, Vargas J, et al. Phakic posterior chamber intraocular lens for high myopia. J Cataract Refract Surg. 2004;30(11):2277–2283. 26. Trindade F, Pereira F, Cronemberger S. Ultrasound biomicroscopic imaging of posterior chamber phakic intraocular lens. J Refract Surg. 1998;14:497–503. 27. Trindade F, Pereira F. Cataract formation after posterior chamber phakic intraocular lens implantation. J Cataract Refract Surg. 1998;24:1661–1663. 28. Fink AM, Gore C, Rosen E. Cataract development after implantation of the Staar Collamer posterior chamber phakic lens. J Cataract Refract Surg. 1999;25:278–282. 29. Petternel V, Koppl CM, Dejaco-Ruhswurm I, et al. Effect of accommodation and pupil size on the movement of a posterior chamber lens in the phakic eye. Ophthalmology. 2004;111(2): 325–331. 30. Zaldivar R, Davidorf JM, Oscherow S, et al. Combined posterior chamber phakic intraocular lens and laser in situ keratomileusis: bioptics for extreme myopia. J Refract Surg. 1999;15:299–308. 31. Arné JL, Lesueur LC, Hulin HH. Photorefractive keratectomy or laser in situ keratomileusis for residual refractive error after phakic intraocular lens implantation. J Cataract Refract Surg. 2003;29(6):1167–1173. 32. Arné JL. Phakic lens implantation versus clear lens extraction in high myopic eyes of 30 to 50 year-old patients. J Cataract Refract Surg. 2004;30:2092–2096. 33. Lesueur LC, Arne JL. Phakic intraocular lens to correct high myopic amblyopia in children. J Refract Surg. 2002;18:519–523.

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Complications of Phakic Intraocular Lenses ROBERTO FERNÁNDEZ-BUENAGA, JORGE ALIÓ-DEL BARRIO, JORGE L. ALIÓ, FÁBIO H. CASANOVA, NORMA ALLEMANN, AND WALLACE CHAMON

Introduction Different surgical techniques have been developed to treat high myopia but it remains a refractive challenge. Corneal procedures fall short of correcting high refractive errors because of low predictability, regression, deep ablation depth, smaller diameter ablation zones, poor quantitative and/or qualitative refractive results, iatrogenic corneal ectasia, and optical aberrations. Alternative surgical procedures that spare corneal tissue, such as clear lens extraction and phakic intraocular lens (PIOL) implantation, have been considered again after advances in technology and microsurgical techniques. Despite having excellent refractive results, clear lens extraction has been related to a high incidence of retinal detachment and loss of accommodation.1,2 To maintain predictability of lens surgery while avoiding loss of accommodation and minimizing vitreoretinal complications, implantation of PIOLs is a very attractive option. In addition, this corneal-spare refractive procedure preserves corneal asphericity, presents less reduction in contrast sensitivity, and usually results in potential gain in lines of vision if compared to keratorefractive surgeries. The gain in visual acuity is secondary to the magnification effect of myopic IOLs leading to an enlargement of the retinal image in these patients.3 Furthermore, these synthetic implant techniques are reversible, and corneal tissue–altering techniques are not. Implanting a PIOL in high myopic eyes has generated a renewed interest because it is one satisfactory surgical technique for correction of high refractive errors. Furthermore, a corneal refractive procedure may be added if there is any residual refractive error or if the patient develops more myopia in the long term. The first PIOL, a minus power anterior chamber phakic intraocular lens (AC PIOL), was described by Strampelli shortly after the introduction of IOLs to correct aphakia in the early 1950s.4 Later, Barraquer5 published the first longterm series of high myopic patients who were implanted with an AC angle-fixated PIOL made of polymethylmethacrylate (PMMA). Both lenses were abandoned owing to

high incidence of complications. PIOL implantation was reintroduced in 1986 by Fechner, van der Heijde, and Worst,6 who used a new biconcave iris-fixated IOL to correct high myopia based on modifications made in the iris-claw IOLs used in cataract surgery; by Baikoff and Joly,7 who modified the Kelman multiflex AC IOL used for aphakia; and by Fyodorov et al.,8 who used a one-piece silicone collar button lens with 500 to 600 nm of Teflon coating implanted in the posterior chamber. All of these models have undergone a series of design improvements to avoid complications related to corneal endothelium, iritis, and cataract formation.

Anterior Chamber IOLs Historic Angle-Supported Models The following lenses are no longer implanted. However, it is necessary to know the history and the complications associated with these models, as we still may find patients with these phakic IOLs implanted. The main concerns with regard to long-term complications of AC PIOLs are related to glare, halos, pupil ovalization, pigment dispersion, and progressive loss of corneal endothelial cells.

Baikoff‘s Lens Models Implantation of negative angle–supported AC PIOLs (ZB models, Chiron Domilens) was developed by Baikoff. There have been reports on progressive endothelial damage with consequent corneal decompensation secondary to intermittent contact with the thick edges of the first-generation angle-supported AC PIOLs.9–12 The haptic angulation was therefore lowered from 25 degrees to 20 degrees, the loops became more flexible, and the optic was thinned in the second-generation Baikoff ZB5M model (Bausch & Lomb/ Chiron Vision), which was later named ZB5MF after adding a fluorine surface treatment to improve its biocompatibility. It was a single-piece, biconcave AC PIOL also 421

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based on a multiflex Kelman AC IOL. It was made of PMMA containing UV blocker, available in overall lengths of 12.5, 13.0, and 13.5 mm, and the optic was 5.0 mm in diameter with an effective optical diameter of 4.0 mm. It was available in 1-diopter (D) increments from −7.0 D to −20.0 D. Some preoperative parameters had to be considered before AC PIOL implantation. Patients had to have at least 2500 cells per mm2 endothelial density and an anterior chamber depth of 3 mm or more. In a series of 16 eyes with a follow-up of 1 year, Baikoff and Colin found little endothelial cell loss (4.2, 4.0, and 4.6%, at 3, 6, and 12 months, respectively) after ZB5M implantation.11,13 However, halos and glare were still reported; they seemed to be related to the small optic zone size of 4.0 mm combined with the physiologic eccentricity of the pupil. Pupillary ovalization could be discrete and stable, and sometimes reversing spontaneously, or progressive and irreversible, requiring additional surgery if goniosynechia did not allow iris contraction (Fig. 32.1).14 Also, sporadic retinal detachment cases have been published related to ZB5M lenses.15,16 After including peripheral iridotomy in the surgical protocol, there was no more pupillary block glaucoma.17,18 Alio et al.17 published a series of 263 eyes with a mean follow-up of 4.89 years (range 1.2 to 7.6 years) after implantation of different angle-supported AC PIOLs, including ZB5M, ZB5MF, and ZSAL-4 models. Only 10% of patients considered the night halos and glare significant at the 7-year follow-up. The authors also found acute postoperative anterior uveitis in 12 eyes (4.56%); increased intraocular pressure (IOP) in 19 cases (7.2%) with no correlation with pupil ovalization or acute anterior uveitis; retinal detachment in eight eyes (3%); and stabilization of endothelial cell loss over time after the second year (1.83% at 1 year, 1.37% at 2 years). Nonetheless, many patients were lost to followup, creating a significant bias for the conclusion about endothelial cell loss stabilization over time. Regarding significant pupil ovalization, defined as pupil border deviation reaching the edge of the optic, these authors noticed it to be present in 16 eyes (6.08%); two eyes required IOL

A

B

• Fig. 32.1  Angle-supported anterior chamber phakic intraocular lens, ZB5MF model. (A) Pupil ovalization. (B) Gonioscopy showing iris depression secondary to haptics, a possible mechanism for iris retraction and pupil ovalization. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

explantation. Lesser degrees of variable ovalization were observed in another 27 eyes (10.3%). These authors postulated that the association of pupil ovalization, iris retraction, and atrophy might suggest the development of ischemic iridopathy and low-grade inflammation, possibly induced by haptic compression of the iris root vessels. In this series, 9 eyes (3.42%) required IOL explantation owing to cataract formation, which probably was age related.19,20 Surgery might increase the speed of cataract formation because of surgical trauma, postoperative inflammation, metabolic changes, and the use of postoperative topical steroids. However, other patients with high myopia and axial length greater than 30.0 mm did not develop a cataract, suggesting that surgery and AC PIOL were not the only factors involved in cataract development. Baikoff et al.14 followed up on 134 eyes implanted with the ZB5M lens for 18 to 52 months (mean 35.8 months) and found endothelial cell loss of 3.3% at 6 months after surgery but declining by an additional 1% to 2% over the remaining follow-up. According to linear regression analysis, most of the observed reduction in endothelial cells over the course of the study was not from postoperative effects of the ZB5M model but was attributable to the acute effects of surgery. They also reported halos and glare in 27.8% of 133 eyes and iris retraction with pupillary ovalization in 22.6% of eyes. The latter increased in incidence over time. In this study, the lens was exchanged in 4 of 133 eyes (3.0%): rotation in two eyes, displacement in one eye, and because of a loop foot in the iridectomy in the fourth eye. It was removed in 3 of 133 eyes (2.3%): halos in one eye, and a flat anterior chamber with severe inflammation in two eyes. Late complications included implant rotation in six eyes (4.5%), and IOL displacement in two eyes (1.5%). Based on this study, Baikoff created a third-generation lens to further reduce complications, the NuVita MA 20 model (Bausch & Lomb/Chiron Vision; Fig. 32.2). Results published by Allemann et al.21 on 21 eyes implanted with the NuVita AC PIOL and followed up for 24 months showed pupil ovalization (difference between the smallest and largest diameters of at least 0.5 mm) in 40% of eyes (8 cases) in contrast to other series published, in which only severe cases of pupil ovalization were reported and IOL rotation of more than 15 degrees in 80% of eyes

A • Fig. 32.2

B

  Angle-supported myopic anterior chamber phakic intraocular lens, NuVita model. (A) Normal clinical aspect. (B) Gonioscopy showing footplates ideally positioned in the angle with no iris depression. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

CHAPTER 32  Complications of Phakic Intraocular Lenses

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A

B

C

the angle-supported Baikoff models. However, this model did not prevent pupil ovalization, IOL rotation, or lowgrade postoperative uveitis. A fifth-generation ZSAL-4/Plus lens (Morcher GmbH) was then designed, with larger effective (5.3-mm) and total (5.8-mm) optical zone diameters and a thinner connecting bridge between both footplates to increase flexibility and disperse compression forces against angle structures.

D

E

F

Phakic 6 IOL

•

Fig. 32.3  Pupil ovalization observed after myopic NuVita model implantation. In mild cases (A), the pupil is slightly ovaling. In (B), a medium degree of ovalization is observed 2 years after surgery. In severe cases (C, D, E, and F), significant pupil ovalization is observed and the pupil ovaling reaches or trespasses the edge of the optic. In all of the series, the IOL diameter was calculated for 0.5 mm in addition to white-to-white measurement. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

Phakic 6 IOL (Ophthalmic Innovations International) is a planoconcave, angle-supported AC PIOL, which is made of PMMA and has a 6.0-mm optical zone diameter. This model was also associated with postoperative pupil ovalization and endothelial cell loss, however.

Foldable Lenses Other angle-supported AC PIOL models have been designed targeting the important issue of decreasing incision size for implantation. Foldable IOLs include the Duet Kelman, the Acrysof foldable AC PIOL (later known as Cachet), and the Baikoff foldable AC PIOL (Vivarte model). Foldable IOLs are more prone to vault and cause intermittent endothelial touch. Therefore long-term endothelial cell density assessment is mandatory.

Duet Kelman Lens

• Fig. 32.4

  Myopic anterior chamber phakic intraocular lens, NuVita model associated with iris atrophy. Note that this region corresponds to haptic position. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

(16 cases). In 60% of eyes, IOL rotation occurred between the first and second year after surgery. A higher incidence of pupil ovalization was observed at 2-year follow-up (Fig. 32.3). It seems to be related to improper position of footplates associated with an ischemic component (Fig. 32.4).

ZSAL Models Perez-Santonja et al. also developed a model (ZSAL) of angle-supported AC PIOL.22 The fourth-generation lens, the ZSAL-4 (Morcher GmbH), is a planoconcave lens made of single-piece PMMA and has Z-shaped haptics, like the NuVita. The optical zone diameter is 5.5 mm, with an effective optical zone diameter of 5.0 mm. The optic has a transitional edge with a three-sided design to reduce refracted glare. The overall length of the lens is 12.5 or 13.0 mm, and the lens power ranges from −6.0 D to −20.0  D in 1-D steps. Perez-Santonja et  al.22 also confirmed the long-term endothelial tolerance for this lens. In addition, the rate of halos and glare was reduced compared to

In a pilot study, involving only three eyes followed for 6 months, the Duet Kelman lens (Tekia Inc.) has confirmed its potential to solve pupil ovalization by selective postoperative haptic exchange of the PIOL.23 The haptic and the optic of the lens are separately implanted and then fixed together inside the eye. The rigid PMMA haptic can be implanted through 2.5-mm incisions and the 6-mm silicone optic is then implanted using an injector through the same incision. The haptic size (12.0, 12.5, and 13.0 mm) is chosen based on the white-to-white measurement.

Acrysof Phakic Implant (Cachet, Alcon) It had a 6-mm optic, implantable with an injector through a 3-mm incision. Preliminary results showed excellent tolerance and minimal induction of pupil ovalization. However, the lens was retired from the market owing to several cases of accelerated endothelial cell loss in 2013.

GBR Vivarte Lens The GBR Vivarte lens (CibaVision-IOLTech), designed by Baikoff and launched in Europe in 2001, is an anglesupported, one-piece hydrophilic acrylic lens with tripodal rigid haptics and a foldable optic that can be inserted in a 3.2-mm incision (Fig. 32.5). As reported at the 2002 AAO meeting, Orlando, 2002, Tanaka et al. found pupil ovalization greater than 0.5 mm in only 1 eye out of 11 eyes with a follow-up of only 6 months. Lens sizing is not very accurate, and complications associated with undersized and oversized lenses are lens rotation and iris tucking, respectively (Fig. 32.6).

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• Fig. 32.5  Vivarte model for myopia. A foldable tripod-haptic anterior chamber phakic intraocular lens developed by Baikoff. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

A

B

C

• Fig. 32.6  Sizing-related Vivarte myopic phakic intraocular lens (PIOL) complications. (A) Undersized PIOL leading to slight decentration and rotation. (B) Same eye in (A) under ultrasound biomicroscopy showing uncorrected positioning of footplates not reaching the angle. (C) Oversized PIOL causing iris tucking seen on gonioscopy. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

Current Anterior Chamber IOLs: Iris-Fixated Models The first iris-claw lens was implanted in 1978 to correct aphakia following cataract surgery. In 1986, Fechner and Worst changed the existing iris-claw lens used for aphakia into a negative biconcave lens for correction of high myopia in phakic patients. Although it showed initially promising results,6 late endothelial damage in a relatively high percentage of cases was noticed with those lenses.24,25 In 1991, after a 5-year European Feasibility Study, the design of the optic was modified to a convex–concave IOL and, in 1998, the name of the lens was changed to Artisan (Ophtec BV). In 2001, the Toric Artisan was launched. In 2002, Advanced Medical Optics (AMO) acquired the global distribution rights to market its own brand of the Artisan lens, known as the Verisyse. The US Food and Drug Administration (FDA) panel recommended the approval, with conditions, of the Verisyse PIOL in February 2004. In September 2004, the FDA approved the Artisan/Verisyse PIOL for use in myopic patients from −5.0 D to −20.0 D.

It was the first phakic lens to receive FDA approval. The Artisan lens is a PMMA rigid IOL that requires a 5.5- to 6-mm incision for its implantation. However, in 2005, the Artiflex phakic IOL was launched. This is a foldable IOL that has silicone optic and PMMA haptics, reducing the incision size to 3.2 mm. Finally, in 2009, the Toric Artiflex became available. As it has been previously described, these iris-clip IOL models have had several design modifications since 1986. We are going to show in this chapter the results and complications published with the Artisan and Artiflex models in the last 2 decades. Many advantages could be highlighted for iris-fixated IOLs, such as longest clinical history and experience, “one size fits all,” versatility (indicated for myopia, hyperopia, astigmatism, and aphakia), reversibility, safe distance from corneal endothelial cells and from crystalline lens, centration, good predictability, and no pupil disturbance. The main problem posed by iris-supported PIOLs is long-term tolerance in relation to endothelial damage, with consequent corneal decompensation that could be related to chronic subclinical uveitis or other long-term factors, as well as the stability of lens fixation to the iris, and the development of complications such as glaucoma, chronic uveitis, cataract formation, or retinal detachment. Menezo et al.26 followed up on 111 eyes implanted with Worst iris-claw myopic lenses for 4 years (mean, 37.73 months; range, 6–52 months) and found a mean endothelial cell loss of 3.85% at 6 months, 6.59% at 1 year, 9.22% at 2 years, 11.68% at 3 years, and 13.42% at 4 years. As in their previous study, although the hexagonality and coefficient variation in cell size returned to the preoperative levels, the endothelial cell density seemed unstable and decreased over time. A significant correlation was found at 6 months after surgery between cell loss and shallow anterior chamber, and between cell loss and IOL power (thickness). The US Clinical Investigation of the Artisan Myopia and Hyperopia Lens considers as inclusion criteria an anterior chamber deeper than 3.2 mm (3.0 mm for the European Clinical Investigation of the Artisan Myopia Lens27) and an endothelial cell density of at least 2000 cells per mm2. In their series, Menezo et al.26 reported surgical reintervention in four eyes: poor IOL fixation in two eyes, traumatic IOL subluxation in one eye, and error in IOL power calculation in one eye. Other complications included hyphema in five eyes, iris trauma in five eyes, intraoperative IOL decentration in 15 eyes (13.5%), iritis in four cases, Urrets–Zavalia syndrome in one eye, increased IOP in five eyes, leakage in two cases, and glare in two eyes. One lens was explanted due to severe corneal edema caused by continuous endothelial touch secondary to IOL displacement. Perez-Santonja et al.24 compared 30 eyes with a Worst– Fechner lens to 28 eyes with a Baikoff ZB5M lens regarding long-term endothelial cell loss. They found that endothelial cell loss was similar with both types of lenses during the first year after surgery (about 13%) but that there was a progressive cell loss in the Worst–Fechner lens group

CHAPTER 32  Complications of Phakic Intraocular Lenses

thereafter and stabilization in the ZB5M group. They concluded that factors other than surgical trauma were involved in cell loss with iris-supported lenses. Some authors have reported that IOL fixation can cause persistent damage to the blood–aqueous barrier.28–30 They suggested that chronic uveitis induced by iris damage could be responsible for progressive endothelial cell loss. Using a laser flare-cell meter, Alio et al.30 found more inflammation in eyes with Worst–Fechner lenses than in eyes with Baikoff ZB5M lenses 1 year postoperatively. Perez-Santonja et al.28 reported similar findings in a study on 60 eyes. Chronic subclinical inflammation was detected with the laser flarecell meter between 1 and 2 years postoperatively with both types of lenses but more in the eyes with Worst–Fechner lenses. However, some authors believed that the high flare values found in these studies were due to artifacts such as light dispersion from the lens surface. Fechner et al.31 studied 68 myopic eyes using a laser flare-cell meter and 23 eyes with iris fluorescein angiography and found no inflammation and dye leakage. Elevated IOP following iris-fixated IOL implantation can be due to pupillary block and chronic inflammation. Proper surgical technique coupled with a preoperative YAG-laser iridotomy or intraoperative iridectomy is fundamental in order to avoid these complications. Other complications have been reported, such as late postoperative uveitis, corneal pigment deposition, cystic wounds, decentration, halos (induced by decentration or a large pupil), and iris atrophy in the area of IOL fixation (Fig. 32.7).25 Traumatic or spontaneous IOL dislocation has been reported (Fig. 32.8).25 Usually, the haptic was not properly fixated to the iris (Video 32.1). A European multicenter study of the Artisan lens on 518 myopic eyes over 8 years was published by Budo et al.27 The authors reported results on 249 myopic eyes followed up for 3 years. The intraoperative complications included wound hemorrhage in 10 eyes, IOL–cornea touch in 14 eyes, and difficulty in lens centration in two eyes. Postoperative complications included poor IOL centration in 22 eyes, hyphema in 4 eyes, persistent corneal edema in two eyes, pupillary block glaucoma in two eyes, retinal detachment in two eyes, and iris atrophy in one eye. Twenty eyes

underwent surgical reintervention during follow-up because of complications related to the IOL: IOL exchange (eight eyes), repositioning (five eyes), and removal (seven eyes) due to wide pupil diameter (one eye), progressive endothelial cell loss (one eye), trauma-induced IOL dislocation (two eyes), and cataract formation (three eyes). At 3 years, halos and glare were present in 8.8% and 6.0% of eyes, respectively. The most striking result was the little postoperative rate of endothelial cell loss (7.2% at 1 year, and 1.7% at 2 years) with a return to physiologic values (0.7% per year) between years 2 and 3. Saxena et al.32 published a series of 26 hyperopic eyes implanted with the Artisan model 203W (Ophtec) with a mean follow-up of 22.4 months. They found an endothelial cell loss of 10.1% after 3 years, which was high despite the introduction of correcting factors (0.6% physiologic cell loss per year). This could be the result of endothelial trauma during implantation intermittent trauma over time in the corneal midperiphery because of a shallow anterior chamber. Two patients experienced posterior synechiae with pigment deposits in both eyes. One of these eyes underwent IOL removal within 2 years with a consequent clear lens extraction and PC IOL implantation. The implantation of the Artisan lens has provided accurate, predictable, and stable refractive results and a low rate of early complications. To answer questions about longterm potential risks to the corneal endothelium and anterior uvea, an important prospective study was initiated in 25 North American centers enrolling myopic patients from October 1998 to December 2001. This FDA phase III clinical trial was named the US FDA Ophtec Study of the Artisan Lens for Myopia and included the first 765 myopic eyes operated on for Artisan implantation and followed up for 24 months in the United States.33 No statistically significant postoperative endothelial cell loss was reported in this group. In a worst-case scenario, 9% of all eyes were at higher risk of a 10% loss of cell density at 12 months after surgery. This study did not reach the conclusion that a significant decrease in endothelial cell count occurs after

A

A

B

• Fig. 32.7  Iris-supported myopic anterior chamber phakic intraocular lens, Artisan model. (A) Iris atrophy in the region of iris fixation. (B) Decentration related to the surgery. Note superior iridectomies in both cases. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

425

B

• Fig. 32.8  Iris-supported anterior chamber phakic intraocular lens luxation. (A) Myopic Artisan lens dislocated into the inferior angle after nasal haptic has escaped from the iris fold spontaneously. (B) Highdiopter power intraocular lens displaced toward inferior angle 1 year after implantation owing to its weight. ((A) Published with permission from Perez-Santonja JJ, Bueno JL, Zato MA. Surgical correction of high myopia in phakic eyes with Worst-Fechner myopia intraocular lenses. J Refract Surg. 1997;13(3):268–281. (B) Courtesy of Wilson de Freitas, MD, Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine, São Paulo, Brazil.)

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Artisan implantation for the general population of high myopic eyes. Another paper, published by Tahzib et al.,34 studied Artisan implantation for moderate and high myopia with a long follow-up of 10 years. The authors found a mean endothelial cell loss of 8.86% ± 16.01% at 10 years. This corresponds to an annual loss of 0.9% compared with the physiologic 0.6%. Therefore these authors state that the Artisan IOL is safe when strict inclusion criteria for surgery are applied. The Toric Artisan lens has been shown to be a safe and effective method of providing correction in myopic and hypermetropic eyes with astigmatism ranging from 1.5 D to 7.25 D.35 Both myopic and hypermetropic astigmatism groups showed good predictability with 88.6% of eyes presenting an uncorrected visual acuity (UCVA) of 20/40 or better and a mean of 4.5% total endothelial cell loss after 6 months of follow-up. This lens measures 8.5 mm in overall length, features a 5-mm convex-concave optic, and is similar to the models for treating myopia and hyperopia, except that the toric optic features a spherical anterior surface and a spherocylindrical posterior surface. In this series of 70 eyes, mild glare was observed in 4.3% of cases (three patients) and moderate glare in 1.4% (one patient). No potentially sight-threatening complications were reported. Two eyes required surgical reintervention. In one eye, a postoperative wound leak occurred, requiring suture; in the other eye, a successful reposition of the lens was performed after 1 week because of a deviation of approximately 15 degrees from the target axis. In another eye, pronounced iris pigment precipitates on the optic of the IOL were observed. A 6-month follow-up is a limitation of this study and longer follow-up is required for better evaluation of possible late complications.35 It is necessary to emphasize that, thanks to the development of new diagnostic tools such as anterior segment optical coherence tomography (OCT) or the Scheimpflug technology, we are now able to study in a much better way the anterior segment anatomy. Accordingly, there are better established criteria for the phakic IOL implantation, thus improving results and safety. The latest papers published show a lower complication rate and very good results in the long term. The Artiflex lens was analyzed in a multicenter prospective study that involved 296 eyes of 191 patients and 2 years of follow-up.36 Two years after the surgery, the safety index was 1.09 and 49.9% of the eyes had gained one line of best spectacle-corrected visual acuity (BSCVA). The efficacy index 2 years after the surgery was 1. After 2 years, the deviation from the intended refraction was within 0.5 D in 75.2% of the eyes and within 1 D in 94.3% of the cases. The endothelial cell loss due to the surgery (6 months later) was 0.05 ± 16.97% being at the end of the follow-up of 1.07 ± 16.35%. In terms of complications, there was mild glare in 3.1% and moderate glare in 0.3%. Mild halos were reported by 3% of the patients. Pigment precipitates were reported in 14 eyes (4.8%); however, it did not result in loss

of visual acuity. Nonpigment precipitates were reported in four eyes (1.4%) of three patients. In three cases, the precipitates also were reported at previous visits. The precipitates were described as giant cells. In one eye, the amount of precipitates was significant and there was a loss of BSCVA of four lines 2 years after surgery. The eye was treated with topical corticosteroids; at a later postoperative examination, the visual acuity had returned to 1.0 Snellen decimals. Synechia was present in three eyes (1.4%) of three patients at 2 years after surgery. In one case, a claw of the Artiflex lens was observed to have perforated the upper layer of the iris tissue. The lens was secure and stable and no complications were reported for this eye. An akinetic iris was reported persistent from the 6-month postoperative visit to the 2-year postoperative visit in another eye. The patient did not lose lines of BSCVA. Earlier in the study, there was one explantation (0.3%) because the patient was not satisfied with the anticipated overcorrection and requested a lens exchange. After the lens exchange, the subjective refraction was plano and the BSCVA was 1.0 (a gain of one line). There was a repositioning of the lens in 4 eyes because of incorrect lens centration (three cases, 1.4%) or synechia (one case, 0.3%). Other transient (nonpersistent) complications reported during the study included synechia (one case, 0.3%; the eye responded to steroid treatment); anterior chamber uveitis (two cases, 0.7%; 1 day and 1 week after surgery and treated with medication); and uveitis (one case, 0.3%; 1 day after surgery and treated with medication). The Toric Artiflex has been analyzed as well. In a study published by Doors et al.,37 115 implanted eyes were studied. At 6 months, 99% of eyes had a UCVA of 20/40 or better and 81.8% of eyes were within 0.5 D of the intended refraction. There was a significant decrease in endothelial cell loss at 3 months of 4.8% ± 11.9% with no additional decline between 3 and 6 months. Mild to moderate glare complaints were reported in 7% of the cases and mild halo was reported by 4.3% at 6 months postoperatively. The incidence of pigment and nonpigment precipitates was 14.8% and 12.2%, respectively, at 6 months. It is evident that the incidence of precipitates is more often reported with the Artiflex lens than with the Artisan lens.36,37 The cause of these precipitates is not very well known. Most of them do not affect visual acuity but if visual acuity is affected, steroid treatment has been shown to be effective.36 Some authors suggest that these precipitates could be related to previous YAG laser iridotomy or to some preoperative parameters.37 The silicone material of the optic could also play a role, as this is the most obvious difference with the Artisan IOL. In any case, at least 4 weeks of topical steroid treatment is recommended in order to prevent these precipitates. In a recent and interesting paper,38 the authors studied 29 patients who had a phakic iris-claw implanted in one eye and corneal refractive surgery in the fellow eye (group 1). Ten years later, mean endothelial cell loss was 6.41% ± 8.02% (standard deviation [SD]; group 1, iris-claw PIOLs), 5.59% ± 5.98% (group 1, corneal refractive surgery); P > 0.05.

CHAPTER 32  Complications of Phakic Intraocular Lenses

These authors also studied 29 patients (group 2) who had an iris-claw PIOL implanted in one eye and no surgery at all in their fellow eye. Ten years later, mean endothelial cell loss was 7.84% ± 6.83% (group 2, iris-claw PIOLs), and 6.74% ± 3.97% (group 2, no surgery); P > 0.05. There were no statistically significant differences between both groups. It seems that the decrease in complication rate associated with this type of IOL goes in tandem with the advances in anterior segment imaging technology and with the establishment of strict implantation criteria based on this technology. The most accepted criteria are ACD of 3.2 or higher from the corneal epithelium to the anterior capsule (or 2.85 from endothelium), angle aperture of 35 degrees or higher, lens rise lower than 600 µ (some authors, as we do, prefer 200 µ) and endothelial count according to age but always higher than 2000 cells.37 Ferreira et al. have recently shown that, in order to minimize endothelial cell loss, the minimal distance between the endothelium and the IOL should always be 1.7 mm.39 Alió et al.40 reported the main causes for PIOL explantation in 240 consecutive cases. The main cause for all the different types of PIOL was cataract development. Indeed, for the iris-claw lenses, the main cause was cataract development in 45.83% of cases whereas endothelial cell loss was the cause for IOL explantation in 8.33% of eyes.

Posterior Chamber IOLs Sulcus-Supported Models In 1986, Fyodorov first conceived the idea of an “intraocular contact lens or implantable contact lens” (ICL), a posterior chamber PIOL (PC PIOL) implanted into the ciliary sulcus in the posterior chamber in front of the crystalline lens and behind the iris, centered on the pupil. This first generation was a one-piece silicone collar button with a Teflon coated lens. The optic was located in the anterior chamber and the haptics were in the posterior chamber behind the iris. Lens design and material were refined over time in an effort to reduce incidences of cataract, uveitis, and endothelial cell loss. Mastropasqua et al.41 described a case with bilateral anterior subcapsular cataract and severe endothelial cell loss and IOL dislocation in one eye 5 years after Fyodorov PC PIOL implantation, requiring IOL explantation associated with phacoemulsification and PC IOL implantation. Chiron-Adatomed GmbH subsequently produced a silicone elastomer PC PIOL for high myopic patients, the model 094M-1 IOL, also known as Fyodorov lens type 094M-1. It was a single-piece, boat-shaped lens with plano haptics composed of polydimethylsiloxane, a thermostable high-grade silicone elastomer with a lower water content (hydrophobic). However, it induced high incidence of cataract, as well as decentration, halos, and a few cases of violent ocular reaction requiring explantation.42 Owing to these complications, the silicone Fyodorov lens type 094M-1 was discontinued.

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In 1993, a hydrogel collagen plate IOL was developed by Staar (Staar Collamer Implantable Contact Lens [ICL], Staar Inc.). The current Staar Surgical AG IOL (ICL) is made of a porcine hydrophilic collagen/HEMA copolymer (63% hydroxyl-ethyl-methyl-acrylate; 0.2% porcine collagen; 3.4% benzofenone for UV absorption). The idea of implanting a PIOL into the posterior chamber to correct high myopia in phakic eyes is to keep the implant separated from the corneal endothelium. The relationship between IOL size and fixation site is very important. The PC PIOL is vaulted so that its optic arches over the crystalline lens while its haptics rest over the ciliary sulcus. An oversized lens causes excessive vaulting, angle closure, and IOL-iris touch, leading to narrow-angle glaucoma and pigment dispersion, whereas an undersized lens presents instability, cataract, rotation, and decentration (Fig. 32.9). There is also midperipheral contact with the natural crystalline lens, potentially causing cataract. The goal is to implant a lens slightly larger than the ciliary sulcus to promote anterior IOL vaulting and secure fixation. Intraoperative complications include inverted IOL implantation, broken IOL, and surgical trauma to the iris causing pigment dispersion and to the natural lens leading to cataract. Causes of increased IOP include corticosteroid responders and pupillary block glaucoma. Iridotomies are mandatory to prevent this latter complication. Usually, two iridotomies are performed 2 weeks before surgery, positioned superiorly between 60 degrees and 90 degrees apart to decrease the likelihood of iridotomy occlusion by the

• Fig. 32.9  Ultrasound biomicroscopy showing a myopic anterior chamber phakic intraocular lens, ICL Staar model, decentered to the left with its optic border toward the anterior chamber. (Courtesy of Walton Nose, MD, Cataract Surgery Service, Federal University of São Paulo, Paulista School of Medicine, São Paulo, Brazil.)

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• Fig. 32.10

  Intraoperative view of anterior subcapsular cataract developed after implantable contact lens implantation in a myopic eye. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

PIOL haptics. However, with the latest ICL version, the iridotomies are not necessary owing to the aquaport, which is a central hole in the lens optic. The main postoperative complication is anterior subcapsular cataract (Fig. 32.10) as a result of direct trauma during implantation, contact between the IOL and the lens, or a metabolic effect. These complications are reported in the following publications. Zaldivar et al.43 reported on 124 myopic eyes that received different models of Staar PIOLs with a follow-up of 11 months (range, 1–36 months). Fourteen eyes had increased IOP: six pupillary block glaucoma, six corticosteroid eyedrop-induced glaucoma, and two with unclear origin. In addition, one IOL was inverted; five IOLs had to be removed owing to glaucoma (two), decentration (five), broken IOL (one); one eye had retinal detachment 3 months after IOL implantation; one IOL was recentered owing to glare, and diplopia required recentration in one eye; three eyes had lens capsule opacities, but 2 of these eyes presented lens opacities preoperatively and did not progress during the study period. Uusitalo et al.44 found pupillary block glaucoma requiring surgical intervention in 3 myopic patients (7.9%) in a series of 38 eyes followed up for 22.3 months (range, 6–35 months). They also reported cataract development in 2 eyes (5.3%) of the same patient 18 months after surgery, requiring IOL explantation, phacoemulsification and PC IOL implantation. Jimenez-Alfaro et al.45 also published their results on 20 eyes treated with the Staar Collamer ICL and studied with ultrasound biomicroscopy (UBM): IOL–crystalline lens touch was found in the periphery in 60% of eyes and in the center in 15% of eyes. There was contact between the PC PIOL and the posterior iris surface in all patients. The haptics were located in the ciliary sulcus in 17 eyes (85%). In three eyes, a footplate was folded and impacted into the ciliary body. Although no clinical appearance of cataract was noted, crystalline lens transmittance decreased progressively

over the first 12 months but appeared to stabilize between 12 and 24 months. Anterior chamber depth decreased from 9% to 12%. Endothelial cell loss was observed during the first 2 postoperative years, probably owing to the traumatic effect of surgery, but became stable thereafter. Finally, the authors observed a 49.19% increase in aqueous flare during the first postoperative month. Cataract development after implantation of different ICL Staar models was best illustrated by Lackner et al.46 In a prospective study, 75 patients (65 myopic, 10 hyperopic eyes) were followed up for a mean time of 22 months. Anterior subcapsular cataract was noted in 25 eyes (33.3%), two of which showed direct contact with the ICL. Eleven eyes (14.7%) were stable in opacification and 14 eyes (18.7%) had progressive opacification. The mean time to opacification was 27.1 months. Cataract surgery was required in 8 cases (10.7%). Several other studies on ICLs mentioned earlier have not found this complication. Nevertheless, in these series, the follow-up was significantly shorter. Cataract formation can be caused by intraoperative trauma, intermittent PC PIOL–crystalline lens contact, alterations in aqueous humor flow, metabolic disturbances, or chronic subclinical inflammation associated with disruption of the blood–aqueous barrier caused by microtraumas resulting from the constant friction between the posterior iris surface on the ICL or its haptic on the ciliary sulcus. The authors also reported intraoperative touch of the crystalline lens with immediate onset of opacification in four eyes. Elevated IOP occurred in six eyes between 1 and 4 months after surgery because of nonfunctional preoperative iridotomies requiring additional YAG laser iridotomy. Sanchez-Galeana et al.47 also published a large series of 170 consecutive patients with ICL implantation (136 myopic and 34 hyperopic eyes) who developed crystalline lens opacities in 14 eyes (8%) 125 days after PIOL implantation. The incidence of lens opacities after PC PIOL was 7% for the myopic group and 12% for the hyperopic group. All 14 eyes had anterior subcapsular opacities and two also had nuclear sclerosis. Nine of the 14 (64%) opacities were asymptomatic. The opacities were clinically diagnosed from 1 week to 14 months after PC PIOL surgery. Ten cases of lens opacity (71%) were noted 3 months postoperatively or sooner, suggesting intraoperative trauma. They also found a correlation between surgeon experience and lens opacities. Results from the FDA clinical trial of the ICL for moderate-to-high myopia using the ICM V4 model, which was initiated in May 1997, were reported from a multicenter study by Sanders et al.48 Twelve centers across the United States enrolled 523 consecutive eyes of 291 patients between November 1998 and July 2001. They found early surgically induced anterior subcapsular opacities in 11 cases (2.1%), an additional early anterior subcapsular opacity (0.2%) because of inadvertent use of preservative-containing solution, and late anterior cataract formation in two cases (0.4%). Eleven cases (2.1%) required ICL removal and reinsertion during the surgery and 6 resulted in anterior subcapsular opacities. Twelve eyes (2.3%) underwent surgical

CHAPTER 32  Complications of Phakic Intraocular Lenses

reintervention. Four cases (0.7%) were repositioned. In 6 eyes (1.2%), the IOL was replaced. Two eyes (0.4%) underwent ICL explantation with cataract extraction and PC IOL implantation. Only 3% of patients complained about halos and only 1 case of retinal detachment and slight pupil ovalization was reported. Increased IOP requiring secondary surgical intervention was observed in 4% of cases because of small iridotomies or viscoelastic retention. To date, there are only four ICL papers with follow-up longer than 5 years. The lens opacification rate reported in these papers was 20% at 8 years49 and 28% at 10 years.49 The rates of phacoemulsification were 5% at 8 years49 and 17% at 10 years.50 However, Guber et al.,51 in a retrospective of 133 eyes, reported that 55% of eyes (95% confidence interval [CI], 45%–63%) showed a degree of lens opacity, which resulted in 18% (95% CI, 10%–26%) of eyes requiring phacoemulsification at 10 years follow-up. Few ICL papers report endothelial cell loss; however, it is important to remember that also with the posterior chamber PIOL there is an endothelial cell loss owing to surgical trauma and, in some cases, there may be a progressive endothelial loss afterwards. Moya et al.,52 in a retrospective study involving 144 eyes and 12 years of follow-up, reported a surgically induced loss of 6.46% and an average annual loss of 1.20% afterwards. Similarly, Igarashi et al.,49 in another retrospective study with 41 eyes and 8 years of follow-up, showed a mean cell loss of 6.2% ± 8.6%. In 2011, Staar Surgical, Inc. released a new ICL model named V4c Visian ICL with KS Aquaport, VICMO. This model incorporates a 0.36-mm diameter port in the center of the optic. The presence of this port obviates the need for preoperative iridotomies. It is also stated by the manufacturer that this central port improves aqueous humor circulation, reducing the incidence of crystalline lens opacities. However, as the lens was marketed in 2011, there are not published papers yet with follow-ups long enough to study lens-opacity formation in the long term. In a recent review, all papers published on the V4c model were analyzed, showing promising early results.53 It is necessary, in any case, to assess the outcomes after longer follow-ups because, as it has been previously described with the former ICL models, the crystalline lens opacification rate increased significantly after the first 5 years.49–51

Zonular-Supported Models Another PC PIOL that was commercially available is the phakic refractive lens (PRL). This lens was developed by Medennium Inc., later acquired by CIBA Vision and then IOLTech for distribution. It was made of highly purified silicone with a refractive index of 1.46. The central optical zone is biconcave or concave–convex with an optical diameter ranging from 4.0 to 5.0 mm depending on the dioptric power, 10.8 to 11.3 mm long and 6.0 mm wide, and the power ranges from −3.0 D to −20.0 D, and +3.0 D to +15.0 D in 0.5-D steps. It was developed with a one-sizefits-all design based on the principle that it could float over

429

• Fig. 32.11

  Haptic tear during myopic phakic refractive lens implantation requiring intraocular lens exchange. (Courtesy of Refractive Surgery Service, Federal University of São Paulo, Paulista School of Medicine.)

the natural lens, not being fixed in the ciliary sulcus, but being supported by the zonules. The models were usually selected according to white-to-white horizontal distance. During implantation, it must be manipulated carefully; being made of a delicate material, it could be damaged easily (Fig. 32.11). While cataract formation was reported much less frequently than with the ICL, an unusual and specific complication consisting of PIOL posterior luxation has been reported.54 The initial symptoms included loss of accommodation, monocular diplopia, and progressive decreased vision. UBM has shown three different positions of this lens: sulcus-to-sulcus, zonular-to-zonular, and sulcus-to-zonular. The latter seems to be related to lens posterior luxation due to “cheesewiring” of the zonular fibers caused by accommodative movements, PC PIOL rotation, or both. Also, inadequate intraoperative manipulation of the lens causing zonular fiber trauma or eye rubbing after the surgery, or even a combination of these factors, could explain PC PIOL posterior luxation. To date, the cause remains unknown. It is advisable to follow these patients with UBM to identify its position and possible decentration toward the zonule and vitreous. Iridotomies are recommended in order to avoid pupillary block glaucoma. García-Feijoó et al.,55 when using UBM on a series of 16 myopic eyes implanted with PRL, also found that the lens had different positions in the posterior chamber: both haptics in the zonules, which is the ideal position (six eyes); in the ciliary sulcus (five eyes), impacted in the ciliary body (one eye), and in mixed positions (four eyes). Oversized

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•

Fig. 32.12  Artemis (Ultralink) 50 MHz vertical arc-scanning of a myopic phakic refractive lens revealing intraocular lens dislocation with asymmetric forward displacement. Note iris indentation and shallowness of the anterior chamber. This complication is related to phakic intraocular lens oversizing. Note also the posterior chamber PIOL–iris contact. (Courtesy of Ronald H. Silverman, Weill Medical College of Cornell University, New York, NY, USA.)

lenses (Fig. 32.12) cause excessive vaulting and lead to angle closure, anterior chamber shallowing, narrow-angle glaucoma, pigment dispersion, and inflammation. Forward vaulting of PRL is more important than the vaulting of the Collamer ICL lens, because PRL is made of silicone, which is more rigid. In this study, all PRL lenses positioned with both haptics in the zonules presented instability and rotation. Results published by Pallikaris et al.56 on 34 eyes implanted with PRL showed crystalline lens opacification related to intraoperative trauma in four eyes. In three of these eyes, the probe of the vitreous cutter caused damage to the anterior capsule of the crystalline lens during surgical iridectomy. The opacification remained focal behind the iridectomy. Another case presented focal anterior capsule opacification on the first postoperative day, probably because of surgical trauma during intraoperative manipulation. The authors also reported elevated IOP in eight eyes (23.53%) during the first month after surgery. Six eyes were corticosteroid responders and returned to normal levels after suspension of steroid drops; the other two eyes—from the same patient—required trabeculectomy, probably because he had preexisting, undiagnosed glaucoma. Six patients (28.5%) complained of glare and halos at night. Five of these patients had pupils larger than 7 mm; the other patient had a 6-mm pupil. Finally, this IOL model is no longer available owing to the complications described earlier, especially posterior luxation to the vitreous cavity owing to progressive zonular damage.

Conclusions The advantages of PIOLs over corneal refractive procedures include image magnification (in myopes), potential gain in lines of vision, preservation of corneal anatomy and asphericity, and less reduction in contrast sensitivity. In addition, they present advantages over clear lens extraction,

avoiding loss of accommodation and minimizing vitreoretinal complications. Although postoperative refractive results were not the goal of the present review, the majority of patients in all studies presented excellent visual outcomes and low incidence of complications during the short-term postoperative period. PIOLs have proved to be safe, predictable, effective, and stable in correcting high myopia. Prospective cohorts with long-term follow-ups are needed to better define safety in the late postoperative periods, especially regarding damage to endothelial cells and crystalline lenses. Posterior chamber PIOLs seem to present less endothelial cell damage and fewer incidences of halos and glare when compared to AC PIOLs. However, they raise more concern of cataract formation. PIOL surgery is a potentially reversible procedure but the surgeon cannot rule out the possibility of complications, such as cataract formation, pigment dispersion, pupillary block glaucoma, and endothelial cell damage. It is an invasive procedure and therefore carries small but definable general risks, such as inflammation and infection. No refractive surgical technique is entirely predictable. Therefore patients about to have PIOL implantation should be aware that an additional corneal refractive surgical procedure, such as laser in situ keratomileusis (LASIK), may be required for correction of residual refractive error. This approach has been termed bioptics. It is very important to note the striking decrease in the complication rate associated with both the Artisan/Artiflex IOLs and the ICLs when the latest publications are compared with the earliest ones. This is a direct consequence of the following two factors: 1. the improvement in the IOL design of both types of PIOLs; 2. the amazing development of anterior segment imaging technology (OCT, UBM, and Scheimpflug devices), which allows a perfect study of the anterior segment anatomy. As a result, we currently have very well-known and strict implantation criteria according to this anterior segment imaging analysis. The IOL design has been also improved according to the anatomy features discovered with these technologies in order to minimize trauma and late complications. Finally, in order to avoid postoperative complications, it is very important to adhere to the following recommendations: • Endothelial cell count must be adequate and measured before and after the surgery in all cases. It is mandatory to calculate endothelial cell loss owing to surgical trauma. Thereafter, the endothelial cell count should be monitored every 6 to 12 months and compared with the first postoperative count. It has to be taken into consideration that the reproducibility of all the endothelial microscopes is limited. Therefore it is essential to analyze trends instead of one single measurement. • As has been previously described, endothelial cell loss may occur not only with anterior chamber IOLs but also

CHAPTER 32  Complications of Phakic Intraocular Lenses

with posterior chamber IOLs. Thus endothelial cell count monitoring must be done with all types of PIOLs. • Patients with PIOLs should avoid rubbing their eyes and avoid putting pressure on their eyes with a pillow in an attempt to sleep. • Patients with PIOLs usually experience a dramatic increase in their quality of life. Because of this, they often forget to attend follow-up appointments. The importance of these follow-up appointments must be emphasized, as it is essential to anticipate complications related to PIOLs or other kinds of complications, such as retinal problems, in these high-myope patients. After considering all of these factors, we believe that there is feasibility for surgical correction of high refractive errors and that PIOLs seem to be the best option to date.

References 1. Barraquer C, Cavelier C, Mejia LF. Incidence of retinal detachment following clear-lens extraction in myopic patients. Retrospective analysis. Arch Ophthalmol. 1994;112(3):336–339. 2. Colin J, Robinet A, Cochener B. Retinal detachment after clear lens extraction for high myopia: seven-year follow-up. Ophthalmology. 1999;106(12):2281–2284, discussion 2285. 3. Applegate RA, Howland HC. Magnification and visual acuity in refractive surgery. Arch Ophthalmol. 1993;111(10):1335–1342. 4. Strampelli B. Sopportabilita’ di lenti acriliche in camera anteriore nella afachia e nei vizi di refrazione. Ann Ottalmol Clin Ocul. 1954;80(2):75–82. 5. Barraquer J. Anterior chamber plastic lenses. Results of and conclusions from five years’ experience. Trans Ophthalmol Soc U K. 1959;79:393–424. 6. Fechner PU, van der Heijde GL, Worst JG. The correction of myopia by lens implantation into phakic eyes. Am J Ophthalmol. 1989;107(6):659–663. 7. Baikoff G, Joly P. Comparison of minus power anterior chamber intraocular lenses and myopic epikeratoplasty in phakic eyes. Refract Corneal Surg. 1990;6(4):252–260. 8. Fyodorov SN, Zuev VK, Aznabayev BM. Intraocular correction of high myopia with negative posterior chamber lens. Ophthalmosurgery. 1991;3:57–58. 9. Mimouni F, Colin J, Koffi V, Bonnet P. Damage to the corneal endothelium from anterior chamber intraocular lenses in phakic myopic eyes. Refract Corneal Surg. 1991;7(4):277–281. 10. Baikoff G. Phakic anterior chamber intraocular lenses. Int Ophthalmol Clin. 1991;31(1):75–86. 11. Baikoff G, Samaha A. Phakic intraocular lenses. In: Azar DT, ed. Refractive Surgery. Stamford, CT: Appleton & Lange; 1997: 545–560. 12. Saragoussi JJ, Cotinat J, Renard G, et al. Damage to the corneal endothelium by minus power anterior chamber intraocular lenses. Refract Corneal Surg. 1991;7(4):282–285. 13. Baikoff G, Colin J. Intraocular lenses in phakic patients. Ophthalmol Clin North Am. 1992;5(4):789–795. 14. Baikoff G, Arne JL, Bokobza Y, et al. Angle-fixated anterior chamber phakic intraocular lens for myopia of −7 to −19 diopters. J Refract Surg. 1998;14(3):282–293. 15. Foss AJ, Rosen PH, Cooling RJ. Retinal detachment following anterior chamber lens implantation for the correction of ultra-high myopia in phakic eyes. Br J Ophthalmol. 1993;77(4):212–213.

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16. Alio JL, Ruiz-Moreno JM, Artola A. Retinal detachment as a potential hazard in surgical correction of severe myopia with phakic anterior chamber lenses. Am J Ophthalmol. 1993;115(2): 145–148. 17. Alio JL, de la Hoz F, Perez-Santonja JJ, et al. Phakic anterior chamber lenses for the correction of myopia: a 7-year cumulative analysis of complications in 263 cases. Ophthalmology. 1999;106(3):458–466. 18. Ardjomand N, Kolli H, Vidic B, et al. Pupillary block after phakic anterior chamber intraocular lens implantation. J Cataract Refract Surg. 2002;28(6):1080–1081. 19. Younan C, Mitchell P, Cumming RG, et al. Myopia and incident cataract and cataract surgery: the Blue Mountains Eye Study. Invest Ophthalmol Vis Sci. 2002;43(12):3625–3632. 20. Alio JL, de la Hoz F, Ruiz-Moreno JM, Salem TF. Cataract surgery in highly myopic eyes corrected by phakic anterior chamber angle-supported lenses. J Cataract Refract Surg. 2000; 26(9):1303–1311. 21. Allemann N, Chamon W, Tanaka HM, et al. Myopic anglesupported intraocular lenses: two-year follow-up. Ophthalmology. 2000;107(8):1549–1554. 22. Perez-Santonja JJ, Alio JL, Jimenez-Alfaro I, Zato MA. Surgical correction of severe myopia with an angle-supported phakic intraocular lens. J Cataract Refract Surg. 2000;26(9):1288–1302. 23. Alio JL, Kelman C. The Duet-Kelman lens: a new exchangeable angle-supported phakic intraocular lens. J Refract Surg. 2003; 19(5):488–495. 24. Perez-Santonja JJ, Iradier MT, Sanz-Iglesias L, et al. Endothelial changes in phakic eyes with anterior chamber intraocular lenses to correct high myopia. J Cataract Refract Surg. 1996;22(8): 1017–1022. 25. Perez-Santonja JJ, Bueno JL, Zato MA. Surgical correction of high myopia in phakic eyes with Worst-Fechner myopia intraocular lenses. J Refract Surg. 1997;13(3):268–281, discussion 281–284. 26. Menezo JL, Cisneros AL, Rodriguez-Salvador V. Endothelial study of iris-claw phakic lens: four year follow-up. J Cataract Refract Surg. 1998;24(8):1039–1049. 27. Budo C, Hessloehl JC, Izak M, et al. Multicenter study of the Artisan phakic intraocular lens. J Cataract Refract Surg. 2000; 26(8):1163–1171. 28. Perez-Santonja JJ, Iradier MT, del Benitez Castillo JM, et al. Chronic subclinical inflammation in phakic eyes with intraocular lenses to correct myopia. J Cataract Refract Surg. 1996; 22(2):183–187. 29. Perez-Santonja JJ, Hernandez JL, del Benitez Castillo JM, et al. Fluorophotometry in myopic phakic eyes with anterior chamber intraocular lenses to correct severe myopia. Am J Ophthalmol. 1994;118(3):316–321. 30. Alio JL, de la Hoz F, Ismail MM. Subclinical inflammatory reaction induced by phakic anterior chamber lenses for the correction of high myopia. Ocul Immunol Inflamm. 1993;1:219–223. 31. Fechner PU, Strobel J, Wichmann W. Correction of myopia by implantation of a concave Worst–iris-claw lens into phakic eyes. Refract Corneal Surg. 1991;7(4):286–298. 32. Saxena R, Landesz M, Noordzij B, Luyten GP. Three-year followup of the Artisan phakic intraocular lens for hypermetropia. Ophthalmology. 2003;110(7):1391–1395. 33. Pop M, Payette Y. Initial results of endothelial cell counts after Artisan lens for phakic eyes: an evaluation of the United States Food and Drug Administration Ophtec Study. Ophthalmology. 2004;111(2):309–317.

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34. Tahzib NG, Nuijts RM, Wu WY, et al. Long-term study of Artisan phakic intraocular lens implantation for the correction of moderate to high myopia: ten-year follow-up results. Ophthalmology. 2007;114(6):1133–1142. 35. Dick HB, Alio J, Bianchetti M, et al. Toric phakic intraocular lens: European multicenter study. Ophthalmology. 2003;110(1): 150–162. 36. Dick HB, Budo C, Malecaze F. Foldable Artiflex phakic intraocular lens for the correction of myopia: two-year follow-up results of a prospective European multicenter study. Ophthalmology. 2009;116(4):671–677. 37. Doors M, Budo C, Christiaans BJ, et al. Artiflex toric foldable phakic intraocular lens: short-term results of a prospective European multicenter study. Am J Ophthalmol. 2012;154(4):730–739. 38. Morral M, Güell JL, El Husseiny MA. Paired-eye comparison of corneal endothelial cell counts after unilateral iris-claw phakic intraocular lens implantation. J Cataract Refract Surg. 2016;42(1):117–126. 39. Ferreira TB, Portelinha J. Endothelial distance after phakic irisfixated intraocular lens implantation: a new safety reference. Clin Ophthalmol. 2014;8:255–261. 40. Alio JL, Toffaha BT, Peña-García P, et al. Phakic intraocular lens explantation: causes in 240 cases. J Refract Surg. 2015;31(1): 30–35. 41. Mastropasqua L, Toto L, Nubile M, et al. Long-term complications of bilateral posterior chamber phakic intraocular lens implantation. J Cataract Refract Surg. 2004;30(4):901–904. 42. Brauweiler PH, Wehler T, Busin M. High incidence of cataract formation after implantation of a silicone posterior chamber lens in phakic, highly myopic eyes. Ophthalmology. 1999;106(9): 1651–1655. 43. Zaldivar R, Davidorf JM. Oscherow S. Posterior chamber phakic intraocular lens for myopia of –8 to –19 diopters. J Refract Surg. 1998;14(3):294–305. 44. Uusitalo RJ, Aine E, Sen NH, Laatikainen L. Implantable contact lens for high myopia. J Cataract Refract Surg. 2002;28(1):29–36. 45. Jimenez-Alfaro I, del Benitez Castillo JM, Garcia-Feijoo J, et al. Safety of posterior chamber phakic intraocular lenses for the

correction of high myopia: anterior segment changes after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2001;108(1):90–99. 46. Lackner B, Pieh S, Schmidinger G, et al. Outcome after treatment of ametropia with implantable contact lenses. Ophthalmology. 2003;110(11):2153–2161. 47. Sanchez-Galeana CA, Smith RJ, Sanders DR, et al. Lens opacities after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2003;110(4):781–785. 48. Sanders DR, Vukich JA, Doney K, Gaston M. US Food and Drug Administration clinical trial of the Implantable Contact Lens for moderate to high myopia. Ophthalmology. 2003;110(2):255–266. 49. Igarashi A, Shimizu K, Kamiya K. Am J Ophthalmol. 2014; 157(3):532–539. 50. Schmidinger G, Lackner B, Pieh S, et al. Long-term changes in posterior chamber phakic intraocular Collamer lens vaulting in myopic patients. Ophthalmology. 2010;117(8):150611. 51. Guber I, Mouvet V, Bergin C, et al. Clinical outcomes and cataract formation rates in eyes 10 years after posterior phakic lens implantation for myopia. JAMA Ophthalmol. 2016. doi:10.1001/ jamaophthalmol.2016.0078.[Epub ahead of print.] 52. Moya T, Javaloy J, Montés-Micó R, et al. Implantable Collamer lens for myopia: assessment 12 years after implantation. J Refract Surg. 2015;31(8):548–556. 53. Packer M. Meta-analysis and review: effectiveness, safety, and central port design of the intraocular collamer lens. Clin Ophthalmol. 2016;10:1059–1077. 54. Martínez-Castillo V, Elies D, Boixadera A, et al. Silicone posterior chamber phakic intraocular lens dislocated into the vitreous cavity. J Refract Surg. 2004;20:773–777. 55. Garcia-Feijoo J, Hernandez-Matamoros JL, Mendez-Hernandez C, et al. Ultrasound biomicroscopy of silicone posterior chamber phakic intraocular lens for myopia. J Cataract Refract Surg. 2003; 29(10):1932–1939. 56. Pallikaris IG, Kalyvianaki MI, Kymionis GD, Panagopoulou SI. Phakic refractive lens implantation in high myopic patients: one-year results. J Cataract Refract Surg. 2004;30(6):1190–1197.

33 

Phakic Intraocular Lens Explantation (PIOL)

Causes and Surgical Techniques of PIOL Exchange and Bilensectomy VERONICA VARGAS AND JORGE L. ALIÓ

Introduction Phakic intraocular lenses (PIOLs) have been used for many years as a backup for patients who cannot have laser refractive surgery. There are three different types of PIOLs: the anterior chamber (AC) angle-supported PIOL, AC irisfixated PIOL, and posterior chamber PIOLs. All three will have to be explanted at one point due to natural phacoesclerosis or to complications related to the PIOL. Depending on the cause of explantation and the patient’s age, they can be changed for either another PIOL or for a posterior chamber in-the-bag intraocular lens (IOL). The main causes of PIOL explantation are cataract formation, endothelial cell loss, corneal decompensation, IOL decentration, pupillary ovalization, high intraocular pressure (IOP), inadequate size or IOL power, and halos and glare (Table 33.1).

Cataract Formation Cataract formation is the principal cause of PIOL explantation (Table 33.2).1,2 The main causes of cataract formation are surgical trauma, high myopia, postoperative use of topical steroids, and inflammation1 secondary to the disruption of the blood-aqueous barrier.3,4 In posterior chamber PIOL, cataract formation may be secondary to intermittent trauma during accommodation, inadequate vaulting, lens trauma from preoperative yttrium-aluminum-garnet (Nd:YAG) laser iridotomy,3 and the use of dispersive viscoelastic, which can produce changes in the epithelial cells of the lens.5 The incidence of cataract formation is higher with posterior chamber PIOLs than with AC PIOLs.6 This is due to the proximity between the IOL and the crystalline lens, which impairs the normal nutrition of the lens. Cataract formation is related to surgical trauma if it appears less

than 3 months after surgery and to poor vault if it occurs 1 year after surgery.6 The anterior subcapsular cataract is the most common type of cataract after the implantation of a posterior chamber PIOL.1,5,7,8 It can be either diffuse or can have a focal dotlike appearance. The former causes glare and progresses slowly; the latter is asymptomatic and usually does not progress.6,8 In angle-supported PIOLs, nuclear cataract formation is the most common (Fig. 33.1).9 The time between PIOL implantation and explantation will depend on the type of PIOL (see Table 33.3).

Endothelial Cell Loss The main reasons for endothelial cell loss are an inadequate anatomy of the AC, PIOL design1 (acute endothelial cell loss is higher in angle-supported PIOLs than with irisfixated PIOLs),10 PIOL intermittent contact with the posterior cornea, inflammatory mediators in the aqueous humor that are released owing to uveal trauma,11 and early postoperative high IOP.12 The indications for PIOL explantation are 1. when the endothelial cell count is less than 1500 cells/ mm,2 2. progressive loss of endothelial cells greater than 20% per year for 2 years regardless of the number of cells, 3. in AC PIOLs when distance between the endothelium and PIOL is 750 µm) increases the risk of pupillary block and angle closure glaucoma,6,7 and in patients with large pupils can cause severe night glare.21

Pupillary Ovalization

Preoperative Assessment

Pupillary ovalization mainly occurs in AC PIOLs; it is secondary to IOL oversizing11 and by a compression of the iris root vessels by the IOL haptics14 that causes ischemia of the iris root,11,14 inducing an iris retraction and atrophy.14 In iris-fixated PIOLs, pupillary ovalization is caused if the haptics are secured asymmetrically.5 Explantation is required when the pupillary ovalization extends beyond the edge of the PIOL or when it causes glare and haloes that diminish the patients quality of vision. Caution should be taken during explantation surgery because of the formation of adhesions between the PIOL, AC, and iris.1

Some evaluations have to be done before the explantation of a PIOL: AC depth, position of the PIOL in relation to the iris, anterior lens capsule and endothelium, presence of synechiae, pupil ovalization, endothelial cell count to ensure that there will not be corneal decompensation after the procedure, and a complete fundus examination.4 Depending on each particular case, the surgeon can perform a bilensectomy, simple PIOL removal, or PIOL exchange.

Pupillary Block Glaucoma Both anterior and posterior chamber PIOLs (especially those for hyperopia correction) can cause pupillary bock.5 High IOP postoperatively can be secondary to steroid response, high lens vault (implantable collamer lens [ICL])15 and retained viscoelastic agent.5,16 The increase of IOP is one of the most common reasons for posterior chamber PIOL explantation.6 Acute angle closure owing to a nonpupillary block mechanism has been described secondary to an oversized ICL17 requiring the explantation of the lens. Malignant glaucoma after ICL implantation also requires the explantation of the lens to control the IOP.18

Pigment Dispersion Pigment dispersion is secondary to the physiologic miosis and mydriasis of the pupil that causes chafing against the lens. Although it occurs in few patients, in severe cases, the PIOL has to be explanted5 owing to an increase in the IOP.

Retinal Detachment Surgical trauma during the implantation of the PIOL and high myopia are risk factors for retinal detachment.7,11 The PIOL has to be explanted for a good visualization during vitrectomy.

Endophthalmitis Cases of this devastating complication were described after angle-supported18 and posterior chamber PIOL implantation,20 requiring its explantation and vitrectomy for its treatment.19,20

Phakic Intraocular Lens Exchange This technique is usually performed when the PIOL is improperly sized, when the patient has subjective visual symptoms, or there is a remaining refractive error.1,2

Simple PIOL Removal This technique is done when lens exchange is contraindicated or in cases of retinal detachment to enhance posterior segment visualization.1

Bilensectomy Joseph Colins introduced this term; it is a surgical technique that involves the explantation of PIOL, phacoemulsification, and posterior chamber lens implantation. It is recommended when best spectacle corrected visual acuity (BSCVA) decreases at least two lines from BSCVA documented after phakic AC IOL implantation secondary to cataract formation, decreased endothelial cell count (1500 cells/mm2) with or without cataract, or in the presence of severe pupillary ovalization in patients older than 45 years.2 The use of microincision cataract surgery (MICS) makes the surgery easier because the AC is more stable.2 The safety of bilensectomy will depend mainly on endothelial cell loss during the surgery.22

IOL Calculation in Bilensectomy The pseudophakic IOL power can be calculated using either ultrasound biometry or optical biometry in phakic mode. In high myopes with long axial lengths and posterior staphylomas, ultrasound biometry may give a false axial length; optical coherence biometry gives a more accurate measurement, although postoperative hyperopic outcomes tend to occur.23 Wang et al. developed the method of optimizing the axial length by back calculation and

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improved the accuracy of IOL power calculation in patients with an axial length greater than 25 mm.23 A slight myopia of −0.1 to −0.2 diopters is aimed in these long eyes.23

Surgical Technique (Videos 33.1 to 33.3) Surgical technique will depend on the lens that is going to be explanted (see the video section). It should be done carefully so that none of the adjacent structures gets damaged. Topical or peribulbar anesthesia can be used.

Angle-Supported PIOL A 6-mm scleral incision is necessary to explant these IOLs.9 Peripheral anterior synechiae should be lyzed gently and they may be difficult to remove,4,24 then the incision is closed to perform usual phacoemulsification9 or IOL exchange.

Iris-Fixated PIOL If an Artisan PIOL is going to be explanted, a 6-mm superior scleral incision with a crescent knife has to be done. If the PIOL is an Artiflex, it can be explanted through the original incision (usually a 3-mm corneal incision). Then two 1.2-mm clear corneal side ports are made to deenclavate the iris haptics,22 either with an enclavation needle or they can be cut; then, the PIOL is rotated in a vertical position and can be pulled out using forceps.4 The scleral incision is sutured with Nylon 10-0. Phacoemulsification is realized through a temporal clear corneal incision; bimanual irrigation/aspiration is performed through the side ports used to deenclavate the haptics22 and the IOL is implanted through the corneal incision.

Posterior Chamber PIOL A posterior chamber PIOL can be explanted through the original incision without enlarging it21; synechiae should be lysed before manipulating the lens. The haptics are dislocated with a hook from behind the iris,6 and it can be pulled to the anterior chamber with a Sinski hook.4 Surgical explantation technique, depending on the lens vaulting, has been described: in low-vault eyes, an ophthalmic viscosurgical device (OVD) can be injected below 1 haptic edge and with a lens manipulator it can be moved nearer to the main incision in the anterior chamber. With tweezers, the area between the 2 haptics is gripped to explant the PIOL.21 In eyes with a high vault, after the injection of the OVD, the PIOL is rotated until the long axis angles 30 degrees to the main corneal incision. Then, tweezers are used to grasp the mid-peripheral part beside the optical zone to explant the PIOL.21 Explantation has been reported to be an easy procedure4 owing to lens flexibility.25 If a PIOL exchange is going to be done, the IOL can be inserted through the main incision.21

Successful outcomes are achieved in patients who have undergone bilensectomy,7 we have to keep in mind that a PIOL exchange increases the risk of cataract formation and infection.21 Femtosecond laser-assisted cataract surgery (FLACS) has also been used along with PIOL explantation. Capsulotomy can be done successfully through iris-fixated and ICL PIOLs, but nuclear fragmentation could be incomplete in eyes with an ICL because the cavitation bubbles get trapped beneath the PIOL.26 FLACS has the advantage of minimizing the corneal incision for PIOL explantation and maintaining a stable AC during surgery.26

Bilensectomy Results In conclusion, we can say that phacoemulsification after PIOL explantation has good and predictable results.2,6,25 It neither affects the visual outcome of cataract surgery nor interferes with the IOL calculation6,8 and high levels of patient satisfaction are achieved.25

References 1. Alió JL, Toffaha BT, Peña-García P, Sádaba LM, Barraquer RI. Phakic intraocular lens explantation: causes in 240 cases. J Refract Surg. 2015;31(1):30–35. 2. Alió JL, Abdelrahman AM, Javaloy J, Iradier MT, Ortuño V. Angle-supported anterior chamber phakic intraocular lens explantation. Ophthalmology. 2006;113:2213–2220. 3. Khalifa YM, Moshirfar M, Mifflin MD, Kamae K, Mamalis N, Werner L. Cataract development associated with collagen copolymer posterior chamber phakic intraocular lenses: clinicopathological correlation. J Cataract Refract Surg. 2010;36:1768–1774. 4. Moshirfar M, Mifflin M, Wong G, Chang JC. Cataract surgery following phakic intraocular lens implantation. Curr Opin Ophthalmol. 2010;21:39–44. 5. Balakrishnan SA. Complications of phakic intraocular lenses. Int Ophthalmol Clin. 2016;56(2):161–168. 6. Chen L-J, Chang Y-J, Kuo JC, Rajagopal R, Azar DT. Metaanalysis of cataract development after phakic intraocular lens surgery. J Cataract Refract Surg. 2008;34:1181–1200. 7. Fernandes P, González-Méijome JM, Madrid-Costa D, FerrerBlasco T, Jorge J, Montés-Micó R. Implantable collamer posterior chamber intraocular lenses: a review of potential complications. J Refract Surg. 2011;27(10):765–776. 8. Sánchez-Galeana CA, Smith RJ, Sanders DR, et al. Lens opacities after posterior chamber phakic intraocular lens implantation. Ophthalmology. 2003;110:781–785. 9. Alió JL, Hoz F, de la Pérez-Santonja JJ, Ruíz-Moreno JM, Quesada JA. Phakic anterior chamber lenses for the correction of myopia: a 7-year cumulative analysis of complications in 263 cases. Ophthalmology. 1999;106:458–466. 10. Aerts AAS, Jonker SMR, Wielders LHP, et al. Phakic intraocular lens: two-year results and comparison of endothelial cell loss with iris-fixated intraocular lenses. J Cataract Refract Surg. 2015;41:2258–2265. 11. Alió JL, Abbouda A, Peña-García P, Huseynli S. Follow-up study of more than 15 years of an angle-supported phakic intraocular lens model (ZB5M) for high myopia: outcomes and complications. JAMA Ophthalmol. 2013;131(12):1541–1546.

CHAPTER 33  Phakic Intraocular Lens Explantation (PIOL)

12. Moshirfar M, Imbornoni LM, Ostler EM, Muthappan V. Incidence rate and occurrence of visually significant cataract formation and corneal decompensation after implantation of Verisyse/Artisan phakic intraocular lens. Clin Ophthalmol. 2014; 8:711–716. 13. Kohnen T, Kook D, Morral M, Güell JL. Phakic intraocular leneses. Part 2: results and complications. J Cataract Refract Surg. 2010;36:2168–2194. 14. Akil H, Dhubhghaill SN, Tassignon M-J. Iris atrophy and erosion caused by anterior-chamber angle-supported phakic intraocular lens. J Cataract Refract Surg. 2015;41:226–229. 15. Lee J, Kim Y, Park S, et al. Long-term clinical results of posterior chamber phakic intraocular lens implantation to correct myopia. Clin Experiment Ophthalmol. 2015;1–7. 16. Almalki S, Abubaker A, Alsabaani NA, Edward DP. Causes of elevated intraocular pressure following implantation of phakic intraocular lenses for myopia. Int Ophthalmol. 2015;1–7. 17. Khalifa YM, Goldsmith J, Moshirfar M. Bilateral explantation of Visian implantable collamer lenses secondary to bilateral acute angle closure resulting from a non-pupillary block mechanism. J Refract Surg. 2010;26(12):991–994. 18. Kodjikian L, Gain P, Donate D, Rouberol F, Burillon C. Malignant glaucoma induced by a phakic posterior chamber intraocular lens for myopia. J Cataract Refract Surg. 2002;28:2217–2221. 19. Pérez-Santoja JJ, Ruíz-Moreno JM, Hoz F, de la Giner-Gorriti C, Alió JL. Endophthalmitis after phakic intraocular lens

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implantation to correct high myopia. J Cataract Refract Surg. 1999;25:1295–1298. 20. Oum BS, Lee JS, Choi HY, Lee JE, Kim SJ, Lee J-E. Endophthalmitis caused by Pseudomonas aeruginosa after phakic posterior chamber intraocular lens implantation to correct high myopia. Acta Ophthalmol. 2011;e209–e210. 21. Zeng Q-Y, Xie X-L, Chen Q. Prevention and management of collagen copolymer phakic intraocular lens exchange: cause and surgical techniques. J Cataract Refract Surg. 2015;41:576–584. 22. Vries NE, de Tahzib NG, Budo CJ, et al. Results of cataract surgery after implantation of an iris-fixated phakic intraocular lens. J Cataract Refract Surg. 2009;35:121–126. 23. Wang L, Shirayama M, Ma XJ, Kohnen T, Koch DD. Optimizing intraocular lens power calculations in eyes with axial lengths above 25.0 mm. J Cataract Refract Surg. 2011;37:2018–2027. 24. Colin J. Bilensectomy: the implications of removing phakic intraocular lenses at the time of cataract extraction. J Cataract Refract Surg. 2000;26:2–3. 25. Kamiya K, Shimizu K, Igarashi A, Aizawa D, Ikeda T. Clinical outcomes and patient satisfaction after Visian Implantable Collamer Lens removal and phacoemulsification with intraocular lens implantation in eyes with induced cataract. Eye (Lond). 2010;24: 304–309. 26. Kaur M, Sahu S, Sharma N, Titiyal JS. Femtosecond laserassisted cataract surgery in phakic intraocular lens with cataract. J Refract Surg. 2016;32(2):131–134.

34 

Physiology of Accommodation and Presbyopia FLORENCE CABOT, FABRICE MANNS, SONIA H. YOO, AND JEAN-MARIE PAREL

Introduction Accommodation is the physiologic ability to change the optical power of the eye to focus at a continuous range of distances, mimicking the autofocus of a camera. The accommodation apparatus includes the crystalline lens and its capsule (lenticular aspect of accommodation) and surrounding structures, such as ciliary muscle, ciliary body, iris, zonule, and vitreous (extralenticular aspect of accommodation).1,2 The onset of presbyopia, progressive and age-related loss of accommodation, varies according to ethnicity but ranges from the end of the third decade to the end of the fourth one. Throughout the past 4 centuries, many scientists have studied and tried to explain the mechanisms of accommodation and its irreversible loss, presbyopia. Currently, a lot of areas in the anatomic and physiologic aspects of accommodation and the development of presbyopia remain unclear and need to be clarified. The two roadblocks of this understanding include, but are not limited to, the number of intraocular structures in the accommodative apparatus and the fact that accommodation is a dynamic phenomenon that lasts between 0.2 and 0.6 seconds and therefore requires high-speed dynamic imaging. The aim of this chapter is to describe the past and current theories attempting to understand the physiology of accommodation-presbyopia, and to understand why some mechanisms are still not fully understood.

demonstrated that it is a change in the shape of the lens that enables accommodation. He thought that the fibers suspending the lens were responsible for the change in lens shape. During the 18th century, William Porterfield (1759) confirmed that accommodation occurs by a change in the crystalline lens and Albrecht Von Haller (1763) showed the constriction of the pupil during accommodation. During the 19th century, Helmholtz (in 1855 and later, in 1909, in his Treaty of Physics) demonstrated that the contraction of the ciliary muscle triggers an increase in curvature of anterior and posterior surfaces of the lens as well as an increase of its thickness.3 He stated that when the eye accommodates, there is a contraction of the ciliary muscle, enabling a relaxation of the zonule that leads to a change in the shape of the lens (increased curvatures and thickness). Tscherning (1895) disagreed with Helmholtz’s theory and claimed that the ciliary muscle contraction triggers an increasing zonular tension that can induce a change in lens shape. Fincham (1937) suggested that the change in the shape of the lens during accommodation can be related to the capsule. He noticed that the thickness of the capsule was greater at the equator than at the poles, thus explaining the anterior and posterior bulging of the lens at the poles and its relative flatness at the equator during accommodation when the zonule relaxes.

Current Understanding of Accommodation

Accommodation Historical Background It is at the beginning of the 17th century that the first theories of accommodation were developed by several scientists. Briefly, Scheiner (1619) demonstrated that the eye includes a specific apparatus that can adjust focus and provide near vision. Kepler (1611) demonstrated that the backward and forward movements of the crystalline lens provide accommodation. Later, Descartes (1637), in his Traite de l’homme, 440

Helmholtz’s theory has been widely accepted by the scientific community to explain the mechanisms of accommodation. According to Helmholtz, after accommodating stimulus, ciliary muscle contracts, which relaxes the anterior and posterior zonules connected to the capsule and the lens.3 The relaxation of the zonule enables the crystalline lens to retrieve its original shape thanks to capsular elasticity (Fig. 34.1). During accommodation, the equatorial diameter decreases while the lens thickness increases with steepening of anterior and posterior radius of the lens. In a

CHAPTER 34  Physiology of Accommodation and Presbyopia

relaxed or unaccommodated state, all the zonular fibers are taught. Currently, many studies have reported data supporting Helmholtz’s theory. The steepening of the anterior and posterior radius of the lens, as well as the thickening of the lens and the decrease in anterior chamber depth during

Equatorial zonules relaxed Anterior zonules relaxed

Posterior zonules relaxed

Accommodated lens

Equator moves away from sclera

Equatorial diameter decreases

Ciliary process

Sclera

• Fig. 34.1

  Schematic of Helmholtz’s theory of accommodation. During accommodation, the ciliary muscle contracts, which relaxes the anterior and posterior zonular fibers connected to the capsule and the lens. The equatorial diameter of the lens decreases during accommodation.

accommodation, have been assessed during multiple in vivo studies using different imaging techniques. Dubbelman et al., in 2005, reported a steepening of the anterior radius greater than the steepening of the posterior radius, a lens thickening of approximately 300 µm during accommodation in a young 29-year-old subject, using the Scheimpflug camera4 (Fig. 34.2). Similar results were found by Strenk et al.5 using magnetic resonance imaging (MRI) and Croft et al.6 using ultrasound biomicroscopy (UBM). The major opponent to Helmholtz’s theory is Ronald Schachar, who published a new theory in 1992 to explain accommodation.7 In his theory, based on Tscherning’s theory, the zonule is divided into the anterior zonule, equatorial zonule, and posterior zonule (Fig. 34.3) and each part has a different role in the accommodation process. In a relaxed state, the zonule is taut. After contraction of the ciliary muscle with the radial fibers pulling outward and posteriorly, the equatorial zonule increases its tension while the anterior and posterior zonules are relaxed, thus explaining the central bulging of the lens and the relative flatness of its periphery during accommodation. However, no experiments presented by Schachar have been able to be reproduced by any other scientific teams. In the 1970s, Coleman was one of the first scientists to point out the extralenticular aspect of accommodation.8 The difficulty in studying these extralenticular structures lies on their location, which is deep inside the eye and therefore difficult to access through in vivo imaging. In his theory, also called the catenary theory owing to its relation with the mathematical catenary model, Coleman described the role of a diaphragm, including crystalline lens, capsule, vitreous, and zonule8–10 (Fig. 34.4). After contraction of the ciliary muscle, the aforementioned diaphragm is pushed forward because of the change in pressure gradient. More recently, due to the development of imaging technology enabling access to micro intraocular structures, 4.1

12 11

Lens thickness ACD & Lens thickness (mm)

Anterior lens radius

Radius (mm)

10 9 8 7 6

3.9

3.7

3.5 Anterior chamber depth

Posterior lens radius

5 4 –1

A • Fig. 34.2

0

1 2 3 4 5 6 Accommodation stimulus (D)

7

441

3.3 –1

8

0

1 2 3 4 5 6 Accommodation stimulus (D)

7

8

B

  Lens thickness, anterior chamber depth (ACD) and radius changes of the crystalline lens during accommodation.4 During accommodation, lens thickness increases while ACD decreases. Both the anterior and posterior radii of the lens steepen during accommodation.

Presbyopia Surgery

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Equatorial zonules increased tension Anterior zonules relaxed

Posterior zonules relaxed

Accommodated lens

Equator moves towards sclera

scientists have developed interest in the extralenticular aspect of accommodation. Using UBM technology, Croft et al. studied the role of the vitreous, zonule, and sclera.11 The architecture of the zonule fibers being more complex than previously assumed, Lütjen-Drecoll et al. showed that some zonule fibers were directly connected to the vitreous membrane and the posterior part of the lens, thus questioning the exact role of the sclera, choroid, and vitreous during accommodation.12

Presbyopia Helmholtz’s theory is now widely accepted by the scientific community as the most plausible hypothesis to explain the mechanisms of accommodation. However, the causes of age-related loss of accommodation, also known as presbyopia, remain unclear. Multiple factors have to be taken into account to study the physiology of presbyopia. They are commonly divided into lenticular causes of presbyopia: continued lens growth in size and mass; loss of capsule elasticity; and extralenticular causes—age-related changes in ciliary muscle, zonular fibers, and vitreous.1,13,14

Equatorial diameter increases

Ciliary process

• Fig. 34.3

Sclera

Schematic of Schachar’s theory of accommodation. After contraction of the ciliary muscle, the equatorial zonule increases its tension while the anterior and posterior zonules are relaxed, thus explaining the central bulging of the lens and the relative flatness of its periphery during accommodation. The equatorial diameter of the lens increases during accommodation.  

Lenticular Causes of Presbyopia The lenticular causes of presbyopia first relied on the HessGullstrand theory, in which the change in shape of the lens causes presbyopia while the function of the ciliary muscle remains constant throughout life.

Lens Model

Ligament of Weiger

Non-accommodated

Mueller’s muscle

Scleral roll Non-accommodated Accommodated

Pylon shift

Pylon shift

AP

A

Reduced tension Steep central radius of curvature

• Fig. 34.4

B

Accommodated

Schematic of Coleman’s theory of accommodation.8 This theory is also called the catenary theory because of its relation to the mathematical catenary model. After contraction of the ciliary muscle, the diaphragm—including the crystalline lens, capsule, vitreous and zonule—is pushed forward because of the change in pressure gradient between the posterior and anterior segments.  

CHAPTER 34  Physiology of Accommodation and Presbyopia

Max. accommodation in vivo & in vitro

12

9 8 7 6

Glassor & Campbell (1999) Howcroft & Parker (1977) Anterior lens radius in vivo Polynomial fit

5

A

5

15

25

35

45

55

65

Posterior lens radius (mm)

Anterior lens radius (mm)

6.5

10

4

Max. accommodation in vivo & in vitro

7

11

443

5.5 5 4.5 Glassor & Campbell (1999) Howcroft & Parker (1977) Anterior lens radius in vivo Polynomial fit

4 3.5

75

Age

6

B

5

15

25

35

45

55

65

75

Age

• Fig. 34.5  Anterior and posterior radius changes of the lens during maximum accommodation depending on age.4 The steepening of the anterior and posterior radii of the lens, for a maximal accommodation, decreases with age.

The partial loss of capsular elasticity and its age-related change in thickness is, with the change in crystalline lens shape, one of the causes of presbyopia.15 As shown by Dubbelman,4 the steepening of the anterior and posterior radii of the lens, for a maximal accommodation, decreases with age (Fig. 34.5). The lens thickness increases throughout life by accumulation of cortical fiber cells.16 This lens thickening is asymmetric: greater in the anterior part of the lens compared to the posterior one, thus moving the lens center of mass anteriorly. Despite the more curved shape of the lens with age, its optical power decreases with age. This phenomenon is known as the Brown lens paradox.17 This more convex shape, expected to lead to an improvement in near vision, is actually partially compensated by a change in the profile of the gradient refractive index (GRIN) of the lens with age.16 These age-related capsule and lens changes affect the mechanical properties of the lens–capsule system, making it stiffer and less deformable. Thus these changes are considered by a majority of scientists as the primary cause of presbyopia. According to Schachar, presbyopia is due to the growth of the crystalline lens equatorial diameter with age. This growth crowds the circumlental space (the space located between the lens and ciliary processes), thus preventing the equatorial zonule from increasing its tension when the ciliary muscle contracts. This theory of presbyopia pushed Schachar to create a new surgical technique to restore accommodation by scleral expansion, either through scleral incisions or insertion of scleral optic bands, in order to enlarge the circumlental space. This gives the equatorial zonule fibers the ability to develop the required tensile strength to change the lens shape and provide accommodation. However, several studies have clearly shown that the lens equatorial diameter decreases with age, thus naturally enlarging the circumlental space. An important fact contradicting the validity of Schachar’s theory of accommodation/

presbyopia is the poor results obtained by scleral expansion surgery. Scleral expansions by scleral optic bands and laserassisted scleral incisions have never proved their clinical and scientific efficacy. Clinical outcomes—in particular, near vision—in patients who underwent scleral expansion surgery were very limited and temporary most of the time. Despite these previous poor results, some biomedical companies are still working on new techniques to perform femtosecond laser-assisted scleral incisions and scleral expansion surgery.

Extralenticular Causes of Presbyopia The extralenticular theories of presbyopia were led by Duane’s and Fincham’s theories, in which the age-related weakening and loss of contractibility of the ciliary muscle is responsible for the onset of presbyopia.18,19 Morphologic changes and age-related atrophy (accumulation of connective tissue) of the ciliary muscle have been demonstrated by Pardue et al. and Sheppard et al.; the contractile ability of the ciliary muscle seems preserved throughout life, which supports the lenticular theory of presbyopia. Other studies also showed that the ciliary muscle apex is shifted inward and anteriorly with age as a result of age-related lens thickening.20–23 Little is known of the function and age-related changes of zonule fibers. The anatomy of the zonular system and its connection to the vitreous, lens, and ciliary bodies has been studied using environmental scanning electronic microscopy (eSEM) by Lütjen et al. on presbyopic human subjects. An age-related change in its architecture or its elasticity might also contribute to the development of presbyopia.12,24 More recently, Croft et al. studied the role of the vitreous, sclera, and choroid in presbyopia but further studies with larger samples are needed to draw conclusions on the exact function of the aforementioned ocular structures.11

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Finally, Weale suggested in 1989 that instead of having one primary cause, presbyopia results from lenticular and extralenticular multifactorial age-related changes.25 Also, neural pathways involved in the regulation and automation of accommodation (not discussed in this chapter) may have an important role to play in the understanding of presbyopia.

Limitations to the Understanding of Accommodation and Presbyopia The understanding of the anatomic structures involved in accommodation and presbyopia has been greatly improved by the relatively recent development of imaging techniques. Confocal microscopy and eSem enable better understanding of the complex architecture of the zonular fibers and their connection to the vitreous, ciliary processes, and lens.12 Despite a high axial resolution (< 1 µm), both technologies can be performed only in vitro owing to the need of tissue fixation to provide image analysis. Therefore these techniques provide information on the structure and anatomy of the accommodative apparatus but cannot give any insight into the function of the analyzed ocular structures. Ideally, to obtain an accurate assessment of the function of the various components of the accommodative apparatus, ocular structures should be analyzed in vivo through a fast and dynamic imaging technique. Multiple studies have assessed naturally induced or pharmacologically induced accommodation using static in vivo imaging techniques, such as Scheimpflug imaging,1 optical coherence tomography (OCT),21,22 custom-made UBM,11,23 or MRI.26 Unlike OCT and its infrared signal, UBM has the advantage that its signal is not stopped by pigments located in the iris or the pigmentary epithelium. However, UBM is a contact technique, thus potentially deforming the underlying surface of the eye and potentially providing erroneous measurements. Moreover, UBM has a low axial resolution in tissue (around 50–100 µm), thus being less accurate than OCT scans (spectral domain OCT devices having a resolution around or < 10 µm). MRI has the advantage of providing a full image of the whole eyeball but the resolution is even lower than UBM (around 100–200 µm), requires long image acquisition time, and is logistically difficult to use with a relatively high cost. All of these techniques are able to provide static images at the beginning and end of the accommodation process. Therefore all the events occurring in between are not recorded, assessed, and taken into account in the measurements. Lens shape change and pupil diameter in these studies are measured as the difference between the final position and the initial position (shift). Dynamic imaging enables a more accurate and in real time assessment of the mechanisms involved in accommodation/disaccommodation since accommodation is a dynamic process. Furthermore, in static imaging, measurements during accommodated and relaxed state are performed at two different time points,

• Fig. 34.6

  Still image montage from OCT dynamic imaging of accommodation. The optical coherence tomography (OCT) scan provided by the ciliary muscle OCT (left). The OCT scan provided by the anterior segment OCT (right).

thus inducing a potential error in alignment. Dynamic imaging has the advantage of providing a steady and more reliable alignment since measurements in accommodated and relaxed states are done consecutively all at once in one single imaging session. The combination of two SD-OCT systems to image dynamically accommodation—one system operating with a wavelength of 1325 nm to visualize the ciliary muscle and the other with a wavelength of 840 nm to visualize the structures of the anterior segment—was described by Ruggeri et al.27 This new technology enabled an in vivo, simultaneous, and dynamic recording of the ciliary muscle and the anterior segment changes during accommodation in human subjects (Fig. 34.6). Further studies are needed to better understand accommodation through this novel and very promising technology.

Conclusion Our understanding of accommodation and presbyopia is still limited. Even if the scientific community agrees on Helmholtz’s theory to explain accommodation, the physiology of presbyopia, with lenticular and extralenticular multifactorial causes, still remains unclear. A better understanding of accommodation and presbyopia is a priority in ophthalmology in order to efficiently and fully restore accommodation. This understanding can only be achieved by improving in vivo dynamic imaging technology. Most of the current methods aiming to restore accommodation are static and passive, with a reduced visual field and sources of multiple visual disturbances (glare, haloes, ghost images, starburst, and so on). In order to truly restore accommodation, the challenge is now to design novel intraocular lenses, devices, or surgical techniques that possess a continuous, variable, adjustable and active, near-focusing ability.

CHAPTER 34  Physiology of Accommodation and Presbyopia

References 1. Strenk SA, Strenk LM, Koretz JF. The mechanism of presbyopia. Prog Retin Eye Res. 2005;24(3):379–393. 2. Atchison DA. Accommodation and presbyopia. Ophthalmic Physiol Opt. 1995;15(4):255–272. 3. Von Helmholtz H. Helmholtz’s treatise on physiological optics. Vol mechanism of accommodation. In: Southall JPC, ed. Handbuch der Physiologischen Optik. Vol. I & II. Southall JPCT (trans.) New York, NY: Dover Publications; 1909. 4. Dubbelman M, Van der Heijde GL, Weeber HA. Change in shape of the aging human crystalline lens with accommodation. Vision Res. 2005;45(1):117–132. 5. Strenk SA, Strenk LM, Guo S. Magnetic resonance imaging of the anteroposterior position and thickness of the aging, accommodating, phakic, and pseudophakic ciliary muscle. J Cataract Refract Surg. 2010;36:235–241. 6. Croft MA, McDonald JP, Katz A, Lin TL, Lütjen-Drecoll E, Kaufman PL. Extralenticular and lenticular aspects of accommodation and presbyopia in human versus monkey eyes. Invest Ophthalmol Vis Sci. 2013;54(7):5035–5048. 7. Schachar RA. Cause and treatment of presbyopia with a method for increasing the amplitude of accommodation. Ann Ophthalmol. 1992;24(12):445–447, 452. 8. Coleman DJ. Unified model for accommodative mechanism. Am J Ophthalmol. 1970;69(6):1063–1079. 9. Coleman DJ. On the hydraulic suspension theory of accommodation. Trans Am Ophthalmol Soc. 1986;84:846–868. 10. Coleman DJ, Fish SK. Presbyopia, accommodation, and the mature catenary. Ophthalmology. 2001;108(9):1544–1551. 11. Croft MA, Nork TM, McDonald JP, Katz A, Lütjen-Drecoll E, Kaufman PL. Accommodative movements of the vitreous membrane, choroid, and sclera in young and presbyopic human and nonhuman primate eyes. Invest Ophthalmol Vis Sci. 2013;54(7): 5049–5058. 12. Lütjen-Drecoll E, Kaufman PL, Wasielewski R, Ting-Li L, Croft MA. Morphology and accommodative function of the vitreous zonule in human and monkey eyes. Invest Ophthalmol Vis Sci. 2010;51(3):1554–1564. 13. Glasser A, Campbell MC. Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia. Vision Res. 1999;39(11):1991–2015.

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14. Glasser A. Restoration of accommodation: surgical options for correction of presbyopia. Clin Exp Optom. 2008;91(3):279–295. 15. Krag S, Andreassen TT. Mechanical properties of the human lens capsule. Prog Retin Eye Res. 2003;22(6):749–767. 16. Koretz JF, Kaufman PL, Neider MW, Goeckner PA. Accommodation and presbyopia in the human eye—aging of the anterior segment. Vision Res. 1989;29(12):1685–1692. 17. Brown N. The change in shape and internal form of the lens of the eye on accommodation. Exp Eye Res. 1973;15(4):441–459. 18. Duane A. Studies in monocular and binocular accommodation, with their clinical application. Trans Am Ophthalmol Soc. 1922;20:132–157. 19. Fincham E. The mechanism of accommodation. Br J Ophthalmol. 1937;8:5–80. 20. Pardue MT, Sivak JG. Age-related changes in human ciliary muscle. Optom Vis Sci. 2000;77(4):204–210. 21. Sheppard AL, Davies LN. In vivo analysis of ciliary muscle morphologic changes with accommodation and axial ametropia. Invest Ophthalmol Vis Sci. 2010;51:6882–6889. 22. Sheppard AL, Davies LN. The effect of ageing on in vivo human ciliary muscle morphology and contractility. Invest Ophthalmol Vis Sci. 2011;52:1809–1816. 23. Richdale K, Sinnott LT, Bullimore MA, et al. Quantification of age-related and per diopter accommodative changes of the lens and ciliary muscle in the emmetropic human eye. Invest Ophthalmol Vis Sci. 2013;54(2):1095–1105. 24. Michael R, Mikielewicz M, Gordillo C, Montenegro GA, Pinilla Cortés L, Barraquer RI. Elastic properties of human lens zonules as a function of age in presbyopes. Invest Ophthalmol Vis Sci. 2012;53(10):6109–6114. 25. Weale R. Presbyopia toward the end of the 20th century. Surv Ophthalmol. 1989;34(1):15–30. 26. Strenk SA, Strenk LM, Guo S. Magnetic resonance imaging of the anteroposterior position and thickness of the aging, accommodating, phakic, and pseudophakic ciliary muscle. J Cataract Refract Surg. 2010;36:235–241. 27. Ruggeri M, de Freitas C, Williams S, et al. Quantification of the ciliary muscle and crystalline lens interaction during accommodation with synchronous OCT imaging. Biomed Opt Express. 2016;7:1351–1364.

35 

Monovision ELENA ALBÉ AND DIMITRI T. AZAR

Introduction Presbyopia refers to the decrease in accommodative capacity that accompanies aging. It occurs when an individual’s accommodative power is no longer able to allow for sustained and comfortable near-vision work. Most clinical efforts have been directed toward optical arrangements that promote simultaneous near and distance acuity for prepresbyopic and presbyopic patients. Monovision is a method of presbyopic correction whereby one eye is optically corrected for distance vision and the other eye for near vision. The near-vision eye may be placed in focus at a reading distance or at an intermediate distance. Currently, monovision may be achieved in practice by means of contact lenses; intraocular lenses; conductive keratoplasty (CK); or refractive techniques, such as photorefractive keratectomy (PRK), laser in situ keratomileusis (LASIK)1 and corneal inlays.2

Achieving Monovision One procedure to achieve monovision in the presbyopic population is NearVision CK, or conductive keratoplasty, a nonincisional and nonlamellar surgical procedure approved by the US Food and Drug Administration (FDA). The procedure uses controlled release of high-frequency, low-energy electric current to generate thermal energy in the cornea and cause corneal steepening by stromal collagen shrinkage (Figs. 35.1 and 35.2). Researchers estimate that 90 million people in the United States either have presbyopia or will develop it in the next 10 years. The clinical technique of monovision is widely accepted and has a long history of use. The monovision approach has been used clinically with contact lenses for years, showing a near monovision success rate of 76%.3 Patient satisfaction after conventional monovision refractive surgery ranges from 72% to 86%.4,5 Monovision may be associated with compromises of binocular visual function, decreased contrast sensitivity, and reduced stereopsis; some people are not able or willing to accept these compromises. It has also been widely reported that patients can experience glare and other night-vision 446

difficulties. These monovision-related issues emphasize the need to balance good near visual acuity with maintenance of comfortable binocular vision providing some intraocular blur suppression. A number of factors contribute to a successful monovision patient. Careful prescreening of patients is important, along with a contact lens monovision trial or a history of successful monovision contact lens wear. Finally, patient education is critical. Patients need to understand that monovision is a compromise between distance vision and near vision. There may be a need for continued spectacle use, even though, in a successful monovision patient, that dependence on spectacles would be substantially reduced. We attempt here to clarify the factors predictive of clinical success and visual performance in monovision patients.

Ideal Monovision Result Ideally, the monovision patient should be able to see clearly at all distances. The depth of focus under binocular viewing conditions should be continuous and equal to the sum of the monocular depths of focus without interference from the blurred image of the other eye.6,7 Inherent in the monovision concept is the fact that, at any given distance, the image in one eye will be blurred and the image in the other eye will be in focus. At any given distance, a patient should be able to suppress the blurred image from one eye so that it does not interfere with the image from the other eye (interocular blur suppression). Blur suppression aids distance binocular vision so that only a slight reduction in distance acuity occurs. Monovision is considered successful in a given individual if it is satisfactory 85% of the time and if spectacles over monovision are needed only 15% of the time.8

Visual Performance in Monovision Binocular Visual Acuity Jain and colleagues3 reviewed six articles addressing the effect of monovision on binocular visual acuity and found the effect to be mild. High-contrast and low-contrast visual

CHAPTER 35  Monovision

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acuities at standard room illumination were reduced by 0.04 to 0.08 logMAR unit and 0.04 to 0.09 logMAR unit, respectively. This reduction was slightly higher (0.10 logMAR unit) under low-illumination conditions. The effect on visual acuity was particularly pronounced when the dominant, distance-corrected eye had a residual astigmatic error at an oblique axis.9

Interocular Blur Suppression

• Fig. 35.1  Radiofrequency energy console. Energy source for the procedure, which is activated only by a treatment card.

Monovision success depends on interocular blur suppression. In successful wearers of monovision lenses, the interocular suppression of blur was approximately two orders of magnitude greater than in unsuccessful wearers of monovision lenses. Of note, interocular blur suppression becomes less effective under dim illumination conditions, which

A

B

C

D • Fig. 35.2  Conductive keratoplasty light touch technique. (A) A circular marker with eight intersections is applied to the center of the visual axis. Markings are made on the 6.0-, 7.0-, and 8.0-mm optical zone. (B) Pressure has to be applied when inserting the Keratoplast tip into the stroma. (C) Pressure is released before depressing the foot pedal to administer the energy. (D) Following a full circle of treatment spots, the peripheral cornea flattens and the central cornea steepens. A round reflex is observed in the central cornea.

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accounts for the well-known poorer visual performance of monovision patients under night driving circumstances.7 Two tests used to measure the ability to suppress interocular blur are the anisometropic blur suppression test and the American Optical (AO) vectographic test. The first measures the suppression of monocular blur of focused contours that is essential for clear binocular vision under monovision conditions. The test target is a back-illuminated circular aperture in a white card with rheostat-controlled front illumination. At zero front illumination, a clear image from the distance-corrected eye and a blurred image from the nearcorrected eye can be perceived. The front illumination is increased until only the clear image is perceived. The anisometropic blur suppression is proportional to the luminance contrast threshold (log% contrast) at which the clear image, not the blurred image, is perceived. Log numbers 1 to 5 correspond to background luminance of 563, 320, 56, 6, and 0.6 cd/m2, respectively. Anisometropic blur suppression increased by approximately an order of magnitude for small spot sizes following short-term (1 day) adaptation to anisometropia. In marked contrast to the preadapted stage, blur suppression was greater when the blurring lens (near correction) was placed over the nondominant eye. In contrast to the anisometropic blur suppression test, the AO vectographic test measures ocular dominance characteristics with nonfused diplopic-like images. It reveals that suppression of the blurred eye in monovision was enhanced by increasing the amount of anisometropia and that a 0.50 diopter (D) to 1 D greater add was required to induce 100% suppression at near than at distance.10

Stereoacuity Reduced stereoacuity is considered to be the major disadvantage associated with monovision.11 The average normal value for stereopsis is 20 arc sec and, for persons older than 40 years, 58 arc sec.12,13 A report by Kirschen and coworkers14 found that near stereoacuity decreased from a median of 50 arc sec with bifocal contact lenses to 200 arc sec with monovision. Patients in whom monovision is successful exhibit a lower reduction in stereoacuity than do unsuccessful monovision patients. Of note, Harris and colleagues15 found a significant increase in stereoacuity in monovision contact lens wearers after an initial adaptation period: initial monovision levels averaged 151 arc sec and, after 3 weeks of adaptation, 90 arc sec.

Contrast Sensitivity The contrast sensitivity function increases when the stimulus is viewed binocularly rather than monocularly (binocular summation).3,16,17 Thus in the absence of monocular defocus, the binocular contrast sensitivity is approximately 42% greater than monocular contrast sensitivity. With increasing monocular defocus, the binocular contrast sensitivity decreases steadily and then falls below the monocular contrast sensitivity, showing binocular inhibition.18 If the

defocus is further increased (beyond +2.5 D defocus), the binocular contrast sensitivity reverts to the monocular level, indicating suppression of the defocused eye. In successful monovision patients, ocular blur reduces binocular summation of middle to high spatial frequencies (> 4 cycles per degree).16 With increasing ocular blur, the binocular summation at lower frequencies is also reduced; in addition, the peak contrast sensitivity shifts toward higher spatial frequencies. When ocular blur is greater than +2 D, binocular summation is essentially lost. Because binocular summation is affected at higher spatial frequencies, monovision is not suited for occupations requiring fine, detailed work.16 The contrast sensitivity function at low photopic levels (10 cd/ m2) shows no significant differences between monovision and other forms of presbyopic corrections.19 At this low luminance, the suppression of interocular blur in monovision is poor.

Peripheral Vision and Visual Fields Monovision causes no significant effect on binocular peripheral visual acuity. Peripheral visual field width is marginally better (1 degree to 3 degrees) in the nondominant eye (corrected for near) than in the dominant eye.20 The average decreases in size of the visual field through the far-point lens and the near-point lens are within the variation in measurements expected when taking fields.21 Static visual fields are not adversely affected by monovision correction.

Binocular Depth of Focus The binocular depth of focus is the range in which an image may move without noticeable blur under binocular viewing conditions (without changing accommodation). In patients in whom neither eye is clearly dominant (i.e., in whom there is no sighting preference), the binocular depth of focus is approximately equal to the sum of the monocular depths of focus. However, in patients with a strong sighting preference, the image becomes blurred as the object moves from the monocular clear range of the dominant eye to the monocular clear range of the nondominant eye. Therefore in patients with a strong sighting preference, the depth of focus under monovision conditions is considerably less than the sum of the monocular depths of focus.6

Phorias Patients using monovision tend to exhibit a small-angle esophoric shift. At distance, this manifests as an esophoria. At near, the effect is offset by the fact that presbyopes generally exhibit a moderate to large exophoria at near. The magnitude of the esophoric shift is believed to correlate with the degree of binocular stress created by monovision. The esophoric shift at distance in a successful monovision contact lens (0–0.6 prism diopters) was found to be less than the shift in unsuccessful monovision wearers (2.1–2.2 prism diopters).22,23 Interestingly, the magnitude of esophoric shift

CHAPTER 35  Monovision

is less when the dominant eye is corrected for distance, thus lending support to the generally accepted custom of correcting the dominant eye for distance.23

Task Performance Monovision appears to be associated with adverse effects on stereoacuity and contrast sensitivity. The question is whether these effects have clinical significance. The effect of monovision on the performance of various visually oriented near tasks can be assessed by comparing an individual’s performance of these tasks under monovision conditions, under monocular viewing conditions11 (i.e., with one eye covered), and under binocular viewing conditions (i.e., with full near correction for both eyes). Use of this method revealed that monovision reduced performance of near tasks by 2% to 6% when compared to performance of the tasks under binocular viewing conditions.15 However, this reduction was minimal when compared with the 30% reduction seen under monocular viewing conditions with near tasks requiring high stereopsis.24

Factors Influencing Monovision Success On the basis of these findings, poor candidates for monovision are patients who exhibit minimal interocular suppression of blur, patients with large esophoric shifts with monovision, and patients with a significant reduction in stereoacuity with monocular correction. Because the contrast sensitivity function is reduced at higher frequencies with monovision, patients engaged in occupations requiring fine work may experience difficulties with monovision. Psychological and personality factors also appear to play a role in determining the success of monovision. An additional consideration is sighting preference. The inputs from the two eyes are not identical in their relative influence on cortical cells. The dominant eye produces a greater response to a given stimulus than does the input from the other eye. Individuals who do not have a strong sighting preference (i.e., who have alternating dominance) appear to have constant interocular blur suppression6 and therefore tend to be more successful with monovision. Jain and coworkers3 found that the average age of successful monovision patients ranged from 48 to 55 years. McDonnell and coworkers25 showed that older persons with monovision correction have some improvements in health-related quality of life, but they have significantly worse scores than younger subjects with emmetropia on all subscales of the National Eye Institute Refractive Error Quality of Life Instrument except suboptimal correction and appearance. Two articles examined the average age of successful versus unsuccessful monovision patients but failed to find any statistically significant difference in age between the two groups.26,27 Godts et al.28 suggested that monovision should be proposed only in patients with equal visual acuity and normal binocular vision with good fusion capacity.

449

Preoperative Patient Evaluation All patients who opt for monovision must be informed of the risk of reduced binocular visual acuity, stereoacuity, and contrast sensitivity. They should also be briefed on the risk of distance and near ghosting as a result of incomplete blur suppression. Blur suppression appears to be particularly problematic under night-driving conditions because interocular blur suppression becomes less effective under dim illumination conditions.6 Therefore patients must be advised of the need to wear distance glasses when driving. Liability is an important consideration when selecting a refractive surgery patient for monovision29; discussions of the risk and benefits associated with monovision should be carefully documented in a patient’s chart. It is important to ascertain the personal preference of the patient. Some patients (particularly those active in sports) wish to have optimal distance vision and are willing to tolerate difficulties with near vision and the associated need for reading glasses in order to achieve this. These patients should be fully corrected for distance vision in both eyes. Other patients (particularly those who do a lot of reading or other fine near work) may be willing to tolerate mildly decreased binocular distance vision in order to be able to perform near tasks comfortably without glasses; these patients may wish to be undercorrected in both eyes.

Monovision Trial Although the best way to demonstrate the effects of monovision preoperatively is with a monovision trial with contact lenses, this often is impractical.29 A monovision trial can also be performed with spectacles. However, spectacles may induce magnification and minimization effects; therefore a monovision trial is more accurately conducted with contact lenses. If a patient has a refractive error of approximately −1.00 D to −2.00 D, a monovision surgical trial can be performed.30 Instead of a bilateral procedure, surgery is initially performed on only one eye, which is targeted for distance. If the patient is unable to adapt to the monovision situation, the other eye is treated and targeted for close plano. It is important to allow for at least a 3-week acclimatization period before concluding whether monovision is appropriate for a given individual. If a patient experiences difficulties with a monovision contact lens trial, two problems must be ruled out before declaring that monovision has failed. First, accurate contact lens fitting must be ascertained. Second, the clinician must ensure that all residual astigmatism has been corrected by performing a spherocylindrical overrefraction. Even small amounts of uncorrected astigmatism can have a substantial negative effect on binocular distance visual acuity.10 A major benefit of a contact lens trial is that adjustments to the monovision arrangement can be made before refractive surgery is performed. One common complaint with monovision is blur at an intermediate distance. Slightly reducing the add in the near eye can relieve this symptom, although this change may

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compromise near vision. Plus power may also be added to the distance eye, although this change may reduce distance vision. Even small (0.25 D) changes can make a large difference in creating an acceptable monovision situation for a patient.30

Determining the Eye for Distance Several theories have been proposed for selection of the corrected distance eye: (1) correcting the dominant eye to maximize performance of visual tasks requiring spatial perception; (2) correcting the left eye for increased driving safety; (3) correcting the less myopic eye to decrease the peripheral blur during distance vision; and (4) correcting the dominant eye for the most commonly used viewing distance to maximize blur suppression. In the absence of rigorous clinical trials to support one method over the others, the most commonly used approach is determining which eye is the dominant eye and correcting that eye for the most commonly used viewing distance,11 which is generally considered to be the far distance. The dominant eye has been shown to be superior for spatial-locomotor tasks such as walking, running, or driving a car.7 Blur suppression appears to be greater when the dominant eye is corrected for the most commonly used distance (i.e., far). Correcting the dominant eye for distance also produces fewer esophoric shifts.22 The dominant eye generally is identified by use of sighting dominance tests.31 One of the more common tests is the hole test whereby the patient, using both eyes simultaneously, lines up an object through a hole, usually formed by the patient’s hands. As the patient constricts the size of the hole, the eye continues to be aligned with the object and the hole is considered the dominant eye.

Determining the Degree of Add No general agreement has been reached regarding the ideal amount of add, as different proponents attach varying importance to the role of binocular summation. Although it has been reported that monovision adds of up to +1.50 D produce binocular summation whereas adds higher than +1.50 D produce binocular inhibition,18 it has also been shown that add power tolerance in monovision can vary considerably, reaching up to +2.75 D. Furthermore, many monovision patients use spectacle correction to obtain optimal visual functioning for driving or detailed nearvision tasks, and a large degree of anisometropia could lead to disabling image size disparity. Ultimately, the add power should be determined by the monovision contact lens trial. In general, it is most advantageous to select the lowest add possible while still maintaining reasonable near vision. This approach serves to maximize binocular function, such as stereopsis and binocular summation. Riegel’s rule of two-thirds32 provides a reasonable guideline: for example, a 50-year-old presbyope requiring a

+1.50  D reading add would receive a correction at +1.00 D. This approach provides the vision required for the majority of activities without excessive compromise in binocular visual function. Others have advocated modified monovision, in which one eye is undercorrected by only 0.50 D to 0.75 D.33 This is almost always well tolerated, serves to postpone the need for reading glasses for early presbyopes, and preserves older patients’ intermediate vision.

Crossed Monovision Crossed monovision occurs when the nondominant eye is corrected for distance and the dominant eye for near. Jain and associates34 showed that all patients with crossed monovision were satisfied with their vision. Crossed monovision can be created intentionally or unintentionally. It can be the intended goal when, for example, a contact lens monovision trial demonstrates better visual function if the nondominant eye is corrected for distance. Patients may also change their mind regarding monovision versus full distance correction for both eyes after the nondominant eye has already been treated for distance and the dominant eye has not yet been treated. Patients who wish to have only one eye treated and who are markedly more myopic in the nondominant eye may elect to have the nondominant eye corrected for distance.

References 1. Pallikaris IG, Panagopoulou SI. Presby. LASIK approach for the correction of presbyopia. Curr Opin Ophthalmol. 2015;26(4): 265–272. 2. Lindstrom RL, Macrae SM, Pepose JS, et  al. Corneal inlays for presbyopia correction. Curr Opin Ophthalmol. 2013;24(4):281–287. 3. Jain S, Arora I, Azar DT. Success of monovision in presbyopes: review of the literature and potential application to refractive surgery. Surv Ophthalmol. 1996;40:491–499. 4. Wright KW, Guemes A, Kapadia MS, et al. Binocular function and patient satisfaction after monovision induced by myopic photorefractive keratectomy. J Cataract Refract Surg. 1999;25: 177–182. 5. Charters L. How to evaluate presbyopic patients for monovision. Ophthalmol Times. 2000;25:109. 6. Schor C, Erickson P. Patterns of binocular suppression and accommodation in monovision. Am J Optom Physiol Opt. 1988;65: 853–861. 7. Schor C, Landsman L, Erickson P. Ocular dominance and the interocular suppression of blur in monovision. Am J Optom Physiol Opt. 1987;64:723–730. 8. Hom MM. Monovision and bifocals. In: Hom MM, ed. Manual of Contact Lens Prescribing and Fitting. Boston, MA: ButterworthHeinemann; 1997. 9. Collins M, Goode A, Brown B. Distance visual acuity and monovision. Optom Vis Sci. 1993;70:723–728. 10. Heath DA, Hines C, Schwartz F. Suppression behavior analyzed as a function of monovision addition power. Am J Optom Physiol Opt. 1986;63:198–201. 11. Erickson P, Schor C. Visual function with presbyopic contact lens correction. Optom Vis Sci. 1990;67:22–28.

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12. Wirt SE. A new near-point stereopsis test. Optom Wkly. 1947;38: 647–649. 13. Emmes AB. A statistical study of clinical scores obtained in the Wirt stereopsis test. Am J Optom Arch Am Acad Optom. 1961;38:398–400. 14. Kirschen DG, Hung CC, Nakano TR. Comparison of suppression, stereoacuity, and interocular differences in visual acuity in monovision and Acuvue bifocal contact lenses. Optom Vis Sci. 1999;76:832–837. 15. Harris MG, Sheedy JE, Gan CM. Vision and task performance with monovision and diffractive bifocal contact lenses. Optom Vis Sci. 1992;69:609–614. 16. Loshin DS, Loshin MS, Cornear G. Binocular summation with monovision contact lens correction for presbyopia. Int Contact Lens Clin. 1982;9:161–165. 17. Rose D. Monocular versus binocular contrast thresholds for movement and pattern. Perception. 1978;7:195–200. 18. Pradhan S, Gilchrist J. The effect of monocular defocus on binocular contrast sensitivity. Ophthalmic Physiol Opt. 1990;10: 33–36. 19. Collins MJ, Brown B, Bowman KJ. Contrast sensitivity with contact lens corrections for presbyopia. Ophthalmic Physiol Opt. 1989;9:133–138. 20. Collins MJ, Brown B, Verney SJ, et al. Peripheral visual acuity with monovision and other contact lens corrections for presbyopia. Optom Vis Sci. 1989;66:370–374. 21. Beddow DR, Martin SJ, Pheiffer CH. Presbyopic patients and single vision contact lenses. South J Optom. 1966;8:9–11. 22. McLendon JH, Burcham JL, Pheiffer CH. Presbyopic patterns and single vision contact lenses II. South J Optom. 1968;10:7–10, 31, 36.

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23. McGill EC, Erickson P. Sighting dominance and monovision distance binocular fusional ranges. J Am Optom Assoc. 1991;62: 738–742. 24. Sheedy JE, Bailey IL, Buri M, et al. Binocular vs. monocular task performance. Am J Optom Physiol Opt. 1986;63:839–846. 25. McDonnell PJ, Lee P, Spritzer K, et al. Associations of presbyopia with vision-targeted health-related quality of life. Arch Ophthalmol. 2003;121:1577–1581. 26. Fonda G. Presbyopia corrected with single vision spectacles or corneal lenses in preference to bifocal corneal lenses. Trans Ophthalmol Soc Aust. 1966;25:78–80. 27. Koetting RA. Stereopsis in presbyopes fitted with single vision contact lenses. Am J Optom Arch Am Acad Optom. 1970;47: 557–561. 28. Godts D, Tassignon MJ, Gobin L. Binocular vision impairment after refractive surgery. J Cataract Refract Surg. 2004;30:101–109. 29. Harris MG, Classé JG. Clinicolegal considerations of monovision. J Am Optom Assoc. 1988;5:491–495. 30. Hom MM. Monovision and LASIK. J Am Optom Assoc. 1999; 70:117–122. 31. Coren S, Kaplan CP. Patterns of ocular dominance. Am J Optom Arch Am Acad Optom. 1973;50:283–292. 32. Rigel L. Which modality works best? When monovision makes sense. Rev Optom. 1998;13:90. 33. Muller J. How to succeed with ‘modified monovision’. Rev Ophthalmol. 2000;2:51–55. 34. Jain S, Ou R, Azar DT. Monovision outcomes in presbyopic individuals after refractive surgery. Ophthalmology. 2001;108: 1430–1433.

36 

Scleral Surgery for Presbyopia PUSHPANJALI GIRI, DIMITRI T. AZAR, AND MIRWAT SAMI

Introduction The earliest attempts to expand the sclera in humans were performed in the mid-1980s1 and consisted of simple radial incisions in the sclera, similar to radial keratotomy (RK) of the cornea. This technique, however, was primarily applicable to young presbyopes, as the average increase in the amplitude of accommodation was only about 1.50 diopters (D).1 Additionally, as the incisions healed, the effect regressed. The first scleral expansion procedures using an encircling band (Fig. 36.1) were performed in 1992.1 This procedure was a development of an initial concept that consisted of a rigid plastic polymethylmethacrylate (PMMA) ring used to increase the scleral circumference. Although the results were dramatic, the procedure was plagued with complications, such as anterior segment ischemia, conjunctival erosions, and variable results. Various modifications were attempted to circumvent these problems. One such method involved passing portions of the bands through the sclera, forming scleral belt loops.2 This method did not include the use of scleral sutures in an effort to simplify the surgical technique, reduce the complications, and decrease the variability of the results. In 1997, six consecutive nonmyopic patients who underwent scleral expansion using a complete encircling band were reported.2 The band was passed through four separate scleral belt loops located at the 12, 3, 6, and 9 o’clock cardinal positions (Fig. 36.2A), which were then ultrasonically fused together at the 1:30, 4:30, 7:30, and 10:30 positions (Fig. 36.2B). Five of the six patients required removal of the scleral expansion bands (SEBs) 3 to 6 months owing due to conjunctival erosion from the roughened areas where the PMMA bands were ultrasonically welded together. After scleral expansion band removal, the accommodative amplitude of these patients returned to preoperative values. An additional three consecutive patients subsequently underwent the same procedure. In an effort to provide a better cosmetic result with more accommodation, the scleral belt loops were made much deeper. These three patients subsequently developed anterior ischemic syndrome (AIS), and the bands were removed 24 to 96 hours after surgery. 452

Given previous reports of treatment of AIS with hyperbaric oxygen,3,4 these patients were treated with hyperbaric oxygen. All responded well, with no loss of vision.5 This was the first known occurrence of AIS as a result of scleral expansion. Despite the posterior insertions of the rectus muscles, these deeper tunnels likely resulted in a significant reduction of blood flow through the anterior ciliary arteries that perforate the sclera at the insertions of the rectus muscles. To avoid compression of the anterior ciliary arteries and AIS, surgeons began placing the scleral belt loops along the 45-degree meridians at 1:30, 4:30, 7:30, and 10:30.

Scleral Expansion Segments— Manual Approach Further modifications to the scleral expansion band followed. In 1998, a new prototype was developed consisting of four individual PMMA segments that were not connected to each other. The result was decreased rates of conjunctival erosion, a simplified procedure, and a significant decrease in instrumentation cost.5,6 To decrease the risk of AIS, these segments were also placed in scleral belt loops along the 45-degree meridians, away from the ciliary artery insertions (Fig. 36.3).

Scleral Expansion Segments—Automated Approach: VisAbility Micro-Insert The Refocus Group has developed an automated approach to insert four scleral implants in the oblique quadrants at a defined and reproducible location from the limbus. They developed a sclerotome docking station to enable performing the sclerotomy with consistency. The procedure involves placing four PMAA injection molded implants about 2000 to 4000 µm from the limbus, to the depth of 400 µm within the sclera. The aim is to lift the sclera and the ciliary muscle to tighten the zonular fibers holding the lens. The procedure takes about 1 hour to perform bilaterally. The micro-insert has received the Conformité Européene (CE) mark approval and is currently undergoing FDA clinical trials.7

CHAPTER 36  Scleral Surgery for Presbyopia

In a 24-month clinical trial with VisAbility Micro-Insert trials presented in 2013, 80 patients were asked to describe their unaided vision as “excellent,” “acceptable,” or “poor,” pre- and postoperatively. At 24 months, 73% patients reported at least “acceptable” vision overall, and 99% reported “acceptable” for distance tasks. About 83% patients were able to perform near tasks such as reading medicine labels, prices, and newspapers. The percentage of patients reporting “acceptable” vision when reading newspapers was reported to improve from 4% preoperatively to 76% at 24 months postoperatively. About 93% eyes were reported to have distance-corrected near visual acuity (DCNVA) of 0.3 logMAR (20/40 Snellen) or better in a 2014 report from the same trial.7 Although the results seem promising, one major risk involved for patients undergoing VisAbility micro-insert implant is anterior segment ischemia (ASI) due to the mechanical vascular compression from the implant. The other major risks include implant infection, endophthalmitis, moderate to severe subconjunctival hemorrhage, and implant displacement. About 75% patients with the first generation of VisAbility micro-insert implants were reported to have had at least one implant movement or displacement by the FDA.7

Complications of Manual Surgery Only one case of AIS has been reported using the latest 5.5-mm scleral expansion segments.8 This complication

• Fig. 36.1

 

may have resulted from improper positioning of the segments. The indications of AIS are as follows: • dilated nonreactive pupil or nonreactive papillary sector • Desçemet fold, grayish look • trace of flare and cells • intraocular pressure (IOP) less than 10 mm Hg • nausea One case of endophthalmitis has also been reported; it was thought to result from a break in sterile technique.9 One case of scleral thinning similar to that observed with scleral buckles has also been reported and may be a result of scleral expansion.10 To date, no cases of malignant glaucoma have been reported using the new scleral expansion segments. Theoretically, however, this is a possibility as the segments may increase posterior pressure, blocking outflow and resulting in aqueous misdirection.11–16 Intravenous mannitol is given to dehydrate the vitreous, decreasing the likelihood of this complication. Other minor complications include the following: • conjunctival hyperemia • subconjunctival hemorrhage • transient ptosis • scleral expansion segment rotation or subluxation • photophobia due to tear film instability • conjunctival erosion • accommodative fatigue

• Fig. 36.3  The scleral expansion procedure. The conjunctiva is opened at the limbus from 2:30 to 10:30 and from 4:30 to 7:30 with vertical relaxing incisions at 12:00 and 6:00. Scleral belt loops, 3.5 mm posterior to the posterior limbus, 4 mm long, 1.5 mm wide, and 300 to 400 µm deep are made in each of the four oblique quadrants.

A complete encircling band.

A

453

B

C

• Fig. 36.2  Passage of a scleral expansion band into a scleral belt loop (A) and ultrasonic fusion of portions of a scleral expansion band (B). View of the full band (C).

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• temporary keratoconjunctivitis • swollen or irregular conjunctiva Astigmatism may last 2 to 3 months; it subsides with intense treatment with artificial tears.

Clinical Outcomes of Manual Surgery Increases in accommodation after this technique have ranged from 1.00 D to 10.00 D.17 Schachar himself has reported 5.80 D to 11.0 D of subjectively measured accommodative amplitude in postoperative patients.1 Two studies8 of 29 and 7 patients have reported an increased range of accommodation in all patients with an average of 3.02 D and 3.13 D, respectively. Similar to our findings, an increased range of near vision was noted in the unoperated eye. This increase approached 20% to 50% of the increase in the operated eye. In an independent study, subjectively measured amplitude increased in three of eight patients 6 months postoperatively but returned to preoperative levels in all eyes within 1 year.18 Another study of 29 patients reported a mean increase in amplitude by 1.70 D ± 1.50 D in the operated eyes and 1.3 D ± 1.20 D in the unoperated eyes.19,20 A phase I, multicenter, prospective, nonrandomized study by the US Food and Drug Administration (FDA) showed promising results. Approximately 59% of patients gained three lines or more of near vision. The response was variable, perhaps because of the surgeon’s learning curve and the band placement variability. However the company filed for bankruptcy.

Clinical Outcomes of Automated Approach The ClinicalTrials.gov filing for the VisAbility micro-insert system indicates that the Refocus Group is evaluating the

safety and effectiveness of the VisAbility MicroInsert System for the improvement of near visual acuity in presbyopic patients. The objective of this study is to evaluate the safety and effectiveness of the VisAbility Implant System (VIS) for the improvement of near visual acuity in presbyopic patients. This is a prospective clinical study that will enroll and determine eligible a total of 360 subjects ranging in age between 45 and 60 years of age at up to 14 clinical sites. The follow-up period was 1 year. The ClinicalTrials.gov filing indicated that the study will also include a 60-subject randomized controlled sub-study at three investigational sites. Subjects enrolled and eligible at these sites will be randomized (1 : 1 ratio) to a surgery group or a control group. Subjects randomized to the surgery group will undergo surgery and will be followed for 24 months in the same manner as the larger non-randomized surgical group. Subjects randomized to the control group will be followed for 6 months, and will be eligible to undergo surgery after completion of this 6-month follow-up period. Encouraging results have been reported at the 2017 and 2018 OIS meetings. Table 36.1 includes some of the preliminary data presented at these meetings of a relatively small subgroup of 20 to 40 patients. At the time of this writing, the FDA status of this technology is not known.21,22

Other Scleral Expansion Procedures Anterior Ciliary Sclerotomy Another method currently used for surgical reversal of presbyopia is anterior ciliary sclerotomy (ACS). This was first suggested by Thornton18 as a method to safely expand the globe over the ciliary body and restore accommodation. When first performed by Fukasaku et al., this procedure consisted of eight equally spaced radial incisions of the conjunctiva and sclera overlying the ciliary body in each of

TABLE 36.1  Summary of Primary Outcome Variables at Each Follow-Up Period (Mean ± 4 SD)

Baseline

3 Months

1 Year

2 Years

Distance corrected near visual acuity at 40 cm (n = 20)

20/40 (J3) or better (%) 20/32 (J2) or better (%) 20/25 (J1) or better (%)

0 0 0

100 90 50

100 95 63

100 90 75

Uncorrected near visual acuity at 40 cm (n = 20)

20/40 (J3) or better (%) 20/32 (J2) or better (%) 20/25 (J1) or better (%)

10 3 0

100 91 84

100 95 90

100 100 90

Mean change in MRSE from baseline (n = 40 at baseline, n = 39 at 3 months, n = 39 at 1 year, and n = 40 at 2 years)

Mean change (−SD) (+SD)

−0.05 −0.37 0.26

Close-up visual performance without glasses (n = 26 at 3 months, n = 24 at 1 year, and n = 25 at 2 years)

Significantly better or better No change Worse or significantly worse

SD, Standard deviation.

0.11 −0.27 0.11 100 0 0

0 −0.25 0.25

−0.03 −0.26 0.25

88 13 0

96 0 0

CHAPTER 36  Scleral Surgery for Presbyopia

the oblique quadrants.11 This was modified to include limbal peritomies overlying the oblique quadrants, which would avoid excessive conjunctival bleeding and allow more accurate measurement of the length and depth of the incision using ultrasound biomicroscopy (UBM). This procedure showed dramatic improvements of several diopters in accommodation, but regression occurred rapidly and within several months only an average of a 0.8 D increase in accommodation was achieved. This procedure was further modified to enhance the surgical effect and decrease regression. Sclerotomy depth was increased to full thickness by a spreading incision technique. This method, termed enhanced ACS by Fukasaku and Marron,11 used a specially designed Fukasaku ACS forceps that allowed for the careful spreading of the scleral tissue down to the uveal plane after the initial incision was made. This was a particularly challenging approach owing to the difficulty in identifying the surgical plane without causing hemorrhage. Fukasaku and Marron11 noted that in approaching the uveal plane, a distinct bluish hue of vascularity is recognizable and is used to identify the uvea. Also, the subscleral space, a potential space, was seen to easily open up to become an actual space. Using this surgical approach, no hemorrhages were reported using the spreading dissection method. This procedure showed enhanced results compared to the simple ACS. However, as before, the effect rapidly regressed to near preoperative levels within several months of surgery owing to wound closure. The next step in the modification of ACS was the introduction of a material into the incision that would keep it patent and prevent regression of the improvement in accommodation. Fukasaku and Marron11 chose silicone as the material because it was inert, stable, and easily molded and manipulated surgically. The silicone was chosen from scleral buckle material and was shaped by hand in the operating room. The dimensions were determined by the size of the incision and the desired circumferential expansion of the sclera. The silicone plugs were placed in the depth of the incisions and sutured in place in a criss-cross fashion. Any unnecessary tension on these sutures was avoided to ensure that the initial gain in accommodation should not be significantly less than simple or enhanced ACS owing to the effect of the sutures holding the silicone plugs in place. To further prevent any wound closure due to suture tension, Fukasaku and Marron11 now use 11-0 Merceline, which should induce less tension and last longer than does nylon. In this way, ACS has evolved through three major modifications from simple, enhanced, to ACS with silicone expansion plugs (ACS-SEP). Although the first two methods showed a significant but unsustained improvement in accommodative amplitude, the ACS-SEP procedure has shown modest initial improvement in accommodation sustained over the 18 months of study in addition to significantly lowering the IOP. Patients expressed immense satisfaction with this procedure despite the modest

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measured increase in accommodative amplitude of only 1.5 D. Future plans for improvement under consideration by Fukasaku and Marron11 include trying other suturing methods to avoid potential conjunctival irritation or erosion. Also, redesigning of the silicone plugs is underway to make them more user friendly and sustainable. Another study that is presently underway by Fukasaku and Marron11 is the titration of IOP using different types of silicone plugs in the treatment of glaucoma.

Laser Scleral Expansion The infrared laser has also been used to make deep scleral incisions11 to treat presbyopia, presumably by mechanisms similar to SEB. Currently, the Surgilight company is in phase II of FDA trials with the Optivision infrared laser. The laser output energy is 20 mJ, frequency 20 Hz, and spot size 400 µm, which is delivered through a fiber and conical contact tip.

LaserACE Approach Scleral laser anterior ciliary excision (LaserACE approach) uses VisioLite 2.94 µm erbium:yttrium–aluminum–garnet (Er:YAG) laser system in four oblique quadrants on the sclera over the ciliary muscle. The array of micro-excisions are 600 µm in diameter to a depth of approximately 500 to 700 µm. The procedure zone in the four oblique quadrants include three critical zones of anatomic and physiologic importance, the scleral spur at the origin of the ciliary muscle (0.5 to 1.1 mm from anatomic limbus [AL]); the mid ciliary muscle body (1.1 to 4.9 mm from AL); and insertion of the longitudinal muscle fibers of the ciliary, just anterior to the ora serrata at the insertion of the posterior vitreous zonules (4.9 to 5.5 mm from AL).7 Hipsler et al.23 performed LaserAce surgery on 26 patients (52 eyes), where the outcomes were analyzed using visual acuity testing, Randot stereopsis, and the CatQuest 9SF patient survey. The preliminary results showed promising outcomes for restoring visual performance for near and intermediate visual tasks without compromising distance vision and without touching the visual axis. The binocular uncorrected near visual acuity (UNVA) improved from +0.20 ± 0.16 logMAR preoperatively, to +0.12 ± 0.14 logMAR at 24 months postoperatively (P = .0014). The binocular DCNVA improved from +0.21 ± 0.17 logMAR preoperatively, to +0.11 ± 0.12 logMAR at 24 months postoperatively (P = .00026). Stereoacuity improved from 74.8 ± 30.3 seconds of arc preoperatively, to 58.8 ± 22.9 seconds of arc at 24 months postoperatively (P = .012). There were no complications such as persistent hypotony, cystoid macular edema, or loss of best-corrected visual acuity (BCVA). Patients surveyed indicated reduced difficulty in areas of near vision, and were overall satisfied with the procedure. High and sustained patient satisfaction was reported postoperatively and over 24 months.23 Table 36.2 includes the long-term visual acuity results after LaserACE procedure.

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TABLE 7 36.2  Patient Long-Term Visual Acuity After LaserACE Procedure

Patient

Years After LaserACE

Eye

UDVA

UIVA

UNVA

CDVA

DCIVA

DCNVA

101

10

OD OS

20/25-3 20/40-2

20/40-2 20/40

20/60 20/40

20/20 20/15

20/20 20/20

20/20 20/20

102

13

OD OS

20/20-2 20/25

20/20-2 20/20-2

20/20-1 20/20-2

20/15 20/15

20/20 20/20

20/20 20/20

103

8

OD OS

20/15-3 20/20-2

20/20 20/20

20/20+1 20/20+1

20/15 20/15

20/20 20/20+1

20/20+1 20/20+1

CDVA, Corrected distance visual acuity; DCIVA, distance corrected intermediate visual acuity; DCNVA, distance corrected near visual acuity; LaserACE, laser anterior ciliary excision; UDVA, uncorrected distance visual acuity; UIVA, uncorrected intermediate visual acuity; UNVA, uncorrected near visual acuity.

The risk factors associated with LaserACE are accidental micro-perforation of the sclera and non-persistent mild subconjunctival hemorrhages. The accidental scleral microperforation can be resolved by temporarily lowering the intraocular pressure, and with a collagen biomatrix.7

Scleral Expansion and Glaucoma Chronic open-angle glaucoma is a genetic disease, but predisposed patients may benefit from scleral expansion owing to anatomic modifications that the procedure produces.12,24 As the ciliary muscle is attached to the area of the scleral spur and the trabecular meshwork, outward expansion of the sclera seems to open the anterior chamber angle and the pore size of the meshwork, facilitating aqueous flow. International clinical trials evaluating scleral expansion for treatment of ocular hypertension and primary open-angle glaucoma in Canada and Mexico have demonstrated excellent preliminary results.12,13 The median decrease in IOP after scleral expansion was 7 mm Hg, and the postoperative IOP decrease appears to be equivalent to the IOP lowering effect of the preoperative physician-prescribed topical glaucoma medications.11 Whereas the risks of topical and/or systemic glaucoma medications are ongoing and additive over time, SEB placement is a single event, with most adverse events being correctable by removal of the SEB. In past cases in which SEB removal has been necessary, there were no lasting adverse effects of the implantation and the eye returned to its preoperative state without any further complications. Similarly, ACS-SEP has also shown a dramatic drop in the IOP, the effect of which is sustained, unlike the previous simple and enhanced ACS procedures. On the contrary, one case report of a patient who underwent bilateral simple ACS and subsequent SEP in his left eye for glaucoma and to restore accommodation presented with uncontrolled IOP and required a trabeculectomy.14 On examination, his conjunctiva was seen to be scarred and retracted, with a small leaking bleb overlying one of the bands. This scarring and hardening of the sclera may have caused the reversion of the previous beneficial effect of these procedures.

References 1. Schachar RA. Cause and treatment of presbyopia with a method for increasing the amplitude of accommodation. Ann Ophthalmol. 1992;24:445–452. 2. Yang GS, Yee RW, Cross WD, et al. Scleral expansion: a new surgical technique to correct presbyopia. Invest Ophthalmol Vis Sci. 1997;38(ARVO Abstracts):S497. 3. de Smet MD, Carruthers J, Lepawsky M. Anterior segment ischemia treated with hyperbaric oxygen. Can J Ophthalmol. 1987;22:381–383. 4. Jampol LM. Oxygen therapy and intraocular oxygenation. Trans Am Ophthalmol Soc. 1987;85:407–437. 5. Yee R, Sami M. Scleral expansion and anterior ciliary sclerotomy. In: Azar DT, Gatinel D, Hoang-Xuan T, eds. Refractive Surgery. Philadelphia: Elsevier; 2007:463–474. 6. Cross WD, Zdenek GW. Surgical reversal of presbyopia. In: Agarwal S, et al, eds. Refractive Surgery. New Delhi: Jaypee Brothers Medical Publishers; 2000:592–608. 7. Hipsley A, Hall B, Rocha KM. Scleral surgery for the treatment of presbyopia: where are we today? Eye Vis (Lond). 2018;5:4. 8. Ruelas V. Surgical reversal of presbyopia: optometric postoperative care. In: Schachar RA, Roy FH, eds. Presbyopia: Cause and Treatment. The Hague: Kugler Publications; 2001:107–109. 9. Zdenek G. Complications in surgical reversal of presbyopia can be avoided, managed. Ocular Surg News. 2001;19:39–44. 10. Singh G, Chalfin S. A complication of scleral expansion surgery for treatment of presbyopia. Am J Ophthalmol. 2000;130:521– 523. 11. Fukasaku H, Marron JA. Anterior ciliary sclerotomy with silicone expansion plug implantation: effect on presbyopia and intraocular pressure. Int Ophthalmol Clin. 2001;41(2):133– 141. 12. Johannes L. Is the end of reading glasses in sight? The Wall Street Journal. 28 March 2001;B1. 13. Rifkind AW, Yablonski ME, Shuster JJ. Effect of scleral expansion band on ocular hypertension: Canadian phase 1 study. Compr Ther. 2001;27(4):333–340. 14. Cross WD, Marmer RH, Shuster JJ. A pilot study to determine the effect of the scleral expansion band (SEB) procedure on ocular hypertension. Am J Ophthalmol. (in press). 15. Law SK, Syed HM, Caprioli J. Glaucoma care in a patient with previous anterior ciliary sclerotomy and scleral expansion procedure. Arch Ophthalmol. 2003;121(11):1646–1648.

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16. Wirbelauer C, Karandish A, Aurich H, et al. Imaging scleral expansion bands for presbyopia with optical coherence tomography. J Cataract Refract Surg. 2003;29(12):2435–2438. 17. Schachar RA, Black TD, Kash RL, et al. The mechanism of accommodation and presbyopia in the primate. Ann Ophthalmol. 1995;27:58–67. 18. Thornton SP, Shear NA. Surgery for Hyperopia and Presbyopia. Baltimore, MD: Williams and Wilkins; 1997:33–36. 19. Malecaze FJ, Gazagne CS, Tarroux MC, et al. Scleral expansion bands for presbyopia. Ophthalmology. 2001;108(12):2165–2171. 20. Qazi MA, Pepose JS, Shuster JJ. Implantation of scleral expansion band segments for the treatment of presbyopia. Am J Ophthalmol. 2002;134(6):808–815.

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21. Progress of Refocus Group’s Clinical Trial. Ophthalmology Innovation & Investment Summit. 2017 Jun. https://www.youtube.com/ watch?v=8GdsutczHuQ. Accessed November 28, 2018. 22. Progress of Refocus Group’s Clinical Trial. Ophthalmology Innovation & Investment Summit. 2018 March. https://www .youtube.com/watch?v=G5ZfnPKlBSY. Accessed November 28, 2018. 23. Hipsley A, Ma DH, Sun CC, Jackson MA, Goldberg D, Hall B. Visual outcomes 24 months after LaserACE. Eye Vis (Lond). 2017;4:15. 24. Schachar RA. Scleral expansion band procedure: therapy for ocular hypertension and primary open-angle glaucoma. Ann Ophthalmol. 2000;32:87–89.

37 

Multifocal Corneal Surgery for Presbyopia DAMIEN GATINEL

Introduction Presbyopia can be defined as the point where accommodative function declines to less than 3 to 4 diopters (D), receding the near point beyond arms’ length at reading distance. It is usually manifested in the fourth decade of life. Theories of the mechanism of presbyopia were traditionally categorized as either lenticular or extra-lenticular.1–4 The compensation of presbyopia by the induction of a controlled amount of multifocality to the cornea is an attractive technique for presbyopes, especially those having concomitant distance ametropia. Surgical techniques to restore full or partial dynamic accommodation using foldable intraocular lenses (IOLs), ciliary sclerotomy, scleral expansion bands, and femtosecond (FS) laser crystalline lens relaxing incisions are not routinely used and are still under investigation.5–8 Inducing optical multifocality requires simpler and less invasive procedures. The results of recent studies suggest that multifocal contact, phakic, and pseudo-phakic IOLs can afford presbyopes a viable alternative to spectacles.5,9–15 Diffractive multifocal (e.g., bifocal and trifocal) intraocular lenses have gained popularity over the last decade, and newer refractive designs have also been introduced.

Theoretical Considerations The human eye exhibits a certain amount of multifocality. The ability to discern a target over a range of distances without noticeable loss in image quality relates to depth of focus.16 Many elements determine the value of the depth of focus of an optical system such as the eye.17 The level of optical aberration that the surgeon can modify to increase the depth of focus in order to compensate for the loss of accommodation and induce a state of “pseudoaccommodation” is an important consideration.

Depth of Focus and Optical Aberrations Depth of focus determines the distance range for which a target can be seen clearly without a change in focusing power. 458

For an emmetropic no-accommodating eye, the depth of focus relates to the position of the hyperfocal distance, which is the nearest distance that the retina can focus on without significant reduction of the visual performance for a target located at infinity.17,18 Thus the age-related reduction in amplitude of accommodation could be ameliorated by increasing the depth of focus of the eye. Atchison and Smith19 have stated that the depth of focus corresponds to “the range of focusing error that does not result in objectionable deterioration in retinal image quality.” According to these authors, depth of field depends on several factors, including the optical properties of the eye (pupil diameter, accommodation level, monochromatic and chromatic aberrations, diffraction), retinal and visual processing properties (photoreceptor size and ganglion cell density, visual acuity and contrast thresholds, ocular pathway disease), and target properties (luminance, space detail, contrast, color spectral profile).16,19 Due to the combined effects of diffraction and aberrations, the image of focused point light is not a point but a patch of light or point spread function, as discussed in Chapter 5. When a target such as a point is defocused, its image is an illuminated blur disc (Fig. 37.1). One can assume that depth of field is set by the range over which the blur produced by defocus is smaller than a certain threshold diameter. For example, if the blur disc produced by defocus is less than half the width of the in-focus of the point spread function (PSF, the width at which the light level is equal to half that of the central maximum value), it may be assumed that it has little chance of being detected (Fig. 37.2). At small pupil diameter (e.g., 2 mm), diffraction theory predicts that the width of the PSF is inversely proportional to the square of the pupil diameter. The increase of the width of the PSF results in an increase in the depth of field with the decrease in pupil diameter, the effect of defocus being proportionally less detectable given the larger initial PSF. The results of a study by Campbell17 show that the depth of field decreases from 1.7 D to 0.3 D between the pupil diameters of 1 mm and 7 mm. Conversely, as pupil diameter increases, the effect of diffraction becomes less

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459

overestimated owing to the depth of field effect, since it is accentuated by the accommodative pupil constriction and increase in the angular subtense of the target.20 Modification of the ocular optical properties can be accomplished accordingly to increase the depth of field of presbyopic subjects and restore unaided near visual acuity while maintaining satisfactory unaided distance visual acuity.

What Is Multifocality?

• Fig. 37.1

  When an optical system (OS) is free of optical aberrations (diffraction limited), the depth of focus is short, due to the rapid increase in the width of the point spread function (PSF) with subsequent loss of visual acuity when the image plane (or object plane) is displaced.

• Fig. 37.2

  When an optical system (OS) suffers from some amount of optical aberrations (here, positive spherical aberration), the depth of focus is increased owing to the relative maintaining of the width of the point spread function (PSF) with the anterior displacement of the image plane.

important and the influence of aberrations increases. As aberrations increase with the pupil diameter, the diameter of the PSF is expected to increase, thus increasing the threshold of blur due to defocus and subsequently the depth of field. Because natural aberrations of the eye are low or irregular, they do not physiologically contribute to a significant increase in the depth of field for large (above 5–6 mm) pupil diameters.17,19 The size and contrast of the target are also positively correlated to the depth of field.16,19 The clinical implications of these facts for measurements of refraction and amplitude of accommodation are important. Subjective accommodation measurements may be

Multifocality reflects the presence of various refractive errors within the area covered by the entrance pupil. An emmetropic eye has refractive power enabling the rays emitted by a source located at infinity to be focused in the retinal plane. Myopic or hyperopic eyes exhibit an excess or a deficit in their refractive power, respectively. The process of determining the subjective refraction of the eye suggests that a nonemmetropic eye exhibits a single refractive power error that can be corrected by a spherocylindrical lens, for example, 2(−1 × 0 degrees). However, with the eye being an “imperfect” biologic structure, its refractive power is not constant throughout the entrance pupil. Subtle local refractive errors remain after the determination of best refractive correction. Despite the addition of a spherocylindrical lens aimed at making the eye emmetropic, not all rays that are refracted throughout the entrance pupil are focused in the same plane. These residual errors would not exceed ±0.75 D across the pupil in normal emmetropic eyes. Our visual system is built around these imperfections, and this tolerance to some local defocus accounts for the natural depth of field of the human eye. However, it is not sufficient to supply the lack of accommodation power of presbyopic eyes. Some aberrometers, such as the OPD-Scan III (NIDEK), allow the display of these local variations of refractive errors in a vergence map called the OPD map. This map plots the local variations of the refractive error across the entrance pupil area of the eye of interest, that is, the local excess (myopia) or deficit (hyperopia) in optical power (or vergence; Fig. 37.3). Astigmatism corresponds to a meridional variation of the ocular refractive error, usually caused by corneal toricity (Fig. 37.4). Wavefront maps are useful to provide a basis for analyzing and titrating the amount of high-order aberrations but may not intuitively bring clinical relevance. Vergence maps allow the clinician to directly estimate the impact of the low-order and high-order aberrations on the refractive properties of the examined eye. The nonsystemized local variations of the refractive error relate to the presence of high-order aberrations. This clinician-friendly interpretation has a profound impact on the understanding and planning of multifocal corrections. Spherical aberration is a type of high-order aberration that describes the presence of a concentric gradient of power between the center and the periphery of the pupil. In consequence, the larger the pupil, the larger the amount of measured spherical aberration. In most human eyes looking at infinity, the measured ocular spherical aberration is positive because, regardless of the refractive status, there is a

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• Fig. 37.3

  Example of an optical path difference (OPD) map obtained with the topographic aberrometer OPD-Scan III (NIDEK) in an emmetropic eye (uncorrected distance visual acuity, 20/15). The result is a wavefront vergence map that is similar to the refractive power maps in corneal topography but addresses the plot of the local refractive error of the whole ocular optical system (cornea + crystalline lens) within the entrance pupil disc zone. In this example, high-order aberrations are responsible for little fluctuations of the refractive error around zero.

OPD MAP = LOCAL VERGENCE = LOCAL REFRACTIVE ERROR

DIOPTERS

Spherocylindrical refraction: -1.50 (-5 x 80o)

• Fig. 37.4

  Example of an optical path difference (OPD) map obtained with the topographic aberrometer OPD-Scan III (NIDEK) in a highly astigmatic eye (best corrected distance visual acuity, 20/20). The specific effect of high-order aberrations is difficult to appreciate, as the vergence map is dominated by the astigmatism-induced meridional changes in the refractive error.

slight increase in refractive power from the center to the edge of the pupil. An emmetropic eye generally exhibits a slight amount of myopic error toward the edges of the pupil (Fig. 37.5). Ocular spherical aberration relates to the difference between the refractive powers of the center and the edge of the functional pupil. The larger this difference, the larger

the value of the spherical aberration, regardless of the mathematical function used to quantify this aberration. Zernike polynomials represent a class of mathematical functions that can be used to model the optical aberrations of the human eye. Z40 is the symbol for spherical aberration, which is weighted by a coefficient c40, whose value is expressed in micron units and refers to a specific pupil diameter.

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OPD HO MAP = LOCAL REFRACTIVE ERROR AFTER THEORETICAL BEST SPECTACLE CORRECTION

DIOPTERS

Myopic shift toward the edge of the pupil = Positive spherical aberration

• Fig. 37.5  Removing the effect of the best spherocylindrical error on the display allows one to plot the specific effects of the residual high-order aberrations. There is a moderate gradient of increased myopic error toward the pupil edge, reflecting the presence of a slight amount of positive spherical aberration.

When the refractive power (vergence) is higher at the pupil center than its periphery, spherical aberration is said to be negative (c40 < 0). Conversely, when the refractive power is lower at the pupil center than its periphery, the spherical aberration is said to be positive (c40 > 0). In terms of refractive power, spherical aberration only characterizes the progressive variation of the refractive power from the center to the edge of the pupil independent of the values of these powers themselves. Multifocality can be induced by increasing the amount of spherical aberration to improve the ability to form retinal images of nearer and farther image targets with reasonable sharpness. The manipulation of spherical aberration may aim at increasing the natural gradient of refractive power from the center to the periphery (i.e., an increase in positive spherical aberration). For combined hyperopic and presbyopic corrections, it is more common to reverse it (i.e., to induce negative spherical aberration). This can be achieved by inducing some myopic defocus at the center of the pupil and reducing some myopic defocus toward the pupil periphery (inducing negative spherical aberration).

Multifocality Versus Monovision In classic monovision, the dominant eye is corrected to achieve satisfactory uncorrected distance visual acuity, whereas the nondominant eye is made myopic to see well at near without any optical aid. In such situations, the nondominant eye becomes “fully” myopic, in the sense that the planned correction results in the same myopic refractive error within the pupil area. This consistent negative defocus reduces significantly the uncorrected visual acuity at distance and compromises binocular stereopsis. When a multifocal correction is planned, although the refraction of the nondominant eye would still be measured

myopic (dominated by the paraxial defocus), there is a relative imbalance between the induced myopic error within the paraxial pupil zone and the low myopic to emmetropic paracentral concentric zone. This reduction of the myopic refractive error toward the edges of the pupil aims at providing the eye with a better uncorrected distance visual acuity. This gradient of defocus from the center to the edge of the pupil is reflected in the induction of negative spherical aberration.

Pseudoaccommodation: The Importance of Corneal Multifocality and Optical Aberrations Refractive corneal procedures, such as radial keratotomy (RK) and photorefractive keratectomy (PRK), have been known to create corneal multifocality.21–26 Multifocal effects of the cornea have also been incriminated for the disparity between residual refractive error and uncorrected visual acuity after refractive surgery.21,24,26 A study in which corneal topography was used showed that corneal multifocality (refractive power gradient within the pupillary area) has a significant positive correlation with the amount of apparent accommodation in pseudophakic eyes.27 The degree of corneal multifocality was determined on corneal topography by measuring the maximum and minimum corneal refractive powers within the pupillary area. Refractive astigmatism, keratometric astigmatism, pupillary diameter, and age were also analyzed. Multiple regression analysis revealed that corneal multifocality and pupillary diameter had significant positive correlations with apparent accommodation, whereas other explanatory variables showed no relationship with apparent accommodation. Based on the results of this study, corneal multifocality has been demonstrated to play an important role in apparent accommodation (pseudoaccommodation) after cataract surgery.

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Oshika et al.28 further tried to assess the relationship between apparent accommodation in pseudophakic eyes, multifocal corneal effects, and wavefront aberrations of the cornea. Wavefront aberrations of the cornea were calculated by expanding the height data of the corneal topography into Zernike polynomials for individual pupil size. The influence of higher-order aberration on retinal image quality was simulated by computing the PSF and modulation transfer function (MTF) from the aberration function. The comalike aberration showed a significant positive correlation with the amount of apparent accommodation, but the sphericallike aberration did not. Among the coma-like aberrations, the component representing vertically asymmetric distribution of corneal refractive power with greater refraction located in the lower part of the eye was most relevant to apparent accommodation. Computer simulation of PSF and MTF indicated that a focus shift of 0.5 D led to deterioration of the retinal image significantly more in eyes without higher-order aberrations than in eyes with a moderate amount of coma-like aberrations. The influences on low-contrast visual acuity and contrast sensitivity were not addressed in this study. Patients with multifocal IOLs generally have lower contrast sensitivity and often report ghosting and halos, especially during scotopic conditions.9–11 Several reports indicate that such measures would be adversely affected in the setting of a multifocal cornea.29–33 Other possible adverse optical effects of a multifocal cornea include monocular diplopia, subjective glare, and halo effects.26 The influence of scotopic pupil size and optical aberrations on visual symptoms in eyes after conventional laser in situ keratomileusis (LASIK) has been investigated.34 The analysis showed positive correlation of double vision with total coma and with horizontal coma for the 5-mm and 7-mm pupil sizes, negative correlation between starburst and total coma for the 7-mm pupil size, positive correlation of double vision with horizontal coma, and glare and starburst with spherical aberration and with total aberrations. Scotopic pupil size had a positive association with starburst and a negative association with double vision. Thus multifocality of the cornea may afford clinical advantages, but such multifocality may increase the noise, or static, in the eye’s optical system and potentially decrease some measures of visual performance. The use of adaptive optics has enabled manipulation of the level of ocular higher-order aberrations35 and enabled investigation of their effects on depth of focus.36

Asphericity Modulation The modulation of corneal asphericity has been proposed by several authors. Increasing negative asphericity (reduction of the local corneal curvature from the apex to the periphery) can successively reduce, cancel, then negate the ocular spherical aberration. In the latter situation, the paraxial area within the pupil has more optical power than its surrounding periphery. In the context of presbyopia compensation with excimer laser surgery, some level of useful multifocality can be achieved by inducing myopic defocus within the paraxial zone and altering the ablation profile to

reduce its amount within the paracentral zone. In such a situation, the eye would be best refracted for distance with a negative spectacle correction and hence can be considered as myopic. However, its uncorrected distance acuity would exceed that of an eye in which the whole pupil area (paraxial and paracentral zone) would be equivalently myopic (full myopic correction is intended in pure monovision strategies). Nuclear cataract can result in a myopic shift, which is unusually predominant within the central pupil zone. This myopic shift results from the increase of the refractive indice of the proteins of the crystalline lens nucleus and is often referred to as indice myopia. In such a situation, an increase in negative spherical aberration is commonly observed and the myopic shift within the paraxial pupil area induces an improvement in uncorrected near visual acuity. However, in contrast with a situation in which the pupil would be affected by a myopic error, the less myopic (or close to emmetropia) paracentral concentric pupil zone provides the eye with improved distance uncorrected visual acuity (Fig. 37.6).

Practical Consequences General Considerations From a clinical perspective and in an optical system such as the presbyopic eye, an increased depth of focus can be used to enlarge the range of distance at which a target that is first brought into focus appears to be too blurred to be discerned. Surgically increasing the depth of focus of the presbyopic eye can be achieved by introducing a controlled amount of multifocality via the insertion of a multifocal designed lens or reshaping the anterior surface of the cornea with a multifocal profile of ablation. Literally, multifocality supposes that a portion of the light of emitting sources located at different distances of the eye can be properly focused on the fovea. In the case of presbyopia compensation, two main foci are expected, which would bring into focus to the fovea images located at infinity and at near, respectively. Because the reading distance and the distance required for near tasks are usually between 25 and 50 cm, the maximum additional power required in a nonaccommodating patient is about 3 D. However, for the eye viewing a near object, it is often the case that the amount of accommodation used will be less than might be expected given the viewing distance. The early presbyopic eye will utilize its depth of focus so that just enough accommodation is used to bring the object to the edge of the depth of field. Here, the eye is actually focused slightly farther away than the object; thus the accommodative effort needed is minimized. When the eye is no longer able to accommodate, multifocal presbyopic compensation relies on the principle of simultaneous vision. Owing to the multiple refractive powers simulatenously present within the entrance pupil of a successfully operated multifocal eye, part of the light

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Myopic shift toward the center of the pupil = Negative spherical aberration

• Fig. 37.6  This left eye optical path difference (OPD) map was obtained in 2016 of a 55-year-old patient referred for early nuclear cataract in the left eye (his 2013 OPD examination appears in Fig. 37.1). The central increase in the index of refraction of the central part of the crystalline lens resulted in a myopic shift: best corrected visual acuity was 20/20 with a −2.50 D correction. The patient can now read Jaeger 2 (J2) without any optical aid with the left eye, whereas the right eye (deprived from cataract) needs an addition of +2 D to read J2. The ocular spherical aberration coefficient measured in 2016 was negative (c40 = −0.283 µm for a 6-mm zone). In 2013, this same coefficient value was c40 = +0.113 for a 6-mm zone. Because there is a relative reduction of the myopic error toward the pupil edges, uncorrected distance visual acuity is 20/30 with the left eye. In the latter, the paraxial pupil myopic shift incurred by nuclear sclerosis has provided some useful multifocality.

rays emitted by a single target source will be in focus at the retinal place, regardless of the location of that source, from reading distance to infinity. As a consequence, the remaining light rays will not be in focus, but if the resulting blur is unnoticed or moderate, the patient will not be experiencing a significant decrease in distance visual quality and will regain the possibility of reading without spectacles. When satisfactory, this whole process corresponds to the state of successful pseudoaccommodation (Fig. 37.7).37

Corneal Multifocal Profile of Ablation The realization of such multifocal ablation patterns on the cornea is designed as an alternative to dynamic accommodation of the lens. Because its optical power is not constant over the entrance pupil, the cornea exhibits physiologically a certain amount of multifocality. This multifocality is often increased after corneal refractive surgery, being incisional, surface, or deep ablation.23,25

The conventional correction of hyperopia aims at increasing the corneal paraxial power to compensate for the lack of optical power of the eye. Such an approach has been shown to introduce an unintended large amount of multifocality owing to increased prolateness of the postoperative corneal profile38,39 (Figs. 37.8 and 37.9). The variation of corneal asphericity after conventional LASIK or PRK40 is not directly related to the predicted change using simple mathematical models.41,42 The conjugate effects of biomechanical changes and wound healing over both the transition and ablation zones result in an increased range of corneal refractive power owing to the rapid changes between the central steepened area and flattened midperiphery. Modern laser profiles of ablation take into account these effects to achieve efficient aspheric remodeling of the corneal profile.

Early Techniques The pioneering techniques to create multifocal corneas to compensate for presbyopia were encouraged by the unintended multifocal lens effects observed after RK that led

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• Fig. 37.7

  Principle of image superposition with a multifocal cornea. In this example, the central part of the cornea has more optical power than the periphery, which allows it to bring closer objects into focus. Objects located at infinity are also brought into focus using the portion of light rays that are refracted by the corneal periphery.

• Fig. 37.8  Hyperopic photoablation with a large planned optical zone (OZ). The preoperative anterior corneal profile is outlined in gray. The immediate postoperative profile is outlined in red. The postoperative profile after regression is outlined in blue. The concentric-colored diagram corresponds to the extrapolated representation of the curvature variations from the post-regression profile. The flattening within the junction of the optical and transition zones results in an increased multifocality within the ablation zone.

to excellent uncorrected visual acuity at near and distance in presbyopic patients. In 1994, Anschütz began human clinical trials to treat myopia–presbyopia with bifocal PRK using a 193-nm Aesculap-Meditec iris diaphragmed excimer laser.43 Two techniques were then tried: the first used a central near zone within a concentric distant zone and the second an inferior paracentral near zone, both having 2 D or 3 D less than the myopic correction (Figs. 37.10 and 37.11). Overall, greater regression occurred with greater preoperative myopic refraction, and no improvement of uncorrected near vision was achieved in eyes with more

• Fig. 37.9

  When the planned optical zone (OZ) diameter is reduced, the gradient of curvature is spread over a shorter radius. For the same pupil diameter, increased multifocality is expected from this reduced OZ diameter for the same entrance pupil diameter.

than 6 D of preoperative myopia. A gain in lines of uncorrected near visual acuity was obtained in lower myopes. Visual disturbances—such as glare, halos, and monocular diplopia—occurred only within the first 6 months postoperatively. Anschütz also studied results of the treatment of hyperopia–presbyopia using an inferior sectoral zone of ablation to induce an additional paracentral zone of steepening. Results showed the same trend as for myopic– presbyopic patients, with greater mean regression in higher hyperopes and disappearance of visual disturbances within 6 months postoperatively. Four emmetropic eyes were involved in that study, with an uncorrected near visual acuity of 20/30 at 18 months follow-up and a postoperative spherical equivalent change of −0.25 D to −0.75 D. In 1998, Vinciguerra et al44 published their study involving zonal PRK for treating presbyopia. They used an inferior semilunar ablation for an intended correction of 3 D of presbyopia. The three patients involved showed a regression of 1 D followed by stabilization of the presbyopic correction; they could read Jaeger 3 at 35 com without correction. Contrast sensitivity was not significantly reduced. Bauerberg used LASIK to compare the effect of center and off-center ablation in 16 eyes of eight patients with hyperopia–presbyopia.45 At 12 months, the off-centered ablation eyes achieved uncorrected near visual acuity of 20/30 or better with no loss of Snellen lines. The centered ablation eyes had uncorrected near visual acuity of 20/40 or better, with two eyes experiencing loss of 1 Snellen line. No glare was reported, but two eyes had induced astigmatism. Subjectively, six patients preferred the eccentric inferior ablation for near vision and two noticed no difference.

CHAPTER 37  Multifocal Corneal Surgery for Presbyopia

• Fig. 37.10  Schematic representation of myopia–presbyopia photorefractive keratectomy with central near zone.

In aberrometric language, this relative increase of refractive power at the center of the pupil with respect to its periphery (or the relative decrease of refractive power at the pupil periphery) translates into an increase in negative spherical aberration (see Fig. 37.6). It is important to keep in mind that, in this context, negative spherical aberration must be accompanied by selective central pupil myopia to provide the operated eye with efficient multifocality. To better understand this constraint, consider a presbyopic eye in which the central pupil portion would be emmetropic, and for which consistent amounts of negative spherical aberration would be found using aberrometry measurement. This eye would only be able to attain satisfactory uncorrected distance visual acuity and may suffer from night halos due to the relative hyperopia present within the peripheral pupil area. Satisfactory uncorrected near vision would not be possible owing to accommodation power being insufficient in a presbyopic eye, as no rays emitted by a near source would be focused at the retinal plane. Changing the Ocular Spherical Aberration With Laser Corneal Ablation

• Fig. 37.11  Multifocal myopia–presbyopia photorefractive keratectomy with sectoral near zone.

Spherical Aberration and Multifocality in Practice

Ocular spherical aberration corresponds to a variation of the ocular power and can be manipulated to increase the ocular depth of field. However, some conditions are required to make spherical aberration a “useful aberration” in the context of presbyopia compensation. There is an obvious benefit to inducing a myopic defocus error at the center of the pupil to make the fovea conjugated with targets located at a reading distance. In such a situation, the paraxial pupil zone corresponds to the near zone, while the refractive power within the paracentral zone (midperiphery and extreme periphery of the pupil) can be reduced toward emmetropia. Placing the “near or reading zone” (inducing a myopic refraction) at the central area of the pupil enables one to take advantage of the near constriction effect of the pupil, which occurs when the eye tries to accommodate and gazes at a near target. The reduced vergence (progressive reduction of the myopic error) at the paracentral zone allows one to achieve a better uncorrected distance visual acuity than if the whole pupil area was myopic.

465

Ocular spherical aberration results from the balance between anterior corneal spherical aberration and internal (posterior corneal surface and crystalline lens) spherical aberration. Ocular spherical aberration is usually mildly positive and governed by the anterior corneal spherical aberration. Anterior corneal spherical aberration depends on the difference between the central and peripheral corneal curvature. A curved surface whose power gradually decreases or increases from its center to its periphery is said to be aspheric. The corneal profile of the human eye has negative asphericity; its curvature decreases from the apex toward the periphery. A geometric variable, named “Q,” can quantify the level of asphericity of the corneal contour modeled as an ellipse (Fig. 37.12). A negative Q value characterizes a prolate asphericity (the curvature decreases toward the periphery), whereas a positive Q value characterizes an oblate asphericity (the curvature increases toward the periphery). The local refractive power of the cornea depends on its local radius of curvature. For the same ray incidence, the lesser the curvature, the lesser the local refractive power. In most normal eyes, the reduction of the corneal curvature toward the periphery is not sufficiently pronounced to reduce the effect of the increase in the angle of incidence of peripheral rays with the corneal surface. Despite local curvature reduction toward the periphery (prolate profile, lesser keratometry toward the corneal periphery), the corneal power at the periphery of the cornea is still more pronounced than at its center; this explains why the physiologic spherical aberration of the cornea is slightly positive (Fig. 37.13). To increase positive spherical aberration, the corneal contour should be made less prolate aspherically or more oblate (less negative positive asphericity values). To cancel spherical aberration, the corneal asphericity should be, on average, more negative than what is found in most human

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corneas. Such a surface, derived from spherical aberration, is referred to as a Cartesian oval. To reverse the corneal positive spherical aberration to a negative value, the corneal asphericity must take a more negative value.

Schematically, two opposite strategies have been proposed to create a multifocal cornea depending on the location of the near addition zone.

Current Proposed Methods

The peripheral near addition zone relies on the realization of a steepening of the peripheral cornea for near vision using the central cornea for distance vision. The obtained corneal profile is oblate and generates positive spherical aberration. There is no risk of phototopic myopization with pupil constriction, since the near addition is delivered in the periphery of the optical zone (OZ). However, the pupil constriction observed during the accommodation convergence reflex may compromise the near vision acuity as the rays passing through the OZ periphery may be stopped by the iris.

From the results gathered among the community of presbyopia surgeons, multifocal corneal ablation procedures have provided superior results with hyperopes. This may be due to the inherent multifocality of hyperopic profiles of ablation, as well as the better acceptance of a compromise between far and near visual acuity by hyperopes as compared to myopes and emmetropes.

Peripheral Near Addition Zone

Distance to optical axis

Central and Paracentral Near Addition

Distance to apex

• Fig. 37.12  The asphericity of the cornea can be calculated by approximating the corneal profile of interest by a best-fit ellipse. The Q value is computed from the ratio of the respective lengths of the major axes of the ellipse. Left: Some theoretical profiles having the same paraxial curvature, but different asphericities, are shown.

Here, the goal of the treatment is to obtain a central, steepened zone for near correction and a peripheral zone targeted for distance. Excimer laser manufacturers have proposed their own variation around that strategy: aspheric ablation profile using the VISX STAR S4 or STAR S4 IR excimer laser system (Abbott Medical Optics), PresbyMax using the SCHWIND platform (SCHWIND eye-tech-solutions), aspheric micromonovision using the MEL 80 excimer laser (Carl Zeiss Meditec), and the Supracor algorithm using the Technolas 217P excimer laser (Technolas Perfect Vision GmbH).46-50 By increasing the optical power of the central pupil area, some negative spherical aberration (SA) is generated. Using adaptive optics, it was determined in one study that the mean optimal SA value determined by the dynamic simulation procedure to optimize depth of focus was −0.18 ± 0.13 µm at 4.5 mm. The impact of higher-order aberrations on depth of focus was investigated using an adaptive

SPHERICAL ABERRATION = VARIATION OF THE REFRACTIVE POWER FROM THE PARAXIAL AREA TO PERIPHERY

i’

i’

i

i

n Q = -0.2

n Q = -0.8

• Fig. 37.13  In this example, the paraxial powers of both corneas are identical and have the same refractive index (n), but the profiles have different asphericities. Spherical aberration depends on the value of the change in asphericity of the corneal profile. Left: The cornea is slightly prolate (Q = −0.2) and flattens toward the periphery. This flattening is not sufficient to cancel spherical aberration, which remains slightly positive. Right: The cornea is highly prolate (Q = −0.8). The important flattening reduces sufficiently the angle of incidence of peripheral rays to revert the sign of spherical aberration, which becomes negative.

CHAPTER 37  Multifocal Corneal Surgery for Presbyopia

However, the theoretical influence of the refractive correction does not significantly influence the value of the change in corneal asphericity necessary to induce the shift toward negative spherical aberration. To achieve a change of Δc40 = −0.4 µm on a 6-mm optical zone, an increase in prolateness of about ΔQ = 0.6 in corneal asphericity should be targeted, regardless of the positive spherical correction programmed in the laser, and of the value of the initial corneal asphericity (Q1; Fig. 37.14). To induce efficient multifocality in a presbyopic hyperopic eye, the following steps are suggested on the nondominant eye (Fig. 37.15): 1. Choose the custom Q mode as the treatment program. 2. Target emmetropia on the dominant eye, with no intended change in corneal asphericity. 3. Target a postoperative refraction of −2.50 D (e.g., if the initial distance correction is +2.25 D, enter +4.75 D for the sphere correction) on a 6-mm optical zone in the nondominant eye. 4. Increase prolateness by targeting a postoperative value Q2, such as Q2 = Q1 − 0.6. For example, if Q1 = −0.25, the target asphericity is Q2 = −0.85. The change in asphericity, which is the mechanism by which negative spherical aberration can be increased, results in a progressive reduction of the induced myopia from the paraxial zone to the pupil periphery through the paracentral zone.51 The clinical results of this multifocal strategy have

optics visual simulator. The imulation of positive or negative spherical aberration had the effect of enhancing depth of focus and resulted in linearly shifting the center of focus by 2.6 D/µm of error (6-mm pupil). Hence, this increase in depth of focus reached a maximum of approximately 2.0 D with 0.6 µm of spherical aberration.36 The level of ocular negative spherical aberration can be altered via the alteration of the corneal contour and some increase in negative asphericity (ΔQ). This is possible using the Wavelight Allegretto and EX500 excimer laser software (Alcon, Wavelight), via the “custom Q” mode. The value for the change in corneal asphericity (ΔQ) that could induce a variation Δc40 = −0.4 µm in spherical aberration on a 6-mm optical zone was computed.51 The theoretical preoperative and postoperative corneal profiles were modeled as ellipses, each having a specific apical radius of curvature (R1, R2) and asphericity (Q1, Q2, with ΔQ = Q2 − Q1). The change in refraction (D) was under the direct influence of the change in apical curvature (R1, R2) while the modification in the corneal asphericity (Q1, Q2) governs the change in spherical aberration (Δc40). The latter is also partly under the influence of the change in the apical curvature of the cornea: increasing the corneal curvature (i.e., steepening the cornea), without changing the asphericity of the corneal profile would result in an increase in the positive spherical aberration.

0.8 0.7

∆c40 =0

∆Q

0.6

(OZ = 6 mm)

0.5

∆40=0 Q0=0.1 ∆Z40=0 Q0=0 ∆Z40=0 Q=-0,1 ∆Z40=0 Q=-0,2 ∆Z40=0 Q=-0,3 ∆Z40=0 Q=-0,4 ∆Z40=-0,2 Q=0,1 ∆Z40=-0,2 Q=0 ∆Z40=-0,2 Q=-0,1 ∆Z40=-0,2 Q=-0,2 ∆Z40=-0,2 Q=-0,3 ∆Z40=-0,2 Q=-0,4 ∆Z40=-0,4 Q=0,1 ∆Z40=-0,4 Q=0 ∆Z40=-0,4 Q=-0,1 ∆Z40=-0,4 Q=-0,2 ∆Z40=-0,4 Q=-0,3 ∆Z40=-0,4 Q=-0,4

0.4 0.3 0.2

∆c40 = -0.2

0.1

-8

-7

-6

-5

-4

-3

-2

-1

0 -0.1 -0.2 -0.3

∆c40 = -0.4

-0.4 -0.5 -0.6

Correction (D) 0

1

2

3

4

5

6

∆Q ~ -0.6

-0.7 -0.8

• Fig. 37.14

To induce a reduction of spherical aberration of Δc40 = −0.4, the change theoretically required in corneal asphericity is close to Q ~ −0.6. This change is robust to the amount of positive sphere correction (D). The X axis represents the amount of sphere correction (from myopic corrections to hyperopic corrections). The Y axis corresponds to the value of the theoretical change in asphericity. The higher the intended change in spherical aberration, the larger the required change in corneal asphericity, which must always be planned toward increased prolateness in the case of positive (hyperopic) correction. (From Gatinel D, Azar DT, Dumas L, Malet J. Effect of anterior corneal surface asphericity modification on fourthorder Zernike spherical aberrations. J Refract Surg. 2014;30(10):708–715.)  

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shown that an uncorrected visual acuity of J2 and 20/30 can be obtained after the wound healing phase and that this would provide the patient with spectacle independence for distance and near vision.

Clinical Recommendations for Successful Multifocal Cornea During the preoperative screening of hypermetropic presbyopic patients, it is important to discuss with patients the limitations of current multifocal cornea treatments and physiologic and optical limitations that may interfere with success. Patients having unrealistic expectations of what can be achieved with current multifocal treatments should be excluded. The neuronal processing of multifocal images would influence the success and acceptability of the

procedure. Previous success with bifocal or multifocal contact lenses may be a good indicator of satisfactory neuronal processing capability. The patient should not expect to achieve optimum vision with multifocal ablation on the first day. The patient should be informed that vision may improve as the brain learns to select the desired image at the proper time. The patient should also be told that there is a possibility of needing a second enhancement procedure if the initial result does not meet expectations. For the myopic presbyopic patient, similar advice should be provided. Additionally, the limitations of extrapolating hyperopic data to myopic patients should be explained before consideration of myopic multifocal treatments. Patients still may have to compromise some near vision, some distance vision, or a little of each. The balance between the aberrations that reduce visual quality and the benefits of multifocality will dictate the success of the procedure

PREOPERATIVE STATUS

NONDOMINANT EYE

A

Distance correction: +2.00 D Near Add: +1.50 D Q: -0.20

DOMINANT EYE

Distance correction: +1.75 D Near Add: +1.50 D Q: -0.20

NONDOMINANT EYE

B • Fig. 37.15  (A) Example of preoperative refractive errors and Q values for a presbyopic hyperopic patient. (B) The nomogram for the nondominant eye is derived from the principles explained in this chapter for the nondominant eye. The induction of very prolate cornea results in a rapid reduction of the amount of induced negative defocus. The latter provides the nondominant eye with improved uncorrected near vision, while the peripheral demyopization reflected in the amount of negative spherical aberration reduces the number of lost lines for distance vision.

CHAPTER 37  Multifocal Corneal Surgery for Presbyopia

Postoperative result

DOMINANT EYE

NONDOMINANT EYE

Target Ref: -2.50 D Q: -0.80

C

Target Ref: -0.00 D Q: -0.20

Central myopia for near acuity Paracentral emmetropia for improved Distance acuity

Emmetropia for distance acuity Low DOF

 Increase in DOF

Profiles of ablation

NONDOMINANT EYE Target Q : -0.8

DOMINANT EYE

Target Q : -0.2

D Topo aberrometry result (OPDscan III) NONDOMINANT EYE

DOMINANT EYE

E • Fig. 37.15, cont’d

(C) Schematic representation of the expected postoperative result. (D) Representation of the ablation profiles for the dominant versus nondominant eye. Targeting a more prolate cornea causes the reduction of the peripheral depth of ablation. (E) Topographic and aberrometric comparison between the preoperative and postoperative data. Note the “myopic island” on the postoperative optical path difference (OPD) map of the nondominant eye (left). DOF, Depth of field.

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(Figs. 37.16 and 37.17). The choice of technique may be dictated by various factors, including the surgeon’s experience and the dominance and refractive status of the operated eye. The variations in size of pupil diameter in various lighting conditions should also be checked. Patients with a large scotopic pupil may be prone to worsened contrast sensitivity loss and night vision disturbances after the treatment. In general, patients involved in tasks such as night driving or working in scotopic or mesopic conditions must be warned of the potentially deleterious effects of the multifocal technique on their night vision quality. Some authors have claimed better results when slightly decentering the near central ablation nasally, therefore mimicking decentered ablation, while others recommended perfect pupil centration. Hyperopes often have a

more pronounced nasal pupil decentration, especially when constricted, which might favor slight nasal decentration for the near addition in this population. The use of topography-guided centration can be beneficial to customize the treatment centration of multifocal ablations by decentering the laser profile deliverance toward the corneal vertex.

Limitations of Current Treatments and Future Orientations Strategies that use the delivery of conventional treatments to achieve corneal multifocality may allow the overlap of the transition zone of the near addition profile on the distance OZ area.

• Fig. 37.16

  Left: Specular axial topography map. Right: Optical path difference (OPD) map of the right cornea of a 52-year-old patient who had laser in situ keratomileusis (LASIK) for hyperopia–myopia (ARK 10000, NIDEK) 3 months before. The preoperative refraction was 20/20 (+3), Jaeger 2 addition +2. Photoablation was delivered in two phases with the Technolas 217 excimer laser (Bausch & Lomb). First, the distance ametropia was treated using a +3 ablation delivered over a 5.5-mm optical zone (OZ) centered on the pupil. Then, an additional ablation of +2 D over a 3-mm OZ was decentered 1 mm inferiorly; uncorrected photopic 3 months postoperative visual acuity was 20/20 (distance) and Jaeger 3 (near). The axial topography map reveals an asymmetric inferior central steepening and an important gradient of axial powers from the central to the paracentral corneal area. The OPD map demonstrates the variation of refraction within the pupil area, which probably accounts for the satisfactory unaided near and distance visual acuity.

• Fig. 37.17  Wavefront high-order map, point spread function (PSF; left) and Zernike polynomial decomposition (right) of the same patient for a 5-mm pupil (OPD scan ARK 10000, NIDEK). Note the vertical elongation of the PSF, which reflects mainly the presence of comatic aberration.

CHAPTER 37  Multifocal Corneal Surgery for Presbyopia

Thus the final outcome may be difficult to predict owing to the complex interaction between the different treatment sequences, wound healing, and the differences between planned versus achieved corneal sculpting.52,53 The pupil position and diameter changes are neither evaluated nor taken into account in the establishment of the ablation profile. The relationship between the pupil diameter and the OZ, however, may be fundamental to determining the theoretical results of this strategy and account for the variable reported effects in practice. Wavefront mapping is not commonly used to assess the multifocal profile of ablation, and the expected result cannot be easily demonstrated to the patient. The multifocal profile of ablation is established from a simplified optical model in which the focal properties of the eye are assumed to depend on far and near correction dioptric values. Evaluating the induced multifocality on vergence maps rather than corneal topography maps may enable the clinician to better apprehend the effect of presbyLASIK procedures. Future multifocal treatment strategy will employ better ways of measuring the residual accommodation amplitude and its relations with the pupil dynamics as well as the whole eye total wave and corneal wave aberrations. These methods will certainly require the quantification of visual quality by analyzing the wavefront with pupil–plane metrics and/or the retinal image quality using image–plane metrics. Adaptive optics simulation of multifocality may help to determine subjectively how to use aberrations to expand the physiologic range of vision without significantly causing major loss of contrast and visual function.

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32. Applegate RA, Hilmantel G, Howland HC, et al. Corneal first surface optical aberrations and visual performance. J Refract Surg. 2000;16(5):507–514. 33. Tomidokoro A, Soya K, Miyata K, et al. Corneal irregular astigmatism and contrast sensitivity after photorefractive keratectomy. Ophthalmology. 2001;108(12):2209–2212. 34. Chalita MR, Xu M, Krueger RR. Correlation of aberrations with visual symptoms using wavefront analysis in eyes after laser in situ keratomileusis. J Refract Surg. 2003;19(6):S682–S686. 35. Rocha KM, Vabre L, Harms F, Chateau N, Krueger RR. Effects of Zernike wavefront aberrations on visual acuity measured using electromagnetic adaptive optics technology. J Refract Surg. 2007;23(9):953–959. 36. Rocha KM, Vabre L, Chateau N, Krueger RR. Expanding depth of focus by modifying higher-order aberrations induced by an adaptive optics visual simulator. J Cataract Refract Surg. 2009;35(11):1885–1892. 37. Tsubota K. Introduction. In: Tsubota K, Boxer Wachler BS, Azar DT, Koch DD, eds. Hyperopia and Presbyopia. New York, NY: Marcel Dekker; 2003:1–15. 38. Vinciguerra P, Camesasca FI. Surgical treatment options for hyperopia and hyperopic astigmatism. In: Tsubota K, Boxer Wachler BS, Azar DT, Koch DD, eds. Hyperopia and Presbyopia. New York, NY: Marcel Dekker; 2003:69–82. 39. Gatinel D. Corneal surface profile after hyperopia surgery. In: Tsubota K, Boxer Wachler BS, Azar DT, Koch DD, eds. Hyperopia and Presbyopia. New York, NY: Marcel Dekker; 2003: 141–150. 40. Chen CC, Izadshenas A, Rana MA, et al. Corneal asphericity after hyperopic laser in situ keratomileusis. J Cataract Refract Surg. 2002;28(9):1539–1545. 41. Jiménez JR, Anera RG, del Barco LJ, et al. Predicting changes in corneal asphericity after hyperopic LASIK. [Letter]. J Cataract Refract Surg. 2003;29(8):1468. 42. Gatinel D, Malet J, Hoang-Xuan T, et al. Corneal asphericity change after excimer laser hyperopic surgery: theoretical effects on corneal profiles and corresponding Zernike expansions. Invest Ophthalmol Vis Sci. 2004;45(5):1349–1359.

43. Anschütz T. Laser correction of hyperopia and presbyopia. Int Ophthalmol Clin. 1994;34(4):107–137. 44. Vinciguerra P, Nizzola GM, Bailo G, et al. Excimer laser photorefractive keratectomy for presbyopia: 24-month follow-up in three eyes. J Refract Surg. 1998;14(1):31–37. 45. Bauerberg JM. Centered vs. inferior off-center ablation to correct hyperopia and presbyopia. J Refract Surg. 1999;15(1):66–69. 46. Jackson WB, Tuan KM, Mintsioulis G. Aspheric wavefrontguided LASIK to treat hyperopic presbyopia: 12-month results with the VISX platform. J Refract Surg. 2011;27(7):519–529. 47. Uthoff D, Pölzl M, Hepper D, Holland D. A new method of cornea modulation with excimer laser for simultaneous correction of presbyopia and ametropia. Graefes Arch Clin Exp Ophthalmol. 2012;250(11):1649–1661. 48. Reinstein DZ, Carp GI, Archer TJ, Gobbe M. LASIK for presbyopia correction in emmetropic patients using aspheric ablation profiles and a micro-monovision protocol with the Carl Zeiss Meditec MEL 80 and VisuMax. J Refract Surg. 2012;28(8): 531–541. 49. Saib N, Abrieu-Lacaille M, Berguiga M, Rambaud C, FroussartMaille F, Rigal-Sastourne JC. Central presbyLASIK for hyperopia and presbyopia using Micro-monovision with the technolas 217P platform and SUPRACOR algorithm. J Refract Surg. 2015;31(8):540–546. 50. Leray B, Cassagne M, Soler V, et  al. Relationship between induced spherical aberration and depth of focus after hyperopic LASIK in presbyopic patients. Ophthalmology. 2015;122(2):233–243. 51. Gatinel D, Azar DT, Dumas L, Malet J. Effect of anterior corneal surface asphericity modification on fourth-order Zernike spherical aberrations. J Refract Surg. 2014;30(10):708–715. 52. Courtin R, Saad A, Grise-Dulac A, Guilbert E, Gatinel D. Changes to corneal aberrations and vision after monovision in patients with hyperopia after using a customized aspheric ablation profile to increase corneal asphericity (Q-factor). J Refract Surg. 2016;32(11):734–741. 53. Netto MV, Wilson SE. Corneal wound healing relevance to wavefront guided laser treatments. Ophthalmol Clin North Am. 2004;17(2):225–231.

38 

Corneal Implants and Inlays PUSHPANJALI GIRI, DIMITRI T. AZAR, ROLA N. HAMAM, AND JOHNNY M. KHOURY

Introduction Presbyopic corneal inlays are implanted in the corneal stromal tissue to increase the eye’s depth of focus and to correct presbyopia. The initial steps toward the development of present-day corneal inlays started with the use of alloplastic lenticules by José Barraquer in 1949, when he described the inclusion of a lenticule within the corneal stroma to modify ametropia.1 A newer generation of corneal inlays offers great potential for the treatment of presbyopia in a minimally invasive way by using the recent advances in femtosecond (FS) laser technology and more advanced inlay designs. Barraquer speculated that stromal lenticules would modify both the anterior curvature of the cornea and the cornea’s index of refraction. He experimented first with Flint glass lenses and later used transparent plastic (Plexiglas). Because all of the lenses were poorly tolerated by the cornea, he abandoned the use of alloplastic materials. The implants that Barraquer initially experimented with resulted in anterior stromal necrosis, followed by extrusion of the implants.1 However, the posterior layer of the cornea, situated behind the lenticule, remained transparent. In their search for an ideal intracorneal lens, Choyce, Belau, Knowles, Dohlman, Steinert and others experimented with different lens materials (Table 38.1). In 1961, Knowles investigated three polymers: polyethylene, polyvinylidine, and polypropylene.2 He consistently observed a degenerative process external to the plastic membrane regardless of the material or depth of placement in rabbit eyes. Most of the eyes developed a dense haze, frequently followed by a dimple or crater in the epithelial surface, with microscopic degeneration and disappearance of the substantia propria (Fig. 38.1). The absence of inflammation and the sharp localization of the defect anterior to the implant suggested the absence of toxic reaction to the plastics used. Knowles attributed the anterior stromal degeneration and crater formation to one of three causes: lack of nutrients from the aqueous humor, accumulation of toxic metabolites, or relative drying of the cornea lying anterior to the plastic. Belau et al. attempted to determine the most suitable material for an intracorneal lens, the most suitable surgical technique for its placement, and the change in refraction of

the eye produced by the lens.3 The following materials were used: polymethylmethacrylate (PMMA); PMMA coated with silicon monoxide; Dow Corning XR-63428, a silicone formed by heating and curing a mixture of equal parts of constituents A and B; and optical crown glass. Although silicone was the most suitable of the various materials used, the PMMA lens was generally well accepted. The best surgical techniques involved the use of a corneolimbal incision with or without a conjunctival flap. Most important, the finding of the study suggests a linear relation that would, with adequate data, make the refractive change predictable. In 1967, Dohlman et al. were the first to examine hydrogel intracorneal inclusions. By implanting discs of glyceryl methacrylate (GMA), containing 88% water, within the corneas of cats and rabbits, the authors investigated the tolerance of the stroma to GMA.4 The lenses were 4 mm in diameter, with thickness ranging from 0.19 to 0.57 mm. There was little or no inflammatory reaction in rabbit corneas, but the membranes slowly extruded within 3 months of the operation. The authors believed that this was related to the water permeability of GMA rather than to the toxicity of the lens material. The GMA implant was well tolerated in the cat cornea for the 11-month follow-up. In 1981, McCarey and Andrews demonstrated that highwater-content hydrogels were biologically compatible in rabbits.5 They also reported that the hydrogel lenticular implant was successful as a refractive keratoplasty implant material. The lenticules used were Permalens (Perfilcon-A), with a 6-mm diameter and a 0.23-mm thickness. Binder et al.,6 using various hydrogel lenses (containing 38%–79% water), have shown these materials to be compatible in nonhuman primates. In 1992, Werblin et al. reported the first human experience with the myopic Permalens hydrogel implantable collamer lens (ICL; 18-month follow-up).7 All surgeries were performed by Barraquer in Bogotá, Colombia. Excellent corneal clarity was reported throughout the follow-up period (Fig. 38.2). No decentration of the lenticule following implantation was observed. Corrections of up to −13 diopters (D) were achieved. Corrections deviated from the predicted correction by a mean of −5.00 ± −2.10 D (range, −2.80 to −8.00 D). Visual recovery was rapid, usually achieving maximum acuity within 1 month. The 473

474 se c t i o n X 474

Presbyopia Surgery

TABLE Materials Used for Alloplastic 38.1  Intracorneal Lenses Flint glass Plexiglas Polyethylene Polyvinylidine Polypropylene Silicone Glyceryl methacrylate Hydroxyethyl methacrylate Polysulfone Polymethylmethacrylate

• Fig. 38.1

  Histologic appearance of a crater in a formative stage, 32 days after insertion of the implant. (From Knowles WF. Effect of intralamellar plastic membranes on corneal physiology. Am J Ophthalmol. 1961;51:1146–1156, with permission from Elsevier.)

major problem was the significant undercorrection of the preoperative refraction. A longer follow-up was reported by Barraquer, in 1997, of five aphakic and five high myopic eyes with hydrogel implants. Corneal clarity was maintained after 6 years in all but one eye. Undercorrection was again observed by an average of 3.37 D ± 0.53 D at 1 month for aphakic eyes. No statistically significant difference was reported in the results of aphakic eyes at 1 month compared to 6 years postimplantation of the hydrogel ICLs. On the other hand, all myopic eyes showed continued regression of achieved correction at 1 month by an average of −7.06 ± 2.28 D in 72 months.8 The current understanding of tolerance of intracorneal inlays is that many variables play important roles in the surgical outcomes of intrastromal corneal inlays. These include biocompatibility of the material used, diameter and thickness of the inlay, corneal depth at which the inlay is

• Fig. 38.2  Hydrogel implantable collamer lens in a human subject 4 months postoperatively. The hydrogel appears as an optically void area at midstromal depth (dark arrows). One or two interface opacities can be seen (open arrow), but the overall appearance of the cornea is very clear. (From Werblin TP, Patel AS, Barraquer JI. Initial human experience with Permalens myopic hydrogel intracorneal lens implants. Refract Corneal Surg. 1992; 8(1):23–26, with permission from Slack, Inc.)

implanted, permeability of the inlay, pore number diameter, refractive index of the material used, power (diopters) and shape of the inlay, and the specific surgical technique used for inlay implantation. Determination of the predictability and long-term outcome of corneal inlay is of utmost importance. Intracorneal inlay material should not alter the posterior-to-anterior movement of water and nutrients. Furthermore, the implant should not interfere with the anterior-to-posterior movement of lactic acid from the epithelium. In addition, the stromal fluid pH, osmolarity, and stromal swelling pressures should not affect the stability of the lens material within the cornea. Ideally, the refractive power correction should be derived from the optics of the implant, comparable to intraocular lens (IOL) diopteric power correction within the aqueous, and the surgical procedure should be simplified by using a corneal flap.

Principles of Corneal Inlays There are three major refracting surfaces in the eye: the anterior corneal surface and the two surfaces of the

CHAPTER 38  Corneal Implants and Inlays

crystalline lens. The effect of the posterior corneal surface is negligible because the difference in refractive index between corneal stroma and aqueous humor is insignificant. The cornea, which has a refractive power three times that of the crystalline lens (approximately +43 D compared with +19 D for the crystalline lens), is an extremely important refracting element in the eye. The greater refractive power of the cornea is due to the difference in refractive index between air (1.000) and cornea (1.376) compared with the refractive index between aqueous and vitreous humor (1.336) and lens (1.406). Corneal inlays affect the refractive power of the cornea in three ways: by altering the radius of curvature of the anterior corneal surface, by altering the refractive index of the cornea, and by changing the depth of focus with small aperture optics. The corneal inlays that are available today are summarized in Table 38.2. Alloplastic materials whose refractive indexes approximate corneal stroma affect refraction only when used in combination with an anterior corneal flap. This causes a significant change in the anterior corneal curvature, thus providing the needed change in refraction.

FDA-Approved Corneal Inlays in Use KAMRA Inlay (Video 38.1) The first corneal inlay to gain US Food and Drug Administration (FDA) approval for use in vision correction surgery in April 2015, KAMRA inlay is an extremely light (lighter than a grain of salt) 3.8-mm, round mini-contact lens–like opaque corneal inlay that has a 1.6-mm opening in the center with a thickness of 5 µm. It is made of proven biocompatible material called polyvinylidene fluoride (PVDF) that is often used in a wide variety of eye and other medical implants (Fig. 38.3). It allows only focused light into the eye through the hole in the central aperture while obscuring the peripheral rays, thus increasing depth of focus. The

475

depth of focus at a point increases the smaller the aperture gets. The KAMRA inlay has been optimized to provide the best depth of focus and image quality for the human eye. It is placed within the stroma in the FS laser–created pocket on the visual axis. The first Purkinje image provides the reference for the placement centration for the inlay. The implantation of the KAMRA inlay does not cause any topographic changes since the inlay is placed relatively deep within the cornea. Although it does not affect distance vision, the KAMRA inlay is typically only implanted in the nondominant eye to provide near vision restoration without compromising the far and intermediate vision. This is done so that the combination of either the untouched eye or the eye corrected for great distance vision—in combination with the KAMRA implanted eye—can provide great near, intermediate, and distance vision by working together. The KAMRA inlay hopes to provide near, intermediate, and distance vision in a more stable, predictable and long-lasting way. The mechanism of how it facilitates accommodation in the presbyopic eye is shown in Fig. 38.4. Further, the existence of 8400 laser-etched openings in the KAMRA inlay provide maximum breathability and health to the cornea by allowing oxygen, nutrients, and water to pass through. Each of these 8400 laser-etched openings is 5 to 11 µm in diameter and is spread throughout the inlay in a random fashion. Because of these designs allowing metabolic homeostasis, the KAMRA inlay is able to avoid complications such as corneal melting or decompensation. As the KAMRA inlay is often close to the visible size of the physiologic pupil diameter, it minimizes apparent anisocoria as well. The KAMRA inlay implantation procedure typically takes less than 15 minutes, without the need for any stitches. The healing time varies by patient, from as little as a few days to longer. The KAMRA website lists the following points as important for use in the United States: 1. There may still be need for reading glasses after the KAMRA inlay implantation. 2. Some complications that can occur after the KAMRA inlay implantation include refractive problems, such as blurred vision, glare, halos, color disturbances, contrast sensitivity difficulties, night vision problems, double vision, and image ghosting, and other complications such as swelling, thinning, or inflammation of the cornea and infection. 3. The KAMRA inlay is a reversible procedure and can be removed; typically, the vision will return to the level prior to the implantation of the inlay.9

Indications and Contraindications for KAMRA Inlay Implantation

• Fig. 38.3

 

KAMRA Inlay.

The indications for the implantation of the KAMRA inlay include phakic or presbyopic patients with general good health and the desire to improve near vision through the mechanism of depth of focus extension. The patients can be between 45 and 60 years of age, who need near visual

2.0 mm

3.6 mm

Corneal reshaping inlay; hyperprolate

Refractive corneal inlay

80% water, made from hydrogel

Hydrophilic, acrylic (Hydroxyethyl methacrylate and methyl methacrylate), contains an UV blocker

Raindrop near vision

Flexivue microlens

LASIK, Laser in-situ keratomileusis; SMILE, small-incision lenticle extraction.

3.8 mm (outer)

Small aperture inlay

Diameter

Principle

Polyvinylidene fluoride (PVDF)

Material

KAMRA

Corneal Inlay

TABLE 38.2  Corneal Inlays Commercially Available Today

15-20 µm

32 µm

5 or 6 µm?

Thickness Lighter than a grain of salt

Weight

Center of the cornea, like multifocal lens/stromal tunnel created through SMILE; placement depth 280–300 µm

Under femtosecondcreated flap, allowing for adherence (residual stromal bed: > 300 µm below the flap; minimum placement depth: 150 µm)

Visual axis within the corneal stroma (residual stromal bed: ≥ 250 µm below the pocket; minimum placement depth: 170–200 µm)

Flap/Pocket Placement

1.6 mm (Placement over the first Purkinje image)

Central overlight constricted pupil

1.6 mm (Placement over the first Purkinje image)

Centration

1 day

A few days to longer

Healing Time

Combination with cataract surgery, intrastromal pocket creation, possible, peer-reviewed data available

Combination with LASIK possible, peer-reviewed data available

Combination with LASIK possible, peer-reviewed data available

Possibility of Combination With Other Refractive Procedures

2016

2007

Year of Development/ Approval

476 se c t i o n X 476 Presbyopia Surgery

CHAPTER 38  Corneal Implants and Inlays

477

A

B • Fig. 38.4  (A) Ray tracing diagram of image formation in the presbyopic eye without any inlay (https:// www.accessdata.fda.gov/cdrh_docs/pdf12/p120023d.pdf). (B) Ray tracing diagram of image formation in the presbyopic eye after the implantation of the KAMRA inlay. (From KAMRA Inlay Professional Use Information. https://www.accessdata.fda.gov/cdrh_docs/pdf12/p120023d.pdf. Accessed October 3, 2018.)22

correction of +1.00 to +2.50 D but do not need glasses or contact lenses for distance vision. The ideal patient should have a cycloplegic spherical equivalent refraction of +0.50 to −0.75 D, with less than 0.75 D of cylinder, less than or equal to 0.50 D in manifest refractive spherical equivalent in the last 12 months prior to the procedure, and with less than 1.00 D difference between the cycloplegic and manifest spherical equivalent refraction. Some contraindications for the implantation of the KAMRA inlay include severe dry eye, ectasia, keratoconus, residual stromal bed of less of 250 µm, active infection and inflammation of the eye, autoimmune or connective tissue disease, and uncontrolled glaucoma and diabetes. Some medications—such as antihistamines, beta blockers, and birth control pills—can worsen dry eye syndrome, while isotretinoin can change patients’ vision following KAMRA implantation.

KAMRA Inlay Safety and Efficacy In the pivotal study specifically designed to support FDA approval of the KAMRA inlay, the FDA specified the primary effectiveness criterion as the achievement of uncorrected near visual acuity (UCNVA) of 20/40 or better at 12

months by 75% of the implanted eyes (out of 508 eyes).10 After the follow-up of the subjects at postoperative 12 months, 24 months, 36 months, and 60 months, whereby 83.5%, 87.2%, 87.1%, and again, 87.1%, respectively, of the subjects had UCNVA of 20/40 or better, they concluded that the KAMRA inlay trial met the efficacy criteria. The FDA also assessed the safety of the inlay primarily based on three points: (1) changes in corrected distance visual acuity (CDVA), (2) the amount of astigmatism induced in the eyes implanted with the KAMRA inlay, and (3) the occurrence of adverse events in the subjects. The changes in CDVA were evaluated on the basis of two criteria: (1) occurrence of persistent loss of two or more lines of CDVA in less than 5% of the eyes at postoperative 12 months and (2) occurrence of CDVA worse than 20/40 in less than 1% eyes with preoperative 20/20 CDVA at postoperative 12 months. The astigmatism induction evaluation was based on less than 5% of eyes developing astigmatism of greater than 2.00 D from the baseline at 12 months postoperatively. Finally, the adverse events evaluation included occurrence of adverse events related to the inlay in no more than 5% of eyes, with any single adverse event occurring in no more than 1% of eyes.10 The major reported

Presbyopia Surgery

478 se c t i o n X 478

TABLE FDA Reported Major Postoperative Adverse 38.3  Events and Complications (n = 508 eyes)

At 12 mo (%)

At 24 mo (%)

At 36 mo (%)

Decrease in CDVA > 2 lines

3.3

5.5

5.9

Inlay removals

3

7.1

8.7

IOP increase > 10 mm Hg above baseline or > 25 mm Hg with clinical findings

3

3.1

3.3

DLK

1.2

1.2

1.2

Conjunctivitis

1

1.4

2

Inlay recentration

0.2

1.2

1.2

Adverse Event

CDVA, Corrected distance visual acuity; DLK, diffuse lamellar keratitis; FDA, US Food and Drug Administration; IOP, intraocular pressure.

postoperative events and complications in the FDA pivotal trial are shown in Table 38.3. We did a Pubmed search of all the published articles that reported the safety and efficacy of the KAMRA inlay, using the search words “KAMRA inlay” from the beginning of time until December 5, 2017. We found 10 papers that published the monocular uncorrected near visual acuity (UNVA), binocular UNVA, monocular uncorrected distance visual acuity (UDVA), and binocular UDVA of the KAMRA implanted patients, and calculated the weighted average of the UNVA and UDVA values preoperatively and at postoperative 3, 6, 12, 24, 48, and 60 months where available (Tables 38.4 through 38.7). If we follow the same efficacy criteria as the FDA did, we see that the KAMRAimplanted eyes pass the efficacy criteria of at least 75% of eyes having UNVA of 20/40 or better postoperatively at all follow-up time periods (Fig. 38.5A). The implanted eyes achieved a weighted average of 86.9%, 84.9%, 92.5%, 87.6%, 97%, 100%, and 82% at 3, 6, 12, 24, 36, 48, and 60 months, respectively. The weighted average of binocular Text continued on p. 485

120 Percentage of patients

100

A

80 60 40 20 0

20/20

20/25

20/30

20/32

20/40

J1 (%)

J2 (%)

J3 (%)

J4 (%)

J5 (%)

Preoperative

At 3 mo

At 6 mo

At 12 mo

At 24 mo

20/50

20/60

J6 (%)

At 36 mo

At 48 mo

At 60 mo

20/50

120

Percentage of patients

100 80 60 40 20 0

B

20/20

20/25

20/30

20/32

20/40

J1 (%)

J2 (%)

J3 (%)

J4 (%)

J5 (%)

Preoperative

At 3 mo

At 6 mo

At 12 mo

At 24 mo

At 36 mo

20/60

J6 (%) At 48 mo

At 60 mo

• Fig. 38.5  (A) Weighted average of monocular uncorrected near visual acuity (UNVA) preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months. (B) Weighted average of binocular UNVA preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months.

2016

2016

Moshirfar14

24

2015

2015

2015

2015

2015

Tomita26

Tomita26

Vilupuru27

Dexl28

2013

2012

2012

2012

2011

Tomita30

30

30

31

Weighted average

Yilmaz

Tomita

Tomita

Tomita

29

Tomita

26

Jalali

25

2016

2017

Moshirfar32

Moshirfar

Year

Study

Monocular UNVA

Turkey

Japan

Japan

Japan

Japan

Austria

USA

Japan

Japan

Japan

Switzerland

USA

USA

USA

Country

39

100

100

100

223

32

507

102

154

21

50

57

21

508

No. of Eyes

Emmetropic or post LASIK presbyopia

Myopic (simultaneous LASIK and inlay)

Emmetropic (simultaneous LASIK and inlay)

Hyperopic (simultaneous LASIK and inlay)

Presbyopic patients who previously had LASIK

Emmetropic presbyopic eyes

Presbyopic patients who underwent contrast sensitivity testing

(Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia

Presbyopia correction using FLASIK

Single site retrospective analysis, presbyopia

Simultaneous PRK and Inlay

Comparison of FDA safety and efficacy data between KAMRA and Raindrop

Treatment

TABLE 38.4  Monocular UNVA for the KAMRA Implanted Eyes

0

0

0

0

0

0

0

0

0

20/20

J1 (%)

4

0

0

0

0

0

4

0

20/25

J2 (%)

1.2

0

0

1

0

2

10

20/30

J3 (%)

3.8

0

1

1

0

16

14

20/32

J4 (%)

Preoperative

8.3

33

0

3

1

10

2

28

14

20/40

J5 (%)

Continued

20.5

4

6

19

44

70

19

20/50

J6 (%)

CHAPTER 38  Corneal Implants and Inlays

479

32

12

62.6

86.9

94.3

31

Tomita

Tomita

50.5

61

71

31

68

41

74

28

42

20/25

80.6

83

86

42

20/30

66

44

58

20/32

74.2

90

86

69

92

84.9

97

81

96

63

83

20/40

95.1

95

100

100

100

92

98

82

100

20/50

FDA, US Food and Drug Administration; LASIK, laser in-situ keratomileusis; PRK, photorefractive keratectomy; UNVA, uncorrected near visual acuity.

Weighted average

27.6

46

89.1

57

30

58.3

25

30

27.6

37

30

27

17

37

5

8

20/20

29

Tomita

Yilmaz

98

89

100

20/50

37

20/20

34

56

21

96

77

92

20/40

34

Tomita

Dexl

28

58

75

20/32

26

95

75

20/30

57

80

33

75

20/25

26

Vilupuru

Tomita

At 6 mo

26

Tomita

Tomita

Jalali

25

36

50

20/20

24

Moshirfar

At 3 mo

At 12 mo

60

84

43

61

76

69

20/25

71.8

62

71

86

88

20/30

80.8

86

75

81

100

20/32

92.5

97

90

92

100

93

20/40

95.6

93

97

100

95

20/50

J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)

Moshirfar14

Moshirfar

Study

Monocular UNVA

TABLE 38.4  Monocular UNVA for the KAMRA Implanted Eyes—cont’d

480 se c t i o n X 480 Presbyopia Surgery

2015 Japan

2015 Japan

2013 Japan

26

29

100

98

100

20/50

J6 (%)

70

20/20

J1 (%)

28.7

81.4

90.5

35.4

36

66.2

90

86.6

83.6

100

90.6

98.6

FDA, US Food and Drug Administration; LASIK, laser in-situ keratomileusis; PRK, photorefractive keratectomy; UNVA, uncorrected near visual acuity.

Weighted average

Yilmaz

31

Seyeddain

42.5

21

Tomita

98

88

75

20/40

J5 (%)

32 97

78

58

20/32

J4 (%)

29

90

50

20/30

J3 (%)

Tomita

77

61

50

20/25

J2 (%)

44

48

31

8

20/20

J1 (%)

26

100

100

20/40

J5 (%)

Tomita

97

83

20/32

J4 (%)

At 6 mo

0

0

65

92

92

20/30

J3 (%)

Emmetropic or post LASIK presbyopia

0

0

0

26

87

75

20/25

J2 (%)

At 3 mo

39

Emmetropic presbyopic eyes

Presbyopic patients who previously had LASIK

(Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia

Emmetropic presbyopic eyes

Presbyopic patients who underwent contrast sensitivity testing

Simultaneous PRK and inlay

20/20

Tomita

17

42

20/20

J1 (%)

2011 Turkey

24

223

102

154

21

32

507

21

No. of Eyes Treatment

Preoperative

70.7

97

55

71

85

90

20/25

J2 (%)

8.7

21

2

5

20/25

80.7

73

84

94

20/30

J3 (%)

44

12

14

22.5

94.9

100

85

100

100

95

20/32

J4 (%)

At 12 mo

23.1

28

14

20/32

97.7

94

100

100

97

20/40

J5 (%)

37.2

54

32

14

20/40

99.6

99

100

100

20/50

J6 (%)

19

19

20/50

J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)

26

Dexl

28

Vilupuru

27

32

23

Moshirfar

Study

Binocular UNVA

Weighted average

Yilmaz

31

Seyeddain

Tomita

Tomita

Tomita

2013 Austria

2015 Japan

26

2015 Austria

2015 USA

2016 USA

Year Country

26

Tomita

Dexl

28

Vilupuru

27

32

23

Moshirfar

Study

Binocular UNVA

TABLE 38.5  Binocular UNVA for the KAMRA Implanted Eyes

CHAPTER 38  Corneal Implants and Inlays

481

2015 Japan

2013 Japan

29

Tomita

Tomita

2012 Japan

2012 Japan

2011 Turkey

30

30

Tomita

Tomita

Tomita

31

Weighted average

Yilmaz

2012 Japan

30

2013 Austria

2015 Japan

26

Tomita

Seyeddain

2015 Japan

26

2015 Austria

2015 USA

2016 Switzerland

Tomita

27

2016 USA

Year Country

26

Dexl

28

Vilupuru

Jalali

25

32

24

Moshirfar

Study

Monocular UDVA

39

100

100

100

24

223

102

154

21

32

507

50

57

Emmetropic or post LASIK presbyopia

Myopic (simultaneous LASIK and inlay)

Emmetropic (simultaneous LASIK and inlay)

Hyperopic (simultaneous LASIK and inlay)

Emmetropic presbyopic eyes

Presbyopic patients who previously had LASIK

(Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia

Emmetropic presbyopic eyes

Presbyopic patients who underwent contrast sensitivity testing

Presbyopia correction using FLASIK

Single site retrospective analysis, presbyopia

No. of Eyes Treatment

TABLE 38.6  Monocular UDVA for the KAMRA Implanted Eyes

44.5

77

100

19

40

43

100

14

53

20/20

53

97

100

27

44

57

100

28

68

20/25

59.6

34

82

20/30

69.2

100

100

53

60

76

100

20/32

77.2

68

75

90

95

20/40

87.1

77

96

20/50

J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)

Preoperative

482 se c t i o n X 482 Presbyopia Surgery

At 6 mon

77.7

100

99

98

96

20/50

96

96

77

45

20/60 20/20

81.4

97

72.7

84.7

85

100

94

97

94.9

93

100

100

100

F-LASIK, Femtosecond–laser in-situ keratomileusis; LASIK, laser in-situ keratomileusis; UDVA, uncorrected distance visual acuity.

Weighted average

58.1

78

Tomita

Yilmaz

100

30

Tomita

31

88

30

Tomita

76

30

Seyeddain

98.2

93

100

100

99

75.2

84

Tomita 100

98

95

20/40

75 97

92

20/32

29

95.3

74

81

20/30

Tomita 87

82

69

65

20/25

82

78

66

54

42

20/20

26

89

98

93

20/50

Tomita

83.5

89

20/40

86

97

20/32

26

97

83

84

20/30

Tomita

82

79

77

20/25

At 12 mon

85.8

100

85

88

86

85

74

20/25

74

74

20/30

94.5

100

93

94

95

97

20/32

96.4

96

96

100

97

20/40

J1 (%) J2 (%) J3 (%) J4 (%) J5 (%)

26

Dexl

28

Vilupuru

32

57

27

49

20/20

25

Jalali

At 3 mon

J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%) J1 (%) J2 (%) J3 (%) J4 (%) J5 (%) J6 (%)

Moshirfar24

Study

Monocular UDVA

CHAPTER 38  Corneal Implants and Inlays

483

2015

2015

2013

2011

26

29

31

27

82.6

91.7

LASIK, Laser in-situ keratomileusis; UDVA, uncorrected distance visual acuity.

Weighted average

63.9

98.6

99.3

99

Tomita

Yilmaz

100

29

Tomita

31

98

100

20/20

26

100

99

20/50

J1 (%)

Tomita

100

98

20/40

J6 (%)

100

100

88

20/32

J5 (%)

Emmetropic or post LASIK presbyopia

99

100

98

100

100

20/25

99.5

100

99

100

100

20/32

J4 (%)

At 12 mo

J2 (%)

Presbyopic patients who previously had LASIK

(Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia

Emmetropic presbyopic eyes

Presbyopic patients who underwent contrast sensitivity testing

Treatment

26

100

75

20/25

J4 (%)

At 6 mo

39

223

102

154

21

32

507

No. of Eyes

Tomita

100

48

20/20

J2 (%)

Turkey

Japan

Japan

Japan

Japan

Austria

USA

Country

26

Dexl

28

Vilupuru

Study

Binocular UDVA

Weighted average

Yilmaz

Tomita

Tomita

Tomita

J1 (%)

2015

Tomita

26

2015

28

26

2015

Vilupuru27

Dexl

Year

Study

Binocular UDVA

TABLE 38.7  Binocular UDVA for the KAMRA Implanted Eyes

100

100

100

100

20/40

J5 (%)

100

100

100

20/20

J1 (%)

100

100

20/20

J1 (%)

At 24 mo

100

100

100

20/25

J2 (%)

Preoperative

100

100

20/25

J2 (%)

100

100

100

20/32

J4 (%)

484 se c t i o n X 484 Presbyopia Surgery

CHAPTER 38  Corneal Implants and Inlays

UNVA is no less than 88% at all follow-up periods (Fig. 38.5B). The weighted averages of monocular and binocular UDVA preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months are shown in Fig. 38.6A, and Fig. 38.6B, respectively. Thus overall, the KAMRA inlay appears to provide significant improvement in UCNVA without significantly impacting the distance visual acuity negatively. A note must be made, however, that AcuFocus has sponsored all currently published studies. In terms of safety measurement through changes in CDVA postoperatively, following the FDA criteria, the implanted eyes showed good efficacy at all postoperative evaluation except at 60 months (Fig. 38.7). These changes in Snellen lines at various postoperative periods of 3, 6, 12, 24, and 60 months were also found by calculating the weighted averages of changes in Snellen lines reported by 6 published studies on Pubmed (Table 38.8). At 60 months, 18.8% of eyes showed loss of two or more Snellen lines of CDVA. Only one study has been published to date with

follow-up of 5 years. At 12 months postoperatively, 11.8% of implanted eyes gained one Snellen line of CDVA and 2.6% of eyes gained two Snellen lines of CDVA. Only one study has been published so far in the literature comparing the stereoacuity before and after KAMRA inlay implantation. Linn et al.11 report no significant change in stereoacuity; they therefore conclude that the inlay is good for improving near vision in presbyopic patients while preserving distance vision and stereoacuity. In terms of contrast sensitivity, Vilupuru et al.12 reported no loss of binocular contrast sensitivity in both mesopic and photopic conditions for 507 KAMRA-implanted eyes. In fact, the KAMRA-implanted eyes showed superior contrast sensitivities. Seyeddain et al.13 reported a statistically significant difference in mesopic and photopic contrast sensitivity measurements in KAMRA-implanted eyes between preoperative and postoperative evaluations. These differences were reported at higher spatial frequencies, however.

120

Percentage of patients

100 80 60 40 20 0

A

20/20

20/25

20/30

20/32

20/40

J1 (%)

J2 (%)

J3 (%)

J4 (%)

J5 (%)

Preoperative

At 3 mo

At 6 mo

At 12 mo

At 24 mo

At 36 mo

20/50

20/60

J6 (%) At 48 mo

At 60 mo

120

Percentag of patients

100 80 60 40 20 0

B

20/20

20/25

20/30

20/32

20/40

J1 (%)

J2 (%)

J3 (%)

J4 (%)

J5 (%)

Preoperative

At 3 mo

At 6 mo

At 12 mo

485

At 24 mo

At 36 mo

20/50

20/60

J6 (%) At 48 mo

At 60 mo

• Fig. 38.6  (A) Weighted average of monocular uncorrected distance visual acuity (UDVA) preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months. (B) Weighted average of binocular UDVA preoperatively and at postoperative 3, 6, 12, 24, 36, 48, and 60 months.

29

32

2015 2015

26

159

9

7

2

1

1

0 1

FDA, US Food and Drug Administration; LASIK, laser in-situ keratomileusis; CDVA, corrected distance visual acuity.

Weighted average

5

2 32

78

81

Tomita

1

14

18

Gain of 1 Line

Loss of 2 or More Lines

2

0

0

1

0

No Change

Gain of 2 or More Lines

26

4

0

Loss of 1 Line

Tomita

86

4

Loss of 2 or More Lines

At 6 mo

33

15

8

10

Loss of 1 Line

222

62

81

81

No Change

At 12 mo

32

19

8

5

Gain of 1 Line

(Age 60–65) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 50–59) Simultaneous LASIK and KAMRA for hyperopic presbyopia

(Age 40–49) Simultaneous LASIK and KAMRA for hyperopic presbyopia

Emmetropic presbyopic eyes

Presbyopic patients who previously had LASIK

Emmetropic presbyopic eyes

Comparison of FDA safety and efficacy data between KAMRA and Raindrop

Single site retrospective analysis, presbyopia

Treatment

0

11

86

Gain of 1 Line

Gain of 2 or More Lines

102

154

21

24

223

32

508

57

No. of Eyes

26

32

11

No Change

At 3 mo

Japan

Japan

Japan

Austria

Japan

Austria

USA

USA

Country

Tomita26

Seyeddain

Tomita29

Dexl

28

0

Moshirfa24

Moshirfar

0

Study

22

Loss of 2 or More Lines

Changes in Snellen Lines for Monocular CDVA

Weighted average

Tomita

Tomita

Loss of 1 Line

2015

Tomita

26

2013

2013

2015

26

Seyeddain

Tomita

Dexl

28

Moshirfar 2017

2016

Moshirfa24

22

Year

Study

Changes in Snellen Lines for Monocular CDVA

TABLE 38.8  Changes on Monocular CDVA for the KAMRA Implanted Eyes

486 se c t i o n X 486 Presbyopia Surgery

CHAPTER 38  Corneal Implants and Inlays

487

100 Percentage of patients

90 80 70 60 50 40 30 20 10 0

Loss of 2 lines Loss of 1 line No change Gain of 1 line Gain of 2 lines At 3 mo

At 6 mo

At 12 mo

At 24 mo

At 60 mon

• Fig. 38.7

  Weighted average of changes in Snellen lines for corrected distance visual acuity (CDVA) in the KAMRA implanted eyes at postoperative 3, 6, 12, 24, and 60 months.

Postoperative Complications for KAMRA Inlay According to the data published by the FDA, risks associated with the KAMRA inlay include visual, ocular, and contrast sensitivity issues already outlined early by KAMRA’s official website, as well as several others. These other risks include the possibility of need for additional time and effort in performing diagnostic tests, such as fundus photography, optical coherence tomography (OCT), binocular indirect ophthalmoscopy, and fluorescein angiography in patients with the KAMRA implanted; the danger of the development of a corneal scar when performing laser photodynamic therapy in implanted eyes; and the possibility of corneal infections, stromal thinning, corneal melting, endothelial cell loss, and inflammation.10 Yet other FDA report outlined additional risks, including the occurrence of the Pulfrich effect (misperceiving of direction, distances, speed, and location of moving objects due to the difference in the amount of light entering the untreated and the implanted eye), especially during the early postoperative period; chance for intraocular press (IOP) increase owing to postoperative steroid drops; earlier and greater impact of cataract in the implanted eye; and even some permanent vision loss after the inlay explantation.10 When simultaneous corneal inlay implantations are done with other refractive procedures, complications can occur. Hoopes et al.14 reported a case of thermal damage to the KAMRA inlay and closure of the nutritional holes owing to inadvertent touching of the inlay with the neodymium:yttrium aluminum garnet (Nd:YAG) laser beam during posterior capsulotomy. Therefore although the Nd:YAG spots are only temporarily visible, careful consideration must be made regarding laser treatments following inlay implantation. However, several successful reports of simultaneous KAMRA implantation with other refractive procedures, such as photorefractive keratectomy (PRK)15 and myopic and hyperopic laser in-situ keratomileusis (LASIK),16,17 have been published. Similarly, good

visual outcomes have been reported for the implantation of KAMRA inlays in eyes that have previously undergone procedures such as cataract surgery,18–20 LASIK,21 pseudophakia,22 and radial keratotomies.23 Good visual outcomes have been reported as well for other refractive procedures such as cataract surgery24,25 following KAMRA inlay implantation. The effect of simultaneous FS laser–assisted cataract surgery (FLACS) and KAMRA inlay implantation have also been investigated in porcine eyes.26 Among the list of postoperative complications reported in the literature for the KAMRA inlay are change in refractive status,27 infectious keratitis,28 cataract development,27 and occurrence of clusters of iron deposits near the Bowman layer.29 Yilmaz et al.27 reported four eyes needing explantation out of their study pool of 39 eyes. The reasons for explantation included the occurrence of buttonhole flap, thin flap, and refractive shifts (myopic shift of −2.00 D and hyperopic shift of +3.00 D). Inlay explantation is reported to be safe, with minimal changes in the corneal topography and aberrometry if removed before 6 months.30 Removal after 6 months may cause permanent changes. Yilmaz et al.27 also reported five eyes (out of 39 eyes) with cataract development and two eyes with change in refractive status. Cataract progression was to be expected in their study because the mean age of their subjects was 52 years and the authors did a long-term follow-up of 48 months.

Raindrop Inlay Raindrop near vision inlay is a 2-mm diameter, 32-µmthick transparent corneal inlay that is made up of approximately 80% water and made using hydrogel similar to soft contact lens (Figs. 38.8A 38.8B).31 The 80% aqueous content of the inlay has a similar refractive index to that of the cornea (1.373); it ensures effective diffusion and transfer of nutrients and oxygen throughout the cornea. The Raindrop inlay is typically placed under a thin FS laser–created flap and allowed to adhere in place. The flap is closed after

488 se c t i o n X 488

Presbyopia Surgery

A

B

C • Fig. 38.8

  (A) Raindrop inlay. (B) The Raindrop inlay is less than one-tenth of an inch in size, only 2 mm in diameter, smaller than the eye of a needle.46 (C) Illustration of the principle of the working mechanism of the Raindrop Inlay.47

inlay placement under the flap. Because the inlay works by increasing the curvature of the corneal surface, it should be placed under the flap close to the surface. However, its placement in the corneal pocket has also been studied. A diagram illustrating the principle by which the Raindrop inlay works is shown in Fig. 38.8C.32 The implantation is done in the nondominant eye to improve near vision, leaving the other eye untouched to achieve good vision at all distances by allowing good coordination between the implanted eye and the untouched eye. The gradient power with smooth transitions for near, intermediate, and distance vision is obtained through reshaping of the Bowman layer and anterior cornea. The reshaped cornea becomes hyperprolate in shape, which helps increase depth of focus. The Raindrop inlay implantation procedure is an outpatient procedure and usually takes just 10 minutes. Healing time is also quite short, allowing most patients to resume their normal activities the following day. The FDA approved the Raindrop inlay in June 2016, making it the second cornea inlay to be approved after the KAMRA inlay.

Indications and Contraindications for Raindrop Inlay Implantation Presbyopic patients desiring improved intermediate and near vision and meeting other criteria who may never have considered eye surgery options can benefit from corneal inlay procedures such as Raindrop. Patients aged between 41 to 65 years needing reading glasses of refractive powers within +1.50 and +2.50 D who do not need glasses for good distance vision and who have not had previous cataract surgery are good candidates for corneal inlays. The manifest refractive spherical equivalent for the ideal patient is between +1.00 D to −0.50 D with refractive cylinder of less than or equal to 0.75 D. Some contraindications for inlays are the presence of dry eye, aqueous deficiency and meibomian gland diseases, corneal ectasia, keratoconus, certain autoimmune or connective tissue diseases, recent herpes infection, uncontrolled glaucoma or diabetes, active infection or inflammation, and abnormal features on the outer part of the eye.31

CHAPTER 38  Corneal Implants and Inlays

489

TABLE 38.9  Monocular UNVA in Eyes with Raindrop Near Vision Inlay Implantation

Study

Year

Country

No. of Eyes

Follow-Up (mo)

J1 (%)

J2 (%)

J3 (%)

Moshirfar

2017

USA

373

24

67

88

95

Verdoorn

2017

Netherlands

16

4

63

79

Chayet

2013

Mexico

16

12

51

92

J4 (%)

J5 (%) 98 100

100

100

UNVA, Uncorrected near visual acuity.

Raindrop Inlay Safety and Efficacy Compared to the KAMRA inlay, relatively fewer studies have been published regarding the safety and efficacy of the Raindrop inlay. Three studies in Pubmed that published the monocular UNVA for the Raindrop implanted eyes are shown in Table 38.9. A study done by Moshirfar et al.33 (a report submitted to the FDA for the pivotal trial of the KAMRA inlay) made comparisons regarding safety and efficacy between the KAMRA inlay and the Raindrop inlay. Overall, the study reported that the Raindrop inlay met the targeted safety parameter of less than 5% of the study subjects, losing greater than or equal to two lines of CDVA at postoperative 24 months and beyond. After 2 years of implantation, 98% of the patients (total of 373 patients) were able to see with 20/40 vision or better at near distances and 67% were able to see with 20/20 vision or better at near distances. Compared to the efficacy shown by the KAMRA inlay at the same trial, these Raindrop results are actually even better than KAMRA’s, with 28% achieving UNVA of 20/20 or better and 87% achieving UNVA of 20/40 or better at postoperative 24 months. Another study comparing the safety and efficacy of the Raindrop inlay with monovision LASIK reported better near and distance visual acuities for the inlay compared to the LASIK procedure. The study reported 60% of inlay patients achieving UNVA of 20/20 or better versus 47% of LASIK patients, and 75% of inlay patients achieving UDVA of 20/32 or better versus 40% of the LASIK patients. In terms of binocular stereopsis, task performance, and patient satisfaction, the inlay group showed better outcomes than the monovision LASIK group, with the inlay group achieving 98 seconds of arc versus the LASIK group achieving 286 seconds of arc for stereopsis, and the inlay group showing patient satisfaction of 79% and 86% versus 66% and 67% for UNVA and UDVA, respectively.34 According to the studies conducted by Revision Optics, the Raindrop inlay met the goal of 75% of patients achieving 20/40 or better UNVA at postoperative 24 months by 92% of the subjects achieving the target UNVA and 87% achieving UNVA of 20/25 or better.31 They also reported refractive stability with a change in manifest refraction spherical equivalent (MRSE) within 1.00 D in at least 98% subjects and a change in MRSE within 0.50 D in at least 88% of the subjects between all consecutive postoperative

time points of 0 to 1, 1 to 3, 3 to 6, 6 to 9, 9 to 12, 12 to 18, and 18 to 24 months.32 ReVision Optics also reported that 98% of patients have been able to read a newspaper or equivalent (20/40 or better at a near distance), 88% of patients have been able to read fine print or equivalent (20/25 or better at a near distance) and 76% of patients have been able to read an onscreen email or equivalent (20/25 or better at an intermediate distance).31 Studies published in the literature have reported patient satisfaction rates of 82%35 and 90%36 in subjects who underwent Raindrop inlay implantation.

Postoperative Complications for Raindrop Inlay Although it provides some clear benefits, Raindrop inlay implantation has been reported to contribute to glare, halos, foreign body sensation, and pain, with a risk for developing infections, inflammation, new dry-eye syndrome or a worsening of existing dry-eye syndrome, retinal detachment, and a decrease in distance vision. Other complications that may result include corneal swelling, inflammation, thinning, clouding, and melting. ReVision Optics lists several complications that could result from the inlay implantation that include dry eyes, decreased vision, decreased contrast sensitivity, clouding, thinning, scarring, infection, and inflammation of the cornea, increased IOP, and the need for inlay explantation or another eye surgery. The major kinds of adverse events reported by ReVision Optics at postoperative 12, 24, and 36 months are shown in Table 38.10. Yoo et al. reported the occurrence of glare and loss of some night vision in approximately 40% of patients.35 Despite these complications, successful FS laser–assisted cataract surgery after Raindrop implantation has also been reported,37 with no interference to the visualization of intraocular structures during surgery, as well as improvements in UDVA and UNVA for patients. More such studies regarding refractive procedures after, simultaneously, and prior to the inlay implantation need to be conducted regarding the Raindrop inlay. More studies investigating the adverse events and safety and efficacy of the Raindrop inlay would provide additional insights into the nature of the inlay.

Presbia Flexivue Microlens Inlay The Flexivue microlens is a 3.2-mm wide hydrophilic acrylic refractive inlay with a 1.6-mm hole in the center, with

Presbyopia Surgery

490 490 se c t i o n X

TABLE 38.10  ReVision Optics Reported Major Postoperative Adverse Events and Complications (n = 373 eyes)

Adverse Event

At 12 mo (%)

At 24 mo (%)

At 36 mo (%)

Second surgical intervention

8.6

11

11.8

Inlay exchange

4.8

4.8

4.8

Inlay explant

3.8

6.4

7.2

Loss of CDVA ≥ 2 lines at 3 mo

2.1

2.7

2.9

Epithelial ingrowth

2.7

2.7

2.7

Ocular infection

1.1

1.3

1.9

Late onset haze beyond 6 mo with loss of 2 lines of BCVA

1.1

1.1

1.1

DLK

1.6

1.6

1.6

Increase in IOP > 10 mm Hg above baseline

1.3

1.6

1.6

BCVA, Best corrected visual acuity; CDVA, corrected distance visual acuity; DKL, diffuse lamellar keratitis; IOP, intraocular pressure.

• Fig. 38.9

 

Flexivue microlens.

power of the ring ranging from +1.5 to +3.5 D in increments of +0.25 D (Fig. 38.9). It is a crystal-clear refractive inlay, with its refractive index different from that of the cornea. The inlay material has refractive power of 1.4583 and improves the depth of focus by altering the path that the light rays take to the cornea. The wavelengths above 410 nm have transmission of 95% through the inlay material. In a similar manner to the multifocal lens, it creates a multifocal effect for good near to distance vision by sitting on the center of the cornea. It also creates a slight myopic shift, thus leading to a small amount of monovision. However, the monovision effect is not so extreme as to cause binocular disparity; neither is the multifocal effect so extreme as to cause glares at night. The central hole within the Flexivue microlens provides distance vision while allowing the free circulation of nutrients through the cornea from the anterior to the posterior part. It is implanted in the eye by inserting it into the opening in the periphery of the channel that is expanding from the area of the central

cornea to the peripheral cornea. An FS laser is used to create this kind of channel or pocket. Although sufficient data is not available yet, the Flexivue microlens may even be implanted through the stromal tunnel created during the minimally invasive small-incision lenticle extraction (SMILE) procedure. Like the KAMRA and Raindrop inlays, the Flexivue microlens is implanted on the nondominant eye. However, unlike the KAMRA inlay, which utilizes the pinhole effect of the camera to achieve the depth of focus, it offers optical correction depending on the refractive defect present. The learning curve is small for the Flexivue microlens, which makes it possible to learn the technique of its implantation within just 1 to 2 days of training. Further, this type of inlay does not affect dry eye, making it suitable for patients suffering with dry-eye syndrome. Still, patient selection is important to consider, especially since there is not sufficient data on the Flexivue microlens yet. Some contraindications for its implantation are keratoconus, significant corneal dystrophies, and significant astigmatism. In the United States, it is currently in phase III of clinical trials, although it received its Conformité Européenne (CE) mark in 2009 and is approved in 42 countries.

Flexivue Microlens Inlay Safety and Efficacy If we follow the FDA’s efficacy definition for KAMRA and Raindrop inlay approvals and apply the same definition to the Flexivue inlay, then several studies have reported favorable efficacy outcomes. At postoperative 12 months, 75% of patients (out of 47 subjects) showed UNVA of 20/32 or better in a report by Limnopoulou et al.,38 and 93% (out of 43 subjects) showed UNVA of 20/25 or better in a report by Bouzoukis et al.39 Although the study published by Limnopolou et al. showed a slight decrease in UDVA in implanted eyes, no statistically significant loss was noted for binocular UDVA. In terms of the visual outcomes for combined inlay implantation and refractive surgery procedures, excellent

CHAPTER 38  Corneal Implants and Inlays

near vision acuity and high patient satisfaction were reported in cases of simultaneous cataract surgery and Flexivue inlay implantation in a pilot study of 15 patients.40 The reported complications with the Flexivue Microlens inlay are halos, glare, and reduced uncorrected distance visual acuity.41 Because of these complications, the authors had to explant the inlays in six eyes (out of 81 eyes). Especially during the early postoperative period, the Flexivue inlay appeared to cause a low level of wound healing response in its immediate surroundings, as was evidenced by corneal inflammation, edema, and deposition of the degenerative material from in vivo confocal microscopy images. These intense cellular activities of wound healing response were observed to subside after 12 months, with no permanent change in corneal structures. Two cases of infectious keratitis have also been reported during the early postoperative stages of the Flexivue inlay implantation (postoperative 6 days for one case and 3.5 weeks for another case).28 These cases of infectious keratitis were reported to be caused by Corynebacterium pseudodiphtheriticum, which were treated by fortified antibiotics.

References 1. Barraquer JI. Modification of refraction by means of intracorneal inclusions. Int Ophthalmol Clin. 1966;6:53–78. 2. Knowles WF. Effect of intralamellar plastic membranes on corneal physiology. Am J Ophthalmol. 1961;51:1146–1156. 3. Belau PG, Dyer JA, Ogle KN, et al. Correction of ametropia with intracorneal lenses: an experimental study. Arch Ophthalmol. 1964;72:541–547. 4. Dohlman CH, Refojo MF, Rose J. Synthetic polymers in corneal surgery: I. Glyceryl methacrylate. Arch Ophthalmol. 1967;77: 252–257. 5. McCarey BE, Andrews DM. Refractive keratoplasty with intrastromal hydrogel lenticular implants. Invest Ophthalmol Vis Sci. 1981;21:107–115. 6. Binder PS, Deg JK, Zavala EY, et al. Hydrogel keratophakia in non-human primates. Curr Eye Res. 1981/1982;1:535–542. 7. Werblin TP, Patel AS, Barraquer JI. Initial human experience with Permalens® myopic hydrogel intracorneal lens implants. Refract Corneal Surg. 1992;8:23–26. 8. Barraquer JI, Gomez ML. Permalens hydrogel intracorneal lenses for spherical ametropia. J Refract Surg. 1997;13:342–348. 9. Is the KAMRA Inlay for Everyone? Kamra; 2018. https://kamra. com/kamra-inlay/is-kamra-inlay-for-everyone/. Accessed October 3, 2018. 10. AcuFocus. KAMRA Inlay Professional Use Information. https://www. accessdata.fda.gov/cdrh_docs/pdf12/p120023d.pdf. Accessed July 23, 2018. 11. Linn SH, Skanchy DF, Quist TS, Desautels JD, Moshirfar M. Stereoacuity after small aperture corneal inlay implantation. Clin Ophthalmol. 2017;11:233–235. 12. Vilupuru S, Lin L, Pepose JS. Comparison of contrast sensitivity and through focus in small-aperture inlay, accommodating intraocular lens, or multifocal intraocular lens subjects. Am J Ophthalmol. 2015;160(1):150–162. 13. Seyeddain O, Bachernegg A, Riha W, et al. Femtosecond laserassisted small-aperture corneal inlay implantation for corneal

491

compensation of presbyopia: two-year follow-up. J Cataract Refract Surg. 2013;39(2):234–241. 14. Hoopes PC Jr, Desautels JD, Moshirfar M, Linn SH, Mamalis N. Neodymium:YAG laser posterior capsulotomy in eye with an intrastromal inlay. J Cataract Refract Surg. 2017;43(5):699–702. 15. Moshirfar M, Wallace RT, Skanchy DF, et al. Short-term visual result after simultaneous photorefractive keratectomy and smallaperture corneal inlay implantation. Clin Ophthalmol. 2016;10: 2265–2270. 16. Igras E, O’Caoimh R, O’Brien P, Power W. Long-term results of combined LASIK and monocular small aperture corneal inlay implantation. J Refract Surg. 2016;32(6):379–384. 17. Jabbur NS, Awwad ST, Bashshur ZF. Sequential pars plana vitrectomy and cataract extraction with intraocular lens implantation in patient with corneal inlay who developed retinal detachment followed by cataract. J Cataract Refract Surg. 2017;43(4):570–571. 18. Eppig T, Spira C, Seitz B, Szentmary N, Langenbucher A. A comparison of small aperture implants providing increased depth of focus in pseudophakic eyes. Z Med Phys. 2016;26(2):159–167. 19. Huseynova T, Kanamori T, Waring GO IV, Tomita M. Smallaperture corneal inlay in presbyopic patients with prior phakic intraocular lens implantation surgery: 3-month results. Clin Ophthalmol. 2013;7:1683–1686. 20. Ziaei M, Mearza AA. Corneal inlay implantation in a young pseudophakic patient. J Cataract Refract Surg. 2013;39(7):1116–1117. 21. Tomita M, Kanamori T, Waring GO IV, Nakamura T, Yukawa S. Small-aperture corneal inlay implantation to treat presbyopia after laser in situ keratomileusis. J Cataract Refract Surg. 2013; 39(6):898–905. 22. Huseynova T, Kanamori T, Waring GO IV, Tomita M. Outcomes of small aperture corneal inlay implantation in patients with pseudophakia. J Refract Surg. 2014;30(2):110–116. 23. Huseynova T, Kanamori T, Waring GO IV, Tomita M. Smallaperture corneal inlay in patients with prior radial keratotomy surgeries. Clin Ophthalmol. 2013;7:1937–1940. 24. Tan TE, Mehta JS. Cataract surgery following KAMRA presbyopic implant. Clin Ophthalmol. 2013;7:1899–1903. 25. Moshirfar M, Quist TS, Skanchy DF, Linn SH, Desautels J, Hoopes PC Jr. Cataract surgery in patients with a previous history of KAMRA inlay implantation: A case series. Ophthalmol Ther. 2017;6(1):207–213. 26. Ibarz M, Rodriguez-Prats JL, Hernandez-Verdejo JL, Tana P. Effect of the femtosecond laser on an intracorneal inlay for surgical compensation of presbyopia during cataract surgery: scanning electron microscope imaging. Curr Eye Res. 2017;42(2):168– 173. 27. Yilmaz OF, Alagöz N, Pekel G, et al. Intracorneal inlay to correct presbyopia: long-term results. J Cataract Refract Surg. 2011;37(7): 1275–1281. 28. Duignan ES, Farrell S, Treacy MP, et al. Corneal inlay implantation complicated by infectious keratitis. Br J Ophthalmol. 2016; 100(2):269–273. 29. Dexl AK, Ruckhofer J, Riha W, et al. Central and peripheral corneal iron deposits after implantation of a small-aperture corneal inlay for correction of presbyopia. J Refract Surg. 2011;27: 876–880. 30. Alió JL, Abbouda A, Huseynli S, Knorz MC, Durrie DS. Removability of a small aperture intracorneal inlay for presbyopia correction. J Refract Surg. 2013;29(8):550–556. 31. https://www.revisionoptics.com/wp-content/uploads/2016/08/ Patient-Information-Brochure-710-0014-Rev-3-Artwork-FDAPatient-Information-Brochure-US_To-Print.pdf.

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32. https://www.revisionoptics.com/wp-content/uploads/2016/ 09/710-0015-Rev-6-Artwork-FDA-Professional-Information -Brochure-US.pdf. 33. Moshirfar M, Desautels JD, Wallace RT, Koen N, Hoopes PC. Comparison of FDA safety and efficacy data for KAMRA and Raindrop corneal inlays. Int J Ophthalmol. 2017;10(9):1446–1451. 34. Verdoorn C. Comparison of a hydrogel corneal inlay and monovision laser in situ keratomileusis in presbyopic patients: focus on visual performance and optical quality. Clin Ophthalmol. 2017;11:1727–1734. 35. Yoo A, Kim JY, Kim MJ, Tchah H. Hydrogel inlay for presbyopia: objective and subjective visual outcomes. J Refract Surg. 2015;31(7):454–460. 36. Garza EB, Chayet A. Safety and efficacy of a hydrogel inlay with laser in situ keatomileusis to improve vision in myopic presbyopic patients: one-year results. J Cataract Refract Surg. 2015; 41(2):306–312.

37. Parkhurst GD, Garza EB, Medina AA Jr. Femtosecond laserassisted cataract surgery after implantation of a transplant near vision corneal inlay. J Refract Surg. 2015;31(3):206–208. 38. Limnopoulou AN, Bouzoukis DI, Kymionis GD, et al. Visual outcomes and safety of a refractive corneal inlay for presbyopia using femtosecond laser. J Refract Surg. 2013;29(1):12–18. 39. Bouzoukis DI, Kymionis GD, Pangopoulou SI, et al. Visual outcomes and safety of a small diameter intrastromal refractive inlay for the corneal compensation of presbyopia. J Refract Surg. 2012;28(3):168–173. 40. Stojanovic NR, Feingold V, Pallikaris IG. Combined cataract and refractive corneal inlay implantation surgery: comparison of three techniques. J Refract Surg. 2016;32(5):318–325. 41. Malandrini A, Martone G, Canovetti A, et al. Morphologic study of the cornea by in vivo confocal microscopy and optical coherence tomography after bifocal refractive corneal inlay implantation. J Cataract Refract Surg. 2014;40(4):545–557.

39 

Multifocal Intraocular Lenses ANA BELÉN PLAZA-PUCHE AND JORGE L. ALIÓ

Introduction With extraordinary advances in instrumentation and techniques for refractive surgery, there are now many options for the surgical correction of myopia, hyperopia, and astigmatism. However, the surgical treatment of presbyopia remains a formidable challenge. While the ametropias reflect static incongruities in the eye’s optical system, presbyopia reflects an acquired loss of the eye’s dynamic function of accommodation. Thus while the surgical correction of ametropias requires only a static alteration in the optical system, the correction of presbyopia requires the restoration (or replacement) of a dynamic process frequently combined with the concomitant correction of ametropia. Therefore the surgical approach for presbyopia correction is a unique challenge. Common methods to address presbyopia include induction of myopia, induction of corneal multifocality, and scleral expansion and relaxation. However, the most promising approach is lenticular surgery with implants capable of providing spectacle independence for all vision distances (far, intermediate, and near) to increase the quality of life of the patient. One of the main treatment modalities for pseudophakic presbyopia is implantation of modern multifocal intraocular lenses (IOLs). The idea of using multifocality to compensate for the loss of accommodation dates back more than two centuries, when Benjamin Franklin invented bifocal glasses in 1784. Spectacle correction of presbyopia relies on the convergence component of the near triad (accommodation, convergence, and miosis) and the inferior field location of most near work. The translating multifocal contact lens designs use this as well, while the aspheric and concentric contact lens designs take advantage of miosis associated with near vision. Unlike spectacles, multifocal IOLs provide simultaneous focus of distant, intermediate, and near objects on the retina, allowing the higher levels of visual processing to determine which image to regard. Issues relating to the optics of multifocality, lens designs, clinical outcomes, and surgical considerations are discussed in this chapter.

Optics of Multifocality (Videos 39.1 and 39.2) For a multifocal IOL to provide good image quality at different distances, incoming rays of light with vergences corresponding to these distance (far, intermediate, and near) objects must be focused on the retina simultaneously. This is achieved through the use of two (or more) distinct focal points, with the primary focal point for distance focus and secondary focal points for near and intermediate foci. There are two basic design approaches that use different optical principles to achieve multifocality refractive and diffractive optics.1 The refractive symmetric multifocal lenses consist of multiple concentric radially symmetric zones that provide different focal lengths. By varying the curvature of the anterior or posterior surface of the lens, light is refracted differently by each zone. The zones can be either spherical or aspherical (Fig. 39.1). This type of IOL is dependent on pupil size.1 Refractive lenses with rotational asymmetry were introduced in 2009. The design of this type of lens includes a segment embedded in the lower half of the optic with the required optical power for near vision. The inferior segment has a progressive change of radius of curvature to provide adequate near vision (Fig. 39.2). Diffractive multifocal lenses (Fig. 39.3) achieve multifocality through the HuygensFresnel principle. Small gratings along the primary curve of the lens diffract light away from the primary (distance) focus toward a secondary (near) focus. The width of each diffraction grating becomes smaller as the distance from the center of the lens increases to provide higher angles of diffraction. By varying the size and pattern of the rings, the relative distribution of light energy and the location of the focal points can be specified. The pupil dependency varies among different IOL models. Recently, diffractive trifocal IOLs that provide three principal foci for distance, intermediate, and near vision became available for clinical use.1 Another recent IOL technology is the extended range of focus IOL technology that combines two complementary technologies: an echelette surface and an achromatic design. 493

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1. Distance vision Bright light 2. Near vision Bright to moderate light 3. Distance vision Moderate to low light 4. Near vision Full range of light 5. Distance vision Low light

1 2 54

3

• Fig. 39.3  Design of diffractive multifocal intraocular lenses. (From https://www.researchgate.net/figure/252417038_fig1_Figure-1 -Principle-of-operation-of-the-diffractive-refractive-IOL.) •

Fig. 39.1  Design of refractive symmetrical multifocal intraocular lenses. (From http://www.finemd.com/procedures/refractive_lens/rfe _ReZoom.html.)

aberrations at the pupil’s periphery to increase the depth of focus to generate progressive multifocality. Its optical design consists of three zones. The inner and middle zones have different spherical aberrations with opposite signs, whereas the outer one is a monofocal zone. Table 39.1 shows the most common multifocal IOLs available on the market.

In vitro Optical Quality

• Fig. 39.2  Design of refractive asymmetric multifocal intraocular lenses. (From https://www.researchgate.net/figure/261916560_fig2_Figure-1The-LS-312-MF30-hydrophilic-refractive-radially-asymmetric-IOL-Onthe-left.)

The former is a diffraction grating that extends the range of vision, and the latter corrects chromatic aberration to enhance contrast sensitivity. Formerly, a progressive multifocal aspherical IOL was introduced that utilizes an appropriate spherical aberration at the pupil’s center and corresponding higher-order

Measuring the optical quality of multifocal lenses on an optical bench has advantages compared to measurements performed in vivo, because limitations such as pupil size, corneal aberrations, and misalignments are avoided. The optical quality of multifocal IOLs in vitro can be evaluated through the modulation transfer function (MTF) measured on an optical bench2–5 or cross-correlation coefficients6 through the visualization of the image of a test chart produced by a multifocal IOL. Terwee et al.,7 Gatinel and Houbrechts,8 and Kim et al.6 were the first authors to provide such images. Cross-correlation coefficients quantify the similarity between the captured images and a perfect reference image. These coefficients have values of −1.0 to 1.0, with 1.0 being the quality of image of the perfect reference image. Many studies have assessed the optical quality of multifocal IOLs on an optical bench.9,10 These studies2–10 reported a better image quality for monofocal IOLs than multifocal IOLs for distance focus. Bifocal IOLs provided better image quality at near focus than monofocal and trifocal IOLs. Trifocal IOLs provided better image quality at an intermediate focus than bifocal and monofocal IOLs.

CHAPTER 39  Multifocal Intraocular Lenses

495

TABLE 39.1  Multifocal Intraocular Lenses (IOLs)

Lens (Manufacturer)

Lens Design

Material (Optic/ Haptic)

Size, mm (Optic/Total)

Asphericity

Implant Location

Add

AcriDIFF (Care Group)

Diffractive-refractive/ bifocal

Hydrophobic acrylic

6/12.5

Yes

Bag

+3.25

Acriva Reviol MF 613 (VSY Biotechnology)

Diffractive-refractive/ bifocal

Hydrophobic acrylic

6/13

Yes

Bag

+3.75

Acriva Reviol MFB 625 (VSY Biotechnology)

Diffractive-refractive/ bifocal

Hydrophobic acrylic

6/12.5

Yes

Bag

+3.75

Acriva Reviol MFM 611 (VSY Biotechnology)

Diffractive-refractive/ bifocal

Hydrophobic acrylic

6/11

Yes

Bag

+3.75

Acriva Reviol Tri-ED 611 (VSY Biotechnology)

Active-diffractive trifocal+EDOF/ achromatic

Hydrophobic

6.0/11.0

Yes

Bag

+3.00/+1.50

AcrySof IQ PanOptix (Alcon)

Diffractive/trifocal

Hydrophobic acrylic

6.0/13.0

Yes

Bag

+3.25 and +2.17

Acrysof IQ ReSTOR MN6AD1 (Alcon)

Diffractive, apodized/bifocal

Acrylic copolymer

6.0/13

Yes

Sulcus

+3.0

Acrysof IQ ReSTOR SN6AD1 (Alcon)

Diffractive, apodized/bifocal

Hydrophobic acrylic

6.0/13

Yes

Bag

+3.0

AF-1 iSii (Hoya)

Refractive

Hydrophobic acrylic

6.0/12.5

Yes

Bag

+3.0

AT LISA 809M/MP (Zeiss)

Diffractive/bifocal

Hydrophilic acrylic

6.0/11.0

Yes

Bag

+3.75

AT LISA tri 839MP (Zeiss)

Diffractive/trifocal

Hydrophilic acrylic

6.0/11.0

Yes

Bag

+3.33 and +1.66

Diff-aA and Diff-aAY (Humanoptics)

Diffractive/bifocal

Hydrophilic MicroCryl

6.0/12.5

Yes

Bag

+3.50

FineVision (PhysIOL)

Diffractive/trifocal

Hydrophilic acrylic

6.15/10.75

Yes

Bag

+3.50 and +1.75

iDIFF Plus 1-P and 1-R (Care Group)

Diffractive/refractive/ bifocal

Hydrophilic acrylic

6.0/11.0/12.50

Yes

Bag

+3.0, +3.50, +4.0

Lentis Comfort LS-313MF15 (Oculentis)

Refractive/bifocal

HydroSmart acrylate copolymer Hydrophobic surface

6.0/11.0

Yes

Bag

+1.50

Lentis Mplus LS-313 MF and Lentis MplusX LS-313 MF (Oculentis)

Refractive/bifocal

HydroSmart acrylate copolymer Hydrophobic surface

6.0/11.0

Yes

Bag

+3.0

M-flex 630-F and 580-F (Rayner)

Refractive/bifocal

Hydrophilic acrylic

6.25/12.50 5.75/12.0

Yes

Bag

+3.00/+4.00

Miniwell Ready (SIFI)

Refractive/ progressive/ EDOF

Hydrophilichydrophobic copolymer

6.0/10.75

Yes

Bag

—

ReZoom NXG1 (Abbott)

Refractive/bifocal

foldable acrylic

6.0/13.0

No

Bag

+3.50

Continued

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TABLE 39.1  Multifocal Intraocular Lenses (IOLs)—cont’d

Lens (Manufacturer)

Lens Design

Material (Optic/ Haptic)

Size, mm (Optic/Total)

Asphericity

Implant Location

Add

SeeLens (Hanita Lenses)

Diffractive adodized/ bifocal

Hydrophilic acrylic

6.0/13.0

Yes

Bag

+3.0D

Sulcuflex 653 F (Rayner)

Refractive/bifocal

Hydrophilic acrylic

6.50/14.0

No

Sulcus

+3.50

Tecnis MF ZKB00 (Abbott)

Diffractive/bifocal

Hydrophobic acrylic

6.0/13.0

Yes

Bag

+2.75

Tecnis MF ZLB00 (Abbott)

Diffractive/bifocal

Hydrophobic acrylic

6.0/13.0

Yes

Bag

+3.25

Tecnis MF ZMB00 (Abbott)

diffractive/bifocal

Hydrophobic acrylic

6.0/13.0

Yes

Bag

+4.00

TECNIS Symfony ZXR00

Achromatic/ diffractive/ echelette extend range of focus

Hydrophobic acrylic

6.0/13.0

Yes

Bag

—

VERSARIO (Bausch & Lomb)

Diffractive/bifocal

Hydrophilic acrylic

6.0/11.0

Yes

Bag

+3.75

VERSARIO 3F (Bausch & Lomb)

Diffractive/trifocal

Hydrophilic acrylic

6.0/11.0

Yes

Bag

+3.00 and +1.50D

Visual Acuity In a previous review of the literature from 2000 to 2016 by our group,11 the following visual outcomes were described. The mean monocular uncorrected distance visual acuity (UDVA) was better than 0.30 LogMAR in 100% and better than 0.10 logMAR in 70.6% of different types of IOLs evaluated. A binocular UDVA of 0.30 logMAR was achieved in 100% and better than 0.10 logMAR in 77.3% of different types of IOLs analyzed. Monocular UDVA was better than 0.10 logMAR in 57.1% and 73.7% of refractive and diffractive IOLs evaluated, respectively.11 The mean monocular uncorrected near visual acuity (UNVA) was better than 0.30 LogMAR in 92.6% of different types of IOLs estudied and better than 0.10 logMAR in 38.3% of different types of IOLs evaluated. The binocular UNVA was at least 0.30 logMAR and better than 0.10 logMAR in 97.3% and 62.16% of different types of IOLs studied, respectively. Monocular UNVA was better than 0.10 logMAR in 19.23% and 47.3% of the refractive and diffractive IOL groups evaluated, respectively.11 The mean monocular uncorrected intermediate visual acuity (UIVA) was better than 0.30 LogMAR and 0.10 logMAR in 95% and 22.5% of different types of IOLs analyzed, respectively. The binocular UIVA was better than 0.30 LogMAR and 0.10 logMAR in 96.0% and 32% of different types of IOL studied, respectively. The monocular UIVA was better than 0.10 logMAR in 19.23% and 47.3% of refractive and diffractive IOL groups evaluated, respectively.11

A meta-analysis by Rosen et al.12 reported visual outcomes after multifocal IOLs in emmetropic patients and a study by Alfonso et al.13 found a postoperative UDVA similar to the preoperative UDVA with a mean UNVA of 0.95 ± 0.07. In the study by Venter et al.,14 a rotationally asymmetric refractive IOL was implanted in 440 eyes of emmetropic presbyopic patients. No statistically significant change was found between the mean preoperative and postoperative UDVA. The mean UNVA was 0.13 ± 0.14 logMAR monocularly and 0.10 ± 0.12 logMAR binocularly. A Cochrane review comparing monofocal and multifocal IOLs found no difference in UDVA, with multifocal IOLs providing better UNVA.15

Depth of Field Pseudoaccommodation by multifocal IOLs is achieved by increasing the depth of field. Bench-top laboratory testing of multifocal IOLs has demonstrated a depth of field increase of approximately two- to three-fold over monofocal IOLs,16 with a difference of 3 to 5 diopters (D) between primary and secondary focal points.17 A previous publication from our research group18 analyzed the defocus curves obtained with two trifocal models (AT LISA tri 839MP [Zeiss] and FineVision [PhysIOL]), a bifocal model (ReSTOR SN6AD1 [Alcon]), and a monofocal model and reported differences among groups for defocus levels ranging from −4.00 D to +0.50 D. Comparing the trifocal IOL groups, differences in defocus levels ranging from −2.00 to +1.00 D were found with better

CHAPTER 39  Multifocal Intraocular Lenses

Contrast Sensitivity Two main testing methods are used to determine clinical contrast sensitivity. The first uses optotypes (letters) of varying size and contrast. As examples, the Pelli-Robson Letter Chart has a constant letter size with decreasing contrast, and the Regan Low Contrast Acuity Test has four charts of different contrast levels (96%, 50%, 25%, and 11%), each with similar lines of decreasing letter size. The second method involves sine-wave gratings of varying spatial frequency (in cycles per degree [cpd]) and decreasing contrast. These include the Vistech Vision Contrast Test System

(VCTS), the VectorVision CSV-1000, and the Functional Acuity Contrast Test (FACT). Rosen et al.12 found in a meta-analysis that one-third of the studies analyzed found no difference in contrast sensitivity between implanted multifocal and monofocal IOLs and two-thirds found reduced contrast sensitivity at the highest spatial frequencies for multifocal IOLs compared with monofocal controls, although contrast sensitivity outcomes generally remained within the age-matched normal range. A previous study by our group21 compared the low mesopic contrast sensitivity of different modern bifocal and trifocal designs of multifocal IOLs with that of a monofocal IOL and reported significant differences among the IOLs only for a spatial frequency of 18 cpd (Fig. 39.5). With this

–0.2

DEFOCUS CURVES Defocus Levels (D) –4.0 –3.5 –3.0 –2.5 –2.0 –1.5 –1.0 –0.5 0.0 0.5 1.0

–0.1

Visual Acuity (LogMAR)

visual acuity in the AT LISA tri 839MP group than in the FineVision group. Comparing bifocal IOLs and trifocal IOLs, differences in defocus levels ranging from −1.50 to -1.00 D were detected between the AT LISA tri 839MP and ReSTOR SN6AD1 groups with better visual acuity in the trifocal group. Differences were observed between the FineVision and ReSTOR SN6AD1 groups for a defocus level of +1.00 D. A visual acuity of 0.3 logMAR or better with all multifocal IOL designs was observed for defocus levels ranging from −3.00 to +1.00 D. These findings indicate that the multifocal IOLs analyzed provide good levels of visual acuity for the most important range of object distances (Fig. 39.4). Cochener compared a bifocal with a trifocal IOL and showed better intermediate visual acuity in the trifocal IOL group.19 Ruiz-Mesa et al.20 described similar defocus curves for an extended range of focus IOL and a trifocal IOL from 0 D to −2 D, but showed significant differences from −2.50 D to −4.00 D with better near visual acuity for the trifocal IOL.

0.0 0.1 0.2 0.3 0.4 0.5 0.6

AT LISA TRI MP839 FINEVISION RESTOR +3.00 ACRISMART 48S

0.7 0.8 0.9 1.0

• Fig. 39.4

  Defocus curve of different models of multifocal intraocular lenses. (From Plaza-Puche AB, Alio JL. Analysis of defocus curves of different modern multifocal intraocular lenses. Eur J Ophthalmol. 2016;26(5):412–417.)

Low Mesopic Contrast Sensitivity

2 1.8

Log Contrast Sensitivity Units

1.6 1.4 1.2 1 0.8 0.6 0.4 0.2 0 –0.2

• Fig. 39.5

AT LISA TRI 839MP FINEVISION LENTIS MPKUS-LS313 ACRI. LISA 366 RESTOR SN6AD1 MONOFOCAL IOL Normal Values Normal Values

1.5

497

3 6 12 Spatial Frequencies (CPD)

18

  Low mesopic contrast sensitivity of different models of multifocal intraocular lenses. (From Plaza-Puche AB, Alio JL, Sala E, Mojzis P. Impact of low mesopic contrast sensitivity outcomes in different types of modern multifocal intraocular lenses. Eur J Ophthalmol. 2016;26(6):612–617.)

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spatial frequency, the ReSTOR SN6AD1 presented significantly inferior values compared with the monofocal IOL. Despite these differences, the contrast sensitivities with all IOLs were within the normal range for the respective age samples.

Photic Phenomena (Glare and Halos) Halos and glare at night have been the most commonly reported visual symptoms after IOL placement, followed by dysphotopsia, shadows, and waxy vision.12 Up to 10% of patients reported visual symptoms or disabling glare, although low-level halos (minimal) were noted by a greater proportion. Three studies assessed photic phenomena quantitatively using halometry and found similar halo size between multifocal and monofocal IOLs21 with less than 1 degree of debilitating light scatter with a rotationally asymmetric refractive multifocal IOL22 and a marginally greater spread with a diffractive trifocal IOL.12,23

Spectacle Use In a previous review,11 a rate of global spectacle independence of 80% or higher was found in 48.7% of the studies analyzed. When object distances were differentiated, the following spectacle independence rates were reported: 80% or more in 91.6% of reports for distance, 100% for intermediate vision, and 70% for near vision.

Posterior Capsular Opacification Posterior capsule opacification (PCO) is a frequent longterm complication of IOL implantation. A Cochrane Review25 showed significantly higher PCO rates after hydrogel IOL implantation than after implantation of IOLs made of other materials, significantly lower PCO rates with sharp posterior optic edge IOLs than with round-edged IOLs, no difference between one-piece and three-piece IOLs, lower PCO rates with IOLs placed in the capsular bag than with those in the sulcus, and lower PCO rates in eyes with a small capsulorhexis than in those with a large capsulorhexis. A previous report comparing the frequency of posterior capsulotomies in patients with multifocal or monofocal IOLs showed that after an average 22-month postoperative follow-up, 15.49% of eyes in the multifocal group had required capsulotomies compared to 5.82% of eyes in the monofocal group.26 The main complaints of patients with multifocal IOLs and PCO are blurred vision and increased photic phenomena.

Patient Satisfaction and Quality of Life Overall patient satisfaction was found to be good with multifocal IOLs. De Vries et al.27 found that the most common symptoms of dissatisfaction with multifocal lenses were blurred vision in 94.7% of eyes and photic phenomena

in 38.2% of eyes. The causes of these symptoms were residual ametropia, PCO, large pupil size, and wavefront anomalies. Woodward et al.28 reported that the most common symptoms of patients with dissatisfaction were blurred vision in 95% of eyes and photopic phenomenon in 42% of eyes. In their study, blurred vision was related to residual ametropia, dry eye, and PCO. Photopic phenomena were associated with dry eye, IOL decentration, and PCO.11 Several reports showed better scores on quality-of-life questionnaires for near tasks with multifocal IOLs. However, better quality-of-life scores regarding glare or driving at night were reported for monofocal IOLs.29–31

Final Considerations It is very important to know the visual requirements of a patient before multifocal IOL implantation to choose the most adequate IOL design and obtain high levels of patient satisfaction. A complete and comprehensive preoperative examination is crucial to discriminate ocular pathologies that could influence the postoperative outcomes negatively. Preoperative treatment of pathologies such as dry eye should be considered prior to implantation of a multifocal IOL to achieve better patient satisfaction. It is essential to study the biometry, topography, and pupil reactivity to avoid patient dissatisfaction owing to residual refractive error, photic phenomena, poor pupil reaction, or extreme pupil size, either large or small. Also, it is very important to inform the patient of realistic visual expectations as well as possible postoperative complications and their management at the preoperative visit to avoid unanticipated patient disappointments in the postoperative period.

References 1. Alio J, Pikkel J. Multifocal Intraocular Lenses: The Art and the Practice. New York: Springer International Publishing; 2014. 2. Maxwell WA, Lane SS, Zhou F. Performance of presbyopiacorrecting intraocular lenses in distance optical bench tests. J Cataract Refract Surg. 2009;35:166–171. 3. Lang A, Portney V. Interpreting multifocal intraocular lens modulation transfer functions. J Cataract Refract Surg. 1993;19: 505–512. 4. Pieh S, Fiala W, Malz A, Stork W. In vitro Strehl ratios with spherical, aberration-free, average, and customized spherical aberration-correcting intraocular lenses. Invest Ophthalmol Vis Sci. 2009;50:1264–1270. 5. Montes-Mico R, Lopez-Gil N, Perez-Vives C, et al. In vitro optical performance of nonrotational symmetric and refractivediffractive aspheric multifocal intraocular lenses: impact of tilt and decentration. J Cataract Refract Surg. 2012;38:1657–1663. 6. Kim MJ, Zheleznyak L, MacRae S, et al. Objective evaluation of through-focus optical performance of presbyopia-correcting intraocular lenses using an optical bench system. J Cataract Refract Surg. 2011;37:1305–1312. 7. Terwee T, Weeber H, van der Mooren M, Piers P. Visualization of the retinal image in an eye model with spherical and aspheric, diffractive, and refractive multifocal intraocular lenses. J Refract Surg. 2008;24:223–232.

CHAPTER 39  Multifocal Intraocular Lenses

8. Gatinel D, Houbrechts Y. Comparison of bifocal and trifocal diffractive and refractive intraocular lenses using an optical bench. J Cataract Refract Surg. 2013;39:1093–1099. 9. Carson D, Hill WE, Hong X, Karakelle M. Optical bench performance of AcrySof IQ ReSTOR, AT LISA tri, and FineVision intraocular lenses. Clin Ophthalmol. 2014;8:2105–2113. 10. Madrid-Costa D, Ruiz-Alcocer J, Ferrer-Blasco T, et al. Optical quality differences between three multifocal intraocular lenses: bifocal low add, bifocal moderate add, and trifocal. J Refract Surg. 2013;29:749–754. 11. Alio J, Plaza-Puche AB, Férnandez-Buenaga R, Pikkel J, Maldonado M. Multifocal intraocular lenses: an overview [review]. Surv Ophthalmol. 2017;62(5):611–634. 12. Rosen E, Alió JL, Dick HB, Dell S, Slade S. Efficacy and safety of multifocal intraocular lenses following cataract and refractive lens exchange: Metaanalysis of peer-reviewed publications. J Cataract Refract Surg. 2016;42:310–328. 13. Alfonso JF, Fernández-Vega L, Valcárcel B, Ferrer-Blasco T, Montés-Micó R. Outcomes and patient satisfaction after presbyopic bilateral lens exchange with the ResTOR IOL in emmetropic patients. J Refract Surg. 2010;26(12):927–933. 14. Venter JA, Pelouskova M, Bull ELC, Schallhorn SC, Hannan SJ. Visual outcomes and patient satisfaction with a rotational asymmetric refractive intraocular lens for emmetropic presbyopia. J Cataract Refract Surg. 2015;41:585–593. 15. Cochener B, Lafuma A, Khoshnood B, Courouve L, Berdeaux G. Comparison of outcomes with multifocal intraocular lenses: a meta-analysis. Clin Ophthalmol. 2011;5:45–56. 16. Holladay JT, van Dijk H, Lang A, et al. Optical performance of multifocal intraocular lenses. J Cataract Refract Surg. 1990;16: 413–422. 17. Ravalico G, Paretin F, Sirotti P. Baccara F. Analysis of light energy distribution by multifocal intraocular lenses through an experimental optical model. J Cataract Refract Surg. 1998;24:647–652. 18. Plaza-Puche AB, Alio JL. Analysis of defocus curves of different modern multifocal intraocular lenses. Eur J Ophthalmol. 2016; 26:412–417. 19. Cochener B. Prospective Clinical comparison of patient outcomes following implantation of trifocal or bifocal intraocular lenses. J Refract Surg. 2016;32:146–151.

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20. Ruiz-Mesa R, Abengózar-Vela A, Aramburu A, Ruiz-Santos M. Comparison of visual outcomes after bilateral implantation of extended range of vision and trifocal intraocular lenses. Eur J Ophthalmol. 2017;27:460–465. 21. Plaza-Puche AB, Alio JL, Sala E, Mojzis P. Impact of low mesopic contrast sensitivity outcomes in different types of modern multifocal intraocular lenses. Eur J Ophthalmol. 2016;26:612–617. 22. Dick HB, Krummenauer F, Schwenn O, Krist R, Pfeiffer N. Objective and subjective evaluation of photic phenomena after monofocal and multifocal intraocular lens implantation. Ophthalmology. 1999;106:1878–1886. 23. Berrow EJ, Wolffsohn JS, Bilkhu PS, Dhallu S, Naroo SA, Shah S. Visual performance of a new bi-aspheric, segmented, asymmetric multifocal IOL. J Refract Surg. 2014;30:584–588. 24. Sheppard AL, Shah S, Bhatt U, Bhogal G, Wolffsohn JS. Visual outcomes and subjective experience after bilateral implantation of a new diffractive trifocal intraocular lens. J Cataract Refract Surg. 2013;39:343–349. 25. Findl O, Buehl W, Bauer P, Sycha T. Interventions for preventing posterior capsule opacification. Cochrane Database Syst Rev. 2010;(2):CD003738. 26. Taketani F, Matuura T, Yukawa E, Hara Y. Influence of intraocular lens tilt and decentration on wavefront aberrations. J Cataract Refract Surg. 2004;30:2158–2162. 27. De Vries NE, Webers CA, Touwslager WR, et al. Dissatisfaction after implantation of multifocal intraocular lenses. J Cataract Refract Surg. 2011;37:859–865. 28. Woodward MA, Randleman JB, Stulting RD. Dissatisfaction after multifocal intraocular lens implantation. J Cataract Refract Surg. 2009;35:992–997. 29. Shah S, Peris-Martinez C, Reinhard T, Vinciguerra P. Visual outcomes after cataract surgery: multifocal versus monofocal intraocular lenses. J Refract Surg. 2015;31:658–666. 30. Alió JL, Plaza-Puche AB, Piñero DP, Amparo F, Rodríguez-Prats JL, Ayala MJ. Quality of life evaluation after implantation of 2 multifocal intraocular lens models and a monofocal model. J Cataract Refract Surg. 2011;37:638–648. 31. Gomez ML. Measuring the quality of vision after cataract surgery. Curr Opin Ophthalmol. 2014;25:3–11.

40 

Refractive Surgical Procedures to Restore Accommodation JEAN-MARIE PAREL, FABRICE MANNS, ARTHUR HO, AND BRIEN HOLDEN

Introduction Presbyopia is the age-related loss of the eye’s ability to focus at near distances. The symptoms of presbyopia generally become perceptible at the age of around 40 years; by the age of 50 years, virtually everyone needs optical aids for reading or other activities that require near visual acuity. The enormity of the presbyopic population (according to current estimates, there are currently more than 1.3 billion presbyopes worldwide) and the associated size of the market for presbyopia-correction products are major driving forces for developments in this area. Additionally, now that laser in situ keratomileusis (LASIK) and other surgical approaches for the correction of myopia and hyperopia approach their maturity, the direction of refractive surgery is rapidly shifting toward presbyopia, which is considered by many to be the “final frontier” of refractive surgery.1 This new focus on refractive surgery is further motivated by continued refinements of cataract surgery techniques and intraocular lens (IOL) designs. The combination of these three factors (market potential, new focus on refractive surgery, and refinement of cataract surgery) has led to an explosion of research and development projects in the area of presbyopia correction. In this chapter, we will briefly discuss current approaches for the correction of presbyopia and present our work on the development of Phaco-Ersatz, a lens-refilling technique designed to restore accommodation.

Accommodation: The Helmholtz Theory Ocular accommodation is the ability of the eye to change its focus in response to a stimulus and thus provide sharp vision over a continuous range of distances, from a near point to a far point. The physiologic response to the accommodation stimulus is a complex optomechanical process that involves primarily the lens, lens capsule, zonules, and ciliary muscle, but is also affected by the biomechanical forces exerted by the ciliary body, choroid, vitreous, aqueous, and the corneoscleral shell. 500

Our current understanding of the mechanism of accommodation relies on the principles set forth by Helmholtz in the mid-1800s.2 According to Helmholtz’s theory, the change in power of the eye during accommodation results from a change in the curvature of the lens surfaces produced when the ciliary muscle contracts or relaxes. When the ciliary muscle is fully relaxed, the zonules are under tension and pull on the lens capsule. The resulting force produces a flattening of the lens surfaces, which brings the focus of the eye to the far point. When the ciliary muscle contracts, the tension on the zonules and capsule is relaxed. The lens takes on a more curved shape, which increases its optical power and shifts the focus to the near point (Fig. 40.1). Even though most of the scientific evidence available today supports the general principles of the Helmholtz theory, many aspects of the optical and mechanical response to the accommodation stimulus are still only partially understood. Examples of topics that are currently under active investigation include quantification of the dynamics of accommodation and disaccommodation,3–5 quantification of the optical structure of the lens and its changes during accommodation,6–12 and quantification of the forces involved in accommodation and their relation to the optical and biometric changes in the lens.13 The lack of a definite proof of Helmholtz’s theory has led to the formation of a number of alternate or complementary theories. Excellent reviews of the development of early theories of accommodation can be found in the classic textbooks of physiologic optics.14–16 Currently, the most notable of these include Coleman’s catenary theory,17–19 which attributes an important role to the vitreous and choroid, and the controversial theory of Schachar,20 which finds very few supporters in the ophthalmic research community.

Presbyopia: The Loss of Accommodation With Age Presbyopia is the age-related loss of accommodation (Fig. 40.2). The cause of presbyopia is most likely a combination

CHAPTER 40  Refractive Surgical Procedures to Restore Accommodation

Ciliary muscle relaxed

Zonular fiber under tension

Unaccommodated (distance vision)

Ciliary muscle contracted

Zonular fiber relaxed

Accommodated (near vision)

• Fig. 40.1  Accommodation according to Helmholtz’s theory. Contraction of the ciliary muscle during accommodation produces a relaxation of the zonular tension. This, in turn, produces a steepening of the lens surfaces and an increase in lens thickness.

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locked at the far point. This theory is strongly supported by anatomic and physiologic studies demonstrating that the ciliary muscle and zonules remain functional in normal subjects even in old age.21,22 The reason why the lens loses its ability to change its shape is still being debated. There is evidence that the lens becomes less compliant with age,23–25 but some argue that this loss of lens compliance could be a consequence rather than a cause of presbyopia.26 A number of alternative theories have been proposed over the years to explain presbyopia, including the current controversial description proposed by Schachar, based on his theory of accommodation. According to Schachar, presbyopia is due to the continuous growth of the lens with age, which progressively leads to crowding of the space between the ciliary muscle and the lens equator.27 Eventually, the distance between the zonular attachments at the ciliary body and at the lens equator becomes insufficient to allow a change of zonular tension when the muscle contracts or relaxes. Because of the lack of convincing scientific evidence to support this theory, it has very few proponents in the ophthalmic community.

Presbyopia Correction: an Overview The current approaches for presbyopia correction can be divided into three broad categories: • “traditional” optical approaches • pseudo-accommodating IOLs • techniques to restore accommodation

7

Accommodation (D)

6 5

Traditional Techniques

4 3 2 1 0 30

40

50

60

70

Age (years)

• Fig. 40.2

  The mean amplitude of accommodation as a function of age from 30 to 70 years, according to Duane. The amplitude of accommodation decreases steadily with age, starting at birth. The onset of presbyopia is at age 45 to 50 years, when the loss of accommodation starts affecting the ability to focus on near objects.

The first category includes traditional techniques relying on bifocal, multifocal, or progressive optical designs as well as monovision treatments. These corrections are achieved conventionally with spectacles or contact lenses, but multifocal IOLs and laser surgery of the cornea have also been employed. These traditional techniques, however, achieve their near power through sacrificing other aspects of optical performance. For example, bifocal spectacles sacrifice field of view for near power while monovision corrections trade binocular/stereoscopic performance for reading ability. While these strategies are the primary form of presbyopia correction, they do not replicate the full-field, full-aperture, continuously variable focus of the young crystalline lens.

Pseudo-Accommodating IOLs of age-related physical (optical, mechanical, and anatomic) and physiologic changes in the lens and the other anatomic structures of the accommodation system. However, there is strong evidence to support the hypothesis that presbyopia is due, for the most part, to a progressive loss of the ability of the lens to change shape. The aging crystalline lens is unable to change shape when the ciliary muscle contracts to relax the tension on the zonules and lens capsule. The focus of the eye (the optical conjugate of the retina) remains

The second category includes pseudo-accommodating IOLs, a new type of IOL specially designed to effect a change of ocular power when the ciliary muscle contracts or relaxes. As suggested by the prefix pseudo, these IOLs do not restore the normal accommodative function of the eye. Instead, they rely on an artificial optomechanical mechanism to increase the power of the eye and provide near vision. These IOLs can be implanted after extracapsular cataract extraction (ECCE).

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Relaxed

Relaxed

Accommodated

Accommodated

A

B • Fig. 40.3  (A) Principle of single-element accommodating intraocular lenses (IOLs). The implant is designed in such a way that contraction of the ciliary muscle produces a forward displacement of the optical element along the optical axis. The decrease in distance between the cornea and the implant produces an increase in the dioptric power of the two-lens system formed by the cornea and IOL. The dioptric power of the eye is increased and the point of focus therefore moves closer to the eye, thus simulating the optical effect of accommodation. (B) Principle of double-element accommodating IOLs. The implant is designed in such a way that contraction of the ciliary muscle produces a forward displacement of the frontal optical element along the optical axis. With two elements, there are different design configurations possible. For instance, the negative element can be placed in front and the implant could be designed so that the two elements are in contact in the accommodated state. The optical design affects the accommodative performance of the implant (From Ho A, Manns F, Evans S, et al. Third-order theory analysis of the spherical aberration of pseudo-accommodating IOLs. Invest Ophthalmol Vis Sci. 2005;46:e-abstract 819, © 2005 ARVO, with permission.)

In principle, the most obvious optical design for a pseudo-accommodating IOL is an implant that would change curvature when the ciliary muscle contracts or relaxes. The feasibility of incorporating this concept into a practical working design remains to be demonstrated. Instead, most current accommodating IOLs rely on an axial displacement of the implant to produce the desired change in power. The basic optical principle (Fig. 40.3) is the same as for a system of two lenses separated by a variable distance. In the case of a pseudo-accommodating IOL, the two lenses are the cornea and the implant. If we assume that the cornea (power PK) and accommodating IOL (power PIOL) are thin lenses separated by a distance d, then the paraxial power of the equivalent thick lens, which is the eye in this case, is given by Peq = Peye = PK + PIOL − d ⋅ PK ⋅ PIOL. Taking the derivative of this equation shows that if the distance, d, between the implant and the cornea decreases when the ciliary muscle contracts, the power of the eye will increase linearly with the amount of displacement as long as the power of the implant is positive: ∆Peye = − PK ⋅ PIOL ⋅ ∆d . For instance, with PK = 43 D and PIOL = 22 D (calculated using a modified version of the optical model of the eye

developed by Navarro et al.28), the power of the eye changes by 0.95 diopters (D) for each millimeter of displacement of the implant. This example shows that a large axial displacement of the implant, of at least 2 to 3 mm, is required to produce a 2 D to 3 D increase in power. Examples of implants employing this principle include the 1CU lens (HumanOptics) used in Europe and the Crystalens (formerly known as AT45; Bausch & Lomb), which was recently approved by the US Food and Drug Administration (FDA) and is now available commercially in the United States (Fig. 40.4A). Initial clinical results are mixed in terms of the amplitude of pseudo-accommodation.29–35 A number of alternative designs using two connected elements to increase the change in power have also been proposed (Fig. 40.4B).36 The long-term efficacy and visual benefit of these implants remain to be demonstrated, particularly with regard to how they affect posterior capsular opacification (PCO) and its treatment with lasers. Another potential issue with these implants is whether their ability to move will be affected by the long-term tissue response, which usually includes a contraction of the capsule due to fibrosis.

Restoration of Accommodation The third category of techniques to correct presbyopia includes all approaches that aim at restoring the ability of

CHAPTER 40  Refractive Surgical Procedures to Restore Accommodation

A

C

B

D

• Fig. 40.4

  Appearance of typical single element. (A) The Crystalens and double element accommodating intraocular lenses (IOLs). (B) The Hara IOL. (C, D) The Visiogen IOL.

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Softening the lens nucleus by photodisruption with a high-power pulsed neodymium:yttrium aluminum garnet (Nd:YAG) laser (photophako modulation) is an intriguing concept that was proposed by Myers and Krueger.47,48 Proof-of-concept experiments conducted on explanted cadaver lenses showed that application of laser pulses at energies above the threshold for bubble formation increased the elasticity of lenses from old donors. A team at the University of Hannover in Germany is currently further investigating this approach using femtosecond lasers.49,50 Unlike scleral expansion or lens softening, which leave the natural crystalline lens in place, the goal of lens refilling is to replace the contents (cortex and nucleus) of the presbyopic lens with a flexible material or implant. The first step of lens refilling is a modified ECCE technique designed to allow removal of the presbyopic lens content through a miniature opening in the lens capsule, on the order of 1 mm in diameter (mini-capsulorhexis). The intact empty capsular bag is then refilled with an artificial lens that ideally possesses the same biomechanical and optical properties as the natural young accommodating lens. This technique is discussed in further detail in the following sections of this article.

Lens Refilling the crystalline lens to change shape when the ciliary muscle contracts or relaxes. There are currently at least three different concepts being investigated, which are at different levels of development: • scleral expansion surgery • lens refilling • lens softening Of these, only scleral expansion surgery has been, and is still, used clinically. The goal of scleral expansion surgery is to expand the eye globe to increase the space between the lens equator and ciliary body. This concept is in accordance with Schachar’s controversial theory of accommodation and presbyopia, which attributes presbyopia to a crowding of the space between the lens equator and ciliary body. The initial scleral expansion technique was devised by Thornton,37 who performed relaxing corneoscleral incisions across the limbus. However, the wound healing response that follows the procedure causes a contraction of the tissue and eventually a closure of the incision, which manifests itself by a progressive regression of the initial effect. To avoid this regression, in an attempt to produce a permanent expansion, Fukasaku and Marron38 inserted soft silicone rubber implants in radial scleral incisions and Schachar developed a modified procedure that uses small rigid polymethyl methacrylate (PMMA) implants inserted in the sclera parallel to the limbus.39,40 There are several reports in scientific publications and meetings claiming that these scleral expansion procedures induce a significant temporary improvement in near vision,41 but more objective assessments have shown that scleral expansion does not have a statistically significant long-term effect and may be difficult to tolerate.42–46

The Development of Lens Refilling Early pioneering work, first by Julius Kessler51–53 and later by Agarwal and coworkers,54 suggested the feasibility of removing the lens contents and refilling the empty capsule with an optically similar substance. Kessler demonstrated the feasibility of this approach in Eye Bank eyes and showed that the refilled lens was well tolerated in a live rabbit model. Agarwal performed studies in the rabbit that confirmed Kessler’s findings. The scope and level of innovation of these studies is nothing less than extraordinary, considering that these attempts precede the advent of the modern cataract surgery techniques and instrumentation that we know today for almost two decades. In 1979, unaware of these initial studies, one of the authors of this chapter (Parel) introduced the concept of Phaco-Ersatz, a cataract surgery technique designed to restore accommodation (Figs. 40.5 and 40.6).55 PhacoErsatz is a direct lens-refilling procedure that involves removal of the lens material (nucleus and cortex) through a small opening in the capsule (mini-capsulorhexis) followed by injection of a suitable polymerized gel into the capsule through the same opening. During this procedure, the capsule, zonules, and ciliary body remain intact. Ideally, the properties of the polymeric gel are chosen to be equivalent to that of the young natural lens. With the help of modern technology and surgical instrumentation that were not available when Kessler and Agarwal conducted their pioneering studies, we were able to demonstrate feasibility of the surgical technique in cadaver eyes and its safety in live rabbits. In addition, we were able to demonstrate the

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B

A

C

D

• Fig. 40.5

  (A) Phaco-Ersatz concept. (B–D) Early results in the rabbit, demonstration of restored accommodation in the rhesus, explanted refilled lens. (From Parel JM, Holden BA. Accommodating intraocular lenses and lens refilling to restore accommodation. In: Azar DT, et al., eds. Intraocular Lenses in Cataract and Refractive Surgery. Philadelphia, PA: WB Saunders, 2001:313–324, with permission.)

technique,66 but the accommodation amplitude decreased with time, to reach less than 1 D after 1 year owing to a fibrotic tissue response that resulted in an encapsulation of the balloon and to a slow leakage of the balloon contents through the capsulorhexis into the anterior chamber. Nishi later modified his technique to allow direct refilling of the empty capsular bag and avoid the complications observed with the endocapsular balloon.67–69 Significant contributions to the development of the surgical technique of direct lens refilling were also made by the group of Lucke and Hettlich at the University of Luebeck in Germany, who proposed the use of intraoperative blue light–induced polymerization to avoid leakage of the injected material.70–74 Other surgical techniques and approaches for lens refilling have also been proposed.75,76 Together, these studies showed that lens refilling is a promising approach but also that a number of complex technical problems remain to be solved before lens refilling can become a clinical reality.

The Challenges of Lens Refilling Lens refilling is an appealing technique for the correction of presbyopia, because it draws on a well-founded theory of accommodation and presbyopia, builds on advances in modern cataract surgery, and aims at truly restoring accommodation. In addition, the preliminary studies demonstrate the merit of the approach. However, a number of technical issues remain to be addressed that make the clinical realization of the technique a challenging and inherently multidisciplinary project. Some of the issues are discussed in the following section. • Fig. 40.6

Current surgical steps for the Phaco-Ersatz procedure. Curing is performed using 400- to 450-nm blue light transmitted via a fiberoptic light guide.  

preservation of accommodation in a small study on young owl monkeys and, later, restoration of accommodation in the senile rhesus monkey.56–58 During that same time, Hara et al.59 and Nishi et al. in Japan published their first experimental results of lens refilling using a different approach: the endocapsular balloon.60–63 In this approach, following ECCE through a miniature capsulorhexis, a thin collapsed empty balloon is inserted into the empty capsular bag. A flexible material is then injected into the balloon through an umbilical tube until the balloon is filled. Nishi et al. developed an ingenious design to seal the capsule and cut the umbilical tube while avoiding leakage of material during the procedure.64 With this technique, they were able to restore up to 6 D of accommodation in a preliminary experiment on a live monkey. However, in a larger series of experiments, the average amplitude of restored accommodation was less than 2 D.65 Sakka and coworkers were later able to demonstrate more than 6 D of accommodation in the monkey using this

Surgical Technique The challenge of lens refilling surgery is to perform an ECCE while maintaining the capsule as intact as possible. During accommodation, it is the tension and relaxation of the capsule that determines the state of stress, and thus the shape, of the crystalline lens contents. Maintaining the integrity of the capsule is therefore a critical point if the accommodation response is to be maintained after lens removal. In addition, to avoid optical distortions in the retinal image, the opening must be performed at the periphery of the lens capsule. Instead of the traditional 5- to 6-mm diameter central anterior capsulorhexis, lens refilling requires a 1-mm diameter peripheral capsulorhexis. Creating such a small smooth circular opening requires special instrumentation and some surgical skill. But the challenge here is not so much to create a small hole in the capsule, but to be able to perform the lens extraction through that small opening (Fig. 40.7). Current phacoemulsification instruments have a diameter on the order of 1.5 to 2 mm. To be usable in lens refilling, the size of these instruments must be reduced by half. Until recently, the only systems that satisfied these size requirements were laser phacoemulsification probes. These systems are not as efficient as the standard ultrasonic probes and require a significantly longer surgery time. The

CHAPTER 40  Refractive Surgical Procedures to Restore Accommodation

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A

A

B

B

• Fig. 40.7

The 0.8- to 1.0-mm peripheral mini-capsulorhexis is either performed manually (A) with capsulorhexis forceps or using a custommade thermal capsule trephine (B). After placement of two side-ports, phacoemulsification is performed with a cold phaco (AMO) and cortex aspiration and bag polishing using a set of custom mini-cannulas or a mini-I/A. (Figure B from Parel JM, Holden BA. Accommodating intraocular lenses and lens refilling to restore accommodation. In: Azar DT, et al., eds. Intraocular Lenses in Cataract and Refractive Surgery. Philadelphia, PA: WB Saunders, 2001:313–324, with permission.)  

current trend in cataract surgery is to minimize the size of the corneal incision performed at the beginning of the ECCE procedure (small-incision surgery). This has led to the recent development of several miniature ultrasonic phacoemulsification probes powered by short-pulse, high peak power, low duty cycle radiofrequency generators, socalled cold-phaco, that are now available commercially, as well as new cataract surgery techniques that are suitable for lens refilling. Even though the miniature capsulorhexis required for Phaco-Ersatz surgery can be performed manually,77 to help reduce the learning curve of the procedure and decrease the duration of surgery we need a surgical instrument capable of making reproducible submillimeter capsule openings with uniform edges to help increase resistance to mechanical tears.

Material Most of the initial studies on lens refilling were conducted using off-the-shelf biocompatible materials that were not optimized in terms of their mechanical or optical properties. Probably the most formidable engineering challenge of lens refilling is to develop a material that mimics the optical and mechanical properties of the lens—including refractive index, transparency, and viscoelastic behavior, all together—while being safe and easy to inject. Materials

• Fig. 40.8

  (A) Ex-vivo accommodation simulator (EVAS). The globe is dissected and mounted on an eight-segment jig and placed in EVAS to record the crystalline lens, IOL implanted and refilled capsular bag diameter, thickness, and optical power in function of stretch distance. A retroilluminator and a slit illuminator (not shown) are used for videorecording and digital photography. EVAS can measure ciliary body and zonular load to approximately 0.25 g accuracy, lens diameters to less than ±0.1 mm, thickness to less than ±0.20 mm, and optical powers to better than less than ±0.5 diopter (D). (B) A charged coupled device camera attached to a digital vernier is moved up and down until the two beams produced by a 635-nm laser Scheiner system coincide on the focal plane of the lens, allowing determination of the optical power and accommodation amplitude. Lens power of 12 D to 100 D, hence all human and nonhuman primate crystalline lenses and all accommodative IOLs, can be assessed with this system.

used for lens refilling can be broadly divided into those with low index (n < 1.4), such as hydrogels, and those with high index (n > 1.4), such as siloxanes. A high index is advantageous because the lens is surrounded by aqueous media and the refractive power of the implant and, in turn, the amplitude of accommodation, will increase as the refractive index difference between the lens and the aqueous media surrounding it increases. While the desired optical properties of the material can be relatively easily characterized using optical modeling,78 determining the mechanical properties is much more challenging because of the lack of published data on the static and dynamic mechanical properties of the normal young crystalline lens and the difficulty in developing an accurate dynamic biomechanical model of lens accommodation. To address this issue, we13 and others24,79–82 have developed and/or used optomechanical lens-stretching systems based on the system originally devised by Fisher83 that allow us to simulate accommodation in normal and refilled explanted lenses while measuring lens equatorial diameter, power, curvature, and/or stretching forces (Fig. 40.8). The availability of these systems will be crucial not

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only to provide baseline data for the mechanical behavior of the Phaco-Ersatz implant but also to provide a better understanding of the optomechanics of lens accommodation in general. An additional practical challenge is to allow delivery of the material into the capsular bag without leakage through the capsulorhexis during or after implantation. If the material is too stiff or viscous, it will remain in the capsule but will not be injectable with a syringe. If it is too compliant, it will be easily injectable but will leak through the opening in the capsule during injection or after refilling. The solution that was adopted by most groups is to inject a lowviscosity precursor of the Phaco-Ersatz material that is polymerized in situ in the capsule to increase its stiffness after the injection is completed. But even with this approach, we still need to prevent leakage during injection and before the in situ polymerization is completed. Our current approach to providing a satisfactory trade-off between injectability and leakage prevention is to inject a polymer that is crosslinked in situ using blue light after sealing the capsulorhexis with a miniature capsulorhexis valve (MCV; Fig. 40.9). The MCV is a foldable polymer disk (valve) with a thin retaining segment. The MCV is introduced through the corneal incision into the capsulorhexis after the lens extrac-

A

The mini-capsulorhexis valve

C

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D •

E

F

Fig. 40.9  (A) Concept schematic of the mini-capsulorhexis valve (MCV). The MCV on the platform of the custom-made loading device (B), after insertion in the capsulorhexis (C) for safe lens refilling, immediately before cross-linking the polymer (D). The MCV can then be removed (E). A second-generation MCV made of transparent crosslinked trimethyl terminated siloxane can be left in situ (F). At POD 38, the proliferation of lens epithelium remnant produced fibrosis folds (*) in this 1-month-old animal. (Figures B, C, D, and E from Parel JM, Holden BA. Accommodating intraocular lenses and lens refilling to restore accommodation. In: Azar DT, et al., eds. Intraocular Lenses in Cataract and Refractive Surgery. Philadelphia, PA: WB Saunders, 2001:313–324, with permission.)

tion is completed so that the valve is positioned against the inner surface of the anterior capsule to seal the hole while the retaining segment rests on the outer surface of the capsule to hold it in place. The assembly allows the insertion of small surgical instruments into the capsular bag to complete the refilling surgery. After refilling, the ersatz material is cured through the MCV. The MCV can then be removed either in its entirety or only partially by cutting off the retaining members and leaving the disk in place.

Optics Ideally, the Phaco-Ersatz implant will not only restore accommodation but also provide a retinal image quality that is comparable to that of a young emmetropic eye. In other words, not only should the paraxial optical properties be taken into account but also both monochromatic and chromatic aberrations. These properties are determined by the shape and refractive index of the implant. The shape of the implant is determined by the volume of material injected in the empty capsular bag. Underfilling the bag produces an implant of low optical power and would result in hyperopia. Overfilling produces the opposite effect. The obvious question is then whether the volume or refractive index of the implant can be controlled with sufficient precision to accurately control the power of the implant. Optical modeling studies using a modified version of the Gullstrand and Navarro eye models78 show that precise control of the final refractive state based solely on the volume injected or the choice of refractive index is not feasible owing to a limited range of power achievable. In addition, the tolerances on volume or refractive index are too low to be achieved in practice. To address this issue, the concept of utilizing an adjustable supplemental endocapsular lens (SECL) has been introduced. The SECL would be a thin implant that can be placed in the capsular bag to adjust the refractive power and aberrations of the lens refilling implant. Preliminary experiments in our laboratory have demonstrated the feasibility of Phaco-Ersatz surgery with the addition of an SECL (Fig. 40.10). In any case, to avoid unintentional overfilling or underfilling of the capsular bag, a microscope-mounted automated refractometer that can be used intraoperatively must be designed to provide feedback that will allow the surgeon to decide when to stop injecting the material.

Secondary Cataract Perhaps the most challenging hurdle in the development of lens refilling is the need to avoid unwanted proliferation of lens epithelial cells (LEC). Epithelial cell proliferation leads to fibrosis and PCO. PCO is a common complication of the standard extracapsular cataract surgery technique employed today, in which the posterior capsule is preserved. The treatment of PCO after standard ECCE is a simple, safe, and very successful procedure that uses short pulses of a high-power laser beam tightly focused on the posterior capsule to create an opening in the central region of the posterior capsule.

CHAPTER 40  Refractive Surgical Procedures to Restore Accommodation

together with polymer chemists at the Commonwealth Scientific and Industrial Research Organization (CSIRO) of Australia, was established to further develop a surgical realization of the Phaco-Ersatz technique and address some of the remaining challenges of the Phaco-Ersatz procedure. This collaborative research effort has led to a number of refinements in surgical technique and significant advances in material development and encouraging results in lenses from Eye Bank eyes.84,85 Results of similar studies by several other groups are encouraging as well.79,80,86–96 While together these recent studies clearly demonstrate the potential of lens refilling as a technique to restore accommodation in experimental models, the refined surgical concept remains to be validated in a live primate model.

A

B

C

507

D

•

Fig. 40.10  The supplementary endocapsular lens (SECL) can be used to compensate the patient’s ametropia while the injected polymer restores the accommodation amplitude. (A) Using a custom device (not shown), the SECL is rolled and loaded in a thin transparent disposable cannula. (B) The cannula is attached to a handheld instrument (C) that allows its placement via the mini-capsulorhexis into the empty capsular bag. The SECL unrolls within 1 minute and an MCV is placed over the capsulorhexis. (D) The capsular bag is then refilled with the Ersatz polymer, which is cross-linked for 30 seconds using blue light.

Unfortunately, since the capsule must be left as intact as possible in lens refilling surgery, laser treatment may not be an option for the treatment of PCO. Even if the properties of the material are such that opening the posterior capsule does not cause leakage in the posterior chamber of the eye, the large opening in the posterior capsule will very likely prevent the lens from changing shape, as expected during accommodation. In our laboratory, we tested a number of approaches to avoid LEC proliferation in a rabbit model, including mechanical removal of LEC, lavage of the capsule with a variety of pharmacologic agents and hyperosmotic solutions, use of a controlled drug-release implant, and even photodynamic therapy. Even though some of these techniques produced encouraging initial results, their long-term safety and efficacy need to be demonstrated. Leakage of pharmaceutical agents into the anterior chamber could have a devastating effect on other ocular tissues.

The Status of Lens Refilling: Where Are We Today? Obviously, significant advances have been made since the initial pioneering work of Kessler and Agarwal. Initial studies in monkeys by the groups of Nishi and Hara and in our laboratory have demonstrated the validity of the concept of lens refilling. In 1997, an international collaborative project led by Brien Holden’s group at the Cooperative Research Centre for Eye Research and Technology (CRCERT) in Sydney and by Jean-Marie Parel’s group at Bascom Palmer Eye Institute’s Ophthalmic Biophysics Center in Miami,

The Accommodation Club In 1989, realizing that the development of lens refilling and other approaches to restoring accommodation would require a large collaborative and multidisciplinary effort, Nishi, Haefliger, Treffers, and Parel, sponsored by Edward W. D. Norton and Joaquin Barraquer, founded the Accommodation Club, an international think tank into the development of presbyopia corrections, created to foster research in methods and techniques designed to preserve and restore accommodation. The Accommodation Club first met in 1991 in Barcelona, with 54 participants. The second meeting was held in Miami in 1992 with 75 participants, and the third meeting was held in Barcelona in 1997.97 The fourth meeting of the Accommodation Club was held in Miami on April 30, 2004, and included more than 118 participants. Several meetings followed, the 8th and last held in 2012 was attended by 167 aficionados listening to 23 presentations (for additional information, see http://www .accommodationclub.org).

References 1. Waring GO. Presbyopia and accommodative intraocular lenses – the next frontier in refractive surgery? Refract Corneal Surg. 1992; 8:421–423. 2. Helmholtz H. Ueber die accommodation des auges. Arch Ophthalmol. 1855;1:1–74. 3. Kasthurirangan S, Vilupuru AS, Glasser A. Amplitude dependent accommodative dynamics in humans. Vision Res. 2003;43: 2945–2956. 4. Vilupuru AS, Glasser A. The relationship between refractive and biometric changes during Edinger-Westphal stimulated accommodation in rhesus monkeys. Exp Eye Res. 2005;80(3):349–360. 5. Vilupuru AS, Kasthurirangan S, Glasser A. Dynamics of accommodative fatigue in rhesus monkeys and humans. Vision Res. 2005;45(2):181–191. 6. Koretz JF, Cook CA, Kaufman PL. Aging of the human lens: changes in lens shape upon accommodation and with accommodative loss. J Opt Soc Am A. 2002;19:144–151. 7. Dubbelman M, Van der Heijde GL. The shape of the aging human lens. Vision Res. 2001;41:1867–1877. 8. Koretz JF, Cook CA, Kaufman PL. Aging of the human lens: changes in lens shape upon accommodation and with accommodative loss. J Opt Soc Am A Opt Image Sci Vis. 2002;19(1):144–151.

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9. Koretz JE, Strenk SA, Strenk LM, Semmlow JL. Scheimpflug and high-resolution magnetic resonance imaging of the anterior segment: a comparative study. J Opt Soc Am A Opt Image Sci Vis. 2004;21(3):346–354. 10. Dubbelman M, Van der Heijde GL, Weeber HA. Change in shape of the aging human crystalline lens with accommodation. Vision Res. 2005;45(1):117–132. 11. Dubbelman M, Van der Heijde GL, Weeber HA, Vrensen GF. Changes in the internal structure of the human crystalline lens with age and accommodation. Vision Res. 2003;43(22): 2363–2375. 12. Dubbelman M, Van der Heijde GL. The shape of the aging human lens: curvature, equivalent refractive index and the lens paradox. Vision Res. 2001;41(14):1867–1877. 13. Parel JM, Manns F, Fernandez V, et al. Dioptric power vs zonular tension during ex-vivo simulated accommodation of primate crystalline lenses before and after refilling. ARVO. 2003; Abstract 236. 14. Le Grand Y, El Hage SG. Physiological Optics. Berlin, Germany: Springer Verlag; 1980:93–100. 15. Southall JPC. Introduction to Physiological Optics. New York, NY: Dover Publications; 1937:79–83. 16. Zoethout WD. Physiological Optics. Chicago, IL: The Professional Press; 1947:67–78, 83–86. 17. Coleman DJ. Unified model for accommodative mechanism. Am J Ophthalmol. 1970;69:1063–1079. 18. Coleman DJ. On the hydraulic suspension theory of accommodation. Trans Am Ophthalmol Soc. 1986;84:846–868. 19. Coleman DJ, Fish SK. Presbyopia, accommodation and the mature catenary. Ophthalmology. 2001;108:1544–1551. 20. Schachar RA, Bax AJ. Mechanism of accommodation. Int Ophthalmol Clin. 2001;41:17–32. 21. Duke-Elder S, Abrams D. Ophthalmic optics and refraction. In: System of Ophthalmology. Vol 5. St. Louis, MO: CV Mosby; 1970:153–183. 22. Glasser A, Kaufman PL. Accommodation and presbyopia. In: Kaufman PL, Alm A, eds. Adler’s Physiology of the Eye. Clinical Application. 10th ed. St. Louis, MO: Mosby; 2003:197–233. 23. Weeber HA, Eckert G, Soergel F, Meyer CH, Pechhold W, van der Heijde RG. Dynamic mechanical properties of human lenses. Exp Eye Res. 2005;80(3):425–434. 24. Glasser A, Campbell MC. Biometric, optical and physical changes in the isolated human crystalline lens with age in relation to presbyopia. Vision Res. 1999;39(11):1991–2015. 25. Soergel F, Meyer C, Eckert G, Abele B, Pechhold W. Spectral analysis of viscoelasticity of the human lens. J Refract Surg. 1999;15(6):714–716. 26. Strenk SA, Strenk LM, Koretz JF. The mechanism of presbyopia. Prog Retin Eye Res. 2005;24(3):379–393. 27. Schachar RA. Cause and treatment of presbyopia with a method for increasing the amplitude of accommodation. Ann Ophthalmol. 1992;24:445–452. 28. Navarro R, Santamaria J, Bescos J. Accommodation-dependent model of the human eye with aspherics. J Opt Soc Am A. 1985;2:1273–1281. 29. Langenbucher A, Seitz B, Huber S, Nguyen NX, Kuchle M. Theoretical and measured pseudophakic accommodation after implantation of a new accommodative posterior chamber intraocular lens. Arch Ophthalmol. 2003;121:1722–1727. 30. Cumming JS, Slade SG, Chayet A. AT-45 Study Group. Clinical evaluation of the model AT-45 silicone accommodating intraocular lens: results of feasibility and the initial phase of a

Food and Drug Administration clinical trial. Ophthalmology. 2001;108:2005–2009. 31. Legeais JM, Werner L, Werner L, Abenhaim A, Renard G. Pseudoaccommodation: BioComFold versus a foldable silicone intraocular lens. J Cataract Refract Surg. 1999;25:262–267. 32. Findl O, Kriechbaum K, Menapace R, et al. Laserinterferometric assessment of pilocarpine-induced movement of an accommodating intraocular lens: a randomized trial. Ophthalmology. 2004;111(8):1515–1521. 33. Kuchle M, Seitz B, Langenbucher A, Gusek-Schneider GC, Martus P, Nguyen NX. The Erlangen Accommodative Intraocular Lens Study Group. Comparison of 6-month results of implantation of the 1CU accommodative intraocular lens with conventional intraocular lenses. Ophthalmology. 2004;111(2): 318–324. 34. Langenbucher A, Seitz B, Huber S, Nguyen NX, Kuchle M. Theoretical and measured pseudophakic accommodation after implantation of a new accommodative posterior chamber intraocular lens. Arch Ophthalmol. 2003;121(12):1722–1727. 35. Cumming JS, Slade SG, Chayet A. AT-45 Study Group. Clinical evaluation of the model AT-45 silicone accommodating intraocular lens: results of feasibility and the initial phase of a Food and Drug Administration clinical trial. Ophthalmology. 2001;108(11):2005–2009. Discussion 2010. 36. McLeod SD, Portney V, Ting A. A dual optic accommodating foldable intraocular lens. Br J Ophthalmol. 2003;87(9):1083–1085. 37. Thornton SP. Anterior ciliary sclerotomy (ACS): a procedure to reverse presbyopia. In: Sher NA, ed. Surgery for Hyperopia and Presbyopia. Baltimore, MD: Williams and Wilkins; 1997:33–36. 38. Fukasaku H, Marron JA. Anterior ciliary sclerotomy with silicone expansion plug implantation: effect on presbyopia and intraocular pressure. Int Ophthalmol Clin. 2001;41:133–141. 39. Schachar RA. Presbyopic surgery. Int Ophthalmol Clin. 2002;42: 107–118. 40. Marmer RH. The surgical reversal of presbyopia: A new procedure to restore accommodation. Int Ophthalmol Clin. 2001;41: 123–132. 41. Cross W. Theory behind surgical correction of presbyopia. Ophthalmol Clin North Am. 2001;14:315–333. 42. Matthews S. Scleral expansion surgery does not restore accommodation in human presbyopia. Ophthalmology. 1999;106:873–877. 43. Singh G, Chalfin S. A complication of scleral expansion surgery for treatment of presbyopia. Am J Ophthalmol. 2000;130:521–523. 44. Kaufman PL. Scleral expansion surgery for presbyopia. Ophthalmology. 2001;108:2161–2162. 45. Malecaze FJ, Gazagne CS, Tarroux MC, Gorrand JM. Scleral expansion bands for presbyopia. Ophthalmology. 2001;108: 2165–2171. 46. Qazi MA, Pepose JS, Shuster JJ. Implantation of scleral expansion band segments for the treatment of presbyopia. Am J Ophthalmol. 2002;134:808–815. 47. Myers RI, Krueger RR. Novel approaches to correction of presbyopia with laser modification of the crystalline lens. J Refract Surg. 1998;14:136–139. 48. Krueger RR, Sun XK, Stroh J, Myers M. Experimental increase in accommodative potential after neodymium:yttrium-aluminumgarnet laser photodisruption of paired cadaver lenses. Ophthalmology. 2001;108:2122–2129. 49. Ripken T, Oberheide U, Heisterkamp A, Ertmer W, Gerten G, Lubatschowski H. Investigations for the correction of presbyopia by FS-laser induced cuts. Proc SPIE Ophthal Technol. 2004;XIV 5314:27–35.

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50. Ripken T, Oberheide U, Ziltz C, Ertmer W, Gerten G, Lubatschowski H. FS-Laser induced elasticity changes to improve presbyopic lens accommodation. Proc SPIE Ophthal Technol. 2005;XV 5688:278–287. 51. Kessler J. Experiments in refilling the lens. Arch Ophthalmol. 1964;71:412–417. 52. Kessler J. Refilling the rabbit lens. Further experiments. Arch Ophthalmol. 1966;76:596–598. 53. Kessler J. Lens refilling and regrowth of lens substance in the rabbit eye. Ann Ophthalmol. 1975;7:1059–1062. 54. Agarwal LP, Narsimhan EC, Mohan M. Experimental lens refilling. Orient Arch Ophthalmol. 1967;5:205–212. 55. Parel JM, Treffers WF, Gelender H, Norton EWD. Phaco-Ersatz: A new approach to cataract surgery. Ophthalmology. 1981;88:S95. 56. Parel JM, Gelender H, Trefers WF, Norton EWD. Phaco-Ersatz: Cataract surgery designed to preserve accommodation. Graefes Arch Clin Exp Ophthalmol. 1986;224:165–173. 57. Haefliger E, Parel J-M, Fantes F, et al. Accommodation of an endocapsular silicone lens (Phaco-Ersatz) in the non-human primate. Ophthalmology. 1987;94:471–477. 58. Haefliger E, Parel J-M. Accommodation of an endocapsular silicone lens (Phaco-Ersatz) in the old rhesus monkey. Refract Corneal Surg. 1994;10:550–555. 59. Hara T, Hara T, Kojima M, Nakaizumi H, Yamamura T, Sasaki K. Specular microscopy of the anterior lens capsule after endocapsular lens implantation. J Cataract Refract Surg. 1988;14: 533–540. 60. Nishi O. Refilling the lens of the rabbit eye after intercapsular cataract surgery using an endocapsular balloon and an anterior capsule suturing technique. J Cataract Refract Surg. 1989;15: 450–454. 61. Nishi O, Hara T, Hara T, Hayashi F, Sakka Y, Iwata S. Further development of experimental techniques for refilling the lens of animal eyes with a balloon. J Cataract Refract Surg. 1989;15:584–588. 62. Nishi O, Hara T, Hara T, Hayashi F, Sakka Y, Iwata S. Various kinds of experimental refilling lenses with endocapsular balloon. Dev Ophthalmol. 1989;18:125–133. 63. Nishi O, Hara T, Sakka Y, Hayashi H, Nakamae K, Yamada Y. Refilling the lens with inflatable endocapsular balloon. Dev Ophthalmol. 1991;22:122–125. 64. Nishi O, Hara T, Hara T, et al. Refilling the lens with an inflatable endocapsular balloon: surgical procedure in animal eyes. Graefes Arch Clin Exp Ophthalmol. 1992;230:47–55. 65. Nishi O, Nakai Y, Yamada Y, Mizumoto Y. Amplitudes of accommodation of primate lenses refilled with two types of inflatable endocapsular balloons. Arch Ophthalmol. 1993;111:1677–1684. 66. Sakka Y, Hara T, Yamada Y, Hara T, Hayashi F. Accommodation in primate eyes after implantation of refilled endocapsular balloon. Am J Ophthalmol. 1996;121:210–212. 67. Nishi O, Nishi K, Mano C, Ichihara M, Honda T. Controlling the capsular shape in lens refilling. Arch Ophthalmol. 1997;115: 507–510. 68. Nishi O, Nishi K, Mano C, Ichihara M, Honda T. Lens refilling with injectable silicone in rabbit eyes. J Cataract Refract Surg. 1998;24:975–982. 69. Nishi O, Nishi K. Accommodation amplitude after lens refilling with injectable silicone by sealing the capsule with a plug in primates. Arch Ophthalmol. 1998;116:1358–1361. 70. Lucke K, Hettlich HJ, Kreiner CF. A method of lens extraction for the injection of liquid intraocular lenses. Ger J Ophthalmol. 1992;1:342–345.

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71. Hettlich HJ, Lucke K, Kreiner CF. Light-induced endocapsular polymerization of injectable lens refilling materials. Ger J Ophthalmol. 1992;1:346–349. 72. Hettlich HJ, Lucke K, Asiyo-Vogel MN, Schulte M, Vogel A. Lens refilling and endocapsular polymerization of an injectable intraocular lens: In vitro and in vivo study of potential risks and benefits. J Cataract Refract Surg. 1994;20:115–123. 73. Hettlich HJ, Lucke K, Asiyo-Vogel M, Vogel A. Experimentelle untersuchungen zu risiken einer endokapsularen polymerisation injizierbarer intraokularlinsen. Ophthalmologe. 1995;92: 329–334. 74. Hettlich HJ, Asiyo-Vogel M. Experimentelle erfahrungen mit ballonformigen kapselsack-implantaten im hinblick auf einen akkommodationsfahigen linsenersatz. Ophthalmologe. 1996;93: 73–75. 75. Gindi JJ, Wan WL, Schanzlin DJ. Endocapsular cataract surgery – I. Surgical Technique. Cataract. 1985;2:6–10. 76. Assia EI, Blumenthal M, Apple DJ. Effect of expandable full-size intraocular lenses on lens centration and capsule opacification in rabbits. J Cataract Refract Surg. 1999;25:347–356. 77. Tahi H, Hamaoui M, Parel J-M, Fantes F. A technique for small peripheral capsulorhexis. J Cataract Refract Surg. 1999;25: 744–747. 78. Ho A, Erickson P, Pham T, Manns F, Parel J. Theoretical analysis of accommodation amplitude and ametropia correction by varying refractive index in Phaco-Ersatz. Optom Vis Sci. 2001;78: 405–410. 79. Koopmans SA, Terwee T, Barkhof J, Haitjema HJ, Kooijman AC. Polymer refilling of presbyopic human lenses in vitro restores the ability to undergo accommodative changes. Invest Ophthalmol Vis Sci. 2003;44:250–257. 80. Michail H, Hamilton P, Ravi N. The development of a uniaxial stretcher for measuring mechanical properties of the lens. ARVO. 2003; Abstract 250. 81. Glasser A, Campbell MC. Presbyopia and the optical changes in the human crystalline lens with age. Vision Res. 1998;38:209–229. 82. Pierscionek BK. In-vitro alteration of the human lens curvatures by radial stretching. Exp Eye Res. 1993;57:629–635. 83. Fisher RF. The force of contraction of the human ciliary muscle during accommodation. J Physiol. 1977;270:51–74. 84. Parel JM, Lee W, Lamar P, et al. Manual lens stretching apparatus (MLSA) for rapid analysis of the optical properties of the natural lens, accommodating IOL and refilled lens capsule (Phaco-Ersatz). ARVO. 2004; Abstract 1724. 85. Acosta AC, Ziebarth N, Denham D, et al. Ex vivo accommodative responses in primates natural and polymer refilled lenses. Invest Ophthalmol Vis Sci. 2005;46. 86. Koopmans SA, Terwee T, Haitjema HJ, Barkhof J, Kooijman AC. Effect of infusion bottle height on lens power after lens refilling with and without a plug. J Cataract Refract Surg. 2003;29:1989–1995. 87. de Groot JH, van Beijma FJ, Haitjema HJ, et al. Injectable intraocular lens materials based upon hydrogels. Biomacromolecules. 2001;2:628–634. 88. Aliyar H, Hamilton P, Fetsch M, Ravi N. Viscoelasticity of lens capsular bag filled by in-situ formed hydrogel. ARVO. 2003; Abstract 243. 89. Murthy SK, Ravi N. Hydrogels as potential probes for investigating the mechanism of lenticular presbyopia. Curr Eye Res. 2001;22:384–393. 90. Koopmans SA, Terwee T, Haitjema HJ, Deuring H, Aarle S, Kooijman AC. Relation between injected volume and optical

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parameters in refilled isolated porcine lenses. Ophthalmic Physiol Opt. 2004;24(6):572–579. 91. Han YK, Kwon JW, Kim JS, Cho CS, Wee WR, Lee JH. In vitro and in vivo study of lens refilling with poloxamer hydrogel. Br J Ophthalmol. 2003;87(11):1399–1402. 92. Koopmans SA, Terwee T, Haitjema HJ, Barkhof J, Kooijman AC. Effect of infusion bottle height on lens power after lens refilling with and without a plug. J Cataract Refract Surg. 2003; 29(10):1989–1995. 93. de Groot JH, Spaans CJ, van Calck RV, van Beijma FJ, Norrby S, Pennings AJ. Hydrogels for an accommodating intraocular lens. An explorative study. Biomacromolecules. 2003;4(3):608–616.

94. Murthy SK, Ravi N. Hydrogels as potential probes for investigating the mechanism of lenticular presbyopia. Curr Eye Res. 2001;22(5):384–393. 95. Barraquer J. Cataract surgery and IOL implantation – More than 40 years of personal experience – my present criteria and considerations. Doc Ophthalmol. 1992;81:267–280. 96. Barraquer J. Surgery of the lens – yesterday, today and tomorrow. Klin Monbl Augenheilkd. 1994;205:255–258. 97. Parel J-M. Summary and conclusions of the 3rd meeting of the Accommodation Club. Annales Instituto Barraquer (Barc.). 1998;27:327–331.

41 

Smart Intraocular Lenses, Accommodating and Pseudoaccommodating Intraocular Lenses for Presbyopia JOEL ADRIAN D. JAVIER, RAMON C. GHANEM, ELENA ALBÉ, AND DIMITRI T. AZAR

Introduction Accommodation is a change in the focus of the eye from distant to near objects. This is defined as a dioptric change in the eye’s optical power.1 Presbyopia, defined as the physiologic decrease in accommodative amplitude during the aging process, may be due in part to a combination of factors, such as loss of elasticity of the crystalline lens, increase of the equatorial diameter of the lens, alterations in the elastic part of the Bruch membrane, or changes in the ciliary muscle.2 The issue of restoring accommodation following cataract surgery or through refractive lens exchange is becoming an increasingly important topic in ophthalmology. Several different approaches can be taken to address this problem. Current approaches for treating presbyopia include monovision (this being the most often chosen method by ophthalmologists for treating their own eyes), presbyLASIK, corneal inlays, and multifocal intraocular lenses (IOLs). Great interest has been generated in the field of presbyopia correction after the approval of the accommodating IOL in the United States in 2001.3 Accommodating IOLs may avoid problems associated with multifocal IOLs, such as decreased contrast sensitivity and glare/halos, and have the potential to provide near, intermediate, and distance vision without correction.3,4 Smart accommodative intraocular lenses equipped with advanced electronics to facilitate accommodation may be the future of presbyopia correction. One important issue with the new accommodative IOL technology is the measurement of the performance of the IOL. To clarify whether accommodation is restored by an IOL, it is necessary to demonstrate objectively that the eye

undergoes an increase in power with accommodation. Although no standardized methods currently exist for measuring phakic or pseudophakic accommodation, a variety of techniques are available and can be routinely used in clinical practice.5–8 It is also important to differentiate the so-called pseudoaccommodation from true accommodation, which can result from multifocality, monovision, a small pupil that increases the depth of focus, and ocular aberrations.9–11 The aim in the implantation of the accommodating IOL is to maintain binocularity at all distances. The aim of pseudoaccommodation is to provide the functional value of accommodation by generating two separate focal points along the optical axis in order to provide good near and distance vision, and functional intermediate vision. The ideal accommodating IOL would be one that mimics the function and properties of the juvenile lens, a lens that changes in shape and dioptric power when the ciliary muscle contracts. Several obstacles will need to be overcome to achieve feasible fluid-/gel-filled capsular bag lens implants, including surgical technique, correct volume and shape of the refilled lens, and capsular opacification. Although different accommodating IOL technologies have been developed and have shown acceptable results, accommodation remains one characteristic of the human lens that no conventional intraocular device can perfectly match. In order to achieve success with true accommodating IOLs, several important steps should be taken, such as the quantification of accommodation by subjective and objective tests; identification of pseudoaccommodation in the outcomes; testing of outcomes by homologated charts for near (40-cm) and intermediate (70-cm) vision; and the confirmation of results by multicentric, longitudinal studies.The approaches for 511

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accommodative IOL are based on the mechanisms of change in axial position, change in the refractive index of the cornea, or change in the shape of the cornea.

Smart Intraocular Lenses The idea behind smart IOLs is based on the need for an actuator and controller that guides the change in the power of the lens and a sensor that detects the information to facilitate accommodation. The mechanism for accommodation can be anything from a variable refractive index lens, deforming liquid optics, to movable multioptic lens and custom lens based on pupil dynamic and wavefront characteristics. Other smart IOLs have been focused on glucose sensing; having clearer vision in low light conditions; having magnified vision; treating glaucoma based on IOP measurements; and on collecting biometric data, such as body temperature and blood alcohol content, and sensing external conditions, such as allergens.9 Among the smart accommodating IOLs focused on treating presbyopia are FluidVision (PowerVision), Dynacurve (NuLens), and FlexOptix (FlexOptix GmbH).

Single-Optic, Flexible Haptic Support Single-power IOLs with flexible haptics allow for the optic of the lens system to displace anteriorly when the ciliary muscles contract. The Crystalens is made of silicone and has an overall diameter of 11.5 mm. It has a 4.5-mm optic and grooved plate haptics with ends of polymide (Fig. 41.1). Cumming et al. postulated that the ciliary muscle, while bulking backwards when it constricts, increases the pressure of the vitreous on the intraocular lens optic. The latter is thus shifted forward, also by the action of the forward shift of the zonular plane. The optic then reverts back to its initial position upon relaxation of the accommodative muscles in the eye.3 The Akkommodative 1CU lens is made of hydrophylic acrylic material. It has an overall diameter of 9.5 mm, a 5.5-mm optic and four haptics (Fig. 41.2). During relaxation of the capsular bag induced by ciliary muscle contraction, the IOL is displaced forward at the hinges of the four haptics. A disadvantage in these types of lens design is that the generated accommodative power induced by a 1-mm anterior displacement is proportional to the power of the IOL; lower-power IOLs will generate less accommodation than higher-power IOLs.12 Using high-precision, high-resolution, dual-beam partial coherence interferometry, Findl and associates determined the movement of accommodating IOLs compared to that of conventional monofocal IOLs. Their results showed that the anterior displacement of the accommodative IOLs was equivalent to approximately 0.5 diopters (D) in the majority of cases (n = 62), which is within the realm of pseudoaccommodation. Neither polishing of the capsule bag nor a posterior capsulorhexis could enhance the accommodative ability.13,14

• Fig. 41.1

  Scanning electron microscopy of the Crystalens, which has a 4.5-mm silicone optic and an 11.5-mm overall diameter. Adjacent to the optic are 50% thickness grooved “hinges” in the plates. At the end of the plates are two polyimide haptics that allow four-point in-the-bag fixation. (From Dick HB. Accommodative intraocular lenses: current status. Curr Opin Ophthalmol. 2005;16(1):8–26, with permission from Lippincott, Williams and Wilkins.)

Results of a clinical study by Mastropasqua et al. showed that the accommodating IOL 1CU provided better useful spectacle correction–free near visual acuity versus a monofocal IOL.15 The mean amplitude in the accommodating IOL group was 1.14 ± 0.44 D (range, 0.75–2.00 D) at 7 days, 2.36 ± 0.28 D (range, 2.00–2.75 D) at 30 and 90 days, and 1.90 ± 0.77 D (range, 0.75–2.75 D) at 6 months as compared to the monofocal IOL group, which showed no accommodative amplitude. In clinical studies by Cumming et al. on the AT-45 Crystalens accommodating IOL, uncorrected distance acuity of better than or equal to 20/40 and near acuity of better than or equal to 20/30 were obtained in 97% of cases.3 Kuchle et al. and Kanellopoulos reported similar results with the 1CU IOL.16,17 Mastropasqua et  al. reported excellent uncorrected distance and near visual acuity as compared to a conventional monofocal IOL.13 However, they also reported a decrease in near vision acuity at 6 months after the surgery in the accommodating IOL, which approximated that of the monofocal IOL group. They noted these results in patients who developed anterior capsular opacity (ACO)

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accommodative property of the 1CU IOL.20 Research in IOL materials and design may improve and maintain the accommodative properties of this simple but effective concept. Physicians must be very judicious and forthcoming in suggesting the use of this type of accommodating lens; although ingenious and effective, valid concerns have been expressed as to their limitations. Sadoughi et al. reported significant improvements in uncorrected and distance corrected near visual acuities with the implantation of Crystalens HD.21 Good visual outcomes have been reported using Crystalens for distance vision; however, some studies reported unfavorable visual outcomes regarding intermediate and near visual acuities in comparison to the monofocal IOLs.21–27 Objective measurements of accommodative response, such as laser ray tracing aberrometry, were reported to be lower by 0.4 D in Crystalens compared to the monofocal IOL.24 Alió et  al. reported poor defocus curves in Crystalens compared to both multifocal refractive IOLs and dual-optic accommodating IOLs.22,23 The authors also reported greater incidence of higher-order aberrations and PCO postoperatively compared to the dual-optic accommodating Synchrony IOL.22

Crystalens Surgical Technique • Fig. 41.2

  The single-piece Akkommodative 1CU consists of hydrophilic acrylate. It has an optical diameter of 5.5 mm and an overall diameter of 9.8 mm (scanning electron microscopy). (From Dick HB. Accommodative intraocular lenses: current status. Curr Opin Ophthalmol. 2005;16(1):8–26, with permission from Lippincott, Williams and Wilkins.)

and posterior capsular opacity (PCO), and in patients who developed both ACO and PCO. These observations lead to the hypothesis that fibrosis may make the capsular bags more rigid, thereby interfering with the flexion of the haptics responsible for the forward displacement of the optic, resulting in increased accommodative power of the IOL. The study suggested that the resultant fibrosis may be avoided with the improvement of IOL edge design and the material used in its manufacture. ACO development has been shown to be related to hydrophilic acrylic IOLs. The 1CU IOL is made of this material and may be the cause for the development of ACO. The anterior displacement of the 1CU optic during ciliary muscle contraction may allow for the migration of lens epithelial cells (LECs) to the posterior capsule, leading to PCO development.18,19 The material and design of static power, axially displacing IOLs may be limited in efficacy owing to the development of capsular fibrosis and opacities that hinder its mechanism for inducing pseudophakic accommodation. In the long term, contraction of the capsule becomes inevitable, and the 1CU IOL loses its accommodative property. A study reported higher incidence of ACO and PCO in 100% of their patients (14 eyes) within postoperative year 1 and a complete loss of the

The protocol is based on our routine protocol for cataract surgery, with some modifications. Pupil dilation is performed using 4 drops of tropicamide 0.5% and phenylephrine 10% at 15-minute intervals, 1 hour prior to surgery. Peribulbar anesthesia with ropivacaine 0.75% is then applied, followed by one drop of 0.5% proparacaine HCl. Before surgery, the following equipment and medications are prepared alongside the routine cataract sets: • Crystalens set • Wescott scissors • eraser cautery • bipolar cautery • crescent blade • 10-0 vicryl suture • lens holder • atropine 1% drops • cyclopentolate 1% drops • Crystalens IOL and spare monofocal IOL. A temporal limbal peritomy is performed and a scleral tunnel 2.50 mm long is made approximately 1 mm from the limbus (Fig. 41.3A). A 1.0-mm width shelved paracentesis is made with a 15-degree blade at the 7 o’clock and 11 o’clock meridians for right eyes and at the 1 o’clock and 5 o’clock meridians for left eyes (Fig. 41.3B). Dispersive viscoelastic material is then injected in the anterior chamber to protect the endothelium and cohesive viscoelastic is injected over the anterior capsule until complete expansion. An anterior continuous curvilinear capsulorhexis (CCC) of approximately 5.5 mm (5.0–6.0 mm) is performed with a capsulorhexis forceps (Fig. 41.3C). Hydrodissection is completed with a flat, 25-gauge cannula. The nucleus is removed by the Phaco-Chop technique or Divide and Conquer, and

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A

B

C

D

E

F

G

H

I

J

K

L

• Fig. 41.3

  Surgical technique for Crystalens accommodative intraocular lens. (A) A scleral tunnel 2.5 mm long is made approximately 1 mm from the limbus. (B) A 1.0-mm width shelved paracentesis is made with a 15-degree blade. (C) An anterior continuous curvilinear capsulorhexis of approximately 5.5 mm is performed with a capsulorhexis forceps. (D) The nucleus is removed by phacoemulsification. (E) Residual cortex is aspirated. (F) The lens is grasped so that the forceps extends across the distal hinge to stabilize the leading plate haptic. The forceps is advanced to place the leading plate haptic into the distal capsular bag. (G) With a second instrument, the proximal polyimide loop is held as the implantation forceps is withdrawn. (H) The tip of the trailing plate haptic is regrasped, leading the proximal polyimide loops into the capsular bag. Note that the optic curves anteriorly during the insertion of the second haptic plate. (I) The lens is rotated 270 degrees to the horizontal position. (J) The incision is sutured with one or two single sutures of 10-0 polyglactin. (K) Residual viscoelastic is aspirated via bimanual technique. (L) The anterior chamber is deepened, ensuring adequate posterior vaulting of the lens.

the residual cortical material is aspirated (Figs. 41.3D and 41.3E). The presence of two paracenteses allows complete cortex removal using a bimanual technique when needed. The incision is enlarged to 3.2 to 3.5 mm, the capsular bag is filled with cohesive viscoelastic, and the Crystalens Model AT-45 IOL is implanted unfolded in the capsular bag with the special designed lens forceps. The lens is grasped so that the forceps extends across the distal hinge to stabilize the leading plate haptic. The forceps is advanced to place the leading plate haptic into the distal capsular bag (Fig. 41.3F). With a second instrument, the proximal polyimide loop is held as the implantation forceps is withdrawn (Fig. 41.3G). The tip of the trailing plate haptic is regrasped, leading the proximal polyimide loops into the capsular bag (Fig. 41.3H). The round knob on the loop should be on the right to ensure that the hinge groove is facing up on implantation. Verification is also possible on high magnification with

side-on viewing of the lens. The IOL is rotated 270 degrees to the horizontal position (Fig. 41.3I). The optic should be vaulted backward in the direction of the posterior capsule. Intraoperative requirements for implantation of this IOL are intact CCC and intact posterior capsule and absence of zonular dialysis. Both haptics should be in the capsular bag for the lens to work. The residual viscoelastic is aspirated via bimanual technique (Fig. 41.3K). The anterior chamber is deepened, ensuring adequate posterior vaulting of the lens (Fig. 41.3L). The incision is tested for water tightness; then, the conjunctiva is closed with bipolar cautery. Anterior vaulting of the IOL optic with pupillary capture can occur if the anterior chamber is shallow or flat in the postoperative days because of incision leakage. A drop of 1% atropine is administered immediately following surgery and 1 day after implantation. In addition, a single drop of 1% cyclopentolate HCl is administered four times a day for

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10 days following surgery. The eye is padded and a shield applied.

Other Single-Optic Systems The Kellen Tetraflex (Lenstec, Inc.) IOL is intended for active lifestyles that require good near vision and crisp intermediate and distance vision. It is a 11.5-mm-long accommodating lens made of hydrophilic acrylic material (medical grade hydroxyethylmethacrylate [HEMA], with 26% water content), with an optic of 5.5 mm and an anterior vault of 5 degrees that is designed to promote movement during ciliary contraction. The Tetraflex IOL can be used for both refractive and cataract lensectomy surgery. Currently, it is available for use only outside the United States and is undergoing US Food and Drug Administration (FDA) review for premarket approval. From the studies done on the mechanism of action of Tetraflex, its positions appear to be relatively fixed in the eye and, although the ocular aberrations of the eye were reported to change with the increasing accommodative demands, the changes did not appear to be consistent among all individuals. Some of the reported benefits of the Tetraflex IOL in terms of near visual acuity therefore appear to be due to optical aberration changes from the IOL flexure rather than due to the forward movement of the lens within the capsular bag.28,29 Owing to high flexibility of the hydrophilic acrylic material of the IOL, there is greater susceptibility of the capsular bag contraction, with subsequent flexing of the haptic part of the lens, making the accommodating IOL exchange necessary.

Dual-Optic System, Telescoping Intraocular Lens Synchrony (Visiogen, Inc.) is a single-piece, silicone, dualoptic accommodating intraocular lens (Fig. 41.4). The entire device is implanted in the capsular bag. It is made up of two lenses kept apart by a spring-like mechanism. The anterior optic is 5.5 mm large and has a 30 D to 35 D optical power; the posterior optic is 6 mm large and has a negative power that varies depending on ocular axial length. The overall length of the intraocular lens is 9.5 mm, its width is 9.8 mm, and its thickness is 2.2 mm when it is compressed. During the nonaccommodative phase, the taut zonules keep the anteroposterior distance close and the energy in the spring mechanism suppressed. On contraction of the ciliary muscles, the zonular fibers become lax and the spring releases its energy, driving the two lenses apart, thereby increasing the anteroposterior distance and leading to an accommodative effect.30 In a study by Werner et al.,31 the Synchrony accommodating IOL had less fibrosis, ACO, and PCO than a conventional IOL group in rabbit eyes. Although there was a greater incidence of anterior chamber IOL dislocation and pupillary block in the accommodating IOL group than in the control group, a possible explanation

• Fig. 41.4

  The single-piece silicone Synchrony intraocular lens features a 5.5-mm high-powered anterior convex optic connected to a 6.0-mm negative power (concave) posterior optic by haptics that have a spring-like action (scanning electron microscopy). (From Dick HB. Accommodative intraocular lenses: current status. Curr Opin Ophthalmol. 2005;16(1):8–26, with permission from Lippincott, Williams and Wilkins.)

for this phenomenon might be the relative discrepancy between the size of the IOL and size of the test animal eye, which has smaller dimensions than the intended use in the human eye. The Synchrony IOL has been reported to have accommodative amplitude of 2.5 D based on a defocus curve.32 The Synchrony IOL got stalled in the process of FDA approval for 3 years; eventually, Abbot Medical Optics (AMO), who acquired Visiogen in 2009, discontinued it.

Dynamic Optic (Lens Refilling) These IOLs do not rely on a fixed power optic displaced axially or on a telescoping effect by increasing the distance between two static powered lenses to induce an accommodative effect. These lenses truly have dynamic powerchanging optics. The SmartLens (Medennium, Inc.) is made up of thermodynamic hydrophobic acrylic material designed to fill the entire capsular bag (Fig. 41.5). Its initial presentation is a solid 30 mm long and 2 mm wide solid rod, which transforms into a soft gel completely filling the capsular bag once it is inserted into the eye.33 The intraocular lens is pliable enough so that ciliary body contraction causing capsular bag contraction results in an increased anteroposterior diameter of the IOL. This IOL depends on the consistent resilience of the capsular bag. Given that the IOL is made up of hydrophobic acrylic and has a shape that may be resistant to lens epithelial cell migration, it has a good potential of delivering reliable accommodation for patients. However, experimental testing has yet to be released to validate all these claims.

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A

B

C

D

• Fig. 41.5

  The hydrophobic acrylic SmartLens. (A) The lens is introduced into 37°C water. (B–D) In approximately 30 seconds, the lens is about 9.5 mm wide and 2 to 4 mm thick.

Magnetic Lens System The Akkommodative Magnetic Lens System (AcriTec Inc.) is an accommodating IOL system currently under development. It features a system involving movements of the entire capsular bag by two inner magnets, which are implanted into the capsular bag on a capsular tension ring (Fig. 41.6), and two pairs of outer magnets, which are fixed under the superior and inferior rectus muscles. The magnets, by repelling each other, induce capsular bag accommodative movements. The problem of capsular bag shrinking and fibrosis thus could be overcome.34

Other Concepts Light Adjustable Lens The light adjustable lens (LAL; Calhoun Vision) is a foldable, three-piece IOL featuring a cross-linked silicone polymer matrix and photosensitive macromers. Selective irradiation with near-ultraviolet (UV) light of the central part of the lens induces macromer polymerization, followed by migration of nonpolymerized macromers from the lens periphery to the center, which swells. The UV light is irradiated to the outer peripheral part of the LAL when myopic correction is needed; conversely, the central part is irradiated when hyperopic correction is required. New irradiation then “locks in” the new lens shape. Reversible multifocal optics are currently under investigation in order to mimic natural crystalline lens accommodation.35 The LAL has been commercially available after having received CE mark approval in the European market since 2008, and in Mexico since

• Fig. 41.6  Akkommodative Magnetic Lens System. Capsular tension ring with two small permanent magnets for implantation in the capsular bag. (From Dick HB. Accommodative intraocular lenses: current status. Curr Opin Ophthalmol. 2005;16(1):8–26, with permission from Lippincott, Williams and Wilkins.)

2012. These LALs are available in trifocal, multifocal, and toric IOL designs. An important feature of LAL technology is that the IOL power can be adjusted postoperatively to reduce and even eliminate residual myopic, hyperopic, and astigmatic corrections of at least 2.00  D. The IOL power can

CHAPTER 41  Smart Intraocular Lenses, Accommodating and Pseudoaccommodating Intraocular Lenses for Presbyopia

also be adjusted to give an increased depth of focus by changing the total amount of aspheric correction. These postoperative IOL power-adjustment capabilities are more attractive because the procedure involved is noninvasive.36 Calhoun Vision is also currently working with LAL technology to treat presbyopia in a treatment called adjustable blended vision (ABV) that has recently been approved by FDA.

Accommodating Optical Shift Concepts Two IOL models developed by Morcher represent an interesting novel concept based on the accommodating optical shift principle. The principles of these IOLs rely on spring forces, which augment with time when capsule fibrosis or adhesion increases.37 One implant, called the capsule clip, uses the spring effect resulting from the posterior angulation of the haptics and the tension of the optic, which is fixated at the anterior capsulorhexis margin, during ciliary muscle contraction. The other implant, called the sulcus-fixed capsular bag implant, undergoes a permanent spring action when its haptics are placed into the ciliary sulcus and its optic is trapped in the anterior capsule opening.

Conclusion The quest for a true reliable, accommodating IOL is still in a relatively early stage. However, technology is developing at such a staggering pace that, within the foreseeable future, we might well be introduced to a real and viable solution to the accommodation problem in lenticular replacement surgeries. It is imperative that surgeons are well informed about the advantages and limitations of the accommodative IOLs currently available on the market. As with all surgical procedures, patients must be kept abreast of the real capabilities of the prospective device because the data and information released about these new products might result in unrealistic expectations, putting strain on the patient– physician relationship. The development of power-changing IOLs may also be used to address refractive surgery concerns in patients who may not qualify as candidates for laser corneal-reshaping procedures. Although phakic IOLs are used as a treatment option for refractive errors, the development of novel accommodating and dynamic adaptive phakic IOLs may have potential therapeutic applications for the treatment of ametropia in the presbyopic age group.

References 1. Keeney AH, Hagman RE, Fratello CJ. Dictionary of Ophthalmic Optics. Newton, MA: Butterworth-Heinemann; 1995:4. 2. Kaufman PL. Accommodation and presbyopia: neuromuscular and biophysical aspects. In: Hart WM Jr, ed. Adler’s Physiology of the Eye; Clinical Application. 9th ed. St. Louis, MO: Mosby; 1992:391–411. 3. Cumming JS, Slade SG, Chayet A. Clinical evaluation of the model AT-45 silicone accommodating intraocular lens: results

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of feasibility and the initial phase of a food and drug administration clinical trial: the AT-45 study group. Ophthalmology. 2001;108:2005–2009. 4. Leyland M, Zinicola E. Multifocal versus monofocal intraocular lenses in cataract surgery: a systematic review. Ophthalmology. 2003;110(9):1789–1798. 5. Ostrin LA, Glasser A. Accommodation measurements in a prepresbyopic and presbyopic population. J Cataract Refract Surg. 2004;30(7):1435–1444. 6. Langenbucher A, Seitz B, Huber S, Nguyen NX, Kuchle M. Theoretical and measured pseudophakic accommodation after implantation of a new accommodative posterior chamber intraocular lens. Arch Ophthalmol. 2003;121(12):1722–1727. 7. Stachs O, Schneider H, Stave J, Guthoff R. Potentially accommodating intraocular lenses – an in vitro and in vivo study using three-dimensional high-frequency ultrasound. J Refract Surg. 2005;21(1):37–45. 8. Nemeth G, Lipecz A, Szalai E, Berta A, Modis L Jr. Accommodation in phakic and pseudophakic eyes measured with subjective and objective methods. J Cataract Refract Surg. 2013; 39(10):1534–1542. 9. Larkin H. Smart lenses: electronic accommodating IOLs and contacts may be next in presbyopia treatment. Eurotimes Stories. http://www.eurotimes.org/smart-lenses/. Accessed November 21, 2018. 10. Thompson HS. The pupil. In: Hart WM Jr, ed. Adler’s Physiology of the Eye; Clinical Application. 9th ed. St. Louis, MO: Mosby; 1992:412–441. 11. Elder MJ, Murphy C, Sanderson GF. Apparent accommodation and depth of field in pseudophakia. J Cataract Refract Surg. 1996; 22:615–619. 12. Masket S. Accommodating IOLs: emerging concepts and designs. Cataract Refract Surg Today. 2004;2(July):32–36. 13. Findl O, Kiss B, Petternel V, et al. Intraocular lens movement caused by ciliary muscle contraction. J Cataract Refract Surg. 2003;29:669–676. 14. Findl O, Kriechbaum K, Menapace R, et al. Laserinterferometric assessment of pilocarpine-induced movement of an accommodating intraocular lens: a randomized trial. Ophthalmology. 2004;111(8):1515–1521. 15. Mastropasqua L, Toto L, Nubile M, et al. Clinical study of the 1CU accommodating intraocular lens. J Cataract Refract Surg. 2003;29:1307–1312. 16. Kuchle M, Seitz B, Langenbucher A, et al. Comparison of 6-month results of implantation of the 1CU accommodative intraocular lens with conventional intraocular lenses. Ophthalmology. 2004;111(2):318–324. 17. Kanellopoulos J Encouraging early results with new accommodating IOL. Paper presented at the 6th ESCRS Winter Refractive Surgery meeting. Barcelona, Spain: January 2002. 18. Tognetto D, Toto L, Ballone E, Ravalico G. Biocompatibility of hydrophilic intraocular lenses. J Cataract Refract Surg. 2002;28:644–651. 19. Nishi O, Nishi K, Sakanishi K. Inhibition of migrating lens epithelial cells at the capsular bend created by the rectangular optic edge of a posterior chamber intraocular lens. Ophthalmic Surg Lasers. 1998;29:587–594. 20. Mastropasqua L, Toto L, Falconio G, et al. Longterm results of 1 CU accommodative intraocular lens implantation: 2-year follow-up study. Acta Ophthalmol Scand. 2007;85:409–414. 21. Sadoughi MM, Einollahi B, Roshandel D, Sarimohammadli M, Feizi S. Visual and refractive outcomes of phacoemulsification

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with implantation of accommodating versus standard monofocal intraocular lenses. J Ophthalmic Vis Res. 2015;10:370–374. 22. Alió JL, Plaza-Puche AB, Montalban R, Ortega P. Near visual outcomes with single-optic and dual-optic accommodating intraocular lenses. J Cataract Refract Surg. 2012;38:1568–1575. 23. Alió JL, Plaza-Puche AB, Montalban R, Javaloy J. Visual outcomes with a single-optic accommodating intraocular lens and a low-addition-power rotational asymmetric multifocal intraocular lens. J Cataract Refract Surg. 2012;38:978–985. 24. Pérez-Merino P, Birkenfeld J, Dorronsoro C, et al. Aberrometry in patients implanted with accommodative intraocular lenses. Am J Ophthalmol. 2014;157:1077–1089. 25. Zamora-Alejo KV, Moore SP, et al. Objective accommodation measurement of the crystalens HD compared to monofocal intraocular lenses. J Refract Surg. 2013;29:133–139. 26. Dhital A, Spalton DJ, Gala KB. Comparison of near vision, intraocular lens movement, and depth of focus with accommodating and monofocal intraocular lenses. J Cataract Refract Surg. 2013;39:1872–1878. 27. Vilupuru S, Lin L, Pepose JS. Comparison of contrast sensitivity and through focus in small-aperture inlay, accommodating intraocular lens, or multifocal intraocular lens subjects. Am J Ophthalmol. 2015;160:150–162. 28. Wolffsohn JS, Davies LN, Gupta N, et al. Mechanism of action of the tetraflex accommodative intraocular lens. J Refract Surg. 2010;26:858–862.

29. Leng L, Chen Q, Yuan Y, et al. Anterior segment biometry of the accommodating intraocular lens and its relationship with the amplitude of accommodation. Eye Contact Lens. 2017;43(2): 123–129. 30. McLeod SD, Portney V, Ting A. A dual optic accommodating foldable intraocular lens. Br J Ophthalmol. 2003;87(9):1083–1085. 31. Werner L, Pandey SK, Izak AM, et al. Capsular bag opacification after experimental implantation of a new accommodating intraocular lens in rabbit eyes. J Cataract Refract Surg. 2004; 30:1114–1123. 32. Dick B. Assessment of three accommodative IOLs. Cataract Refract Surg Today. 2004;2(July):56–57. 33. Fine IH. The SmartLens: a fabulous new IOL technology. EyeWorld. 2002;16(1):24. 34. Preussner PR, Wahl J, Gerl R, et al. Accommodative lens implant. Ophthalmologe. 2001;98(1):97–102. 35. Hoffman RS, Fine IH, Packer M. The light adjustable lens. In: Agarwal S, Agarwal A, Agarwal A, eds. Phacoemulsification. Vol. II. 3rd ed. Section X. New Jersey: Slack; 2004:321–330 (chap 67). 36. Berdahl J. Light adjustable lens: customizable and predictable refractive results. The pipeline. Millennial Eye. 2014;Jul/Aug. https://millennialeye.com/articles/2014-jul-aug/light-adjustable -lens-customizable-and-predictable-refractive-results/. 37. Dick HB. Accommodative intraocular lenses: current status. Curr Opin Ophthalmol. 2005;16:8–26.

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Postkeratoplasty Astigmatism: Etiology, Management, and Femtosecond Laser Applications SALIM I. BUTRUS, M. FAROOQ ASHRAF, AND DIMITRI T. AZAR

Introduction Penetrating keratoplasty (PK) involves resecting and suturing a donor corneal tissue to a recipient corneal bed. It requires meticulous attention to detail by the corneal surgeon. The surgeon’s task begins with communication with the eye bank and ends with lengthy postoperative management of the patient. Different degrees of graft astigmatism may arise postoperatively and can be attributed to poor surgical technique.

Pathogenesis of Postkeratoplasty Astigmatism The factors that can contribute to postkeratoplasty astigmatism are listed below. Some are beyond the surgeon’s control, while others are totally or partially controlled by the surgeon: • Preoperative factors, recipient related • native astigmatism • topographic changes • recipient corneal scarring, vascularization, thinning • recipient uneven scleral rigidity • aphakia or pseudophakia (anterior chamber intraocular lens [ACIOL], prior vitrectomy, or scleral fixation) • Preoperative factors, donor related • nonuniform peripheral changes (scarring, thinning, vascularization) • donor topographic variations (undetected keratoconus, high astigmatism) • Intraoperative factors, recipient related • effect of pressure of eyelid speculum and Flieringa ring on trephination • dull trephine or overused trephine blade • trephine tilt • eccentric trephination scissors 520

• uneven wound architecture, poor resection • asymmetric wound edges • Intraoperative factors, donor related • inadequate punch technique • dull trephine or overused trephine blade • eccentric trephination • oval trephination • punch tilt during freehand trephination • intraoperative donor–recipient relationship • donor–recipient diameter disparity • suture tension • donor–recipient torquing (improper suture orientation and location, wound override) • eccentric donor–recipient trephination • postoperative factors • wound microdehiscence, override • trauma with macrodehiscence • timing of suture removal or adjustment • graft rejection, melting, necrosis, infectious keratitis • pharmacologic agents • scleral fixated intraocular lens (IOL), ACIOL • other (contact lens, intraocular pressure [IOP] elevation)

Preoperative Factors In general, surgeons have access to high-quality donor tissues that can be preserved and transported for days. Donors may have undetected astigmatism. Whether donor native astigmatism has any effect on final-graft astigmatism is not known. Certainly, recipient pathologic conditions can lead to astigmatism. Sectorial vascular invasion, thinning, or uneven rigidity in keratoconus will lead to uneven donorto-recipient wound apposition, wound healing, and the creation of uneven forces within the cornea. Irregular recipient

CHAPTER 42  Postkeratoplasty Astigmatism: Etiology, Management, and Femtosecond Laser Applications

corneas (scars, vessels, thinning, unequal rigidity) result in irregular opening after trephination and hence irregular astigmatism.

Operative Factors Most donor corneal buttons today are trephined in an endothelial cell-up position in a concave Teflon block, as described by Vannas.1 This method yields a perfectly round edge graft. It is done in a more controlled fashion than when trephined epithelial cell-up in an intact globe. The donor corneoscleral rim is placed and fixated in a Teflon block to be punched with a piston-guided trephine or by a freehanded trephine. The piston-guided punch method is more precise and usually results in a circular tissue with vertical edges. If the trephine is slightly tilted, the freehanded technique may yield an oval button with shelved edges.2–4 A dull trephine will leave irregular edges, leading to irregular wound healing and astigmatism. More recent and sophisticated trephines, such as the Krumeich and Hanna-Moria trephines, cut donor corneas through the epithelial side, giving more reproducible results. Although donor corneas can be correctly punched with reproducible results, recipient corneas are less likely to be trephined with the same accuracy, since more variables are involved and less predictable results are obtained. Freehand trephination is a common practice, but other trephines, such as the Hessburg-Barron, are more popular despite setting a reverse shelved wound. Other, more expensive trephines such as the Krumeich cam-guided trephine, automated Hans-Gueder trephine, and mechanized HannaMoria trephine, theoretically should give more reproducible results. The Krumeich cam-guided system cuts the cornea in an applanated shape, perpendicular to the limbal plane, and theoretically produces round grafts5: • freehand—disposable, Weck, Storz, Pharmacia • reusable—Grieshaber • disposable suction—Hessburg-Barron • automated—Hans-Gueder • mechanized—Hanna-Moria • cam-guided—Krumeich, Lieberman Many factors can affect adequate trephination in the recipient cornea. Freehanded trephination is subject to more factors that may affect the outcome, such as external pressure by the eyelid speculum, Flieringa ring, or forceps stabilizing the globe.6 Dull trephines or trephines made by different manufacturers should not be used because they result in irregular edges.7 Hold trephines perpendicular to the plane of the globe, hugging the recipient tissue 360 degrees, because minor tilts can cause asymmetric corneal grooves and oval openings.8,9 Eccentric trephination results in a high degree of astigmatism with an axis toward the displacement direction.10 Finally, poor excision of the corneal tissue due to inadequate trephination or dull scissors may result in poor wound architecture, poor wound opposition and healing, and a high degree of astigmatism. Trephine tilts should be minimized during trephination of

521

recipient corneas. This can be difficult to accomplish under the operating microscope, and a tilt more than 5 degrees can easily occur. Olson’s mathematic model has shown that buttons should be round, with 0 degrees of tilt.11 Ovality increases with higher degrees of tilt. Cohen and associates12 showed that maximum ovality appeared in 20 to 25 degrees tilt; however, buttons were oval and asymmetric at 0 to 15 degrees of tilt in eye bank eyes (Fig. 42.1). They concluded that neither ovality nor asymmetry correlated with degrees of tilt and that factors other than tilt contribute to wound ovality and irregularity. Troutman and Buzard attempted to use intraoperative keratometry and rotate the donor button while inside the recipient wound to minimize disparity but without eliminating astigmatism.13 The use of oversized donor buttons is believed to reduce hyperopia and glaucoma in aphakic patients.14 The donor button is punched from the endothelial surface and hence is smaller due to retraction of the tissue. Oversized is, in fact, superior to undersized and there is no difference in

Direction of trephine rotation

Cutting edge

Fulcrum at 12:00 Direction in which tissue is pulled

Cornea

Direction of tilt 12:00

Fulcrum

Trephine rotation

Compressed tissue

• Fig. 42.1

Compressed tissue

  Side view of oblique trephination (top) showing pulling of corneal tissue. This results in oblong tissue resection in the recipient cornea (bottom). (From Cohen KL, Holman RE, Tripoli NK, et al. Effect of trephine tilt on corneal button dimensions. Am J Ophthalmol. 1986; 101:722–725, with permission from Elsevier.)

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astigmatism, less wound leak, and less chance of collapse of the trabecular meshwork with oversized donor buttons. Corneal wound disparity defined by mismatch between size and shape of donor button wound and its recipient wound determines degree, direction, and amount of astigmatism created. Multifactorial elements contribute to corneal wound disparity. Donor or recipient trephine, tilt, size, and eccentricity all contribute to disparity and ultimately astigmatism. The donor button is punched from the donor endothelial side; approximately 0.2 mm in diameter is lost in this process. Thus a 0.2-mm oversized graft is practically the same size as the recipient. The use of oversized donor over recipient (0.25–1 mm) gained popularity because it is believed to reduce hyperopia and the incidence of glaucoma in aphakic patients. It also has the advantages of less wound leak, easier suturing, less collapse of the trabecular meshwork, and lower incidence of glaucoma. Most studies found that oversized grafts did not increase the incidence of astigmatism. However, the study by Perl and coworkers showed that oversized grafts compared with same-sized grafts did not affect intraocular pressure and refractive state and increased the amount of induced astigmatism.14 The extent of myopic error following PK in keratoconus patients can be decreased by reducing recipient–donor trephine disparity.15

Suturing Technique Many uncontrollable factors discussed previously contribute to postkeratoplasty astigmatism. However, much attention has been focused on factors that the surgeon can manipulate operatively and postoperatively such as suture type, size, and technique. Different studies have shown that the final corneal astigmatism follows suture removal regardless of suture technique used. It is extremely difficult to draw conclusions from earlier studies because most studies (1) are retrospective, (2) lack controls, (3) involve different surgeons, (4) draw conclusions based on data before final suture removal, and (5) depend only on either refraction or keratometry. More recent studies, however, are prospective and employ vector analysis and computer-assisted topographic analysis. Although most established techniques to reduce postkeratoplasty astigmatism employ either selective suture removal or postoperative suture adjustment relying on keratometry or computer-assisted topographic analysis, a recent study advocated suture adjustment.16,17 Serdarevic and coauthors observed that after suture removal, at 15 months postoperatively, astigmatism was less in the intraoperative adjustment group (1.75 ± 1.04 diopters [D]) than in the postoperative adjustment group (2.23 ± 1.72 D), but this was not statistically significant.17 The authors concluded that low astigmatism and good visual results can be obtained with either intraoperative or postoperative running suture adjustment, but intraoperative suture adjustment permits more rapid visual rehabilitation, increased safety, and increased refractive stability.

Management of Significant Postkeratoplasty Astigmatism The amount of postkeratoplasty astigmatism declines as the surgeon’s experience increases. Most surgeons feel that astigmatism greater than 3 D to 3.5 D is significant enough to warrant manipulation to minimize astigmatism. The most important factor is whether the sutures have been removed. Adjusting the sutures helps reduce the amount of astigmatism and possibly the final outcome. There is no definite postoperative time period when the graft becomes “fixed,” although some surgeons believe that this does not occur before 1 year. The final astigmatic stabilization occurs when all sutures are removed. For example, removing a running suture can theoretically change the amount and the axis of astigmatism up to 6 years after surgery.

Management of Astigmatism While Sutures Are In: Suture Manipulation Surgeons try to manipulate corneal sutures to control and minimize astigmatism. To reduce suture tension at the steep meridian, sutures are adjusted either by selective removal or by adjusting the tension of single running sutures. Each approach has advantages and disadvantages. Both will reduce the amount of astigmatism for as long as the sutures are in. However, the cornea is not “fixed,” and removing the running sutures any time after surgery creates large degrees of astigmatism. Because 10-0 nylon is biodegradable, it may loosen, disintegrate, and/or break, possibly leading to potentially serious problems such as microbial keratitis, epithelial breakdown, suture abscesses, graft vascularization, and rejection. The complications of 10-0 nylon permanently left in corneal graft include: • spontaneous breakage or degradation • exposed knots and giant papillary conjunctivitis (GPC) • suture abrasion • suture erosion • vascularization and fibrosis along suture tract • infection • inflammation graft rejection after suture removal Both techniques assume only compression suture effects on astigmatism, ignoring wound healing or other relevant variables that may affect astigmatism.

Selective Suture Removal This technique was popularized by Binder and colleagues,18,19 and results of recent studies show a mean reduction of astigmatism from 2.5 D to 3.0 D after selective suture removal. It is based on the assumption that the cornea assumes a different curvature after the tight suture is selectively decompressed at a particular time. The change of astigmatism after long-term removal of the remaining sutures is less dramatic, suggesting that additional suture removal results in minimal curvature change after the corneal wound becomes fixed.

CHAPTER 42  Postkeratoplasty Astigmatism: Etiology, Management, and Femtosecond Laser Applications

It is not difficult to remove one or two 10-0 nylon sutures under a slit lamp using topical anesthesia, but it does require an increased number of patient office visits. It can also be unpredictable and irreversible, and it may result in wound dehiscence, suture-induced irritation, infection, vascularization, and graft rejection. This technique also regulates the amount of astigmatism at a specific meridian of that tight suture and not the whole corneal circumference.

Suture Adjustment A single 10-0 nylon running suture is performed and usually left somewhat on the loose side so that suture adjustment can be done 1 day and up to 6 weeks postoperatively.20 The technique involves rotating the suture from an area of flat meridian (cool colors) to areas of steep meridian (hot colors; Fig. 42.2). Nabors and associates took a step further by opening the anterior third of the wound along the steep meridian.21 Suture adjustment achieves early visual rehabilitation and relatively regular keratometry mires. This is beneficial when an IOL is inserted 3 months after keratoplasty. It is a titrated procedure in which adjustment is continued and stopped until stable Ks are obtained. It is reversible and more predictable and results in regular astigmatism along the entire circumference of the cornea, not along a single meridian. Suture adjustment can be performed under a slit lamp with a calm, cooperative patient. The procedure must be repeated and sometimes requires a loose running suture, which may compromise the graft wound, lead to wound disruption, leak, cause infection, or recess the wound. Suture breakage occurs rarely. If it occurs, the patient usually must go to the operating room for suture placement. McNeill and Wessels encountered a broken suture in five eyes of a total of 330 eyes studied.16

Management of Astigmatism After Suture Removal Relaxing Incisions (Video 42.2) The surgical approach using relaxing incisions to minimize graft astigmatism is undertaken in cases of astigmatism high enough to cause blurring of vision with or without spectacle correction. Although the eye can often be visually rehabilitated through special contact lenses, some patients require a surgical attempt to correct high astigmatism. Before relaxing incisions are entertained in postkeratoplasty patients, all sutures should be removed, and stable refractions, keratometry, and topographic analyses observed for at least 3 months. The above three methods for evaluating postkeratoplasty astigmatism are important and should be performed before relaxing incisions are made. In individuals with high degrees of astigmatic error (> 10 D), wound overrides should be suspected, ruled out, and corrected.22–28 We recommend arcuate relaxing incisions made 1 mm on the graft itself and not in the graft–host interface (Fig. 42.3). Compression sutures can be placed in the orthogonal meridian to enhance the surgical effect. The technique of arcuate relaxing incisions is simple to perform, requiring office setup and topical anesthesia. The postoperative recovery period is extremely short, and visual rehabilitation is rapid and dramatic.

Operative Technique The eye is anesthetized with topical anesthetic drops. The particular meridian is marked on the slit lamp with a surgical blue marker, and the periocular skin is prepped with povidone iodine solution and draped with a plastic adhesive aperture drape. The lids are separated with a wire speculum, and the patient is asked to fixate using the surgical eye on

Against-the-rule postkeratoplasty astigmatism 120

105

90

75

45

135

30

150 165

15

180

0

A

345

195 210 225 240

•

Steep horizontal meridian

60

255

270

285

330 rad = 0 315 pwr = 0 deg = 300 dis = 5

Fig. 42.2  Corneal videokeratography of against-the-rule astigmatism. The arrows indicate direction of adjustment of running suture.

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B Flattening of steep horizontal meridian

• Fig. 42.3  Top (A) and side (B) views of arcuate keratotomy to correct steep horizontal meridian in against-the-rule postkeratoplasty astigmatism.

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Against-the-rule postkeratoplasty astigmatism Steep horizontal meridian

Horizontal arcuate incision vertical compression sutures

• Fig. 42.4  Surgeon’s view of horizontal arcuate incisions and “augmenting” vertical compression sutures.

a fixation mark built in the surgical microscope. Ultrasonic pachymetry is used to measure corneal thickness at different sites, especially at those where the cuts are planned. The Arc-T diamond knife’s depth is set at approximately 95% of corneal thickness. Two arcuate relaxing incisions are made at two hemi-meridians that the refraction, keratometry, or topographic analysis have depicted. Most of the time, the two hemi-meridians are 180° apart. While using the Arc-T diamond blade, the surgeon must roll his or her fingers to achieve an arcuate incision. Some corneal surgeons tended to perform relaxing incisions of three-quarters depth in the corneal recipient–host interface with the patient situated on the slit lamp. This technique became less popular recently because of lower predictability and effectiveness and increased risk of perforations and infections. If, after the first attempt, astigmatism is not reduced as desired, another double arcuate incision can be performed 1 mm inside the previous ones. Alternatively, the incisions can be deepened if slit lamp evaluation shows shallow incisions. Compression sutures can be used to augment the effect of the arcuate incisions (Fig. 42.4).

Femtosecond Laser-Assisted Arcuate Keratotomy (Video 42.1) A femtosecond (FS) laser with standard hardware configuration can also be used to create the cuts in arcuate keratotomy. To create an arcuate cut in the donor cornea, a 5.0- or 6.0-mm cut (flap diameter) is performed with a side cut at 90 degrees and depth set at 400 µm. The suction ring is not applied to allow appropriate decentration of the cuts. Using a micropore tape applied to the applanating contact lens, the length of the laser cut can be mechanically restricted to the desired arc length.

Wedge Resections In 1967, Troutman devised the corneal wedge-resection procedure for high astigmatism.29 Before this, a repeat keratoplasty was often the procedure of choice to correct excessive graft astigmatism. Today, wedge resection is reserved for cases of extremely high astigmatism and is recommended for astigmatism of 10 D or more. The procedure involves excising corneal tissue across the axis of the longer or flatter

corneal meridian and suturing the two opposing ends of the resected tissue. The corneal meridian is shortened and the meridian steepened to correct the astigmatism. Although limited in number, previous clinical studies show an approximate 40% to 70% reduction of mean astigmatism after corneal wedge resection. Compared with relaxing incisions, wedge resections can correct large amounts of astigmatism. Moreover, the wounds are sutured, unlike the gaping wounds of relaxing incisions, and astigmatism can be customized by selective suture removal. However, it may take months for the wound to stabilize and hence for stable keratometer readings.

Operative Technique As with relaxing incisions, all sutures should be removed and stable refractions, keratometry, and topographic analyses should be observed for at least 3 months. A retrobulbar block is used for anesthesia and akinesia. Intraoperatively, the axis of the flattest meridian is identified. A keratometerequipped surgical microscope is recommended. The surgeon should attend to intraoperative factors that may induce iatrogenic astigmatism, especially the lid speculum. Ultrasonic pachymetry is used in the axis where the resection is performed. Simultaneous partial penetrating incisions are made across the scar using a double-bladed diamond knife. The total excision area should be 90 degrees wide and at a depth of 90% to 95%. This wedge of tissue is excised with the diamond knife or by corneal scissors by freehand dissection. For approximately every 0.1 mm of resected tissue, a 1- to 2-D correction is obtained.30 Six to eight interrupted deep sutures are placed using 10-0 nylon. Suture loop tension is adjusted using slip knots under direct visualization of the surgical keratometer. Sutures are then tied down with square knots and buried. Tension should be placed to overcorrect the astigmatism by approximately 30% to 50%. To compensate for the astigmatic overcorrection in the meridian 90 degrees away from the wedge resection, two compression sutures may be placed during the immediate postoperative period until the wedge-resected sutures are removed. Selective suture removal can begin 8 to 10 weeks postoperatively. Sutures can be removed every 3 to 5 weeks until a satisfactory result is obtained. Sutures may be left indefinitely if the desired astigmatic correction occurs before all sutures are removed.

Femtosecond Laser-Assisted Wedge Resection (Video 42.3) FS laser-assisted wedge resection can overcome one important drawback of the manual technique: the difficulty in excising the exact amount of tissue in width and depth, which may account for the low predictability of the manual technique. The surgical technique using an FS laser is based on two arcuate cuts with different radii of curvature that intersect each other in the corneal periphery, creating a wedge-shaped wound. The depth of the FS laser ablation is set at 400 µm; the smaller-diameter cut (usually 6.0 mm) is performed with a side cut at 45 degrees and

CHAPTER 42  Postkeratoplasty Astigmatism: Etiology, Management, and Femtosecond Laser Applications

With-the-rule postkeratoplasty astigmatism Flat horizontal meridian

A Excised tissue (wedge)

B Wedge resection in flat (horizontal) meridian

• Fig. 42.5  Top (A) and side (B) views of wedge resection to correct extreme postkeratoplasty astigmatism.

the larger-diameter cut (usually 7.0 mm) is performed with a side cut at 90 degrees. This creates a wedge resection as shown in Fig. 42.5. A micropore tape attached to the applanating contact lens is used to limit the arc length for the laser cuts to approximately 90 degrees for the smallerdiameter area (6.0 mm) and to approximately 75 degrees for the larger-diameter area (7.0 mm). The contact lens can be rotated to create the wedge 180 degrees away. Feasibility of the technique was observed in porcine corneas and subsequently applied to treat high residual astigmatism after penetrating keratoplasty.31

Excimer Laser Another option for the correction of post-PK astigmatism is use of the excimer laser. This approach is fast becoming a primary procedure for patients who no longer tolerate spectacles or contact lenses. This new technology offers the advantage of effective and predictable results. Although several variations exist for both surface and lamellar ablations, to date only photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) have been extensively studied in patients following PK. The widespread use of PRK for the correction of refractive errors in otherwise normal eyes has prompted clinicians to use this method in patients after PK.32–45 Several studies have reported the efficacy of PRK for correction of astigmatism in post-PK patients. Although PRK has yielded acceptable results in many PK patients, significant problems—including corneal haze and significant postoperative regression—result in decreased predictability compared to PRK performed on native corneas. In addition, there have been reports of induced graft rejection following PRK.46 Advantages of LASIK over PRK for the correction of postoperative astigmatic errors in PK patients include decreased incidence of postoperative haze and the ability to

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correct over a broader range of myopia, hyperopia, and astigmatism. LASIK also provides for rapid visual rehabilitation, decreased stromal scarring, decreased irregular astigmatism, and minimized postsurgical regression.47–51 LASIK following PK should be performed by a specialist experienced in both LASIK and PK. Potential complications include those inherent in all LASIK procedures plus graftrelated complications, including the potential for wound dehiscence, induced graft rejection, reactivation of herpes simplex virus, irregular wound healing leading to higherorder astigmatism, and complications due to dry eye. Restrictions and contraindications to performing laser vision correction after PK are the same as for patients with normal corneas. Patients with a single functional eye, active connective tissue disease, and/or altered healing mechanisms are poor surgical candidates. Post-PK patients should undergo a full ocular exam prior to refractive surgery, including uncorrected and best spectacle-corrected visual acuity. Special attention to early signs of early graft rejection, recurrent herpetic ocular disease, or other inflammatory conditions that may adversely affect the surgical outcome are critical during the slit lamp examination. All phakic patients should undergo cycloplegic refraction. The status of the lens should be carefully evaluated, as cataracts are common after phakic keratoplasty and are a typical contraindication to laser correction. Patients with posterior IOLs are usually good candidates for LASIK. In contrast, patients with anterior chamber IOLs are at increased risk for lens-endothelial touch secondary to compression during the microkeratome pass.52–58 Preexisting retinal conditions that may impact bestcorrected visual acuity (BCVA) must be recognized. One of the most common indications for PK is pseudophakic bullous keratopathy, and 42% to 50% of these patients may have concomitant chronic cystoid macular edema.59–61 Patients may benefit from focal laser early in the postoperative period to accelerate visual acuity improvements. It should be noted that there is a 6% to 24% incidence of involutional macular degeneration following PK.58 All of these factors can lead to decreased postoperative BCVA and a protracted visual rehabilitation. In general, there are two different surgical approaches to performing LASIK in post-PK patients. Some authors advocate a staged procedure in which a lamellar flap is initially created, followed by a variable period of healing with late flap lifting and ablation if needed. These authors assert that cutting the lamellar flap alone has a significant positive impact on astigmatism.3,17,21 In this way, after the corneal flap has healed and the cornea has stabilized, the flap may be lifted and ablation may be performed to correct any residual astigmatic error. Other authors report similar results with a single procedure including keratotomy and ablation. This method offers the advantage of less manipulation of the corneal tissues with the theoretical benefit of decreased epithelial ingrowth, haze, and/or allograft rejection.4 To date, studies have shown no inherent advantage in the utilization of topography-supported customized ablations.

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Postsurgical topographical analysis shows significant reduction of regular astigmatism while higher-order astigmatic errors persist postoperatively. This approach has been largely abandoned. Studies to compare newer customized wavefront or prolate ablations are needed.

Toric Intraocular Lenses With the advent of toric intraocular lenses, several authors have described implementing such implants to correct for post-PK astigmatism. Frohn et al. in 1999 were the first to report the use of phacoemulsification combined with a toric intraocular lens to correct for cataract with associated post-PK astigmatism.53 Other attempts include the iris-clawed toric lenses in the anterior chamber of phakic patients.54 So-called “piggy-back” IOLs to correct for sphere and astigmatism separately have also been used with good results.54 Implantation of toric IOLs has multiple advantages over keratorefractive surgery. Toric IOLs allow for the correction of higher degrees of astigmatism than do refractive procedures. Toric lenses may be a good alternative in post-PK patients with contraindications to keratorefractive surgery, including cataracts, corneal ectasia, and corneal thinning. In addition, as such procedures are nonablative and not destructive to the transplanted corneal tissue, direct manipulation of the grafted corneal stroma is minimized. In the event of failure or complication, IOLs are easily removed or replaced, whereas corneal stromal ablation, being tissue destructive, is irreversible unless by regrafting. Use of toric lenses also eliminates some of the inherent risks of LASIK, including diffuse lamellar keratitis, buttonhole flaps, and flap dehiscence. Limitations of toric IOLs include surgically induced astigmatism with placement of the rigid polymethyl methacrylate (PMMA) lens through a 5-mm incision. Surgically induced astigmatism may be greater and more unpredictable in grafted versus native corneas.62,63 One study reports the improvement of BCVA from 20/40 with –0.25 sph –5.0 cycl 500 to 20/25 with –0.5 sph –3.25 cycl 800 after the combined procedure of phacoemulsification and toric IOL implantation.62 The results remained stable during the 2-year follow-up, and the patient reported visual satisfaction although a residual astigmatism of –3.25 D persisted after the procedure. This residual astigmatism was an unexpected outcome as only regular astigmatism was noted preoperatively from Scheimpflug imaging. However, a difficulty in visual outcome prediction is to be expected since the eye has previously been subjected to PKP. Of note is that the toric IOL is suited to PKP patients with predominantly regular astigmatism.63 Another thing to note is the pronounced endothelial cell loss in PKP patients during cataract surgery.

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45. Alessio G, Boscia F, Gabriella La Tergola M, et al. Corneal interactive programmed topographic ablation customized photorefractive keratectomy for correction of postkeratoplasty astigmatism. Ophthalmology. 2001;108:2029–2037. 46. Bilgihan K, Özdek SC, Akata F, et al. Photorefractive keratectomy for post-penetrating keratoplasty myopia and astigmatism. J Cataract Refract Surg. 2000;26:1590–1595. 47. Buchwald HJ, Lang GK. Cataract surgery with implantation of toric silicone lenses to correct high astigmatism after keratoplasty. Klin Monatsbl Augenheilkd. 2004;221:489–494. 48. Yoshida K, Tazawa Y, Demong TT. Refractive results of post penetrating keratoplasty photorefractive keratectomy. Ophthalmic Surg Lasers. 1999;30:354–359. 49. Campos M, Hertzog L, Garbus J, et al. Photorefractive keratectomy for severe postkeratoplasty astigmatism. Am J Ophthalmol. 1992;114:429–436. 50. Lazzaro DR, Haight DH, Belmont SC, et al. Excimer laser keratectomy for astigmatism occurring after penetrating keratoplasty. Ophthalmology. 1996;103:458–464. 51. Tuunanen TH, Ruusuvaara PJ, Uusitalo RJ, et al. Photoastigmatic keratectomy for correction of astigmatism in corneal grafts. Cornea. 1997;16:48–53. 52. Amm M, Duncker GI, Schroder E. Excimer laser correction of high astigmatism after keratoplasty. J Cataract Refract Surg. 1996;22:313–317. 53. Frohn A, Dick HB, Thiel HJ. Implantation of a toric poly (methyl methacrylate) intraocular lens to correct high astigmatism. J Cataract Refract Surg. 1999;25:1675–1678. 54. Tehrani M, Stoffelns B, Dick HB. Implantation of a custom intraocular lens with a 30-diopter torus for the correction of high astigmatism after penetrating keratoplasty. J Cataract Refract Surg. 2003;29:2444–2447. 55. Nuijts RM, Abhilakh Missier KA, Nabar VA, et al. Artisan toric lens implantation for correction of postkeratoplasty astigmatism. Ophthalmology. 2004;111:1086–1094. 56. Tehrani M, Dick HB. Implantation of an ARTISAN toric phakic intraocular lens to correct high astigmatism after penetrating keratoplasty. Klin Monatsbl Augenheilkd. 2002; 219:159–163. 57. Vajpayee RB, Sharma N, Sinha R, et al. Laser in-situ keratomileusis after penetrating keratoplasty. Surv Ophthalmol. 2003;48: 503–514. 58. Donnenfeld ED, Solomon R, Biser S. Laser in situ keratomileusis after penetrating keratoplasty. Int Ophthalmol Clin. 2002; 42(4):67–87. 59. Heidemann DG, Dunn SP. Transsclerally sutured intraocular lenses in penetrating keratoplasty. Am J Ophthalmol. 1992;113: 619–625. 60. Kornmehl EW, Steinert RF, Odrich MG, et al. Penetrating keratoplasty for pseudophakic bullous keratopathy associated with closed-loop anterior chamber intraocular lenses. Ophthalmology. 1990;97:407–414. 61. Busin M, Zambianchi L, Garzione F, et al. Two-stage laser in situ keratomileusis to correct refractive errors after penetrating keratoplasty. J Refract Surg. 2003;19:301–308. 62. Allard K, Zetterberg M. Toric IOL implantation in a patient with keratoconus and previous penetrating keratoplasty: a case report and review of literature. BMC Ophthalmol. 2018;18(1):215. 63. Kersey JP, O’Donnell A, Illingworth CD. Cataract surgery with toric intraocular lenses can optimize uncorrected postoperative visual acuity in patients with marked corneal astigmatism. Cornea. 2007;26(2):133–135.