This book focuses on Gems of Ophthalmology--Cornea and Sclera. Cornea is one of the important structures of the eyeball.
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Gems of Ophthalmology
CORNEA AND SCLERA
Gems of Ophthalmology
CORNEA AND SCLERA
Editors HV Nema MS Former Professor and Head Department of Ophthalmology Institute of Medical Sciences Banaras Hindu University Varanasi, Uttar Pradesh, India
Nitin Nema MS DNB Professor Department of Ophthalmology Sri Aurobindo Institute of Medical Sciences Indore, Madhya Pradesh, India
The Health Sciences Publisher New Delhi | London | Panama
Jaypee Brothers Medical Publishers (P) Ltd Headquarters Jaypee Brothers Medical Publishers (P) Ltd. 4838/24, Ansari Road, Daryaganj New Delhi 110 002, India Phone: +91-11-43574357 Fax: +91-11-43574314 E-mail: [email protected] Overseas Offices JP Medical Ltd. 83 Victoria Street, London SW1H 0HW (UK) Phone: +44-20 3170 8910 Fax: +44(0)20 3008 6180 E-mail: [email protected] Jaypee Brothers Medical Publishers (P) Ltd. 17/1-B, Babar Road, Block-B, Shyamoli Mohammadpur, Dhaka-1207 Bangladesh Mobile: +08801912003485 E-mail: [email protected]
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Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2018, Jaypee Brothers Medical Publishers The views and opinions expressed in this book are solely those of the original contributor(s)/author(s) and do not necessarily represent those of editor(s) of the book. All rights reserved. No part of this publication may be reproduced, stored or transmitted in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, without the prior permission in writing of the publishers. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. Medical knowledge and practice change constantly. This book is designed to provide accurate, authoritative information about the subject matter in question. However, readers are advised to check the most current information available on procedures included and check information from the manufacturer of each product to be administered, to verify the recommended dose, formula, method and duration of administration, adverse effects and contraindications. It is the responsibility of the practitioner to take all appropriate safety precautions. Neither the publisher nor the author(s)/editor(s) assume any liability for any injury and/or damage to persons or property arising from or related to use of material in this book. This book is sold on the understanding that the publisher is not engaged in providing professional medical services. If such advice or services are required, the services of a competent medical professional should be sought. Every effort has been made where necessary to contact holders of copyright to obtain permission to reproduce copyright material. If any have been inadvertently overlooked, the publisher will be pleased to make the necessary arrangements at the first opportunity.
Inquiries for bulk sales may be solicited at: [email protected] Gems of Ophthalmology—Cornea and Sclera First Edition: 2018 ISBN: 978-93-5270-248-0
Contributors Vinay Agarwal MS
Frank Joseph Goes MD
Consultant Ophthalmologist Mumbai, Maharashtra, India
Director Oagchirurgie-Oagheekunde Antwerp, Belgium
Sreedharan Athmanathan MD DNB Virologist LV Prasad Eye Institute Hyderabad, Telangana, India
Mohamed El Bahrawy MD Consultant, VISSUM Institute of Ophthalmology Alicante Alicante, Spain
Jorge L Alió Del Barrio MD PhD Consultant VISSUM Institute of Ophthalmology Alicante Alicante, Spain
Jaya Gupta MS Vision Research Foundation Sankara Nethralaya Chennai, Tamil Nadu, India
Nidhi Gupta MS Vision Research Foundation Sankara Nethralaya Chennai, Tamil Nadu, India
Noopur Gupta MD Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India
MS FMRF FNAMS FIC Path, FAICO
Director Department of Uveitis and Ocular Pathology Sankara Nethralaya Chennai, Tamil Nadu, India
Charmaine Chai MBBS MMed (Ophth) Associate Consultant National University Hospital Singapore
Rajesh Fogla MS DNB FRCS Consultant Sankara Nethralaya Chennai, Tamil Nadu, India
Ashok Garg MS PhD FAIMS FIAO Chairman and Medical Director Garg Eye Institute and Research Centre Hissar, Haryana, India
Stephen Hilton OD Department of Ophthalmology West Virginia University Morgantown, West Virginia, USA
Soosan Jacob MS FRCS DNB Director and Chief Dr Agarwal’s Refractive and Cornea Foundation Dr Agarwal’s Group of Eye Hospitals Chennai, Tamil Nadu, India
Joveeta Joseph PhD Microbiologist Jhaveri Microbiology Centre Brien Holden Eye Research Centre LV Prasad Eye Institute Hyderabad, Telangana, India
vi Gems of Ophthalmology—Cornea and Sclera
G Madhavi DNB
N Venkatesh Prajna FRCOphth
Consultant Srikiran Institute of Ophthalmology Kakinada, Andhra Pradesh, India
Professor Aravind Eye Hospital and Postgraduate Institute Madurai, Tamil Nadu, India
Parthopratim Dutta Majumder MS Consultant Department of Uveitis and Ocular Pathology Sankara Nethralaya Chennai, Tamil Nadu, India
Quresh Maskati MS FCPS DOMS FICS Director Cornea Services, Eye Clinic Mumbai, Maharashtra, India
Francisco Arnalich Montiel MD VISSUM Institute of Ophthalmology Alicante Alicante, Spain
G Mukherjee MD Director Mukherjee Eye Klinik New Delhi, India
Rajib Mukherjee MS Director and Senior Consultant Cornea and Ocular Surface Mukherjee Eye Klinik New Delhi, India
Prema Padmanabhan DNB FRCOphth Director Nethralaya and Cornea Services Medical Research Foundation Sankara Nethralaya Chennai, Tamil Nadu, India
Gunisha Pasricha PhD Assistant Manager Research and Development Hi Tech Biosciences India Ltd Pune, Maharashtra, India
Shaila Patel MS Dr Agarwal’s Group of Eye Hospitals and Eye Research Centre Chennai, Tamil Nadu, India
Lalitha Prajna MD DNB Consultant Microbiologist Aravind Eye Hospital and Postgraduate Institute Madurai, Tamil Nadu, India
VK Raju MD FRCS FACS Professor of Clinical Ophthalmology West Virginia University Morgantown, West Virginia, USA
Srinivas K Rao MD Consultant Sankara Nethralaya Chennai, Tamil Nadu, India
Manotosh Ray MD FRCS Associate Consultant National University Hospital Singapore
Ritika Sachdev MD Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India
Gagan Sahni OD Senior Consultant Contact Lens Designing and Fitting Mukherjee Eye Klinik New Delhi, India
Jorge L Alió y Sanz MD PhD Director, VISSUM Institute of Ophthalmology Alicante Alicante, Spain
Savitri Sharma MD Director of Laboratory Services LV Prasad Eye Institute Network Head, Jhaveri Microbiology Centre Brien Holden Eye Research Centre LV Prasad Eye Institute Hyderabad, Telangana, India
Rajesh Sinha MD FRCS Professor Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India
Jerry Tan FRCS FRCOphth FAMS Consultant Camden Medical Centre Orchard Boulevard, Singapore
Radhika Tandon MD DNB FRCS MRCOphth Professor Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India
George N Thomas MD National University Hospital Singapore
Jeewan S Titiyal MD Professor Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India
M Vanathi MD
Professor Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India
C Veerajayalakshmi MS Fellow Aravind Eye Hospital and Postgraduate Institute Madurai, Tamil Nadu, India
Shefali Vyas MD FAAP Associate Director Children’s Kidney Center RWJ Barnabas Health West Orange, New Jersey, USA
Preface Cornea is one of the important structures of the eyeball. It serves as a window to convey visual images. Diseases of the cornea impair vision and an individual loses his independence. In spite of marked reduction in the incidence of infectious diseases of the anterior segment of the eye, congenital anomalies, vitamin A-deficiency, traumatic and degenerative diseases of the cornea cause significant blindness. The corneal blindness can be prevented or cured by adopting suitable measures. Cornea is the main source of refractive errors because a major part of refraction occurs at the corneal surface. Refractive errors contribute to a high percentage of impairment of vision worldwide. The present book on cornea is designed to provide an up-to-date information on current important topics. Corneal topography not only helps in diagnosing refractive errors, but also ectatic conditions like keratoconus and Pellucid marginal degeneration. It aids in planning the refractive surgery and fitting of contact lenses. Corneal confocal microscopy is another diagnostic tool which can distinguish between normal and abnormal corneal structures at cellular level which is used in the diagnosis of corneal diseases. Current topics on refractive surgery, such as Laser assisted in situ keratomileusis (LASIK), LASIK in hyperopia, small incision lenticular extraction (SMILE) vs LASIK and complications of LASIK and its management have been described in the book. Chapter on diagnostic procedures in infectious keratitis presents a detail account of investigations for the benefit of interested readers. Relatively uncommon infections like fungal keratitis and Acanthamoeba keratitis are also included. Corneal dystrophies are described comprehensively with their latest classification and management. Keratoconus causes severe visual impairment. Recently, increasing interest is generated in its management with the introduction of corneal cross-linking. The book contains chapters on the management of keratoconus by corneal cross-linking, intrastromal corneal ring segments (INTACS) and lamellar keratoplasty. Recent procedures in lamellar keratoplasty are tissue targeted. In endothelial keratoplasty, normal stroma and the surface are persevered and Descemet’s membrane and endothelium are targeted resulting in quicker rehabilitation. While in deep anterior lamellar keratoplasty (DALK), corneal stroma with Bowman membrane and epithelium are replaced leaving the healthy Descemet’s membrane and endothelium intact, thus minimizing the
x Gems of Ophthalmology—Cornea and Sclera
chances of rejection. The other procedure is Descemet’s stripping automated endothelial keratoplasty (DSAEK). It is a much faster keratoplasty and has a shorter visual recovery time. Introduction of different types of lamellar keratoplasty may facilitate more corneal transplants because one cornea can be used for more than one patient. DALK has been described in some detail while a brief account of various types of lamellar keratoplasty has been given in the chapter on Advances in keratoplasty. Chapters on Diagnosis of dry eye, Ocular surface disorder, Keratoprosthesis, Cystinosis and Corneal changes in contact lens users are also included in the book. The editors assure the readers that the major part of the work presented in this book comes from the Recent Advances in Ophthalmology series edited by Dr HV Nema and Dr Nitin Nema. In each chapter, author/s have provided references for the benefit of those who want to read the topic in detail. The book is multi-authored, therefore, repetition could not be avoided. Readers can take the advantage of knowing the views of different authors. However, special effort has been put to avoid ambiguity. The book is concise and information on corneal diseases is presented in an easily readable form. The book is profusely illustrated. Postgraduate students, residents, and general ophthalmologists will find it useful in their day-to-day clinical practice.
HV Nema MS Nitin Nema MS DNB
Acknowledgments We wish to record our grateful thanks to all authors of chapters for their spontaneity, cooperation and hard work. Some of them have revised their chapters. Our special thanks go to Drs. Soosan Jacob, Savitri Sharma and Rajib Mukherjee for contributing their chapters on a short notice. Credit goes to Mr Jitendar P Vij (Group Chairman), Jaypee Brothers Medical Publishers (P) Ltd who has agreed to start a new series—Gems of Ophthalmology. Cornea and Sclera is the first book of this series. Ms Kritika Dua, Development Editor deserve our appreciation for her continued interest in refining chapters and eliminating plagiarism.
Contents 1. Corneal Topography
Francisco Arnalich Montiel, Jorge L Alió Del Barrio, Jorge L Alió y Sanz
2. Corneal Confocal Microscopy
4. SMILE versus LASIK
5. LASIK in Hyperopia
6. LASIK—Complications and Management
7. Zyoptix Wavefront-guided Customised Ablation in Retreated Corneas
8. Diagnostic Procedures in Infectious Keratitis
9. Fungal Keratitis
10. Herpetic Keratitis
11. Acanthamoeba Keratitis—Pathogenesis and Diagnosis
12. Corneal Dystrophies
13. Management of Keratoconus
14. Corneal Collagen Cross-linking
15. Intrastromal Corneal Ring Segments
16. Deep Anterior Lamellar Keratoplasty
Manotosh Ray, George N Thomas Frank Joseph Goes
Jorge L Alió y Sanz, Mohamed El Bahrawy VK Raju, Stephen Hilton, G Madhavi Rajesh Fogla, Srinivas K Rao, Prema Padmanabhan
Savitri Sharma, Sreedharan Athmanathan
N Venkatesh Prajna, Lalitha Prajna, C Veerajayalakshmi Charmaine Chai, Manotosh Ray Savitri Sharma, Joveeta Joseph, Gunisha Pasricha
Rajesh Sinha, Noopur Gupta, Ritika Sachdev, Radhika Tandon, Jeewan S Titiyal Prema Padmanabhan, Nidhi Gupta Ashok Garg
Shaila Patel, Soosan Jacob
Jaya Gupta, Prema Padmanabhan
xiv Gems of Ophthalmology—Cornea and Sclera
17. Dry Eye Disease
18. Ocular Surface Reconstructions
19. Advances in Keratoplasty
22. Corneal Changes in Contact Lens Users
23. Episcleritis and Scleritis
Manotosh Ray, Rajesh Sinha, M Vanathi, Noopur Gupta Soosan Jacob
Quresh Maskati Shefali Vyas
Rajib Mukherjee, Gagan Sahni, G Mukherjee
Parthopratim Dutta Majumder, Jyotirmay Biswas
Corneal Topography Francisco Arnalich Montiel, Jorge L Alió Del Barrio, Jorge L Alió y Sanz
BACKGROUND The cornea is the most important refractive element of the human eye, providing approximately two-thirds of its optical power, accounting for about 43–44 diopters at the corneal apex.1 Since its surface is irregular and aspherical, it is not radially symmetric, and simple measurement techniques are inadequate. The great upsurge in refractive surgery led to a need for improved methods to analyze corneal shape since refraction and keratometric data alone were insufficient to predict surgical outcomes. Understanding and quantifying corneal contour or shape has become essential in planning modern surgical intervention for refractive surgery, as well as in corneal transplantation, and it is also very valuable for assessing optical performance of the eye. The different methods for evaluating the anterior surface of the cornea, developed over several centuries, have, in the present era, led to the modern corneal topography.
FIRST STEPS IN CORNEAL MEASUREMENT In 1619, Scheiner analyzed corneal curvature by matching the image of a window frame reflected onto a subject’s cornea with the image produced by one of his calibrated spheres.
Keratometer In 1854, Helmhotz described the first true keratometer, which he called an ophthalmometer.2 With some minor improvements, it is still being used clinically for calculating refraction, intraocular lens power and contact lens fitting normal corneas.
2 Gems of Ophthalmology—Cornea and Sclera
This apparatus is based on the tendency of the anterior corneal surface to behave like a convex mirror and reflect light. The projection of four point, mire, onto the cornea, creates a reflected image that can be converted into a corneal radius, ‘r’, using a mathematical equation that considers distance from the mire to cornea (75 mm in the keratometer), image size and mire size (64 mm in the keratometer). The corneal radius can be transformed into dioptric power using the formula: DP =
(Index of refraction of the lens − 1) r
The standard keratometric index represents the combined refractive index of the anterior and posterior surfaces of the cornea, considers the cornea as a single refractive surface, and is 1.3375. Thus, the equation can be simplified to: DP =
Although keratometers are still common in ophthalmology clinics, they do have specific limitations that need to be considered in order to avoid misleading conclusions. • Most traditional keratometers measure the central 3 mm of the cornea, which only accounts for 6% of the entire surface. • It assumes that the cornea is a perfectly spherocylindrical surface, which it is not. The cornea is aspheric in shape, flattening between the center and the periphery. Usually the central corneal curvature is fairly uniform, and this is the reason why it can be used to calculate corneal power in normal patients. However, this is not true in some pathologies like ectatic disorders or after refractive surgery. • The keratometer provides no information as to the shape of the cornea either inside or outside the contour of the mire. Several corneal shapes can all give the same keratometric value so this apparatus is of little use should it become necessary to reconstruct the whole corneal morphology.
Keratoscopy and Photokeratoscopy Goode presented the first keratoscope in 1847. Placido was the first to photograph the corneal reflections of a series of illuminated concentric rings (known as Placido’s rings) in 1880 (Fig. 1.1). Finally, in 1896, Gullstrand was the first to develop a quantitative assessment of photokeratoscopy.3 The keratoscope, like a keratometer, projects an illuminated series of mires onto the anterior corneal surface, usually consisting of concentric rings. The distance between the concentric rings or mires gives the observer an idea of the corneal shape. A steep cornea will crowd of the mires, while a flat cornea will spread them out. Surface irregularity is seen as mire distortion.
Corneal Topography 3
Fig. 1.1: Placido rings.
When a photographic camera is attached to the keratoscope, we have a photokeratoscope, which gives semiquantitative and qualitative information about the paracentral, midperipheral and peripheral cornea. Based on the mathematical equation, it is possible to calculate corneal power from object size. Still, photokeratoscopy gives limited information on the central area, which is not covered by the mires.
Videokeratoscopy At the beginning of this century, modern corneal topographers were based on videokeratoscopy.4 A video camera is attached to the keratoscope, and the information is analyzed by a computer that displays a color-coded map of power distribution or corneal curvature of the anterior corneal surface (Fig. 1.2). It overcomes some of the limitations of other methods, since it measures larger areas of the cornea, with a much larger number of points thus increasing resolution. Computer technology makes it possible to create permanent records and do multiple data analyses.
FUNDAMENTALS AND TECHNOLOGICAL APPROACHES TO CORNEAL TOPOGRAPHY Shape of the Normal Cornea The anterior corneal surface is a refractive surface characterized by an almost spherical shape. The human cornea is not a perfect sphere and is usually assumed to have a conic section. This model could be represented in a simple way by means of the equation: X 2 + Y 2 + (1 + Q) Z 2 − 2 RZ = 0
4 Gems of Ophthalmology—Cornea and Sclera
Fig. 1.2: Videokeratography system.
where the Z-axis is the axis of revolution of the conic, R is the radius at the corneal apex, and Q is asphericity, a parameter that is used to specify the type of conicoid. For a perfect sphere this parameter takes the value of zero (Q = 0), for an ellipsoid with the major axis in the X-Y plane (oblate surface) the asphericity is positive (Q > 0), for an ellipsoid with the major axis in the Z-axis (prolate surface) asphericity is negative (- 1 < Q < 0), while for a paraboloid with its axis along the Z-axis the value is - 1, and it is less than - 1 for a hyperboloid. Other parameters have been defined to classify the conicoid form of the cornea: ‘P,’ the shape factor (P = Q + 1), or the eccentricity value, ‘e,’ defined as e = − Q . Several studies have shown that the anterior corneal configuration tends to be prolate, i.e., the cornea progressively flattens out periphery by 2–4 diopters of flattening.5 The asphericity of the normal cornea depends on the study ranges from - 0.26 to - 0.11. This tendency can be detected in the topographic map. Toward the periphery, dioptric power appears to decline, and the nasal area flattens more than the temporal area (Fig. 1.3). This could be helpful in distinguishing right eye topography from the left eye topography. The topographic patterns of the two corneas of the same individual often show mirror-image symmetry. Corneal topographic patterns (Figs. 1.4A to D) have been studied in normal eyes and the following shapes have been found:5 round (23%), oval (21%), symmetric bow-tie typical for regular astigmatism (18%), asymmetric bow-tie (32%) and irregular astigmatism (7%). In the round and oval shapes there is an area of uniform dioptric power close to 43 diopters (D) in the center of the cornea. The bow-tie configuration reflects the existence of corneal
Corneal Topography 5
Fig. 1.3: Corneal topography in a normal right eye. There is a flattening toward the periphery, more pronounced at the nasal area.
astigmatism. Depending on the position of the axes, corneal astigmatism is defined as against-the-rule (the steepest axis is horizontal), with-the-rule (the steepest axis is vertical) or oblique (the steepest axis is near the meridian angles of 45° or 135°).
CORNEAL TOPOGRAPY: CURRENT TECHNOLOGIES Corneal topography is a noninvasive exploratory technique that graphically describes the geometric characterization of the morphology of the cornea, that permits us differentiating standard normal patterns form the pathological cornea.6 Current topographers are based on either systems based on the light reflection on the cornea, or systems based on the projection of a slit light into the cornea with different technology.
Systems Based on the Light Reflection on the Cornea: Curvature Based Topographers Placido Disk System A Placido disk system consists of a series of concentric illuminated rings or mires that are reflected off of the cornea and recorded by videocomputerized systems.4 The topographer uses an algorithm to translate these reflected images into radial curvature of the corneal surface. Height and slope data derived from the radial curvature of the anterior corneal surface are represented as a corneal keratometric map that follows a color scale developed by the University of Louisiana. Flat curves are represented with
6 Gems of Ophthalmology—Cornea and Sclera
Figs. 1.4A to D: Normal corneal topographic patterns: (A) Oval topographic pattern, (B) bow-tie pattern that shows an against-the-rule astigmatism, (C) with-the-rule astigmatism and (D) oblique astigmatism.
Corneal Topography 7
cool colors (blue or violet), while warm colors (red or orange) correspond to high curvature. Mild colors (green or yellow) correspond to medium curvature equal to the reference sphere. Currently, several companies manufacture instruments called videokeratoscopes that picture corneal shape based on the Placido disk method, and, in fact, this approach has been the most clinically and commercially successful up to the last decade. Two types of Placido targets have been used: 1. Large diameter target (disk-shaped): This is less sensitive to misalignment due to a long working distance, but there can be a loss of data due to interference by the patient’s brow and nose. 2. Small diameter target (cone-shaped): This is designed for a short working distance and can be influenced by automatic alignment and focusing or compensation of misalignment for accuracy. It does not present data loss due to shadows. Limitations: 1. Placido-based apparatus creates a 3D system by making geometric assumptions about the cornea since the apparatus does not measure corneal surface directly. These assumptions are not accurate for irregular and aspheric corneas. 2. The reflection technique depends on the integrity and normality of the tear layer.
Interferometric Method-based Systems In essence, a reference surface (or its hologram) is compared to the tested surface, the corneal surface and interference fringes are produced as a result of differences between the two shapes, which can be interpreted as a contour map of surface elevations.7 Interference techniques are used in the optical industry to detect lens and mirror aberrations of subwavelength dimensions. High accuracy is theoretically possible, but clinical use has not been very wide-spread as yet.
Moire Deflectometry-based Systems The deflections of the rays reflected off the corneal surface are analyzed to build up a surface elevation map.7
Systems Based on the Projection of a Slit Light onto the Cornea: Elevation-based Topographers The common denominator of this technology is the projection of a slit light onto the cornea. Interestingly many of these corneal topographies integrate a dual technology, and in a first stage they use light reflection on the cornea by means of a Placido disk to obtain curvature and refractive power data, followed by capturing the image of the scattered light from the slit light to measure corneal elevations of the entire corneal segment. From these
8 Gems of Ophthalmology—Cornea and Sclera
two-dimensional (2D) cross-sections, it is possible to create a reliable threedimensional model. Depending on the spatial arrangement of the photographic systems, we can distinguish the following two different systems.
Systems Based on the Principle of Normal Photography Its main feature is that the plane of the camera lens is located parallel with the image.8 When the slit image is on the cornea, it splits into a specular reflection and a refracted beam that penetrates the corneal surface and is scattered by the tissue of the cornea. An image of this scattered light within the corneal tissue is captured by an imaging system, which consists of a camera lens located in parallel with the image. It uses triangulation to measure the elevation of the anterior and posterior corneal surface with respect to a reference plane.8 The most popular system using this principle is the Orbscan (Bausch & Lomb Incorporated, USA) (Fig. 1.5), which was the first commercial device that was able to assess the posterior corneal surface.8 It has dual technology as it uses Placido disk and slit-based systems to obtain 40 slit images of the cornea. These images are captured over one second and are then recorded providing different maps of the anterior and posterior corneal surfaces, and also pachymetric data.
Systems Based on the Principle of Scheimpflug Photography Its main feature is that the plane of the camera lens is placed sideways to the image. Scheimpflug imaging is based on the Scheimpflug principle, which
Fig. 1.5: Orbscan II system.
Corneal Topography 9
Fig. 1.6: Scheimpflug-based topographer—Pentacam.
occurs when a planar subject is not parallel to the image plane. In this scenario, an oblique tangent can be drawn from the image, object and lens planes, and the point of intersection is the Scheimpflug intersection, where the image is in best focus.9 With a rotating Scheimpflug camera, the devices can obtain many Scheimpflug images in seconds. The main commercial systems based on this principle are Pentacam (Oculus, USA), Galilei (Ziemer, Switzerland) and Sirius (CSO, Italy), which offer repeatable measurements of the corneal curvature and other anatomical measurements of the anterior segment (Fig. 1.6). Although the instruments based on rotating Scheimpflug cameras are considered the most comprehensive and accurate, they also have some limitations. Lower imaging speed can increase the risk of motion artifacts, even though there is an inbuilt second camera to control for eye movements. For example, commercially available Pentacam uses a rotating Scheimpflug camera (180°) to provide a 3D scan of the anterior segment of the eye. It requires 2 seconds to complete 25 radial scans. Moreover, radial scanning may not provide sufficient scan density of the corneal periphery, needing interpolation. Another limitation is that the instruments using the Scheimpflug principle are less accurate in comparison to Placido-based ones in providing traditional curvature maps of the anterior surface, and only show moderate agreement in simulated keratometry values. The Sirius system has a dual technology and combines Scheimpflug camera and a small-angle Placido disk topographer with 22 rings. The data for the anterior surface are finally determined by merging the Placido image and the Scheimpflug image using a proprietary method. Systems with a single Scheimpflug channel use a mathematical equation to estimate compensation for an off-center measurement, however, to
10 Gems of Ophthalmology—Cornea and Sclera
properly compensate for an off-center measurement, a dual Scheimpflug technology is needed.9 Galilei uses a monochromatic slit-light source which combines dual Scheimpflug cameras and a Placido disk to measure both anterior and posterior corneal surfaces.
Systems Based on Optical Coherence Tomography Optical coherence tomography (OCT) of the cornea and anterior segment is an optical method of cross-sectional scanning based on reflection and scattering of light from the structures within the cornea.10 Measuring different reflectivity from structures within the cornea by a method of optical interferometry produces the cross-section image of the cornea and other anterior segment structures. In optical interferometry, the light source is split into the reference and measurement beams. The measurement beam is reflected from ocular structures and interacts with the reference light reflected from the reference mirror, a phenomenon called interference. The coherent or positive interference characterized by an increased resulting signal is measured by the interferometer, and, subsequently, the position of the reflecting structure of the eye can be determined.10 In this way, the structures of the anterior segment can be visualized with a high degree of resolution (currently 18 microns axial and 60 microns transverse). In 2005, a commercial 1310 time-domain OCT system for anterior segment imaging was launched under the name Visante OCT (Carl Zeiss, Inc.). Currently although it is widely used OCT device for dedicated in vivo anterior segment imaging and creates pachymetry maps, it cannot perform topographic analysis of the cornea, mostly because of limitations in acquisition time. The introduction of Fourier domain OCT in 2002 with the primary advantage of increased sensitivity or speed and the possibility of 3D imaging promised to improve the ability of OCT to quantitatively assess the corneal topography.10 Nowadays, commercial high speed 3D anterior segment OCT based on swept source OCT provide higher resolution cross-sectional images that can be used to obtained OCT-based corneal topography. The commercially available OCT-based topographer is SS-1000 CASIA (Tomey Corporation, Inc., Nagoya, Japan) (Fig. 1.7).
PERFORMING A GOOD TOPOGRAPHY EXAMINATION Corneal topography is a noninvasive imaging technique for mapping the surface curvature of the cornea. The specific method varies depending on the device used, but some aspects are common. The patient is seated facing a bowl containing an illuminated pattern which is focused on the anterior surface of his cornea. The reflected pattern is analyzed by a computer that calculates the shape of the cornea by means of different graphic formulae.11 Although computer programs are created to be very accurate, they cannot
Corneal Topography 11
Fig. 1.7: Optical coherence tomography (OCT)-based topographer—CASIA SS-1000.
Fig. 1.8: Distortion of the placido rings because of tear film breakup.
recognize, and account for, every problem. Critical points for precise measurement are accurate alignment, centring and focusing. They depend on the ability of the examiner to take a good measurement. Another potential source of error is tear film irregularities, for example focal flattening over a dry patch. These may be most easily identified on the raw image. Tear film breakup causes mistracking of the mires and artefacts in the topography pattern and will apparently look like significant irregularities (Fig. 1.8). These corneal irregularities could suggest a corneal pathology, such as keratoconus, and result in wrong diagnosis (Figs. 1.9A and B). To avoid
12 Gems of Ophthalmology—Cornea and Sclera
Figs. 1.9A and B: (A) Raw image and (B) topographic irregularities and patches of the map in the same eye because of a tear film with large instability.
disturbing the tear film, corneal topography should be performed before administering dilating drops and taking intraocular pressures. In addition, one must avoid artefacts induced by the nose or the eyelids, which can lead to a loss of information in certain areas (Figs. 1.10A and B). These errors are transformed into black areas or areas without data on the
Corneal Topography 13
Figs. 1.10A and B: Loss of information of certain areas of the cornea due to eyelids not opened enough. (A) Topographic map (B) Scheimpflug image.
topographic map. Correct positioning of the head, eyes and eyelid opening should be ensured to avoid these problems.
INTERPRETATION OF CORNEAL TOPOGRAPHY MAPS Accurate interpretation of corneal shape using color-coded topographic maps is difficult and confusing for many clinicians, even experienced cornea specialists. In order to obtain the best performance in the analysis of corneal maps, several important points must be taken into consideration.
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Fig. 1.11: Photokeratoscope raw image.
It is critical to check the raw image first. After that it is necessary to focus on the scale and step intervals with which the color-coded topographic map is built up. It is also important to review different topographic displays, especially when evaluating irregular or postsurgery corneas.
Raw Photoqueratoscope Image The photokeratoscope image displays the Placido’s rings projected onto the cornea (Fig. 1.11). When considering a color-coded map, the clinician must check that the unprocessed data upon which it is based are reliable. If the videokeratoscope image is irregular, data cannot be processed by the instrument in a meaningful way. Thus, for Placido disk-based computerized videokeratoscopes, the videokeratoscope image should not be ignored. In fact, it is recommended to check this map before referring to any of the other topographic displays, and to go back to it when there are any doubts regarding the accuracy of the displayed data. This image provides important information for assessing tear film quality, mire centring on the cornea, lid opening, or the causes of local irregularities, and other artefacts. If the device used displays computer tracking of the Placido mires it is important to rule out tracking errors. Devices that rely only on scanning slit technology to analyze the anterior corneal surface lack of the valuable information provided by the rawvideokeratoscope image.12 Whether the resulting map is based on reliable primary data or not is impossible to verify without the raw image. Some instruments identify regions of uncertainty, showing mire distortions that cannot be reliable, by leaving blank areas on the color-coded map. Other
Corneal Topography 15
instruments merely extrapolate onto the uncertain regions information gathered from adjacent regions with reliable data. For Scheimpflug technology, its images should also be checked before looking at the resulting maps, and correct centration and focus should be assured.
Color-coded Scales The shape of a cornea can be measured and represented by color-coded maps in which a given color indicates a different curvature or elevation. The usual color spectrum for corneal powers shows near-normal power as green, lower-than-normal power as cool colors (blues) and higher-than-normal powers as warm colors (reds). Most topographers offer absolute as well as normalized scales to allow the clinician to customize the information for maximal clinical value (Figs. 1.12A and B): • Normalized scale (variable scale) uses a given color for different curvatures or elevations on each cornea analyzed, depending on the range for that particular cornea, determined by its flattest and steepest values. These maps are difficult to interpret and can lead to an incorrect diagnosis since they may magnify subtle changes in corneal surface if the scale is too narrow, or minimize large distortions if the scale is too wide. In addition, color recognition, one of the primary clues used to interpret on corneal topography, is lost with a variable scale, since it uses different colors for different eyes. • Absolute scale (fixed scale) uses the same color for the same curvature or elevation no matter which eye is examined. However, there are many different absolute scales since the examiner can choose different variables such as range or step size (intervals in color changes). For the specified scale, however, each display will use the same colors, steps and range. In order to facilitate comparisons over time and between patients, it is recommended to stick with a given fixed scale for routine examinations and to change the scale in the particular cases in which this becomes necessary. As an example, the popular Klyce/Wilson scale ranges from 28 D to 65 D in equal 1.5 D intervals. Currently, there is no consensus as to the best absolute scale, but in general, dioptric scales with intervals smaller than 0.5 D are not clinically useful and provide details that are not relevant and may complicate map interpretation. For corneas with large dioptric ranges, for instance in advanced keratoconus intervals greater than 0.5 D are recommended. Regarding scales for elevation maps, elevation steps of approximately 5 microns appear to be clinically useful. As mentioned earlier, color pattern recognition makes it possible to identify common topographic patterns such as the corneal cylinder (Fig. 1.13), keratoconus (local area of inferonasal steepening) or pellucid marginal degeneration (butterfly pattern or inferior arcuate steepening), as well as features associated with refractive surgery (Fig. 1.14), such as optical zone size, centration and central islands.
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Figs. 1.12A and B: Corneal topography map represented using (A) a normalized relative scale and (B) an absolute scale.
Corneal Topography 17
Fig. 1.13: Bow-tie pattern.
Fig. 1.14: Corneal topography after myopic laser in situ keratomileusis (LASIK).
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Topographic Displays: Corneal Maps Maps can be obtained from the anterior and posterior surface except in the case of pure Placido disk technology. • Axial map (sagittal map): Although this is the original and most commonly used map, its values only provide a good approximation for the paracentral cornea (Fig. 1.15A). The axial map measures the radius of
Corneal Topography 19
Figs. 1.15A to D: Different kinds of topography maps for the same cornea: (A) Sagittal axial map, (B) instantaneous or tangential map, (C) elevation map and (D) pachymetry map.
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curvature for a comparable sphere (with the same tangent as the point in question) with a center of rotation on the axis of the videokeratoscope. Localized changes in curvature and peripheral data are poorly represented, because of the spherical bias of the reference optical axis.4 However, newer algorithms in some devices (e.g., arc-step method) have improved the accuracy of curvature measurements in the peripheral region. Local tangential curvature map (instantaneous map): The tangential map displays the tangential/instantaneous/local radius of curvature or tangential power, which is calculated by referring to the neighboring points and not to the axis of the videokeratoscope (Fig. 1.15B). Tangential maps reflect local changes and peripheral data better than axial maps. They are very useful in detecting local irregularities, corneal ectatic diseases, or surgically induced changes. For example, in keratoconus corneas with a displaced apex, tangential maps are less influenced by peripheral distortion, and can determine the position and extent of the cone more precisely than axial maps.9 Refractive map: The refractive map displays the refractive power of the cornea, which is calculated based on Snell’s law of refraction, assuming optical infinity. This map correlates corneal shape to vision, and is useful in understanding the effects of surgery.13 Elevation map: The elevation map displays corneal height or elevation relative to a reference plane (Fig. 1.15C), with a presumed assumption of the shape, which may be the best-fit sphere, best-fit asphere, average corneal shape, or even based on preoperative data. Points above the reference surface are positive (hot colors), and points below the reference surface are negative (cool colors). This map shows the 3D shape of the cornea and is useful in measuring the amount of tissue to be removed by a procedure, assessing postoperative visual problems, or planning and/ or monitoring surgical procedure.9 Difference map: The difference map displays the changes in certain values between two maps (Fig. 1.16). It is used to monitor any type of change, such as recovery from contact lens-induced warpage or surgery-induced changes. Relative map: The relative map displays some values by comparing them to an arbitrary standard (e.g., sphere, asphere or normal cornea) and a specific mathematical model. This map enhances or magnifies unique features of the cornea being examined. Irregularity map (surface quality maps): The irregularity map uses the same technique as the elevation map, but takes as a reference surface the best-fit spherocylindrical toric surface. The difference between the actual surface and the theoretical surface represents that part of the cornea which cannot be optically corrected. Like refractive power maps, the irregularity map only has clinical meaning when considering the values over the pupillary area.
Corneal Topography 21
Fig. 1.16: Difference map for evaluating the evolution after implanting a corneal Myoring with central aplannation.
Corneal thickness maps (Fig. 1.15D): Numerous other displays, including 3D maps, astigmatic vector analysis, etc. are available but less used.
QUANTITATIVE DESCRIPTORS OF CORNEAL TOPOGRAPHY: CORNEAL INDEXES Color-coded maps provide a rapid visual method for clinical diagnosis, but do not supply numerical values that can be used for clinical management. Several corneal indexes describe different features of corneal topography quantitatively and are of great aid in contact lens fitting, for improved assessment of the optical quality of the corneal surface, and can be used in artificial intelligence systems to aid in the diagnosis of corneal shape anomalies. Some of the most useful indexes have been described hereunder.
Basic Topographic Indexes Simulated Keratometry Reading (SimK Values) This is a simple descriptor of corneal topography that provides the power and axes of the steepest and flattest corneal curvatures just as K1 and K2 are provided by the classic keratometer, to which it correlates well.3 The cylinder is calculated from the difference between SimK1 and SimK2. Its common uses are: • Fitting contact lenses • Refractive surgery calculations • Supplying a starting point when assessing an irregular corneal shape, since it gives the quantity and axis of astigmatism
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Minimum Keratometry Reading Minimum keratometry reading (MinK) is the minimum meridional power from rings 7, 8 and 9. The average power as well as axis are displayed.
Corneal Eccentricity Index Corneal eccentricity index (CEI) estimates the eccentricity of the central cornea, and is calculated by fitting an ellipse to the corneal elevation data.12 A positive value is for a prolate surface, negative value for an oblate surface (e.g., flattened corneas after myopic refractive surgery), and zero value for a perfect sphere. Normal central corneas are prolate, meaning they are steeper in the center than in the periphery, and tend to be around 0.30. This value is used for: • Fitting contact lenses • Approaching to the global shape factor
Average Corneal Power This is the area-corrected average of corneal power in front of the pupil. It usually corresponds to the spherical equivalent of the classic keratometer, except after decentered refractive surgery. It may be helpful in determining central corneal curvature when calculating the appropriate intraocular lens.
Surface Regularity Index, and Potential Visual Acuity Surface regularity index (SRI) measures the regularity of the corneal surface that correlates with the best spectacle-corrected visual acuity assuming the cornea to be the only limiting factor.14 This index adds up the meridional mire-to-mire power changes over the apparent pupil entrance. The SRI value increases with increases in the irregularity of the corneal surface, and its normal value is less than 1.0. It measures optical quality. Potential visual acuity (PVA) is a range of the expected visual acuity that is achievable based on the corneal topography and can be calculated based on SRI.
Surface Asymmetry Index Surface asymmetry index (SAI) is a descriptor of the corneal surface that measures the difference between points located 180° apart in a great number of equally spaced meridians.15 Therefore, as the cornea becomes less symmetric, the index differs more from 0. Other indexes, some of which will be mentioned below, have been developed, and might be exclusive to one particular topographer. The clinician should evaluate the meaning, utility and validity of each index since some indexes have been tested in peer-reviewed literature while others have not.
Corneal Topography 23
Screening Tools and Artificial Intelligence Programs (Neural Networks) for Classification and Auto Diagnosis As mentioned earlier, even for experienced personnel, interpretation of topography can be difficult, particularly when trying to differentiate the early stages of a disease from a normal cornea (suspected keratoconus), or when trying to differentiate between two similar conditions (contact lens warpage versus early keratoconus). Several mathematical algorithms have been developed to help solve this problem, with high sensitivity and specificity. Rabinowitz and McDonnell developed the first numerical method for detecting keratoconus using only topographic data.16 They use the I-S value, which measures the differences between the superior and inferior paracentral corneal regions, the central corneal power (MaxK), and the power difference between both eyes. Their study determined the following results: • Keratoconus suspect: central corneal power > 47.2 D or I-S > 1.4 • Clinical keratoconus: central corneal power > 47.8 D or I-S > 1.9 However, using only these simple measurements for a diagnosis could create specificity problems. To solve the specificity problem, the new strategy must be able to detect and consider the unique characteristics of keratoconus maps, such as local abnormal elevations. The keratoconus prediction index, developed by Maeda et al.,17 is calculated from the differential sector index (DSI), the opposite sector index (OSI), the center/surround index (CSI), the SAI, the irregular astigmatism index (IAI) and the percent analyzed area (AA). This method partially overcomes the specificity limitation. Maeda et al. also developed the neural network model, based on artificial intelligence.17 It is a much more sophisticated method for classifying corneal topography and detecting different corneal topographic abnormalities; it employs indexes that were empirically found to capture specific characteristics of the different corneal pathologies, including keratoconus. Further modifications in neural network approach developed by Smolek and Klyce supposedly produce 100% accuracy, specificity and sensitivity in diagnosing keratoconus. The Pentacam system for instance has developed seven indices of corneal irregularity within the central cornea for the grading and classification of keratoconus (TKC), as well as the postoperative assessment (Fig. 1.17). These indices include index of surface variance (ISV), index of vertical asymmetry (IVA), keratoconus index (KI), central keratoconus index (CKI), index of height asymmetry (IHA), index of height decentration (IHD) and index of minimum radius of curvature (Rmin). This machine also provides with two diagrams that describe the change of corneal thickness in relation to location, and a progression index of this thickness/location relationship to suggest the presence or not of an ectatic disease. In addition to this, the Pentacam tomography includes a new software adaptation called the Belin/Ambrosio
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Fig. 1.17: Indices of cornea irregularity—Pentacam.
enhance ectasia display (BAD) that combines both the anterior and posterior elevation data and pachymetric data to orient in the diagnosis of corneal ectasia. The Sirius system displays a keratoconus summary to aid in the diagnosis and the follow-up of keratoconus combining indices based on curvature, pachymetry and elevation such as the symmetry index of the front and back surface, or the Baiocchi Calossi Versaci front and back index (BCV f and BCV b) to evaluate coma and trefoil aberrations. The Casia OCT system has a built-in software that estimates ectasia similarity of a scan, and this is calculated as the ectasia similarity score (Fig. 1.18). This score is presented in percentage of similarity.
CORNEAL ABERROMETRY: FUNDAMENTALS AND CLINICAL APPLICATIONS Whenever a point object does not form a point image on the retina, as it should be in an ideal optical system, one encounters an optical aberration.18 Although one may feel that he is measuring the total refractive error, when refracting a patient, one is actually only considering two components of a whole host of refractive components in the optics of the eye. However, these two components—sphere and cylinder—do constitute the main optical aberrations of an eye. Even in a normal eye with no subjective need for refraction, optical aberrations can be detected. Since the cornea has the highest refractive power, more than 70% of the eye’s refraction, it is the principal site of aberrations, although the lens and the tear film may also contribute to aberrations.19
Fig. 1.18: Ectasia similarity score by Casia S-100.
Corneal Topography 25
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MEASURING WAVEFRONT ABERRATION Measuring Total Wavefront Aberration It is possible to express ideal image formation by means of waves. An ideal optical system will provide a spherical converging wave centered at the ideal point image. However, in practice, the resulting wavefront differs from this ideal wavefront. The deviation from this ideal wavefront is called wavefront aberration, and the more it differs from zero, the more the real image differs from the ideal image and the worse the image quality. Ocular wavefront sensing devices use five main technologies to determine the resulting or output wave:20 1. The Shack-Hartmann method is the most widely used and is inspired by astronomy technology. It consists of analyzing the wave emerging from the eye after directing a small low energy laser beam. This reflected wave is divided by means of a series of small lenses (lenslet array), which generates focused spots. The position of spots is recorded and compared to the ideal one. This type of aberrometer provides reproducible measurements in normal eyes but is limited in eyes with significant amounts of aberrations due to the overlapping of the spots.18 2. The Tscherning technique uses typically a grid that is projected onto the retina. The distortion of the pattern is analyzed and used to calculate the wavefront aberration of the eye.21 3. The Ray Tracing system is similar to the Tscherning technique. However, instead of a grid, a programmable laser serially projects light beams that form spots on the retina at different locations.21 4. The spatially resolved refractometer evaluates the wavefront profile using the subjective patient response. This technology is not practical for clinical use. 5. Piramidal aberrometry is a new wavefront sensor based on the Foucault knife edge.22 The Osiris pyramidal aberrometry system bases his working principle on a high-resolution four-faced pyramid wavefront sensor on the focal plane that provides the wavefront gradients in two orthogonal directions and four pupil images (known as sub-pupil) distributed by their intensity: each sub-pupil performs a Foucault knifeedge test to derive slope and shape of the wavefront. Since wavefront is sampled in the very last stage of the optical path, the resolution of the device is extremely high compared to commercial sensors. Finally, the device seems to make possible the analysis of very irregular corneas probably due to his fuzzy dynamic range and to the absence of problems related to sample overlapping, so it might allow higher sensitivity than Hartmann-Shack wavefront sensor.
Measuring Corneal Wavefront Aberration It is known that 80% of all aberrations of the human eyes occur in the corneal area and only 20% of aberrations originate from the rest of the ocular
Corneal Topography 27
Fig. 1.19: Corneal wavefront analysis derived from height topography data.
structures.23 The effect of corneal aberrations is especially important after corneal surgery such as keratorefractive procedures since the anterior corneal surface is the only one modified.24 The corneal wavefront aberration, which is the component of the total ocular wavefront aberration attributed to the cornea, can be derived from the corneal topographic height data. Specifically, the calculation of wavefront aberrations is performed by expanding the anterior corneal height data into a set of orthogonal Zernike polynomials (Fig. 1.19).
Zernike Polynomials For a quantitative description of the wavefront shape, there is a need for a more sophisticated analysis than conventional refraction, as the latter only divides the wavefront in two basic terms: sphere and cylinder. One can obtain more information by breaking down the wavefront into terms, which are clinically meaningful, besides the sphere and the cylinder. For this purpose, a standard equation has been universally accepted by refractive surgeons and vision scientists, known as Zernike polynomials.25 Zernike polynomials are equations which are used to fit the wavefront data in a 3D way. The wavefront function is decomposed into terms that describe specific optical aberrations such as spherical aberration, comma, etc. (Fig. 1.20). Each term in the polynomial has two variables, r (rho) and q (theta), where r is the normalized distance of a specific point from the center of the pupil, and q is the angle formed between the imaginary line joining the pupillary center with the point of interest and the horizontal. According to that, we can imagine that aberrations are strongly influenced by pupil size,
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Fig. 1.20: Zernike polynomial expansion.
and, therefore, aberrometric measurements should be related to the diameter of the patient’s pupil. Zernike terms (Znm ) are defined using a double index notation: (1) a radial order (n) and (2) an angular frequency (m). When talking about first, second, third, etc., aberrations we point to indicate the radial order (n). Each radial order involves n + l terms. There are an infinite number of Zernike terms that can be used to fit an individual wavefront. However, for clinical practice, terms up to the fourth radial order are usually considered:25 1. Zernike terms below third order can be measured and corrected by conventional optical means the first order term, the prism, is not relevant to the wavefront as it represents tilt and is corrected using a prism. The second order terms represent low order aberrations that include defocus (spherical component of the wavefront) and astigmatism (cylinder component). Wavefront maps that measure only defocus and astigmatism can be perfectly corrected using spectacles and contact lenses. 2. After the second radial order come the high order aberrations. These are not measured by conventional refraction or autorefraction. The aberrometer is the only method available that can quantify these complex kinds of distortions. 3. Third order terms describe comma and trefoil defects. 4. Fourth order terms represent tetrafoil, spherical aberration and secondary astigmatism components. Because spherical and comma aberrations refer to symmetrical systems and the eye is not rotationally symmetrical, the terms spherical-like and comma-like aberrations are normally used (Fig. 1.21).
Fig. 1.21: Complete corneal wavefront aberration map.
Corneal Topography 29
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Wavefront Maps Wavefront map describes the optical path difference between the measured wavefront and the reference wavefront in microns at the pupil entrance.18 The wavefront error is derived mathematically from the reconstructed wavefront by one of the techniques described earlier. It is plotted as a 2D or 3D map for qualitative analysis in a similar fashion to corneal topography maps. In wavefront error maps, each color represents a specific degree of wavefront error in microns (Fig. 1.21) and like in corneal topography maps, it is necessary to consider the range and the interval of the scale.
Optical and Image Quality In order to evaluate the impact of aberrations on visual quality following quantitative parameters have been defined (Fig. 1.22): • Peak to valley error (PV error): This is a simple measure of the distance from the lowest point to the highest point on the wavefront and is not the best measurement of optical quality since it does not represent the extent of the defect.25 • Root mean square error (RMS error): This measure is by far the most widely used. In a simple way, the RMS wavefront error is a statistical measure of the deviation of the ocular or corneal wavefront from the ideal25 (Table 1.1). In other words, it describes the overall aberration and indicates how bad individual aberrations are. • Strehl ratio: This represents the ratio of the maximum intensity of the actual image to the maximum intensity of the fully diffracted limited image, both being normalized to the same integrated flux.25 This ratio measures optical excellence in terms of theoretical performance results and it is linked to the RMS by the Maréchal formula. • Point spread function (PSF): This is the spread function observed on the retina when the object is a point in infinity.25 PSF measures how well one object point is imaged on the output plane (retina) through the optical system. In the eye, small pupils (~1 mm) produce diffraction-limited PSFs because of the pupil border. In larger pupils, aberrations tend to be the dominant source of degradation. • Modulation transfer function, phase transfer function and optical transfer function: Sinusoidal gratings greatly simplify the study of optical systems, because irrespective of the amount of eye aberrations, sinusoidal grating objects always produce sinusoidal grating images.26 Consequently, there are only two ways that an optical system can affect the image of a grating, by reducing contrast or by shifting the image at a specific resolution; are called respectively the modulation transfer function (MTF) and the phase transfer function (PTF). The eye’s optical transfer function (OTF) is made up of the MTF and the PTF. A high-quality OTF is, therefore, represented by high MTF and low PTF.
Fig. 1.22: Visual quality summary obtained with the Sirius CSO topographer. It is possible to visualize the wavefront map (gray scale), Strehl ratio, point spread function (PSF) and modulation transfer function (MTF) function.
Corneal Topography 31
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Table 1.1: Reference values for corneal aberrations in the normal population. (RMS: root mean square; Coma primary coma: terms Z3; Spherical aberration and primary spherical aberration: term Z4; Spherical-like: terms fourth and sixth order; Coma-like: terms third and fifth order). Source: Vinciguerra P, Camesasca Fl, Cafossi A. Statistical analysis of physiological aberrations of the cornea. J Refract Surg. 2003;19(Suppl):S265-9. Pupil (mm)
Astigmatism Spherical RMS aberration
0.19 ± 0.07 0.14 ± 0.08
0.04 ± 0.03
0.05 ± 0.03 0.07 ± 0.02
0.09 ± 0.03
0.53 ± 0.21 0.43 ± 0.24
0.15 ± 0.05
0.14 ± 0.08 0.18 ± 0.05
0.20 ± 0.08
1.26 ± 0.43 0.92 ± 0.53
0.52 ± 0.17
0.42 ± 0.23 0.57 ± 0.16
0.52 ± 0.22
Clinical Applications Aberrometers allow practitioners to gain a better understanding of vision by measurement of high-order aberrations. These aberrations reflect a refractive error that is beyond conventional spheres and cylinders. There may be a large group of patients whose best-corrected visual acuity (BCVA) may improve significantly by removing the optical aberrations and this new refractive entity has been called aberropia. Reduced optical quality of the eye produced by light scatter and optical aberrations may actually be the root cause of blurred vision associated with dry eye syndrome and tear film disruption. Measurement of these aberrations are also helpful in keratoconus, post-graft fitting, irregular astigmatism or when refractive surgery has reduced the patient’s optical quality.20 Customized ablation patterns, currently in constant evolution, are the future step in laser technology that should address not only spherical and cylindrical refractive errors (low-order aberrations), but also high-order aberrations such as trefoil and comma (Figs. 1.23A to C). Thus, vision can be optimized to the limits determined by pupil size (diffraction) and retinal structure and function.
PATHOLOGICAL CORNEA Corneal topography is a very important tool in the detection of corneal pathologies, especially ectatic disorders. Screening for these anomalies or their potential development is a critical point in preoperative evaluation for refractive surgery. Keratorefractive procedures are contraindicated in these abnormal corneas.
Keratoconus Keratoconus is characterized by a localized conical protrusion of the cornea associated with an area of corneal stromal thinning, especially at the apex of the cone. The typical associated topographic pattern is the presence of an inferior area of steepening (Fig. 1.24A to D). In advanced cases, the dioptric
Corneal Topography 33
Figs. 1.23A to C: Customized ablation profile designed according to corneal aberrations: (A) Case of early keratoconus with an unaided and corrected distance visual acuity of 0.5, (B) customized transepithelial PRK ablation profile in order to treat only the coma with the minimal possible ablation depth, (C) topographic outcome 6 months after simultaneous transPRK and corneal collagen crosslinking with an unaided vision of 0.8 and corrected distance vision of 1 due to the regularization of the astigmatism.
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power at the apex is at or above 55 D.27 In a small group of patients, the topographic alterations may be centered at the central cornea. In these cases, there may be an asymmetric bow-tie configuration, and usually the inferior loop is larger than the superior loop (Figs. 1.23A to C). Keratoconic corneas have three common characteristics that are not present in normal corneas: 1. An area of increased corneal power surrounded by concentric areas of decreasing power. 2. An inferior-superior power asymmetry. 3. A skewing of the steepest radial axes above and below the horizontal meridian. Keratoconus suspects are problematic. They may signal impending development of a clinical keratoconus, but they may also represent a healthy cornea.
Corneal Topography 35
Figs. 1.24A to D: Keratoconus topography pattern. It can be observed the inferior steepening with posterior elevation and corneal thinning.
The lack of ectasia in the fellow cornea does not indicate that the keratoconus suspect will not progress to true keratoconus. In these cases, the ideal management is close follow-up of the signs of keratoconus in order to check on their stability, and a thorough analysis of the videokeratographic indexes.
Pellucid Marginal Degeneration Pellucid marginal degeneration is characterized by an inferior corneal thinning between 4 and 8 o’clock positions, a narrow band of clear thinned corneal stroma.28 The ectasia is extremely peripheral and it appears just over the
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thinned area, presenting a crescent-shaped morphology. This pattern has a classical ‘butterfly’ appearance that results in a flattening of the vertical meridian and a marked against-the-rule irregular astigmatism (Fig. 1.25A to D).
Keratoglobus Keratoglobus is a rare bilateral disorder in which the entire cornea is thinned out, most markedly near the corneal limbus, in contrast to the localized central or paracentral thinning of keratoconus. It is very difficult to obtain reliable and reproducible measurements in these cases due to the high level of irregularity and the poor quality of the associated tear film. Reliable
Corneal Topography 37
Figs. 1.25A to D: Pellucid marginal degeneration topography pattern. It can be observed the crescent-shaped inferior ectasia with posterior elevation and inferior thinning.
topographic examinations show an arc of peripheral increase in corneal power (steepening) and a very asymmetrical bow-tie configuration.28
Terrien’s Marginal Degeneration In Terrien’s marginal degeneration, there is a flattening over the areas of peripheral thinning. When thinning is restricted to the superior and/or inferior areas of the peripheral cornea, there is a relative steepening of the
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corneal surface approximately 90° away from the midpoint of the thinned area.29 Therefore, high against-the-rule or oblique astigmatism is a common feature, as this disorder involves more frequently the superior and/or inferior peripheral cornea. If the area of thinning is small or if the disorder extends around the entire circumference of the cornea, central cornea may remain relatively spared with a spherical configuration.
Pterygium Pterygium is a triangular encroachment of the conjunctiva onto the cornea usually near the medial canthus. When the lesion continues to grow out onto the cornea, it could lead to a high degree of astigmatism. When the growth of pterygium is about 2 mm or more, a flattening of the cornea at the axis of the lesion occurs. This produces a marked with-the-rule astigmatism, even of more than 4 D. The evolution of the pathology and the surgical outcome could be monitored by changes in corneal topography.
Postoperative Cornea in Refractive Surgery Keratorefractive procedures attempt to alter the curvature of the central and midperipheral cornea, and usually have a minimal effect on the corneal periphery. The area in which the curvature is modified is called the optical zone. This tends to be surrounded by a small zone of altered curvature before normal cornea is reached at the periphery. The corneal effect of surgery could be determined by analyzing the difference map between the preoperative and postoperative measurements.30
Postradial Keratotomy Radial keratotomy (RK) corrects myopia by placing a series of radial incisions (nearly full corneal thickness) leaving a central clear zone (optical zone). These incisions cause a flattening of the central cornea due to retraction of the most anterior collagen fibers and the outward pressure of the intraocular force. This area of flattening is surrounded at an approximately 7 mm zone by a bulging ring of steepening called the paracentral knee or inflection zone. This increases asphericity and corneal irregularity. A very typical finding in these corneas is a topographic pattern with a polygonal shape.18 Depending on the number of incisions made, squares, hexagons or octagons can be seen. The angles of the polygons correspond closely to the central ends of the incisions (Fig. 1.26A to D).
Postastigmatic Keratotomy Astigmatic keratotomy (AK) is a simple modification of the RK that is used to correct astigmatism. Rather than placing incisions radially on the cornea, incisions are strategically placed circumferentially on the peripheral cornea at
Corneal Topography 39
the steepest meridian. The incisions induce a flattening in that meridian, but provoke steepening in the perpendicular meridian, in a process called coupling18 (Figs. 1.27A and B). Coupling results from the presence of intact rings of collagen lamellae that run circumferentially around the base of the cornea. With the surgery, these rings become oval in the operated meridian and transmit forces to the untouched meridian. The astigmatic change achieved is the sum of the flattening in one meridian and the steepening on its perpendicular meridian.
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Figs. 1.26A to D: Postradial keratotomy cornea. Observe the anterior and posterior circumferential elevation but without any alteration in the corneal pachymetry.
Postphotorefractive Keratectomy Photorefractive keratectomy (PRK) is a procedure which uses a kind of laser (excimer laser, a cool pulsing beam of ultraviolet light) to reshape the cornea. To correct myopia, the excimer laser flattens the central cornea by removing tissue in that area. However, the optical zone needs to be steepened to correct
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Figs. 1.27A and B: (A) Before and (B) after astigmatic keratotomy. Observe the considerable flattening induced by the keratotomy, in this case excessive, generating a secondary significant astigmatism in the previously flat axis.
hyperopia. This is achieved by removing an annulus of tissue from the midperiphery of the cornea. The topographic pattern in myopic corrections shows a flattening of the central cornea, an oblate profile (Fig. 1.28A to D). Hyperopic corrections have a pattern of central steepening surrounded by a ring of relative flattening at the edge of the treatment zone, a prolate profile (Fig. 1.29A to D). In astigmatic corrections, the treatment zone is oval.18
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Inadequate ablations during surgery can be detected postoperatively by analyzing the resulting corneal topography. Decentrations can only be identified by a relatively asymmetric location of the treatment area (Fig. 1.30). Other complicated patterns that may lead to severe visual disturbances are the presence of focal irregularities or central islands produced by an inhomogeneous laser beam or an irregular process of corneal healing.
Postlaser in situ Keratomileusis Laser in situ keratomileusis (LASIK) is an excimer laser procedure like PRK, but in this case, tissue is ablated of under a superficial corneal flap in order to
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minimize the influence of the epithelium. The topographic patterns for myopic and hyperopic corrections are the same as in PRK (Figs. 1.28 and 1.29). Although the ablation is covered by a flap of corneal tissue, surface irregularities and central islands may still occur. Decentrations may also occur in a LASIK ablation, depending on the patient’s ability to maintain eye fixation during surgery (Fig. 1.30). Epithelial in-growth at the periphery of the flap-stromal interface produces an area of steepening surrounded by an area of marked flattening making the corneal surface more irregular.
Figs. 1.28A to D: Topographic pattern after myopic ablation.
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Postlaser Thermal Keratoplasty In laser thermal keratoplasty (LTK), a Holmium laser, is used to heat corneal stromal collagen in a ring around the outside of the pupil. The heat causes the tissue to shrink, producing a zone of localized flattening centered on the spot, and a surrounding zone of steepening. This bulging effect of the central cornea makes it possible to correct hyperopia. The typical topographic pattern shows the central corneal steepening and a ring of flattening overlying the spots (Fig. 1.31).
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Figs. 1.29A to D: Topographic pattern after a high-hyperopic ablation. In contrast to a real corneal ectasia, after a hyperopic treatment the posterior corneal surface and the central corneal thickness are normal.
Postintrastromal Corneal Rings Implantation Intrastromal rings are small segments or rings, made of a plastic-like substance, that are inserted into the periphery of the cornea to correct small degrees of myopia or hyperopia. They act as spacers and by changing the orientation of the collagen lamellae, depending on their shape and position,
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Fig. 1.30: Pattern of a decentered myopic ablation.
Fig. 1.31: Topographic pattern after laser thermal keratoplasty (LTK) for hyperopia.
flatten or steepen the central cornea. Nowadays, intrastromal rings are mainly used to reduce the corneal steepening and irregular astigmatism associated with keratoconus (Figs. 1.32A and B).
Postoperative Cornea in Keratoplasty Surgery Keratoplasty topographies exhibit a wide variety of patterns, depending on the type of keratoplasty performed, the quality of the surgical procedure,
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Figs. 1.32A and B: (A) Before and (B) after intracorneal ring segment implantation for keratoconus.
whether sutures are still in place in the cornea, and the time elapsed after the procedure. Sutures usually induce a central bulge in the corneal graft and its removal results in a decrease of the astigmatic component (Figs. 1.33A and B). The prolate configuration after keratoplasty is the most frequent pattern with a high degree of irregularity. There can be multiple regions of abnormally high or low power, or both simultaneously in the map. Irregular astigmatism over the entrance pupil may be detrimental to optimum visual acuity in the keratoplasty patient.31
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Figs. 1.33A and B: (A) Before and (B) after graft suture removal on a previous penetrating keratoplasty. Observe the significant reduction of the topographic cylinder.
Contact Lens-induced Corneal Warpage or Molding Corneal warpage is characterized by topographic changes in the cornea following contact lens wear (most frequently in wearers of hard or RGP lenses) as a result of the mechanical pressure exerted by the lens. There are at least four different forms of noticeable topography changes that usually occur mixed with one another: (1) peripheral steepening, (2) central flattening, (3) furrow depression and (4) central molding or central irregularity.18
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Inferior corneal steepening (pseudokeratoconus) is caused by a superiorly riding contact lens that flattens above the visual axis with an apparent steepening below. The topographic image could appear similar to keratoconus, but both conditions are easily differentiated (Figs. 1.34A and B). In corneal warpage, the shape indexes do not indicate any keratoconic condition, and the steep K is not as steep as it is in keratoconus.
Other Uses of Corneal Topography Corneal topography is a diagnostic tool, but it is also essential before all refractive procedures, to enable the surgeon to understand the refractive status of an individual eye, and plan the optimum refractive treatment. The corneal topography is also used for the following purposes:
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Figs. 1.34A and B: Corneal warpage: (A) soft contact lens removed 1 day before the measurement; (B) same patient 1 week later without using contact lenses. Observe how it disappears the inferior asymmetry on the topographic astigmatism.
• • •
To guide removal of tight sutures after corneal surgery (keratoplasty, cataract surgery, etc.) that are causing steepening of the cornea (Figs. 1.33A and B). To help in the AK surgical plan. To guide contact lens fitting: election of the probe lens and design of the lens. To calculate the keratometry values for the calculation of the required intraocular lens power before cataract surgery or refractive lens exchange. This is an important issue in corneas that have undergone previous refractive surgery, because it is more difficult to estimate the real keratometric values in order to avoid hyper- or hypocorrections. To evaluate the effect and evolution of a keratorefractive procedure.
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REFERENCES 1. Kaufman H, Barron B, McDonald M, Kaufman S. Companion handbook to the cornea. London, Butterworth Heinemann, 1999. 2. Dabezies OH, Holladay JT. Measurement of corneal curvature: keratometer (ophthalmorneter). In Contact lenses: the CLAO guide to basic science and clinical practice. Kendall/Hunt Publishing Co. 1995. pp. 253-89. 3. Wilson SE, Klyce SD. Advances in the analysis of corneal topography. Surv Ophthalmol. 1991;35:269-77. 4. Corbett M, O’Brart D, Rosen E, Stevenson R. Cornea l topography: principles and applications. BMJ Publishing Group, 1999. 5. Bogan SJ, Waring GO, Ibrahim O, Drews C, Curtis L. Classification of normal corneal topography based on computerassisted videokeratography. Arch Ophthalmol. 1990;108:945-9. 6. Corneal Topography. American Academy of Ophthalmology. Ophthalmol. 1999;106:1628-38. 7. Mejia-Barbosa Y, Malacara-Hernandez, D. A review of methods for measuring corneal topography. Optom Vis Sd. 2001;78:240-53. 8. Cairns G, McGhee CNJ. Orbscan computerized topography: Attributes, applications, and limitations. J Cataract Refract Surg. 2005;31:205-20. 9. Cavas-Martinez F, De la Cruz Sanchez E, Nieto Martinez J, FernandezCañavate FJ, Fernandez-Pacheco D.G. Corneal Topography in Keratoconus: state of the art. 10. Steinberg J, Casagrande MK, Frings A, Katz T, Druchkiv V, Richard G, Linke SJ. Screening for Subclinical Keratoconus Using Swept-Source Fourier Domain Anterior Segment Optical Coherence Tomography. Cornea. 2015 Nov;34(11):1413-9. 11. Miller D, Greiner JV: Corneal measurements and tests. In Principles and practice of ophthalmology. Philadelphia, WB Saunders, 1994. 12. Rao SK, Padmanabhan P. Understanding corneal topography. Curr Opin Ophthalmol. 2000;11:248-59. 13. Ambrosio R Jr, Klyce SD, Wilson SE. Corneal topographic and pachymetric screening of keratorefractive patients. J Refract Surg. 2003;19:24-9. 14. Courville CB, Smolek MK, Klyce SD. Contribution of ocular surface to visual optics. Exp Eye Res. 2004;78:417-25. 15. Klyce SD. Corneal topography and the new wave. Cornea. 2000;19:723-29. 16. Rabinowitz YS, Nesbum AB, McDonnell Pl Videokeratography of the fellow eye in unilateral keratoconus. Ophthalmol. 1993;100:181-6. 17. Maeda N, Klyce SD, Smolek MK. Neural network classification of corneal topography. Preliminary demonstration. Invest Ophthalmol Vis Sci. 1995; 36:1327-35. 18. Boyd BF, Agarwal A, Alio JL, Krueger RR, Wilson SE (eds). Wavefront analysis, aberrometers and corneal topography. Highlights ofophthalmology, 2003. 19. Wilson SE, Ambrosio R. Computerized corneal topography and its importance to wavefront technology. Cornea. 2001;20:441-54. 20. Rozema JJ, Van Dyck DE, Tassignon MJ. Clinical comparison of 6 aberrometers. Part 1: Technical specifications. J Cataract Refract Surg. 2005;31: 1114-1127.
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21. Molebny VV, Panagopoulou SI, Molebny SV, Wakil YS, Pallikaris IG. Principles of ray tracing aberrometry. J Refract Surg. 2000;16:S572-575. 22. Chamot SR, Dainty C, Esposito S. Adaptive optics for ophthalmic applications using a pyramid wavefront sensor. Opt Express. 2006;14:518-526. 23. Vincigerra P, Camesasca FI, Calossi A. Statistical Analysis of phisiological aberrations of the cornea. J Refract Surg. 2003;19(suppl):265-9. 24. Joslin CE, Wu SM, McMahon TT, Shahidi M. Higher-order wavefront aberrations in corneal refractive therapy. Optom Vis Sci. 2003;80:805-11. 25. Thibos LN, Applegate RA, Schwiergerling JT, Webb R. Standards for reporting the optical aberrations of eyes. J Refract Surg. 2002;18:S652-60. 26. Hamam H. A new measure for optical performance. Optom Vis Sci. 2003;80: 174-84. 27. Rabinowitz YS. Keratoconus. Surv Ophthahnol. 1998;42:297-319. 28. Karabatsas CH, Cook SD. Topographic analysis in pellucid marginal corneal degeneration and keratoglobus. Eye. 1996;10:451-55. 29. Wilson SE, Lin DT, Klyce SD, Insler MS. Terrien’s marginal degeneration: corneal topography. Refract Corneal Surg. 1990;6:15-20. 30. Vang L, Koch DD. Corneal Topography and its integration into refractive surgery. Comp Ophthalmol Update. 2005;6:73-81. 31. Krachmer JH, Mannis MJ, Holland EJ, (ed). Cornea. Surgery of cornea and conjunctiva. St Louis, Elsevier-Mosby, 2005.
2 Corneal Confocal Microscopy Manotosh Ray, George N Thomas
Confocal microscopy is an advanced imaging technology that offers several advantages over conventional wide-field optical microscopy. The operator has the ability to control the depth of field, eliminate or reduce the background noise from the focal plane and the capability to obtain precise serial optical sections from thick specimens. The fundamental of confocal microscopy is its use of spatial filtering techniques to eliminate out-of-focus light or glare. The application of this technology permits the acquisition of images of high spatial resolution and contrast as compared to conventional microscopy. There has been tremendous interest in confocal microscopy in recent years, due in part to the relative ease of which extremely high quality images can be obtained from tissue samples, including the ability to image the cornea in vivo. The major limiting factor of conventional light microscopy is that when a particular point of interest is viewed, the reflected light from the surrounding structures obscures the image produced. The fringing effect produced by this reflection reduces the image contrast. Therefore, the useful magnification in slit-lamp biomicroscopes and other similar ophthalmic instruments is limited to approximately 40 times. Further magnification compromises the image quality and produces significant image blur. The confocal microscope, on the other hand, utilizes a principle in which both the illumination and observation system are focused on a single point. Thus, the spatial resolution is improved dramatically and the system allows a usable magnification of up to 600 times. Confocal microscopy employs an oscillating slit aperture in an ophthalmic microscope configuration, especially suitable for the analysis of cell layers of cornea. It can focus through the entire range of a normal cornea from epithelium to endothelium. A series of scan shows: (a) epithelium, (b) corneal nerves, (c) keratocytes, (d) endothelium, and (e) a computer-generated slice of cornea. There are distinct advantages of the confocal microscope over a
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regular light microscope. When a transparent tissue like the cornea is imaged with a regular microscope, the unfocused layers affect the visibility of the focused layer. A confocal microscope, on the other hand, can focus on a specific layer distinctly without being affected by artifact from other layers.
OPTICS A halogen light source passes through movable slits (Nipkow disk), which is then passed through a condenser lens (front lens) that projects the light to the cornea. Only a small area inside the cornea is illuminated to minimize light scatter. The reflected light passes through the front lens again and is directed to another slit of same size via a beamsplitter. Finally, the image is projected onto a highly sensitive camera and displayed on a computer monitor (Fig. 2.1). The confocal microscope utilizes a transparent viscous sterile gel that is interposed between the front lens and cornea, to improve the optical interface between the two media. The front lens works on the ‘Distance Immersion Principle.’ In this principle, the anteroposterior movement of the front lens enables scanning of the entire cornea starting from anterior chamber and corneal endothelium to most superficial corneal epithelium. The standard
Fig. 2.1: Optics of confocal microscope.
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working distance (distance between front lens and the cornea) is 1.92 mm. Use of standard × 40 immersion lens gives magnified cellular detail and an image field of 440 × 330 μm. Other lenses (e.g., × 20) can deliver a wide field image but with less distinct cell morphology. Newer confocal microscopes (such as the Confoscan 2.0) capture up to 350 images per examination at a rate of 25 frames per second. The thickness of the imaged layers can be varied from 3–5 microns depending on the scanning slit characteristics. Every recorded image is characterized by its position on the Z-axis of the cornea. Every time a confocal scan is performed, a displayed diagram shows the depth coordinate on the Z-axis and the level of reflectivity on the Y-axis. The diagram also displays the distance between two images along the antreoposterior line. This simultaneous graphic recording is called the Z-scan graphic. The reflectivity on the Z-scan is entirely dependent on the tissue being scanned. A transparent tissue displays low reflectivity, whereas a higher reflectivity is obtained from an opaque layer. Therefore, different corneal layers would display different reflectivities on the Z-scan. The corneal endothelium displays the maximum reflectivity while that of the stroma is the lowest. An intermediate reflectivity is obtained from epithelial layers. A typical Z-scan of entire normal cornea shows high endothelial reflection curves followed by low stromal reflection and then a late intermediate reflectivity from superficial corneal epithelium. Thus, confocal miscroscopy allows the user to perform corneal pachymetry or measure the distance between two specific corneal layers.
CONFOCAL MICROSCOPY OF THE NORMAL CORNEA This is a noninvasive technique of imaging of corneal layers that provides excellent resolution and contrast. A well-executed scan can visualize the corneal endothelium, stroma, subepithelial nerve plexus and epithelial layers distinctly. The limitations are the inability to image a normal Bowman’s layer and Descemet’s membrane, since these structures are not visible through this microscope. However, it is sometimes possible to view these structures when they are pathological. Eyes with corneal opacity or edema can also be successfully scanned.1 The quality of an image depends on: (a) centration of the light beam, (b) stability of the eye, and (c) optimum brightness of the illumination.
Epithelium The corneal epithelium has five to six layers. Three different types of cellular components are recognized in the epithelium: 1. Superficial (2–3 layers): Flat cells 2. Intermediate (2–3 layers): Polygonal cells 3. Basal cells (single layer): Cylindrical cells
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The superficial epithelial cells appear as flat polygonal cells with welldefined borders, prominent nuclei and a uniform density of cytoplasm. The main identifying features of superficial epithelial cells are nuclei, which are brighter than surrounding cytoplasm and usually associated with perinuclear hypodense rings (Fig. 2.2A and B). The intermediate epithelial cells are similar polygonal cells as compared to the superficial layers but their nuclei are not evident (Fig. 2.3). Basal cell layers are smaller in size and appear denser than other two layers (Fig. 2.4A and B). The nucleus is also not evident in the basal layers. The corresponding Z-scans for the superficial and basal layers have been included, showing the depth of each scan.
Subepithelial Nerve Plexus Corneal nerves originate from the long ciliary nerve, a branch of the ophthalmic division of the trigeminal nerve. Nerve fibers from the long ciliary nerve form a circular plexus at the limbus. Radial nerve fibers originate from this circular plexus and run deep into the stroma to form the deep corneal plexus. Deep vertical fibers that proceed from the deep corneal plexus, run anteriorly
Figs. 2.2A and B: Superficial epithelial cells with prominent nuclei with corresponding Z-scan.
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Fig. 2.3: Intermediate epithelial cells. High cell density with well-demarcated cell borders.
Figs. 2.4A and B: Basal epithelial cells with corresponding Z-scan. A high cell density seen with well-demarcated cell borders.
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(B) Figs. 2.5A and B: Subepithelial nerve fibers with corresponding Z-scan.
to form the subbasal and subepithelial nerve plexuses. Small nerve fibers from the subbasal plexus terminate at the superficial epithelium. This complex anatomy was not visualized in vivo until the advent of the corneal confocal microscope. Generally, the nerve fibers appear bright and are well-contrasted against a dark background (Fig. 2.5A and B). Confocal microscopy can visualize the orientation, tortuosity, width, branching pattern and other abnormalities of the corneal nerves.2
Stroma The corneal stroma represents 90% of the total corneal thickness. It has three components: 1. Cellular stroma: Composed of keratocytes and constitutes 5% of the entire stroma. 2. Acellular stroma: Represents the major component (90–95%) of the stroma, comprising of regular collagen tissue (types I, III and IV) and interstitial substances. 3. Neurosensory stroma: Represented by stromal nerve plexus and nerve fibers originating from it.
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The keratocyte concentration is much higher in the anterior stroma and progressively decreases towards the deep stroma. Generally, the keratocyte count is approximately 1,000 cells/mm2 in the anterior stroma while the average value drops to 700 cells/mm2 in the posterior stroma. The confocal image of stroma shows multiple irregularly oval, round or bean-shaped bright structures that represent keratocyte nuclei. These nuclei are well-contrasted against the dark areas which represent acellular matrix (Fig. 2.6). Anterior stromal keratocyte nuclei assume rounded and bean-shaped morphology while the same in the rear stroma are more often irregularly oval. A bright highly reflective keratocyte represents a metabolically activated keratocyte of a healthy cornea. In a normal healthy cornea, collagen fibers and interstitial substances appear transparent to the confocal microscope and are impossible to visualize. It is possible to identify stromal nerve fibers in the anterior and mid stroma. These nerve fibers belong to the deep corneal plexus and appear as linear bright thick lines. The stromal nerve fiber thickness is greater than epithelial nerves. Occasionally, nerve bifurcations are also clearly
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Fig. 2.6: Anterior (top image), intermediate (middle image) and deep (bottom image) stromal keratocytes.
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visible. Representative Z-scans have been included below for the anterior and intermediate stromal scans.
Endothelium The endothelium is a non-innervated single layer of cells at the most posterior part of the cornea. The endothelial cell density is maximal at birth and progressively declines with age. The normal endothelial cell count varies from 1,600 to 3,000 cells/mm2 (average 2,700 cells/mm2) in a healthy adult.2-4 However, the cornea can still maintain its integrity until the cell count declines below 300–500 cells/mm2. Homogeneous hexagonal cells with uniform size and shape represent healthy endothelial cells. Increasing age and endothelial damage cause pleomorphism and polymegathism. Confocal microscopy easily identifies these endothelial cells. These cells appear as bright hexagonal and polygonal cells with no recognizable nucleus. The cell borders are represented by a thin, nonreflective dark line (Fig. 2.7). A × 20 objective lens provides wide field with less magnification. It is possible to perform cell count and study the minute details of cellular morphology. Figure 2.8 shows the corresponding Z-scan of the corneal endothelium. Newer confocal microscopes have the ability to perform reliable and accurate endothelial cell count measurements (Fig. 2.9A and B).
CONFOCAL MICROSCOPY IN CORNEAL PATHOLOGY Keratoconus Keratoconus is a noninflammatory ectatic disorder of the cornea characterized by a localized conical protrusion associated with an area of stromal thinning. The thinning is most apparent at the apex of the cornea. The steep conical protrusion of the corneal apex causes high myopia with severe irregular astigmatism. Other features of keratoconus include an iron ring, known as Fleischer’s ring, that partially or completely encircles the cone.5 The cone appears as an ‘oil drop’ reflex on distant direct ophthalmoscopy due to internal reflection of light. Deep vertical folds oriented parallel to the steeper axis of the cornea at the level of deep stroma and Descemet’s membrane are known as Vogt’s striae. An acute corneal hydrops appears when there is a break in the Descemet’s membrane. The corneal edema usually subsides after few months leaving behind a scar and flattening of the cornea. The corneal nerves become more readily visible due to thinning of the cornea. High irregular astigmatism precludes adequate spectacle correction. In the early stages, use of contact lenses may improve the visual acuity. However, contact lens fitting can be extremely difficult and in advanced cases, it ceases to improve visual acuity optimally necessitating corneal transplantation.
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Fig. 2.7: Hexagonal endothelial cells in a healthy cornea in high magnification (above) and low magnification (below).
The most effective way to identify early cases of keratoconus is computerized corneal topography that has become a gold standard for diagnosis and follow-up of the disease in recent years.6,7 Confocal microscopy is a relatively newer investigative modality to assess the keratoconic cornea. Morphological changes in keratoconus are mostly confined to the corneal apex and depend on the severity of the disease. The rest of the cornea may appear
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Fig. 2.8: Z-scan of the endothelium.
Figs. 2.9A and B: Reliable automated endothelial cell counting by confocal microscopy.
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Fig. 2.10: Obliquely elongated superficial epithelium in keratoconus.
normal. The typical polygonal shape of superficial epithelial cells is lost. They appear distorted and elongated in an oblique direction with highly reflective nuclei (Fig. 2.10). Cell borders are not distinguishable. There may be areas of basal epithelial loss as evident by a linear dark, nonreflective patch seen on confocal microscopy. The subepithelial nerve plexus generally appears normal. However, the subbasal nerve fibers are curved and take the course of stretched overlying epithelium. The corneal stroma is also affected by keratoconus. The confocal images of the stroma are highly specific to the disease. The characteristic stromal changes are multiple ‘striae’ represented by thin hyporeflective lines oriented vertically, horizontally or obliquely (Fig. 2.11A and B). These are confocal microscopic representation of Vogt’s striae.8 In advanced stages of keratoconus, the keratocyte concentration is reduced in the anterior stroma. The shape of the keratocytes is also altered. Occasionally, highly reflective bodies with tapering ends are visible in the anterior stroma near the apex. The nature of these abnormal bodies is not yet known, however, it may represent altered keratocytes. The corneal endothelial changes vary from none to occasional pleomorphism and polymegathism.
Corneal Dystrophies Corneal dystrophies are inherited abnormalities that affect one or more layers of cornea. Usually both eyes are affected but not necessarily symmetrically. They may present at birth but more frequently develop during adolescence and progress gradually throughout life. The effect on vision is highly variable, depending on the disorder.
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Figs. 2.11A and B: Advanced keratoconus: Striae are seen in the stroma.
Granular Dystrophy This is an autosomal dominant bilateral noninflammatory condition that results from deposition of eosinophilic hyaline deposits in the corneal stroma.9 It specifically affects the central cornea and eventually can cause decreased vision and eye discomfort. Initially, the lesions are confined to superficial stroma but with progression of the disease they can involve the posterior stroma as well.
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Confocal microscopy reveals highly reflective, bright, dense structures in the anterior and midstroma. Keratocytes are not involved. Depth of stromal involvement may be ascertained by using the Z-scan function. This is an added advantage over other contemporary investigations that enables the surgeon to plan for surgical procedures. Confocal microscopy is also useful in the differential diagnosis and follow-up of the disease.
Posterior Polymorphous Dystrophy Posterior polymorphous dystrophy (PPMD) is a rare inherited disorder of the posterior layer of the cornea. It is a bilateral disorder with early onset, although early stage diagnosis is rare since most of the affected individuals remain asymptomatic. The characteristic endothelial changes are small vesicles or areas of geographic lesions. In fact, endothelial cells lining of the posterior surface of the cornea have epithelial-like features.10,11 These cells can also cover the trabecular meshwork, leading to glaucoma in some patients. Most severe cases may develop corneal edema due to compromised pump function of the endothelial cells. Confocal microscopy shows multiple round vesicles at the level of Descemet’s membrane and endothelium.12 PPMD usually distorts the normal flat profile of the endothelial cells and present as large dark, cystic impressions on confocal scan. The endothelial cells surrounding the lesion appear large and distorted.
Fuchs Endothelial Dystrophy Fuchs endothelial dystrophy is a chronic bilateral hereditary (variable autosomal dominant or sporadic) disorder of the corneal endothelium. It typically presents after the age of 50 and is more common in females. There is a loss of endothelial cells that results in deposition of collagen materials in Descemet’s membrane. These focal excrescences in Descemet’s membrane are called corneal guttata, which is the hallmark of this disease. The integrity of the corneal endothelium is essential to maintain the metabolic and osmotic properties of the entire cornea. Corneal edema in Fuchs dystrophy initially involves the posterior and midstroma. As the disease advances, the edema progresses to involve the anterior cornea; resulting in bullous keratopathy. Confocal microscopy is useful to visualize corneal guttata. This technique has a distinct advantage over conventional specular microscopy that fails to visualize the endothelium when there is significant corneal edema.13 The corneal guttata appears dark with a bright central reflex14 (Fig. 2.12). In advanced stages, the endothelial morphology is altered completely but distorted cell borders can still be visualized.14 In the early stages of bullous keratopathy, intraepithelial edema is seen as distorted cellular morphology with increased reflectivity. Confocal microscopy can also identify the bullae in the basal epithelial layer.
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Fig. 2.12: Guttata seen in the endothelium in mild Fuchs endothelial dystrophy (above) and severe disease (below).
Laser in situ Keratomileusis Traditionally, the cornea is evaluated with slit-lamp biomicroscopy and computerized corneal topography both pre- and postoperatively. Confocal microscopy adds a new perspective to the commonly employed investigations. The functional outcome of laser in situ keratomileusis (LASIK) depends on many factors including biomechanics, the healing process and the inflammatory response of the flap interface that is created between the epithelial flap and stromal bed. A confocal scan is useful in the following scenarios.
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LASIK is one of the newer techniques of excimer laser refractive surgery that has a strong record of being successfully used by refractive surgeons for the correction of various types of refractive errors. LASIK has become the technique of choice to correct myopia and hyperopia with or without astigmatism.15 LASIK is a modification of photorefractive keratectomy (PRK) where an excimer laser is used to ablate superficial corneal stroma after the epithelium has been removed. LASIK involves the use of a microkeratome or laser to prepare a hinged corneal flap of uniform thickness. The excimer laser is subsequently used to ablate the mid-corneal stromal bed and thereafter the flap is returned to its original position without suturing. After LASIK, the healing of corneal tissue occurs quickly since there is minimal damage to the corneal epithelium and the Bowman’s layer. • Study of corneal flap thickness • Interface study: Healing process Inflammatory response Abnormal deposits • Corneal nerve fiber regeneration • Residual stromal thickness A well-designed flap is the key to a successful outcome in LASIK. Thinner flaps are at higher risk for developing flap complications. A few studies employing confocal microscopy had suggested that the actual flap thickness after LASIK is consistently lower than the predicted thickness.16 The reasons are not yet understood. However, corneal edema that may be caused by microkeratome cut and suction may play an important role. Postoperative scarring and tissue remodeling could be other possible factors. Using a Z-scan, it is possible to identify the interface that corresponds to a very low level of reflectivity. The flap thickness is obtained by measuring the distance between the highly reflective spike from the front surface of the cornea and the low reflective interface (Fig. 2.13). The interface usually appears as a hyporeflective space in between the relatively hyperreflective cellular stroma. This interface can be easily imaged by a confocal microscope. Typically, the keratocyte concentration is lower than the normal in the interface. Bright particles and microstriae are consistently visible in the interface. These bright particles most probably originate from the microkeratome blade and are represented by highly reflective white bodies (Fig. 2.14). Microstriae are present at the Bowman’s layer. Excessive interface microstriae and bright particles may lead to astigmatism and eventually a poor outcome after LASIK. These microstriae can be imaged with a confocal microscope, even when the slit-lamp examination is unremarkable. Diffuse lamellar keratitis (DLK) also known as the ‘Sands of Sahara syndrome,’ is a noninfectious inflammation of the interface. The etiology is not known but it is assumed to be toxic or allergic in nature. In confocal scan, DLK appears as diffuse and multiple infiltrates in the interface with no anterior or posterior extension (Fig. 2.15).
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Fig. 2.13: Measurement of flap thickness in LASIK via the Z-scan.
Fig. 2.14: Bright high reflective particles at the flap-stroma interface in laser in situ keratomileusis (LASIK).
Subepithelial nerve fibers are also affected by LASIK. Nerves are not usually visible in immediate postoperative period. However, the regenerating nerve fibers appear as thin irregularly branching lines when a confocal scan is performed 5–7 days after surgery. The residual stromal thickness can also be measured using Z-scan technique as described, while also evaluating the epithelial flap. A confocal scan image below demonstrates a foreign body seen under the flap after LASIK (Fig. 2.16).
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Fig. 2.15: Diffuse lamellar keratitis after laser in situ keratomileusis (LASIK). Multiple infiltrates are seen as bright spots.
Fig. 2.16: A foreign body seen under the flap after laser in situ keratomileusis (LASIK).
Infectious Keratitis Acanthamoeba Keratitis Accurate and prompt diagnosis of sight threatening infectious keratitis is one of the major challenges in ophthalmic practice today. Delay in diagnosis and inappropriate treatment can adversely affect the visual outcome. Current microbiological diagnostic techniques can identify most of the offending organisms if the tests are carried out meticulously. However, confocal microscopy can play a significant role in keratitis with a prolonged course, polymicrobial keratitis and in scenarios when conventional techniques are
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Fig. 2.17: In vivo confocal microscopy demonstrating active Acanthamoeba represented by bright refractile bodies. A few trophozoites are also visible.
unable to identify any organism. The usefulness of confocal microscopy was demonstrated in eyes with Acanthamoeba17 and fungal keratitis.18,19 It is frequently difficult to identify Acanthamoeba on the ocular surface since its presentation can mimic herpetic keratitis and several forms of bacterial keratitis. This diagnostic dilemma has often led to delays in making the correct diagnosis and may affect the visual outcome significantly. Most cases of Acanthamoeba keratitis is diagnosed on tissue culture, corneal biopsy and histological analysis.20-22 Confocal microscopy offers a useful noninvasive technique to diagnose Acanthamoeba keratitis in vivo. Although, confocal microscopy lacks sufficient resolution to be the only method of diagnosis, it can be used in screening patients suspected of having Acanthamoeba keratitis.23,24 On confocal microscopy, Acanthamoeba are visualized typically as round or ovoid, highly reflective structures ranging in size from 10 to 25 mm, which is larger than leucocytes (Fig. 2.17). Sometimes, the internal structure of Acanthamoeba along with vacuoles are also visible. The double-walled cystic forms of the parasite are also often well-visualized (Fig. 2.18). Acanthamoeba are smaller and much more iridescent than corneal parenchymal cells such as epithelial cells and keratocyte nuclei.
Mycotic Keratitis Mycotic keratitis is common in many countries, especially in tropical latitudes. Filamentous fungi are the commonest cause of mycotic keratitis.25 It is important to establish a specific diagnosis as early as possible to ensure prompt institution of antifungal therapy. Although confocal microscopic examination may help in reaching a rapid presumptive diagnosis, the in vivo confocal microscopic characteristics of fungal keratitis continues to confuse
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Fig. 2.18: In vivo confocal microscopy showing typical double-walled cystic form of Acanthamoeba.
Fig. 2.19: In vivo confocal microscopy showing fungal hyphae.
ophthalmologists. A clear understanding of the confocal characteristics of fungal hyphae and spores may play an important role in establishing a rapid diagnosis. Identification of fungal organisms by confocal microscopy is important, not only for rapidly diagnosing fungal keratitis, but also for monitoring response to antifungal therapy. On confocal microscopy, the mycotic organisms appear as thin, extensively branching and beaded filaments. Sometimes, round to oval spores can also be found (Fig. 2.19). In vivo, confocal microscopy reveals four types of morphologies of mycotic keratitis, such as: (a) branching hyper-reflective structures, (b) long linear hyper-reflective structures, (c) short rod hyper-reflective structures, and (d) round to oval structures (spores). The hyphae must not be confused with corneal nerves which appear regular, elongated and uniform with sharp margins.
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Corneal Grafts The confocal microscope is a useful tool to follow-up corneal grafts and to detect abnormalities that may occur postoperatively. It provides images at the cellular level to identify pathological changes even before they become clinically evident. It can also be used to assess the donor cornea. Corneal graft survival is heavily dependent on the number of healthy endothelial cells present. Endothelial cell loss occurs rapidly after corneal transplantation.26 Majority of cell loss takes place during the first two postoperative years.27 Several studies have suggested that endothelial cell loss is much higher after corneal grafting when the primary indications are bullous keratopathy or hereditary stromal dystrophy in comparison to keratoconus and corneal leukomas.28,29 Another interesting fact is that endothelial cell loss is greater when corneal transplantation is performed on phakic eyes than on aphakics.30 Confocal microscopy supersedes conventional specular microscopy while evaluating endothelial cell characteristics, especially in eyes with stromal edema. During the immediate postoperative period, the endothelium looks normal and healthy. However, as time progresses, endothelial cell density decreases as evidenced by pleomorphism and polymegathism. Occasionally, bright pre-endothelial deposits appear, the significance of which is not yet known (Fig. 2.20). Reinnervation after grafting is another clinical phenomenon that is imaged well by confocal microscopy. The first sign of innervation that starts a few months after keratoplasty is new nerve growth at the periphery of the graft stroma. However, complete innervation may take many years to develop. Regenerated nerve fibers look similar to those found in the normal cornea.
Fig. 2.20: Pleomorphism, polymegathism and pre-endothelial deposits in a corneal graft.
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Fig. 2.21 Coexistence of degenerated and normal endothelial cells in early endothelial allograft rejection.
Occasionally, they may take a tortuous and convoluted course depending on age (e.g., older patients) and primary indications of keratoplasty (e.g., bullous keratopathy, corneal dystrophies). It is well-known that allograft rejection is one of the most common causes of graft failure. Graft rejection can be classified as epithelial, subepithelial and endothelial rejection, of which the endothelial subtype has the worst prognosis. The confocal microscopic features of epithelial rejection are distorted basal epithelial cells with altered subepithelial reflectivity. Subepithelial rejection is identified by discrete opacities underneath the epithelial layer.31 Endothelial rejection, on the other hand, is characterized by coexistence of normal looking and degenerated endothelial cells, focal endothelial cell lesions and bright highly reflective microprecipitates32 (Fig. 2.21).
Intracorneal Deposits Sources of intracorneal deposits can be exogenous or endogenous. They can involve various layers of cornea individually or in combination. • Exogenous sources: Long-term use of contact lenses Refractive surgery Vitreoretinal surgery using silicone oil Drugs including amiodarone, chloroquine • Endogenous sources: Wilson’s disease Hyperlipidemia Fabry’s disease Hemosiderosis
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Fig. 2.22: Intracellular deposits at basal epithelial layer in amiodarone toxicity.
The clinical diagnosis of these conditions is based on slit-lamp biomicroscopy and systemic features. The knowledge of confocal microscopic features in these disorders is limited, except in drug-induced keratopathies.
Vortex Keratopathy Vortex keratopathy, also known as cornea verticillata, is characterized by whorl-like corneal epithelial deposits. It can be induced by various drugs [e.g., amiodarone (used for cardiac arrythmias) and antimalarials (chloroquine, hydroxychloroquine)]. Clinically, vortex keratopathy is manifested as golden-brown opacities at the level of the inferior corneal epithelium. On electron microscopy, they appear as intracytoplasmic lysosome-like lamellar inclusion bodies located at the basal epithelial layer.33 Confocal microscopy adds a new perspective to the imaging of this condition. It demonstrates involvement of the entire cornea, although vortex keratopathy is primarily a corneal epithelial pathology. The characteristic features are presence of highly reflective, bright intracellular deposits at the basal epithelial layer (Fig. 2.22). The overlying epithelium is usually normal. In advanced cases these microdeposits may extend to the stroma and eventually to the endothelium.34 Stromal keratocyte density is often reduced.
CONCLUSION Ophthalmic investigations and imaging modalities have advanced tremendously over the past few decades. The confocal microscope is one of these wonderful innovations that has shed much light on the anatomy and pathology of the human cornea. It is becoming increasingly useful in clinical practice and its indications are continually expanding. Confocal microscopy is truly an exciting tool that can be useful for the clinical diagnosis, follow-up and analysis of many corneal lesions.
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ACKNOWLEDGMENT We would like to acknowledge Nidek Technologies for their contribution of clinical photographs, as well as Aria Mangunkusumo and Vanathi Ganesh for their help.
REFERENCES 1. Weigand W, Thaer AA, Kroll P, et al. Optical sectioning of the cornea with a new confocal in vivo slit-scanning videomicroscope. Ophthalmology. 1995;102(4):485-92. 2. Oliveira-Soto L, Efron N. Morphology of corneal nerves using confocal microscopy. Cornea. 2001;20(4):374-84. 3. Tuft SJ, Coster DJ. The corneal endothelium. Eye (Lond). 1990;4(Pt 3):389-424. 4. Nucci P, Brancato R, Mets MB, et al. Normal endothelial cell density range in childhood. Arch Ophthalmol. 1990;108(2):247-8. 5. Gass JD. The iron lines of the superficial cornea: Hudson-Stahi line, Stocker’s line and Fleischer’s ring. Arch Ophthalmol. 1964;71:348-58. 6. Maguire LJ, Bourne WM. Corneal topography of early keratoconus. Am J Ophthalmol. 1989;108(2):107-12. 7. Maguire LJ, Lowry JC. Identifying progression of subclinical keratoconus by serial topography analysis. Am J Ophthalmol. 1991;112(1):41-5. 8. Somodi S, Hahnel C, Slowik C, et al. Confocal in vivo microscopy and confoal laser-scanning fluorescence microscopy in keratoconus. Ger J Ophthalmol. 1996;5(6):518-25. 9. Werner LP, Werner L, Dighiero P, et al. Confocal microscopy in Bowman’s and stromal corneal dystrophies. Ophthalmology. 1999;106(9):1697-704. 10. Hirst LW, Waring GO. Clinical specular microscopy of posterior polymorphous endothelial dystrophy. Am J Ophthalmol. 1983;95(2):143-55. 11. Mashima Y, Hida T, Akiya S, et al. Specular microscopy of posterior polymorphous endothelial dystrophy. Ophthalmic Paediatr Genet. 1986;7(2):101-7. 12. Chiou AG, Kaufman SC, Beuerman RW, et al. Confocal microscopy of posterior polymorphous endothelial dystrophy. Ophthalmologica. 1999;213(4): 211-3. 13. Chiou AG, Kaufman SC, Beuerman RW, et al. Confocal microscopy in cornea guttata and Fuch’s endothelial dystrophy. Br J Ophthalmol. 1999;83(2):185-9. 14. Rosenblum P, Stark WJ, Maumenee IH, et al. Hereditary Fuch’s dystrophy. Am J Ophthalmol. 1980;90:455. 15. Reviglio VE, Bossana EL, Luna JD, et al. Laser in situ keratomileusis for the correction of hyperopia from + 0.50 to + 11.50 diopters with Keracor 117C laser. J Refract Surg. 2000;16(6):716-23. 16. Durairaj VD, Balentine J, Kouyoumdjian G, et al. The predictability of corneal flap thickness and tissue laser ablation in laser in situ keratomileusis. Ophthalmology. 2000;107(12):2140-3. 17. Cavanagh HD, Petrol WM, Alizadeh H, et al. Clinical and diagnostic use of in vivo confocal microscopy in patients with corneal disease. Ophthalmology. 1993;100:1444-54. 18. Winchester K, Mathers WD, Sutphin JE. Diagnosis of aspergillus keratitis in vivo with confocal microscopy. Cornea. 1997;16(1):27-31.
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19. Florakis GJ, Moazami G, Schubert H, et al. Scanning slit confocal microscopy of fungal keratitis. Arch Ophthalmol. 1997;115:1461-3. 20. Mathers WD, Sutphin JE, Folberg R, et al. Outbreak of keratitis presumed to be caused by Acanthamoeba. Am J Ophthalmol.1996;121(2):129-42. 21. Auran JD, Starr MB, Jakobiec FA. Acanthamoeba keratitis: A review of the literature. Cornea. 1987;6(1):2-26. 22. D’Aversa G, Stern GA, Driebe WT Jr. Diagnosis and successful medical treatment of Acanthamoeba keratitis. Arch Ophthalmol. 1995;113(9):1120-3. 23. Winchester K, Mathers WD, Sutphin JE, et al. Diagnosis of Acanthamoeba keratitis in vivo with confocal microscopy. Cornea. 1995;14(1):10-7. 24. Chew SJ, Beuerman RW, Assouline M, et al. Early diagnosis of infectious keratitis with in vivo real time confocal microscopy. CLAO J. 1992;18(3): 197-201. 25. Wang L, Zhang J, Sun S, et al. In vivo confocal microscopic characteristics of fungal keratitis. Life Science J. 2008;5(1):51-4. 26. Harper CL, Boulton ML, Marcyniuk B, et al. Endothelial viability of organ cultured corneas following penetrating Keratoplasty. Eye. 1998;12(5):834-8. 27. Vasara K, Setälä K, Ruusuvaara P. Follow-up study of human corneal endothelial cells, photographed in vivo before eneucleation and 20 years later in grafts. Acta Ophthalmol Scand. 1999;77(3):273-6. 28. Obata H, Ishida K, Murao M, et al. Corneal endothelial cell damage in penetrating keratoplasty. Jpn J Ophthalmol. 1991;35(4):411-6. 29. Abott RL, Fine M, Guillet E. Long-term changes in corneal endothelium following penetrating keratoplasty. A specular microscopic study. Ophthalmology. 1983;90(6):676-85. 30. Ing JJ, Ing HH, Nelson LR, et al. Ten-year postoperative results of penetrating keratoplasty. Ophthalmology. 1998;105(10):1855-65. 31. Cohen RA, Chew SJ, Gebhardt BM, et al. Confocal microscopy of corneal graft rejection. Cornea. 1995;14(5):467-72. 32. Cho BJ, Gross SJ, Pfister DR, et al. In vivo confocal microscopic analysis of corneal allograft rejection in rabbits. Cornea. 1998;17(4):417-22. 33. Ghose M, McCulloch C. Amiodarone-induced ultrastructural changes in human eyes. Can J Ophthalmol. 1984;19(4):178-86. 34. Ciancaglini M, Carpineto P, Zuppardi E, et al. In vivo confocal microscopy of patients with amiodarone induced keratopathy. Cornea. 2001;20(4): 368-73.
3 LASIK Frank Joseph Goes
INTRODUCTION The goal of refractive surgery is to improve the refraction of the eye so that an ametropic eye becomes emmetropic or approaches emmetropia. The cornea takes care of two-thirds of the refractive component of the eye and the natural eye lens of the other one-third. This means that the refractive state of the eye can be improved by working either on the cornea or the lens. The refractive power of the cornea can be changed by changing the curvature and/or the thickness. The same is not applicable on the lens. However, the natural lens may be removed to decrease the refractive power of the eye as performed in high myopia (clear lens extraction). Alternatively, the natural lens may be replaced by a better adapted lens or by a lens which restores or improves accommodation using ‘refractive lensectomy’. If need be a supplementary lens (phakic lens) is implanted to change the refractive power of the eye. Theoretically, the natural cornea may be replaced by an artificial cornea to approach emmetropia but the right material for that purpose is not yet available. However, an extra material in the cornea (corneal inlay) can be introduced to modify and improve the refractive power of the cornea.
CHANGE IN CORNEAL CURVATURE Let us focus on modifying the refractive power of the cornea by a technique called laser in situ keratomileusis (LASIK). ‘Laser-assisted in situ keratomileusis,’ commonly referred to as LASIK, has become the single most common operation with over 35 million procedures performed worldwide by 2010. It has evolved into a 10 minutes process that can correct refractive errors with minimal discomfort and a recovery time of a few hours. It is the result of
numerous brilliant ideas and bioengineering accomplishments that have led to one of the most spectacular medical procedures in the history of medicine.
PERSONAL EXPERIENCE We were privileged to be the first to introduce an excimer laser (Mel 60 from Aesculap-Meditec) in the Benelux (Belgium-Netherlands-Luxemburg) in 1992. Later, switched to better adapted models, Mel 70 and 80. We introduced the VisuMax femtosecond laser from Carl Zeiss Meditec in 2008. A femtolaser is used for excision of corneal tissue in our center since 2011. The LASIK is preferred over photorefractive keratectomy (PRK) from the year 2000. The differences between both approaches concerning the healing, patient satisfaction and outcomes are remarkable. With LASIK, patients can enjoy good vision after a few hours and return to work at the latest after 24 hours. The postoperative treatment is minimal; a bandage contact lens overnight, artificial tears during 4 weeks (to be prolonged in some patients) and combined drops (corticosteroids antibiotics) for 1 week. Patient wears protective goggles for the first 24 hours and has to be instructed not to rub the eye the first 24 hours and to sleep with the protective glasses first night. In order to make the switch from PRK to LASIK the surgeon has to learn the handling of the microkeratome. This is now much easier compared to so many years ago when we started. Training courses, wet labs etc. are available for the starters and microkeratomes have evolved and became much safer and more reliable. The introduction of the femtosecond laser eliminating the need of the microkeratome, made the technique even more reliable, easier and safer.
BIRTH OF LASIK Keratomileusis The concept that a refractive error could be corrected by sculpting corneal stromal tissue to change its curvature was the idea of José Ignacio Barraquer Moner in 1948. Barraquer developed a procedure coined as ‘keratomileusis.’ Keratomileusis literally means ‘sculpting of the cornea which involved resecting a disk of anterior corneal tissue which was then frozen in liquid nitrogen’ (Fig. 3.1). The resection was achieved using a manually driven microkeratome designed specifically for this purpose based on a carpenter’s plane. Barraquer developed the formulas to derive the volume of tissue removal required for a particular refractive error correction. His earliest patients were treated in the early 1960s in Bogotá, Colombia. Around that time, others were experimenting with Barraquer’s idea. Krwawicz in Poland, published a paper in 1964 describing a series of three highly myopic eyes in which he had performed manually a ‘stromectomy.’ Pureskin in Russia described the concept of an incomplete anterior corneal resection to leave a naturally hinged flap in 1967, after which a stromal
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Fig. 3.1: Jose I Barraquer Moner using his first cryolathe to mill the underside of a resected disk of anterior corneal tissue. This original lathe was a modified Watchmaker’s lathe. Courtsey: Carmen Barraquer.
disk was removed by trephination. Early to mid-1980s surgeons from around the world came to learn this difficult, but miraculous technique.
Barraquer-Krumeich-Swinger Technique Two of Barraquer’s disciples, Krumeich and Swinger, worked on a refinement of the technique to perform keratomileusis without freezing referred to as the Barraquer-Krumeich-Swinger (BKS) technique (Figs. 3.2A and B). The BKS technique aimed to reduce surgical trauma to the tissues and improve visual recovery time.
In situ Keratomileusis At around the same time, another non-freeze technique called, in situ keratomileusis, was developed. The procedure was first performed by Ruiz. He came up with the idea of passing the microkeratome a second time to resect the required lenticule directly from the stromal bed.
Automated Lamellar Keratoplasty Ruiz was then responsible for designing a gear system to automate the passage of the microkeratome head. This eased the technical challenges of using a manual microkeratome, therefore avoiding irregular resections and greatly improving the accuracy. The procedure became known as ‘automated lamellar keratoplasty (ALK)’.
Figs. 3.2A and B: (A) Technical diagram of the first manually driven microkeratome developed by Barraquer for corneal disk resection in keratomileusis (B) photo. Courtsey: Carmen Barraquer.
In 1988, Ruiz presented a paper demonstrating how a flap could be produced by stopping the microkeratome before the end of the pass. The flap would then be tucked under the second microkeratome ring applied for the stromal resection thus leaving a hinge to simplify the replacement and reduce cap related complications.
Excimer Laser In the early 1990s, in situ keratomileusis was combined with the emerging technology of excimer lasers for corneal tissue ablation to finally become ‘LASIK,’ with the birth of LASIK as we know it today. In 1970, the
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term excimer laser was introduced to describe a laser built by Basov using a xenon dimer gas, the name excimer coming from an abbreviation of ‘excite dimer’. The argon-fluoride excimer laser was developed in 1976 (Fig. 3.3). Plume may be seen after an excimer laser pulse (Fig. 3.4).
Fig. 3.3: Basic components of an excimer laser demonstrates the active laser medium as gas in the storage tank and in the laser cavity, the exciting energy pumping source initiates the stimulated emission of radiation which is amplified by the mirrors to create the laser beam.
Fig. 3.4: Plume immediately after an excimer laser pulse. Courtsey: Alfred Vogel.
It was not until 1981 that an argon-fluoride excimer laser (193 nm) was fired onto organic tissue when Blum, Wynne and Srinivasan, demonstrated that complex patterns could be made at a micronic level with each pulse removing a fraction of a micron. This research culminated in excimer lasers being used for etching microchips. This process of direct splitting of molecular bonds with minimal adjacent heating using excimer laser-tissue interaction was coined ‘photoablation.’ Trokel and Marshall later studied the ultrastructural aspects of corneal photoablation. They compared the quality of the wounds made by an excimer laser at 193 nm with one at 248 nm as well as made by steel and diamond blades (Fig. 3.5A to D). The quality of the wounds was best with 193 nm. The wound quality suggested to Marshall that large area ablation could be performed in the central cornea, rather than just for peripheral linear incisions (Fig. 3.6). This was described as ‘photorefractive keratectomy (PRK)’. Then, Marshall demonstrated no changes in corneal transparency 8 months after PRK in 12 monkey corneas, and McDonald reported stable dioptric change in a primate cornea with good healing and long-term corneal clarity up to one year after PRK. In 1985, Seiler performed the first large area ablation in a human eye to remove a corneal scar having previously performed Tincisions with an excimer laser to correct for astigmatism. This led to PRK being performed in humans. In the early 1988s McDonald performed the first PRK on a sighted eye due for enucleation, while at around the same time L ’Esperance and Seiler began also performing PRK, but in blind eyes. In 1991, Dausch and Schroeder presented results in high myopes with the Aesculap-Meditec excimer laser and later, in 1993, presented the first hyperopic ablation profiles.
Figs. 3.5A to D: Light micrographs of rabbit corneas incised by: (A) an argon-fluoride excimer laser (193 nm), (B) a krypton fluoride excimer laser (248 nm), (C) a Micra diamond knife and (D) a sharp point steel blade. The wound quality can be seen to be best with the argon-fluoride excimer laser. With permission from: Marshall J, Trokel S, Rothery S, et al. A comparative study of corneal incisions inducedby diamond and steel knives and two ultraviolet radiations from an excimer laser. Br J Ophthalmol. 1986;70(7):482-501.
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Fig. 3.6: Myopic ablation performed using a broad beam laser and a moving iris diaphragm. The diameter of the iris diaphragm was gradually reduced which created a series of small steps. The number of steps was increased to better approximate a curved surface. Courtesy: John Marshall.
Laser in situ Keratomileusis The idea of using an excimer laser to ablate tissue under a flap was springing up independently in various parts of the world. In 1988, Razhev and co-workers in Novosibirsk, USSR began using a 5 mm trephine to produce a central 100 mm deep circular keratotomy and then a scalpel to create a lamellar hinged flap. They then used an excimer laser to ablate the stromal bed before replacing the lamellar flap in four myopic and five hyperopic eyes and presented their results with up to 2 years’ follow-up in September 1990 at Columbia University. At around the same time, Burrato was performing classical keratomileusis but from October 1989 he used an excimer laser for ablation on the underside of the cap and published his first 30 high myopic eyes with few complications and 1 year follow-up in 1992. In December, 1989 he decided instead to perform the excimer laser ablation directly on the stromal bed before replacing the cap. Pallikaris also independently conceived of a hinged flap using a microkeratome, he had specifically designed for rabbit studies and performed the ablation with an excimer laser on the exposed bed followed by replacement of the flap without sutures. The term LASIK was first used to describe this procedure in his 1991 paper. Pallikaris treated his first patient in October 1990 and published his results on 10 high myopic human eyes with 1 year follow-up in 1994.
LASIK COMPLICATIONS LASIK comes with a number of short- and long-term risks and complications. Complications typical for PRK are haze, characterised by subepithelial fibrosis caused by an abnormal wound healing response, leading to epithelial hyperplasia, presence of newly formed and disorganised collagen III. Besides that, regression is also a much more common complication after PRK than after LASIK, especially in eyes that have a higher attempted correction (Cosar). Topical anesthesia complications can create superficial punctate keratopathy or epithelial defect. A bandage contact lens will usually solve the problem. Complications with eyelashes, drape and speculum may interfere with the movement of the keratome. Conjunctiva related complications such as pinguecula, pterygia can make suction impossible or difficult. Important chemosis causing insufficient suction, has to be avoided and may lead to postponing the surgery. Anatomical variations such as a prominent orbital rim, narrow palpebral fissure, may make placement of the microkeratome difficult. Insertion of the suction ring without a speculum or using a special speculum can be helpful. A lateral canthotomy may be tried. If this does not work, one has to convert towards PRK or laser epithelial keratomileusis (LASEK). Subconiunctival hemorrhage is a relatively common aesthetic complication and patient should be informed about it beforehand. Corneal bleeding may happen when there is limbal hyperemia in contact lens wearers. Application of a dry sponge or eventually soaked with 2.5% adrenaline (cave the pupil will dilate) may be used. Flap problems: Faced with a decentered flap or incomplete cut the treatment can be continued if the exposed stromal bed is large enough to perform the laser ablation. If this is not the case, a new flap can be planned after 1 week. Free cap; if the diameter of exposed stroma is large enough, proceed with treatment and put the flap back with on top a bandage contact lens. A perforated or buttonholed flap may occur when the cornea is very steep (more than 46 D) or in case of mechanical defects. In that case, stop the procedure, place a bandage lens and come back in 3-6 months. Anterior chamber entry may occur in case of keratoconus or irregular cornea. It should be sutured immediately with 10/0 nylon. Pizza slicing may occur in case of LASIK after previous radial keratotomy. The pieces have to be put into place (which is easy) and a bandage lens to be placed for 24 hours.
Photoablation Related Complications Decentration occurs less frequently with lasers with eye tracking systems. Central islands (a central zone of minimal 1.5 mm and steepening of at least 3D) may occur with broad beam lasers but is now exceptional. Retreatment
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Fig. 3.7: Customized Topolink ablation with the Mel 80 (F. Goes). Right inferior before-right superior after ablation; left power difference map showing the ablation retreatment.
with topoguided ablation is necessary when this does not resolve after 6 months (Fig. 3.7). Interface debris should be cleaned out manually. Flap wrinkles and folds may induce irregular astigmatism and loss of best spectacle-corrected visual acuity (BCVA). Wrinkles, occurring during the procedure should be treated by stretching and repositioning. Wrinkles, occurring in the early postoperative period may be caused by dry eye syndrome or rubbing. Treatment consists of lifting the flap, refloating after stretching, ironing the flap, hydrating the flap with hypotonic saline, or suturing the flap in recalcitrant cases.
Postoperative Complications Diffuse lamellar keratitis or sands of the Sahara syndrome (DLK) may have several reasons and has four stages. In stages 1 and 2, intensive corticosteroid treatment may suffice. From stage 3-4 lifting of the flap, cleaning and irrigation of corticosteroids and antibiotics becomes urgent. Epithelial ingrowth (epithelial cells proliferating in the lamellar interface) can lead to irregular astigmatism and opacification of the interface resulting in loss of BCVA and corneal melting. Only when there is a risk of loss of BCVA, one should intervene. The flap is to be lifted, the bed and the flap are scraped with a blunt spatula and sponges and a bandage contact lens is applied. Eventually the flap has to be sutured.
RETREATMENT In a British study of 360 myopic eyes treated with LASIK about 10% cases required retreatment (Dick VII). At 1-year follow-up, 56% of the eyes were within ± 0.50 D spherical equivalent (SE), and 78% were within ± 1.00 D SE. Seventy-eight percent of the eyes examined at 1-year post-retreatment managed unaided vision of 0.66 or better.1 Among hyperopes, there is a correlation between the preoperative degree of farsightedness and the achievement of a postoperative refractive error within ± 1 D: in a long-term follow-up study from Stanford University, the percentage of eyes within ± 1.0 D of emmetropia was 82.4% for low hyperopia (up to + 2.0 D), 75.0% for medium hyperopia (+ 2.0 to + 4.0 D), and 66.7% for high hyperopia (more than + 4.0 D). In case of under and or overcorrection, a retreatment has to be considered in 3 months. In case of severe miscorrection (erroneous treatment planning) immediate retreatment can be performed. Regression after LASIK may be caused by epithelial hyperplasia and abnormal corneal wound healing. Modifying the regression with corticosteroid treatment can be tried. Iatrogenic ectasia can, most of the time, be avoided by good patient selection. Candidates with abnormal corneas, the so-called keratoconus suspects, have to be rejected for treatment. The minimum thickness of residual stroma to prevent ectasia should be 250 mm. However, some unknown factors can still be responsible for iatrogenic keratectasias. We are now lucky to have ‘corneal cross-linking’ as a retreatment option. Besides that, intracorneal ring segments, hard contact lenses and eventually keratoplasty are also available. The experience of keratomileusis shows that ectasia is a rare phenomenon as there were only 45 cases out of 1,606 (2.8%) keratomileusis performed within 21-year follow-up (Barraquer, 1998 #1298). This population also included some extremely high myopia. Detecting keratoconus through the use of front surface topography has been followed by the use of tomography, enabling evaluation of the posterior surface and corneal thickness progression. Many keratoconus screening indices have been developed using these data. Other keratoconus screening techniques have used wave front analysis, and measurements of ocular biomechanics using the Ocular Response Analyzer. Dan Reinstein introduced the concept of detecting keratoconus using epithelial thickness profiles. The other factor in reducing the risk of ectasia has been the introduction of femtosecond lasers, giving surgeons the ability to make ultra-thin flaps and hence maximize the residual stromal thickness. Femtosecond lasers also have improved the reproducibility of flap thickness compared to mechanical microkeratomes, meaning that there are fewer cases where an unexpectedly thick flap occurs. Mechanical microkeratomes have also improved dramatically from the early models which had reproducibility as high as 30 μm, whereas modern models have a reproducibility of 10 μm. Night vision problems and glare are present in most of the patients during the early weeks after surgery. Usually the patient adapts. In case of decentered
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ablation, with large scotopic pupils or induced astigmatism, the complaints will persist and topography-guided laser has to be considered. Dry eye is the most frequent complication after LASIK because of the disruption of the corneal innervation. Patients with preexisting dry eyes should be preoperatively detected and eventually other treatment modality should be chosen. Usually, complaints disappear in the first 3 months post LASIK. Infectious keratitis should be treated aggressively. Culture of the flap, followed by cleaning and irrigation with fortified antibiotics may help in control. Slipped or dislodging flap should be repositioned as soon as possible to avoid fixed folds.
CUSTOMIZED EXCIMER LASER TREATMENT The standard ablation pattern treatment using PRK or LASIK consists of treating only the refractive error of the patient using the nomogram of the particular platform used. This means that all eyes with a similar refraction receive the same treatment. When doing customized excimer laser treatment, each eye is regarded as unique, is measured using wavefront and or topography systems and a particular unique program is calculated for each eye and applied accordingly (De Langhe). Differences exist between ‘wavefront guided’ and ‘topography guided’ customized ablation. Corneal asphericity is described with a Q value. A cornea which is perfectly spherical will have a Q value of 0. If the peripheral cornea is less spherical (flatter) than the central part, the Q value will be negative; we call this condition a prolate cornea. In case where the peripheral cornea is more spherical (steeper) than the central part, the Q value will be positive; we call this condition an oblate cornea. A prolate cornea will produce better contrast sensitivity and better night vision than an oblate cornea and therefore all treatment profiles aim to make the cornea more spherical (prolate) with the peripheral cornea being flatter than the central cornea. Wavefront-guided treatment is based upon data acquisition of the total optical system of the eye; all the media of the eye; cornea, anterior chamber, lens and vitreous. Measurement is done with a wavefront measuring device and the differences between a perfect wavefront projected into the eye and the reflected wavefront from the eye represents the aberrations of the eye. These aberrations are measured and converted into a specific treatment program for that particular eye to obtain an ideal cornea (periphery less spherical than the central part). LASIK has proved to be effective in reducing refractive errors but it is known to cause or increase high order aberrations (HOAs) especially spherical aberration and coma. Even with reasonable good central visual acuity, patients may complain of visual symptoms such as night vision disturbances and ghosting. Wavefront measurements are used to measure HOAs. Wavefront-guided ablation can prevent and reduce
unwanted side effects, reduce enhancement rates and improve upon the quality of vision. The goal of wavefront-guided LASIK is to correct all optical aberrations of the eye which reduce vision. Topography-guided treatment is based upon data acquisition of the cornea with the help of a topography system. The primary indication is decentered ablation and night vision problems. Some laser platforms (Carl Zeiss Meditec) use a standard wavefront optimized treatment program. Other laser systems use different devices to measure and to calculate. The CRS-Master from Carl Zeiss Meditec was used to design optimal ablation profiles taking into account wavefront data, keratometry, pachymetry, pupillometer and target refraction.
INDICATIONS AND LIMITATIONS OF LASIK LASIK is probably the most frequently used corneal refractive procedure worldwide, particularly popular with younger and predominantly myopic patients. There are limits to its efficiency compelling ophthalmologists to consider other options (like refractive lens surgery) in patients with severe myopia or hyperopia. Among ophthalmological societies, there is generally a consensus that LASIK is best suited for mild and moderate myopia. The German Ophthalmological Society (DOG) recommends LASIK for up to - 8.0 D myopia, + 3.0 D hyperopia and 5.0 D astigmatism (Burkhard Dick). In myopia, Walter Sekundo would be prepared to do femto-LASIK up to - 6.0 D. In reality he only performs LASIK for the low myopes up to - 2.0. All the rest is small-incision lenticule extraction (SMILE). He believes that LASIK for low myopia is a good procedure, but in high myopia it gives poor results and risks. The results appear to be much better with SMILE. He is convinced that SMILE is about to replace femto-LASIK. In the last 2 years a snow-ball effect, in terms of publications, was seen in this field. LASIK for hyperopia can be safely performed up to + 6.50 D according to using a third-generation excimer laser with a modern ablation profile, a large optical zone and a large transition zone (Reinstein). It is possible to measure epithelial thickness that can be used as a true indicator of how much steepening can be safely performed after the primary procedure. Therefore, according to Reinstein, the best approach is to perform the primary LASIK based on traditional corneal curvature limits and then assess whether further steepening can be safely performed based on epithelial thickness measurements. Another critical component for safely treating high hyperopia is for the ablation to be centered on the corneal reflex (or corneal vertex to approximate the visual axis), particularly given that hyperopic patients tend to have a larger angle kappa. According to Dan Reinstein LASIK can be safely performed up to - 14.00 D in the majority of patients, although there will always be some patients ruled out by insufficient corneal pachymetry. With the advent of femtosecond
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lasers, it is possible to create ultrathin flaps, for example as thin as 80 mm using the VisuMax femtosecond laser due to its precision of 4.4 mm. Advances with aspheric ablation profiles have meant that the spherical aberration is rarely increased above the tolerable threshold for most patients. We personally set our limits for LASIK at - 8.0 D for myopia, + 3.5 D for hyperopia and + 4.0 D for astigmatism, on condition that the patient is a good candidate.
FEMTOSECOND LASER Techniques for postoperative management of complications are continually improving as well. We now have topography-guided custom ablation solutions that can correct the main causes of irregular astigmatism in small optical zones and decenterations. Transepithelial PTK can be used to treat irregular astigmatism by using the epithelium as a natural masking agent for the stromal surface irregularities very effectively. The femtosecond laser has become a choicest tool in the hands of many LASIK surgeons as a result of low incidence of LASIK complications (such as flap and buttonholes). Additionally, it has good predictability, safety and a low retreatment rate. In 800 hyperopic eyes of Leccisotti’s series (mean preoperative SE: + 3.41 D) undergoing femto-LASIK, 9 months postoperatively showed that the mean SE was - 0.06 ± 0.26 D, 3 eyes (0.4%) lost two lines of corrected distance visual acuity (CDVA) and 58 eyes (7.3%) lost one line. In the long run, an iatrogenic keratectasia becomes less likely but cannot be ruled out completely. The main risk factor is a preoperative irregular topography. But thin corneas, deep ablations, thin residual stromal beds and young patient age at the time of the laser surgery also are other risk factors (Bragheeth Winkler von Mohrenfels et al.). The versatility of the femtosecond laser and its effectivity in ophthalmic surgery (currently a major topic in cataract surgery) has led to the development of refractive lenticule extraction (ReLEx)/SMILE (VIII). Both methods have so far surprised many of the surgeons who have begun to use them. They are extremely precise and associated with less loss in corneal sensibility than expected and have proven to be mechanically stable. SMILE seems to lead to less early corneal nerve damage than LASIK. Presently, only one platform is available in the market to perform the procedures. The indications for ReLEx/SMILE are myopia between - 3.0 D and - 8.0 D, and astigmatism up to - 5.0 D.
Future of SMILE ReLEx In 2010, Carl Zeiss Meditec introduced the femtosecond VisuMax approach, ReLEx technique, whereby tissue is excised with the help of the femtosecond laser to adjust the refractive power of the cornea. This approach does, exactly what Barraquer was doing in the years 1960–1970 but in a more precise and
safer way. ReLEx uses the laser to carve out an intrastromal lenticule, which is then removed in one of two ways to bring about a change in refraction. The first ReLEx method that was devised, known as femtosecond lamellar extraction or FLEx, involves using a LASIK-like flap to gain access to the lenticule to remove it. In small-incision lenticule extraction (SMILE), the surgeon induces a refractive change by removing an intrastromal lenticule without having to create a flap. This method is less invasive, and involves teasing out the lenticule through a small corneal incision, between 2 and 4 mm wide, leaving the rest of the cornea intact. It is expected that ReLEx, SMILE all-femtosecond approach will become the procedure of future as the cutting precision and visual recovery time continue to improve. The VisuMax is part of the first-generation of femtosecond lasers, and there is a scope for improving the technology. The main disadvantage at the moment is the relatively slow visual recovery with fewer patients experiencing the ‘wow’ effect the day after surgery compared to LASIK. However, this has been significantly improved by adjusting the energy and femtosecond spot spacing settings to increase the ease of extracting the lenticule and reducing the total energy being put into the stroma. The other missing piece of the puzzle is that it cannot be used to treat hyperopia. However, studies are proceeding in Germany and Nepal where a hyperopic profile is being developed. It is possible that hyperopic SMILE could turn out to be more accurate and stable than hyperopic LASIK because the transition zone may be more reliable. However, the excimer laser will never be completely replaced. It will be needed in in the treatment of irregular profiles. The PTK is another procedure that will always require an excimer laser, while the majority of retreatments after SMILE will also need to be done as either a LASIK or PRK procedure.
ALTERNATIVES For higher refractive errors, refractive lens surgery is a viable alternative to corneal procedures. Phakic lenses (PIOLs) are one of the available choices. The main advantage of procedure is that the intervention is reversible. However, it comes at a price that there are number of potential complications associated with implantation of a phakic IOL. They include inflammations, infection and toxic reaction may be severe. Both implantable contact lens (ICL) and iris-fixated PIOL have a tendency to stimulate cataract formation in the natural lens. More worrisome is the fact that there is usually a considerably higher loss of endothelial cells than would physiologically occur. In a recently published Japanese study, the mean endothelial cell loss from preoperative levels after ICL implantation was 6.2% at 8 years. Patients with a phakic IOL usually appear to be more comfortable with the quality of their vision than LASIK patients. Phakic IOLs are a temporary measure according to some authors (W Sekundo). After having used the Artisan lens for almost
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two decades he switched to cachet, but left it 1 year later and is using now the ICL. This behavior clearly reflects the experience that sooner or later the phakic IOLs start to produce problems. Fortunately, we can now repair both the corneal problems (DMEK) and the lenticular problems (Phako). The other choice is refractive lens exchange, replacing the natural lens by a better adapted lens. There are no limits for this technique since refractive anomalies between - 30 and + 30 can be treated. We know that the most feared complication infection is extremely rare and that the retinal detachment is nearly nonexistent in hyperopia. Therefore, hyperopic eyes are the best suited for such a treatment. It will be up to the surgeon if he will take the risk to operate on an eye with a clear lens.
CONCLUSION LASIK is an established refractive procedure for correction of mild to moderate myopia, hyperopia and astigmatism. Introduction of femtosecond laser has made the technique more easy and safe. In the event of complications, they can be managed using modern repair tools. This is not true for IOLs since intraocular surgery introduces a number of (albeit rare) catastrophic complications such as endophthalmitis, suprachoroidal hemorrhage, retinal detachment and macular edema. The intraocular surgery should be reserved only for those cases that are outside the limits of LASIK. Presently or in coming future, LASIK is and will remain the most frequently performed refractive procedure. It should be remembered that in some patients the success of the surgery may be marred by dry eyes, keratectasia and visual disturbances like glare and halos. However, the LASIK operated is likely to face a problem in old age especially for calculating the right IOL power for cataract surgery. But why worry: who knows what kind of technology may be available by 2030 or 2040?
ACKNOWLEDGMENT My thanks go to my friends and leaders in refractive surgery: Professor Walter Sekundo, Germany who introduced the all femtosecond procedure in 2009, professor Burkhard Dick, Germany and professor Dan Reinstein, UK. They were very instrumental with their advice in preparing this manuscript.
BIBLIOGRAPHY 1. Banu CC. Lasik. In: Garg A, Alio JL (Eds). Surgical Techniques in Ophthalmology. Refractive Surgery. Jaypee Highlights Medical Publishers, Inc; 2010. pp. 67-76. 2. Barraquer JI. Queratoplastia refractiva. Est e Inf. Oftal Inst Barraquer; 1949. pp. 2-10. 3. Barraquer JI. Keratomileusis. Int Surg. 1967;48(2):103-17.
4. Bragheeth MA, Fares U, Dua HS. Re-treatment after laser in situ keratomileusis for correction of myopia and myopic astigmatism. Br J Ophthalmol. 2008;92(11):1506-10. 5. Buratto L, Ferrari M, Rama P. Excimer laser intrastromal keratomileusis. Am J Ophthalmol. 1992;113(3):291-5. 6. Dausch D, Klein R, Schröder E. [Photoablative, refractive keratectomy in treatment of myopia. A case study of 134 myopic eyes with 6-months follow-up]. Fortschr Ophthalmol. 1991;88(6):770-6. 7. De Lange J. Customized excimer laser treatment using the Wavelight Allegretto eye q laser. In: Garg A, Rosen E (Eds). Instant Clinical Diagnosis in Ophthalmology. Refractive Surgery. Jaypee Brothers Medical Publishers; 2009. pp. 156-91. 8. Desai RU, Jain A, Manche EE. Long-term follow-up of hyperopic laser in situ keratomileusis correction using the Star S2 excimer laser. J Cataract Refract Surg. 2008;34(2):232-7. 9. Dick B. Personal communication; 2014. 10. Goes FJ. Topoguided customized ablation Topolink. In: Garg A, Alio JL (Eds). Surgical Techniques in Ophthalmology. Refractive Surgery. Jaypee Highlights Medical Publishers, Inc; 2010. pp. 77-78. 11. Goes FJ. The Eye in History, India: Jaypee Highlights; 2013. pp. 1-502. 12. Igarashi A, Shimizu K, Kamiya K. Eight-year follow-up of posterior chamber phakic intraocular lens implantation for moderate to high myopia. Am J Ophthalmol. 2014;157(3):532-9.e1. 13. Krwawicz T. Lamellar corneal stromectomy for the operative treatment of myopia. A preliminary report. Am J Ophthalmol. 1964;57:828-33. 14. Lebedeva LI, Akhmamet’eva EM, Razhev AM, et al. [Cytogenetic effects of UV laser radiation with wavelengths of 248, 223 and 193 nm on mammalian cells]. Radiobiologiia.199;30(6):821-6. 15. Leccisotti A. Femtosecond laser-assisted hyperopic laser in situ keratomileusis with tissue-saving ablation: analysis of 800 eyes. J Cataract Refract Surg. 2014;40(7):1122-30. 16. L’Esperance FA Jr, Taylor DM, Del Pero RA, et al. Human excimer laser corneal surgery: preliminary report. Trans Am Ophthalmol Soc. 1988;86:208-75. 17. 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):40-7. 18. Marshall J, Trokel S, Rothery S, et al. An ultrastructural study of corneal incisions induced by an excimer laser at 193 nm. Ophthalmology. 1985;92(6):749-58. 19. Marshall J, Trokel S, Rothery S. Photoablative reprofiling of the cornea using an excimer laser: Photorefractive keratotomy. Lasers Ophthalmol. 1986;1:21-48. 20. Marshall J, Trokel SL, Rothery S, et al. Long-term healing of the central cornea after photorefractive keratectomy using an excimer laser. Ophthalmology. 1988;95(10):1411-21. 21. Mohamed-Noriega K, Riau AK, Lwin NC, et al. Early corneal nerve damage and recovery following small-incision lenticule extraction (SMILE) and laser in situ keratomileusis (LASIK). Invest Ophthalmol Vis Sci. 2014;55(3):1823-34.
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22. Pallikaris IG, Papatzanaki ME, Siganos DS, et al. A corneal flap technique for laser in situ keratomileusis. Human studies. Arch Ophthalmol.1991; 109(12): 1699-702. 23. Pallikaris IG, Siganos DS. Excimer laser in situ keratomileusis and photorefractive keratectomy for correction of high myopia. J Refract Corneal Surg. 1994;10(5):498-510. 24. Pureskin NP. [Weakening ocular refraction by means of partial stromectomy of cornea under experimental conditions]. Vestn Oftalmol. 1967;80(1):19-24. 25. Razhev A, Lantukh V, Pyatin M. [Ophthalmic devices for corneal microsurgery on excimer lasers]. Journal de Physique. 1991;1(Suppl III):C7-235. 26. Reinstein D. The birth of LASIK. In: Goes FJ (Ed). The Eye in History; 2013. Jaypee-Highlights, New Delhi, pp. 431-439. 27. Reinstein D. Personal communication; 2014. 28. Ruiz L. In Situ Keratomileusis. Invest Ophthalmol Vis Sci. 1988;29:392. 29. Sekundo W. Personal communication; 2014. 30. Seiler T, Wollensak J. Myopic photorefractive keratectomy with the excimer laser. One-year follow-up. Ophthalmology. 1991;98(8):1156-63. 31. Winkler von Mohrenfels C, Salgado JP, Khoramnia R, et al. [Keratectasia after refractive surgery]. Klin Monbl Augenheilkd. 2011;228(8):704-11.
4 SMILE versus LASIK Jorge L Alio, Mohamed El Bahrawy
RECENT EVOLUTION OF LASER REFRACTIVE SURGERY OF THE CORNEA The concepts of modern refractive surgery witnessed its breakthrough when Professor Jose I Barraquer described his coined technique of keratomileusis in 1949, setting the foundation for all following innovations in this field. The name ‘excimer laser’ came as an abbreviation of ‘excited dimer’, introduced by the Russian, Nikolay Basov, in 1970 using a xenon dimer gas. A few years later, the argon-fluoride excimer laser was developed and was first tried on an organic tissue by IBM scientists. The introduction of excimer laser to be used in the human eye was done by Stephen Trokel as a precise and safe tool of corneal shaping, these concepts later defined the refractive techniques which are widely used now, when Marguerite McDonald under the supervision of Steve Kaufmann, performed the most commonly used epithelium removal technique photorefractive keratectomy (PRK). Peyman, presented the first patency using excimer laser as a corneal refractive tool, and it was accepted in June 1989 (personal correspondence Gholam Peyman). Following Ioannis Pallikaris, among others, introduced the most widely used and commonly accepted technique of laser in situ keratomileusis (LASIK) in 1990.1 Laser refractive surgery has been performed for decades, and there have been tremendous advancements in terms of technique and technology, making it increasingly precise and highly predictable.2 LASIK is currently the most common laser refractive procedure for the treatment of myopia—its advantages include early postoperative improvement in visual acuity and minimal postoperative patient discomfort. Although LASIK patients report 95% satisfaction, a spectrum of complicated side effects can negatively impact results.3
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Femtosecond laser technology was first developed by Dr. Kurtz at the University of Michigan in the early 1990s4 and was rapidly adopted in the surgical field of ophthalmology. Femtosecond lasers emit light pulses of short duration (10−15 seconds) at 1,053 nm wavelength that cause photodisruption of the tissue with minimum collateral damage.5 The femtosecond laser has revolutionized corneal and refractive surgery with respect to its increased safety, precision and predictability over traditional microkeratomes. Advantages of bladeless femtosecond-assisted LASIK (FS-LASIK) over conventional microkeratome-assisted LASIK (MK-LASIK) include reduced dry eye symptomatology, reduced risk of flap button hole or freecap formation.6,7 Ever since femtosecond lasers were first introduced into refractive surgery, the ultimate goal has been to create an intrastromal lenticule that can then be manually removed as a single piece thereby circumventing the need for incremental photoablation by an excimer laser. A precursor to modern refractive lenticule extraction (ReLEx) was first described in 1996 using a picosecond laser to generate an intrastromal lenticule that was removed manually after lifting the flap;8,9 however, significant manual dissection was required leading to an irregular surface. The switch to femtosecond improved the precision10 and studies were performed in rabbit eyes in 199811 and in partially sighted eyes in 2003,12 but these initial studies were not followed up with further clinical trials. Following the introduction of the VisuMaxÒ femtosecond laser (Carl Zeiss Meditec, Jena, Germany) in 2007,13 the intrastromal lenticule method was reintroduced in a procedure called femtosecond lenticule extraction (FLEx). The 6-month results of the first 10 fully seeing eyes treated were published in 200814 and results of a larger population have since been reported.15,16 The refractive results were similar to those observed in LASIK, but visual recovery time was longer due to the lack of optimization in energy parameters and scan modes; further refinements have led to much improved visual recovery times.17 Following the successful implementation of FLEx, a new procedure called small-incision lenticule extraction (SMILE) was developed. This procedure involves passing a dissector through a small 2–3 mm incision to separate the lenticular interfaces and allow the lenticule to be removed, thus eliminating the need to create a flap. The SMILE procedure is now gaining popularity following the results of the first prospective trials.18-29
SMILE OUTCOME Since the development of the SMILE technique, the exciting new concept of the flapless nature of the technology, namely the 3rd generation laser refractive surgery, has driven many authors to approach it and report the results of SMILE outcomes alone or in comparison with LASIK. In a study we conducted, we compared the outcomes of a matched cases of SMILE versus 6th generation excimer laser LASIK patient, where the cases
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Table 4.1: Refractive outcome of comparative study between SMILE and LASIK. Comparison 20/20 or more 20/25 or more
Lost more than 2 lines Gained lines % of cases
20/40 or more No loss of lines Efficacy
± 0.5 D % of cases ± 1.0 D
FS-LASIK (%) 92.18 96.87 100
18.75 (1 line)
18.64 (1–3 lines)
SMILE: Small-incision lenticule extraction; LASIK: Laser assisted in situ keratomileusis; FS-LASIK: Femtosecond-assisted LASIK.
were matched by age, gender and spherical equivalent. In the SMILE group; 50% females, 34 years (23:49), - 4.59 diopters (- 2.125:8.37), the LASIK group; matching SMILE/FLEx cases: of same gender, age (± 1 year), spherical equivalent (± 0.5 D). The study included 16 eyes in each group, and we reported both SMILE and LASIK had comparable results in terms of safety, efficacy and predictability, in follow-up of 6 months duration (Table 4.1). Many other authors reported similar outcomes, still with a disadvantage of slower refractive recovery in SMILE patients, which is currently witnessing significant improvements due to the development of different energy and spot spacing setting.17,21 Kim et al. reported that age may be a predictor that influenced visual outcome, as outcomes were better in younger patients of his study sample but its effect appeared clinically insignificant.22 SMILE surgery was effective and safe in correcting low-to-moderate astigmatism, and stable refractive outcomes were observed at the long-term follow-up. The preoperative cylinder ranged from - 2.75 D to - 0.25 D (average of - 0.90 ± 0.68 D), and the mean postoperative cylinder values were - 0.24 ± 0.29 D, - 0.24 ± 0.29 D and - 0.20 ± 0.27 D at 1 month, 6 months and 12 months, respectively.23 On the other side, topographic changes and aberrometric changes were significantly lower in SMILE patients compared with LASIK patients whether in mild-to-moderate myopia or high myopia as reported by results of our study (Figs. 4.1A and B and 4.2A and B).
ADVANTAGES OF SMILE IN CASES OF DRY EYE AND OCULAR SURFACE DISEASE The flapless nature of SMILE will preserve the important anterior corneal phase, this will preserve the natural integrity of corneal nerves, which will significantly influence the ocular surface and tear film stability (Fig. 4.3).
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Figs. 4.1A and B: Topographical changes in moderate myopia. SMILE: Small-incision lenticule extraction; LASIK: Laser assisted in situ keratomileusis.
Central corneal sensitivity exhibited a small decrease and a faster recovery after the SMILE procedure compared to FS-LASIK during the first 3 postoperative months. Corneal sensitivity after SMILE and FS-LASIK was similar at 6 months after surgery.24 Qiu et al. in a longitudinal retrospective study studied 97 consecutive patients (194 eyes) who underwent SMILE for myopia. Parameters evaluated included: subjective dry eye symptoms (dryness, foreign body sensation and photophobia), tear film breakup time (TBUT), Schirmer’s test without anesthesia, tear meniscus height (TMH) and corneal fluorescein staining. Each parameter was evaluated before, and subsequently at 1 day, 1 week, 1 month and 3 months after surgery. The results showed that compared with preoperative data, dryness was noted to be significantly increased at 1 week and 1 month postoperatively ( 2 nmol 0.5 cystine/mg protein in affected patients, whereas normal subjects have LCL 10 times), in part because of the low pH of the solution, they cause burning and thus noncompliance. In addition, the free thiol can oxidize at room temperature, so it is recommended to store frozen aliquots. A commercial 0.44% cysteamine ophthalmic solution (cystaran) has been approved for clinical use in United States. A 0.55% gel formulation (cystadrops) has also been developed and is recommended to be used only 4 times a day. Unfortunately, if not treated with topical cysteamine eye drops, patients can develop severe photophobia and progress to develop corneal lesions severe enough to require a corneal transplant. Cystine crystals can reappear in the transplanted cornea due to invading host cells, if topical cysteamine treatment is not used. But, if used even after crystals develop, it has been shown to reverse the ocular symptoms and clear the cornea in few months.
Gene Therapy Various therapies to cure and control cystinosis are in progress and may be available in near future. Early studies are now available on hematopoietic stem cell (HSC) transplantation in a mouse model of cystinosis wherein adult bone marrow stem cells are used as vehicles to bring wild-type CTNS to tissues.7 Currently research is focused in developing an autologous HSC
transplantation approach whereby the patient’s own stem cells are genemodified using a lentiviral vector and reinjected into the patient to introduce a functional CTNS copy in tissues. These early reports are exciting as it may pave road to cure for cystinosis in future.
SUMMARY The overall prognosis of children with cystinosis has improved with cystinedepleting therapy and there is ongoing research to find cure with gene therapy. It is critical to identify and treat these patients early to prevent end-organ damage. The role of ophthalmologists to treat and monitor the ocular manifestations of this rare disorder is important part of the multidisciplinary care needed for patients with cystinosis.
ACKNOWLEDGMENT I acknowledge Dr Rudolph Wagner, pediatric ophthalmologist, who provided the picture for the crystals in the cornea.
REFERENCES 1. Abderhalden E. Familiare cystindiathese. Z Physiol Chem. 1903;38:557-61. 2. Usui T, Hara M, Satoh H, et al. Molecular basis of ocular abnormalities associated with proximal renal tubular acidosis. J Clin Invest. 2001;108(1): 107-15. 3. Niaudet P. Cystinosis. Available at: https:// www.uptodate.com, May 2016. 4. Middleton R, Bradbury M, Webb N, et al. Cystinosis. A clinicopathological conference. “From toddlers to twenties and beyond” Adult-Paediatric Nephrology Interface Meeting. Manchester 2001. Nephrol Dial Transplant. 2003;18:2492. 5. Gahl WA, Thoene JG, Schneider JA, et al. Cystinosis. N Engl J Med. 2002; 347(2):111-21. 6. Tsilou E, Zhou M, Gahl W, et al. Opthalmic manifestations and histopathology of infantile nephropathic cystinosis: report of a case and review of the literature. Surv Opthalmol. 2007;52(1):97-105. 7. Emma F, Nesterova G, Langman C, et al. Nephropathic cystinosis: an international consensus document. Nephrol Dial Transplant. 2014;29(Suppl 4): iv87-94.
22 Corneal Changes in Contact Lens Users Rajib Mukherjee, Gagan Sahni, G Mukherjee
INTRODUCTION ‘DO NO HARM’ is one of the basic principles of medicine. It also applies to the practice of contact lens (CL) selection, fitting and prescription. The use of CL may induce problems in patients, and therefore, the CL practitioners must know corneal changes in CL users and altered corneal physiology after the wear of CL. Essentially, corneal pathophysiological changes,1 seen with CL wear, can be due to the following mechanisms such as, hypercapnia and hypoxia, allergy and toxicity, mechanical effects and osmotic effects.
HYPOXIA AND HYPERCAPNIA It is well-known that since the cornea is an avascular structure, the oxygen needed specially by the corneal epithelium is obtained by diffusion from air when the eye is open; and from the tarsal conjunctiva, when the eye is closed; and the use of a CL markedly reduces this oxygen availability to the corneal tissue. Oxygen deprivation (Hypoxia)2 on using CL depends on the material of CL and the duration of wear. Along with hypoxia there is also carbon dioxide accumulation (hypercapnia) in the cornea. Deprivation of oxygen and accumulation of carbon dioxide (hypercapnia) in the cornea suppress the normal corneal metabolism and stimulate anerobic glycolysis. The anerobic glycolysis is responsible for lowered epithelial metabolic rate and decreased epithelial mitotic rate. It also increases epithelial lactate production, which induces an acidic shift in corneal stromal pH.3 Clinically, this gamut of CL induced corneal insult, in this category, results in: • Epithelial thinning and epithelial abrasion4 (corneal epithelial defects): Corneal changes increase susceptibility to injury due to increased
Corneal Changes in Contact Lens Users 425
Fig. 22.1: Dimple veiling in rigid contact lens (CL) user.
fragility of the corneal epithelium. This may translate in the CL wearer presenting with signs of ocular discomfort, reduced wearing time,5 contact lens intolerance, watering, etc. Epithelial microcysts6-9 (Sattler’s veil): They appear as small translucent irregularly shaped dots scattered across cornea (Fig. 22.1), which may disappear within 2 to 12 weeks after discontinuation of CL wear. These are best seen on high magnification slit-lamp retroillumination evaluation and these patients may complain diminution of vision and seeing haloes around light. Superficial punctate keratopathy (SPK): They are commonly seen due to compromised epithelial junctional integrity.9 The SPKs show staining with fluorescein. Microbial keratitis:10-14 A devastating complication, which occurs due to the breakdown of the natural defense and the sick corneal epithelial integrity. It is seen more commonly in extended wear as compared to daily wear CL users (Fig. 22.2). Corneal infection associated with RGP CL occurs less frequently. Pseudomonas aureginosa and Staphylococcus aureus are the most common organisms responsible for this catastrophe, while Streptococcus pneumonia, Serratia marcescens and other bacteria and fungi are less common. Acanthamoeba is another infection, which may be associated with infectious keratitis in CL users. Corneal stromal edema:15 It is caused by stromal acidosis,16 consequent to lactate and bicarbonate accumulation in the cornea. Apart from over wear, a tight fit, more so in rigid CL, leads to this complication (Fig. 22.3).
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Fig. 22.2: Contact lens (CL)-induced infective keratitis.
Fig. 22.3: Scleral compression with scleral contact lens (CL).
Stromal striae:17 The striae appear as fine vertical lines mostly affecting the posterior stroma. They appear as dark lines in the posterior stroma. Specular reflection is of great help in their evaluation and on direct illumination, they are seen as white lines. Usually, if stromal edema exceeds 10%, striae are clinically visible. Endothelial blebs:18,19 These are sometimes seen in initial CL users as a transient phenomenon,20 appearing about 30 minutes after CL use and subsides over several hours. Decreased pH causes patchy endothelial edema, which appears as defects (black holes) on specular reflection.
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Fig. 22.4: Contact lens (CL)-induced endothelial changes.
Endothelial polymegathism:3,21 Increased variation in cell size (Fig. 22.4) is noticed as long-term/chronic changes on corneal endothelium.19 It has a direct relation of material of CL and duration of wear. Corneal warpage: Long-term users of PMMA CL may develop irregular astigmatism and distortion of central and peripheral cornea. It is attributed to both mechanical molding and hypoxic influences.22,23 The various presentations documented on corneal topography are Central Corneal Molding Irregularity (Fig. 22.5), Central Corneal Flattening (Fig. 22.6), Corneal Furrow Depression (Fig. 22.7) and Peripheral Corneal Steepening (Fig. 22.8). These changes tend to disappear within 2 to 14 days of abstinence from contact lens use. Corneal hypoesthesia: Alteration in the afferent corneal nervous supply occurs because of hypoxia and hypercapnia.24 Superficial vascularization: There occurs dilatation of existing limbal capillaries due to chronic hypoxia.25,26
ALLERGY AND TOXICITY The material used in the manufacturing the contact lens is usually biological inert. However, in certain instances, it may challenge the immune system of the body. Usually the main causes of reactions are preservatives in contact lens solution, deposits on contact lens and deposit of debris between cornea and CL. Complications due to allergy/toxicity are: • Immobile lens syndrome: It is also referred to as ‘toxic lens syndrome’, where an inflammatory response is noticed. It is usually due to debris
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Fig. 22.5: Contact lens (CL) warpage, central molding irregularity.
Fig. 22.6: Contact lens (CL) warpage, central flattening.
trapped behind a CL. It is seen mostly in patients using extended wear CL.27 Unilateral severe pain, photophobia and watering are the usual presenting features; along with limbal congestion and infiltrates in the corneal periphery. The corneal epithelium most often remains intact. Keratic precipitates (KPs) may also be seen in some cases. Discontinuation
Corneal Changes in Contact Lens Users 429
Fig. 22.7: Contact lens (CL) warpage, furrow depression.
Fig. 22.8: Contact lens (CL) warpage, peripheral steep.
of CL use and use of lubricants and broad spectrum topical antibiotic drops usually resolves the condition in 48 to 72 hours. Thiomersal hypersensitivity:28 Thiomersal can activate both humoral and cellular immune responses on the ocular surface and the cornea. By conjugating with carrier protein, thiomersal acts as an HAPTEN, in order to act as a complete antigen. Patients present with bilateral conjunctival
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hyperemia and itching. Corneal epithelial punctate staining and superficial infiltrates are features of thiomersal hypersensitivity. Another presentation of thiomersal hypersensitivity is superior limbic keratoconjunctivitis, where one finds congestion of superior bulbar conjunctiva along with superior punctate epithelial staining. Contact lens solution preservative hypersensitivity/toxicity: The common offending agents in CL solution have been identified as benzalkonium chloride, alkyl triethanol ammonium chloride (ATAC) and chlorhexidine gluconate. Principal corneal signs of toxicity are superficial diffuse punctate staining associated with stinging and burning sensation. Pseudo-dendrite in the cornea may be seen in some cases, who present raised branching epithelial plaques, that stain very lightly with fluorescein, accompanied with papillary cum follicular conjunctivitis.29
MECHANICAL EFFECTS Cornea is a very sensitive tissue, susceptible to injury on contact lens use, either due contact lenses itself, CL deposits, or during CL manipulations (wearing, removing, etc.) • Lens edge imprint: A rigid CL on the cornea may leave an imprint on CL removal. This is seen on the corneal epithelium as the outline of the inferior rim of the CL. This manifestation is more often seen in ill-fitting or overnight use of RGP CL.30 Further, it will be prudent to look into any damage to the contact lens too, altering the dynamics (Fig. 22.9).
Fig. 22.9: Scratches on RGP contact lens (CL).
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Tight lens syndrome: It is also known as contact lens adhesion, which can occur due to inadequate wetting, excessive tear evaporation or because of over wear/overnight wear. The syndrome is mainly due to contact lens drying/desiccation; causing tightening and adherence to the cornea.31 This usually seen in Soft CL over wear, swimming with CL or sleeping with CL in the eye. These cases present with photophobia, decreased vision, irritation, circumcorneal congestion. Key to diagnosis is that on slit lamp evaluation there is minimal to no movement of the CL on blinking or even no movement on manual intervention by the contact lens care personal. Remedy is to re-fit the patient with a centrally flatter and peripherally steeper CL of high Dk value. Epithelial wrinkling:32 Wrinkling is seen in PMMA CL users.33 It is asymptomatic and recovers rapidly after CL removal. Air bubble dimpling (Fenestrated CLx2): Entrapment of air bubbles under a PMMA CL is sufficient to cause small indentations on the corneal epithelium (Fig. 22.10). These appear as discrete green dots, because of pooling, as seen on fluorescein study.34 This is a very significant feature to be kept in mind during the era of scleral contact lens use. Keep a watch on patients using rigid Fenestrated contact lenses (with holes) (Fig. 22.11). If there is any entrapment of air in the interface, may lead to potential visual problems. However, it can be diagnosed by fluorescein staining (Fig. 22.12). Contact lens and interface deposits (Fig. 22.13): They cause contact lens intolerance and reduced wearing time.35 The common reasons and source of these deposits are:
Fig. 22.10: Trapped air bubbles in scleral lens.
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Fig. 22.11: Fenestrated rigid contact lens (CL).
Fig. 22.12: Large air bubble in fenestrated rigid contact lens (CL).
ear deposits:36 Tear lysozyme and mucin deposits occur mostly due T to tear component deficiency as well as ocular surface inflammation. Protein deposits:37 These are more common deposits, which originate primarily from albumin, globulin and lysozyme in the tears. They have an opaque, white filmy appearance (Fig. 22.14), and may
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Fig. 22.13: Interface debris in rigid scleral lens.
Fig. 22.14: Protein deposit contact lens (CL) and clear CL.
have cracks when the film is thick. It is found primarily on the front surface of soft contact lenses and on both surfaces of GP lenses. Lipid deposits:38 They have a smeared, greasy whitish appearance. Source of these deposits are the meibomian glands of the eye-lids. Silicone hydrogel CL materials are most prone to this phenomenon.
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Rubbing and rinsing these lenses with an alcohol-based daily cleaner normally takes care of the issue.
OSMOTIC EFFECTS Altered tear film osmolarity on contact lens wear can be attributed to increased tear evaporation, stimulated reflex tearing and altered blinking rate. Localized areas of tear film depletion can contribute to epithelial desiccation in the cornea. • Staining at 3 and 9 o’Clock: Usually seen in persons using rigid CL, where we find fluorescein staining at the nasal and temporal margins of the cornea, always adjacent to the area of lens coverage.39 This phenomenon is due to the tear film breakdown near the CL edge. Clinical findings in this situation show a variety of lesions like, punctuate epithelial fluorescein staining, epithelial microerosions, corneal dellen formation as well as corneal neovascularization. Contact lens refitting with a smaller diameter CL and with a thinner edge generally solves this problem. • Coarse punctate erosions: These erosions mostly occur in patient using thin high-water content hydrogel CL. The coarse punctate lesions are white in appearance. These have also been described as crumb like flakes. The theory responsible for this condition is the water loss through the CL.26
REFERENCES 1. Liesegang, TJ. Physiologic changes of the cornea with contact lens wear. CLAO J. 2002;28(1):12-27. 2. Harvitt DM, Bonanno JA. Re-evaluation of the oxygen diffusion model for predicting minimum contact lens Dk/t values needed to avoid corneal anoxia. Optometry and Vision Science. October 1999. 3. Connor CG, Zagrod ME. Contact lens-induced corneal endothelial polymegathism: functional significance and possible mechanisms. Am J Optom Physiol Opt. 1986;63(7):539-44. 4. Pérez JG, Méijome JM, Jalbert I, et al. Corneal epithelial thinning profile induced by long-term wear of hydrogel lenses. Cornea. 2003;22(4):304-7. 5. Haque S, Fonn D, Simpson T, et al. Corneal and epithelial thickness changes after 4 weeks of overnight corneal refractive therapy lens wear, measured with optical coherence tomography. Eye Contact Lens. 2004;30(4):189-93; discussion 205-6. 6. Lambert SR, Klyce SD. The origins of Sattler’s veil. Am J Ophthalmol. 1981; 91(1):51-6. 7. Bourne WM. Soft contact lens wear decreases epithelial microcysts in Meesmann’s corneal dystrophy. Trans Am Ophthalmol Soc. 1986;84:170-82. 8. Keay L, Jalbert I, Sweeney DF, et al. Microcysts: clinical significance and differential diagnosis. Optometry. 2001;72(7):452-60.
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9. Liesegang TJ. Physiologic changes of the cornea with contact lens wear. CLAO J. 2002; 28(1):12-27. 10. Liesegang TJ. Contact lens-related microbial keratitis: Part I: Epidemiology. Cornea. 1997;16(2):125-31. 11. Eltis M. Contact-lens-related microbial keratitis: case report and review. J Optom. 2011;4(4):122-27. 12. Borazjani RN, Levy B, Donald G. Relative primary adhesion of Pseudomonas aeruginosa, Serratia marcescens and Staphylococcus aureus to HEMA- type contact lenses and an extended wear silicone hydrogel contact lens of high oxygen permeability. Con Lens Anterior Eye. 2004;27(1);3-8. 13. Robertson DM, Cavanagh HD. The clinical and cellular basis of contact lens-related corneal infections. Clin Ophthalmol. 2008;2(4):907-17. 14. Stapleton F, Carnt N. Contact lens-related microbial keratitis: how have epidemiology and genetics helped us with pathogenesis and prophylaxis. Eye (Lond). 2012;26(2):185-93. 15. Bonanno JA, Polse KA. Corneal acidosis during contact lens wear: effects of hypoxia and CO2. Invest Ophthalmol Vis Sci. 1987;28(9):1514-20. 16. McNamara NA, Polse KA, Bonanno JA. Stromal acidosis modulates corneal swelling. Invest Ophthalmol Vis Sci. 1994;35(3):846-50. 17. Bergmanson JP, Chu LW. Corneal response to rigid contact lens wear. Br J Ophthalmol. 1982;66(10):667-75. 18. Campbell R, Caroline P. Contact lens wear ‘Bugged’ by endothelial blebs. Contact Lens Spectrum. December 1997. 19. Chang SW, Hu FR, Lin LL. Effects of contact lenses on corneal endothelium– a morphological and functional study. Ophthalmologica. 2001;215(3): 197-203. 20. Antti V, Jukka M, Jukka S, et al. Contact lens induced transient changes in corneal endothelium. Acta Ophthalmol (Copenh). 1981;59(4):552-59. 21. Orsborn GN, Schoessler JP. Corneal endothelial polymegathism after the extended wear of rigid gas-permeable contact lenses. Am J Optom Physiol Opt. 1988;65(2):84-90. 22. Schornack M. Hydrogel contact lens-induced corneal warpage. Con Lens Anterior Eye. 2003;26(3):153-9. 23. Tseng SS, Hsiao JC, Chang DC, et al. Mistaken diagnosis of keratoconus because of corneal warpage induced by hydrogel lens wear. Cornea. 2007; 26(9):1153-5. 24. Martin XY, Safran AB. Corneal hypoesthesia. Surv Ophthalmol. 1988;33(1): 28-40. 25. Papas E. On the relationship between soft contact lens oxygen transmissibility and induced limbal hyperaemia. Exp Eye Res. 1998;67(2):125-31. 26. Bruce AS, Brennan NA. Corneal pathophysiology with contact lens wear. Surv Ophthalmol. 1990;35(1):25-58. 27. Moshirfar M, Kurz C, Ghajarnia M, et al. Contact lens-induced keratitis resembling central toxic keratopathy syndrome. Cornea. 2009;28(9):1077-80. 28. Wilson LA, McNatt J, Reitschel R, et al. Delayed hypersensitivity to thimerosal in soft contact lens wearers. Ophthalmology. 1981;88(8):804-9.
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29. Mondino BJ, Salamon SM, Zaidman GW, et al. Allergic and toxic reactions of soft contact lens wearers. Surv Ophthalmol. 1982;26(6):337-44. 30. Varsha MR, Preeji SM, Srikanth D, et al. Contact lens in Keratoconus. Ind J Ophthalmol. 2013;61(8):410-15. 31. Michael AL, Joseph BG. The effects of extended-wear hydrophilic contact lenses on the human corneal epithelium. Am J Ophthalmol. 1986;101(3): 274-77. 32. Giese MJ. Corneal wrinkling in a hydrogel contact lens wearer with Marfan syndrome. J Am Optom Assoc. 1997;68(1):50-4. 33. Rosenthal JW. Corneal epithelial wrinkling with contact lenses. Am J Ophthalmol. 1963;55:138-9. 34. Dixon JM, Lawaczeck E. Corneal dimples and bubbles: under corneal contact lenses. Am J Ophthalmol. 1962;54(5):827-31. 35. Zhao Z, Naduvilath T, Flanagan JL, et al. Contact lens deposits, adverse responses, and clinical ocular surface parameters. Optom Vis Sci. 2010;87(9): 669-74. 36. Zhao Z, Wei X, Aliwarga Y, et al. Proteomic analysis of protein deposits on worn daily wear silicone hydrogel contact lenses. Mol Vis. 2008;14:2016-24. 37. Omali NB, Zhao Z, Zhong L, et al. Quantification of individual proteins in silicone hydrogel contact lens deposits. Mol Vis. 2013;19:390-9. 38. Hart DE, Tidsale RR, Sack RA. Origin and composition of lipid deposits on soft contact lenses. Ophthalmology. 1986;93(4):495-503. 39. van der Worp E, de Brabander J, Swarbrick HA, et al. Evaluation of signs and symptoms in 3- and 9-o’clock staining. Optom Vis Sci. 2009;86(3):260-5.
23 Episcleritis and Scleritis Parthopratim Dutta Majumder, Jyotirmay Biswas
INTRODUCTION Episcleritis and scleritis are important causes of acute red eye. Even though both are inflammation of the outer coat of the eyeball, they are clinically, etiologically and morphologically distinct and different. Therefore, it is essential to differentiate between these two clinical entities, particularly from treatment point of view.
ANATOMICAL CONSIDERATIONS The term sclera is derived from Greek word ‘scleros’ meaning ‘hard.’ Sclera is an opaque, elastic and resilient tissue of the eye. It can be compared with an incomplete shell comprising approximately 90% (five-sixths) of the outer coat of the eye. Anteriorly it begins at the limbus and terminates at the optic nerve canal posteriorly. It is predominantly composed of collagen and some elastin fibrils and is relatively avascular and acellular. The episclera is the thin densely vascularized layer of connective tissue overlying the sclera and situated below the Tenon’s capsule. Apart from the vessels and unmyelinated nerve fibers, it contains bundles of collagen. Anteriorly episclera blends with subconjunctival tissues and Tenon’s capsule 1–3 mm behind the limbus and it becomes very thin and indistinct posterior to the equator. Scleritis is always accompanied by an overlying episcleritis. On the other hand, episcleritis per se is very rarely associated with scleritis. However, sclera is supplied with nerves particularly near the extraocular muscle insertions. Direct damage to or the stretch of these nerves is the cause for pain in scleritis. Scleritis occurs more commonly anterior to the equator because of the more abundant anterior vascular supply. The circulation overlying the sclera includes three vascular layers.1,2 The location, configuration of vessels
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Table 23.1: Layers of vessels of episclera and sclera. Conjunctival
Most superficial in Arteries are
Can be easily moved on the
underlying structure blanch with
tortuous and veins straight
Lies at the level of
In episcleritis, maximal
straight with a
congestion occurs within this
Can be easily moved on the
underlying structure Blanch with 10% phenylephrine Deep vascular
Lies deep to the
Maximal congestion in scleritis
Cannot be moved on the
and directly over
Does not blanch with 10% phenylephrine
Fig. 23.1: Diagram showing vascular plexuses.
and their clinical significance is tabulated in Table 23.1 and shown in the Figure 23.1.
NOMENCLATURE AND CLASSIFICATION The classification system proposed by Watson and Hayreh is widely accepted.3 Scleritis can be divided into anterior and posterior scleritis. Anterior scleritis has further been classified into four subgroups: (1) Diffuse, (2) nodular, (3) necrotizing with inflammation and (4) necrotizing without inflammation. Necrotizing scleritis without inflammation is also called scleromalacia perforans (Flowchart 23.1).
Episcleritis Episcleritis was first called ‘subconjunctivitis’ by von Graefe, then subsequently ‘hot eyes’ by Hutchinson. The name ‘episcleritis’ was first used
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Flowchart 23.1: Classification of episcleritis and scleritis
by Fuchs, who described the condition as ‘episcleritis periodica fugax’ in 1895. Episcleritis is a transient, self-limited disease of adults. It is seen more frequently in young- to middle-aged women. The chief complaint of patients with episcleritis is usually ocular redness with or without irritation. The redness typically persists for 24–72 hours and then resolves spontaneously. Rarely, patients may experience more severe redness and mild pain. Episcleritis occurs most commonly in the exposed zone of the eye and is generally recurrent in nature. More than one-third of patients have bilateral disease. Half of the episcleritis cases are idiopathic in nature. Systemic diseases associated with episcleritis are rheumatoid arthritis, relapsing polychondritis, Cogan’s syndrome, polyarteritis nodosa, etc.4 The majority of patients with episcleritis recovers completely through treatment with NSAIDs5 and has no residual changes. However, episcleritis can sometimes be associated with corneal involvement, uveitis and glaucoma. Episcleritis is diagnosed clinically by the presence of inflamed episcleral vessels, which typically radiate from the limbus, have a salmon pink color in natural sunlight, can be moved over the deeper sclera with a cotton tipped applicator and will blanch with topical 10% phenylephrine.6,7 Episcleritis is classified as diffuse or nodular. A localized mobile nodule develops in nodular episcleritis. Episcleritis can be differentiated from the scleritis on cetain clinical features. The distinguishing features between episcleritis and scleritis are tabulated in Table 23.2.
Scleritis Scleritis is a relatively more severe ocular inflammation than episcleritis. It is a severe painful inflammatory process characterized by edema and cellular infiltration of the sclera and episclera. If not treated properly and well in time,
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Table 23.2: Distinguishing features of episcleritis and scleritis. Episcleritis
Generally redness, irritation are the main
Severe boring pain is the main presenting
complaint of the patient
No or minimal tenderness
Moderate to severe tenderness
Congested vessels are bright red in color
Congested vessels are purple-red in color
and vessels can be moved easily with the
and vessels cannot be moved easily with
help of a cotton bud
the help of a cotton bud
Blanching of the vessels occurs with 10%
Blanching of the vessels does not occur
with 10% phenylephrine
it can be a significant threat to vision. Scleritis affects women more often than men, with a peak incidence in the fifth decade. It frequently starts in one eye and become bilateral in more than half of the cases.3,7 Half of the patients with scleritis have evidence of an underlying systemic disease. Scleritis can be a presenting manifestation of a life-threatening systemic autoimmune disease. Rheumatoid arthritis is the most common systemic condition associated with scleritis. The incidence of rheumatoid arthritis in patients with scleritis ranges from 10 to 33%.3,4,7 Scleritis may be associated with the following systemic diseases:3,4,7-13 • Rheumatoid arthritis • Relapsing polychondritis • Systemic lupus erythematosus and antiphospholipid syndrome • Wegener’s granulomatosis • Polyarteritis nodosa • Cogan syndrome • Juvenile rheumatoid arthritis • Ankylosing spondylitis • Ulcerative colitis • Polymyositis • Sarcoidosis • Syphilis • Tuberculosis • Herpes zoster ophthalmicus • Acanthamoeba keratitis
DIAGNOSIS Diagnosis of scleritis is almost always clinical; however, when the posterior sclera is involved, clinical signs may be less obvious, and imaging studies are necessary to confirm the diagnosis. Patients with anterior scleritis presents with redness and pain. The onset is usually gradual, extending over several days. Ocular pain is severe and typically dull and boring (piercing) in nature, exacerbated by eye movement and, occasionally, may worsen at night and
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Perhaps Galileo had sufferered with scleritis associated with rheumatoid arthritis. He became totally blind at the age of 74 years probably due to complcations of sclerits.8
waken the patients from sleep. The pain often radiates to the ear, scalp, face and jaw. The sine qua non of scleritis is the presence of scleral edema and congestion of the deep episcleral plexus. Slit-lamp examination using red-free light is extremely helpful in determining the pattern and depth of episcleral vascular congestion and engorgement. In diffuse scleritis (Fig. 23.2), the sclera assumes a violaceous hue in natural sunlight. It is very important to examine patients in daylight with the unaided eye to note the subtle color differences of the vessels. Also inflamed scleral vessels have a crisscross pattern. They are adherent to the sclera and cannot be moved with a cotton-tipped applicator. Engorged scleral vessels cannot by blanched with 10% phenylephrine, whereas phenylephrine easily blanches engorged vessels in the superficial episcleral and conjunctival plexuses.6,7,9,10 There is tenderness of the globe. Nodular anterior scleritis (Fig. 23.3) is characterized by a localized area of scleral edema and congestion of the scleral vessels. The scleral nodule is deep red to purple in color, immobile, tender to palpation and separated from the overlying episcleral tissue, which is elevated by the nodule. These features
Fig. 23.2: Diffuse scleritis.
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Fig. 23.3: Nodular scleritis.
distinguish the nodular scleritis from diffuse episcleritis. The lack of necrosis within the nodule and the localization of inflammation within the borders of the nodule differentiate this form from necrotizing anterior scleritis with inflammation. All of the vascular layers overlying the nodule are displaced forward. Sometimes, multiple nodules may be present and there may be an overlying episcleritis.7-10 Necrotizing anterior scleritis with inflammation (Fig. 23.4) is the most severe of all the types and is a potential threat to visual loss. It is seen in patients with rheumatoid arthritis (Fig. 23.5). It is bilateral in 60% cases. The patient presents with severe pain out of proportion to inflammatory signs. Examination reveals white, avascular areas of localized scleral edema and congestion; edges of these lesions are more inflamed than the center. Underlying uveal tissue becomes visible as the sclera becomes thin and translucent. If not treated, the necrotizing scleritis may spread to the equator and circumferentially and can involve the entire globe.14,15
Necrotizing Anterior Scleritis without Inflammation Necrotizing anterior scleritis without signs of inflammation (scleromalacia perforans), occur predominantly in patients with long-standing rheumatoid arthritis. There are minimal signs of inflammation and generally no pain accompanying with this type of scleritis. As the disease progresses, the sclera progressively thins and the underlying dark uveal tissue becomes visible (Fig. 23.6). Staphylomas can develop if the intraocular pressure (IOP) is elevated. Though spontaneous perforation is rare, these eyes are prone to rupture with minimal trauma.14,15 Occasionally, patients may present with blurred vision because of astigmatism due to thinning and distortion of the globe.
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Fig. 23.4: Necrotizing anterior scleritis with inflammation (necrotizing scleritis). Note the avascular area (white arrow)
Fig. 23.5: Bilateral necrotizing scleritis in a patient of rheumatoid arthritis.
Posterior Scleritis Posterior scleritis is defined as an inflammation of the sclera, posterior to the ora serrata. Posterior scleritis may occur in association with anterior scleritis or may be isolated. Posterior scleritis, without anterior scleritis, is difficult to
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Fig. 23.6: Necrotizing anterior scleritis without signs of inflammation (scleromalacia perforans).
diagnose. Patients with posterior scleritis present with pain, tenderness, proptosis, visual loss and occasionally restricted motility, macular or paramacular edema (Figs. 23.7 and 23.8) choroidal folds, exudative retinal detachment (RD), papilledema, and angle-closure glaucoma secondary to choroidal thickening. Most cases of posterior scleritis need ancillary imaging modalities like ultrasonography (USG) (Fig. 23.9) and a magnetic resonance imaging for confirmation of the diagnosis. An infiltration of extraocular muscles in the region of the posterior scleritis may lead to retraction of the lower lid in the upper gaze.6,7,16,17 Surgically induced necrotizing scleritis (SINS) can occur after any type of ocular surgery with excessive scleral manipulation, mostly after cataract surgery18,19 (Fig. 23.10), but may also be seen after glaucoma, RD, squint or pterygium surgery. SINS may occur from few days to few years after surgery. Inflammation is typically localized around the site of the surgical wound or adjacent to the site of surgery, but may progress to involve the entire sclera. SINS is mostly necrotizing in nature and sometimes may even be the initial manifestation of serious systemic disease. So, all patients with SINS need to be investigated appropriately.
Infectious Scleral Inflammation Scleritis with purulent exudates or infiltrates should raise the suspicion of an infectious etiology. Formations of granulomas or fistulas, painful nodules, conjunctival and scleral ulcers are often seen in infectious scleral inflammations. Endogenous spread of bacteria (Staphylococci, Haemophilus
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Fig. 23.7: A circular whitish-yellow patch of edema is seen temporal of the macula in posterior scleritis.
Fig. 23.8: Fundus fluorescein angiography (FFA): Angiography of the patient with posterior scleritis showing punctate leaks at the level of the retinal pigment epithelium and pooling into the subneurosensory retinal space.
influenzae, Treponema pallidum, Mycobacterium tuberculosis); fungi19 (Aspergillus); viruses (Herpes simplex or Herpes zoster) or parasites (Toxocara, Toxoplasma, Onchocerca) are reported to cause infective scleritis.6,7 Also, in
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Fig. 23.9: Ultrasonography (USG) scan of posterior scleritis. Note the characteristic T-sign (white arrow) and thickened sclera.
Fig. 23.10: Surgically induced necrotizing scleritis.
rare instances, infections of adjacent tissues like the conjunctiva, cornea may involve the sclera by contiguous spread. In chronic cases, possibility of a foreign body must be ruled out. Scleral infections can often follow buckling procedures for RD.
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DIAGNOSTIC EVALUATION OF SCLERITIS As we know that scleritis can occur in association with various systemic diseases. Sometimes scleral inflammations can be the presenting signs of an underlying systemic disease. Thus workup of scleritis should include a thorough physical examination, with attention to the joints, skin and cardiovascular and respiratory system. The following routine investigations should be performed: • Hemoglobin • White blood cell count and differential count • Erythrocyte sedimentation rate • If connective tissue disease is suspected, full immunologic workup should be undertaken, including levels of immunoglobulins and immunofluorescent studies for autoantibodies (including rheumatoid factor and antinuclear and anti-ds-DNA antibodies) and circulating immune complexes. If Wegener’s granulomatosis and polyarteritis nodosa are suspected, the antinuclear cytoplasmic antibody (ANCA) tests should be performed. The C-reactive protein is an important laboratory parameter of an active generalized inflammatory response.4,6 • Serum uric acid • Full serologic tests for syphilis • X-ray chest • Ultasonography • Ultrasound biomicroscopy (UBM)
B-scan Ultrasonography B-scan ultrasonography should always be included in the examination of patients with scleritis. Many patients who were formerly thought to have only anterior segment disease have been found to have extensive and sight threatening posterior scleritis as well. It also has become known that many patients with posterior scleritis with minimum symptoms and signs may have much more extensive disease than had previously been considered possible. The hallmark features of posterior scleritis seen with B-scan ultrasonography are helpful in differentiating posterior scleritis from other conditions. B-scan ultrasonography may reveal the characteristic flattening of the posterior aspect of the globe due to retrobulbar edema. Abnormally increased thickening of the posterior ocular coats of the globe (> 2 mm), optic disc swelling, distension of the optic nerve sheath, RDs, and choroidal detachments can be detected. Fluid can accumulate in the posterior subtenon space and extend around the optic nerve, forming the characteristic ‘T-sign’ on B-scan.17
Ultrasound Biomicroscopy This can be valuable for better delineation of scleral thinning and evaluation of scleral edema (Fig. 23.11) and nodules. It is also an important boon
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Fig. 23.11: Ultrasound biomicroscope (UBM) picture of a case of scleritis showing scleral edema (white arrows).
for ruling out any malignancy. An underlying squamous cell carcinoma or a medulloepithelioma can extend to the sclera and can masquerade as scleral inflammation.
Complications of Scleritis Unlike episcleritis, scleritis is associated with potentially sight threatening ocular complications. Vision may be limited in scleritis due to keratitis, anterior uveitis, cataract, change of refractive status, macular edema, optic disc edema, or atrophy, exudative RD. Decreased vision occurs most frequently with posterior scleritis followed by necrotizing scleritis, nodular scleritis and least often with diffuse anterior scleritis. During any stage of scleral inflammation, the IOP may be elevated due to several mechanisms, such as obstruction of the aqueous outflow channels, elevated episcleral pressure, angle-closure or secondary to a steroid response. Signs of corneal infiltrate, thinning or stromal keratitis may be present with corneal ulceration. Cataract formation may be accelerated by long-standing inflammation or secondary to steroid use.6,7,15 Necrotizing scleritis is a serious diease. Scleral thinning is most common and it may progress to staphyloma in the presence of raised IOP. Though increased scleral transparency and thinning is a frequent complication of necrotizing scleritis but perforation is relatively uncommon Both ocular and systemic complications are reported in abot 60% of cases and approximately 40% of the patients suffer from serious visual impairment or visual loss. It can be fetal. About 29% of patients die within 5 years of onset mainly due to complications of vasculitis.
Episcleritis and Scleritis 449
TREATMENT The primary aim of the treatment of scleral inflammation is to control the inflammatory process to relieve the symptoms and thereby reduce the damage to the eye. However, the effective management of a case of scleral inflammation involves timely diagnosis, prevention of complications and identification of underlying systemic or local cause, if any. Generally, episcleritis is self-limiting benign inflammation, whether treated or not, it will resolve in 10–21 days. If the condition is recurrent, medications such as topical nonsteroidal anti-inflammatory drugs (NSAIDs) like flurbiprofen, bromfenac and nepafenac or topical weaker corticosteroid (loteprednol, fluorometholone) are often required to control the symptoms of irritation, foreign body sensation, etc. However, prolonged use of topical corticosteroid should be avoided because of the side effects. It should be kept in mind that though simple episcleritis resolves spontaneously and rapidly, resolution of nodular episcleritis is much slower and may require oral medications. Systemic medications like oral NSAID and very rarely oral corticosteroids are required in the treatment of indolent episcleritis.5,6 Anterior non-necrotizing scleritis readily responds to topical steroid and systemic NSAIDs. Both non-selective cyclooxygenase (COX) inhibitors (e.g., flurbiprofen, indomethacin, and to a lesser extent ibuprofen) and the more selective COX-2 inhibitors have successfully been used. Sustained-release indomethacin 75 mg twice daily has been found to be very effective in controlling the inflammation. However, prolonged use of NSAIDs should be avoided in view of their significant side effects on long-term use. Corticosteroids are helpful in patients not responding to COX-inhibitors or those with posterior or necrotizing disease. A starting dose of 1 mg/kg/day is standard with weekly reduction by 10 mg/week until a dose of 40 mg/day is reached. After this dose is reached, the rate of reduction is individualized, according to the clinical findings and patients’ response but is in the order of 5 mg/week until cessation or an acceptable maintenance dose is reached. Intravenous methylprednisolone is advocated in cases with threatened scleral or corneal perforation in necrotizing scleritis, which requires a rapid control of the inflammation.3,5-7,9 Necrotizing scleritis, particularly associated with autoimmune diseases, is difficult to treat and almost always requires systemic immunosuppressive therapy, not only for ocular involvement, but also for life threatening systemic complications. For example, prompt and effective immunosuppression is required to control the necrotizing scleritis associated with systemic vasculitis like Wegener’s granulomatosis because mortality is higher in this group of patients because of the systemic complications. This group of patients also requires a consultation with rheumatologist for their systemic ailments.20 Indications for immunosuppressive therapy in scleral inflammation are: • Anterior necrotizing scleritis • Posterior scleritis • Scleritis associated with a systemic disease
450 Gems of Ophthalmology—Cornea and Sclera
Various immunosuppressants have been tried for treatment of scleritis and these include antimetabolites (methotrexate, azathioprine and mycophenolate mofetil), alkylating agents (chlorambucil and cyclophosphamide), T-cell inhibitors (cyclosporine and tacrolimus). Newer biological agents like tumor necrosis factor-alpha (TNF-a) inhibitors (infliximab or adalimumab), rituximab are reported to be used for the treatment of scleritis. Methotrexate is commonly used to treat scleritis not responding to oral corticosteroid and less sever anterior necrotizing scleritis with inflammation. Often the drug is used as a first line treatment in patients in whom oral steroid cannot be started because of systemic ailments. Among steroid sparing immunosuppressives, methotrexate has gained the most widespread usage due to its relatively safe profile. Methotrexate, a folic acid analog, inhibits the enzyme dihydrofolate reductase and thus the production of thymidylate, which is essential for DNA replication. This results in the inhibition of rapidly dividing cells, including leukocytes. The drug is used with or without a short course of oral steroid in tapering dosage. Dosage of methotrexate is 0.1– 0.5 mg/kg/week; low dose therapy is started at a dose of 7.5 mg/week and it can be increased up to 25 mg/week. Generally, it is given orally once a week. It has been observed that methotrexate immunosuppressive therapy is moderately effective. The drug takes months to achieve adequate tissue concentration for the therapeutic success. Severe side effects such as hepatotoxicity, cytopenias and interstitial pneumonia are not uncommon.20,21 Treatment of scleritis associated with necrotizing systemic vasculitis should be prompt and effective if immunosuppression is required. Treatment in such patients should be guided both by the ophthalmic response and control of the underlying disease. Cyclophosphamide is an effective immunosuppressive drug used in patients with necrotizing scleritis associated with systemic vasculitis like Wegener’s granulomatosis (Fig. 23.12A to C), relapsing polychondritis. Antineutrophil cytoplasmic antibody test is a useful laboratory parameter to monitor therapeutic response in patients with Wegener’s granulomatosis. Concomitant administration of prednisone at a dose of 1 mg/kg/day may be needed. Oral corticosteroids can usually be tapered and often discontinued over the first 6–12 weeks of cyclophosphamide therapy. Cyclophosphamide in a dose of 100 mg/day (2 mg/kg/day) orally and tapered monthly, should be the first choice in treating patients with associated potentially lethal vasculitic diseases, such as Wegener’s granulomatosis or polyarteritis nodosa. The patient should drink copious amounts of fluid to prevent hemorrhagic cystitis. In severe and nonresponsive cases, infusion of 500 mg of cyclophosphamide (given over 1–2 hours) is often required. Because of potential life threatening complications, it should be administered under the supervision of a rheumatologis. Other immunosuppressive agents, including methotrexate, azathioprine, cyclosporine and newer agents like biologicals have been successfully used for the treatment of necrotizing systemic vasculitis, but reports available are based on small case series.6,20,22
Episcleritis and Scleritis 451
Figs. 23.12A to C: Necrotizing scleritis associated with Wegener’s granulomatosis.
452 Gems of Ophthalmology—Cornea and Sclera
Fig. 23.13: Scleral patch graft.
Treatment of Infectious Scleritis Systemic treatment with topical antimicrobial therapy is the mainstay of treatment of scleritis of infectious origin. Differentiating infectious scleritis from non-infectious scleritis is of paramount importance because corticosteroid therapy and immunosuppressive therapy (often used in noninfectious autoimmune scleritis) are contraindicated in active infections. Prior to microbiological determination of the causative organism and its antibiotic sensitivity spectrum, vancomycin or cephalosporins in combination with aminoglycosides usually are chosen. Any foreign body, if present, may need to be removed before the infection can be brought under control.20,22
SURGICAL TREATMENT Tectonic surgical procedures rarely may be required to preserve the integrity of the globe. Scleral grafts from fresh sclera or glycerin-preserved sclera those are available through eye banks. Grafting (Fig. 23.13) may be performed in cases of threatening perforation before the effects of systemic immunosuppressive agents manifest.23,24
SUMMARY Scleral inflammations are important causes of red eye and need to be differentiated from other causes. Though episcleritis is a benign self-limiting disease, scleritis is highly associated with potentially sight threatening ocular complications and serious systemic diseases. Early diagnosis and treatment
Episcleritis and Scleritis 453
of scleritis is important in preventing and diminishing ocular and systemic morbidity. Hence, attempts should be made to achieve good long-term prognosis with careful clinical history, detailed ocular examination and use of immunosuppressant drugs whenever necessary without any delay. Graphics: Dr Parthopratim Dutta Majumder
REFERENCES 1. Snell R, Lemp M. Clinical Anatomy of the Eye. Malden: Blackwell Scientific Publications; 1989. pp. 125-6. 2. Remington LA. Clinical Anatomy and Physiology of the Visual System (3rd edition). Butterworth-Heinemann; 2011. pp. 29-32. 3. Watson PG, Hayreh SS. Scleritis and episcleritis. Br J Ophthalmol. 1976;60(3): 163-91. 4. Pavesio CE, Meier FM. Systemic disorders associated with episcleritis and scleritis. Curr Opin Ophthalmol. 2001;12(6):471-8. 5. Lyons CJ, Hakin KN, Watson PG. Topical ﬂurbiprofen: an effective treatment for episcleritis? Eye (Lond). 1990;4(Pt 3):521-5. 6. McCluskey P. Scleritis. BMJ Publishing Group; 2001. pp. 39-100. 7. Okhravi N, Odufuwa B, McCluskey P, et al. Scleritis. Surv Ophthalmol. 2005; 50(4):351-63. 8. Germani GM. Rheumatoid disease and the blindness of Galileo Galilei. Osp Maggiore. 1964;59:193-6. 9. Watson PG. Anterior segment changes in connective tissue disease. Trans Ophthalmol Soc U K. 1974;94(3):773-84. 10. Watson PG, Hazelman BL. The Sclera and Systemic Disorders. Philadelphia, PA: WB Saunders; 1976. 11. Sainz de la Maza M, Foster CS, Jabbur NS. Scleritis associated with rheumatoid arthritis and with other systemic immune-mediated diseases. Ophthalmology. 1994;101(7):1281-6; discussion 1287-8. 12. McGavin DD, Williamson J, Forrester JV, et al. Episcleritis and scleritis. A study of their clinical manifestations and association with rheumatoid arthritis. Br J Ophthalmol. 1976;60(3):192-226. 13. Power WJ, Rodriguez A, Neves RA, et al. Disease relapse in patients with ocular manifestations of Wegener granulomatosis. Ophthalmology. 1995; 102(1): 154-60. 14. Sainz de la Maza M, Jabbur NS, Foster CS. Severity of scleritis and episcleritis. Ophthalmology. 1994;101(2):389-96. 15. Tuft SJ, Watson PG. Progression of scleral disease. Ophthalmology. 1991; 98(4):467-71. 16. McCluskey PJ, Watson PG, Lightman S, et al. Posterior scleritis: clinical features, systemic associations, and outcome in a large series of patients. Ophthalmology. 1999;106(12):2380-6. 17. Biswas J, Mittal S, Ganesh SK, et al. Posterior scleritis: clinical profile and imaging characteristics. Ind J Ophthalmol. 1998;46(4):195-202.
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18. Scott JA, Clearkin LG. Surgically induced diffuse scleritis following cataract surgery. Eye (Lond). 1994;8(Pt 3):292-7. 19. Sawant SD, Biswas J. Fungal scleritis with exudative retinal detachment. Ocul Immunol Inflamm. 2010;18(6):457-8. 20. Thomas AA, Narsing AR, Ronald ES. The diagnosis and management of anterior scleritis. Int Ophthalmol Clin. 2005;45(2):191-204. 21. Kaplan-Messas A, Barkana Y, Avni I, et al. Methotrexate as a first-line corticosteroid-sparing therapy in a cohort of uveitis and scleritis. Ocul Immunol Inflamm. 2003;11(2):131-9. 22. Rachitskaya A, Mandelcorn ED, Albini TA. An update on the cause and treatment of scleritis. Curr Opin Ophthalmol. 2010;21(6):463-7. 23. Nguyen QD, Foster CS. Scleral patch graft in the management of necrotizing scleritis. Int Ophthalmol Clin. 1999;39(1):109-31. 24. O’Donoghue E, Lightman S, Tuft S, et al. Surgically induced necrotising sclerokeratitis (SINS)—precipitating factors and response to treatment. Br J Ophthalmol. 1992;76(1):17-21.
Index Page numbers followed by f refer to figure and t refer to table.
A Aberrations, high order 88, 102 Aberrometer 137 Aberropia 32 Ablation-related complications 110 Absidia sp. 170 Acanthamoeba 71, 72f, 139, 140, 145, 148, 152, 156, 202-205, 211, 425 adhesion 206 and hartmanella, stages of 203 castellanii 204, 206, 207 classification of 203 cysts 152, 152f, 210, 211 detection of 212 diagnosis of 211 double walled cysts of 210f genotypes of 212 genus 148 in corneal stroma 140 infection 205, 209 interactions of 207 keratitis 70, 71, 140, 143, 202, 208f, 210f, 440 diagnosis 202, 210 diagnosis molecular methods of 211 immune-biology of 207 pathogenesis 202, 205 morphological classification of 203t pathogenicity of 207 plasma membrane of 206 rhysodes 204 species 205 treatment of 202 trophozoites 149f, 206, 209 Acid phosphatase, zymograms of 204 Acid-fast bacilli 154f
Acremonium sp. 170 Acridine orange 146 ACS See Automated corneal shaper Acute red eye, causes of 437 Adalimumab 450 Adenoviral keratoconjunctivitis 159 diagnosis of 162 Air bubble dimpling 431 in scleral lens, trapped 431f large 432f Air injection in big bubble technique 302f Air pump-assisted PDEK 386 Air-guided deep stromal dissection 300 AK See Astigmatic keratotomy Albumin 432 Alcohol dehydrogenase 204 ALK See Automated lamellar keratoplasty Alkyl triethanol ammonium chloride 430 Alkylating agents 450 Allergy 427 Allogenic grafts 366 Alport syndrome 253 AM See Amniotic membrane American Society of Microbiology 141 Amethocaine eye drops 128 Ametropic eye 78 AMG See Amniotic membrane graft Amiodarone 75 Amniotic graft 339 Amniotic membrane 345, 345f, 350 characteristics of 345 extract 353 for corneal perforation 350 graft 337, 349f advantages of 352 multilayered 352f
456 Gems of Ophthalmology—Cornea and Sclera
histology of 345f inlay 347, 348f with overlay 348 overlay 347 patch technique 350 preparation of 347 transplantation 196, 344, 345, 349f, 351, 353f, 359f indications for 346 surgical techniques 347 wound healing of 345 Amphotericin B 179, 183, 347 intracameral injection of 180 AMT See Amniotic membrane transplantation AMX See Amniotic membrane extract Anerobic glycolysis 424 Aniridia 357 Ankylosing spondylitis 440 Antibiotic susceptibility 156 Antifungal agents 178 drug 182, 183 classes of 179 susceptibility testing 156 therapy 72 Antigenic tissues, types of 362 Antiglaucoma agents 252 drops 412 Anti-inflammatory proteins 345 Antimicrobial susceptibility testing 148 Antineutrophil cytoplasmic antibody test 450 Antinuclear cytoplasmic antibody 447 Antiphospholipid syndrome 440 Anwar’s big bubble 384 DALK technique 304, 378 Aqueous layer 316 Aqueous tear production, assessment of 327 Aqueous-deficient dry eye 366 Argon-fluoride excimer laser 83, 83f Aspartyl acid 172 Aspergillus 169, 170, 179, 181, 182, 445 fumigatus 171, 172, 178 niger 331 strains of 171 Astigmatic keratotomy 38, 41f Astigmatism 88 Autoimmune diseases 346, 449
Autologous conjunctival transplantation 339 Autologous limbal grafts 366 Autologous oral mucosal tissue, transplantation of 367 Automated corneal shaper 128 Automated lamellar keratoplasty 80, 107 therapeutic keratoplasty 376 technique 376 Autosomal recessive disorder 417 Avellino corneal dystrophy 243 Azathioprine 450
B Bacterial and fungal keratitis 202 Bacterial infections 172 Bacterial keratitis 169, 175, 184 Bacterial susceptibility 156 Balamuthia species 212 Balanced salt solution 117 Barraquer’s disciples 80 Barraquer-Krumeich-Swinger technique 80 Basal epithelia of limbus 355f Basal epithelial cells 57f Basal limbal epithelium 355f Basement membrane dystrophy 222f Benzalkonium chloride 321, 330, 430 Best corrected visual acuity 32, 120, 129f Best spectacle corrected visual acuity 285 Big bubble technique 304, 306, 378 Blepharitis 321f posterior 320 Blepharoconjunctivitis 188 Blood agar 144, 147f aerobic 144 anaerobic 144 Bowman’s layer 68 absence of 226 dystrophy 221, 231 Bow-tie pattern 17f Brain heart infusion 144, 177 broth 144, 145 with antibiotic 144 Breakup test, noninvasive 325t Bromfenac 449 BSCVA See Best spectacle corrected visual acuity Bubble technique, small 304, 378
Buccal mucosal Graft inner surface 395f outer surface 395f incision 394f Bulbar conjunctiva 333f superior 430 Bullous keratopathy 66, 74, 193, 281, 339, 346 aphakic 382 chronic 357 early stages of 66 pseudophakic 382 Burns chemical 299 thermal 299 BUT See Breakup test
C Calibrated spheres 1 Candida 175, 178, 179, 181, 182 albicans 172, 178 keratitis 171 Candidal keratitis 179 Canthal angle, reconstruction of 339 Carbohydrate sulfotransferase 244 Carbon dioxide 424 Carboxymethylcellulose 328, 329 Cardiac arrythmias 75 Carnitine 421 deficiency 418 Cataract and implant surgery 112 Cataractous lens 137 Cellular components, types of 55 Cellular dysfunction 419 Cellulose esters 329 Central cornea 38 Central corneal marker stitch 396f sensitivity 98 thickness 45f Cephalosporins 452 Cephalosporium 182 Chlorhexidine gluconate 430 Chlorobutanol 330, 331 Chloroquine 75 Chocolate agar 144 Chronic renal failure 102 Cidofovir 198 Ciliary nerve, long 56
Cincinnati procedure 362 Clear lens extraction 78 Clotrimazole 180 Coarse punctate erosions 434 Cogan’s microcystic epithelial dystrophy 224f Cogan’s syndrome 439, 440 Color-coded scales 15 Coma primary 32t Confocal microscope 66, 68 advantages of 53 optics of 54f Confocal microscopy employs 53 fundamental of 53 in corneal pathology 61 in SMILE 102 of normal cornea 55 Congenital erythrokeratodermia 357 Congenital glaucoma, coexisting 255 Congenital hereditary endothelial dystrophy 255, 256, 256f, 257f Congenital stromal corneal dystrophy 246 Conidiophores 178 Conjunctiva 240, 338 Conjunctival autograft 339, 340f, 343, 343f, 344t efficacy of 340 for pterygium 341 in situ 344f procedure 339 Conjunctival congestion 172 Conjunctival cul-de-sac 387 Conjunctival epithelial cells 313 Conjunctival goblet cells 313 Conjunctival granulomas 344 Conjunctival inflammation 366 Conjunctival lesions 346 Conjunctival limbal allograft, living-related 362 autograft 359, 360, 361f Conjunctival plexus 438 Conjunctival tissue 361, 362 Conjunctival transdifferentiation 339 Conjunctival transplantation 339 procedure of 339 Conjunctival tumor, post-excision of 339 Conjunctivochalasis 346 Contact lens 268, 368, 424, 427f, 428f, 430f, 431 assisted corneal collagen cross-linking 291
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fenestrated rigid 432f fitting for keratoconus 269 induced corneal molding 48 warpage 48 induced infective keratitis 426f soft 50f solution preservative hypersensitivity/ toxicity 430 warpage 23, 428f, 429f wear 357, 434 Cornea 1, 19f, 78, 338, 395, 419f, 430 bioengineered 368 deep vascularization of 358 donor 73 entire circumference of 38 guttata, stage of 250 in keratoplasty surgery, postoperative 46 in refractive surgery, postoperative 38 in SMILE, biomechanical properties of 100 in vivo 53 irregular 14, 24f lower area of 323f normal 23 pathological 32 postsurgery 14 projection of slit light onto 7 range of normal 53 retreated 128 sculpting of 79 shape of 15 normal 3 steep 115 verticillata 75 Corneal aberrations 33f effect of 27 in normal population 32t Corneal aberrometry 24 Corneal allogenic intrastromal ring segment 288, 289f Corneal asphericity 88 Corneal astigmatism 344 Corneal biopsy tissue 143, 145 Corneal blindness 337 vision to 222 Corneal button 158 section 208f Corneal cap precision in SMILE 102 Corneal clouding, diffuse 257f
Corneal collagen 280 cross-linking 270, 276, 283f physiology of 277 Corneal confocal microscopy 53, 140 culture methods 145 interpretation of microbiology results 151 molecular methods 150 Corneal cross-linking technique, steps of 279 treatment, indications for 278 Corneal curvature, change in 78 Corneal cystine crystals 422 Corneal decompensation 281 Corneal dystrophy 64, 74, 219, 221, 230f anterior 219 classification of 219 gelatinous drop-like 229 histopathology 230 inheritance 229 management 230 signs 230 symptoms 229 granular 241 signs 241 symptoms 241 lisch epithelial 221, 228 histopathology 229 inheritance 229 management 229 signs 229 symptoms 229 management 224 posterior 219 posterior amorphous 248 histopathology 249 inheritance 248 management 249 signs 248 symptoms 248 posterior polymorphous 253 management 255 signs 253 symptoms 253 prevalence of 219, 220t signs 223 subepithelial mucinous 226 histopathology 227 inheritance 226 management 227
signs 226 symptoms 226 symptoms 223 types of lattice 236 X-linked endothelial 258 histopathology 258 management 258 signs 258 symptoms 258 Corneal eccentricity index 22 Corneal ectasia 276 postoperative 137 Corneal edema 66, 254, 281 Corneal endothelial monolayer, bioengineered 367 Corneal endothelium 54, 55, 61, 219, 246, 272 disorder of 66 Corneal epithelial cell 189, 206 defects 75, 346, 424 Corneal epithelium 55, 313, 356, 365, 428 superficial 54 Corneal erosions, recurrent 237 Corneal fibers, strengthening of 278f Corneal fluorescein staining 98, 323f Corneal graft 73, 73f Corneal guttata 66 Corneal hydrops, acute 61 Corneal hypoesthesia 427 Corneal impression smear 158 Corneal indexes 21 Corneal inlay 78 Corneal lamellae 175, 240, 298 Corneal lesions 75 post-excision of 299 Corneal leukomas 73 Corneal limbal epithelial stem cells 356t, 365f Corneal maps 18 Corneal measurement 1 Corneal melting 281 Corneal myoring with central aplannation 21f Corneal nerves 53, 56 Corneal opacification 233 Corneal pachymetry 55, 127 alteration in 40f Corneal perforation 117, 193 glue in management of 350
Corneal phenotype, marker of 358 Corneal photoablation 83 Corneal power, average 22 Corneal resistance factor 276 Corneal rings in keratoconus, indications for 285 Corneal samples collection of 142 transport of 142 Corneal scar 193 Corneal scraping 145, 152, 154f, 158, 160f collection 143f procedures for 146t processing of 143 stained with gram stain 153f transportation of 142 Corneal signs of toxicity 430 Corneal steepening, inferior 49 Corneal stem cells 354 Corneal stroma 219, 238f, 298 posterior 378 Corneal stromal dystrophy 234 inheritance 236 lattice 236 signs 236 symptoms 236 Corneal stromal edema 425 Corneal surface, anterior 3, 99f Corneal tensile properties, calculation of 101f Corneal thickness increased 249f maps 21 Corneal tissue 248 Corneal topographic patterns, normal 6f Corneal topography 1, 3, 5, 10, 16f, 17f in normal right eye 5f maps, interpretation of 13 quantitative descriptors of 21 uses of 49 Corneal transplant 392 Corneal ulcer 140, 150f infectious 351 management of 141 with serrated and immune ring 174f Corneal warpage 48, 50f, 427 Corneal wavefront aberration, measuring 26 analysis derived 27f Corneal/conjunctival swab 158 Corneal/corneoscleral ulcers 346
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Corneoscleral junction 354 limbus 355 perforation 344 ulcers 346 Corticosteroids antibiotics 79 Corynebacterium species 155 CRF See Chronic renal failure Cryopreservation of corneal lenticules, technique of 103 Cryoprobe 400f Cryptococcus 179 neoformans 172 Curvularia sp. 170, 181 Cycloheximide 177 Cyclophosphamide 450 Cyclosporin A 195, 334 Cyclosporine 450 Cystadrops 422 Cystaran 422 Cysteamine 422 hydrochloride eye drops, treatment with 422 ophthalmic solution 422 Cysteine, intracellular burden of 419 Cystinosis 416, 417 Cystinosis clinical manifestations 417 diagnosis of 421 early diagnosis of 421 gene 417 genetics 417 management 421 pathogenesis 419 treatment 421 gene therapy 422 ophthalmic 422 symptomatic 421
D Dacron mesh sutured to cornea 401f DALK See Deep anterior lamellar keratoplasty Debulking after air injection, anterior 303f Deep anterior lamellar keratoplasty 247f, 272, 298, 309f, 378, 379f advantages of 381 ondications of 299 Deep lamellar keratoplasty 298 Dehydrating agents 252 Dellen formation 344
Dematiaceous fungi 174 Dendritic ulcer 189, 194f Descemet’s folds and interface infection 379 Descemet’s membrane 61, 66, 171, 172, 175, 219, 248, 256, 272, 298, 304f, 305f, 363, 378 and endothelial dystrophy 221, 249 endothelial keratoplasty 253, 383 lamination of 257 part of 251 perforation 306 Descemet’s stripping automated endo thelial keratoplasty 252, 382, 382f Descemetorhexis 386 performed 388f Diabetes 279 Diffuse lamellar keratitis 68, 70f, 86, 119, 119f DLK See Diffuse lamellar keratitis DMEK See Descemet’s membrane endothelial keratoplasty DMEK and PDEK, ancillary techniques for 385 Dohlman keratoprosthesis, parts of 409f Doughnut-shaped flap 115, 116f Dry eye 319 cases of 97 diagnosis of 321 forms of 326 inflammation and 319 patients 325 severe 339 status 311 syndrome 321 treatment of 327 Dry eye disease 311, 312, 316, 318, 320 and allergies 319 and blepharitis 320 and conjunctivitis 320 and eyedrops 320 causes of 333 diagnosis of 328t epidemiology of 312 induction of 319 prevalence 312 scale of problem of 312 vicious cycle of 319f Dry Weck-Cel sponge 302 DSAEK See Descemet’s stripping automated endothelial keratoplasty Dystrophy epithelial 220, 222
map-dot-fingerprint 222 subepithelial 220, 222
E EBMD See Epithelial basement membrane dystrophy Econazole 180, 181 Eczema, severe 191f EK See Endothelial keratoplasty ELISA See Enzyme-linked immunosorbent assay Embryonic organogenesis 416 Endocrine deficiencies, multiple 357 Endoilluminator-assisted DMEK 385 PDEK 385 Endophthalmitis 92, 272 Endothelial blebs 426 Endothelial cell 61, 63f, 73, 74f epithelialization of 255 hexagonal 62f loss of 73, 91, 309 Endothelial corneal dystrophy, X-linked 258 Endothelial decompensation 249f Endothelial keratiits 189, 197 Endothelial keratoplasty 192, 193f, 252, 298, 381 Endothelial polymegathism 427 Endothelium 53, 61, 63f, 378 Enzyme-linked immunosorbent assay 161 Eosinophilic hyaline deposits, deposition of 65 Epidermal keratinocytes 365 Epikeratophakia 107 Episclera 437 Episcleral plexus, superficial 438 Episcleritis 437-440, 440t, 448, 449 classification of 439 Epithelial abrasion 424 Epithelial basement membrane dystrophy 222, 223f Epithelial cell 315 intermediate 57f proliferating 86 shape of superficial 64 superficial 56, 56f Epithelial inclusion cyst 344 Epithelial ingrowth 122, 123f management of 123
Epithelial keratitis 187, 191f, 194, 197 Epithelial layers distinctly 55 Epithelial microcysts 425 Epithelial microerosions 434 Epithelial thinning 424 Epithelial wrinkling 431 Epithelium 53, 55 in keratoconus, superficial 64f Erosion dystroph 225f epithelial recurrent 225 histopathology 226 management 226 signs 226 symptoms 225 Escherichia coli 147, 149f, 211 Eukaryotic and heterotrophic organisms 169 Ex vivo stem cell expansion 363 Excimer laser 81 pulse 82f tissue interaction 83 treatment, customized 88 Exogenous sources 74 Eye of immunocompetent 171 pathogenesis involving 420 Eyeball 437 Eyelid 433 scarring 339
F Fabry’s disease 74 Fanconi syndrome 416 Fehr corneal dystrophy 244 Femtosecond laser 87, 90, 92, 288 eliminating 79 intrastromal lenticular implantation 103 LASIK 100 platform 102 technique 286 Femtosecond lenticule extraction 99, 101 Femtosecond posterior lamellar keratoplasty 389 Femtosecond-assisted corneal transplantation 388 deep anterior lamellar keratoplasty 389 lamellar keratoplasty 377 LASIK 96, 97, 101f
462 Gems of Ophthalmology—Cornea and Sclera
superficial anterior lamellar keratoplasty 389 Fenestrated rigid contact lens 432f Fibrin glue 344f Fibrin substrate 367 Filamentous fungi 170 Flap complications 108 decentered 117f problems 85 striae 120f Fleck corneal dystrophy 247 histopathology 248 inheritance 247 management 248 signs 248 symptoms 248 Fleshy pterygium 340f FLEX See Femtosecond lenticule extraction Fluconazole 180, 181, 183 Flucytosine 182, 183 Fluorescein 322 staining 322 tear breakup test 326 Fluorinated pyrimidines 182 Fluorometholone 449 Flurbiprofen 449 Food and Drug Administration 422 Forme fruste keratoconus 123 Fornix reconstruction 339 Foscarnet 198 Free flap 116f FS-LASIK See Femtosecond-assisted LASIK Fuchs’ dystrophy 66, 249f, 250, 382 Fuchs’ endothelial corneal dystrophy 249 dystrophy 66 Fundus fluorescein angiography 445f Fungal filaments 176f in gram staining 177f Fungal hyphae 72f Fungal keratitis 71, 139, 140, 169, 184 clinical features 172 diagnosing 72 epidemiology 169 incidence of 169 laboratory diagnosis 176 medical treatment 178 pathogenesis 171
principles of therapy 182 risk factors 170 surgical treatment 184 treatment for 182, 183 Fungal species, identification of 148 Fungal ulcer, typical 172f Fungi classification of 169 detection of 152 dimorphic 170 nonreplicating, nonreplicating 175 Fusarium sp 169-171, 181, 182
G GCD See Granular corneal dystrophy Gene mutations in cystinosis gene 417 Genetic locus 222 Giant cell, multinucleated 159f Giemsa stain 144, 146, 159, 163, 177 Glaeseria 203 Glaucoma coexisting 255 congenital 257 incidence of 406 intractable 368 medications, multidose 331 secondary 272 steroid induced 344 Globulin 432 Glucose phosphate isomerase 204 Gold fish analogy for functions of tear layers 317f Gomori methenamine 177 silver stain 211 Graft adhesion 387 centration 387 edema 344 edge unfolding 387 failure, primary 377f floatation 387 hemorrhage 344 inversion 344 necrosis in inverted graft 344 rejection 308, 389 retraction 344 unwrinkling 387 Gram stain 144, 146, 176 techniques 177
Gram-negative bacteria 152 Gram-positive bacteria 152 Granular corneal dystrophy 242f, 243 Granular dystrophy 65 Grayson-Wilbrandt corneal dystrophy 221, 234 histopathology 234 inheritance 234 signs 234 symptoms 234
H Haemophilus influenzae 444 HAM See Human amniotic membrane Hank’s balanced salt solution 158 Hansatome microkeratome 128 Hartmanella 203 species 212 Harvesting conjunctival autograft 342 Hazy cornea 256f HBSS See Hank’s balanced salt solution Healthy cornea in high magnification 62f in low magnification 62f Healthy endothelial cells, number of 73 Hematopoietic stem cell 422 Hemosiderosis 74 Hepatitis B 347 C 347 Hereditary corneal stromal dystrophies, types of 300 Herpes keratitis 279 Herpes simplex virus 160f, 161, 445 keratitis 159f, 160f, 187-192, 196 classification of 189t prevention of recurrent 197 risk factors for 191t type of 189 necrotizing keratitis 351 vaccination 198 Herpes zoster 445 ophthalmicus 440 Herpetic disciform keratitis 196 Herpetic endothelitis 196 Herpetic epithelial keratitis, treatment of 194 Herpetic eye disease 187 study 188 Herpetic infection 346
Herpetic keratitis 71, 187, 193 clinical presentation 189 complications 193 epidemiology 187 etiology 188 management 194 manifestations of 187 prevention 197 risk factors 190 High-hyperopic ablation 45f Homogeneous hexagonal cells 61 HSV See Herpes simplex virus Human amniotic membrane 365f Human anterior lens capsular scaffold 367 Human immunodeficiency virus 347 infection 362 Human leukocyte antigen 375 Hydroxychloroquine 75 Hydroxyethyl-cellulose 329 Hypercapnia 424 Hyperlipidemia 74 Hyperopia 103, 112 surgical correction of 107 Hyperopic LASIK, complications of 108 Hyperreflective cellular stroma 68 Hypertonic sodium chloride 224 Hyphe 170 Hypokalemia 418 Hypophosphatemia 418 Hypoxia 424 Hypromellose 329
I Iatrogenic ectasia 87 Iatrogenic keratectasias 87 ICL See Implantable contact lens ICRS 284, 285, 292 Imidazoles 180 Immobile lens syndrome 427 Immunological disorders 357 Immunoperoxidase technique 211 Immunosuppressive therapy 452 Implantable and prosthetic devices 368 Implantable contact lens 91 In situ keratomileusis 80 In vivo confocal microscopy 71f, 72, 72f of cornea 210f Infection, initial 207 Infectious scleritis, treatment of 452
464 Gems of Ophthalmology—Cornea and Sclera
Infectious suppurative keratitis, cause of 169 Infective scleritis, causes of 445 Inflammatory response 207 Infliximab 450 Insulin 421 Intacs regular segment 284 Interblink interval 325 Intracapsular crystalline lens extraction 400f Intracorneal deposits 74 sources of 74 Intracorneal ring segments 269 types of 284t Intracytoplasmic lysosome-like lamellar inclusion 75 Intraepithelial edema 66 Intraocular lens 1, 400 Intraocular pressure 301, 366, 442 accurate 110 reduction of 115 Intraocular surgery 92 Intrastromal corneal ring segments 282 advantages of 284 complications 288 contraindications 284 disadvantages of 285 indications for 283 intraoperative complications 288 postoperative complications 288 structure of 283 surgical techniques 285 types of 282 Iris excision 400f Itraconazole 180, 181
J Juvenile rheumatoid arthritis 440
K KCS See Keratoconjunctivitis sicca Keratconus, management of 268 Keratectomy, postphotorefractive 40 Keratic precipitates 428 Keratitis 160f, 183, 357 cause of 171 diagnosis of nonviral 144t, 146t, 150 diagnostic procedures in infectious 139 diffuse 189
disciform 189, 190, 196f fungal etiology of 211 infectious 70, 88, 346, 425 linear 189 medicamentosa 330f microbial 139, 143, 190, 425 non-necrotizing 195 role in 70 type of 197 Keratoconic cornea 62, 270 Keratoconjunctivitis sicca 311, 323f, 324f Keratoconus 15, 23, 32, 47f, 61, 253, 285, 289 advanced 65f cases of 62 early 33f optical effects of 268 prediction index 23 progressive nature of 268 surgical management of 271 suspect 23, 34, 87 topography pattern 35f treatment options for 268 Keratocyte 53, 246 depletion 207 nuclei 59 Keratoglobus 36, 253 Keratolimbal allograft 359, 363, 364f graft 363f Keratometer 1 Keratometric index, standard 2 Keratometry reading minimum 22 simulated (SimK values) 21 Keratomileusis 79 experience of 87 literally 79 Keratopathy, drug-induced 75 Keratoplasty 220t, 252, 309, 338, 392 advances in 375 classification advances in 375 conductive 112 indications of 74 manual 375 procedure 392 repeat penetrating 377f superficial 338 Keratoprosthesis 392 Keratorefractive procedures 32 Keratoscopy 2
Keratotomy hexagonal 107 overcorrected radial 112 photorefractive 40, 68, 79, 83, 95, 99, 107, 114 Ketoconazole 180, 181, 183 Kinyoun method 154 Kinyoun’s modification of acid-fast stain 146 Kontur lens 415 Krypton fluoride excimer laser 83f
L Lacrimal gland 313, 318, 319, 337 atrophy, cause of 318 Lactophenol cotton blue 146 Lamellar keratoplasty 272, 298, 375, 376 anterior 376 posterior 376, 381 superficial anterior 376 LASEK See Laser epithelial keratomileusis Laser cavity 82f Laser correction for myopia 284, 285 Laser epithelial keratomileusis 85, 107 Laser lenticular extraction 103 Laser thermal keratoplasty 44, 46f, 112 for hyperopia 46f Laser-assisted in situ keratomileusis 42, 67, 69f, 70f, 78, 84, 95-103, 109f, 114, 127 ablation 43, 135 birth of 79 central islands 124 complications 85, 90, 114 contraindication for 110 decentered ablations 124 flap 117 early postoperative complications 119 epithelial defect 118, 119 ingrowth 122 flap displacements 121 wrinkling/striae 120 free cap 116 group 97 hyperopic 108, 109f, 111, 111f, 112 ablation-related complications 110 flap complications 108 management of complications 110
in hyperopia 107, 110 indications of 89 infections 122 interface debris 121 intraoperative bleeding 118 complications 114 keratectasia 123 late postoperative complications 122 limitations of 89 management 114 overcorrected myopic 112 partial flap 114, 115 primary 135 regression and haze 125 retinal complications 125 surgery 127 wavefront-guided 134 LASIK See Laser-assisted in situ keratomileusis Lasiodiplodia sp. 170 Lattice corneal dystrophy 237, 238, 238f Leaking blebs 346 Lens and cornea distance between front 55 front 54 edge imprint 430 supplementary 78 syndrome, tight 431 Lenticular problems 92 Lenticule creation 102 Leucine aminopeptidase 204 Lid 394f lower 394f Lignocaine hydrochloride 141 Limbal allograft 339 rejection 362 Limbal autograft 339 transplantation 360 Limbal cell transplantation, surgical techniques for 359 Limbal dermoid 346 Limbal epithelium 313, 356 Limbal stem cell 355, 367 cultivated 363 deficiency 338, 356, 359f causes of 357t total and partial 357f location of 354f transplantation 339, 354, 366
466 Gems of Ophthalmology—Cornea and Sclera
Limbal tumors 357 Limbic keratoconjunctivitis, superior 322 Limbitis, chronic 357 Limbus 338 Lipid deposits 433 Lipid layer 316 LK See Lamellar keratoplasty Local tangential curvature map 20 Loteprednol 449 Lowenstein-Jensen medium 144 LSCD See Limbal stem cell deficiency LTK See Laser thermal keratoplasty Lycoprotein 270 Lymphoproliferative syndromes 319 Lysophospholipase 206 Lysosomal enzymes 209 Lysosomal storage disorder 419 Lysozyme 432
M Macula in posterior scleritis 445f Macular corneal dystrophy 244, 245f, 300 Macular dystrophy 246, 247f Macular edema 92 Malate dehydrogenase 204 Mannose-binding protein 205 Matrix metalloproteinases 270, 351 Matted eyelashes 321f Maumenee corneal dystrophy 227, 256 histopathology 228 management 228 signs 228 symptoms 227 Meibomian gland 313, 433 dysfunction 320 obstructed 321f Meniscus height 326 Metaherpetic ulcer 193f healing 348f Methotrexate 450 dosage of 450 Miconazole 180, 183 Microbial keratitis 140 diagnosis of 141 Microkeratome-assisted LASIK 96 Moire deflectometry-based systems 7 Molecular methods 156 Mooren’s ulcer 357 Mucin in goblet cells 358 Mucin layer 316
Mucoepidermal junction of lid 313 Mucor 170 Mucosal epithelium, biopsy of 365 Mucosal flap, central opening in 401f Mueller-Hinton agar 148, 150f Mycobacterium chelonae keratitis 154f Mycobacterium tuberculosis 150, 445 Mycophenolate mofetil 450 Mycotic keratitis 71 diagnosis of 177 Myopia 282, 284 high 78, 99f low 89 moderate 98f treatment of 95 Myopic ablation 43f, 84f decentered 46f Myopic corrections 41 Myopic eyes 87 Myopic laser in situ keratomileusis 17f Myopic LASIK 108
N Natamycin 179, 183 Near-Descemet’s deep lamellar keratoplasty 299 Necrotizing anterior scleritis 442, 444f with inflammation 442, 443f without inflammation 442 Necrotizing keratitis 195 Necrotizing scleritis 438, 442, 443f, 448, 449, 451f surgically induced 444 Nephropathic cystinosis 417, 420f Nerve fibers, small 58 growth factor 100 plexuses, sub-basal 58 plexuses, subepithelial 58 Neurotrophic keratitis 171 Neurotrophic keratopathy 193, 346 Neurotrophic ulcer 349f healed 353f Neutrophils 171 kill ameba 209 Newer biological agents 450 Nipkow disk 54 Nocardia species 154 Nodular scleritis 442, 442f Non-amniotic substrate 367
Noninflammatory ectatic disorder 61 Non-nutrient agar 143, 144 Nonpreserved drugs 331 Non-Sjögren’s syndrome 319 Nonsteroidal anti-inflammatory drugs 449 Nonviral corneal ulcer 143 Nonviral keratitis 140, 144f, 157, 211 NSAIDs See Nonsteroidal anti-inflammatory drugs Nuclear sclerotic cataract 137 Nystatin 180
O Ocular adnexa 337 chemical injury 346 cicatricial pemphigoid 347, 357 disease, active 279 Ocular protection index 325 calculating 325t Ocular surface 313, 313f, 338 comprises 337 damage 317 disease 97, 299 disorders 337 dysfunction of 316 epithelium 354 equivalents, bioengineered 363 inflammatory reactions of 318 multiple 357 reconstruction 337 indications for 339t squamous neoplasia 299, 339, 346 resection 352f staining 322, 323t transplantation, evolution of 338 Oculopalpebral and reconstructive surgery 347 Oil glands, assessment of 327 Onchocerca 445 Opaque corneal stroma 305 Ophthalmic practice 70 Ophthalmometer 1 Optical coherence tomography 11f Optics 54 Optimum refractive treatment 49 Oral ketoconazole 183 Oral steroids, starting 191f Orbicularis muscle 397 suturing 396f
Orbscan II system 8f Orbscan, postoperative 133f OSD See Ocular surface disorders Osmotic effects 434 OSR See Ocular surface reconstruction OSSN See Ocular surface squamous neoplasia Oxychloro complex, stabilized 331
P Pachymetry 89 Paecilomyces 182 Pallikaris 84 Papanicolaou stain 159 Papillary cum follicular conjunctivitis 430 PBIKP See Pintucci biointegrated keratoprosthesis PBS See Phosphate buffered saline PDA See Potato dextrose agar PDEK See Pre-Descemet’s endothelial keratoplasty Pellucid marginal corneal degeneration 292 Pellucid marginal degeneration 35 Penetrating keratoplasty 48f, 271, 375, 376 Perilimbal injection 362 Perinuclear hypodense rings 56 Periodic acid-schiff stains 177, 211 Peripheral cornea 38, 355f Peripheral iridectomy 387 Peripheral ulcerative keratitis 357 Phakic lens 78, 91 Phosphate buffered saline 158 Phosphoglucomutase 204 Phospholipase A 206 Photoablation related complications 85 Photokeratoscope raw image 14f Photokeratoscopy 2 Photophobia 256, 356, 428, 431 Phototherapeutic keratectomy 125 Pigmented fungal ulcer 175f Pintucci biointegrated keratoprosthesis 392, 393, 399f surgical technique 393 Pintucci keratoprosthesis 393f Piramidal aberrometry 26 Placido’s disk 7 method 7 system 5
468 Gems of Ophthalmology—Cornea and Sclera
Placido’s targets, types of 7 Placido’s rings 3f, 14 Plano refraction 136 Pleomorphism 73f PMMA See Polymethyl methacrylate Polyarteritis nodosa 439, 440, 447 Polyenes 179 Polyglycolic acid 396 Polymegathism 73f Polymerase chain reaction 151, 158 Polymethyl methacrylate 282, 368, 401 Polymorphous dystrophy, posterior 66 Polymorphous membranous dystrophy, posterior 254f Polymyositis 440 Polyphaga 204 Polyvinyl alcohol 329 Polyvinyl pyrrolidone 329 Postastigmatic keratotomy 38 Postintrastromal corneal rings implantation 45 Postlaser in situ keratomileusis 42 Postlaser thermal keratoplasty 44 Post-LASIK ectasia 282, 289, 292 eye 137 surgery 154f, 276 Post-PRK ectasia 282 Postradial keratotomy 38 cornea 40f Post-refractive keratectasia 276, 280 Potassium hydroxide 144, 176, 176f preparation 146 Potato dextrose agar 144, 145 Potential visual acuity 22 Povidone 329 Preclude iris 256f Precorneal tear film, layers of 316t Pre-Descemet’s endothelial keratoplasty 381, 383, 384 Prednisolone 308 Preocular tear film 314 PRK See Photorefractive keratectomy Prokera 353 Prolate surface 4 Propionibacterium acnes 150 species 155 Propionyl esterase 204 Protein deposit 432 contact lens 433f
Pseudoanterior chamber 307 Pseudokeratoconus 49 Pseudomonas aeruginosa 147f, 425 isolated 150f Pseudomonas keratitis 156 Pseudomonas spp 143 Pterygium 38, 299, 339, 346, 357 excision 340f, 342, 343f surgery 343 complications of 344t Punctate epithelial staining, superior 430 Punctate keratitis, superficial 321 Punctum patch 333f Pupillary block glaucoma 307 Pupillometer 89 Pure placido disk technology 18 Pythium insidiosum 148
R Rabbit corneas 83f Ray tracing system 26 Reactive oxygen species 277 Recipient eye 406f, 407f button removed 405f Rectus muscle 396 disinsertion 344 Reflection of buccal mucosa, second stage 398f Refractive lens surgery 89 Refractive lensectomy 78 Refractive map 20 Refractive outcome 308 Refractometer, spatially resolved 26 Reis-Bucklers corneal dystrophy 231, 232f histopathology 232 inheritance 231 management 233 signs 232 symptoms 232 Relapsing polychondritis 439, 440 ReLEx technique 90 Renal dysfunction 422 Renal manifestations, extra 418 endocrine 418 gonads 418 growth retardation 418 myopathy 418 neurology 418 Renal tubular acidosis 416 Residual hyperopia 135
Residual pachymetry 131 Residual stroma, thickness of 87 Retinal detachment 92 Retreated corneas 127 RGP lenses See Rigid gas permeable lenses Rheumatoid arthritis 440, 442, 443f Rheumatoid factor 447 Rhizopus sp. 170 Riazole antifungal agents 182 Riboflavin acts 270 Rigid contact lens 425f Rigid gas permeable lenses 48, 116, 268, 269 Rigid scleral lens, interface debris in 433f Robertson’s cooked meat broth 144 Root mean square 32t Rose bengal 324 staining of conjunctiva 324f RTA See Renal tubular acidosis
S Sabouraud dextrose agar 144, 145 Sahara syndrome 86 SAI See Surface asymmetry index Sands of Sahara 119 syndrome 68 Sarcoidosis 440 Satellite lesions 173 multiple 174f Sattler’s veil 425 Scedosporium 182 Scheimpflug camera 9 Scheimpflug photography, principle of 8 Scheimpflug technology 15 Scheimpflug-based topographer 9f Schirmer’s test 98, 327 Sclera 437 Scleral contact lens 426f Scleral edema 442, 448f Scleral inflammation 452 infectious 444 treatment of 449 Scleritis 437, 439, 440, 440t, 444, 447-449 anterior 438, 443 necrotizing 449, 450 non-necrotizing 449 classification of 439 complication of 448 necrotizing 448
diagnosis of 440 diagnostic evaluation of 447 diffuse 441f posterior 438, 443, 444, 446f, 447, 449 treatment of 450, 452 Scleromalacia perforans 438, 442 Scotopic pupils, large 88 SDA See Sabouraud dextrose agar Securing conjunctival autograft 342 Septate fungal filaments 152f Serratia marcescens 425 Serum uric acid 447 Sexual hormones 335 Shack-Hartmann method 26 Sheep blood agar 145, 177 chocolate 145 Sheimpflug-based noncontact tonometer 100 Shield ulcer 346 Silver sulfadiazine 183 Sirius system 9 Sjögren’s syndrome 171, 319 primary 319 secondary 319 Slice of cornea, computer-generated 53 Small-incision lenticule extraction 89, 91, 96-99, 101, 101f advantages of 97 all-femtosecond 91 surgery, enhancements after 103 technique 96 SMILE See Small-incision lenticule extraction SMILE ReLEx, future of 90 Sodium perborate 331 Spherical aberration 32t primary 32t Spherical configuration 38 Spherical equivalent 287 SPK See Superficial punctate keratopathy Staphylococcus aureus 425 Staphylococcus epidermidis 155 Stem cell cultures 347 transplantation 360f, 366 Stevens-Johnson syndrome 299, 339, 357, 368, 392 Stocker-Holt variant encompasses 228 Strabismus, surgical correction for 247 Streptococcus pneumonia 149, 152, 425
470 Gems of Ophthalmology—Cornea and Sclera
Stroma 55, 58 acellular 58 cellular 58 neurosensory 58 Stromal corneal dystrophy 219, 235, 235t Stromal disease, surgical treatment of 378 Stromal dystrophy 221, 234 Stromal edema 254f Stromal herpes simplex keratitis 351 Stromal keratitis 175, 187, 189, 190, 195, 197 Stromal keratocyte 60f nuclei 59 Stromal necrosis 207 Stromal nerve fibers 59 Stromal opacities 245f Stromal striae 426 Subconiunctival hemorrhage 85 Subconjunctival miconazole 183 Subconjunctival tissues 437 Subconjunctivitis 438 Subepithelial nerve fibers 58f, 69 plexus 55, 56 Subneurosensory retinal space 445f Sulfacetamide 183 Superficial punctate keratopathy 321, 425 Suprachoroidal hemorrhage 92 Symblephara 395 Symblepharon 346 formation 339 shell in situ 349f Syphilis 347, 440 serologic tests for 447 Systemic autoimmune disease 440 Systemic diseases 439 Systemic lupus erythematosus 440 Systemic tetracyclines 334
T Tacrolimus 450 T-cell inhibitors 450 Tear artificial 328 breakup time, noninvasive 325 deposits 432 drainage system, occlusion of 332 evaporation in ocular surface disease, role of 318f
inflammatory mediators in SMILE 100 lysozyme 432 meniscus height 98 nonpreserved artificial 331 preservation 332 preservatives in artificial 329 substitutes, artificial 329t substitution 328 Tear film 313, 313f composition of 315 dysfunction of 316 functional unit 313t normal 316f osmolarity, altered 434 regulation 314 stability, assessment of 325 Tenon’s capsule 437 Terrien’s marginal degeneration 37 Testosterone 421 Tetraene antibiotic 179 Therapeutic DALK 380 Therapeutic keratoplasty 184 Thiel-Behnke corneal dystrophy 233 histopathology 234 inheritance 233 signs 233 symptoms 233 Thioglycollate broth 144 Thiomersal hypersensitivity 429 Threatening infectious keratitis 70 Thyroxine 421 Tissue culture methods 161 TMH See Tear meniscus height Topical antibiotic drops 308 Topical autologous serum 335 Topical corticosteroids 334 Topographers curvature-based 5 elevation-based 7 Topographic indexes, basic 21 Topography examination 10 improvement in 290f Topography-guided treatment 89 Toxic epidermal necrolysis 346, 357 Toxic lens syndrome 427 Toxicity 427 Toxocara 445 Toxoplasma 445 gondii 150 Transient amplifying cells 355f
Transporters-preceding cell atrophy 420 Trauma 357 Treponema pallidum 445 Triazole 180 water-soluble 181 Trichiasis 339 Trifluridine 195, 198 Trigeminal nerve 314 Trophozoites of acanthamoeba 152 Troublesome artefacts 152 Tscherning aberrometry 135 Tscherning technique 26 Tuberculosis 440 Tubular glomeruli 417 Tumor necrosis factor-alpha 100
U Ulcer 173f Ulcerative colitis 440 Undercorrected hyperopic 111 LASIK 111 Unmyelinated nerve fibers 437 Urrets-Zavalia syndrome 379
V Valacyclovir 198 Vancomycin 452 drops 410 Varicella zoster virus 159, 161 Vascular plexuses 438f Vessels of episclera and sclera, layers of 438t Videokeratography system 4f Videokeratoscopes 7 Videokeratoscopy 3 Viral disease 157 infections, diagnosis of 156 Viral keratitis 157, 158t collection of samples 157 diagnosis of 157, 163 diagnostic tests for 161t protocol for 156 transport of samples 157
Virology results, interpretation of 163 Visante ocular coherence tomography 307f Visual acuity 308 assessment 279 best corrected 270 corrected distance 103 decreases 243 spectacle-corrected 86 uncorrected 131f, 308 Visual disturbances, severe 42 Visualize corneal guttata 66 Vogt’s striae 61 Voriconazole 181 Vortex keratopathy 75 VZV See Varicella zoster virus. 161
W Wegener’s granulomatosis 440, 447, 449-451, 451f Wilson’s disease 74 Witschel dystrophy 246
Y Yeasts 170
Z Zeihl Neelsen acid-fast stain 146 Zeiss achroplan lens 141f Zernike polynomial 27 expansion 28f Zernike second order 134 Ziehl-Neelsen staining 154f technique 154 Zylink software program 128 Zyoptix enhancement program 132 surgery 129 Zyoptix system 127, 135 Zyoptix wavefront-guided customised ablation 127, 128