Current Concepts in Refractive Surgery [1 ed.] 9789354652134

Table of contents :
Contents
Section 1 Historical Perspective
1 Evolution of Refractive Surgery
Section 2 Preoperative Workup and Decision Making
2 Corneal Wound Healing in Keratorefractive Surgery
3 Corneal Topography
4 Corneal Biomechanics
5 Aberrometry and Wavefront Analysis
6 Posterior Segment Screening and Refractive Surgery C H
7 Preoperative Evaluation,Patient Counseling, and Decision Making
Section 3 Corneal Ablative Procedures
8 Surface Ablation
9 Complications of Surface Ablation
10 Laser-assisted in Situ Keratomileusis
11 Complications of Flap-Based Corneal Ablation
12 Customized Corneal Ablation
Section 4 Small Incision Lenticule Extraction
13 Small Incision Lenticule Extraction
14 Complications of Small Incision Lenticule Extraction C
Section 5 Lens-based Refractive Surgeries
15 Phakic Intraocular Lenses
16 Complications of Phakic Intraocular Lenses
Section 6 Enhancements and Retreatments
17 Retreatment after Corneal Laser Ablation
18 Retreatment after SMILE
Section 7 Presbyopia
19 Refractive Surgery for Presbyopia: An Overview
20 Presbyopic Excimer Laser Ablation
21 Corneal Inlays
Section 8 Miscellaneous
22 Bioptics
23 Corneal Collagen Cross-linking and Refractive Surgeries
24 Refractive Surgery in Challenging Scenarios
25 Intrastromal Corneal Ring Segments
26 Incisional Refractive Surgery
INDEX

Citation preview

CURRENT CONCEPTS IN REFRACTIVE SURGERY

CURRENT CONCEPTS IN REFRACTIVE SURGERY

Comprehensive Guide for Decision Making & Surgical Techniques

Editors

Jeewan S Titiyal MD

Professor and Head Cornea, Cataract and Refractive Surgery Services Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Manpreet Kaur

Sridevi Nair

MD

MD

Assistant Professor Cornea, Cataract and Refractive Surgery Services Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Research Officer Cornea, Cataract and Refractive Surgery Services Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Foreword

Walter Sekundo

JAYPEE BROTHERS MEDICAL PUBLISHERS The Health Sciences Publisher New Delhi | London

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Website: www.jaypeebrothers.com Website: www.jaypeedigital.com © 2022, 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]

Current Concepts in Refractive Surgery: Comprehensive Guide for Decision Making & Surgical Techniques First Edition: 2022 ISBN: 978-93-5465-213-4

Dedicated to My parents, my dear wife Basanti Titiyal My children, Dr Hemant Titiyal and Dr Renuka Titiyal Jeewan S Titiyal My Alma mater and mentors, for being the guiding light My family, for their unwavering support, love and time Manpreet Kaur My teachers, for motivating me to excel My parents and husband, for believing in my abilities Sridevi Nair Our patients, who constantly inspire us to perform better Jeewan S Titiyal Manpreet Kaur Sridevi Nair

Contributors Anand Singh Brar MD

Fellow LV Prasad Eye Institute Bhubaneshwar, Odisha, India

Anubha Rathi MD

Faculty The Cornea Institute LV Prasad Eye Institute Hyderabad, Telangana, India

Brijesh Takkar MD

Faculty Retina Service, IHOPE Research Center LV Prasad Eye Institute Hyderabad, Telangana, India

Farin Shaikh MD

Senior Resident Cornea, Cataract and Refractive Surgery Services Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Harathy Selvan MD

Senior Resident Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Harika Regani MD

Senior Fellow Sitapur Eye Hospital Sitapur, Uttar Pradesh, India

Jeewan S Titiyal MD

Professor and Head Cornea, Cataract and Refractive Surgery Services Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Manpreet Kaur MD

Assistant Professor Cornea, Cataract and Refractive Surgery Services Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Meghal Gagrani MD

Fellow Department of Ophthalmology University of Pittsburgh Medical Center Pittsburgh, Pennsylvania, USA

Neelam Runda MD

Specialist (Ophthalmology) Central Government Health Scheme (CGHS) Prayagraj, Uttar Pradesh, India

Priyanka MS

Assistant Professor Mahaveer Institute of Medical Sciences Bhopal, Madhya Pradesh, India

Rinky Agarwal MD

Assistant Professor Department of Ophthalmology Lady Hardinge Medical College New Delhi, India

Sana Tinwala MD

Consultant Department of Ophthalmology University Hospitals of Derby and Burton United Kingdom

Saurabh Verma MD

Senior Resident Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Sridevi Nair MD

Research Officer Cornea, Cataract and Refractive Surgery Services Dr Rajendra Prasad Centre for Ophthalmic Sciences All India Institute of Medical Sciences New Delhi, India

Foreword The field of refractive surgery has witnessed quantum leaps over the past decades in terms of cutting-edge technologies, novel surgical techniques and more precise visual outcomes. At present, refractive surgeons have a wide armamentarium of refractive surgical procedures at their disposal that may be customized based on the patient profile. This excellent book provides a comprehensive synopsis of modern-day refractive surgery in an easy to read format along with abundant excellent illustration and photographs. Hence, for trainees this work will provide the theoretical knowledge required for a successful fellowship. For established surgeon it will serve as a useful reference handbook. The book has been divided into sections to enable an easy flow of understanding, with the initial section tracing the evolution of refractive surgery over the years. The preoperative assessment is detailed in the subsequent section with well-written chapters elucidating the finer nuances of corneal topographical assessment, aberrometry and biomechanics. Of note, the chapter on patient selection and decision-making encompasses the most useful aspects of refractive screening and patient counseling, with flowcharts and algorithms to enable selection of appropriate refractive technique in different scenarios. Each of the present refractive surgical techniques is covered in detail, with techniques, outcomes and management of complications. Surface ablation, laser-assisted in situ keratomileusis and refractive lenticule extraction constitute the cornerstones of corneal refractive procedures and are comprehensively highlighted in this book. Customized ablation may be the future of refractive surgery and the book provides an insight into different algorithms, case selection and outcomes with various ablation profiles. Phakic intraocular lenses are a viable alternative to patients not suitable for corneal-based procedures and are covered in detail in the subsequent section paying attention to pitfalls and complications prevention. Surgical management of presbyopia is still challenging for even experienced refractive surgeons, and the section on presbyopia provides an overview of where we stand today and the way forward to tackling this still-elusive problem. Thereafter, the complex issue of retreatment after corneal procedures is tackled in depth for both corneal ablative procedures and small incision lenticule extraction. The frontiers of refractive surgeries are ever expanding, and the last section highlights the management of hyperopia, refractive surgery in thin corneas, role in pediatric cases as well as bioptics. The role of collagen cross-linking as an adjunct is discussed with different refractive procedures including ring segments. As mentioned above, the highlight of this book is the easy readability, with the text interspersed with tables, flowcharts and high-definition photographs to enhance reader experience and understanding. And yet, it includes all the important details of the field. Even for those of us, who read and wrote numerous books and papers, to read this handbook is truly a joy. I congratulate the authors on their endeavor and believe the readers will be enriched by the experience this book provides.

Walter Sekundo 

MD PhD

Professor and Chairman Department of Ophthalmology Philipps University of Marburg Marburg, Germany

Preface Refractive surgery is one of the most dynamic and exciting fields in ophthalmology, with fast-evolving surgical techniques, state-of-the art diagnostics and sophisticated laser platforms and machinery. Present day refractive procedures offer a high index of safety and efficacy, and we have come close to achieving the elusive goal of guaranteeing ‘perfect’ visual outcomes for a majority of patients. This book is an endeavour to provide a comprehensive insight into the current concepts of various refractive surgical procedures—the techniques, outcomes, complications and their management. The salient points of each chapter are reiterated in the form of easy-to-understand flowcharts and tables, to allow the readers to grasp the significant concepts and protocols at a glance. Today we have a plethora of refractive procedures to choose from, and selection of the appropriate refractive technique based on the patient characteristics and requirements is a skill in itself. The highlight of this book is an exhaustive section on preoperative assessment and decision-making, which is the cornerstone to optimizing outcomes and patient satis­ faction for any refractive practice. Advanced diagnostic modalities to screen for risk of ectasia have enhanced the safety of refractive procedures, and the newer indices and parameters with their clinical applicability are covered in detail. Each refractive technique is comprehensively addressed in separate sections, with an emphasis on the different laser platforms for corneal procedures, technical specifications and laser parameters and the types of intraocular implants. We are slowly but surely moving forward towards the goal of customized refractive surgery as per individual requirements, and our book highlights various customized ablation patterns as well as the role of integrated aberrometry and corneal biomechanics in optimizing outcomes. Despite the leaps forward, some refractive frontiers are yet to be conquered including efficacious and predictable techniques for presbyopia. The current status of surgical management of presbyopia is well-elucidated in the book. In addition, the management of various challenging case-scenarios is highlighted, including hyperopia, borderline corneas, pediatric patients and irregular corneas. The book is intended to serve as a comprehensive guide for all refractive surgeons and will be an invaluable addition to their reading list. We hope the readers enjoy perusing the book and can integrate the practical aspects to enhance their decision-making skills and clinical practice.

Jeewan S Titiyal Manpreet Kaur Sridevi Nair

Acknowledgments We express our sincere gratitude to the entire staff of our Cornea and Refractive Investigative Laboratories, who were of invaluable help in the meticulous maintenance of the clinical records. We gratefully acknowledge the immense efforts of the scientists, optometrists, data entry operators and research staff in ensuring comprehensive evaluation of each and every patient despite a heavy workload. We wish to thank the staff of our refractive operation theater for providing an organized and efficient working environment. We thank all our colleagues and residents of the Cornea and Refractive Surgery Units for their support. We also wish to thank all our contributors for their valuable efforts. We acknowledge our patients who are an integral part of this entire venture, for placing their trust in us, and providing us with an opportunity to assist them to the best of our ability. We sincerely appreciate the entire production team of Jaypee Brothers Medical Publishers (P) Ltd., New Delhi, India for their exemplary hard-work, support and commitment towards this project.

Contents SECTION 1 HISTORICAL PERSPECTIVE Chapter 1. Evolution of Refractive Surgery..........................................................................................3 Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal   The Past: A Historical Overview of Refractive Surgery  3   The Present: Current Trends in Refractive Surgery  5  �  The Future of Refractive Surgery  5

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SECTION 2 PREOPERATIVE WORKUP AND DECISION MAKING Chapter 2. Corneal Wound Healing in Keratorefractive Surgery............................................................... 11 Sridevi Nair, Harika Regani, Manpreet Kaur, Jeewan S Titiyal   Anatomy of the Cornea  11  �  Corneal Wound Healing Following Surface Ablation  11   Corneal Wound Healing Following LASIK  13  �  Corneal Wound Healing Following SMILE  14 �  Clinical Relevance of Corneal Wound Healing after Keratorefractive Surgery  15 � �

Chapter 3. Corneal Topography..................................................................................................... 18 Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal  Keratometry 18  � Keratoscopy 18    Color LED Ray Tracing Topography  31

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  Elevation-based Topography Systems  23

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Chapter 4. Corneal Biomechanics.................................................................................................. 33 Saurabh Verma, Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal   Corneal Biomechanics and Refractive Surgery  33  �  Corneal Biomechanical Assessment  33 �  Limitations and Future Directions  40  �  Emerging Technologies  40

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Chapter 5. Aberrometry and Wavefront Analysis................................................................................. 42 Anand Singh Brar, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal   Lower- and Higher-order Aberrations  42  � Wavefronts 43  �  Zernike Polynomials  44  Aberrometry 44  �  Importance in Refractive Surgery  46  �  Future Developments  50

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Chapter 6. Posterior Segment Screening and Refractive Surgery............................................................. 52 Priyanka, Brijesh Takkar, Manpreet Kaur, Jeewan S Titiyal   Preoperative Posterior Segment Screening  52   Postrefractive Surgery Vitreoretinal Complications  54

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Chapter 7. Preoperative Evaluation, Patient Counseling, and Decision Making............................................ 58 Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal   Clinical History  58  �  Clinical Examination  60    Patient Counseling  65

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  Decision Making  62

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SECTION 3 CORNEAL ABLATIVE PROCEDURES Chapter 8. Surface Ablation......................................................................................................... 71 Neelam Runda, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Patient Selection  71  �  Surgical Techniques  71  � Outcomes 75  � Complications 76 �

  Excimer Laser Ablation  74

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Chapter 9. Complications of Surface Ablation.................................................................................... 78 Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal   Postoperative Pain  78  �  Corneal Haze  78  �  Delayed Epithelial Healing  81   Epithelial Flap-related Complications  81  �  Glare and Halos  81  �  Decentered Ablation  81 �  Central Islands  82  �  Corneal Infiltrates  82  �  Infectious Keratitis  82  � Ectasia 82 �  Dry Eyes  82  �  Raised Intraocular Pressure  82 � �

Chapter 10. Laser-assisted in Situ Keratomileusis................................................................................ 84 Anubha Rathi, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Indications and Patient Selection  84  �  Lasik Flap Creation  84   Excimer Laser Ablation  90  �  Clinical Outcomes  92

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Chapter 11. Complications of Flap-Based Corneal Ablation..................................................................... 94 Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal   Intraoperative Complications  94 

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  Postoperative Complications  100

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Chapter 12. Customized Corneal Ablation.........................................................................................111 Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal   Classical Ablation Profiles and Need for Customization  111  �  Customized Corneal Ablation Profiles  111   Wavefront-optimized Ablation  111  �  Wavefront-guided Ablation  114 �  Topography-guided Ablation  116  �  Aspheric or Q Factor Adjusted Ablation Profile  119 �  Ray Tracing-based Ablation  119

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SECTION 4 SMALL INCISION LENTICULE EXTRACTION Chapter 13. Small Incision Lenticule Extraction..................................................................................125 Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Evolution of Refractive Lenticule Extraction  125  �  Patient Selection  125   Machine and Laser Settings  126  �  Surgical Technique  129 � Outcomes 132  �  SMILE for Astigmatism  132  �  SMILE for Hyperopia  132 � �

Chapter 14. Complications of Small Incision Lenticule Extraction.............................................................135 Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Intraoperative Complications  135 

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  Postoperative Complications  141

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SECTION 5 LENS-BASED REFRACTIVE SURGERIES Chapter 15. Phakic Intraocular Lenses.............................................................................................151 Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Types of Phakic IOLs  151    Surgical Techniques  157 

  Preoperative Evaluation and Case Selection  155   Postoperative Assessment of Vaulting  158  � Outcomes 159

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Chapter 16. Complications of Phakic Intraocular Lenses........................................................................161 Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Intraoperative Complications  161  �  Postoperative Complications  162

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SECTION 6 ENHANCEMENTS AND RETREATMENTS Chapter 17. Retreatment after Corneal Laser Ablation..........................................................................173 Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal  Incidence 173  � Indications 173  �  Risk Factors  173   Preoperative Evaluation and Decision Making  174  �  Surgical Techniques of Retreatment  175 � Outcomes 177 � �

Chapter 18. Retreatment after SMILE..............................................................................................179 Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair  Incidence 179 

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  Risk Factors  179 

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 Management 179

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SECTION 7 PRESBYOPIA Chapter 19. Refractive Surgery for Presbyopia: An Overview...................................................................187 Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Cornea-based Refractive Surgical Procedures  187  �  Lens-based Approach for Presbyopia Correction  189  �  Sclerociliary Complex Based Procedures for Presbyopia  192 �

Chapter 20. Presbyopic Excimer Laser Ablation..................................................................................193 Sana Tinwala, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal   Patient Selection  193  �  Corneal Approach to Presbyopia Correction  194 �  Multifocal Laser Vision Correction  194  �  Laser-blended Vision  197  � Counseling 198 �

Chapter 21. Corneal Inlays...........................................................................................................200 Sana Tinwala, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Corneal Inlays  200 

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  Corneal Onlays  204

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SECTION 8 MISCELLANEOUS Chapter 22. Bioptics...................................................................................................................207 Farin Shaikh, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Patient Selection and Preoperative Work-up  207   Classification of Surgical Techniques of Bioptics  207 �  Surgical Outcomes with Different Procedure Combinations  209 � �

Chapter 23. Corneal Collagen Cross-linking and Refractive Surgeries........................................................213 Sridevi Nair, Harathy Selvan, Manpreet Kaur, Jeewan S Titiyal   Corneal Collagen Cross-linking Xtra  213 

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  Corneal Collagen Cross-linking Plus  217

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Chapter 24. Refractive Surgery in Challenging Scenarios......................................................................221 Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal   Refractive Surgery in Pediatric Patients  221  �  Refractive Surgery for Hyperopia  222 �  Refractive Surgery in Post-keratoplasty Patients  225  �  Refractive Surgery in Pseudophakia  226 �

Chapter 25. Intrastromal Corneal Ring Segments................................................................................229 Rinky Agarwal, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal   Mechanism of Action  229  �  Indications and Patient Selection  230   Intrastromal Corneal Rings and Ring Segments  230  �  Surgical Technique  231 �  Additional Procedures  232  � Outcomes 232  � Complications 232 � �

Chapter 26. Incisional Refractive Surgery.........................................................................................235 Meghal Gagrani, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair   Radial Keratotomy  235 

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  Astigmatic Keratotomy  236

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Index������������������������������������������������������������������������������������������������������������������������������������������������������������������������241

SECTION

1

Historical Perspective

1. Evolution of Refractive Surgery

Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

CHAPTER

1

Evolution of Refractive Surgery Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

  INTRODUCTION Refractive surgeries are one of the most commonly performed elective ophthalmic procedures worldwide. The journey of refractive surgery has been a continual evolution from the now archaic corneal incisional surgeries to excimer laser-based corneal ablative procedures, to the present-day minimally invasive femtosecond laser-based techniques such as small incision lenticule extraction (SMILE). Till date, more than 40 million laser-assisted in situ keratomileusis (LASIK) and 2 million SMILE procedures have been performed worldwide.1 Advancements in corneal diagnostics and laser techno­ logy have paved way for the development of customized corneal ablation profiles with a revival of interest in surface ablative procedures. Despite the excellent outcomes observed with the current procedures in treating myopic errors, their results in presbyopia and hyperopia are not as predictable. Ongoing research in this ever-expanding field may help us to improve our understanding of these conditions and optimize their management in the foresee­ able future. We herein trace the evolution of refractive surgeries in ophthalmology, the current trends and the future frontiers (Figs. 1 and 2).

  THE PAST: A HISTORICAL OVERVIEW OF REFRACTIVE SURGERY The concept of reshaping the cornea to correct refractive errors was first proposed by Hjalmar Schiotz in 1885, who employed limbal relaxing incisions to correct post­ cataract surgery astigmatism. Subsequently, Leendert Jan Hans studied the utility of corneal incisions for treating astigmatism and proposed the concept of corneal flattening occurring in the meridian perpendicular to the incision. The introduction of radial keratotomy (RK) by Sato in 1939 heralded the era of incisional corneal refractive surgeries. He performed anterior and posterior radial corneal incisions to flatten the central cornea and correct myopic refractive errors; however, the posterior corneal incisions were associated with endothelial cell damage and bullous keratopathy in up to 70% of patients.2 Fyodorov, a corneal surgeon from Russia modified the technique to perform only anterior corneal keratotomy incisions and employed various multifactorial nomograms to improve predict­ ability of outcomes.3 Meanwhile, hexagonal keratotomy was introduced by Dr Antonio Méndez for treating hyperopic refractive errors, wherein, corneal incisions were placed circumferentially in a hexagonal configuration

Fig. 1: A timeline describing the evolution of refractive surgery. (FS: femtosecond; LASIK: laser-assisted in situ keratomileusis; SMILE: small incision lenticule extraction; FDA: Food and Drug Administration; PRK: photorefractive keratectomy; ICL: implantable collamer lens)

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SECTION 1: Historical Perspective

Fig. 2: The past, the present, and the future of refractive surgeries. (LASIK: laser-assisted in situ keratomileusis; PRK: photorefractive keratectomy; SMILE: small incision lenticule extraction)

to cause steepening of the central cornea.4 RK enjoyed widespread popularity through the 1970s and 80s; however, it was eventually discontinued due to unpredictable and fluctuating visual outcomes and the introduction of more accurate excimer laser technology for corneal ablation.5,6 The concept of keratomileusis or “corneal carving” was pioneered by José Ignacio Barraquer in 1964. Epikerato­plasty was described in 1980s based on Barraquer’s technique wherein a lathed donor stromal lenticule was sutured onto the cornea.3 The 1970s and 80s saw the emergence of corneal reshaping techniques including radial thermal keratoplasty and conductive keratoplasty, which were less invasive and technically simpler. Fyodorov introduced radial thermal keratoplasty to treat hyperopia and astigmatism. The shrinkage of collagen fibrils gave rise to a midperi­ pheral purse string effect with corresponding steepening of central cornea. Conductive keratoplasty was developed in 1990s for low-moderate hyperopia and presbyopia, wherein central corneal steepening was achieved with the controlled delivery of high-frequency and low-energy electric current to the mid-peripheral stroma. The corneal reshaping techniques were discontinued due to associated complications, lack of long-term stability, and significant regression.7-10 The introduction of argon fluoride (ArF) lasers in 1983 for corneal ablation marked a paradigm shift in the field of corneal refractive surgery. It enabled removal of precise amounts of stromal tissue within a fraction of microns while causing negligible damage to the adjacent tissue.11 Photorefractive keratectomy (PRK) was the first procedure to employ excimer laser-mediated corneal ablation for reshaping the cornea in order to correct myopic refractive errors, and received FDA approval in 1995.12 Over the years, innovations in excimer laser technology such as the use of higher frequency lasers, introduction of flying spot lasers, advanced eye-tracking systems, and the introduction of Gaussian beam profile have enhanced the safety and efficacy of visual outcomes. Postoperative pain and corneal haze associated with epithelial removal in PRK led to the development of flap-based corneal ablative procedures. In 1990, Pallikaris described LASIK wherein he created a corneal flap with a guarded microkeratome and

ablated the underlying stromal bed with excimer laser; the procedure received FDA approval in 1999.13 Advancements in corneal diagnostics, including corneal imaging and aberrometry, facilitated the development of customized laser vision correction. Customized corneal ablation aimed to treat the pre-existing ocular aberrations or minimize their induction during the procedure. Wavefront optimized LASIK minimizes the induction of new spherical aberrations during LASIK and continues to remain the most commonly used ablation profile. 14 Wavefrontguided ablation aims to objectively correct the total ocular aberrations measured preoperatively by an aberrometer or wavefront sensor.15 Corneal topography-guided ablation was essentially introduced as a modality to treat irregular corneas including keratoconus, postkeratoplasty astigmatism, and healed keratitis.16 The advent of femtosecond laser (FS) technology in early 2000s revolutionized the field of refractive surgery.17 The use of a highly focused photodisruptive laser, employing ultra-short pulses, heralded the era of high precision flapbased and flapless procedures. Femtosecond laser-assisted flaps were associated with better precision, reproducibility, faster visual recovery, and lesser incidence of postoperative dry eyes as compared with microkeratome flaps.18 Femtosecond lenticule extraction (FLEx), introduced in 2006, was the first procedure to utilize a single FS laser platform (VisuMax, Carl Zeiss Meditec AG, Jena, Germany) for creating the corneal flap and an intrastromal lenticule, thus eliminating the need for excimer laser-mediated stromal ablation.19 The technique was further modified to extract the intrastromal lenticule via a small side cut incision instead of a flap, known as SMILE.20 The history of lens-based procedures for treating refractive errors dates back to the late 18th century when Abbé Desmonceaux of France proposed the removal of crystalline lens to treat high myopic errors. Removal of crystalline lens with intraocular lens (IOL) implantation for treating refractive errors or refractive lens exchange gained popularity following advancements in the field of cataract surgery.21 Phakic IOLs for the correction of myopia were first introduced in 1953 by Benedetto Strampelli. Initial phakic IOLs were meant to be implanted in the anterior chamber and fell out of favor due to associated endothelial decompensation and glaucoma. The 1980s saw a revival of phakic IOL surgery with advancements in IOL design and material. Iris fixated lens and posterior chamber phakic IOLs were developed with a favorable safety profile.22 The Artisan (Ophtec) iris claw lens received FDA approval in 2004; subsequently, its modification, Artiflex (Ophtec), made of flexible silicone with a larger optic size was introduced. Implantable Collamer lens (ICL), a posterior chamber phakic IOL, was first introduced in 1993. The enhanced biocompatibility and superior optics of ICL

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CHAPTER 1: Evolution of Refractive Surgery afforded a favorable safety profile while providing excellent visual outcomes. The earlier models of ICL were associated with a significant incidence of lenticular opacities caused by the intermittent contact between the ICL and crystalline lens. This was reduced in the subsequent models due to improvements in the ICL design and material, furthering the widespread acceptance of these lenses.23

  THE PRESENT: CURRENT TRENDS IN REFRACTIVE SURGERY Cornea-based refractive surgeries are the current standard of care, with LASIK and SMILE being the most widely performed corneal refractive surgeries. Femtosecond laser for creation of corneal flaps prior to ablation has further enhanced the safety and predictability of LASIK; however, it is associated with its unique set of complications related to suction loss and cavitation bubbles breakthrough. The advent of newer femtosecond lasers employing a higher frequency, lower energy, and tighter spot and line separation has led to a decrease in the laser-related complications. The prospect of a flapless corneal refractive surgery, which was at par with LASIK in terms of precision, efficacy, and safety profile, became a reality with the introduction of SMILE. Though associated with a considerably steeper learning curve, the procedure has distinct advantages over LASIK including a better corneal biomechanical profile, less dry eyes, lesser induced higher-order aberrations, and absence of flap-related complications. SMILE has recently received FDA approval for the treatment of astigmatism up to 3D in addition to myopia, further enhancing its scope for refractive correction.24,25 The technique has also shown promising results for correction of hyperopia in various clinical trials.26 A resurgence in surface ablation techniques has been witnessed in the recent times owing to the advent of customized corneal ablative treatments, transepithelial ablations, and its utility in performing retreatments following SMILE or LASIK. Topography-guided ablation was first introduced for treatment of irregular corneas; however, it has recently shown promising results in virgin eyes, with studies implying its significant potential for superior visual outcomes, both in terms of visual acuity and quality. Topography-guided ablation for treating myopia with or without astigmatism received US FDA approval in 2016.27 Among the lens-based refractive procedures, posterior chamber phakic IOL implantation remains the most commonly performed surgery today. The newer fourthgeneration ICL (V4c or EVO Visian ICL) with a central 360 microns hole at the center of its optic (KS-AquaPORT) was introduced in 2011 with the aim of preventing secondary cataract and eliminating the need for peripheral iridotomy. Subsequently, the V5 model (EVO+ Visian ICL) with a large diameter optic was introduced in 2016 to alleviate

the night vision symptoms in patients with larger mesopic pupil. The long-term efficacy and safety of ICL implantation has been demonstrated in patients with high-refractive errors unsuitable for corneal procedures as well as low and moderate myopia, making it a feasible alternative to corneal refractive surgeries.28,29

  THE FUTURE OF REFRACTIVE SURGERY The unparalleled safety and efficacy of FS-LASIK and SMILE has led to their soaring popularity over the years; however, certain issues such as iatrogenic ectasia and postoperative dry eye disease remain unresolved. Recent advances in corneal imaging have allowed us to look beyond placido disk technology for preoperative screening of patients at risk to develop postoperative ectasia. While newer technologies such as Scheimpflug technology, corneal biomechanical assessment, and high-resolution optical coherence tomography (OCT) imaging are more sensitive at detecting subclinical keratoconus, the ideal tool that can identify the patients predisposed to postoperative ectasia with optimal sensitivity and specificity continues to elude us. The use of techniques such as machine learning, which rely on artificial intelligence to improve the diagnostic accuracy of subclinical keratoconus in refractive surgery patients, may help us to eliminate iatrogenic ectasia following laser vision correction.30 Postoperative dry eye remains another common side effect observed after LASIK and SMILE, though the incidence is lower with latter. Agents that promote corneal re-innervation may help to mitigate this postoperative adverse effect in the future.31 SMILE is a less invasive alternative to LASIK for laser vision correction while being comparable in terms of efficacy and safety. The need for retreatment following SMILE is considerable and has been reported to be around 2–4.4% in various studies. Retreatment options following SMILE include surface ablation, thin flap LASIK, and converting the cap to flap using the CIRCLE software. Re-SMILE is being investigated as an enhancement option owing to its benefit in preserving the biomechanical strength of the eyes while ensuring patient comfort.32 Corneal laser treatment for correction of hyperopia remains a challenge. The outcomes of LASIK for hyperopic refractive error correction remain confounded with issues such as increased regression due to epithelial remodeling and visual disturbances resulting from the hyperprolate corneal shape, especially in patients with higher magnitudes of error. Hyperopic SMILE is a relatively new procedure that entails the creation of a negative meniscus lenticule, which is then extracted. The lenticular profile for hyperopic SMILE is still evolving and its efficacy and safety are still being investigated in clinical studies.26 Stromal tissue addi­ tive procedures for correction of hyperopia may be more

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SECTION 1: Historical Perspective suitable in patients with higher refractive errors or those unsuitable for corneal ablative procedures. These investi­ gational procedures entail the intrastromal implantation of a SMILE lenticule beneath a flap (lenticule intrastromal keratoplasty) or in a stromal pocket (small incision lenticule intrastromal keratoplasty) for hyperopic correction.33 Presbyopia is another frontier yet to be conquered by refractive surgeons. Presbyopia correction is presently the most dynamic domain in laser vision correction owing to increasing demands of spectacle independence among older population. Presbyopic corneal ablation relies on the creation of a multifocal corneal profile or an increased depth of focus; however, a satisfactory approximation of the dynamic physiological accommodation necessary for countering the presbyopic symptoms is not provided. Furthermore, presbyopic corneal ablation performed in phakic patients predisposes them to unpredictable refractive outcomes following cataract surgery, which may be required subsequently.34 Newer generation multifocal intraocular lenses are a viable alternative for patients requiring con­ comitant cataract surgery. In addition, phakic presbyopic IOLs are a promising addition to the armamentarium of presbyopic surgeries.

  CONCLUSION Rapid strides have been made in the field of refractive surgery over the past few decades, propelled by the increasing demands for precision and safety by surgeons and patients alike. Femtosecond laser-assisted corneal ablative and lenticule extraction procedures continue to enjoy overwhelming popularity for myopic correction. Posterior chamber phakic IOLs have excellent efficacy and safety and are a feasible alternative to LASIK or SMILE across the spectrum of myopic refractive correction. Today, the field of refractive surgery offers us endless opportunities to not just rid the patients of their spectacles but also elevate their quality of vision and life. While newer technology and scientific advances continue to emerge in the field of presbyopia correction, a therapeutic intervention, which can successfully simulate the dynamic features of the natural accommodative process, will be the future of refractive surgery. The evolution of refractive surgery will require to keep pace with the growing demands for superlative vision while ensuring long-term stability, optimal patient comfort, and a favorable side effect profile.

  REFERENCES 1. Aristeidou A, Taniguchi EV, Tsatsos M, Muller R, McAlinden C, Pineda R, et al. The evolution of corneal and refractive surgery with the femtosecond laser. Eye Vis (Lond). 2015; 2:12. 2. Beatty RF, Smith RE. 30-year follow-up of posterior radial keratotomy. Am J Ophthalmol. 1987;103(3 Pt 1):330-1.

3. McAlinden C. Corneal refractive surgery: past to present. Clin Exp Optom. 2012;95(4):386-98. 4. Grady FJ. Hexagonal keratotomy for corneal steepening. Ophthalmic Surg. 1988;19(9):622-3. 5. Mehta KR. Radial keratotomy. Indian J Ophthalmol. 1990; 38(3):124-31. 6. Rowsey JJ, Balyeat HD. Preliminary results and compli­ cations of radial keratotomy. Am J Ophthalmol. 1982;93(4): 437-55. 7. Haw WW, Manche EE. Conductive keratoplasty and laser thermal keratoplasty. Int Ophthalmol Clin. 2002;42(4): 99-106. 8. Bende T, Jean B, Oltrup T. Laser thermal keratoplasty using a continuous wave diode laser. J Refract Surg. 1999;15(2): 154-8. 9. Kohnen T, Koch DD, McDonnell PJ, Menefee RF, Berry MJ. Noncontact holmium:YAG laser thermal keratoplasty to correct hyperopia: 18-month follow-up. Ophthalmologica. 1997;211(5):274-82. 10. Pallikaris IG, Naoumidi TL, Astyrakakis NI. Long-term results of conductive keratoplasty for low to moderate hyperopia. J Cataract Refract Surg. 2005;31(8):1520-9. 11. Trokel SL, Srinivasan R, Braren B. Excimer laser surgery of the cornea. Am J Ophthalmol. 1983;96(6):710-5. 12. Munnerlyn CR, Koons SJ, Marshall J. Photorefractive keratectomy: a technique for laser refractive surgery. J Cataract Refract Surg. 1988;14(1):46-52. 13. 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. 14. Seiler T, Dastjerdi MH. Customized corneal ablation. Curr Opin Ophthalmol. 2002;13(4):256-60. 15. Kim A, Chuck RS. Wavefront-guided customized corneal ablation. Current Opinion Ophthalmol. 2008;19(4):314-20. 16. Pasquali T, Krueger R. Topography-guided laser refractive surgery. Curr Opin Ophthalmol. 2012;23(4):264-8. 17. Ratkay-Traub I, Ferincz IE, Juhasz T, Kurtz RM, Krueger RR. First clinical results with the femtosecond neodymiumglass laser in refractive surgery. J Refract Surg. 2003;19(2): 94-103. 18. Salomão MQ, Wilson SE. Femtosecond laser in laser in situ keratomileusis. J Cataract Refract Surg. 2010;36: 1024-32. 19. Blum M, Kunert K, Schröder M, Sekundo W. Femtosecond lenticule extraction for the correction of myopia: preliminary 6-month results. Graefes Arch Clin Exp Ophthalmol. 2010;248(7):1019-27. 20. Sekundo W, Kunert KS, Blum M. Small incision corneal refractive surgery using the small incision lenticule extraction (SMILE) procedure for the correction of myopia and myopic astigmatism: results of a 6 month prospective study. Br J Ophthalmol. 2011;95(3):335-9. 21. Alio JL, Grzybowski A, El Aswad A, Romaniuk D. Refractive lens exchange. Surv Ophthalmol. 2014;59(6):579-98. 22. Lovisolo CF, Reinstein DZ. Phakic intraocular lenses. Surv Ophthalmol. 2005;50(6):549-87. 23. Güell JL, Morral M, Kook D, Kohnen T. Phakic intraocular lenses part 1: historical overview, current models, selection criteria, and surgical techniques. J Cataract Refract Surg. 2010;36(11):1976-93.

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CHAPTER 1: Evolution of Refractive Surgery 24. Dishler JG, Slade S, Seifert S, Schallhorn SC. Small-Incision Lenticule Extraction (SMILE) for the Correction of Myopia with Astigmatism: Outcomes of the United States Food and Drug Administration Premarket Approval Clinical Trial. Ophthalmology. 2020;127(8):1020-34. 25. Moshirfar M, McCaughey MV, Reinstein DZ, Shah R, Santiago-Caban L, Fenzl CR. Small-incision lenticule extraction. J Cataract Refract Surg. 2015;41(3):652-65. 26. Wang Y, Ma J. Future Developments in SMILE: Higher Degree of Myopia and Hyperopia. Asia Pac J Ophthalmol (Phila). 2019;8(5):412-6. 27. Stulting RD, Fant BS, T-CAT Study Group, Bond W, Chotiner B, Durrie D, et al. Results of topography-guided laser in situ keratomileusis custom ablation treatment with a refractive excimer laser. J Cataract Refract Surg. 2016;42(1):11-8. 28. Packer M. The Implantable Collamer Lens with a central port: review of the literature. Clin Ophthalmol. 2018;12: 2427-38.

29. Packer M. Meta-analysis and review: effectiveness, safety, and central port design of the intraocular collamer lens. Clin Ophthalmol. 2016;10:1059-77. 30. Lopes BT, Ramos IC, Salomão MQ, Guerra FP, Schallhorn SC, Schallhorn JM, et al. Enhanced Tomographic Assessment to Detect Corneal Ectasia Based on Artificial Intelligence. Am J Ophthalmol. 2018;195:223-32. 31. Shtein RM. Post-LASIK dry eye. Expert Rev Ophthalmol. 2011;6(5):575-82. 32. Siedlecki J, Luft N, Priglinger SG, Dirisamer M. Enhancement Options After Myopic Small-Incision Lenticule Extraction (SMILE): A Review. Asia Pac J Ophthalmol (Phila). 2019; 8(5):406-11. 33. Moshirfar M, Bruner CD, Skanchy DF, Shah T. Hyperopic small-incision lenticule extraction. Curr Opin Ophthalmol. 2019;30(4):229-35. 34. Hossain P, Barbara R. The future of refractive surgery: presbyopia treatment, can we dispense with our glasses? Eye (Lond). 2021;35(2):359-61.

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SECTION

2

Preoperative Workup and Decision Making 2. Corneal Wound Healing in Keratorefractive Surgery Sridevi Nair, Harika Regani, Manpreet Kaur, Jeewan S Titiyal

3. Corneal Topography

Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

4. Corneal Biomechanics

Saurabh Verma, Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

5. Aberrometry and Wavefront Analysis

Anand Singh Brar, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal

6. Posterior Segment Screening and Refractive Surgery

Priyanka, Brijesh Takkar, Manpreet Kaur, Jeewan S Titiyal

7. Preoperative Evaluation, Patient Counseling, and Decision Making Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

CHAPTER

2

Corneal Wound Healing in Keratorefractive Surgery Sridevi Nair, Harika Regani, Manpreet Kaur, Jeewan S Titiyal

  INTRODUCTION Corneal wound healing is an important determinant of the visual and anatomical outcomes after keratorefractive surgeries such as photorefractive keratectomy (PRK), laser-assisted in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE). Post-refractive surgery wound healing may be influenced by various factors including the type of surgery, anatomical level of treatment, amount of refractive correction, postoperative inflammatory response and the patient’s genetics. A more comprehen­ sive understanding of this aspect may help us to further improve the refractive predictability and safety of keratorefractive procedures.

  ANATOMY OF THE CORNEA The knowledge of the anatomical structure of cornea is a prerequisite for understanding the corneal wound healing response following refractive surgeries. The corneal epithelium is the uppermost layer having a 5–6-layered struc­ ture. The epithelial basement membrane (EBM) is a highly specialized extracellular matrix (ECM), about 40–60 nm in thick­ness composed of laminins, collagens, heparan sulfate proteoglycans, and nidogens. The Bowman’s layer lies beneath the epithelial layer and is composed of randomly oriented type-1 collagen fibrils. The anterior one-third of stromal layer is made of collagen lamellae, which are oriented in an oblique direction to the surface. The stromal lamellae show extensive branching and are interwoven with each other both horizontally and anteroposteriorly. Posterior stromal lamellae are oriented parallel to the surface and are thicker and wider as compared to the anterior lamellae. Peripheral cornea exhibits more extensive and deeper lamellar inter­ weaving, unlike the central cornea with less interwoven posterior lamellae.1 Keratocytes within the corneal stroma are interspersed between these lamellae. The density of keratocytes is higher in the anterior as compared to the middle and posterior stroma. The cornea is densely packed with nerve fibers that originate from the ophthalmic division of the trigeminal nerve. The nerves enter the corneal limbus in a radial centripetal manner parallel to the collagen

fibers and form bundles in the anterior one-third of stroma. The nerves then run perpendicularly toward the epithelium to form a sub-basal plexus between the basal epithelial cells and Bowman’s membrane. Fine terminals arising from this plexus innervate the epithelial cells.2 The corneal epithelial cells and the keratocytes are the two main cell types involved in wound healing after kerato­ refractive surgeries (Fig. 1). The basic elements of corneal wound healing following keratorefractive procedures are as follows:3 ■■ Epithelial changes including hypertrophy ■■ Keratocytes apoptosis, activation and differentiation into fibroblasts ■■ Conversion of fibroblasts to myofibroblasts ■■ Absorption, remodeling, and deposition of ECM ■■ Formation of hyper- and hypocellular stromal scar.

  CORNEAL WOUND HEALING FOLLOWING SURFACE ABLATION Photorefractive keratectomy remains a popular procedure for correcting myopic and hyperopic refractive errors. The surgery involves the removal of corneal epithelium followed by excimer laser ablation of the stroma.

Epithelial Changes The damage to the corneal epithelial cells initiates the wound healing response by inducing apoptosis of the stromal keratocytes lying beneath it (Flowchart 1). Epithelial cells migrate and proliferate from the limbus to reestablish the layer within the next 3–5 days. The regenerated epithelial layer following PRK is about 20% thicker than preoperative levels and its stabilization may take up to 1 year. This is in contrast to the epithelial thickening observed after LASIK, which stabilizes earlier, in about a month. The thickening of the epithelium is more in areas with deeper stromal ablation and is probably a biological response to restore the original curvature of the cornea and smoothen out the stromal surface irregularities created by excimer laser ablation. The increase in epithelial thick­ ness is associated with myopic regression observed after

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Fig. 1: Anatomy of cornea and elements of corneal wound healing. (EBM: epithelial basement membrane; ECM: extracellular matrix; PRK: photorefractive keratectomy; TGF-b: transforming growth factor-beta) Flowchart 1: Corneal wound healing after keratorefractive surgeries.

(EBM: epithelial basement membrane; ECM: extracellular matrix; LASIK: laser-assisted in situ keratomileusis; DLK: diffuse lamellar keratitis; MMC: mitomycin C)

the procedure.4 Various factors have been attributed for epithelial thickening after keratorefractive surgeries including the elongation of basal epithelial cells, thickening of superficial epithelial cells, absence of the mechanical

influence of the upper lid on the epithelial layer owing to the corneal flattening, and the abrupt curvature changes observed with smaller optical zone and deeper ablations.

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CHAPTER 2: Corneal Wound Healing in Keratorefractive Surgery

Stromal Changes Stromal keratocytes are instrumental in facilitating corneal wound healing after PRK. They play an important role in stromal remodeling and EBM deposition. Epithelial cell damage leads to release of pro-apoptotic mediators that trigger an initial wave of apoptosis followed by necrosis of stromal keratocytes in the involved region. An influx of inflammatory cells including monocytes, polymorphonuclear cells, fibrocytes, and other bone marrow-derived cells from the limbal vessels is noted immediately after the ablation. A compromised epithelial barrier potentiates the effects of cytokines such as inter­ leukin 1 (IL-1), tumor necrosis factor (TNF), fibroblast growth factor (FGF), platelet-derived growth factor (PDGF), epidermal growth factor (EGF), transforming growth factorbeta (TGF-b) derived from epithelial cells, lacrimal glands, and bone marrow-derived cells, by providing an unhindered access to the stroma. Following the initial stage of apoptosis, surviving keratocytes from the adjacent areas proliferate, transform into fibroblasts, and repopulate the stroma under the influence of these cytokines. The stromal fibroblasts actively participate in the process of repair by secreting ECM components such as fibronectin, proteinases, and integrins. During the subsequent weeks, TGF-b facilitates the conversion of some of the stromal fibroblasts into myofibroblasts. These cells are characterized by the expres­ sion of smooth muscle α-actin and play a role in the reparative phase by facilitating the development of fibrotic tissue and deposition of disorganized collagen and glycosaminoglycans (GAGs). Myofibroblasts may also be derived from bone marrow derived cells sequestered from limbal blood vessels. Myofibroblasts are the main effectors of the corneal fibrotic response. A transient reduction in the corneal transparency mediated by stromal hypercellu­ larity, decreased intracellular crystallins in the fibroblasts, and the deposition of disorganized components of the matrix are observed during this phase. Deeper stromal ablation for higher myopic corrections has been associated with greater keratocyte apoptosis and myofibroblast cell conversion.5-7 Epithelial basement membrane regeneration is an important component of corneal remodeling. The regularity of the stromal surface is an important factor, which influences its assembly. Stromal keratocytes, fibroblasts derived from keratocytes, and epithelial cells mainly contribute to the secre­tion of EBM. Complete restoration of basement membrane is essential to stem the inflow of factors such as TGF-β and PDGF and promote the gradual apoptosis and disappearance of the myofibroblasts. This heralds the phase of corneal remodeling. The normal transparency of the cornea is restored during the remodeling phase. It is characterized by a prolonged process of synthesis, degradation, and resynthesis, which entails the regularization of the diameter of the collagen fibrils and a spatial reorganization of stromal

fibrils. During the remodeling process, collagen fibril size becomes progressively more regular and attains a more orderly arrangement.8 The failure of the EBM to regenerate properly may lead to the persistent dissemination of TGF and PDGF into the anterior stroma, resulting in the develop­ ment of opacity generating myofibroblasts, which may contribute to late postoperative corneal haze. Since anterior stromal keratocytes secrete components of EBM and play an important role in its regeneration, deeper stromal ablations with greater associated keratocyte apoptosis could lead to slower regeneration of EBM.9

Corneal Nerve Regeneration Excimer laser ablation during PRK sever the nerves at the sub-basal plexus and the superficial anterior stromal level. The advent of confocal microscopy has allowed us to qualitatively and quantitatively study in vivo corneal nerve regeneration after keratorefractive surgeries. New neurites have been shown to arise from the severed endings on confocal microscopy as early as the first postoperative week following PRK. Though about 50% of subepithelial nerve regeneration is completed by 6–8 months, structural and morphological changes may be observed on confocal microscopy for up to an year after surgery (Figs. 2A to F).10 The sub-basal density of nerve fibers approaches the preoperative levels at about 2 years postoperatively; the degree and rate of corneal nerve regeneration are inversely proportional to the amount of refractive correction.11,12 While corneal stromal fibroblasts exert neurotrophic effects and promote nerve regeneration, an increased fibrotic response during the corneal wound healing may lead to delayed reinnervation due to the inhibitory effect of myofibroblasts on corneal nerve regeneration.13,14

  CORNEAL WOUND HEALING FOLLOWING LASIK The corneal wound healing response and the asso­ciated fibrotic response are usually less pronounced after LASIK as compared with PRK. LASIK, being a lamellar procedure, does not entail the disruption of the central epithelium or the EBM. The complex epithelial-stromal interactions, fibroblast generation, and myofibroblast-related haze that are observed with PRK are essentially limited to the flap edge area after LASIK. This is clinically characterized by a circumferential haze at the flap edge (Fig. 3).8 The lamellar cut created by a microkeratome or femto­ second (FS) laser induces localized keratocyte apoptosis and necrosis at the site of epithelial injury and just in the vicinity of the lamellar interface. Localized apoptosis and necrosis observed around the interface by the microkera­ tome blade are due to the tracking of epithelial debris with IL-1 into the interface.15 Cytokines from the injured peripheral epithelium could also diffuse along the lamellar interface and into the central stroma. This may be important

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SECTION 2: Preoperative Workup and Decision Making

A

B

C

D

E

F

Figs. 2A to F: Sub-basal corneal nerve fiber layer regeneration after photorefractive keratectomy (PRK), laser-assisted in situ keratomileusis (LASIK), and small incision lenticule extraction (SMILE): (A) Preoperative sub-basal corneal nerve fiber layer in a patient undergoing PRK; (B) Preoperative sub-basal corneal nerve fiber layer in a patient undergoing LASIK; (C) Preoperative sub-basal corneal nerve fiber layer in a patient undergoing SMILE; (D) Postoperative sub-basal corneal nerve fiber layer at 1 year after PRK; (E) Postoperative sub-basal corneal nerve fiber layer at 1 year after LASIK; (F) Postoperative sub-basal corneal nerve fiber layer at 1 year after SMILE.

Fig. 3: Circumferential haze at flap edge after laser-assisted in situ keratomileusis (red arrows—fibrosed flap edge).

since it influences the localization of other events such as proximity between myofibroblasts and wound healing fibroblasts that produce hepatocyte growth factor (HGF), which tends to promote epithelial hyperplasia. This is one of the mechanisms of post-LASIK regression. The wound healing response following FS-LASIK differs from that observed with microkeratome LASIK. The older,

high-energy, low-frequency FS laser systems resulted in increased stromal keratocyte cell death. The cell death in these cases was mediated by necrosis rather than apoptosis and incited a greater inflammatory and fibrotic response as compared to microkeratome LASIK. Stromal nerve bundles and sub-basal nerve plexus (at flap edge) are transected during LASIK owing to lamellar flap creation. In addition, the early postoperative period is marked by degeneration of the remaining sub-basal nerve plexus within the flap. Confocal microscopy has demons­ trated intense denervation for up to 3 months following surgery. The nerve regeneration commences at the flap edge and progresses in a centripetal manner towards the center. The sub-basal nerve fiber regeneration is slower as com­ pared to PRK, taking up to 5 years to reach the preoperative levels. Also, the nerve fibers regenerating from the residual stromal bed are not capable of crossing over the interface and connecting to the fibers within the flap.11

  CORNEAL WOUND HEALING FOLLOWING SMILE Corneal wound healing following SMILE has been less extensively studied than LASIK or PRK. Current evidence on the subject is derived from animal or human ex vivo studies

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CHAPTER 2: Corneal Wound Healing in Keratorefractive Surgery and is suggestive of a less robust wound healing response as demonstrated by lesser keratocyte apoptosis, prolifera­ tion, and inflammation compared with FS-LASIK. Unlike FS-LASIK and PRK, SMILE does not employ excimer laser or require the creation of a lamellar corneal flap. This results in less trauma to the epithelial cells, reduced stromal tissue damage and cytokine release, which may contribute to the significantly milder healing response after SMILE. There is less damage to stromal nerves, better preservation of the sub-basal nerve plexus, and faster nerve recovery compared to LASIK.16,17

  CLINICAL RELEVANCE OF CORNEAL WOUND HEALING AFTER KERATOREFRACTIVE SURGERY Post-refractive surgery regression, corneal haze, and dry eye are primarily influenced by corneal wound healing. A more severe wound healing response is associated with a higher incidence of regression and haze. Postoperative haze and regression are higher in cases undergoing PRK and higher refractive error corrections. Postoperative dry eye has been reported to be more severe after LASIK than PRK or SMILE. Table 1 compares the corneal wound healing after LASIK and PRK with emphasis on its clinical relevance.

Refractive Regression Postoperative regression is the gradual complete or partial loss of the attempted refractive correction following a keratorefractive procedure. The reported incidence varies from 6.7 to 13.8% after PRK and 3 to 11.9% after LASIK.8 Postoperative regression is attributed to differential changes in the thickness of the cornea due to a combination of stromal remodeling and epithelial hyperplasia. These processes predominate in regions of greater tissue removal leading to relative ‘‘reversal” of the initial correction. The relative contributions of the stroma and the epithelium in regression appear to be a function of postoperative time, type of refractive surgery, and type of refractive

error in addition to other factors. The more robust wound healing response observed with deeper stromal ablations and PRK may lead to a higher associated potential for regression.8,18

Postoperative Haze Corneal haze following keratorefractive surgery is charac­ terized by a reduction in corneal transparency. Two types of postoperative haze are observed following PRK. The first is the transient, clinically insignificant corneal haze seen during the initial weeks of corneal repair, mediated by the fibroblasts, stromal hypercellularity and disorganized deposition of stromal matrix components. This haze gradually clears up within a year of surgery during the remodeling phase that follows. The second is the late haze, which usually develops around 2–3 months, peaks at about 6 months, and may persist for more than 3 years after surgery. This haze can cause clinical symptoms such as decreased visual acuity, glare, or haloes. Myofibroblasts derived from keratocytes and bone marrow-derived precursor cells as well as the opaque ECM secreted by these cells are thought to be responsible for late haze after PRK. Risk factors for development of increased haze include higher refractive correction (>6D myopia), stromal surface irregularity associated with persistent defects in EBM, delayed healing of epithelial defect, ultraviolet (UV) light exposure, decreased tear production, use of older excimer lasers with larger spot sizes, and certain genetic predispositions.9,19 The use of a rotating brush to remove the epithelium as compared to a blade has been associated with increased cellular infiltrates postoperatively, owing to increased release of interleukins into the stroma. 6 Studies have reported a lesser incidence of postoperative haze with the use of excimer laser for epithelial ablation (in transepithelial PRK) as compared to mechanical debridement.20 The reported incidence of postoperative haze and regression after LASIK is much lower owing to the pre­serva­ tion of the central epithelium and basement membrane.

TABLE 1: Comparative evaluation of corneal wound healing response after laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK). Corneal wound healing

PRK

LASIK

Clinical significance

Epithelial healing

Increased damage to epithelial cells, EBM, and keratocytes; associated with increased inflammatory mediator release

Lesser damage to epithelial cells, EBM, and keratocytes

Increased thickening of the regenerated epithelial layer after PRK, leading to increased regression

Stromal healing and remodeling

Increased keratocyte damage, apoptosis, inflammatory mediator release, and myofibroblast conversion

Lesser keratocyte damage, apoptosis, and activation

Increased ECM deposition leading to higher incidence of stromal haze and regression after PRK

Nerve regeneration

Lesser corneal nerve damage; limited to sub-basal plexus and superficial stromal bundles

More extensive nerve damage involving the sub-basal plexus (at flap edge) and anterior stromal nerve bundles

Higher incidence of postoperative dry eye with LASIK due to increased damage and slower regeneration of corneal nerves

(EBM: epithelial basement membrane; ECM: extracellular matrix)

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SECTION 2: Preoperative Workup and Decision Making However, direct implantation or ingrowth of epithelium into the lamellar interface provides a local source of epithelial cytokines and can result in interface haze, regression, and diffuse lamellar keratitis (DLK).21 An increased risk of haze and regression has also been observed with thin flaps ( 47.2 D •• I-S > 1.4 D

Cone location magnitude index (CLMI)

Difference between the average curvature of the 8 mm zone and the steepest 2 mm zone

•• PPK > 20% suggestive of KC suspect •• PPK > 45% suggestive of keratoconus

KISA index (Rabinowitz and Rasheed)

KISA% = K × (I-S) × AST × SRAX × 0.3

•• 60–100 KC suspect •• >100 keratoconus

Keratoconus prediction index (KPI)

Composite index based on Sim K1, Sim K2, SAI, DSI, OSI, CSI, IAI, and AA

0.23

Keratoconus classification index (KCI)

Combines KPI with DSI, OSI, CSI, and Sim K2 indices within a decision tree

>100 keratoconus

Keratoconus severity index (KSI)

Obtained by a combination of network model and decision tree analysis

•• >0.15 keratoconus suspect •• >0.30 keratoconus

(PPK: percent probability of keratoconus)

  ELEVATION-BASED TOPOGRAPHY SYSTEMS Elevation-based topographers or “tomographers” refer to devices, which measure the shape of the cornea in the true sense by measuring the X, Y, and Z coordinates. This is in contrast to the conventional placido-based systems, which measure X and Y coordinates and derive the third coordinate from these two based on certain assumptions.6

Concept of Best-Fit Sphere Elevation-based topography systems reconstruct the corneal shape in three dimensions. The elevation of the cornea or the “Z coordinate” is calculated in context to a reference shape known as the “best-fit sphere (BFS)” (Fig. 6). The BFS may be defined as the algebraic sum of the flatter and steeper meridians of the cornea. Elevation maps depict the difference between the actual corneal curvature and the BFS in microns.6

Fig. 6: Schematic depiction of the flatter and steeper meridian with respect to the best-fit sphere (BFS).

The BFS is usually calculated for the central 8–9 mm zone of the cornea, as it allows for ease of under­ standing and analysis of the elevation maps. A larger zone of >9 mm will result in a flatter BFS, which may lead to exaggeration of normal curvature. Smaller zones of 7.35 mm/46 D

Radius of posterior corneal curvature

>6.5 mm/52 D

BFS power on the posterior profile

>55 D

Mean keratometric power

>46 D

Ratio of radii of the anterior BFS and posterior BFS (Efkarpides criteria)

>1.23; value >1.27 sug­ gestive of keratoconus

Posterior elevation difference from BFS

>40 microns

Anterior elevation difference from BFS

>25 microns

Relative difference between the highest and lowest point on posterior elevation map (Roush criterion)

>100 microns

Thinnest pachymetry (especially if displaced inferotemporally)

100 microns

Difference between the thinnest and central pachymetry

>30 microns

Distance between thinnest point and the center

>2.5 mm

Power map

•• Broken bow-tie or lazy C on axial map with astigmatism axis showing >20° devia­ tion from straight line •• Irregularity at central 3-mm zone >1.5 D •• Irregularity at central 5-mm zone >2 D

Change in power in the central 3-mm zone

>3 D

Difference of astigmatism between two eyes

>1 D

(BFS: best-fit sphere; OZ: optical zone)

pupil camera aids in controlling fixation and detecting any residual eye movements for alignment compensation. The camera acquires data from anterior and posterior corneal surfaces, iris, and lens.11

Evaluating Pentacam Maps The quality of data and color scale should be determined before analyzing Pentacam maps. Quality of captured data may be assessed by Qs or the Quality specification. An unsatisfactory Qs is indicative of missing or extrapolated data. Choosing the color scale and color bar is important, as the color scale determines the visual appearance pattern of the map, which is often the first parameter to be noted during screening. The color scales may be absolute or normalized (relative). Different color bars are available in Pentacam with their own distinctive color palettes, including the Belin Intuitive color bar, Ambrósio 2 color bar, OCULUS (European) color scheme, American color bar, Holladay primary color bar, and Smolek-Klyce classic

A

B

Figs. 8A and B: Common color scales used in Pentacam: (A) Smolek/ Klyce absolute color scale; (B) Belin intuitive relative scale at 2.5 microns steps.

absolute color bar (Figs. 8A and B). For elevation maps, Belin intuitive color bar with an elevation scale of ±75 microns is recommended with a total of 61 shades. Q-value represents the asphericity of the anterior corneal surface ideally measured over the central 6 mm. Normal values lie between 0 and −1, while values 0 are suggestive of oblate cornea like that seen post-photoablation or post-radial keratotomy. Pentacam generates topographic, topometric, and Belin-Ambrósio display maps, which may be evaluated to obtain a comprehensive overview of corneal shape.12-14 The 4-map refractive display is commonly analyzed first during refractive surgery screening. It consists of four maps similar to Orbscan, depicting the axial or sagittal curvature, anterior elevation, posterior elevation, and pachymetry (Figs. 9 to 11). In addition, it also provides information regarding corneal asphericity, corneal volume, anterior chamber volume, angle and depth, pupil diameter, and lens thickness: ■■ Anterior curvature map: Sagittal or the axial map is most commonly used for refractive surgery screening. In this map, one should look for an asymmetric bowtie pattern with attention to the I-S asymmetry (cutoff 1.4 D) or S-I asymmetry (cutoff 2.5 D) with or without skewing of the radial axis (cutoff 22°). Other suspicious patterns include round, oval, irregular pattern, butterfly pattern, claw pattern, smiling face pattern, or vertical D pattern. ■■ Anterior and posterior elevation maps: A BFS of 8-mm diameter is the preferred reference shape to evaluate patients before undergoing refractive surgery. The size of the BFS is important, as the anterior and posterior elevation cut off values differ based on it. Table 4 details the values suggested in the manufacturer’s Pentacam Interpretation Guidelines. Elevation maps are considered more sensitive than curvature maps when screening for the presence of ectatic areas or cones. ■■ Pachymetry map: It provides a global overview of the corneal thickness at different points. Usually, the

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SECTION 2: Preoperative Workup and Decision Making

Fig. 9: The 4-map refractive display on a Pentacam with description of the indices along with normal range of values.

absolute color scale is used for pachymetry maps with 10-µ steps, measuring a range of corneal thickness from 300 to 900 microns. Thinnest location (TL) in a normal cornea ideally corresponds to the corneal apex and an increased vertical displacement between the two is considered suspicious. Tables 5 and 6 detail the normative values for the anterior, posterior elevation,15 and pachymetry16 in the normal population. The topometric display is based on the anterior curvature values and is less commonly used for refractive screening. The various indices provided by this display to detect ectasia include the Index of Surface Variance (ISV), Index of Vertical Asymmetry (IVA), Keratoconus Index (KI), Center Keratoconus Index (CKI), Index of Height Asymmetry (IHA), and Index of Height Decentration (IHD) (Table 7).12,13 The Belin/Ambrósio-enhanced ectasia display (BAD) provides a comprehensive evaluation of the cornea by combining the pachymetry-derived graphs and indices along with the elevation-based parameters (Table 8). It has >90% sensitivity and specificity for detecting ectasia and is the most useful display for refractive screening (Fig. 12).13,14

■■ Concept of enhanced best-fit sphere: The BAD III display

is based on the concept of “enhanced best-fit sphere” rather than the conventional BFS. The enhanced BFS is derived from the data within the central 8-mm corneal zone, after excluding the data from the 3.5–4-mm zone around the thinnest corneal point (Fig. 13). The rationale for the enhanced reference surface is that the con­ ventional BFS incorporates data from the normal as well as the steep parts in cases with an abnormal cornea with ectasia. This results in a steepening effect on the reference BFS, which may in turn lead to masking of the steep areas in the patient’s cornea and decrease the sensitivity for detecting subtle cases of ectasia. The enhanced reference surface resembles the patient’s normal cornea and is thus able to highlight the ectatic areas more efficiently. The enhanced BFS and the conventional BFS will be similar in a normal cornea; however, enhanced BFS will more effectively highlight an ectatic cornea. ■■ Elevation maps: The left half of the BAD III display shows the anterior and the posterior elevation data, each with 3 maps (Fig. 12). The topmost maps depict the anterior (left side) and posterior (right side) elevation maps with the conventional BFS as the reference surface.

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CHAPTER 3: Corneal Topography

Fig. 10: Regular astigmatism on the 4-map refractive display: Elevation map shows normal elevation values toward the center with the raised areas seen at the periphery.

Fig. 11: True corneal ectasia on the 4-map refractive display—raised elevation area lies in the central area corresponding to the thinnest location.

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SECTION 2: Preoperative Workup and Decision Making TABLE 4: Cut-off values for anterior and posterior elevation based on best-fit sphere (BFS) size as per manufacturer manual on Pentacam. Normal

Suspicious

Keratoconus

Elevation parameter

BFS—9 mm

BFS—8 mm

BFS—9 mm

BFS—8 mm

BFS—9 mm

Anterior elevation

15 microns

Posterior elevation

16 microns

Above values pertain to elevation in the central and paracentral regions in an island pattern.

TABLE 5: Mean anterior and posterior elevation values in myopes and hyperopes in the normal population.

TABLE 8: Interpreting Belin-Ambrósio enhanced ectasia display. BAD display

Maps, graphs, and indices

Interpretation

Elevation display (6 maps)

Top: Anterior and posterior elevation maps using BFS

Based on conventional best-fit sphere as reference surface

10.6 ± 5.7 microns

Middle: Anterior and posterior elevation maps using enhanced BFS

Based on enhanced bestfit sphere as reference surface

TABLE 6: Mean values of various corneal thickness parameters in the normal population.

Bottom: Difference between elevation maps using BFS and enhanced BFS

Three colors: 1.  Green: Normal 2.  Yellow: Suspect/ borderline 3.  Red: Ectasia

Pachymetry map

•• Thickness of apex and thinnest point •• Displacement and direction of thinnest point from apex

•• Corneal thickness spatial profile •• Percentage thickness increase

•• Graphical representation of change in corneal thickness from thinnest point to periphery •• Red slope should lie within 2 SD (black lines)

Pachymetric progression index (PPI) and the Ambrósio relational thickness (ART)

•• Pachymetry indices to depict the change in corneal thickness from thinnest point to periphery •• Normal PPI average < 1.2

Parameter

Myopes (mean ± SD)

Hyperopes (mean ± SD)

Anterior elevation (apex)

1.6 ± 1.3 microns

0.4 ± 1.9 microns

Anterior elevation (thinnest)

1.7 ± 2.0 microns

−0.1 ± 2. 2 microns

Posterior elevation (apex)

0.8 ± 3.0 microns

5.7 ± 3.6 microns

Posterior elevation (thinnest) 3.6 ± 4.1 microns

Corneal thickness parameter

Corneal thickness in normal population in microns (mean ± SD)

Corneal apex

539.3 ± 36.8

Thinnest pachymetry

536.1 ± 37.12

Pupillary center

538.8 ± 36.9

Apex—thinnest

2.99 ± 4.34

Apex difference between two eyes

8.8 ± 7.2

Thinnest difference between two eyes

9.0 ± 8.3

Pachymetric data

TABLE 7: Topometric indices on Pentacam along with their cutoff values.

Pentacam topometric index

Cut-off sugges­tive of Pathological abnormal value value

Index of surface variance (ISV)

37

41

Index of vertical asymmetry (IVA)

0.28

0.32

Index of height asymmetry (IHA)

19

21

Index of height decentration (IHD)

0.014

0.016

Minimum radius of curvature (R-min) 1.03

Keratoconus index (KI)

>1.07

The middle two maps depict the anterior and posterior elevation data with enhanced BFS as the reference surface. The bottom two maps are difference maps, depicting the relative change from the baseline elevation maps using BFS to that of the elevation maps using enhanced BFS.

Deviation index (D value)

Based on five parameters: •• 2.6 SD—red (ectasia/ 2. Db (back): Change in abnormal) posterior elevation from standard to enhanced reference surface 3. Dt: Corneal thickness at the thinnest point 4. Dp: Pachymetric progression 5. Da: Displacement of the thinnest point

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CHAPTER 3: Corneal Topography

Fig. 12: Belin–Ambrósio enhanced ectasia display of a normal cornea.

Fig. 13: Enhanced best-fit sphere (BFS): The upper image depicts a conventional BFS while the lower depicts an enhanced BFS excluding the central 4 mm zone of abnormality, thus accentuating the area of cone.



The difference map has only three colors, each depicting the magnitude of change between the first two maps. For anterior elevation difference maps, green signifies 7 microns difference between the maps based on conventional or enhanced BFS. Similarly, for posterior elevation difference maps, green signifies 16 microns difference between the maps based

on conventional or enhanced BFS. Green indicates normal corneas, yellow indicates suspect or borderline cases, and red indicates ectasia. ■■ Pachymetric evaluation: The pachymetric data on the right-hand side of BAD display includes the pachy­ metry map, two graphs, and the pachymetric indices. The pachymetry map identifies the corneal thickness at apex, the thinnest point and the location, direction and distance of the thinnest point relative to the apex. The progression of corneal thickness is displayed in two graphs—the corneal thickness spatial profile (CTSP) and the percentage thickness increase (PTI) (Figs. 14 and 15): zz The corneal thickness spatial profile (CTSP) depicts the change in corneal thickness (or increase) from the thinnest point outward. The average values of 22 concentric rings separated by 0.4-mm steps are used to depict the CTSP. zz The percentage thickness increase (PTI) is calculated as (corneal thickness at x-TP)/TP. Corneal thickness at “x” is the mean thickness in the ring (x) centered on the thinnest point and increases as we move out. TP is the thickness of the thinnest point. Both PTI and CTSP are represented in graphical manner. The 2 standard deviations (SD) and average value for normal population are depicted by black

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SECTION 2: Preoperative Workup and Decision Making

Fig. 14: The corneal thickness spatial profile (CTSP) and percentage thickness increase (PTI) display of a normal cornea: The patient’s graph lies within the two standard deviations of the normal population.

Fig. 15: The corneal thickness spatial profile (CTSP) and percentage thickness increase (PTI) display of a keratoconus patient: The patient’s graph lies outside the two-standard deviations within the 6-mm zone.

dotted lines and the patient’s data is depicted as a red line. Normally, the red slope should lie between the upper and lower black ones. Abnormal patterns

include a “Quick slope” where the red line ventures outside the two SD limit before the 6-mm zone (Figs. 14 and 15).17

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CHAPTER 3: Corneal Topography The pachymetric indices include the pachymetric progression index (PPI) and the Ambrósio relational thickness (ART): zz The pachymetric progression index (PPI) describes the increase in the corneal thickness from the thinnest point along each hemi-meridian with reference to a mean normal population base. The average of all meridians is the “PPI-Avg”, while the meridians with the maximum and minimum values are repre­ sented as “PPI-Max” and “PPI-Min”, respectively. The higher the value of the index, more accentuated is the increase in corneal thickness from TP outward. The normal “PPI-Avg” values are usually below 1.2, but there may be an overlap between the normal and abnormal corneas with about 7% of the normal corneas having a value between 1.2 and 1.8, and 10% of the keratoconic eyes having a “PPI-Avg” value of less than 1.2. zz The Ambrósio relational thickness: It is the ratio between single point metrics (TP) and PPIs. ART-Max is defined as TP/PPI-Max, ART-Avg as TP/PPI-Avg, and ART-Min as TP/PPI-Min. Table 9 gives the cut-off values of ART for detecting keratoconus and ectasia susceptibility.14,18 ART-Avg and ART-Max have been found to be superior to TP and CCT for detecting ectasia, and PPI-Max, PPI-Avg, and ART-Max have the best sensitivity for detecting subclinical keratoconus.18,19 ■■ Belin-Ambrósio deviation index: The Belin-Ambrósio deviation index or D index is calculated from five parameters provided in a BAD display, namely the Df, Db, Dt, Dp, and Da: 1. Df (front): Change in anterior elevation from standard to enhanced reference surface. 2. Db (back): Change in posterior elevation from standard to enhanced reference surface. 3. Dt: Corneal thickness at the thinnest point. 4. Dp: Pachymetric progression. 5. Da: Displacement of the thinnest point. Each of these values depicted in the numerical form gives the standard deviation for that parameter from the population mean. The final D value represents the overall reading of the five parameters and is calculated using regression analysis. The values are color coded with 2.6 SD depicted in red suggesting abnormality. A BAD-D value of more than 2.11 had a sensitivity and specificity of 99.59% and 100% respectively for detecting keratoconus, while a value of >1.22 had a sensitivity of 93.62% and specificity of 94.56%.8

  COLOR LED RAY TRACING TOPOGRAPHY Cassini (i-Optics, The Hague, The Netherlands) is a corneal topography device based on the principle of color LED ray tracing. Topography systems based on color-coded specular reflection utilize a spot pattern made of 679 light emitting diode (LED) spots projected on to the cornea. The feature points in the reflected image of these spots are processed by an image processing software, which then accounts for the deformation on the corneal surface irregularities based on the point-to-point reconstruction of these images. They overcome the limitations of the placido-based topo­ graphers, which tend to neglect skew-ray reflections and can be erroneous in assessing abrupt corneal curvature changes. They have been found to be precise in measuring even irregular corneas with comparable results to placidobased and elevation-based systems.20

  CONCLUSION Screening patients for refractive surgery is a compre­ hensive task encompassing the use of various investigative modalities such as topography, tomography, anterior segment OCT (for epithelial thickness mapping), and corneal biomechanical parameter evaluation in addition to a thorough clinical work-up. The primary objective of corneal topography in patients planned for refractive surgery is to screen for the presence of subclinical or forme fruste keratoconus in order to prevent postoperative ectasia. We have progressed from simple keratometry devices to sophisticated elevation-based topography systems with automated predictive algorithms and development of various predictive indices. The newer topography systems enable measurement of both the anterior and posterior corneal curvatures, allow assessment of true corneal elevation, and help in a three-dimensional reconstruction of the anterior segment. The future lies in integrating artificial intelligence strategies that will efficiently take into account both the pre-existing risk assessed by corneal topography and the magnitude of anticipated biomechanical change due to corneal ablative treatment, and will help us to screen patients in a more efficient and accurate manner.

  REFERENCES 1. Gutmark R, Guyton DL. Origins of the keratometer and its evolving role in ophthalmology. Surv Ophthalmol. 2010; 55(5):481-97.

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SECTION 2: Preoperative Workup and Decision Making 2. Rabinowitz YS, McDonnell PJ. Computer-assisted corneal topography in keratoconus. Refract Corneal Surg. 1989; 5(6):400-8. 3. Maeda N, Klyce SD, Smolek MK, Thompson HW. Automated keratoconus screening with corneal topography analysis. Invest Ophthalmol Vis Sci. 1994;35:2749-57. 4. Rabinowitz YS, Rasheed K. KISA% index: A quantitative video­ keratography algorithm embodying minimal topographic criteria for diagnosing keratoconus. J Cataract Refract Surg. 1999;25(10):1327-35. 5. Mahmoud AM, Roberts CJ, Lembach RG, Twa MD, Herderick EE, McMahon TT; CLEK Study Group. CLMI The Cone Location and Magnitude Index. Cornea. 2008;27(4): 480-7. 6. Cavas-Martínez F, De la Cruz Sánchez E, Nieto Martínez J, Fernández Cañavate FJ, Fernández-Pacheco DG. Corneal topography in keratoconus: state of the art. Eye and Vis (Lond). 2016;3:5. 7. Belin MW, Khachikian SS. An introduction to understanding elevation-based topography: how elevation data are dis­ played—a review. Clin Exp Ophthalmol. 2009;37(1):14-29. 8. Ambrósio R, Faria-Correia F, Ramos I, Valbon BF, Lopes B, Daniela J, et al. Enhanced Screening for Ectasia Susceptibility Among Refractive Candidates: The Role of Corneal Tomo­ graphy and Biomechanics. Curr Ophthalmol Rep. 2013;1:28-38. 9. Cairns G, McGhee CNJ. Orbscan computerized topography: Attributes, applications, and limitations. J Cataract Refract Surg. 2005;31(1):205-20. 10. Jafarinasab MR, Shirzadeh E, Feizi S, Karimian F, Akaberi A, Hasanpour H. Sensitivity and specificity of posterior and anterior corneal elevation measured by orbscan in diagnosis of clinical and subclinical keratoconus. J Ophthalmic Vis Res. 2015;10(1):10-5. 11. Oliveira CM, Ribeiro C, Franco S. Corneal imaging with slitscanning and Scheimpflug imaging techniques. Clin Exp Optom. 2011;94(1):33-42.

12. John AK, Asimellis G. Revisiting keratoconus diagnosis and progression classification based on evaluation of corneal asymmetry indices, derived from Scheimpflug imaging in keratoconic and suspect cases. Clin Ophthalmol. 2013;7:1539-48. 13. Hashemi H, Beiranvand A, Yekta A, Maleki A, Yazdani N, Khabazkhoob M. Pentacam top indices for diagnosing subclinical and definite keratoconus. J Curr Ophthalmol. 2016;28(1):21-6. 14. Ambrósio R, Valbon BF, Faria-Correia F, Ramos I, Luz A. Scheimpflug imaging for laser refractive surgery. Curr Opin Ophthalmol. 2013;24(4):310-20. 15. Kim JT, Cortese M, Belin MW, Ambrósio R Jr, Khachikian SS. Tomographic normal values for corneal elevation and pachymetry in a hyperopic population. J Clinic Experiment Ophthalmol. 201;2:130. 16. Khachikian SS, Belin MW, Ciolino JB. Intrasubject corneal thickness asymmetry. J Refract Surg. 2008;24(6): 606-9. 17. Ambrósio R Jr, Alonso RS, Luz A, Coca Velarde LG. Cornealthickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus. J Cataract Refract Surg. 2006;32(11):1851-9. 18. Ambrósio R Jr, Caiado AL, Guerra FP, Louzada R, Sinha RA, Luz A, et al. Novel pachymetric parameters based on corneal tomography for diagnosing keratoconus. J Refract Surg. 2011; 27(10):753-8. 19. Ruiseñor Vázquez PR, Galletti JD, Minguez N, Delrivo M, Fuentes Bonthoux F, Pförtner T, et al. Pentacam Scheimpflug tomography findings in topographically normal patients and subclinical keratoconus cases. Am J Ophthalmol. 2014; 158(1):32-40. 20. Kanellopoulos AJ, Asimellis G. Color light-emitting diode reaction topography: validation of keratometric repeatability in a large sample of wide cylindrical-range corneas. Clin Ophthalmol. 2015;9:245-52,256.

CHAPTER

4

Corneal Biomechanics Saurabh Verma, Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

  INTRODUCTION The earliest characterization of ocular biomechanics dates back to 1937 when Friedenwald defined the ocular rigidity coefficient. Ocular rigidity refers to the mathematical relationship between volume tended by the eyes and pres­ sure within it, and primarily reflects the elastic properties of the ocular coats.1 Structural properties of cornea are central to its role as a resilient barrier to external injury. It affects the accuracy of intraocular pressure (IOP) assessment and may be implicated in the pathogenesis of various diseases including glaucoma, corneal ectasia, age-related macular degeneration, and uveitis. Corneal rigidity provides an indirect measure of the ocular rigidity and may be altered after corneal based refractive surgeries. We herein evaluate the impact of refractive surgeries on corneal biomechanics and its clinical significance.

  CORNEAL BIOMECHANICS AND REFRACTIVE SURGERY Corneal biomechanical properties including density, geometry, elasticity, viscosity, and viscoelasticity deter­ mine its response to external stress. Human cornea behaves as a viscoelastic substance and exhibits elements of both viscosity and elasticity. This implies that tissue deformity or strain is nonlinear, such that higher levels of stress are associated with a greater tissue stiffness or elastic modulus. Stress–strain response is also a function of strain rate. Faster strain rate or quicker tissue stretching produces a stiffer response.2 Since cornea is the principal refractive surface of the eye, the biological or mechanical response to a stress such as corneal refractive surgery can significantly alter its optical performance. Postoperative variability in outcomes including discrepancies between the intended and achieved refractive correction and development of post-laser in situ keratomileusis (LASIK) ectasia may be explained in part by corneal biomechanics. The ability to predict the postsurgical biomechanical changes in each patient may help us to improve the predictability of laser vision correction (LVC)

procedures. Moreover, an in-depth understanding of bio­ mechanics may help us to screen patients predisposed to develop postoperative ectasia and enhance the safety of the procedure. An enhanced ectasia screening approach that effectively integrates the objective susceptibility of a patient to develop postoperative ectasia along with the biomechanical impact of the procedure would be an effective strategy in this direction.3

  CORNEAL BIOMECHANICAL ASSESSMENT Evaluation of the corneal biomechanical properties requires a dynamic assessment of the corneal response to an applied load or stress. Various ex vivo and in vivo methods have been described to measure the corneal biomechanical properties; non-invasive in vivo measurement of corneal biomechanical properties may be performed using devices such as the Ocular Response Analyzer (ORA, Reichert Inc.) and Corvis-ST (Oculus, Germany).

Ocular Response Analyzer Ocular response analyzer (ORA, Reichert Inc, Depew, NY) was the first instrument introduced for in vivo corneal biomechanical assessment. It measures the corneal rigidity and intraocular pressure by measuring its response to a pulse of air. The biomechanical properties of cornea as measured by ORA influence the measured IOP and undergo significant alterations after refractive surgeries.

Principle Ocular response analyzer employs a dynamic, bidirectional applanation process for measurement. A collimated rapid pulse of air is directed toward the central 3–6-mm zone of the cornea. The bidirectional movement of the cornea is monitored through an electro-optical system using infrared rays. The air pulse is shut off after the first applanation; however, the inertia in the piston leads to a continual increase in pressure causing the cornea to move further inward into slight concavity. Thereafter, the air pressure decreases causing the cornea to return to its original state.

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SECTION 2: Preoperative Workup and Decision Making During this process, it passes through a second applanation event. The entire process takes about 20 milliseconds, which ensures minimal variability due to changes in eye position. The speed at which these processes occur and the amount of indentation are influenced by corneal rigidity and intraocular pressure. ORA acquires corneal biomechanical data by measuring differential corneal response during inward and outward applanation events.4 The result is displayed in form of curves, which have the following components (Fig. 1): ■■ Green curve: Symmetrical curve corresponding to air pulse pressure. ■■ Red curve: Asymmetric curve demonstrating raw signal corresponding to the applanation event. ■■ Blue curve: Asymmetric curve designed to identify optimum applanation points. Both red and blue curves have two peaks, which correspond to the applanation events. The first peak

corresponds to first applanation during inward corneal motion and point where it intersects the green curve is expressed as P1. Similarly, the second peak corresponds to second applanation during outward corneal motion and the point where it intersects the green curve is expressed as P2. P1 and P2 are shown as blue-colored squares on graph. P2 is always less than P1 because of the property of viscous dampening. The clinical parameters assessed by ORA include corneal hysteresis (CH), corneal resistance factor (CRF), cornealcompensated intraocular pressure (IOPcc), Goldmanncorrelated intraocular pressure (IOPg), and the central corneal thickness (Table 1).5,6 ORA in refractive surgery: Corneal ectatic disorders such as keratoconus and PMD have a lower CH and CRF than normal individuals.7 An inverse relation between CH or CRF and grade of keratoconus has also been demonstrated.8 Though the use of ORA as a standalone tool is not recommended for diagnosing subclinical keratoconus, CH and CRF have been found to be useful adjuncts to posterior float and central corneal thickness for detection of early keratoconus.9,10 Creation of flap or cap, excimer laserassisted ablation of corneal stroma, and stromal lenticule extraction result in the reduction of ocular rigidity para­ meters such as CH and CRF proportional to the amount of refractive error corrected.8 A reduction in IOPcc and IOPg has been demonstrated following LASIK, with IOPcc providing a more accurate estimate of true IOP in post-LASIK eyes. Dou et al. demonstrated more predictable alterations in corneal biomechanics after small incision lenticule extrac­tion (SMILE) as compared with LASIK, with a lesser reduction in CH and CRF.11

Corneal Visualization Scheimpflug Technology Fig. 1: Corneal biomechanical assessment with an ocular response analyzer (ORA). The pressure exerted on the cornea during applanating events is depicted by the green line on the ORA signal plot. The amplitude of the infrared signal is depicted by the red line. The first (“in” signal peak) and second (“out” signal peak) peaks occur during the inward and outward applanation events.

Corneal Visualization Scheimpflug Technology (Corvis-ST) is a non-contact tonometer with an integrated Scheimpflug camera. Like ORA, a pulse of air is directed towards the cornea, which deforms it resulting in an inward and outward movement with two applanations. Corvis-ST employs ultra-high speed Scheimpflug imaging for visualization

TABLE 1: Biomechanical parameters assessed using ocular response analyzer. Parameter

Measurement

Clinical significance

Corneal hysteresis (CH)

Difference of P1 and P2 (Normal value—10.8 ± 1.5 mm Hg)

Viscous dampening property of cornea—higher value signifies a stiffer cornea, which is more resistant to pressure changes

Corneal resistance factor (CRF)

P1-kP2 (k is a constant) (Normal value—11.0 mm Hg ± 1.6 mm Hg)

Measurement of overall resistance and elasticity of cornea— lower value denotes decreased stiffness

Corneal compensated intra­ ocular pressure (IOPcc)

Derived from both IOP and corneal biomechanical data

Less affected by corneal thickness as compared to normal applanation tonometry

Goldmann correlated intra­ ocular pressure (IOPg)

Average of P1 and P2

Correlates closely with Goldmann applanation tonometry

Central corneal thickness

Measured using in-built ultrasonic pachymeter

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CHAPTER 4: Corneal Biomechanics and measurement of the corneal deformation process facilitating a more detailed analysis of the deformation parameters. It takes 4,330 images in 1 second, enabling precise recording of the deformation of cornea by air pulse. Corvis-ST integrates corneal biomechanical properties with corneal tomography.12

Parameters Assessed The biomechanical parameters are assessed during three stages of corneal deformation—the inward defor­ mation, the stage of maximum concavity, and outward deformation. The corneal deformation is accompanied by a whole eye movement in response to the air pulse hitting the globe. The dynamic corneal response parameters, which take this whole globe motion into account and com­ pensate for it, are referred to as “deflection” parameters; those which do not account for it are referred to as “deformation” parameters. The Dynamic Corneal Response Display (Figs. 2A and B) and the Vinciguerra Screening Report (Figs. 3A and B) give an insight into the biomechanical properties of the cornea. Table 2 describes the various parameters displayed along with their clinical significance.

Role of Corvis-ST in Evaluation of Refractive Surgery Patients Corvis-ST plays an important role in both the preopera­ tive screening of refractive surgery patients and the post­ operative biomechanical assessment of cornea following refractive surgery.

Refractive Surgery Screening Corneal biomechanical changes are hypothesized to precede topographic and tomographic abnormalities in corneal ectatic diseases. Two new indices—the ‘Corvis Biomechanical Index’ (CBI) and ‘Tomographic and Biomechanical Index’ (TBI) have been introduced in Corvis-ST for early detection of corneal ectatic changes.13 The Corvis Biomechanical Index or CBI, a parameter available on the Vinciguerra Screening Report of Corvis ST, is derived from logistic regression analysis based on Ambrosió’s Relational Thickness to the horizontal (ARTh) profile and defor­mation parameters, namely, applanation 1 velocity, deformation amplitude ratio (DAR) at 1 and 2 mm, Stiffness parameter at first applanation (SP A-1), and standard deviation (SD) of deformation amplitude at highest concavity (Figs. 3A and B). Vinciguerra et al. demonstrated that the use of CBI alone (without concurrent topographic or tomo­graphic aids) could successfully distinguish kerato­ conic eyes from normal with a high sensitivity and specificity. A cut-off value of 0.5 or higher for CBI was observed to accurately classify 98.8% cases as healthy or keratoconic with 98.4% specificity and 100% sensitivity. 14 While CBI remains a valuable tool for evaluating the corneal

biomechanical changes that occur prior to topographic or tomographic changes in corneal ectasia, its sensitivity and specificity in differentiating cases of subclinical ectasia from normal eyes is much lower, thus limiting its utility as a tool for refractive screening. Tomographic and Biomechanical Index or TBI, available on the integrated Pentacam and Corvis-ST software (ARVDisplay), is derived from tomographic data obtained from Pentacam HR and biomechanical data from Corvis-ST using artificial intelligence (Figs. 4A and B). Its sensitivity and specificity in detecting clinical and subclinical cases of keratoconus has been found to be superior to CBI and Belin-Ambrósio Enhanced Ectasia total deviation index (BAD-D) value. 13 An optimized cut-off value of 0.29 demonstrated a 90.4% sensitivity and 96% specificity for detecting sub­clinical ectasia. A cut-off value of 0.79 was found to diagnose clinical ectasia with 100% sensitivity and specificity.13 Superiority of TBI over other established parameters and indices has been externally validated in multiple study populations; however, the cut-off values for differentiating subclinical keratoconus vary from 0.1– 0.29 based on the sample population studied. A cautious approach is recommended while making clinical decisions based on these indices, keeping in mind the possibility of false-positive and false-negative cases associated with their use.15

Postrefractive Surgery Evaluation Corneal biomechanical evaluation plays a crucial role in assessing the corneal stability post-corneal refractive surgery. It can help to characterize the biomechanical impact of an LVC procedure on the cornea. Various studies have demonstrated a change in the frequently analyzed dynamic corneal response parameters such as DAR, SP-A1, integrated inverse ratio, and ARTh, indicating a decrease in biomechanical strength following LVC.16 Studies using Corvis-ST to compare the corneal bio­ mechanical changes following Photorefractive keratec­tomy (PRK), Femtosecond laser-assisted in situ keratomileusis (FS-LASIK), and SMILE have failed to demonstrate a clear advantage with SMILE or PRK, indicating that the amount of corneal tissue removal may have a greater influence on the long-term biomechanical changes in cornea than the type of procedure. 17,18 Post-refractive surgery assessment on Corvis-ST is confounded by factors such as corneal thick­ness and IOP.19 Parameters, which take into account the change in CCT following surgery or are independent of CCT change, may provide a more accurate estimate of the actual corneal biomechanical properties following the different LVC procedures. Among the newer biomechanical parameters, SP-A1 has shown promise as an indicator to predict the biomechanical properties of the cornea following LVC, independent of the tissue volume or corneal thickness removed.20

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SECTION 2: Preoperative Workup and Decision Making

A

B Figs. 2A and B: Dynamic corneal response display on Corvis-ST. (A) Dynamic corneal response display of a normal patient; (B) Dynamic corneal response display of a keratoconus patient with increased deformation amplitude (DA), DA ratio, and inverse concave radius.

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CHAPTER 4: Corneal Biomechanics

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B Figs. 3A and B: Vinciguerra screening report to assess corneal biomechanics on Corvis-ST. (A) Vinciguerra screening report of a normal patient; (B) Vinciguerra screening report of a keratoconus patient with decreased stiffness parameter-A1 (SP-A1) and increased Corvis biomechanical index (CBI).

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SECTION 2: Preoperative Workup and Decision Making TABLE 2: Dynamic corneal response parameters assessed using Corvis-ST. Parameter

Response measured

Clinical implication

Parameters at first applanation (A1) and second applanation (A2): Deflection amplitude at first (DefA1) and second (DefA2) applanation

Displacement of corneal apex in the anterior–posterior direction from its initial state to A1 and A2 respectively, compensated for whole eye movement

Greater value denotes lesser resistance of cornea to deformation

Applanation time 1 and 2 (A1T and A2T) and applanation length 1 and 2 (A1L and A2L)

•• Time to first and second applanation of the cornea from the beginning of measurement (in milliseconds) •• The length of the applanation during the first and second applanation (in mm)

Greater value of A1T and applanation lengths and earlier/shorter A2T denote stiffer cornea

Corneal velocity (A1V)/(A2V)

Velocity of corneal apex during the first (A1V) and second applanation (A2V)

Lower velocity denotes stiffer cornea

Parameters measured at highest concavity: Deflection amplitude at highest concavity

Displacement of corneal apex at highest concavity with reference to initial state

Greater value denotes lesser resistance of cornea to deformation

Deformation amplitude at highest concavity

The largest displacement of corneal apex in the anterior– posterior direction at the moment of highest concavity. Sum of the deflection amplitude and the whole eye movement

Greater value denotes lesser resistance of cornea to deformation

Highest concavity radius

Radius of the central cornea at the maximum concavity state, based on a parabolic fit

Lower value denotes lesser resistance of cornea to deformation

Peak distance

The length of the distance between the two bending peaks of the cornea at its maximum concavity (in millimeters)

Greater value denotes lesser resistance of cornea to deformation

Deflection amplitude/ deformation amplitude ratio (1 or 2 mm)

Ratio between the deformation/deflection amplitude at the apex and the average deformation/deflection amplitude measured at 1 or 2 mm from the center

Greater value denotes lesser resistance of cornea to deformation

IOPnct

NCT measurement at time of first applanation

Normal IOP, uncorrected for the influence of corneal thickness, age, etc.

Biomechanically-corrected intraocular pressure (bIOP)

Estimate of the true IOP developed using finite element analysis, which considers the age, biomechanical response of the cornea, effects of variation in central corneal thickness, and its material behavior

Better estimate of the true IOP than GAT, especially after LVC surgery

Ambrósio’s relational thickness to horizontal profile (ARTh)

Ratio of the corneal thickness at the thinnest location to the pachymetric progression index (PPI)

Lower value indicates a thinner cornea and/or a faster thickness increase toward the periphery

Maximum inverse radius

Reciprocal of the radius during the maximal state of concavity

Greater value of inverse concave radius denotes lesser resistance to deformation or lesser corneal stiffness

Integrated inverse radius

Integrated total value of the inverse radius of corneal curvature between the first and second applanation moments

Greater value denotes lower the resistance to deformation or lesser corneal stiffness

Stiffness parameter (SP-A1) after first applanation

Defined as the ratio of resultant pressure (air pressure minus bIOP) at inward applanation (A1) divided by corneal displacement or deflection from the undeformed state to A1

•• Higher value denotes greater corneal stiffness •• Useful as a screening parameter for keratoconus; as a single parameter with high sensitivity and specificity

Stiffness parameter (SP-HC) at highest concavity

Defined as the resultant pressure at inward applanation divided by corneal displacement from the first applanation state to highest concavity

Higher value denotes greater corneal stiffness

Other important parameters:

(Corvis-ST: corneal visualization Scheimpflug technology; GAT: Goldmann applanation tonometry; LVC: laser vision correction; IOP: intraocular pressure; NCT: non-contact tonometry)

Corneal densitometry, a measurement of corneal backscattered light, depends on the structural composition of the cornea including its level of hydration. Static assess­ ment of corneal densitometry performed using Scheimpflug technology has been found to increase transiently following LVC procedures. Dynamic assessment of corneal

densitometry using Corvis-ST entails the study of the fluctuations in collagen fibril arrangement and stromal fluid movement during its deformation with the air-puff. Fernandez et al. observed an increase in the dynamic corneal densitometry during air-puff deformation both before and after SMILE, with a higher prevalence of the

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CHAPTER 4: Corneal Biomechanics

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B Figs. 4A and B: Tomographic biomechanical index (TBI) on integrated Pentacam and Corvis-ST software (ARV-display). (A) ARV—display of a normal patient; (B) ARV—display of a keratoconus patient with increased Corvis biomechanical index (CBI), TBI, and Belin-Ambrósio Enhanced Ectasia total deviation index (BAD-D) value.

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SECTION 2: Preoperative Workup and Decision Making “inclined brightness fringe” sign in the peripheral corneal peaks at the highest concavity stage.20,21 Another important aspect while evaluating post-laser vision correction patients is screening for iatro­genic corneal ectasia. Indices such as TBI, CBI, and BAD-D, which were primarily developed to differentiate a normal eye from an ectatic eye or forme fruste keratoconus (FFKC) are unsuitable for detecting post-LVC ectasia. The new CBILVC index; however, performs an automatic assessment of biomechanical stability in post-LVC patients and aims to differentiate stable LVC cases from post-LVC ectasia. A cut-off value of 0.5 has been observed to differentiate stable LVC from post-LVC ectasia with a 98.5% specificity and 86.7% sensitivity, while a cut-off of 0.2 was able to separate stable LVC from ectasia with a sensitivity of 93.3% and a specificity of 97.8%.22 In addition to diagnosing postLVC ectasia, this novel index could also function as a useful clinical decision-making aid, especially while planning repeat laser ablative procedures in these patients.

  LIMITATIONS AND FUTURE DIRECTIONS Clinical devices employed at present lack the ability to quantitatively measure the corneal biomechanical pro­ perties such as the elastic modulus. Currently available devices may assess generalized corneal biomechanics; however, point-specific stiffness mapping is not feasible at present with the commercially available devices. Since biomechanical changes are often precursors to alteration in shape metrics due to an ectatic disease, detecting focal biomechanical abnormalities may help in earlier diagnosis of the condition.18 The role of artificial intelligence (AI) and machine learning algorithms for ectasia screening is well-recognized. Indices such as TBI and Pentacam Random Forest Index (PFRI) are based on artificial intelligence. AI techniques often require data from large sample sets, limiting their application in diagnosing relatively rare conditions such as FFKC. Special techniques, which extrapolate the data from smaller sets to expand them into larger numbers, are being envisaged to overcome this limitation.23

  EMERGING TECHNOLOGIES Novel techniques such as Brillouin microscopy, ultrasound elastography, and Optical Coherence Tomography (OCT) elastography are being investigated for the evaluation of corneal biomechanical properties in an effort to mitigate the limitations of the currently employed techniques. Brillouin microscopy optically assesses and measures the spectral shift of a probing laser beam, as it scatters through a localized corneal tissue volume. The spectral shift in the laser correlates with the mechanical compressibility of the tissue, and a high-resolution confocal spectrometer computes a volumetric map of tissue elastic properties.

It is a noncontact optical procedure that allows assessment of localized tissue properties while providing a microscopic three-dimensional resolution. Identifying focal variations in elastic modulus may enable earlier detection of corneal ectatic diseases. A decreased Brillouin frequency at the cone region and an asymmetry in its levels between both eyes may serve as potential diagnostic metrics for identifying early ectatic disease. Local elastic properties elaborated by Brilluoin microscopy may enable surgeons to create custo­ mized patient-specific treatment nomograms and minimize variability of outcomes among the patients undergoing LVC.24 Elastography is an imaging modality capable of mapping the biomechanical properties of soft tissues and has been employed in various disease conditions such as liver fibrosis and atherosclerosis as a diagnostic aid. Ultrasound elastography employs high-frequency ultrasound to determine local material properties by measuring the corneal response or displacement to an external stress. Likewise, OCT elastography employs light scatter to measure local tissue displacement as a function of applied stress.25 Initial research employing these techniques demon­ strates their potential for spatially resolved biomechanical assessment of the cornea, which may potentially enable early detection of ectatic disorders as well as individualized custom planning of LVC based on the corneal biomechanics.18

  CONCLUSION Our understanding of corneal biomechanics has rapidly progressed over the past two decades. Novel indices have been formulated for enhanced accuracy of ectasia detection and have emerged as a useful adjunct for assessment of refractive surgery patients. Despite initial promising results, studies evaluating their efficacy in larger patient population are required to establish their accuracy. Increasing use of artificial intelligence is expected to play an important role in this direction. Newer emerging technologies such as Brillouin microscopy may provide a more detailed corneal biomechanical analysis and potentially transform the approach of refractive surgery planning in the coming years.

  REFERENCES 1. Detorakis ET, Pallikaris IG. Ocular rigidity: biomechanical role, in vivo measurements and clinical significance. Clin Experiment Ophthalmol. 2013;41(1):73-81. 2. Roberts CJ, Mahmoud AM, Bons JP, Hossain A, Elsheikh A, Vinciguerra R, et al. Introduction of two novel stiffness parameters and interpretation of air puff-induced biomechanical deformation parameters with a dynamic scheimpflug analyzer. J Refract Surg Thorofare NJ 1995. 2017;33(4):266-73. 3. Ferreira-Mendes J, Lopes BT, Faria-Correia F, Salomão MQ, Rodrigues-Barros S, Ambrósio R. Enhanced ectasia detection

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CHAPTER 4: Corneal Biomechanics using corneal tomography and biomechanics. Am J Ophthalmol. 2019;197:7-16. 4. Kaushik S, Pandav SS. Ocular response analyzer. J Curr Glaucoma Pract. 2012;6(1):17-9. 5. Deol M, Taylor DA, Radcliffe NM. Corneal hysteresis and its relevance to glaucoma. Curr Opin Ophthalmol. 2015; 26(2):96-102. 6. Johnson RD, Nguyen MT, Lee N, Hamilton DR. Corneal bio­ mechanical properties in normal, forme fruste keratoconus, and manifest keratoconus after statistical correction for potentially confounding factors. Cornea. 2011;30(5):516-23. 7. Sedaghat MR, Ostadi-Moghadam H, Jabbarvand M, Askarizadeh F, Momeni-Moghaddam H, Narooie-Noori F. Corneal hysteresis and corneal resistance factor in pellucid marginal degeneration. J Curr Ophthalmol. 2018;30(1): 42-7. 8. Ortiz D, Piñero D, Shabayek MH, Arnalich-Montiel F, Alió JL. Corneal biomechanical properties in normal, post-laser in situ keratomileusis, and keratoconic eyes. J Cataract Refract Surg. 2007;33(8):1371-5. 9. Pniakowska Z, Jurowski P. Detection of the early keratoconus based on corneal biomechanical properties in the refractive surgery candidates. Indian J Ophthalmol. 2016;64(2):109. 10. Mohammadpour M, Etesami I, Yavari Z, Naderan M, Abdollahinia F, Jabbarvand M. Ocular response analyzer parameters in healthy, keratoconus suspect and manifest keratoconus eyes. Oman J Ophthalmol. 2015;8(2):102-6. 11. Dou R, Wang Y, Xu L, Wu D, Wu W, Li X. Comparison of corneal biomechanical characteristics after surface ablation refractive surgery and novel lamellar refractive surgery. Cornea. 2015;34(11):1441-6. 12. Yang K, Xu L, Fan Q, Zhao D, Ren S. Repeatability and comparison of new Corvis ST parameters in normal and keratoconus eyes. Sci Rep. 2019;9:15379. 13. Ambrósio R, Lopes BT, Faria-Correia F, Salomão MQ, Bühren J, Roberts CJ, et al. Integration of Scheimpflugbased corneal tomography and biomechanical assessments for enhancing ectasia detection. J Refract Surg. 2017;33(7): 434-43. 14. Vinciguerra R, Ambrósio R, Elsheikh A, Roberts CJ, Lopes B, Morenghi E, et al. Detection of keratoconus with a new biomechanical index. J Refract Surg. 2016;32(12):803-10.

15. Moshirfar M, Motlagh MN, Murri MS, Momeni-Moghaddam H, Ronquillo YC, Hoopes PC. Advances in biomechanical parameters for screening of refractive surgery candidates: a review of the literature, Part III. Med Hypothesis Discov Innov Ophthalmol J. 2019;8(3):219-40. 16. Jędzierowska M, Koprowski R. Novel dynamic corneal response parameters in a practice use: a critical review. Biomed Eng Online. 2019;18:17. 17. Guo H, Hosseini-Moghaddam SM, Hodge W. Corneal biomechanical properties after SMILE versus FLEX, LASIK, LASEK, or PRK: a systematic review and meta-analysis. BMC Ophthalmol. 2019;19:167. 18. Dackowski EK, Lopath PD, Chuck RS. Preoperative, intra­ operative, and postoperative assessment of corneal bio­ mechanics in refractive surgery. Curr Opin Ophthalmol. 2020;31(4):234-40. 19. Fernández J, Rodríguez-Vallejo M, Martínez J, Tauste A, Piñero DP. Corneal thickness after smile affects scheimpflugbased dynamic tonometry. J Refract Surg Thorofare NJ 1995. 2016;32(12):821-8. 20. Fernández J, Rodríguez-Vallejo M, Martínez J, Tauste A, Salvestrini P, Piñero DP. New parameters for evaluating corneal biomechanics and intraocular pressure after smallincision lenticule extraction by Scheimpflug-based dynamic tonometry. J Cataract Refract Surg. 2017;43(6):803-11. 21. Fernández J, Rodríguez-Vallejo M, Martínez J, Tauste A, Piñero DP. Corneal biomechanics after laser refractive surgery: unmasking differences between techniques. J Cataract Refract Surg. 2018;44(3):390-8. 22. Vinciguerra R, Ambrósio R, Elsheikh A, Hafezi F, Yong Kang DS, Kermani O, et al. Detection of Post-Laser Vision Correction Ectasia with a new Combined Biomechanical Index. J Cataract Refract Surg. 2021; Online ahead of print. 23. Klyce SD. The future of keratoconus screening with artificial intelligence. Ophthalmology. 2018;125(12):1872-3. 24. Yun SH, Chernyak D. Brillouin microscopy: assessing ocular tissue biomechanics. Curr Opin Ophthalmol. 2018;29(4): 299-305. 25. Qian X, Ma T, Shih CC, Heur M, Zhang J, Shung KK, et al. Ultrasonic microelastography to assess biomechanical properties of the cornea. IEEE Trans Biomed Eng. 2019; 66(3):647-55.

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CHAPTER

5

Aberrometry and Wavefront Analysis Anand Singh Brar, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal

  INTRODUCTION Optical aberrations may be defined as the “departure of the performance of an optical system from the predictions of paraxial (Gaussian) optics".1 In simple words, when light from one point of an object does not converge/diverge into a single point after transmission through the system, it is said to be “distorted” or “aberrated”. Aberrations may be monochromatic or chromatic. Monochromatic aberrations occur when light is reflected or refracted; they are not a function of the wavelength of light and may be observed with monochromatic light as well. They may be further classified as lower-order aberrations (LOAs) or higher-order aberrations (HOAs) (Table 1). These aberrations are typically evaluated by wavefront-sensing systems and are amenable to correction by laser refractive surgeries. Chromatic aberrations occur due to focusing of different wavelengths of light at different points. They result from dispersion of light due to the variation of the refractive index of the lens with wavelength. They cannot

be corrected by any refractive surgical procedure and are typically not assessed by the wavefront analysis systems. Aberrometers are instruments devised to analyze the wavefront of the human eye to provide detailed infor­ mation regarding lower- and higher-order aberrations of the optical system. Knowledge of optical aberrations and the clinical application of wavefront analysis is essential for the refractive surgeons to ensure optimal visual acuity as well as quality in refractive practice.

  LOWER- AND HIGHER-ORDER ABERRATIONS Lower-order aberrations (LOAs) include piston (zero order), tilt (first order), defocus (second order), and astig­ matism (second order) (Fig. 1). Defocus is considered as a true optical aberration, as the tilt and piston still form an aberration-free image, only at a screen located at a different position in space. Higher-order aberrations (HOAs) consist of third order aberrations—coma and trefoil; fourth order aberrations—

TABLE 1: Monochromatic aberrations of the human eye. Order of aberrations

Types

Clinical significance

Management

Zero order

Piston

Lower order aberrations—80–90% of total aberrations

•• Piston—perfect optical system •• Easily corrected with spectacles, contact lenses, or refractive surgeries

•• Higher order aberrations—15% of total aberrations •• Impact visual quality—lead to night vision disturbances, glare, and halos

•• Wavefront optimized ablation— prevent induction of new HOAs •• Wavefront-guided ablation—correct pre-existing HOAs

First order

Tilt (prism)

Second order

•• Defocus (myopia, hyperopia) •• Astigmatism

Third order

•• Coma •• Trefoil

Fourth order

•• Spherical aberration •• Tetrafoil •• Secondary astigmatism

Fifth order

•• Pentafoil •• Secondary trefoil •• Secondary coma

Sixth order

•• Hexafoil •• Secondary tetrafoil •• Tertiary astigmatism

(HOA: higher order aberration)

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CHAPTER 5: Aberrometry and Wavefront Analysis

Fig. 1: Lower-order aberrations (LOAs) including piston (zero order), tilt (first order), defocus (second order), and astigmatism (second order).

Fig. 2: Higher order aberrations (HOAs).

spherical aberration, quadrafoil (or tetrafoil) and secondary astigmatism; and so on (fifth order and above) (Fig. 2). The majority of higher order aberrations observed in normal eyes are constituted of third, fourth, fifth, and sixth order aberrations.

  WAVEFRONTS A “wavefront” is a surface described by a set of points on a wave, which are in the same phase, at a given time. The direction of propagation of the wavefront is perpendi­ cular to the surface of the wavefront at each point. Rays of light emanating from an object can be described in terms of the shapes formed by the wavefront (Fig. 3). The various lower order aberrations (in their orderly arrangement) can thus be understood in terms of wave­ fronts. The piston aberration (order = 0) represents the

position of the entire wavefront along the z-axis of the eye. This zero-order component has no known role in visual optics. The first order tilt (horizontal and vertical tilt of the wavefront) refers to displacement of the image across the retina. Wavefront tilt is corrected by prism or by eye movements, and tilt is not routinely included in clinical wavefront analysis. Defocus (order = 2) consists of myopia, hypermetropia, and regular astigmatism. Myopia (also called positive defocus) and hyperopia (negative defocus) can be easily corrected by spectacles. Regular (cylindrical) astigmatism produces a wavefront aberration that resembles a cylinder and is corrected by spectacles, whereas the higher order aberrations cannot be corrected by spectacles alone. The most important higher order aberrations affecting visual quality (after spectacle correction has been provided)

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SECTION 2: Preoperative Workup and Decision Making are coma, spherical aberration, and trefoil (Table 2). With coma, a third-order aberration, rays at one edge of the pupil come into focus before rays at the opposite edge do. The effective image resembles a comet—a zone of sharp focus at one end and a tail of fuzzy focus at the other. Coma may be either vertical or horizontal. When peripheral rays focus in front of more central rays, the effect is termed as spherical aberration (fourth order). Furthermore, complex shapes can be used to describe wavefronts formed in various optical aberrations.

  ZERNIKE POLYNOMIALS Frits Zernike, the 1953 Nobel Prize winner in physics and inventor of the phase-contrast microscopy, described long and complicated polynomial equations—the Zernike polynomials (Fig. 4), which are mathematical formulae to represent the basic shapes of the wavefronts (Table 3). Graphical representation in an aberration-free eye, i.e., a flat wavefront would be coded as green color, but a realworld wavefront would reveal aberrations, which are color coded as blue and red areas. The red depicts the part of the wavefront that is in front of the reference plane (positive error, μm), and blue depicts the part that is behind this plane (negative error, μm). The magnitude of the

Fig. 3: Diagrammatic representation of an ocular wavefront.

various aberrations can be averaged out over the wavefront in terms of root mean square error which help in quanti­ fying optical aberrations. Root mean square (RMS) error (in microns) is the average deviation of the measured wave­ front from an ideal optical system with no aberrations, and provides a magnitude of the total aberrations of the wavefront being analyzed. A higher magnitude of RMS values signifies higher amount of aberrations. Majority of patients have 0.40 microns HOA better suited for wavefront-guided ablations •• Increased lenticular aberrations—may not be ideal candidate for cornea-based refractive procedures

Wavefront maps used as a guide for wavefront-guided ablations

Objective assessment of visual quality— correlate with visual complaints such as blur, glare, and halos

(HOA: higher-order aberration)

TABLE 6: Fourier analysis of corneal wavefront. Fourier component

Aberration measured

Significance of Fourier map

Spherical component

Corneal sphere

•• Represent total sphere of cornea •• Used to calculate corneal asphericity

Decentration

Corneal coma

Useful for topography-guided treatment

Regular astigmatism

Corneal astigmatism

•• Central astigmatism from this map more consistent with subjective refraction •• Dissociation between axis of central and peripheral astigmatism signifies presence of higher-order astigmatism

Irregularities

Residual HOAs

Represents trefoil, tetrafoil, pentafoil, and hexafoil

(HOA: higher-order aberration)

Wavefront-guided LASIK takes into account the preopera­ tive wavefront of the optical system and has the distinct advantage of correction of pre-existing higher-order aberrations.12,13 Compared with myopic eyes, hyperopic eyes undergoing a laser refractive procedure experience a higher increase in the post-operative HOAs.14 Newer modalities such as small incision lenticule extraction (SMILE) lead to lesser induction of aberrations as compared with conventional femtosecond LASIK (FS-LASIK). This may be attributed to the absence of a flap with a better preservation of corneal integrity in SMILE as compared with a circumferential LASIK flap. Moreover, more energy is delivered to the cornea with FS-LASIK in higher attempted corrections, while energy levels are constant in SMILE and independent of the attempted correction.15

  FUTURE DEVELOPMENTS Fourier Analysis The application of Zernike polynomials’ descriptions of aberrations to the human eye is less than perfect. It is not accurate with elliptical pupils and calculations of higher orders of HOAs (ninth or above) may not be effective. Moreover, linear irregularities such as flap striae and cap amputation may not be accurately reflected in Zernike’s polynomials. Fourier analysis is an alternative method of evaluating the wavefront of an optical system and quantifying the higher order aberrations. Mathematically, it may be defined as the expression of a complex waveform as a series of sinusoidal functions. The frequencies of the sinusoidal functions form a harmonic series, also known as Fourier

series. It allows for the measurement and treatment of more highly aberrant corneas as compared with using Zernike polynomials.16 Fourier analysis transforms the corneal wavefront into its spatial frequency components to allow ease of analysis; the four components are spherical components, which refer to corneal sphere, decentration, which refers to corneal coma, regular astigmatism, which refers to corneal astigmatism, and irregularities, which refer to residual higher order aberrations (Table 6).

Quantifying Irregular Astigmatism in Clinical Practice Irregular astigmatism is conventionally detected as a “scissoring” reflex observed during retinoscopy. There is no definite axis of cylindrical correction on refraction, which complicates the prescription of accurate refractive correction. In optical engineering, irregular astigmatism is described as additional shapes superimposed on a sphere and a cylinder; the additional shapes can be determined by aberrometry in the form of Zernike polynomials. With the increasing integration of wavefront analysis in refractive practice, optical prescriptions may include a description of the irregular astigmatism in terms of Zernike polynomials or Fourier maps, in addition to the conven­ tional spherocylindrical correction.

  CONCLUSION With advances in refractive surgical techniques, the focus has shifted to provide optimal visual quality and patient satisfaction as well as precise visual acuity. Surgeons are increasingly aware of the significance of assessing higher order aberrations and corneal wavefront during preopera­tive

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Stage: 3rd Proof Time/Date: 12:14 PM/04 Aug 21

CHAPTER 5: Aberrometry and Wavefront Analysis assessment before any refractive surgical procedure. Newer treatment algorithms of cornea-based refractive surgeries take into account the corneal wavefront and irregularities of the optical system in addition to the magnitude of refractive error. Wavefront analysis forms the cornerstone of customized corneal ablations and has paved the way for development of individualized treatment algorithms.

  REFERENCES 1. Guenther BD. Modern optics. New York: Wiley; 1990. p. 696. 2. Netto MV, Ambrósio R, Shen TT, Wilson SE. Wavefront analysis in normal refractive surgery candidates. J Refract Surg. 2005;21(4):332-8. 3. Thibos LN. Principles of Hartmann-Shack aberrometry. J Refract Surg. 2000;16(5):S563-565. 4. Liang J, Grimm B, Goelz S, Bille JF. Objective measurement of wave aberrations of the human eye with the use of a Hartmann–Shack wave front sensor. J Opt Soc Am. 1994; 11(7):1949. 5. Rozema JJ, Van Dyck DEM, Tassignon MJ. Clinical comparison of 6 aberrometers. Part 1: Technical specifications. J Cataract Refract Surg. 2005;31(6):1114-27. 6. Molebny VV, Panagopoulou SI, Molebny SV, Wakil YS, Pallikaris IG. Principles of ray tracing aberrometry. J Refract Surg. 2000;16(5):S572-5. 7. Win-Hall DM, Glasser A. Objective accommodation measure­ ments in prepresbyopic eyes using an auto­refractor and an aberrometer. J Cataract Refract Surg. 2008;34(5):774-84. 8. Tabernero J, Atchison DA, Markwell EL. Aberrations and Pupil Location under Corneal Topography and Hartmann-Shack

Illumination Conditions. Invest Opthalmol Vis Sci. 2009; 50(4):1964-70. 9. Salmon TO, van de Pol C. Normal-eye Zernike coefficients and root-mean-square wavefront errors. J Cataract Refract Surg. 2006;32(12):2064-74. 10. Li M, Zhao J, Miao H, Shen Y, Sun L, Tian M, et al. Mild Decentration Measured by a Scheimpflug Camera and Its Impact on Visual Quality Following SMILE in the Early Learning Curve. Invest Opthalmol Vis Sci. 2014;55(6): 3886-92. 11. Bottos KM, Leite MT, Aventura-Isidro M, Bernabe-Ko J, Wongpitoonpiya N, Ong-Camara NH, et al. Corneal aspheri­ city and spherical aberration after refractive surgery. J Cataract Refr Surg. 2011;37(6):1109-15. 12. Stonecipher KG, Kezirian GM. Wavefront-optimized versus wavefront-guided LASIK for myopic astigmatism with the ALLEGRETTO WAVE: three-month results of a prospective FDA trial. J Refract Surg. 2008;24(4):S424-30. 13. Feng Y, Yu J, Wang Q. Meta-analysis of wavefront-guided vs. wavefront-optimized LASIK for myopia. Optom Vis Sci. 2011;88(12):1463-9. 14. Chen CC, Izadshenas A, Rana MAA, Azar DT. Corneal asphericity after hyperopic laser in situ keratomileusis. J Cataract Refract Surg. 2002;28(9):1539-45. 15. Chen X, Wang Y, Zhang J, Yang S-N, Li X, Zhang L. Com­ parison of ocular higher-order aberrations after SMILE and Wavefront-guided Femtosecond LASIK for myopia. BMC Ophthalmol. 2017;17(1):42. 16. Cade F, Cruzat A, Paschalis EI, Espírito Santo L, Pineda R. Analysis of Four Aberrometers for Evaluating Lower and Higher Order Aberrations. PLoS One. 2013;8(1): e54990.

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Posterior Segment Screening and Refractive Surgery Priyanka, Brijesh Takkar, Manpreet Kaur, Jeewan S Titiyal

  INTRODUCTION Refractive surgery is an anterior segment procedure; however, the eye being a closed compartment that allows transmission of mechanical and biochemical changes, it may have posterior segment consequences as well. The risk is further compounded by the fact that many of these patients are quite outside the normal range in terms of refractive error and ocular biometric parameters, which predisposes to the development of untoward posterior segment complications. Simultaneously, this also makes the relationship between the refractive procedures and vitreoretinal (VR) complications difficult to establish, since most of these complications occur with a higher incidence in patients with high refractive errors in comparison to the normal population. We herein discuss the preopera­ tive screening and management of treatable retinal lesions as well as the various posterior segment complications associated with refractive surgeries.

  PREOPERATIVE POSTERIOR SEGMENT SCREENING A preoperative posterior segment screening is mandatory to detect and treat pre-existing posterior segment patho­ logies before undertaking any refractive surgical procedure (Flowchart 1).

Significance A dilated fundus examination is a prerequisite before undertaking any refractive surgery, as it may uncover other eye diseases or causes of decreased visual acuity. The patient's vitreous may have opacities such as posterior vitreous detachments (PVD) that cannot be corrected by refractive surgery. In addition, peripheral retinal lesions and vision-threatening macular complications may be present in cases with high refractive errors. Pre-existing degeneration (lattice) or retinal holes may worsen after the procedure.

Flowchart 1: Preoperative peripheral retinal screening and management.

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Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:15 PM/04 Aug 21

CHAPTER 6: Posterior Segment Screening and Refractive Surgery Post-laser in situ keratomileusis (LASIK) rhegmato­ genous retinal detachment (RRD) usually occurs in eyes with complex retinal breaks. 1,2 Arevalo et al. reported that vitreous traction and deformity induced by antero– posterior compression and expansion may lead to the development of peripheral retinal tears or macular injury during LASIK.3-5 Lesions such as lattice degenera­ tion and holes should undergo prophylactic laser barrage preoperatively and may not progress further into RRD.

Types of Treatable Peripheral Retinal Lesions and Their Management The peripheral retinal lesions that may be observed in eyes planned for refractive surgery include peripheral retinal degeneration, lattice degeneration, and snail track degeneration.

Peripheral Retinal Degeneration Peripheral retinal degenerations are disorders in the peripheral part of the retina, and may include retinoschisis, atrophic holes, lattice degeneration, white without pressure (WWOP), paving stone, and snail track degenerations.

These lesions and retinal breaks have been characterized in Tables 1 and 2. Areas of interface where the vitreous is particularly adherent to the retina are most relevant clinically. These regions include the pre-existing developmental lesions that includes lattice degeneration, zonular traction tufts, cystic retinal tufts, vitreous base which is 3–4-mm wide and straddling the ora serrata, and retinal vessels. These points of adhesion are the likely cause of full-thickness retinal breaks during mechanical change following refractive surgery, responsible for most cases of retinal detachment. These lesions have been considered for prophylactic treatment; however, studies providing definitive evidence are lacking. The incidence of retinal detachment post-LASIK is low, necessitating the need of a large sample size for an evidence-based study. Laser photocoagulation has become a preferred practice pattern in modern days for such lesions prior to refractive surgery because of theoretical risk of retinal detachment post-LASIK.

Lattice Degeneration It is a common peripheral condition present in 6–8% of eyes, more commonly observed in myopes. It commonly

TABLE 1: Different types of peripheral retinal degenerations. Peripheral degeneration

Risk factor for RRD (if no other risk factor is present and refractive surgery is not being contemplated)

Action (if no other risk factor is present and refractive surgery is not being contemplated)

Paving stone

No

None required

CHRPE

No

None required

Reticular

No

None required

Peripheral drusen

No

None required

WWOP

No

None required

Microcystoid

No

None required

Retinoschisis without holes

Very rare progression

Refer routinely for confirmation of diagnosis then monitor annually

Atrophic round holes

Rare

Retinal detachment warning, then monitor annually

Lattice

Rare

Retinal detachment warning, then monitor annually

(CHRPE: congenital hypertrophy of the retinal pigment epithelium; WWOP: white without pressure)

TABLE 2: Different peripheral retinal breaks. Feature

Atrophic hole

Operculated tear

Flap tear

Shape

Round or oval

Round with disk shaped operculum floating above the break

U shaped with central flap

Vitreous traction

None

•• Break induced by traction •• Absent once operculum has separated

Usually continuous

Location

Far periphery

Far to mid-periphery

Far to mid-periphery

Retinal or vitreous hemorrhage

Never

Rarely

Often

Symptoms (Flashes or floaters)

Never (unless clinically significant RD occurs)

Possible in traction phase (or if clinically significant RD occurs)

Frequent in traction phase (or if clinically significant RD occurs)

Incidence of RD

Rare

About 16% (much less if asymptomatic)

30–50% in symptomatic cases

(RD: retinal detachment)

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SECTION 2: Preoperative Workup and Decision Making develops in early adulthood with peak incidence in second and third decades. The classic appearance is spindleshaped areas of retinal thinning and the usual location is between posterior border of vitreous base and equator with characteristic fine white lines within the islands. The vitreous overlying the area of lattice is synchytic, but vitreous attachments around margins are exaggerated. The risk factors for tractional tears following PVD in lattice degeneration are the combination of retinal thinning, vitreous liquefaction overlying the thinned retina with vitreous condensation, and exaggerated vitreoretinal attach­ ments at the borders of these lesions. A 10-year follow-up study showed that only 1% of eyes with lattice changes developed RRD; therefore, prophylactic treatment is not always recommended, if refractive surgery is not being contemplated. Prophylactic treatment may not always prevent detachment, as new breaks can occur in areas not visibly affected by lattice and new lattice degenerations.6,7 High myopes have a higher risk for RRD, and surgical stress related to the intraoperative mechanics may pose a threat for RRD.

Snail Track Degeneration It is characterized by sharply demarcated bands of white, crinkled, or frostlike changes of the inner retinal surface, and is commonly observed in young and myopic eyes in the area of the equator. It is considered to be an early stage of lattice degeneration by many authors and may lead to development of retinal breaks and RD in 10–20% of cases. Prophylactic intervention for this lesion has been debated.6

Posterior Segment-related Contraindications for Refractive Surgery Unrepaired retinal detachment is an absolute contra­ indication for any refractive surgical procedure. In addition, relative contraindications include macular diseases, angioid streaks, traumatic choroidal ruptures, and diabetic retinopathy. Patients with high myopia and lacquer cracks are at higher risk to develop macular hemorrhage or choroidal neovascularization (CNV) after raised intraocular pressure with application of the suction ring during the procedure. Stage-1 macular holes may progress due to traction on the posterior pole during LASIK. Patients with diabetic retinopathy should not undergo LASIK. If refractive procedures are performed, LASEK or PRK is a better suited procedure for patients with ischemic retinal disorders because they do not require suction leading to additional retinal ischemia. Eyes that are at risk of needing vitreoretinal surgery in the future should also not undergo any refractive procedure. This is for two reasons—firstly, refractive surgery may lead on to accentuation of a retinal lesion and secondly, presence of flap and even phakic intraocular lenses (IOLs)

can make VR surgery difficult. The flap is known to dislocate along with occurrence of haze during the surgery. If the patient accepts limitation of his visual acuity, refractive surgery may be performed in cases of stable macular disease based on refractive surgeons’ criteria. Refractive surgery may also be considered in cases of residual refractive errors after retinal detachment surgery; however, conjunctival scarring and poor suction generation may cause intraoperative difficulties during LASIK.8

Timing of Refractive Surgery after Prophylactic Laser Therapy Laser retinopexy is generally considered to be a safe procedure; complications may occur due to inadvertent laser to the macula, choroidal effusions in case of large amount of laser, and anterior segment laser burns. Other complications include hemorrhage of the retina, vitreous or choroid, angle closure glaucoma, epiretinal membrane formation, choroidal neovascular membrane formation, and the formation of new retinal breaks. After laser retinopexy, follow-up examination is manda­ tory, especially 2–3 weeks after the procedure. Indirect ophthalmo­s copy with or without scleral depression is recommended. Retreatment is indicated in cases of inadequate chorio­ retinal scarring, especially if the initial treatment does not completely surround the anterior margins of retinal tears. Retreatment or surgical intervention may be indicated in cases of old retinal breaks seen on re-examination, in entirely new retinal breaks (approximately 10% of all patients) or in subretinal fluid extending over the area of previous treatment. Generally, it takes around 1 week to 10 days of time for the laser-induced reaction to nearly complete. Hence, if examination findings are suggestive of adequate laser therapy, it is usually safe to undergo LASIK after 2–3 weeks of time.

Postoperative Screening and Follow-up Periodic fundus screening should be continued even after an uneventful laser procedure as new degenerations may appear. The patients should be warned of potentially ominous symptoms including flashes, floaters, and visual field loss, as retinal breaks can develop in clinically normal areas also.

  POSTREFRACTIVE SURGERY VITREORETINAL COMPLICATIONS Pathophysiology The precise role of refractive surgery as a potential additive risk factor for rhegmatogenous retinal detachment (RRD) in myopic eyes has long been an issue of debate. The frequency of RRD after LASIK is reported to be 0.06–0.25%.9-11

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:15 PM/04 Aug 21

CHAPTER 6: Posterior Segment Screening and Refractive Surgery Retinal tears, retinal and vitreous hemorrhage, macular holes, and choroidal neovascular membranes are relatively rare posterior segment complications after refractive surgery. PVD is the principle pathophysiology behind the vitreo­ retinal complications. Because of the pressure changes and deformation of globe involved in these procedures, an early PVD is likely to occur and may be associated with the above-mentioned compli­c ations. Myopic maculo­ pathies may progress after the surgery and PVD occurs at a higher rate following flap-based refractive surgery. Experimental evaluations have demonstrated axial length changes during refractive surgery. Further, some authors have even blamed shock waves generated due to the highfrequency ablation during cornea-based refractive surgeries to result in postoperative retinal pathologies.

Corneal Suction and Retinal Nerve Fiber Layer Changes Most of the patients operated for refractive surgery are myopic and experience a transient elevation in intraocular pressure (IOP) by the suction ring, raising concerns regarding retinal nerve fiber layer (RNFL) damage, and optic nerve affection.12

Microkeratome-associated RNFL Changes Increase in pressure induced by the suction ring used to fixate the eye while the microkeratome creates the flap may elongate the eye along the antero-posterior axis with resulting contraction of the horizontal axis. Pushing of the lens anteriorly by these events results in vitreoretinal traction at the base of vitreous and the posterior pole that facilitates PVD.

Femtosecond Laser and RNFL Femtosecond laser-assisted flap creation is associated with a lower IOP rise as compared with traditional mechanical microkeratomes; however, duration of suction is consi­ derably higher. Vetter et al. showed IOP elevation of up to 150 mm Hg with flat corneal applanation interfaces and up to 65 mm Hg with curved corneal interfaces.13,14 Retinal nerve fiber layer thickness decrease has been observed after uncomplicated LASIK.15 Gürses-Özden et al. did not observe a significant decrease in post-LASIK RNFL thickness, as measured by optical coherence tomography (OCT), scanning laser polarimetry (SLP), and scanning laser tomography.16 Post-LASIK thinning of RNFL measured using SLP with a fixed corneal compensator may be attributed to altered corneal birefringence rather than an actual thinning.17,18 Changes in corneal birefringence should be compensated for individually to obtain accurate RNFL thickness measurements. In 2004, Hosny et al., in an attempt to evaluate the RNFL function found no significant visual field changes after LASIK.12 In conclusion, application of

suction ring during LASIK surgery causing rise of IOP does not affect the RNFL thickness as measured by spectral domain-OCT.

Posterior Segment Complications of Refractive Surgeries The posterior segment complications associated with cornea and lens-based refractive surgery procedures are summarized in Table 3.

Complications of Cornea-based Refractive Surgeries Retinal complications after cornea-based refractive surgery include retinal tear and detachment, macular hemorrhage, macular hole, and choroidal neovascular membrane. Retinal detachment: The frequency of RRD after LASIK is reported to be 0.06–0.25%.9-11 The normal lifetime risk of rhegmatogenous retinal detachment in high-myopic patients without surgery has been estimated to be 40 times the life risk of retinal detachment in emmetropes. Recom­ mendations for prevention are based on preferred practice patterns. Post-LASIK RRD, if managed promptly, is asso­ ciated with favorable visual outcomes.4 When planning surgical treatment of RRD following LASIK, certain factors should be considered. Alternative techniques (such as segmental scleral buckling, vitrectomy, or pneumatic retinopexy) may be considered, if patient is not satisfied with the myopic shift following encircling scleral buckling post-LASIK. If pars plana vitrectomy (PPV) is chosen to treat RD, gentle repositioning and bandage contact lens can successfully manage flap dislocations during surgery. In severe cases, minimal suturing may be needed. Sometimes, haziness occurs due to debris or fluid in the interface, which requires gentle washing and flap repositioning. If epithelial debridement is being done during the surgery, the location of the hinge of the flap should be considered to avoid displacements. TABLE 3: Posterior segment complications following cornea- and lens-based refractive surgeries. Complications of cornea-based Complications of lens-based refractive surgeries refractive surgeries Retinal tear and detachment

Perforated globe (if done under LA)

Macular hemorrhage

Suprachoroidal hemorrhage

Macular hole

Dropped nucleus

Choroidal neovascular membrane

CME

Retinal phlebitis

Macular phototoxicity

CME

Retinal detachment

Retinal vein occlusion

Postoperative endophthalmitis

(CME: cystoid macular edema; LA: local anesthesia)

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SECTION 2: Preoperative Workup and Decision Making Macular hole: Macular hole has been reported to occur 6 months to 1 year after LASIK for myopia. Arevalo et al. described 19 patients (20 eyes) who developed macular hole after undergoing bilateral LASIK for the correction of myopia. 19 The macular hole formed at a mean of 12.1 months after LASIK. Macular hemorrhage: Macular hemorrhage is observed rarely after refractive surgeries, and is related to pressure changes, or may even follow a choroidal neovascular membrane. Choroidal neovascular membrane (CNVM): Choroidal neovascularization may be observed in 4–11% patients with high myopia and is related to myopia itself. In addition, up to 82% of cases with myopia have been found to have association between lacquer cracks and CNVM.20 Theoretically, choroidal neovascular complex may progress following a break in Bruch’s membrane. Suction with the microkeratome with suction ring placed up to 4 mm posterior to the limbus may cause elevated intraocular pressure over 60 mm Hg that may exert posterior traction and compression, resulting in further opening of Bruch’s membrane gap. Success in stabilizing or improving vision in patients with subfoveal CNVMs from pathologic myopia after LASIK with photodynamic therapy (PDT) using verte­ porfin has been reported. Currently, anti-VEGF injections are presumed to be a better option.

Complications of Lens-based Refractive Surgeries Lens-based surgeries including phakic intraocular lens implantation and refractive lens exchange involve intra­ ocular manipulations and may be associated with perforated globe, dropped nucleus, cystoid macular edema, macular phototoxicity, macular infarction (due to aminoglycosides), and retinal detachment. Globe perforation is a well-known accidental complication of peribulbar and retrobulbar anesthesia, with high myopia being an important additional risk factor. There is also a potential risk of developing rare sight-threatening events such as endophthalmitis, sympathetic ophthalmia, and suprachoroidal hemorrhage. For these reasons, and more so, the young age of these patients who usually have a firmly attached cortical vitreous, all preventive efforts must be made.

  CONCLUSION Although no randomized controlled trials are available, most of the recent studies hint at no direct cause-effect relationship between refractive surgery and vitreoretino­ pathy. The incidence of vitreoretinal pathologic conditions in myopic eyes after refractive surgery is low, but it is neces­ sary to strictly screen candidates and apply preventive measures as appropriate. Prophylactic laser should be the rule, as the lesions can develop near lattice or other

predisposing degenerations. Retinal screening should be performed periodically even after successful refractive surgery. Patients should be made to understand that treatment of pre-existing lesions does not eliminate the risk of retinal complications after refractive surgery.

  REFERENCES 1. Daftarian N, Dehghan MH, Ahmadieh H, Soheilian M, Karkhaneh R, Lashay A, et al. Characteristics and Surgical Outcomes of Rhegmatogenous Retinal Detachment Following Myopic LASIK. J Ophthalmic Vis Res. 2009;4(3):151-9. 2. Hernáez-Ortega MC, Soto-Pedre E. Bilateral retinal detach­ ment associated with giant retinal tear following LASIK. J Refract Surg Thorofare NJ. 2003;19(5):611. 3. Arevalo JF, Ramirez E, Suarez E, Cortez R, Ramirez G, Antzoulatos G, et al. Incidence of vitreoretinal pathologic conditions within 24 months after laser in situ keratomileusis. Ophthalmology. 2000;107(2):258-62. 4. Arevalo JF, Ramirez E, Suarez E, Cortez R, Antzoulatos G, Morales-Stopello J, et al. Rhegmatogenous retinal detach­ ment in myopic eyes after laser in situ keratomileusis. Frequency, characteristics, and mechanism. J Cataract Refract Surg. 2001;27(5):674-80. 5. Arevalo JF, Ramirez E, Suarez E, Cortez R, Ramirez G, Yepez JB, et al. Retinal detachment in myopic eyes after laser in situ keratomileusis. J Refract Surg Thorofare NJ. 2002;18(6):708-14. 6. Engstorm RJ, Glasgow B, Foos R, Straatsma B. Chapter 26: Degenerative diseases of the peripheral retina. In: Tasman W, Jaeger EA (Eds). Duane’s Clinical Ophthalmology on DVD-ROM, Volume 3. Philadelphia: Lippincott Williams & Wilkins; 2013. 7. Lewis H. Peripheral retinal degenerations and the risk of retinal detachment. Am J Ophthalmol. 2003;136:155-60. 8. Sinha R, Dada T, Verma L, Chaudhury DB, Tandon R, Vajpayee RB. LASIK after retinal detachment surgery. Br J Ophthalmol. 2003;87:551-3. 9. Arevalo JF, Lasave AF, Torres F, Suarez E. Rhegmatogenous retinal detachment after LASIK for myopia of up to -10 diopters: 10 years of follow-up. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2012;250:963-70. 10. Ruiz-Moreno JM, Alió JL. Incidence of retinal disease following refractive surgery in 9,239 eyes. J Refract Surg Thorofare NJ. 2003;19:534-47. 11. Ruiz-Moreno JM, Pérez-Santonja JJ, Alió JL. Retinal detach­ ment in myopic eyes after laser in situ keratomileusis. Am J Ophthalmol. 1999;128(5):588-94. 12. Hosny M, Zaki RM, Ahmed RA, Khalil N, Mostafa HM. Changes in retinal nerve fiber layer thickness following mechanical microkeratome-assisted versus femtosecond laser-assisted LASIK. Clin Ophthalmol Auckl NZ. 2013;7: 1919-22. 13. Vetter JM, Schirra A, Garcia-Bardon D, Lorenz K, Weingärtner WE, Sekundo W. Comparison of intraocular pressure during corneal flap preparation between a femtosecond laser and a mechanical microkeratome in porcine eyes. Cornea. 2011;30(10):1150-4. 14. Vetter JM, Faust M, Gericke A, Pfeiffer N, Weingärtner WE, Sekundo W. Intraocular pressure measurements during

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Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:15 PM/04 Aug 21

CHAPTER 6: Posterior Segment Screening and Refractive Surgery flap preparation using 2 femtosecond lasers and 1 micro­ keratome in human donor eyes. J Cataract Refract Surg. 2012;38(11):2011-8. 15. Gürses-Ozden R, Pons ME, Barbieri C, Ishikawa H, Buxton DF, Liebmann JM, et al. Scanning laser polarimetry measure­ ments after laser-assisted in situ keratomileusis. Am J Ophthalmol. 2000;129(4):461-4. 16. Gürses-Ozden R, Liebmann JM, Schuffner D, Buxton DF, Soloway BD, Ritch R. Retinal nerve fiber layer thickness remains unchanged following laser-assisted in situ keratomileusis. Am J Ophthalmol. 2001;132:512-6. 17. Centofanti M, Oddone F, Parravano M, Gualdi L, Bucci MG, Manni G. Corneal birefringence changes after laser assisted in situ keratomileusis and their influence on retinal

nerve fibre layer thickness measurement by means of scanning laser polarimetry. Br J Ophthalmol. 2005;89(6): 689-93. 18. Zangwill LM, Abunto T, Bowd C, Angeles R, Schanzlin DJ, Weinreb RN. Scanning laser polarimetry retinal nerve fiber layer thickness measurements after LASIK. Ophthalmology. 2005;112(2):200-7. 19. Arevalo JF, Mendoza AJ, Velez-Vazquez W, Rodriguez FJ, Rodriguez A, Rosales-Meneses JL, et al. Full-thickness macular hole after LASIK for the correction of myopia. Ophthalmology. 2005;112(7):1207-12. 20. Maturi RK, Kitchens JW, Spitzberg DH, Yu M. Choroidal neovascularization after LASIK. J Refract Surg Thorofare NJ. 2003;19:463-4.

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Preoperative Evaluation, Patient Counseling, and Decision Making Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

  INTRODUCTION The field of refractive surgery has witnessed tremendous growth over the past three decades. The demand for spec­ tacle independence is continuously rising among the young and old patients alike owing to their active lifestyles and professional requirements. Currently, the most frequently performed refractive procedures are laser-assisted in situ keratomileusis (LASIK), small incision lenticule extraction (SMILE), photorefractive keratectomy (PRK) and phakic intraocular lens (pIOL) implantation. The exceptional visual outcomes and patient satisfaction rates associated with modern refractive surgery have led to very high patient expectations.1 A comprehensive preoperative work-up is crucial to ensure good visual outcomes, safety, and patient satisfaction. Key components of preoperative evaluation include selection of the appropriate procedure based on the clinical history and examination, risk assessment, and patient counseling.

  CLINICAL HISTORY History taking is an art, and obtaining a comprehensive history is the first step while working up a patient for refractive surgery. The patient’s age, occupation, expectations and demands from surgery, ocular history, and systemic history should be documented. The reason for undergoing the surgery should be considered, as a significant proportion of the patients may be seeking refractive surgery to fulfill their professional requirements of spectacle independence. The surgeon must take into consideration the specific guidelines or requirements in terms of the refractive proce­ dures to apply for specific jobs and visual acuity criteria when treating such patients. The salient features of the demographic, ocular, and systemic history pertinent to preoperative assessment in refractive surgery patients are detailed in Table 1.

Ocular History The foremost consideration while planning a refractive procedure is to document the stability of the refractive error.

Refractive error should be stable, with less than 0.5 D change in sphere or cylinder over the past 1 year. History of contact lens use is significant to ensure reliable corneal topography. Rigid gas permeable lenses and soft contact lenses should be discontinued at least 4 and 2 weeks respectively before evaluation. Past ocular diseases or surgeries should be documented. Prior ocular herpes is a relative contraindication for refrac­ tive surgery, as the disease may recur post-surgery and compromise the visual and anatomical outcomes. There should be no active episode in the preceding 1 year, and peri-operative oral antiviral prophylaxis for at least 2 weeks before and after surgery is recommended.2 Ocular comorbidities that may affect the final visual outcome are relative contraindications for refractive surgeries, including glaucoma, retinal pathologies, stromal or endothelial corneal dystrophies, and amblyopia (Table 2).

Family History A family history of ectatic disorders such as keratoconus, pellucid marginal degeneration, or postsurgical ectasia must be elicited, as patients with positive family history may be predisposed to develop postoperative ectasia even in the absence of obvious topographical signs. Ectasia is one of the most feared complications after refractive surgery and it may not be possible to accurately predict the risk of postoperative ectasia in 100% of cases. A positive family history should ideally be a deterrent to refractive surgery and may help in targeted counseling.

Systemic History Systemic disorders including uncontrolled diabetes mellitus (DM), active connective tissue disorders (CTD), immune deficiency states such as acquired immunodeficiency syndrome (AIDS), pregnancy, and lactation are absolute contraindications for undergoing any refractive procedure, as they are associated with suboptimal outcomes and an increased risk of complications (Table 2).

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Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:15 PM/04 Aug 21

CHAPTER 7: Preoperative Evaluation, Patient Counseling, and Decision Making TABLE 1: Salient points in the clinical history of refractive surgery patients. History Social/personal/ occupational history

Ocular history

Systemic history and medication history

Important considerations

Comments

Age

Minimum age criteria: ≥18 years for LASIK/PRK ≥22 years for SMILE ≥21 years for phakic IOL >40 years for presbyopic LASIK

Should meet the minimum age criteria for the procedure

Personality type

Extremely anxious or calm

Anxious patient—uncooperative during surgery

Patient motivation/ expectations

Reason for opting for surgery

Whether for cosmesis or professional reasons

Occupational demands/risks

Whether required for professional reasons—active contact sports/armed or police forces

Avoid flap-based procedures in contact sports Consider professional criteria for vision and type of refractive procedures

Refractive error

Stability of refractive error

20/25 •• Rule out pathological cause/amblyopia, if BSCVA < 20/25

Refraction

Cycloplegic and manifest refraction

Cycloplegic refraction to relax accommodation; important in hyperopes to unmask latent error

Binocular vision assessment/ocular dominance

•• Assessment of phorias/tropias •• Convergence amplitude •• Dominant eye assessment for monovision planning

•• Preoperative phoria may decompensate to full blown tropia postoperatively •• Convergence insufficiency in high myopes after surgery

Adnexa

•• Deep set eyes •• Prominent brow •• Small palpebral fissure

•• Difficulty in docking •• Suction loss

Slit-lamp examination

•• •• •• •• •• ••

Superficial scars Dystrophies Dry eye assessment Limbal vascularization Healed uveitis/pigment dispersion Lenticular assessment

•• •• •• ••

Ocular surface/dry eye assessment

•• •• •• •• •• •• ••

Schirmer’s test Tear film break-up time Ocular surface staining scores Tear osmolarity Tear MMP-9 Meibography Tear lipid layer thickness (Lipiview II)

•• Preoperative DED can worsen after surgery •• Raised MMP-9 (>40 ng/mL) suggestive of inflammatory process—consider topical steroids •• Tear osmolarity > 315 mOsm/L—mild–moderate dry eye •• Tear osmolarity > 336 mOsm/L—severe dry eye •• LLT < 60 nm—obstructive Meibomian gland dysfunction

Gonioscopy

Anterior chamber angle assessment

General physical assessment

Ocular evaluation

EBMD—epithelial sloughing during LASIK Granular dystrophy—recurrent opacities after surgery FECD/endothelial guttae—poor LASIK flap adherence Increased limbal vessels—risk of bleeding while creating flap

>Grade III angle required for phakic IOL implantation Contd…

Code: Del-590 Name: Md Iqbal

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CHAPTER 7: Preoperative Evaluation, Patient Counseling, and Decision Making Contd… Parameter assessed

Salient considerations

Topography/tomography

Videokeratography Pentacam/Sirius/Galilei

High-risk parameters for ectasia on Pentacam: •• Km > 47 D •• Inferior steepening > 1.4 D •• Skewing of axis > 22° •• Raised anterior/posterior elevation •• Thinnest pachymetry 500 microns •• BAD-D value > 1.6 •• ART-Max < 416 •• Increased postoperative aberrations, if K < 34 D; >50 D

Pachymetry

•• Scheimpflug tomographers •• ASOCT

Risk of ectasia: •• RSBT < 250 microns •• PTA > 40%

Corneal biomechanical assessment

Corvis-ST

Risk of ectasia: •• TBI > 0.29 (90% sensitivity) •• CBI > 0.07 (68% sensitivity)

Wavefront analysis

Aberrometry—total, corneal, and internal aberrations

•• WG ablation, if HOAs > 0.4 microns •• TG ablation, if significant corneal aberrations present

Pupillometry Angle kappa

Pupil diameter and angle kappa assessment with topographers/tomographers or aberrometers

•• Larger pupil—risk of increased visual disturbances after surgery •• Centre treatment on visual axis in large angle kappa

Ocular biometry

•• •• •• ••

•• ACD >2.8 mm required for phakic IOL •• AL and keratometry assessment in refractive lens exchange patients

Objective lenticular opacity assessment

•• Dysfunctional lens index (ray-tracing aberrometry) •• Lens densitometry (Pentacam)

Consider refractive lens exchange in pre-presbyopic/ presbyopic patients with early lenticular changes

Corneal endothelial cell density

Specular microscopy

Minimum ECC for age as per FDA criteria required

Posterior segment evaluation

Screen for high-risk lesions

Laser high-risk lesions before proceeding with surgery

Ancillary investigations

ACD White to white diameter Axial length Keratometry

(UCVA: uncorrected visual acuity; BSCVA: best spectacle corrected visual acuity; EBMD: epithelial basement membrane dystrophy; FECD: Fuchs’ endothelial corneal dystrophy; ASOCT: anterior segment optical coherence tomography; WG: wavefront guided; TG: topography guided; ECC: endothelial cell count; PTA: percentage tissue altered; RSBT: residual stromal bed thickness; ART-Max: Ambrosio relational thickness maximum; BAD-D: Belin Ambrosio enhanced ectasia display deviation value; CBI: Corvis biomechanical index; TBI: tomographic biomechanical index)

Determination of ocular dominance is important, especially in patients being planned for monovision or presbyopic correction. Basic ocular motility examination including the assess­ ment of the phoric posture, near point of convergence, and fusional reserves should be performed to screen for ocular alignment anomalies. Patients with preoperative phorias may decompensate into tropias and are prone to develop asthenopic symptoms after surgery. Hyperopes with large exophorias may progress to exotropia post-surgery due to loss of accommodative control. A transient increase in convergence demand for near work and accommodative insufficiency may occur after high myopic corrections. Patients with a manifest strabismus should be considered for squint correction before planning refractive correction.

Slit-lamp Evaluation A detailed slit-lamp examination should be performed to rule out ocular comorbidities. Meibomian gland

dysfunction, blepharitis, or allergic keratoconjunctivitis should be treated appropriately before proceeding with refractive surgery. Corneal ectatic disorders and stromal dystrophies are absolute contraindications for corneal refractive procedures. Crystalline lens should be docu­ mented preoperatively and any visually significant lenticular opacities should be ruled out.

Ocular Surface Assessment Pre-existing dry eye disease (DED) may be present in up to 10–55% of patients undergoing refractive surgery; it worsens after surgery and adversely affects visual outcomes.6 A poor tear film can affect the reliability of preoperative measurements such as topography and wavefront analysis. A comprehensive ocular surface assessment should be performed to diagnose and grade the severity of dry eye disease. Slit-lamp assessment with ocular surface staining, Schirmer’s test, and tear film break-up time help to assess ocular surface stability. In addition, tear osmolarity

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SECTION 2: Preoperative Workup and Decision Making and matrix metalloproteinase-9 (MMP-9) levels have emerged as useful diagnostic adjuncts. Tear osmolarity >307 mOsm/L or an inter-eye difference >7 mOsm/L is considered abnormal. Elevated tear MMP-9 levels (>40 ng/mL) may suggest an inflammatory component. Meibomian gland atrophy has been reported in up to 72.5% of patients seeking refractive surgery.7 Reduced tear lipid layer thickness (LLT) is associated with obstructive MGD or MGD atrophy; LLT values 0.5 mm) are at risk for decentered ablations and significant induction of higher order aberrations (HOAs) with pupil-centric ablation.11,12 Patients with large angle alpha may have increased HOAs and visual disturbances after refractive lens exchange with multifocal IOL implantation.

Corneal Topography Detailed corneal topography assessment is essential for refractive planning and to rule out any subclinical ectasia. Various techniques for evaluation of corneal topography, indices to detect ectasia, and their significance have been discussed in detail in Chapter 3.

Corneal Biomechanical Assessment Corneal biomechanics is a useful adjunct in refractive work-up and has been detailed in Chapter 4. Corvis-ST has emerged as a complimentary diagnostic tool to corneal tomography for screening refractive surgery patients. 13,14 Combined use of the tomographic and biomechanical indices is superior to the use of tomographic parameters alone in detecting preclinical ectasia.15

Corneal Pachymetry Corneal thickness may be ascertained with Scheimpflug tomographers, anterior segment optical coherence tomo­ graphy (ASOCT), or an ultrasonic pachymeter. Approxi­ mately 12–14 microns of stromal tissue is ablated for each diopter of refractive correction. The estimated postopera­ tive residual stromal bed thickness (RSBT) after laser refractive surgery should be at least 250–300 microns. Santiago et al. introduced the term “percentage tissue altered (PTA)”, which is calculated as the sum of flap/cap thickness and stromal ablation depth/lenticule thickness divided by the total preoperative central corneal thickness. PTA of >40% is indicative of a high risk of developing postoperative ectasia even in the presence of normal tomo­ graphy and RSBT.16

Ocular Wavefront Analysis The advent of customized corneal ablation has led to wavefront analysis becoming an integral part of refractive surgery work-up. Ocular wavefront analysis helps in decision-making and patient selection for customized corneal ablations. The accuracy and outcomes of wavefront and topography-guided LASIK depend on the acquisition of good quality ocular wavefront and topography scans.17

Ocular Biometry Patients planned for a pIOL implantation require an objective assessment of aqueous depth with an ASOCT, Scheimpflug imaging, or optical biometer. Anterior chamber angle assessment by gonioscopy or ASOCT should be performed to determine suitability for pIOL implant. In addition, white to white diameter is required to determine the pIOL size, which may be measured with an optical biometer, Scheimpflug tomo­grapher, or a digital caliper.18 Corneal endothelial specular microscopy should be performed before any intraocular procedure.

  DECISION MAKING Decision-making regarding the type of refractive surgery is a holistic process that encompasses various aspects of patient history, examination, and investigative modalities to determine suitability for a specific procedure as well as takes into account patient expectations (Fig. 1). The choice of procedure may in part be determined by patient’s age, occupation, lifestyle, magnitude and type of refractive error, and anatomical parameters such as corneal thickness, anterior chamber depth, and the lenticular status. Table 4 enumerates the approved range of refractive correction for different refractive procedures.

Cornea-based Procedures Cornea-based procedures, namely, LASIK, SMILE, and PRK, are the most commonly performed refractive surgeries

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:15 PM/04 Aug 21

CHAPTER 7: Preoperative Evaluation, Patient Counseling, and Decision Making

Fig. 1: Refractive surgery—preoperative evaluation and decision-making. (EDOF: extended depth of focus; IOL: intraocular lens; MFIOL: multifocal intraocular lens; LASIK: laser-assisted in situ keratomileusis; RSBT: residual stromal bed thickness; AC: anterior chamber; ACA: anterior chamber angle; PTA: percentage tissue altered; PRK: photorefractive keratectomy; SMILE: small incision lenticule extraction; ECC: endothelial cell count)

TABLE 4: United States Food and Drug Administration (US-FDA) approved ranges of refractive error correction for refractive surgeries. Myopia

Hyperopia

Procedure

Sphere

Cylinder

Sphere

Cylinder

LASIK*

0 to −14 DS

0 to 6 DC

0 to +6 DS

0 to 6 DC

PRK*

0 to −13 DS

0 to 4 DC

0.5 to +6 DS

0.5 to 4 DC

SMILE

−1 to −10 DS

0.75 to 3 DC

Off-label

Off-label

Phakic IOL

−3 D to −20 DS

1 to 4 DC

Off-label

Off-label

(SMILE: small incision lenticule extraction; LASIK: laser-assisted in situ keratomileusis; PRK: photorefractive keratectomy; IOL: intraocular lens; D: diopter; S: sphere; C: cylinder) *Approved range of correction varies with different laser platforms

Flowchart 1: Decision-making for corneal based refractive surgeries.

(EBMD: epithelial basement membrane dystrophy; RSBT: residual stromal bed thickness; LASIK: laser-assisted in situ keratomileusis; SMILE: small incision lenticule extraction; PRK: photorefractive keratectomy; PTA: percentage tissue altered; AZ: ablation zone)

and are preferred in patients with mild–moderate refractive errors (Flowchart 1). Patients should be within the pre­ scribed refractive error range, have a sufficient RSBT, normal topography, and an estimated postoperative keratometry ranging from 34 to 50 D. PRK or SMILE, being flapless, may be a better choice for patients involved in contact sports or employed in military or paramilitary forces. Surface ablation is preferred in epithelial basement membrane dystrophy (EBMD) due to an increased risk of epithelial sloughing during flap creation. It may also

be preferred in cases with superficial stromal scars that may hamper penetration of femtosecond laser. Surface ablation is a safer choice for patients with borderline ectasia or suspicious topography and may be combined with adjuvant collagen cross-linking procedure (PRK Xtra). It may also be considered in hyperopic patients requiring large ablation zones but having a relatively small corneal diameter. Patients with higher magnitude of refractive errors are better suited for SMILE or LASIK. Surface ablation in these cases is associated with higher risk of regression and

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SECTION 2: Preoperative Workup and Decision Making postoperative haze. SMILE has a larger effective optical zone as compared with LASIK or PRK, and may be preferred in patients with larger mesopic pupil. The enhanced ocular surface stability and faster corneal nerve regeneration also makes SMILE a preferred modality in patients with mild preoperative dry eye. Customized ablation including wavefront-guided procedures may be preferred in cases with significant HOAs of more than 0.4 microns. Topography-guided ablation is indicated in presence of significant corneal HOAs. Though all corneal refractive surgeries increase the HOAs, the induction of aberrations is lesser with SMILE and wavefront-guided ablations. Presbyopic LASIK may be

considered in patients above 40 years with a clear lens (Flowchart 2).

Lens-based Procedures Lens-based procedures include phakic IOL implantation and refractive lens exchange (Flowchart 3). Phakic IOL implantation is usually reserved for patients with high myopia and a sufficient anterior chamber depth and endothelial cell density. It is also the procedure of choice for patients having a moderate myopia with stable subclinical or clinical keratoconus. The procedure is seldom feasible in hyperopic eyes, as they mostly have an extremely shallow anterior chamber.

Flowchart 2: Decision-making in refractive surgery of presbyopic patients.

(ACD: anterior chamber depth; ECC: endothelial cell count; EDOF: extended depth of focus; MFIOL: multifocal intraocular lens; IOL: intraocular lens) Flowchart 3: Decision-making in lens-based refractive procedures.

(ACD: anterior chamber depth; ECC: endothelial cell count; MFIOL: multifocal intraocular lens; RSBT: residual stromal bed thickness; EDOF: extended depth of focus)

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:15 PM/04 Aug 21

CHAPTER 7: Preoperative Evaluation, Patient Counseling, and Decision Making Presbyopic phakic IOL may be a viable alternative in pres­ byopic patients with large refractive errors, clear lens, and adequate anterior chamber depth. Cataract surgery with implantation of newer-generation multifocal IOLs should be considered in myopic or hyperopic patients above the age of 40 years with any cataractous changes.

Bioptics Bioptics involve the combination of more than one refractive procedure and may be considered in cases with extremely large refractive errors, which cannot be treated fully with a single procedure.

  PATIENT COUNSELING Preoperative patient counseling is the key to a successful refractive practice. Patient expectations and motivation require as much consideration as the technical measure­ ments and clinical parameters assessed while planning a refractive procedure. Setting realistic expectations tailored to the individual patient profile ensures a happy postopera­ tive patient. Patients should be made aware of the choice of procedures suitable for them along with associated visual outcomes and possible complications (Table 5). Majority of patients are expected to gain excellent uncor­ rected visual acuity after corneal refractive procedures;

TABLE 5: Visual outcomes and common complications associated with refractive procedures. Outcomes/incidence

Comments

Visual outcomes

•• >90% had UCVA ≥ 20/20 •• Nearly 100% within 1 D of target

Risk of residual error/undercorrection in hyperopes and high myopes

Dry eye

•• In 20–40% •• Mild in most cases

Peaks around 3 months; resolves by 6 months

DLK

Rare; 20/20 •• >98.7% within 1 D

•• Visual recovery delayed •• May take up to 3 months •• Halo effect for 4–6 weeks due to slow healing

Delayed epithelial healing

•• Normal epithelium heals by 3–4 days •• Delayed healing in 3–4%

•• Can delay visual recovery •• Causes photophobia/watering

Postoperative pain

Mild–moderate pain in 10% patients

Peaks around 24–48 hours after surgery and then resolves

Haze

•• Visually significant in about 1–4% cases •• Higher incidence in high myopes/ hyperopes

•• May affect visual acuity •• Requires steroid therapy •• Peaks at about 3 months; subsides by 6 months

Visual outcomes

•• >90% had UCVA > 20/20 •• >95% within 1 D

Visual quality superior to laser-based surgeries in high myopia

Glaucoma

Rare; 0.5%

Incidence lower in V4c model of ICL

SMILE

PRK

Phakic IOL implantation

Cataract

Visually insignificant cataract in 2.3% cases 1% visually significant lens opacities

Endothelial cell loss

2–6% at 2 years with ICL

•• Higher with anterior chamber pIOL •• Long-term endothelial cell loss is more

Endophthalmitis and RD

Very rare; 3 D astigmatism, and hyperopia •• Ablation depth > 75 µm •• Smaller optical zone •• Younger age •• Male sex •• UV exposure •• Atopy •• Autoimmune disease •• Retreatment and enhancements

•• Intraoperative mitomycin C •• Topical corticosteroids •• Epithelial-preserving techniques

•• Topical corticosteroids •• PTK with MMC •• Mechanical debridement with 0.02% MMC •• LK/full-thickness keratoplasty (rare)

Delayed epithelial healing

Poor ocular surface and healing

•• •• •• ••

•• Preoperative assessment of the •• Topical lubricants •• Soft BCL ocular surface and tear film •• Avoid large size of the epithelial defect with respect to the ablation zone

Epithelial flap-related complications

Stromal incursion of the blade

Blunt epikeratome blades in epi-LASIK

Poor ocular surface Preoperative dry eye Excessive use of topical drugs Excessively steep BCL

Glare and halos Aberrant deflection •• Smaller optical zones of the light rays at the •• Low refractive errors edges of the ablation •• Decentered ablations zone in scotopic pupil Decentered ablation

Misalignment of laser beam with respect to pupillary center

Bandage contact lens Topical anesthetics Topical NSAIDs Other drugs—topical morphine, sumatriptan, oral analgesics, and oral gabapentin

Avoid blunt blades/multiple reuse of blades

•• BCL and lubricants •• Retreatment, if required

Avoid too small optical zones

Customized ablations with wider diameter of optical zones

•• Inability of the patient to •• Patient positioning and maintain fixation counseling •• Improper positioning of the •• Machine calibration check patient’s head •• Proper centration by surgeon •• Improper alignment of the optics of the laser delivery system •• Incorrect centration by surgeon

Retreatment with topography-guided or wavefront-guided ablation profiles

(BCL: bandage contact lens; LASIK: laser-assisted in situ keratomileusis; NSAID: nonsteroidal anti-inflammatory drug; MMC: mitomycin C; PTK: phototherapeutic keratectomy; LK: lamellar keratoplasty; UV: ultraviolet)

postoperative haze occurs almost universally after PRK and spontaneously resolves without any sequelae. Late visually significant postoperative haze is observed in 0.6–4% cases after PRK (Figs. 1A and B).3,4

Pathophysiology Corneal haze is a result of the wound healing response that occurs after stromal ablation. The disruption of the epithelial cells and basement membrane in PRK increase the incidence of postoperative haze, as the inflammatory mediators including cytokines and growth factors can easily flow from the epithelium to the corneal stroma. This causes an upregulated expression of the matrix metal­ loproteinases and there is a transient anterior stromal fibroplasia with new extracellular matrix production of type III collagen, type VII collagen, and keratan sulfate. Corneal

haze is associated with the proliferation of myofibroblasts and disorganized deposition of collagen fibers.

Clinical Evaluation of Haze Corneal haze is clinically characterized as an early transitory haze and a late persistent haze. The early haze is more common and observed 1–3 months after surface ablation. It reaches a peak at 3–6 months and then spontaneously resolves over a course of 6–12 months. The late corneal haze occurs 3–5 months after surface ablation, may cause central corneal scar, and leads to a fall in visual acuity. It can persist up to 3 years and surgical management is often required. Various modalities are available to evaluate corneal haze, including slit-lamp biomicroscopy, Scheimpflug imaging, high-frequency ultrasonic biomicroscopy, scattero­ metry, or confocal microscopy.

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SECTION 3: Corneal Ablative Procedures

A

B Figs. 1A and B: Persistent postoperative haze after photorefractive keratectomy.

The corneal haze may be graded clinically on a scale of 0–4 as per the Fantes’ grading system (0—no haze, 0.5—trace haze, 1—iris details visible, 2—mild obscuration of iris details, 3—moderate obscuration of the iris and lens, 4—complete opacification of the stroma in the area of the scar with total obscuration of anterior chamber).5

Predisposing Factors Various factors predispose to the development of corneal haze such as high refractive correction, younger age, male sex, ultraviolet (UV) light exposure, atopy, autoimmune disease, and multiple surgical interventions.6-8 Higher magnitude of refractive error of more than −6.0 D of myopia, hyperopia and high astigmatism of more than 3 D are associated with corneal haze. A depth of ablation of >75 microns leads to increased subepithelial haze. Smaller optical zones are associated with increased haze, and optical zones of 4.5 mm or more may be protective. Exposure to high UV radiation levels increases the incidence of late-onset corneal haze. Enhance­ment and re-treatment procedures have a higher risk of developing corneal haze.

Prevention Mitomycin C (MMC) is used as an adjunct intraoperatively during surface ablation to minimize the incidence of postoperative haze. MMC is applied directly on the stromal bed after removing the epithelium and excimer laser ablation. Various dosing regimens have been described employing 0.002–0.02% of MMC for a duration ranging from 12 to 120 seconds.9 Haze has been reported with the use of lower concentrations of 0.002% MMC, or with the duration of application 500 fs

500 fs

>500 nJ

1,053 nm

5 MHz

200–300 fs

40%, pachymetry 0.4 microns), moderate refractive errors, and reliable ocular wavefront data with regular corneas

Suited for patients with reliable topography scans with significant corneal HOAs, large angle kappa (e.g., hyperopes) or even virgin eyes

Advantages

•• Does not require preoperative •• Aims to correct all pre-existing HOAs •• Takes into account entire ocular aberrometry •• Allows creation of larger OZ than aberration profile conventional treatments

•• Treats HOAs based on corneal aberration profile •• Surgeon can specify the target asphericity

Limitations

•• Does not corrected pre-existing HOAs •• Precompensation of HOAs is computed over an emmetropic eye model •• Greater tissue ablated in periphery

•• Treatment accuracy relies on repeatable and reliable topography scans •• Does not take into account internal aberrations •• Treatment protocols evolving— no consensus for patients with different refractive and corneal astigmatism

•• Treatment relies on accurate acquisition of wavefront data •• Expensive aberrometers required •• WF data acquired is static, while the patient’s actual WF is dynamic •• Not feasible in highly aberrated corneas •• Treatment accuracy affected by pupil centroid shift, lenticular accommodation, and intraoperative cyclorotation

(HOAs: higher order aberrations; OZ: optical zone; WF; wavefront) Flowchart 1: Decision-making algorithm for planning customized corneal ablation.

(HOA: higher order aberration; TG: topography-guided; VA: visual acuity; WG: wavefront-guided; WO: wavefront-optimized; WF: wavefront; RE: refractive error; D: diopters; SA: spherical aberrations)

Mrochen et al. first described a model of wavefrontoptimized ablation algorithm where the subjective refraction of the patient and the amount of spherical aberrations

induced by the classic aberration profiles were used to create a nomogram to modify the existing ablation profile. The WO profiles lead to a more aspheric shape without a

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

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CHAPTER 12: Customized Corneal Ablation

Fig. 1: Wavefront-optimized ablation profile.

substantial increase in the central ablation depth; however, the depth of peripheral ablation is 35% more than that seen with the classical profiles.7 The WaveLight Allegretto Wave excimer laser system received United States Food and Drug Administration approval for WO laser-assisted in situ keratomileusis (LASIK) in 2003.

Preoperative Considerations and Patient Selection The excellent visual outcomes observed with WO LASIK, the lack of requirement for any expensive aberrometry device and complex, time-consuming interpretation of wavefront or topography measurements make it the preferred technique for corneal laser refractive surgery by most surgeons. Majority of the patients presenting for corneal ablative refractive surgery are well-suited for WO LASIK. Exceptions being those with significantly high preoperative HOAs or extremely irregular corneas, who may benefit more with a WG or TG ablative procedure, respectively. Patients with larger pupil size may also have a slight benefit with a WG procedure.

Visual Outcomes The visual outcomes of WO LASIK are superior to con­ ventional LASIK. The US FDA trial investigating the WaveLight Allegretto Wave Laser System in myopic patients reported 84% of the eyes with an uncorrected visual

acuity (UCVA) of 20/20 or better; 32.4% of eyes gained one line of VA as compared to the preoperative best spectaclecorrected visual acuity (BSCVA). Patients also reported a subjective improvement in glare, light sensitivity, and night driving symptoms after the procedure. Among patients undergoing hyperopic LASIK, 67.5% reported an UCVA of 20/20 or better at 3 months.

Advantages The WO treatment algorithm predicts the precompensation required based on patient’s subjective refraction alone, without requiring any preoperative aberrometry or topography measurements. It allows the creation of larger optical zones with more realistic dimensions and takes average epithelial remodeling into account while planning treatments.

Disadvantages The assumptions on precompensation for the HOAs are applicable to an average eye only. Better results may be obtained, if each surgeon creates his own nomogram for wavefront optimized treatments based on his patients’ outcomes. In addition, precompensation is performed only for rotationally symmetrical aberrations. Pre-existing HOAs are not corrected. Spherical and cylindrical errors are treated in two steps, one following the other. Lastly, more tissue is ablated per diopter of refractive error with a greater amount of tissue ablated in the periphery.

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SECTION 3: Corneal Ablative Procedures

  WAVEFRONT-GUIDED ABLATION Ocular wavefront-guided ablation profile aims to treat both the pre-existing higher order aberrations and minimize the induction of new HOAs in order to improve the visual quality and contrast sensitivity as compared with con­v entional and aspheric treatment profiles. 10 The ocular aberration data of the patient obtained by a wavefront sensor is fed electronically into the treating laser and used to program the pattern of laser ablation. The CustomCornea LASIK with LADARVision 4000 Excimer Laser (Alcon) in combination with a LADARWave CustomCornea Wavefront System (Hartmann Shack aberrometer) was the first system approved for WG LASIK in 2002. Table 2 lists the various FDA approved wavefront-guided LASIK systems.

Operative Considerations The important operative considerations, which determine the success of WG LASIK include appropriate patient selection, accurate acquisition of preoperative wavefront data, algorithm to plan treatment with the aim of treating

existing HOAs as well as proper intraoperative centration and eye tracking.10,11

Patient Selection Wavefront-guided LASIK is indicated for patients who suffer from high pre-existing ocular HOAs (>0.4 microns) and associated visual disturbances such as glare, haloes, and starbursts. In addition, patients with larger mesopic and scotopic pupil size may benefit from WG LASIK as lower postoperative HOAs will result in better visual quality in low light conditions. Wavefront-guided LASIK should be avoided in cases where repeatable ocular wavefront (WF) measurements cannot be acquired successfully. The accuracy of WF measurements is adversely affected in eyes with tear film abnormalities or highly aberrated corneas due to scars or keratoconus. Patients with large consistent differences between the manifest refractive error and lower order aberrations (LOAs) as computed by the aberrometer are also not suited for the procedure. Moreover, the clinical benefit of treating pre-existing HOAs is often dwarfed in patients undergoing LASIK for higher refractive errors (>−4 D).

TABLE 2: Commercially available customized corneal ablation platforms. Name of treatment

Aberrometer used

Planning algorithm and features

Approved refractive error range

Wavefront-guided ablation platforms CustomCornea LASIK LADARVision 4000 excimer laser system (Alcon, 2002)

LADARWave •• Zernike-based algorithm CustomCornea wavefront •• Active infrared eye tracking system system •• Limbal marks based registration/ (Hartmann–Shack device) cyclotorsion compensation

Myopia ≤ −8 D, Astigmatism of –0.5 to –4 D

Personalized vision correction, Technolas 217Z Zyoptix System (Bausch and Lomb, 2003)

Zywave wavefront •• Zernike-based algorithm •• Active infrared eye tracking system system (Hartmann–Shack device)

Myopia ≤ −7 D Astigmatism ≤ 3 D MRSE < −7.5 D

CustomVue LASIK VISX STAR S4 IR (AMO, 2005)

Visx WaveScan system •• Fourier-based algorithm (Hartmann–Shack device) •• Three-dimensional active infrared eye tracking •• Automated alignment using iris registration

Myopia and myopic astigmatism up to 11.00 D MRSE Astigmatism ≤ 3.00 D Mixed astigmatism: 1–5 D Hyperopia and hyperopic astigmatism up to 3D MRSE and cylinder of 0–2 D

WaveLight ALLEGRETTO WAVE Excimer Laser System (2006)

WaveLight ALLEGRO Analyzer (Tscherning device)

•• Zernike-based algorithm •• Active infrared eye tracking system

MRSE ≤ −7 D Or Spherical component ≤ −7 D and ≤ 3 D astigmatism

Advanced CustomVue LASIK, VISX STAR S4 IR (AMO, 2015)

iDesign Advanced WaveScan Studio (High-resolution Hartmann–Shack device)

•• Fourier-based algorithm •• Three-dimensional active infrared eye tracking •• Automated alignment using iris registration

Up to −11 D of myopia and −5 D of astigmatism as measured by the iDesign system Mixed astigmatism: 1–5 D Hyperopia ≤ +4 D sphere, astigmatism ≤ 2 D

Topography-guided ablation platforms WaveLight ALLEGRETTO WAVE EYE-Q excimer laser system (Alcon, 2013)

WaveLight ALLEGRO Topolyzer

Topography-guided customized ablation treatment (T-CAT) software for treatment planning

Myopia ≤ −8 D, Astigmatism ≤ 3 D MRSE ≤ −9 D

Final Fit Custom Ablation (Nidek EC-5000, 2013)

OPD-scan ARK-10,000

Final Fit™ software for treatment planning

Myopia −1.0 to –4.0 D Astigmatism –0.5 to –2 D

(D: diopters; MRSE: manifest refraction spherical equivalent; LASIK: laser-assisted in situ keratomileusis)

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:17 PM/04 Aug 21

CHAPTER 12: Customized Corneal Ablation

Wavefront Measurements Accurate wavefront measurements are critical for optimal outcomes with WG LASIK. The two commonly used aberro­ meters for clinical wavefront assessment are Hartmann– Shack aberrometers and Tscherning aberrometers. The resolution of aberrometers depends on the number of the lenslet data points analyzed. The iDesign, an advanced version of earlier WaveScan aberrometer, is a newer highresolution aberrometer and can sample up to 1,250 points across a 7-mm pupil, which is five times higher than its predecessor. It has a larger field of view and uses an enhanced iris registration algorithm.12

Wavefront Analysis and Ablation Algorithm The quality of a wavefront-guided ablation relies on accurate WF measurements. The optical aberrations of the eye may be represented mathematically using either the Zernike polynomials or the Fourier transform. The Fourier transform acquires information from 240 fitting parameters and provides a more detailed analysis of the wavefront with a more accurate ablation shape. In addition, it captures all valid data points even from elliptical or irregular pupils, is faster to implement computationally, and can better depict the aberration data.10 In contrast, the Zernike analysis utilizes only 28 fitting parameters from the Hartmann Shack sensor, provides an overtly smooth wavefront analysis due to the fewer number of fitting parameters used, and derives data from a circular aperture only.13,14 The WaveScan system employs Fourier algorithms while the LADARWave, Allegro Analyzer, and Zywave systems employ Zernike polynomials in their algorithms for WF data reconstruction (see Table 2).

Torsional Alignment and Eye Tracking Torsional registration during WG LASIK is important, as HOAs such as astigmatism are not radially symmetrical. Torsional misalignment may occur either due to head tilt, cyclotorsion, and inadvertent eye movements during laser delivery and can adversely affect treatment outcomes.11 Torsional alignment may be performed with the aid of limbal marks or automated iris registration. Most modern platforms including the VISX, Zyoptix, and Allegretto systems incorporate iris registration. In addition, passive or active pupil trackers using infrared camera images are employed by all customized excimer laser platforms to interrupt or steer the laser, if the eye moves during laser delivery.

Centration Limbal or pupil-based centration is performed by current platforms. Pupil center may shift up to 0.7 mm, as it dilates and constricts. The pupil centroid shift should be consi­ dered in treatments based on pupil centration, as it may

induce new HOAs in up to 40% of cases. Iris registration can reliably detect and compensate for most of the pupil centroid shift.15

Accommodative Status and Pupil Size Accommodative status of the patient may impact the accuracy of both manifest refraction and measured wavefront, especially with devices that capture the wave­front on the natural pupil. Accommodation is less of a concern with devices relying on cycloplegic capture. A pupillary dilation of about 5 mm is usually required by most aberrometry systems for capturing the ocular WF data. The new iDesign system can capture the WF and treat patients with pupil size as small as 4 mm.

Outcomes United States FDA trial for WaveLight Allegretto Wave Excimer Laser System compared the outcomes of WG and WO LASIK and observed comparable visual and refractive outcomes in 83% of eyes. WG LASIK led to a signifi­ cantly better postoperative HOA profile in patients with >0.4 microns of pre-existing HOAs.16 Improved visual outcomes, better astigmatism control, fewer photic symptoms, and HOAs have been reported with high-resolution aberrometry systems. This may be attributed to better axial and torsional registration with centroid shift and high-resolution detection of the aberrations allowing a more detailed ablation profile.12,17

Advantages Wavefront-guided ablation aims to correct all pre-existing HOAs in addition to sphere and astigmatism by taking into account the entire eye’s HOAs. Postoperative induction of new HOAs is lesser as compared with WO treatments.

Disadvantages Wavefront-guided LASIK relies on accurate and repeatable measurement of ocular aberrations by the aberrometer. The WF measurements are acquired at a single time point preoperatively and are thus static, while the ocular optical system and its WF are dynamic in nature, being affected by various other factors such as ambient lighting and accommodative status of the eye. It considers only monochromatic aberrations and precompensates for rotationally symmetrical aberrations alone. Wavefront-guided LASIK may not be feasible in eyes with highly aberrated corneas where acquiring an accurate ocular wavefront map is not possible. In addition, the accuracy of treatment may be affected by the degree of lenticular accommodation, intraoperative cyclorotation, and pupil centroid shift. WG LASIK cannot accurately account for factors such as changes in ocular aberrations with aging, biomechanical changes induced by the ablation,

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SECTION 3: Corneal Ablative Procedures wound healing, corneal hydration, and damping effects of the flap or flap-induced aberrations. It results in more stromal tissue ablated per diopter of refractive error.

  TOPOGRAPHY-GUIDED ABLATION Topography-guided ablation takes into account only the corneal HOAs and aims to regularize corneal surface irregularities based on the topographic images. Topography may be assessed using a Placido disk topographer (Topolyzer) or a Scheimpflug tomographer (Oculyzer) (Fig. 2). Scheimpflug-based tomographers are less dependent on tear film and can directly evaluate the central corneal area. Placido-based systems extrapolate the data for the central area and may be less accurate in eyes with central corneal irregularities. The data to construct the corneal maps are derived from the assessment of a large number of points (about 22,000 with Allegro Topolyzer). The images are analyzed using a proprietary algorithm for devising the laser treatment plan. The manifest refraction entered by the surgeon and the corneal HOAs measured by the topographer are used to plan the final laser ablation pattern. Topographic measurements are centered on the corneal vertex and free of pupil-centroid shift errors.18 The commercially available laser platforms approved by US FDA for TG ablation are described in Table 2.

Patient Selection Topography-guided ablation was initially introduced for treatment of irregular corneas; it was later approved to treat virgin eyes. Patients with significant corneal HOAs causing visual disturbances are good candidates for TG ablation, provided good quality repeatable topography scans may be acquired. Patients with high irregular astigmatism, post-LASIK ectasia, decentered ablation, small optical zones, post-radial keratotomy astigmatism, post-keratoplasty astigmatism, and keratoconus are also potential candidates for TG ablation. Patients with hyperopia with or without astigmatism are also suitable candidates for TG ablation. Such patients often have a large angle kappa, thus, a corneal vertex-centered TG ablation will induce lesser astigmatism as compared with a pupil-centered WG ablation. Further, postoperative regression after hyperopic correction is more in cases with increased corneal surface irregularity and these patients benefit from TG ablation.19,20 TG LASIK has received US FDA approval for normal eyes with regular astigmatism, and leads to an improvement in subjective night-driving symptoms in about a quarter of the patients. Acquisition of good quality scans is imperative for patients undergoing TG LASIK. Cases with a poor ocular surface, dry eye, or deep-set eyes, which preclude the acquisition of good quality scans, are unsuitable for TG ablation. A WO ablation may be a better option for

Fig. 2: Topography-guided ablation profile.

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:17 PM/04 Aug 21

CHAPTER 12: Customized Corneal Ablation these patients. Eyes where the magnitude of astigmatism measured on topography differs substantially from the manifest astigmatism may be better suited for a WO ablative procedure.

Treatment Protocols and Outcomes Topography-guided ablation has evolved over the years with different protocols gaining popularity for treatment of virgin eyes with regular corneas (Flowchart 2). The original FDA protocol was described for eyes with minimal difference between the topographic and manifest astigmatism.21 Manifest refraction data is combined with the topography images, and TG LASIK is recommended for cases with 6.00 D, and astigmatism more than 3.00 D are risk factors for postoperative undercorrection. The standard companyadvised nomogram has a tendency to undercorrect the refractive error. Suction loss is an important risk factor for postoperative enhancement. An inexperienced surgeon may experience an increased probability of suction loss and repeated docking attempts, thereby resulting in poor refractive outcomes.

Management In a majority of cases with epithelial ingrowth, small epith­ elial islands are noted at the incision site. These cases may be observed, since majority may spontaneously resolve with time. Neodymium-doped:yttrium aluminum garnet (Nd:YAG) laser may be used to disrupt localized islands of ingrowth. More extensive localized epithelial ingrowth warranting intervention may be managed by scraping off the epithelial cells after opening the side-cut. In cases of extensive epithelial ingrowth involving the visual axis, surgical treatment may be needed. The stromal cap may have to be converted into a flap in order to effectively scrape the epithelial cells from the interface.

Outcomes Epithelial ingrowth in cases of SMILE may present as nests of epithelium at the incision site, which is

A

Prevention Careful patient selection for SMILE is of great importance. Those above 35 years of age should be dissuaded from surgery. It has been observed that overcorrection is more common in low refractive errors and undercorrection is more likely in high-refractive errors. An optimization of the nomogram may help in minimizing postoperative undercorrections and overcorrections.

Management Various procedures have been described for enhance­ ment in patients with suboptimal visual gain after SMILE, including surface ablation, LASIK, or circle pattern. Refractive stability for a minimum period of 3 months should be ensured prior to any intervention.

B Figs. 10A and B: (A) Epithelial ingrowth in small incision lenticule extraction (SMILE) interface; (B) anterior segment optical coherence tomography (ASOCT) showing interface epithelial cell nests.

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:17 PM/04 Aug 21

CHAPTER 14: Complications of Small Incision Lenticule Extraction

Outcomes

Management

The visual outcomes after enhancements are usually satisfactory. In a retrospective study done by Liu et al., 93% patients undergoing enhancement gained a vision of 6/12–6/6, with a mean residual spherical equivalent of 0.13 D. 19 Postoperative haze may limit the visual outcomes after PRK, as observed in cases with irregular topography.

Mild cases may be observed, as re-enhancement procedures may not help in the resolution of higher order aberrations. Topography-guided PRK seems to be a good option in patients with disabling symptoms due to irregular topography.6

Irregular Topography Incidence Irregular topography may be observed in 0.5–1% cases after SMILE.5,6

Predisposing Factors Difficulties in lenticule separation and extraction, dense opaque bubble layer, laser settings with lower spot energy and closer spacing, and excessive intraoperative manipulations may predispose to the development of postoperative irregular corneal topography. Retained lenticule fragments also result in irregular astigmatism.4

Management Spontaneous improvement of vision is noted in majority of cases due to corneal or epithelial remodeling, stabilization of the tear-film, and neuronal adaptation. In cases of non-improvement of vision, topographyguided PRK can be attempted. PRK may result in postopera­ tive haze and prolonged visual recovery time. It should therefore be considered only after several months and in cases with significant visual symptoms. Rigid gas permeable contact lens may be useful in some cases.

Outcomes Topography-guided PRK results in improvement in visual acuity and remission of visual symptoms such as halos and ghost images. Postoperative haze limits the visual outcomes, and concurrent MMC application is advocated to achieve optimal results.17

Optical Aberrations Incidence Optical aberrations and dysphotic symptoms in the form of glare, halos, and ghost images may be observed after SMILE in 0.2–0.4% of cases.5,6

Predisposing Factors Excessive intraoperative manipulations, retained lenticule fragments, decentered treatment profile, and epithelial ingrowth in the stromal interface may cause irregular topography and hence cause visual symptoms.

Outcomes Remission of symptoms with good visual outcomes is observed in patients treated with topography-guided PRK. However, postoperative haze may limit the visual outcomes.

Decentered Treatment Incidence A decentration >0.3 mm has been observed to induce higher order aberrations with suboptimal visual quality.20 In a study by Li et al., the ablation profile was decentered within 0.20 mm in 70% eyes, within 0.30 mm in 90% eyes, and within 0.50 mm in all eyes.21

Predisposing Factors Patients with a large angle kappa and a large disparity between the visual axis and corneal axis may be at a high risk of decentered treatment. The absence of an active eye tracker during the procedure makes it more surgeon dependent, thereby increasing the risk of decentration in SMILE.

Prevention Corneal vertex centration is deemed most accurate in corneal refractive surgeries. Patients with a large angle kappa may be excluded from the surgery.21 To ensure proper centration during docking, the patient bed should be moved slowly. At the point when the cone touches the cornea, the corneal vertex should automatically fit the apex of the cone. In cases with eccentric docking, the suction should be released, and the patient re-docked in order to prevent an eccentric treatment.

Management Minimal decentration up to 0.3 mm from the corneal center does not cause visual symptoms and hence no intervention is needed. Surgical intervention should be considered in presence of dysphotic symptoms or loss of more than two lines of Snellen’s visual acuity. Topography-guided PRK can be attempted in such cases; however, persistence of haze and prolonged postoperative visual recovery may be seen with some patients.

Outcomes The decentration has a greater influence on HOAs in eyes with LASIK than SMILE, and the aberrations induced are

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SECTION 4: Small Incision Lenticule Extraction majorly coma and trefoil. SMILE is better tolerated for horizontal displacement than LASIK but there exists a positive correlation between vertical displacement and HOAs, which could adversely affect visual outcomes.

Ectasia Incidence Ectasia following SMILE is rare and there have been few case reports about the same.22,23

Pathophysiology The biomechanical strength of the cornea is greater in its anterior layer due to stronger intralamellar collagen bonding. SMILE is essentially a flapless surgery, where the lenticule is extracted through a small incision. This results in minimal disruption of peripheral collagen fibers compared with LASIK, thus providing superior corneal biomechanics. However, the actual removal of corneal stromal tissue in SMILE does weaken the cornea to some extent, and hence there is always a theoretical risk of ectasia.

Predisposing Factors The predisposing factors include forme fruste keratoconus, high magnitude of refractive correction, thin corneas, and low RSBT (3.5

12.6

≤3.5

12.6

>3.5

13.2

Gonioscopy-open angles with iridocorneal angle aperture atleast 30° (Shaffer grade 3 and 4 or Scheie grade 0 and 1)

Posterior segment pathology including macular degeneration and retinal pathologies

≤3.5

13.2

>3.5

13.2

≤3.5

13.2

No ocular pathology (corneal disorders, glaucoma, uveitis, cataract, maculopathy, etc.)

Previous corneal or intraocular surgery

>3.5

13.7

≤3.5

13.7

No previous ocular surgery

Systemic diseases (such as autoimmune disorder, connective tissue disease, atopy, diabetes mellitus)

>3.5

13.7

Any

Not recommended

10.7–11 11.1 11.2–11.4

(ACD: anterior chamber depth; pIOL: phakic intraocular lens; ICL: implantable collamer lens; MPL: Medennium phakic lens)

Sizing The iris-claw pIOLs have fixed overall diameter and sizing is generally not altered based on the ocular anatomy, as these lenses are fixated to the mid-peripheral iris. Sizing assumes importance during sulcus-fixated posterior chamber pIOL implantation in order to ensure adequate clearance of the ICL from the crystalline lens as well as the corneal endothelium. ICL is available in four different overall diameters for myopia (12.1–13.7 mm) as well as hyperopia (11.6–13.2 mm), and the appropriate size is determined by the horizontal WTW and the ACD measurements. The lens size is calculated by adding 1.1 mm to the horizontal WTW in cases with ACD of 3.5 mm or less. In cases with ACD >3.5 mm, 1.6 mm is added to the WTW to determine the lens size up to a maximum length of 13.7 mm. The calculated lens size is rounded off to the nearest available lens diameter; it is rounded down to the lesser size in cases with ACD of 3.5 mm or less and rounded up to the higher size in cases with ACD >3.5 mm (Table 4).

Peripheral Iridotomy Conventionally, one-to-two neodymium-doped:yttrium aluminum garnet (Nd:YAG) peripheral iridotomies (PIs)

11.5–11.6 11.7–12.1 12.2 12.3–12.9 ≥13

with at least 500 microns width are performed 1–2 weeks preoperatively as a prophylactic measure to prevent postoperative pupillary block glaucoma. Intraoperative peripheral iridectomy may also be performed instead of preoperative PIs. However, the introduction of central KS-Aquaport in latest models of ICL with CentraFLOW technology to ensure continuous aqueous flow has obviated the need for a PI before ICL implantation. PI is still recommended before iris-claw pIOL and hyperopic pIOL implant.

  SURGICAL TECHNIQUES The surgical steps vary with the type of pIOL. We will briefly discuss the surgical techniques of the two FDA approved phakic IOLs—Artisan/Verisyse and ICL.

Artisan/Verisyse pIOL A local anesthesia (retrobulbar or peribulbar block) is preferred during Artisan/Verisyse implantation. A biplanar 5.2-mm or 6.2-mm (based on the optic size) posterior corneal incision is made superiorly (12’o clock) along with two paracenteses incisions at 2’o clock and 10’o clock, directed towards the site of enclavation. The pupil is constricted using pilocarpine. The center may be marked to ensure proper centration of the pIOL optic over the pupil center. The anterior chamber (AC) is filled with a cohesive ophthalmic viscosurgical device (OVD); the pIOL is

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SECTION 5: Lens-based Refractive Surgeries inserted in the AC and rotated 90° into a horizontal position. The enclavation needle is introduced through the paracentesis port and used to hold a thin fold of the midperipheral iris. The iris fold is enclaved into the claw of the pIOL by slightly depressing the pIOL with the implantation forceps. The enclavation needle is then introduced through the other paracentesis port to fixate the second haptic in a similar fashion. Peripheral iridectomy is performed at the end of surgery, if preoperative PIs have not been performed. The wound is closed using interrupted 10-0 monofilament sutures (MFS). In case of toric pIOL implantation, the reference axis is marked preoperatively. It is implanted either at 0° or 90° based on the axis, in a similar fashion. Implantation of the foldable Artiflex/Veriflex pIOL is similar except for the insertion of the lens, which is performed using a especially designed spatula via a smaller incision of 3.2 mm.

Implantable Collamer Lens Implantable collamer lens may be inserted under either topical or local anesthesia. Preoperative full mydriasis is essential before ICL implant. Loading the ICL into its cartridge is crucial for proper implantation. The ICL is gently loaded on the cartridge filled with OVD, with the dome side up. The two tiny holes on the footplates (distal right and proximal left)

help in the correct antero–posterior orientation of the lens. The ICL is gently pulled into the hub of the cartridge using an ICL-holding forceps. The cartridge is placed in the shooter, and a soft tip (Staar foam tip) is placed before the plunger to protect the lens. A 3.2-mm clear corneal incision is made temporally or superiorly (surgeon preference) along with an MVR port on either side of the main incision placed 90° away. The AC is filled with OVD, the cartridge is inserted bevel down, and the ICL is carefully injected. The unfolding of the ICL should be slow and controlled to avoid inverse opening of ICL. The haptics are gently pushed beneath the iris with a blunt spatula, followed by centration of the ICL, OVD removal, and hydration of the wounds (Figs. 5A to D).

  POSTOPERATIVE ASSESSMENT OF VAULTING Vault is defined as the distance from the center of the posterior surface of the pIOL to the anterior lens capsule of the crystalline lens. For ICL, the vault should be in the range of 250–750 microns.5,10,11 It may be assessed clinically on slit lamp, wherein an ideal vault for ICL is approximately equivalent to the central corneal thickness (Fig. 6A). Alter­natively, ASOCT allows for the objective assessment of postoperative vaulting (Fig. 6B). The development of

A

B

C

D

Figs. 5A to D: Surgical steps for implantation of posterior chamber phakic intraocular lens. (A) Phakic IOL placed on cartridge coated with ophthalmic viscosurgical device (OVD) and balanced salt solution (BSS) and pulled to tip of cartridge with forceps; (B) Implantable collamer lens (ICL) inserted in eye via 3.2-mm incision; (C) ICL haptics tucked beneath the iris; (D) Intraoperative optical coherence tomography (iOCT) used to assess vault at end of surgery.

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 3rd Proof Time/Date: 12:18 PM/04 Aug 21

CHAPTER 15: Phakic Intraocular Lenses

A

B Figs. 6A and B: Postoperative assessment of phakic intraocular lens vault. (A) Slit-lamp assessment of vault; (B) Anterior segment optical coherence tomography (ASOCT) to assess vault.

microscope-integrated intraoperative OCT allows for the on-table real-time assess­ment of vault immediately after ICL implantation, which correlates well with the post­ opera­tive vaulting (see Fig. 5D).12

  OUTCOMES The angle-supported phakic IOLs have been withdrawn from the market in view of unacceptable endothelial cell loss observed 2–3 years after implantation.13-15 Kohnen et al. observed more than 30% endothelial cell loss in 8.0% of eyes implanted with Acrysof Cachet pIOL, which led to an explant of the pIOL in 3.4% eyes.16 Excellent refractive outcomes were observed in the FDA trial evaluating Artisan/Verisyse pIOL implantation in myopia ranging from −4.5 to −22 D, with an uncorrected distance visual acuity of 20/40 or better in 84.0% eyes and 20/25 or better in 51.9% eyes.8 Titiyal et al. observed predictable and stable postsurgical refractive outcomes with iris-fixated pIOL for myopia in the Asian–Indian population.17 Huang et al. reviewed the outcomes of FDA approved pIOLs (ICL and Artisan/Verisyse) and concluded that phakic IOL implantation is safe and effective in the correc­ tion of myopia and myopic astigmatism. The efficacy, pre­dictability, and safety of pIOLs is superior to con­ventional corneal ablative procedures in cases of high myopia of −8 D or more.7 Albarrán-Diego et al. observed better corrected distance visual acuity and contrast sensitivity after implantation of foldable Artiflex pIOL as compared with conventional femtosecond LASIK in cases with myopia of −6 to −9 D.2 Sanders et al. compared 559 cases of LASIK with 210 cases of ICL (from 14-site US-FDA clinical trial for ICL) in myopia ranging from –8 to –12 D. ICL had better safety, efficacy, and predictability as compared with LASIK for the treatment of moderate-to-high myopia. Moreover, an uncorrected distance visual acuity of 20/20 or better was achieved by 50% eyes with ICL as compared with only 35% eyes with LASIK (p < 0.001).1 The outcomes of ICL implantation in cases with low-to-moderate myopia

( anterior chamber pIOLs

•• Early-onset cataract—direct trauma to crystalline lens •• Late-onset cataract—altered metabolic status of the lens due to disturbance of aqueous flow •• Predisposing factors: –– Older age >40 years –– High magnitude of refractive errors –– Pre-existing lenticular opacities –– Extremely low vaults posterior chamber pIOL

•• Steroid response •• Retained ophthalmic viscosurgical device •• Pupillary block

•• Medical therapy—topical antiglaucoma drugs •• Trabeculectomy or glaucoma drainage devices in refractory cases

Chronic uveitis and inflammation

Anterior chamber pIOL

Inflammation and pigment dispersion due to breakdown of the blood aqueous barrier

•• Topical and oral corticosteroids •• Explant pIOL in persistent cases

Pigment dispersion

Anterior chamber pIOL > posterior chamber pIOL

Iris chafing and pigment dispersion may be observed after pIOL implant, which may even result in raised IOP

•• Topical and oral corticosteroids •• Explant pIOL in persistent cases

Endothelial cell loss and corneal decompensation

Angle-supported pIOLs

•• Shallow anterior chamber depth posterior chamber

•• Spontaneous disenclavation/decentration •• Trauma

•• Re-enclavation of the iris tissue in the haptic •• Explant of the lens, if re-enclavation not possible •• Repositioning of decentered/ dislocated pIOL

Glare and halos

Anterior chamber pIOLs

•• Decentration of the pIOL relative to the pupil •• Large mesopic pupil size •• Distortions from the optic edge

•• Topical miotics •• Use expanded optic ICL in patients with larger mesopic pupils

Surgically induced astigmatism

Rigid pIOLs

Large incision and suture-assisted wound closure

Prefer foldable pIOLs

Retinal complications

All phakic IOLs

Related to pathological myopia

Vitreoretinal surgery, if required

(FLACS: femtosecond laser-assisted cataract surgery; pIOL: phakic IOL; IOP: intraocular pressure)

Uveitis–Glaucoma–Hyphema Syndrome The uveitis–glaucoma–hyphema (UGH) syndrome was observed with older generations of angle-supported pIOLs due to constant trauma of the uveal tissue and angle structures leading to a breakdown of the blood-aqueous barrier, iris chafing, pigment release, and glaucoma.

Cataract Incidence Cataract formation is the most common indication for explant of pIOL and is observed more commonly with

posterior chamber pIOLs (Figs. 3A and B). The incidence of cataract after pIOL implantation as reported by Chen et al. in a meta-analysis of 6,338 eyes is 1.29% with anglesupported pIOLs, 1.11% with iris-claw pIOLs, and 9.6% with posterior chamber pIOLs.2 Amongst posterior chamber pIOLs, the incidence was 25.66% with Adatomed IOL, 8.48% with Visian ICL, and 3.59% with PRL.2 The FDA trial for Visian ICL reported a 6–7% cumulative probability of developing anterior subcapsular opacities 7 years after ICL implantation; however, only 1–2% eventually developed clinically significant cataract.3 The latest models of Visian ICL are

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SECTION 5: Lens-based Refractive Surgeries

A

B Figs. 3A and B: Cataract after posterior chamber phakic intraocular lens (IOL) implant. (A) Slit-lamp photograph; (B) Anterior segment optical coherence tomography (ASOCT) showing extremely low vault.

associated with the development of cataract in only 5.2% cases, and the incidence of clinically significant cataract is 0.8% for V4 ICL.4,5 Alfonso et al. did not observe any case of cataract with the newer V4b and V4c lenses.6

Morphology The predominant morphology is nuclear sclerosis type of cataract with anterior chamber pIOLs (60% in anglesupported and 50% in iris-claw pIOLs) and anterior subcapsular cataract in posterior chamber pIOLs (90.6%).2 Of these, majority were nonprogressive and surgical intervention was required in 30.2% cases.2

Pathophysiology The pathogenesis of early-onset cataract is related to direct trauma to the crystalline lens sustained either intraoperatively or as a result of pIOL-lenticular contact. Late-onset cataract occurring more than 1 year after pIOL implantation is caused by the altered metabolic status of the lens due to disturbance of aqueous flow.

Predisposing Factors Older age: Age > 40 years is associated with an increased risk of cataract formation after ICL implant.3,4,7 High magnitude of refractive errors: Patients with higher refractive errors >−10 D are predisposed to develop cata­racts. Also, patients with hyperopia are more prone to develop cataract.3,4,7 Pre-existing lenticular opacities: Progression of pre-existing lenticular opacities is observed after ICL implant. Surgeon learning curve: An inexperienced surgeon is more prone to cause iatrogenic damage to the crystalline lens during pIOL implantation. Insufficient vault: Extremely low vaults of 1 D has been reported in up to 11.3–59% of patients undergoing myopic LASIK, and is the most common indication for post-LASIK retreatment.5 Overcorrection is less common and associated with higher myopic correction.

In contrast, retreatment after PRK is most commonly performed for regression. Naderi et al. reported regression in 19% of post-PRK patients.10 Less common indications for retreatment include visual disturbances such as glare, halos and starbursts secondary to irregular ablations, decentered ablation, small optical zones, previous flap-related complications such as button­holed flaps or incomplete flaps, and epithelial ingrowth.11,12

  RISK FACTORS Various risk factors have been associated with an increased predisposition to retreatment. These factors may be broadly classified as patient related, surgery related, and environ­ mental (Table 1).

Patient-related Factors A high preoperative spherical error, high astigmatism (>1 D), and hyperopic ablation are associated with higher rates of retreatments. Steeper preoperative keratometry (>46 D) and older age (>40–50 years) also predispose to retreatment.6,13-15 Individual wound healing response can affect the postoperative refractive error and may be influenced by the presence of pathologies such as diabetes or disorders of the immune system. Abnormal tear-film may adversely affect the lamination of the epithelium during the healing process.16 The use of rigid gas permeable contact lens has been reported as a risk factor for retreatment when used within 6 months of primary surgery.17 Better preoperative best spectacle-corrected visual acuity (BSCVA) has been associated with higher rates of retreatment, possibly attributed to higher expectations among these patients.18

Surgery-related Factors Low- (120 microns), as well as smaller optical zones (6.5 mm vs. 7 mm), pre­ dispose to increased retreatment rates. Transepithelial PRK and longer intraoperative mito­ mycin C (MMC) exposure are also associated with increased post-PRK retreatment rates.3,10

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SECTION 6: Enhancements and Retreatments TABLE 1: Risk factors for retreatment after corneal laser ablation. Risk factors

Factor

Etiology

Patient-related factors

Older age (>40–50 years)

•• More conservative approach followed leading to undercorrection •• Reduced accommodation •• Coexistent lenticular changes, which may induce a refractive error

Higher refractive error

•• Inaccurate nomogram •• Increased regression

Hyperopic error

•• Increased regression •• Increased visual disturbances due to smaller OZ, decentered ablation and increased HOAs

Higher preoperative astigmatism

•• Epithelial hyperplasia, regression •• Inaccurate nomograms

Steeper preoperative keratometry

•• Higher associated incidence of intraoperative complications—risk for retreatment •• Less biomechanically stable— higher regression rates

Surgery-related Smaller ablation factors zones

Higher risk of decentered ablation, especially in eyes with large angle kappa

Excimer laser frequency (lower frequency laser)

•• Longer ablation time •• Ablation profile •• Difference in nomograms

Type of microkeratome used (Moria M2-90)

•• Thicker flaps •• Variable flap thickness

Depth of ablation Inaccurate nomogram (too shallow or too deep)

Environmental factors

Surgeon experience

•• Different treatment criteria •• Nomogram variation •• Technique differences

Operating room humidity (increased humidity)

•• Moisture in the air may decrease the laser energy absorbed by the stroma •• Patient’s corneas may become more hydrated before the procedure, resulting in suboptimal tissue ablation

(OZ: optical zone; HOAs: higher order aberrations)

The rate of retreatment has shown a decline with the advances in laser technologies. Lower-frequency excimer lasers (WaveLight EX200) are associated with higher rate of retreatments. Flanagan et al. reported a higher retreatment rate with the Summit Apex plus excimer laser (30%) as compared to 10.1% with VISX and 11.4% with LADARVision excimer lasers.19 WaveLight Allegretto laser is associated with a much lower retreatment rate of 5.7%. Hersh et al. reported a higher retreatment rate with LADARVision laser than the Summit Apex Plus laser (18.2% vs. 9.8%).14 The retreatment

rates with the fifth- and sixth-generation excimer lasers are much lower, ranging from 0 to 1.8% and 0 to 0.3%, respectively.6,8,9

Environmental Factors Higher operating room humidity levels and lower operating room temperatures are associated with increased rates of retreatment.18,20

  PREOPERATIVE EVALUATION AND DECISION MAKING A comprehensive evaluation including a cycloplegic and manifest refraction, corneal tomography, biomechanics, ocular wavefront analysis, dilated fundus examination, and detailed ocular surface assessment to rule out dry eye disease should be conducted: ■■ A minimum of one line of improvement between uncor­ rected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA) is usually seen. ■■ Refractive and keratometric stability for at least 3–6 months is a prerequisite before proceeding with retreatment. Etiology of the residual error, whether regression or progression, should be determined. ■■ Pre-existing ocular surface disease such as dry eyes should be adequately treated before proceeding with the enhancement. Enhancement procedures can worsen or exacerbate pre-existing post-LASIK dry eyes. Tear osmolarity and tear inflammatory markers such as matrix metalloproteinase-9 have been reported to be raised in post-LASIK dry eyes and may be used as an adjunct for diagnosing and strategizing treatment of dry eyes in these patients.21 Furthermore, chronic dry eye disease itself is a risk factor for regression.22 ■■ Ocular wavefront analysis should be performed to assess the corneal and internal higher order aberrations (HOAs). The assessment would help in planning the type of ablation. A patient with significant corneal higher order aberrations due to a previous irregular or decentered ablation may not be suited for a wavefrontguided ablation, as the ocular wavefront measurements in such eyes are highly inconsistent. ■■ Accurate assessment of the RSBT and post-LASIK flap thickness may be performed using anterior segment optical coherence tomography (ASOCT) or very highfrequency ultrasonic devices. Intraoperative assessment using hand-held ultrasonic devices is less accurate owing to high inter-user variability, alteration of stromal bed hydration, and variability of cornea’s perpendicular orientation.23 ■■ Ruling out early ectasia, which may masquerade as regression, is extremely important. The Corvis Biomechanical Index-Laser Vision Correction (CBILVC index) performs an automatic assessment of biomechanical stability in post-LASIK patients and

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CHAPTER 17: Retreatment after Corneal Laser Ablation aims to differentiate stable cases from post-LVC (laser vision correction) ectasia. A cut off value of 0.2 has been found to differentiate stable LVC from post-LVC ectasia with a 97.8% specificity and 93.3% sensitivity.24 ■■ Epithelial thickness mapping is important in patients planned for transepithelial PRK to avoid errors in stromal ablation depth. The epithelial thickness profile after the primary surgery demonstrates the presence and amount of epithelial hyperplasia, which may be an important contributor to regression.

  SURGICAL TECHNIQUES OF RETREATMENT Retreatment after PRK can be performed with a repeat PRK, LASIK with or without adjuvant corneal collagen crosslinking, and PTK (Flowchart 1). The surgical options for post-LASIK retreatment include relifting the original flap followed by stromal ablation, PRK, and laser-assisted sub-epithelial keratectomy (LASEK) (Table 2). Rarely, cutting a new flap with microkeratome or femtosecond laser, undersurface ablation of flap stroma,

conductive keratoplasty, and arcuate keratotomy may be performed.25

Surface Ablation A repeat PRK is the most common method for retreatment after PRK. The technique is similar to routine PRK, while ensuring a similar sized optic zone. Intraoperative MMC use may be titrated according to the amount of refractive error being treated. Post-LASIK surface ablation is considered in patients with insufficient estimated RSBT ( 300 microns •  Primary surgery < 2 years ago/flap lifting possible

Consider PRK for retreatment, if: •  Difficulty in flap relifting •  >2 years after primary surgery •  Borderline RSBT •  Previously operated PRK •  Previous flap buttonhole/ingrowth

(LASIK: laser-assisted in situ keratomileusis; PRK: photorefractive keratectomy; UCVA: uncorrected visual acuity; BSCVA: best spectacle-corrected visual acuity; OCT: optical coherence tomography; RSBT: residual stromal bed thickness; HOA: higher order aberrations; OZ: optical zone; WG: wavefront-guided; WO: wavefront-optimized; TG: topography-guided; VA: visual acuity)

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SECTION 6: Enhancements and Retreatments TABLE 2: Comparison of patient profile, advantages, and limitations of relifting the flap and performing surface ablation for retreatment after laser-assisted in situ keratomileusis. Factors

Relifting the original flap

Surface ablation

Preoperative stromal thickness

Sufficient residual stromal bed thickness

Thin corneas with borderline RSBT

Time of surgery

Retreatment within 1–2 years of primary surgery

Retreatment >2–3 years of primary surgery

Original flap characteristics

Microkeratome created; or femtosecond laser created with minimal fibrosis

•• Significant flap edge fibrosis; difficulty in flap lifting •• Past flap-related complications like buttonhole, incomplete flap, or flap tears

Advantages

•• Better visual outcomes •• Better patient comfort •• Fewer visually significant complications

•• More residual stromal thickness retained •• Can expand the optical zone beyond the original one, if needed

Limitations

•• Reduced stromal biomechanical strength •• Increased ingrowth, if done after 3 years of original surgery •• Potential for flap-related complications such as flap tears and striae •• Ablation zone size limited by the original flap dimensions

•• •• •• •• ••

Postoperative haze Postoperative pain Delayed epithelial healing Visual outcomes less accurate Flap may dislodge during epithelial removal

(RSBT: residual stromal bed thickness)

Relifting the LASIK Flap for Retreatment

Customized Ablation Profiles

Relifting the previous LASIK flap followed by excimer laser ablation of the stromal bed is the preferred technique in cases with sufficient RSBT and 35 years at the time of primary surgery is asso­ ciated with a higher incidence of post-SMILE retreatment. This may be attributed to the unpredictable stromal cellular response and a stronger epithelial thickening response observed with increasing age.1

An increased incidence of post-SMILE enhancement has been observed in right eyes. The right eye was the dominant eye in these cases and patients may be more sensitive to minor refractive errors in their dominant eye.1 Manifest refraction spherical equivalent (MRSE) of >6.0 D is associated with a greater risk of retreatment. Increased wound remodeling and epithelial thickening are observed in higher refractive errors, resulting in post­ operative regression.1 Intraoperative suction loss is a significant risk factor for post-SMILE enhancement and retreatment.1,7 Redocking and completing SMILE after suction loss may result in collagen lamellae distortion and creation of irregular dissection planes. Centration may not be accurate during redocking, resulting in eccentric lenticules. Abandoned surgical procedures after suction loss and partially created lenticules also require retreatment. Surgeon inexperience may result in a myriad of compli­ cations during the learning curve, which may lead to irregular astigmatism, suboptimal visual outcomes, and need for retreatment. Excessive surgical manipulation in cases with difficult lenticule extraction may result in persistent interface haze and posterior stromal damage.7

  MANAGEMENT A thorough refractive work-up is essential before proceeding for retreatment. An anterior segment optical coherence tomography (ASOCT) may be undertaken to determine the cap thickness as well as the residual stromal bed thickness. ■■ Timing of surgery: It is advisable to allow a time period of at least 3 months to elapse before undertaking retreatment in order to ensure refractive stability.1,7 ■■ Decision-making: The various factors guiding decision making include the initial cap thickness, presence of inter­face haze, RSBT, patient profile, and the expertise of the operating surgeon in various techniques (Flowchart 1).

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SECTION 6: Enhancements and Retreatments Flowchart 1: Decision-making in post-small incision lenticule extraction (SMILE) retreatment.

*Further clinical testing required for this technique. (ASOCT: anterior segment optical coherence tomography; PRK + MMC: photorefractive keratectomy + mitomycin C; RSBT: residual stromal bed thickness)

TABLE 1: Surgical modalities for retreatment after small incision lenticule extraction (SMILE). Surgical procedure

Technique

Advantages

Disadvantages

Clinical outcomes

Photorefractive keratectomy (PRK)

•• Transepithelial/epithelium off •• Mitomycin C (0.02%) for 60 seconds after excimer laser ablation

Flapless

Postoperative haze

•• Satisfactory outcomes in majority •• Postoperative haze in irregular astigmatism

Thin-flap LASIK

•• Flap diameter 7.9–8.1 mm (larger than cap diameter) •• Nasal hinge (width ~3.5 mm) •• Flap thickness 90–100 µm

•• No postoperative haze •• Above the SMILE interface •• Avoids multiple dissection planes

Flap-related complications

Satisfactory outcomes

CIRCLE pattern (cap-to-flap)

Pattern D (lamellar ring adjacent to the SMILE pocket cut, at the same depth of the pocket)

•• Utilizes original SMILE interface •• Minimizes risk of multiple dissection planes •• Can extract retained lenticule •• No postoperative haze

Flap-related complications

Satisfactory outcomes

Sub-cap lenticule extraction

Modified repeat SMILE—original SMILE pocket cut acts as superior border of new lenticule

Flapless

•• Technically •• Satisfactory outcomes challenging •• Thin lenticules may be •• Requires further clinical testing difficult to extract— risk of cap tears

■■ Surgical techniques: The options for retreatment include

surface ablation, flap-based excimer laser ablation, or CIRCLE pattern of VisuMax laser (Table 1).7 A subcap lenticule extraction has been tried, though further clinical testing is required before its widespread usage.5

Photorefractive Keratectomy Photorefractive keratectomy (PRK) is a surface ablation technique to correct mild–moderate refractive errors.

An excimer laser ablation is performed with an optical zone of 6.5 mm. The corneal epithelium may be removed with the application of 20% absolute alcohol for 45 seconds. Alternatively, a transepithelial PRK may be performed. Topography-guided PRK may be performed in cases with irregular astigmatism. The major advantage of the technique is that it is a flapless procedure that preserves the integrity of the SMILE cap and does not interfere with the previous SMILE interface.

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CHAPTER 18: Retreatment after SMILE The major limitation is the narrow range of refractive correction and development of postoperative haze. Intraoperative application of topical mitomycin C 0.02% for 60 seconds is effective in preventing postoperative haze.

Outcomes Siedlecki et al. observed surface ablation with mitomycin C to be safe and effective for post-SMILE enhancement. 80% of cases were within ±0.50 D and 92.5% of cases were within ±1.00 D of target refraction.8 A gain of at least one line of visual acuity was observed in 65% of patients; 15% lost one line of corrected distance visual acuity (CDVA). Aspherically optimized profile should be avoided during retreatment, as it may result in overcorrection.

Thin-flap LASIK A thin-flap LASIK may be performed within the initial cap in cases with a thick cap of 130–140 µm. The flap settings should be customized in post-SMILE cases to avoid the initial incisions. The flap diameter should be larger than the SMILE cap diameter and a nasal position of the hinge should be planned away from the site of the initial side cut (Figs. 1A and B). The flap thickness should be set at 90–100 microns. The creation of a flap negates the biomechanical advantage of SMILE and is associated with the risk of flap-related complications. In addition, creating a LASIK flap is not advisable in cases with cap thickness of 110–120 microns due to the increased likelihood of inter­ section of the previous SMILE interface with the flap. Reinstein et al. advise multiple preoperative assess­ments of the cap thickness using optical coherence tomography or very high-frequency ultrasound, and recommend a safety margin of at least 40  μm between the maximum

A

epithelial thickness and minimum cap thickness in order to avoid inadvertent intersection of the interfaces.9 In addition, careful flap lifting has been advised to avoid flap tears and tears of previous SMILE cap side-cut.

Outcomes Excellent visual outcomes have been observed with thinflap LASIK for retreatment after SMILE.6 A post-enhance­ ment uncorrected visual acuity of 20/20 or better was achieved by 81% cases, with 74% within ±0.50 D of target refraction.6,9 Overcorrection may be observed in cases undergoing myopic retreatments pointing towards the need for modified nomograms specific to post-SMILE enhancement.

CIRCLE Pattern of SMILE A CIRCLE pattern of VisuMax laser (Carl Zeiss Meditec AG) has been developed to convert the original SMILE cap into a complete flap.10,11 The procedure consists of creating a lamellar ring, a side-cut, and a junction cut (Figs. 2A and B). The lamellar ring is an incision plane encircling the original cap cut. A side-cut with a hinge is created around the new incision plane, and the junction cut joins the original cap with the new incision plane to create one larger surface. The flap thus created can be easily lifted and enhancement can be done using excimer laser ablation. Alternatively, a completely retained lenticule can be removed after lifting the flap. Four patterns of circle cut have been described, based upon the plane of the lamellar ring and the position of side cut and junction cut. Pattern D creates a lamellar ring adjacent to the SMILE pocket cut, at the same depth as the pocket, and has been observed to be the most optimal pattern with the easiest flap lifting in cases of post-SMILE retreatment (Figs. 3A to D).10

B

Figs. 1A and B: Thin-flap laser-assisted in situ keratomileusis (LASIK) for post-small incision lenticule extraction (SMILE) enhancement. (A) Case of suction loss during SMILE converted into LASIK in same sitting; (B) Post-SMILE enhancement with nasal hinge-based LASIK flap to avoid original cap side-cut (yellow arrows—original cap side-cut).

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SECTION 6: Enhancements and Retreatments The advantage of the technique is avoidance of multiple interfaces, as the original SMILE cap is converted in to a flap. The procedure may also be performed in cases with completely retained lenticule, and the lenticule may be peeled off from the underlying stroma after lifting the flap. On the flip side, all the flap-related complications may be observed.

Outcomes CIRCLE technique is a safe and effective method for postSMILE enhancement. Siedlecki et al. observed 100% of eyes treated with CIRCLE pattern to be within 1 D of target refraction, with 90.9% within 0.5D.3 Two eyes (9.1%) lost one line of CDVA in their series and no eye lost two or more lines. The visual outcomes of CIRCLE are comparable

to that of surface ablation; however, the visual recovery is significantly faster with CIRCLE treatment.4

Sub-cap Lenticule Extraction Sub-cap lenticule extraction is a modified repeat SMILE procedure, which is performed at the same depth as the first procedure without the upper cut. The previous interface acts as the superior border of the new lenticule (Figs. 4A to C). The advantages of a flap-less procedure are preserved; however, the surgery may be technically challenging in cases with a thin lenticule.

Outcomes Only few studies have described the successful appli­ cation of this technique for post-SMILE enhancement.2,5

A

B Figs. 2A and B: Circle pattern of VisuMax laser with a lamellar ring, a side cut and a junction cut.

A

A

B B

C

D

Figs. 3A to D: Circle pattern of VisuMax laser to convert the original small incision lenticule extraction (SMILE) cap into a complete flap.

C Figs. 4A to C: Diagrammatic representation of sub-cap lenticule extraction. (A) Primary small incision lenticule extraction (SMILE) interface used as cap cut for the secondary lenticule; (B) A new posterior plane and side cut made to create a new lenticule (dotted red line). (C) The primary cap incision can be used to extract the new lenticule.

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CHAPTER 18: Retreatment after SMILE Further clinical trials are required to establish the safety and efficacy of this procedure.

  CONCLUSION Satisfactory visual outcomes can be achieved in a majority of cases that undergo retreatment after SMILE with any of the established surgical options.1,7 Postoperative haze may limit the visual recovery in cases undergoing PRK. Optimal results may also not be achieved after enhancement in cases with irregular astigmatism. A repeat SMILE procedure may be promising; however, further clinical trials are required to enhance the efficacy of the surgical technique and establish its safety.

  REFERENCES 1. Liu YC, Rosman M, Mehta JS. Enhancement after SmallIncision Lenticule Extraction: Incidence, Risk Factors, and Outcomes. Ophthalmology. 2017;124(6):813-21. 2. Sedky AN, Wahba SS, Roshdy MM, Ayaad NR. Cappreserving SMILE Enhancement Surgery. BMC Ophthalmol. 2018;18(1):49. 3. Siedlecki J, Luft N, Mayer WJ, Siedlecki M, Kook D, Meyer B, et al. CIRCLE Enhancement after Myopic SMILE. J Refract Surg Thorofare NJ. 2018;34(5):304-9. 4. Siedlecki J, Siedlecki M, Luft N, Kook D, Meyer B, Bechmann M, et al. Surface Ablation versus CIRCLE for Myopic Enhancement after SMILE: A Matched Comparative

Study. J Refract Surg Thorofare NJ 1995. 2019;35(5): 294-300. 5. Donate D, Thaëron R. Preliminary Evidence of Successful Enhancement after a Primary SMILE Procedure with the Sub-Cap-Lenticule-Extraction Technique. J Refract Surg Thorofare NJ. 2015;31(10):708-10. 6. Reinstein DZ, Carp GI, Archer TJ, Vida RS. Outcomes of Re-treatment by LASIK after SMILE. J Refract Surg Thorofare NJ. 2018;34(9):578-88. 7. Titiyal JS, Kaur M. Small Incision Lenticule Extraction (SMILE): Surgical Technique and Challenges (Comprehen­ sive Text and Video Guide), 1st edition. New Delhi: Jaypee Brothers Medical Publisher (P) Ltd.; 2018. 8. Siedlecki J, Luft N, Kook D, Dirisamer M. Enhancement after Myopic Small Incision Lenticule Extraction (SMILE) Using Surface Ablation. J Refract Surg Thorofare NJ. 2017;33(8):513-8. 9. Reinstein DZ, Carp GI, Archer TJ, Vida RS. Inferior pseudohinge fulcrum technique and intraoperative complications of laser in situ keratomileusis retreatment after smallincision lenticule extraction. J Cataract Refract Surg. 2018; 44(11):1355-62. 10. Chansue E, Tanehsakdi M, Swasdibutra S, McAlinden C. Safety and efficacy of VisuMax® circle patterns for flap creation and enhancement following small incision lenticule extraction. Eye Vis Lond Engl. 2015;2:21. 11. Riau AK, Ang HP, Lwin NC, Chaurasia SS, Tan DT, Mehta JS. Comparison of four different VisuMax circle patterns for flap creation after small incision lenticule extraction. J Refract Surg Thorofare NJ. 2013;29(4):236-44.

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SECTION

7

Presbyopia

19. Refractive Surgery for Presbyopia: An Overview Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair

20. Presbyopic Excimer Laser Ablation

Sana Tinwala, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal

21. Corneal Inlays

Sana Tinwala, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair

CHAPTER

19

Refractive Surgery for Presbyopia: An Overview Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair

  INTRODUCTION Presbyopia is an age-related process associated with loss of accommodative amplitude of the intraocular lens (presbyopia means “old eye” in Greek). It is the inability of the eye to change its focus between far and near due to increasing rigidity of the lens with age. In the present scenario, there is no way to halt or reverse this natural aging process. The correction of this refractive error, giving independence from spectacles and contact lenses (CLs), remains the Holy Grail for refractive surgeons. In 2005, there were an estimated one billion people having presbyopia. With the aging population, it is expected to increase to 1.8 billion by 2050.1 Therefore, there is an increasing emphasis on the development of novel treat­ ments for the surgical correction of presbyopia. Presbyopia is a dynamic physiological process, with accommodation being the target and is thus difficult to replicate. Due to its complex mechanism and several theories regarding its causes, presbyopia remains the most challenging visual defect to correct. Numerous surgical techniques (accommodative and pseudoaccommodative approaches) are available to correct presbyopia (Table 1). Each has its own benefits and limitations and may involve some degree of compromise between the distance and near visual acuities (VA). Accommodative approaches (dynamic methods) aim to restore the continuous range of the defocusing ability of the eye. These include scleral implants and accommoda­ tive intraocular lenses (IOLs).2 Pseudoaccommodative approaches (static methods) attempt to increase the depth of focus, thereby providing functional near vision from a

variety of nonaccommodative factors.2 They include corneal inlays, laser-based procedures (monovision, presbyLASIK, laser-blended vision, and intrastromal femtosecond laserbased procedures), corneal shrinking techniques (conduc­ tive keratoplasty), and lens-based procedures (multifocal IOLs) (Fig. 1). We herein briefly discuss the cornea-, lens-, and sclero­ ciliary complex-based approaches for the surgical correction of presbyopia.

  CORNEA-BASED REFRACTIVE SURGICAL PROCEDURES A corneal approach for presbyopia correction seems the safest and most widely practiced, since it is the least invasive. Various surgical options have been described over the years, including conductive keratoplasty, laser thermal kerato­plasty, corneal ablation targeting monovision, or multi­focality and corneal inlays.

Conductive Keratoplasty

Pseudoaccommodative

Accommodative

Conductive keratoplasty involves the controlled shrinkage of the midperipheral collagen lamellae to cause a steepening of the central cornea with an increase in refractive power. Controlled release radiofrequency current (350–400 kHz) is delivered within the peripheral corneal stroma to a depth of 500 µm through a thin hand-held probe. The electrical impedance to energy flow through collagen fibrils increases the tissue temperature to the 65°C target resulting in controlled shrinkage of the peripheral collagen lamellae. Circles of eight spots are created by the repeated insertion of the probe at 6, 7, or 8 mm circumference optical zones as determined by the nomogram, for a total of 8, 16, 24, or 32 spots. The technique is currently not preferred by surgeons owing to the high rates of regression and lack of stability of the refractive outcomes.

•• Corneal inlays •• Laser-based procedures •• IOL-based procedures

•• Scleral Implants •• Accommodative IOLs

Corneal Ablation

TABLE 1: Accommodative and pseudoaccommodative approaches for surgical correction of presbyopia.

(IOL: intraocular lens)

Excimer laser ablation in presbyopia involves the creation of multifocal corneal ablation profiles after raising a

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SECTION 7: Presbyopia

Fig. 1: Pseudoaccommodative approaches for presbyopia correction. (LASIK: laser-assisted in situ keratomileusis; RLE: refractive lens exchange; IOL: intraocular lens)

corneal flap. In addition, monovision laser-assisted in situ kerato­mileusis (LASIK) may be performed with the dominant eye corrected for distance with traditional monofocal ablation profiles, and the nondominant eye corrected for near. Different techniques of presbyopic LASIK with their outcomes and limitations are covered in detail in Chapter 20. Multifocal presbyopic LASIK or PresbyLASIK involves the creation of a multifocal cornea with either a peripheral near zone (peripheral PresbyLASIK) or a central near zone (central PresbyLASIK). Presbyond laserblended vision (Carl Zeiss Meditec, Jena, Germany) is an attempt to improvise on traditional monovision by providing functional vision in near, intermediate, and distance range by allowing the eyes to work together. It works by increasing the depth of field in each eye by introducing subtle changes in the corneal spherical aber­rations. Supracor utilizes an aberration-optimized presbyopic algorithm to treat hyperopic presbyopia and minimizes the aberrations normally induced during treatment.

Intracor Intracor (Technolas Perfect Vision GmbH, München, Germany) involves the application of intrastromal femto­ second ring incisions to create a multifocal corneal surface. Femtosecond laser pulses are applied in a concentric ring within the corneal stroma, without disrupting the endothelium, Descemet’s membrane, Bowman’s layer, or epithelium. Typically, five concentric rings are created in the stroma between 2 mm and 4 mm from the line of sight. The ring structure induces a localized biomechanical

change in the stroma, causing a slight central steepening of the anterior corneal surface (1–2 Diopters). This steepening improves the near vision by changing the spherical aber­ rations and corneal asphericity. The procedure does not involve the creation of a corneal flap, and there is no epithelial disruption with minimal pain and inflammation. It is a unilateral procedure performed in nondominant eyes. Careful patient selection is mandatory and the subjective spherical equivalent for this procedure is in the range of +0.50 to +1.00 D and cylinder of 0.5 D or less. The procedure is mainly of historical interest and has fallen out of favor due to associated reduction of mesopic contrast sensitivity and an increase in glare. Loss of corrected distance visual acuity has been reported in various studies, along with a myopic shift of −0.3 to −0.5 D magnitude. There are safety concerns with reports of post-surgical keratectasia as well.

Corneal Inlays Corneal inlays involve the insertion of synthetic or allogenic implants in the corneal stroma to modulate the corneal power and increase the depth of focus. Corneal inlays have been described in detail in Chapter 21. Commercially available corneal inlays may be classified into three types based on the mechanism of action—(1) small aperture inlays that rely on small aperture optics to increase the depth of focus (KAMRA, AcuFocus, Irvine, California), (2) refractive inlays that have a bifocal optic that alters the refractive index of the cornea (Flexivue Microlens, Los Angeles and Icolens, Neoptics AG, Switzerland), and (3) corneal reshaping inlays that

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CHAPTER 19: Refractive Surgery for Presbyopia: An Overview alter the corneal curvature (Raindrop Corneal Inlay/ PresbyLens, ReVision Optics, Lake Forest, California). In addition, presbyopic allogenic refractive lenticule (PEARL) inlays involve the transplant of an allogenic lenticule in a stromal pocket to correct presbyopia. The refractive lenticule is obtained after small incision lenticule extraction (SMILE) from a myopic patient and is implanted in the corneal stroma of a presbyopic patient to achieve refractive correction. The advantage of corneal inlays is that it is an additive procedure, potentially reversible, and does not involve corneal ablation. However, these stromal implants are prone to develop associated stromal melt, thinning, and extrusion. In addition, the visual quality is suboptimal with an increased incidence of glare, haloes, and reduced contrast sensitivity.

  LENS-BASED APPROACH FOR PRESBYOPIA CORRECTION A lenticular approach to presbyopia correction may be preferred in patients with early cataractous changes or significant cataract necessitating phacoemulsification. Lens-based approach for surgical correction of presbyopia includes phacoemulsification followed by monofocal IOL implantation targeting monovision, implantation of multifocal IOLs, or accommodative IOLs. A refractive lens exchange may be performed in patients without concomitant cataract. Presbyopic phakic IOLs are a relatively recent concept and may gain widespread acceptability owing to the potential reversibility of the procedure and sparing of the crystalline lens.

Pseudophakic Monovision Monovision may be attempted in patients undergoing bilateral cataract surgery to provide spectacle indepen­ dence for a majority of work. The concept of monovision involves creating ametropia between the two eyes by correcting one eye, traditionally the dominant eye for distance and the other eye for near. The magnitude of ametropia usually ranges from 1–2 D. Patient selection and preoperative counseling are essential in patients planned for monovision, as some degree of neuroadaptation is required postoperatively. Spectacles may still be required for fine near work. In addition, a decrease in depth perception has been reported with increasing magnitude of ametropia.

Multifocal IOLs Multifocal intraocular lenses are a viable option for patients undergoing phacoemulsification and desiring spectacle independence for near and distance. At present, they are the procedure of choice in patients with concomitant nuclear sclerosis requiring removal of the cataractous lens along

with correction of presbyopia. A careful patient selection and preoperative counseling is essential to achieve optimal outcomes, as a certain degree of neuroadaptation is required by the patient in the postoperative period to become accustomed to the multifocal IOLs. Any ocular comorbidity including inflammation, glaucoma, and posterior segment pathologies must be ruled out. In addition, a ray-tracing aberrometry provides an objective assessment of the suitability for multifocal IOLs based on the analysis of the patient’s angle alpha and pre-existing higher order aberrations (Fig. 2). Conventional bifocal IOLs provide two primary foci for near and distance. They may be refractive or diffractive in design. Early generation multifocal IOLs had the inherent disadvantage of a reduction in contrast sensitivity and significant dysphotic symptoms including glare and halos. With an improvement in IOL technology, the newer generation multifocal IOLs provide excellent visual acuity and visual quality, with minimal visually disturbing phenomenon. Trifocal IOLs incorporate two diffraction gratings alternately on the anterior surface of the IOL. Zero-order diffraction from both patterns gives useful distance vision, the first order diffraction from one pattern gives near add of +3.50 D (40 cm) and the other gives intermediate vision equivalent to +1.50 D (80 cm). Second order diffraction from the latter adds up to the near vision and decreases the lost light to 15%. The major trifocal IOLs in clinical use include FineVision Micro F (PhysIOL), AT LISA tri 839 MP (Carl Ziess), Rayner RayOne, Sulcoflex, and Oculentis Mplus. Quadrifocal diffractive technology with three diffractive gratings provides three near and intermediate focal points in addition to distance vision. PanOptix is the first lens introduced with this technology and it modifies the quadrifocal design to a functionally trifocal one. It has three foci for near, intermediate, and distance vision—(1) a near vision point at 40 cm (+3.25 D), (2) intermediate vision point at 60 cm (+2.17 D), and an extended intermediate focal point at 120 cm. The light to be focused at 120 cm is redirected to the distance using proprietary Enlighten™ Optical Technology. PanOptix lens transmits 88% of the light to retina even at small pupil diameter of 3 mm. Extended depth of focus (EDOF) or extended range of vision (ERV) IOLs are diffractive lenses that elongate the single point of near focus into a continuous focal zone with resultant continuous range of vision across all distances. These IOLs also employ negative dispersion refractive technology to neutralize for spherical and chromatic aberrations. Examples include Tecnis Symfony, Sifi Mini Well, and Zeiss AT LARA. Optimal visual quality and stereoacuity have been demonstrated with these IOLs in addition to excellent distance, intermediate, and near vision.

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SECTION 7: Presbyopia

Fig. 2: Ray tracing aberrometry to assess suitability of a patient for multifocal intraocular lens implantation.

Accommodative IOLs Accommodative IOLs have been developed to simulate the dynamics of a physiological lens during accommodation and thereby correct presbyopia. The accommodative IOLs alter their dioptric power to focus various points in the line of sight and may be based on the principle of changing the axial position, shape, or refractive index of the IOL with accommodation. Majority of accommodative lenses are “pseudo­ accommodative” rather than true accommodative in nature and are based on the mechanism of changing axial position of the IOL optic with accommodation. They may have a single-optic or dual-optic design, and 1 mm of positional change induces a 2-D change in the power. Single-optic accommodative IOLs are implanted in the capsular bag and they translate the accommodative effort to change in the position of the IOL. Examples include Morcher BioComFold 43E, Human Optics 1 CU, Lenstec Tetraflex, Crystalens AO, Trulign Toric, Lumina AIOL, Atia Vision lens (designed for placement in ciliary sulcus), and others. These IOLs are limited by the degree of anterior movement and hence offer a limited near add to the magnitude of 0.5 D. Dual-optic IOLs involve a system of two IOLs placed right behind each other—(1) a biconvex lens in the front with a concavo-convex lens behind and (2) a string haptic connecting the two optics. This dual lens system is placed inside the capsular bag. Accommodative effort deforms this system in such a way that the gap between the two lenses increases with an increase in the dioptric power of

the system. Examples include Sarfarazi elliptical accom­ modating IOL and Synchrony IOL. Synchrony IOL has been reported to impart good visual acuity for near and distance and an accommodative amplitude from 1 to 5 D.1 True accommodating IOLs have deformable optics with potentially higher amplitudes of accommodation. Examples include Medennium Smart IOL, FlexOptix by AMO, NuLens, and FluidVision IOL. Smart IOL involves insertion of a thin rod through a microincision in the lens capsule that expands at room temperature to a fullsize lens. Challenges include a requirement of small capsulorhexis to seal the gel and need for timely refill to restore the intracapsular pressure built up by proliferation of lens epithelial cells. NuLens Dynacurve accommodative IOL (NuLens, Ltd., Herzliya Pituach, Israel) consists of polymethyl methacrylate (PMMA) haptics for sulcus place­ ment, a PMMA anterior reference surface, small chamber filled with silicone gel, and a piston posteriorly with a central aperture. Accommodative effort pushes the piston forward and deforms the silicone gel, pushing it anteriorly and hence altering the anterior surface and facilitating near vision. FluidVision IOL has a fluid reservoir around the lens optics that alters the optics of IOL by a hydraulic system in accordance with accommodative effort generated by the ciliary body. Electro-activated accommodating IOL changes the refractive index of the optic material by a lithium powered battery system in proportion to accom­ modation required for near vision. LiquiLens is a bifluidic IOL with gravity-based mechanisms to shift the focal

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CHAPTER 19: Refractive Surgery for Presbyopia: An Overview plane and impart large amplitudes of accommodation, which are independent of ciliary body function. The true accommodative IOLs with deformable optics are still in early experimental stages. Accommodative IOLs still require further technological advancements to increase the acceptability of the procedure and ensure optimal refractive outcomes. Ciliary sulcus is emerging as a preferred site of placement of these IOLs rather than an in-the-bag implantation.

Presbyopic Phakic IOL Presbyopic implantable phakic contact lens (IPCL, Care Group India, Gujarat, India) is a novel posterior chamber phakic IOL devised for the surgical correction of presbyopia. It is a hybrid hydrophilic acrylic lens indicated in patients between 40 and 60 years of age with a clear lens (Fig. 3).2,3 The presbyopic phakic IOL allows correction of coexistent myopia of up to −25 D, hyperopia of up to +10 D and astigmatism of up to 8 D, and a near add ranging from +1.50 to +4.0 D. 4 Satisfactory visual and anatomical outcomes have been reported; however, the multifocal phakic IOL may be associated with a reduced contrast sensitivity and dysphotic symptoms including glare and halos.4 An extended depth of focus implantable collamer lens (EDOF ICL, STAAR Surgicals, Monrovia, California) with aspheric optic has been developed to provide up to 2.0 D extended depth of focus in patients with myopia and presbyopia. Initial results are promising and an improve­ ment in the uncorrected near, intermediate, and distance visual acuity has been observed with optimal visual quality and patient satisfaction.5

Presbyopic phakic IOL spares both the cornea as well as the crystalline lens. The main advantage of phakic IOL implantation is the potential reversibility of the procedure, as it may easily be explanted via a 2.8-mm incision without damaging the clear lens. Dysphotopsia, higher order aberrations, and decrease in visual quality may be experienced due to the inherent nature of the multifocal design, which may limit patient satisfaction in the long run. Further, long-term studies are required to establish the safety and efficacy of this procedure.

Femtosecond Laser Lentotomy The underlying pathophysiology of presbyopia is related to stiffening of the aging lens leading to a decrease in the accommodative amplitude. Lens softening procedures have been developed that aim to increase the elasticity of lens by delivering low-energy femtosecond laser pulses in the lens.6 The role of femtosecond laser lentotomy in treating presbyopia is being evaluated in clinical trials by two companies—Lensar (Orlando, Florida) and Rowiak (Hanover, Germany). Low-energy femtosecond laser pulses (2–10 µJ) with a high repetition rate are employed in various patterns, sparing the central 2 mm of the crystalline lens. Initial results demonstrate a restoration of up to 2 D of accommodative amplitude with an improvement in the objective accommodation in one-third of patients, and an improvement in near vision reported by 40% of patients. The predictability and stability of the refractive outcomes over long-term have not been demonstrated. In addition, there are significant concerns regarding the safety of the procedure and the potential to develop lenticular opacities

Fig. 3: Presbyopic phakic intraocular lens (IOL).

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SECTION 7: Presbyopia at the site of laser delivery.7 Femtosecond laser lentotomy has the potential to extend the useful range of accommoda­ tion for 5–10 years; however, at present, the treatment is experimental and requires validation in long-term studies.

  SCLEROCILIARY COMPLEX BASED PROCEDURES FOR PRESBYOPIA Anterior ciliary sclerotomy and scleral expansion surgeries have been proposed to restore the accommodative amplitude in patients with presbyopia; however, these procedures are not performed owing to lack of definite benefits, lack of stability of refractive outcomes, and associated adverse effects.8,9 Anterior ciliary sclerotomy involves the creation of radial scleral incisions overlying the ciliary muscles in order to increase the potential space between the lens equator and the ciliary body. The mechanism involves the creation of a resting tension on the equatorial zonules in order to allow for an increase in tension to develop during the contraction of the ciliary muscle. Laser presbyopia reversal (LAPR) involves creation of radial sclerectomy incisions with an erbium-doped yttrium aluminum garnet (Er:YAG) laser. Scleral laser anterior ciliary excision (LaserACE, Ace Vision Group, Newark, CA, USA) uses an Er:YAG laser to create a matrix array of scleral micro­ excisions in four oblique quadrants. Polymethyl methacrylate bands have also been placed in tunneled partial–scleral thickness incisions overlying the ciliary body in order to create scleral expansion and partially restore the accommodative amplitude. The VisAbility Micro-Insert scleral implant (Refocus Group, Dallas, TX, USA) utilizes four PMMA injection-molded implants, which are placed at a depth of 400 μm within the sclera, 3–4 mm posterior to the limbus to correct presbyopia. He et al. observed a preservation of the inherent accom­ modative ability of the ciliary muscle in presbyopia, implying a lack of significant benefit of the sclerociliary-based approaches.8 The sclerociliary complex based procedures are not preferred for the correction of presbyopia at present.

  CONCLUSION The past few decades have witnessed the development of various cornea- and lens-based surgical techniques for the correction of presbyopia. The safety, predictability, and stability of the cornea-based techniques are still not at par with corresponding treatments for other refractive errors. The compromise of distance visual acuity as well as quality of vision is the major limiting factor with a majority of

presbyopia-correcting surgeries. In addition, postoperative neuroadaptation is required to adjust to the changed optics. Present-day multifocal IOLs are an excellent alternative for patients with concomitant cataract, with optimal visual acuity at all distances, minimal dysphotic symptoms, and excellent stereoacuity. Presbyopic phakic IOLs are pro­ mising and may be preferred over cornea-based procedures; however, the long-term impact on the crystalline lens needs to be studied to establish their safety. Techniques such as Intracor, anterior ciliary sclerotomy, and scleral expansion bands are mainly of historical interest owing to a lack of adequate predictability and safety of the outcomes. Pharmacotherapy for presbyopia is also being explored and is based on the mechanism of inducing a pinhole effect using miotics, or inducing lens softening with investi­ gational pharmacological agents. At present, there is no treatment that can reverse the underlying pathophysio­logy of presbyopia and restore true accommodation.

  REFERENCES 1. Ossma IL, Galvis A, Vargas LG, Trager MJ, Vagefi MR, McLeod SD. Synchrony dual-optic accommodating intra­ ocular lens. Part 2: pilot clinical evaluation. J Cataract Refract Surg. 2007;33(1):47-52. 2. Schmid R, Luedtke H. A Novel Concept of Correcting Presbyopia: First Clinical Results with a Phakic Diffractive Intraocular Lens. Clin Ophthalmol Auckl NZ. 2020;14:2011-9. 3. Stodulka P, Slovak M, Sramka M, Polisensky J, Liska K. Posterior chamber phakic intraocular lens for the correction of presbyopia in highly myopic patients. J Cataract Refract Surg. 2020;46:40-4. 4. Pineda R, Chauhan T. Phakic Intraocular Lenses and their Special Indications. J Ophthalmic Vis Res. 2016;11(4): 422-8. 5. Packer M, Alfonso JF, Aramberri J, Elies D, Fernandez J, Mertens E. Performance and Safety of the Extended Depth of Focus Implantable Collamer® Lens (EDOF ICL) in Phakic Subjects with Presbyopia. Clin Ophthalmol Auckl NZ. 2020;14:2717-30. 6. Krueger RR, Kuszak J, Lubatschowski H, Myers RI, Ripken T, Heisterkamp A. First safety study of femtosecond laser photodisruption in animal lenses: tissue morphology and cataractogenesis. J Cataract Refract Surg. 2005;31(12): 2386-94. 7. Roach L. Softening the Presbyopic Lens with a Femtosecond Laser. (2014). [online] Available from: https://www.aao. org/eyenet/article/softening-presbyopic-lens-withfemtosecond-laser. [Last accessed June, 2021]. 8. He L, Donnelly WJ, Stevenson SB, Glasser A. Saccadic lens instability increases with accommodative stimulus in presbyopes. J Vis. 2010;10(4):14.1-16. 9. Torricelli AA, Junior JB, Santhiago MR, Bechara SJ. Surgical management of presbyopia. Clin Ophthalmol Auckl NZ. 2012;6:1459-66.

CHAPTER

20

Presbyopic Excimer Laser Ablation Sana Tinwala, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal

  INTRODUCTION Presbyopic excimer laser ablation techniques involve the creation of a multifocal corneal surface in combination with monovision to increase the depth of focus and achieve optimal uncorrected near visual acuity. Moreira et al. first created a multifocal corneal profile to correct presbyopia as well as myopia by attempting to create a central steeper area.1 Subsequently, Ruiz introduced the term presbyLASIK in 1996. Excimer laser ablation is a viable option for young presbyopes with a crystalline lens and has the added advantage of being an extraocular procedure. We herein discuss the various techniques of presbyopic excimer laser ablation, their outcomes and limitations with an emphasis on patient selection.

  PATIENT SELECTION Presbyopic excimer laser ablation is more demanding than conventional refractive surgery with a greater emphasis on careful patient selection and preoperative counseling to avoid postoperative dissatisfaction. Thorough patient screening, in-depth explanation of the procedure for realistic expectations, careful planning, selecting the correct

procedure based on the patient requirements, and highly accurate laser application are an absolute must for achieving satisfactory outcomes. Each of the corrective procedures for presbyopia has some limitations and a 100% outcome should never be guaranteed. Presbyopia is a progressive condition affecting the lens, and it is critical to understand that the patient will require lens replacement at some point in time. When evalua­ting a patient who is having difficulty with reading glasses and bifocals, it is imperative to educate the patient that their refractive vision may change over lifetime. Under­ standing dysfunctional lens syndrome and its stages can help us in deciding the best modality of treatment for each individual patient. With the availability of a wide range of options for the correction of presbyopia, it is important to select the right procedure (Flowchart 1). The general rules of patient selection for conventional flap-based corneal ablative procedures also apply to presbyopic laser-assisted in situ keratomileusis (LASIK). Patients with unfavorable corneal topography at risk to develop postoperative ectasia should be counseled against undergoing presbyopic LASIK. Patients with any lens opacity that may or may not be affecting day-to-day activities should also be avoided. In addition, presbyopic LASIK hinges on

Flowchart 1: Dysfunctional lens syndrome and presbyopia.

(LASIK/PRK: laser-assisted in situ keratomileusis/photorefractive keratectomy; LBV: laser blended vision; RLE: refractive lens exchange; IOL: intraocular lens)

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SECTION 7: Presbyopia the creation of monovision to increase the depth of focus, and patients requiring prisms to correct diplopia may not be suitable for monovision. Monovision is also not a good option for those with a dominant eye ocular pathology, which precludes them from having uncorrected visual acuity (UCVA) of 20/20 or better.

  CORNEAL APPROACH TO PRESBYOPIA CORRECTION A corneal approach is entirely extraocular and LASIK being a long-established familiar technique to most, makes laser correction of presbyopia an attractive option for surgeons and patients. Excimer laser procedures for the correction of presbyopia may involve different appro­ aches, including targeting monovision with a conventional monofocal corneal profile, pseudoaccommodative appro­ aches with the creation of a multifocal corneal ablation profile, or laser-blended vision (Flowchart 2 and Table 1).

Monovision The concept of monovision is well established in reducing spectacle dependency in presbyopes. 2 Monovision is based on the principle of interocular blur suppression. Conventional corneal ablation is performed with the dominant eye being corrected for distance and the nondominant eye for near vision. This intentional anisometropia thus created results in the formation of a blur zone (Fig. 1). Monovision provides functional near and distance vision and success rates ranging from 80 to 98% have been reported after surgery.2-5 Limitations of monovision include compromised intermediate vision, suboptimal distance vision, loss of

stereoacuity, a reduction in contrast sensitivity and lowcontrast visual acuity.6,7

Pseudoaccommodative Approaches A pseudoaccommodative cornea can be achieved either by creating a peripheral near zone (peripheral presbyLASIK) or a central near zone (central presbyLASIK).8,9 In addition, it is essential to achieve extended binocular depth of focus to provide optimal distance and near vision with good contrast sensitivity. This can be attained in most presbyopes by targeting for residual post-ablation higher order aberra­ tions (HOAs).10 This is in contrast to conventional corneal ablation, wherein HOA induction is minimized. Various presbyopic laser vision correction procedures have been described, including multifocal laser vision cor­ rection, Presbyond laser-blended vision, and Supracor.9,11,12

  MULTIFOCAL LASER VISION CORRECTION PresbyLASIK aims to create a multifocal corneal surface in presbyopic patients using excimer laser ablation. It aims to provide distance correction with a reduction in spectacle dependency for near.13 The three main types of multifocal corneal profiles include multifocal transition profile, peri­ pheral presbyLASIK, and central presbyLASIK.13

Multifocal Transition Profile A transitional vertical multifocal ablation profile is created by intentional decentration of a hyperopic ablation profile. The technique led to an improvement in uncorrected near visual acuity in hyperopic presbyopes; however, it has fallen out of favor due to induction of significant levels of vertical coma.13

Flowchart 2: Excimer laser procedures for the correction of presbyopia.

(LASIK: laser-assisted in situ keratomileusis; PRK: photorefractive keratectomy)

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CHAPTER 20: Presbyopic Excimer Laser Ablation TABLE 1: Techniques of presbyopic corneal ablation. Technique

Principle

Advantages

Limitation

Monovision

•• Interocular blur suppression •• Intentional anisometropiadominant eye for distance, nondominant eye for near

•• Easy planning and technique •• Compromised intermediate •• Does not induce significant vision aberrations—maintains visual quality •• Suboptimal distance vision •• More suited for myopes •• Loss of stereoacuity •• Reduced low-contrast visual acuity and contrast sensitivity

Peripheral presbyLASIK

Increased range of pseudoaccommodation—central cornea for distance vision and midperipheral cornea for near vision

Good results in hyperopes

•• Not suitable for myopes— significant amount of corneal tissue ablated •• Loss of CDVA •• Loss of contrast sensitivity and night vision disturbances

Central presbyLASIK

Creates bifocality—central cornea ablated for near and periphery for distance

•• For all refractive errors (myopes/ hyperopes/emmetropes) •• Minimal corneal ablation

•• Induction of coma aberrations •• Pupil dependent •• Dependent on adequate centration •• Loss of CDVA

Laser-blended vision

•• Increased depth of field in each eye by introducing subtle changes in the corneal spherical aberrations •• Dominant eye—distance to intermediate •• Nondominant eye—intermediate to near •• “Blend Zone” in intermediate range

•• Functional vision in near, intermediate and distance range •• No dissociation as occurs in monovision •• Higher levels of myopia can be treated without removing large amounts of corneal tissue

•• Period of adaptation varies from a few weeks up to a year •• 3% not fully adapted at 1 year •• Visual discomfort and dizziness during initial phase of adaptation

Multifocal corneal ablation

(CDVA: corrected distance visual acuity; LASIK: laser-assisted in situ keratomileusis)

Fig. 1: Excimer-laser monovision approach for presbyopia with creation of intentional anisometropia and blur zone.

Peripheral PresbyLASIK Peripheral presbyLASIK is based on increasing the range of pseudoaccommodation. In this technique, the central cornea is corrected for distance and the midperipheral cornea is corrected for near (Fig. 2). The depth of field is increased by using a peripheral ablation pattern so as to create a negative peripheral asphericity.13

Limitations The technique is associated with the ablation of a significant amount of corneal tissue especially in myopes; therefore,

it is limited to a narrow range of refractive errors and mainly preferred for hyperopes. An efficient excimer laser beam profile is necessary to mitigate the loss of energy that occurs while ablating the peripheral cornea; this may be challenging when aiming for high negative asphericity.

Central PresbyLASIK Central presbyLASIK essentially creates bifocality.13 In contrast to peripheral presbyLASIK, the central cornea is ablated for near and the periphery for distance (Fig. 2). It is pupil-dependent and adequate centration is crucial for

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SECTION 7: Presbyopia

Fig. 2: Multifocal corneal ablation profiles created with PresbyLASIK. (LASIK: laser-assisted in situ keratomileusis)

the procedure. An advantage is that it can be performed for all refractive errors (myopes/hyperopes/emmetropes) with minimal corneal ablation. It is the commonly pre­ ferred technique of presbyLASIK and includes AMO VISX hyperopia–presbyopia multifocal approach, SCHWIND PresbyMAX®, and Technolas SUPRACOR.14 Alio et al. reported an uncorrected distance visual acuity (UDVA) of 20/20 or better in 64% hyperopes at 6 months, with 72% achieving an uncorrected near visual acuity (UNVA) of 20/40 or better. A loss of two lines of corrected distance visual acuity (CDVA) was reported in 28%; in addition, there was an increase in coma aberrations with decrease in spherical aberrations.9 The main limitation of the technique is related to the induction of coma, which adversely impacts quality of vision. HOAs may be induced due to lack of adequate alignment among the line of sight, the central pupil, and the corneal vertex.

PresbyMAX PresbyMAX software (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany) is a central presbyLASIK technique utilizing biaspheric cornea modulation. It aims to create a bi-aspheric multifocal corneal surface with a central hyperpositive area for near correction (+0.75 to +2.50 D), and the pericentral cornea being ablated to correct for distance vision.15,16 Three treatment modules are available with presbyMAX—a presbyMAX symmetric module wherein both eyes are treated symmetrically to achieve a depth of focus of 1.5 D, presbyMAX μ-monovision wherein a difference of 0.8 D in target refraction is induced between the two eyes, and presbyMAX hybrid with a differential induction of depth of focus and target refraction in dominant and nondominant eyes. Uthoff et al. evaluated presbyMax in hyperopes, myopes, and emmetropes. An uncorrected distance visual

acuity (UDVA) of 0.1 logMAR or better was achieved by 100% hyperopes, 80% emmetropes, and 70% myopes.17 In addition, UNVA of 0.3 logRAD or better was achieved by 90% of the emmetropes and 80% of hyperopes and myopes. A loss of two lines or more of CDVA was observed in 10% hyperopes and emmetropes, with 40% losing at least one line of CDVA. Myopic patients reported a loss of three lines of CDVA in 10%, two lines in 10%, and one line in 10%, respectively.17

AMO VISX Hyperopia–Presbyopia Multifocal Approach The software is based on the technique of central presbyLASIK with the central zone corrected for near vision and the peripheral zone for distance. It is indicated for hyperopes with up to +4.0 D of spherical error and −2.00 D of cylindrical error.18 Jackson et al. reported 1-year outcomes of wavefrontguided hyperopic LASIK treatment with the VISX STAR S4 excimer laser (AMO). 18 Optimal distance and near binocular visual acuity were achieved in all patients, with 100% having a UDVA of 20/25 or better and UNVA of J3 when assessed binocularly. A total of 10% patients lost two or more lines of CDVA. There was an increase in the higher order aberrations (mainly negative spherical aber­ rations) after surgery, which correlated with the improve­ ment in near vision.

Supracor Supracor (Technolas Perfect Vision GmbH, Munich, Germany) is a central presbyLASIK technique based on the principles of an aberration-optimized presbyopic algorithm. The technique is indicated for presbyopes with hyperopia and minimizes the induction of HOAs. The Supracor creates a hyperpositive area in the central 3.0 mm zone by providing a near add of approximately 2 D.19 The treatment may be based on the symmetrical

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CHAPTER 20: Presbyopic Excimer Laser Ablation

Fig. 3: Presbyond laser-blended vision.

technique or the asymmetrical technique. In the former, 0.50 D of myopia is targeted in both eyes.20 In the latter, a plano refractive target is set for the dominant eye and a target of −0.50 D is set for the nondominant eye. 21 The symmetrical technique is preferred in cases with requirement of a good near vision. The asymmetrical technique may be preferred in cases with a requirement of both good near and distance vision. The Supracor algorithm is integrated in the Technolas Teneo 317 and in the Technolas 217P excimer lasers (Bausch and Lomb Technology, Munich Germany). 19 The first results of Supracor were reported by Ryan et al. Binocular UDVA of 0.2 logMAR or better and UNVA of N8 or better were achieved by 91% patients. A loss of two or more lines of CDVA was observed in 6% patients. Complete inde­ pendence from reading glasses was seen in 93% patients.20

  LASER-BLENDED VISION Laser-blended vision techniques aim to increase the depth of focus by altering the spherical aberrations or corneal asphericity. Presbyond laser-blended vision (Carl Zeiss Meditec, Jena, Germany) and custom-Q treatments are based on the principle of laser-blended vision. Presbyond laser-blended vision (Carl Zeiss Meditec, Jena, Germany) is an attempt to improvise on traditional monovision. The technique is based on the principle of increasing the depth of field in each eye by modifying the corneal spherical aberrations.22 The dominant eye is corrected for the distance to intermediate range while the nondominant eye is corrected for the intermediate to near range. This leads to a “Blend Zone” in the intermediate range, contributing to an overlap in the visual acuities of each eye (Fig. 3). The brain fuses the images between the eyes in the blend zone and provides binocularity. This is unlike traditional monovision where the significant image disparity between the two eyes does not allow fusion by the brain and instead results in suppression of the blurred eye.

Fig. 4: Challenges of monovision as compared with laser-blended vision.

Laser-blended vision effectively provides functional vision in near, intermediate, and distance range by allowing the eyes to work together (no dissociation as occurs in monovision). The distance vision is largely preserved with this technique due to an increased depth of field in both eyes (Fig. 4). A varied range of preoperative refractive errors can be treated by this technique. Laser-blended vision (Carl Zeiss Meditec MEL80 excimer laser) has showed optimal results for the correction of presbyopia in a wide range of refrac­ tive errors, including myopia up to −9.00 D, hyperopia up to +6.00 D, myopic or hyperopic astigmatism, and emmetropia.23,24 Due to enhancements in the controlled induction of spherical aberrations, higher magnitude of myopic correction can be achieved with minimal removal of corneal tissue.22 At 1 year, UDVA of 20/20 or better has been reported in 95% patients with good near visual acuity allowing the patients to read the newsprint type size for near.23,25 In contrast, patient satisfaction with monovision is signifi­ cantly less, with only 59–67% of patients able to adapt to monovision.23,25

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SECTION 7: Presbyopia Custom-Q treatments are indicated in hyperopic pre­ sbyopic patients where surgeon needs to target a negative asphericity for achieving monovision.26 The dominant eye is corrected for distance and a central myopic refraction with negative asphericity is induced in the nondominant eye. This negative asphericity provides a central hyperprolate zone that aids in near vision and increases the depth of focus.

Limitations and Potential Complications There is no increased surgical risk associated with this procedure as compared to conventional LASIK. There is a significant period of neuroadaptation postoperatively, which may vary from few weeks to an year, and preoperative patient counseling plays a very important role in ultimate outcomes and patient satisfaction. Reports indicate an average adaptation period of 3 months after laser-blended vision treatment; however, up to 3% patients may not be fully adapted even at the end of 1 year.24 Patients may experience visual discomfort or dizziness during the initial neuroadaptation phase. There may be a feeling of the distance vision being “strange”. Spectacle correction may be given in this period to reverse the difference between the eyes.

  COUNSELING Patient selection and addressing expectations are critical factors that need to be strictly addressed prior to under­ taking any presbyopic corneal ablation. These are as important to the ultimate outcome as the procedure itself. It is important to discuss that presbyopia is not reversed or cured by multifocal LASIK. The following should be discussed in detail: ■■ If the patient’s vision is normal except for presbyopia prior to multifocal LASIK, there is a possibility that distance vision may be blurry immediately after the surgery. This problem may persist over long-term. ■■ There is a possibility of reduced contrast sensitivity and halos around lights at night. Reduced contrast sensiti­ vity implies difficulty seeing objects against similar colored backgrounds. It may be temporary and disappear in 3–6 months; rarely, it may persist long-term. ■■ If cataract develops after multifocal LASIK, cataract surgery is possible without any significant increase in surgical risk. But, corneal changes induced during the LASIK procedure make it more challenging to deter­ mine the accurate power for the intraocular lens to give a perfect visual outcome after cataract surgery. This implies that there is a possibility that there may be a need to wear spectacles after cataract surgery or the need to undergo additional corneal refractive surgery to regain adequate vision for driving and/or reading without glasses.

■■ Most studies show loss of best-corrected distant visual

acuity (BCDVA), which should be highlighted. ■■ Period of adaptation of 3–6 months (sometimes up to a

year) should be explained. ■■ Finally, the results of multifocal LASIK may not be

permanent. Presbyopia is a condition affecting the intraocular lens (not the cornea). With the progression in lens changes (dysfunctional lens syndrome) after LASIK, surgical enhancements may be needed. ■■ Realistic expectations are essential: Patients should be made aware that they may still need reading glasses for certain tasks after the procedure. A realistic expectation is that one will be less dependent on reading glasses and will be able to see adequately well to read and perform most (not necessarily all) close-up tasks without glasses. ■■ For multifocal approaches, a reversal of effect is difficult to achieve, and a re-treatment may be a compromise between attempted refraction and quality of vision. There is always a compromise while trying to achieve a good optical system for both near and distance vision. Whether done in the form of monovision correction or adopting a multifocal approach, some clarity is lost. Neural adaptation and corneal regression are long-term effects, which will not be noticed with 3 or 6 months of follow-up; hence, follow-up of at least a year is essential to evaluate outcomes of a presbyopic procedure.

  CONCLUSION Despite all the advances in refractive surgery, presbyopia correction continues to be a major challenge. Unlike laser vision correction for other refractive errors, the results are much less gratifying. A sizeable number of patients come back unhappy due to poor intermediate vision or due to problems in night driving. At present, all the techniques for presbyopia correction require some adaptation. Reduction of contrast sensitivity and corrected distance visual acuity may be attributed in part to dry eyes or the induction of HOAs. Patient selection is the most crucial factor for achieving good results; the patient expectations, their job profile, lifestyle, and hobbies have to be taken into consideration prior to offering any surgical procedure. Several procedures exist to help patients become less spectacle dependent for intermediate and near vision, but none of them look ideal yet. PresbyLASIK treatments have most commonly been used to treat hyperopic patients. These patients are better candidates and are generally more satisfied with the results. Myopes, on the other hand, being accustomed to good near vision, are more critical of the results.27 Individualizing treatment options according to patient needs is essential. All the available techniques (corneal and intraocular) have significant limitations.

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CHAPTER 20: Presbyopic Excimer Laser Ablation There are also some promising novel non-invasive appro­ aches to treat the condition. Electrostimulation of the ciliary muscle may be helpful in delaying presbyopia at least in younger patients. Encouraging reports have been seen with some pharmacologic approaches. The solution may lie in the combination of different tech­niques or using more than one procedure. Develop­ ment of different procedures to reverse or correct presbyopia continues in our search for successfully conquering the Holy Grail.

  REFERENCES 1. Moreira H, Garbus JJ, Fasano A, Clapham TN, McDonnell PJ. Multifocal corneal topographic changes with excimer laser photorefractive keratectomy. Arch Ophthalmol Chic Ill. 1992;110:994-9. 2. Jain S, Arora I, Azar DT. Success of monovision in presbyopes: review of the literature and potential applications to refrac­ tive surgery. Surv Ophthalmol. 1996;40:491-9. 3. Jain S, Ou R, Azar DT. Monovision outcomes in presbyopic individuals after refractive surgery. Ophthalmol. 2001;108: 1430-3. 4. Levinger E, Trivizki O, Pokroy R, Levartovsky S, Sholohov G, Levinger S. Monovision surgery in myopic presbyopes: visual function and satisfaction. Optom Vis Sci Off Publ Am Acad Optom. 2013;90:1092-7. 5. Reilly CD, Lee WB, Alvarenga L, Caspar J, Garcia-Ferrer F, Mannis MJ. Surgical monovision and monovision reversal in LASIK. Cornea. 2006;25:136-8. 6. Goldberg DB. Laser in situ keratomileusis monovision. J Cataract Refract Surg. 2001;27:1449-55. 7. Richdale K, Mitchell GL, Zadnik K. Comparison of multifocal and monovision soft contact lens corrections in patients with low-astigmatic presbyopia. Optom Vis Sci Off Publ Am Acad Optom. 2006;83:266-73. 8. Cantú R, Rosales MA, Tepichín E, Curioca A, Montes V, Bonilla J. Advanced surface ablation for presbyopia using the Nidek EC-5000 laser. J Refract Surg Thorofare NJ. 2004;20:S711-3. 9. Alió JL, Chaubard JJ, Caliz A, Sala E, Patel S. Correction of presbyopia by technovision central multifocal LASIK (presbyLASIK). J Refract Surg Thorofare NJ. 2006;22:453-60. 10. Charman WN. Ablation design in relation to spatial frequency, depth-of-focus, and age. J Refract Surg Thorofare NJ. 2004;20:S542-9. 11. Vinciguerra P, Nizzola GM, Bailo G, Ascari A, Epstein D. Excimer laser photorefractive keratectomy for presbyopia: 24-month follow-up in three eyes. J Refract Surg Thorofare NJ. 1998;14:31-7. 12. Luger MHA, Ewering T, Arba-Mosquera S. One-year experience in presbyopia correction with biaspheric multifocal central presbyopia laser in situ keratomileusis. Cornea. 2013;32:644-52. 13. Alió JL, Amparo F, Ortiz D, Moreno L. Corneal multifocality with excimer laser for presbyopia correction. Curr Opin Ophthalmol. 2009;20:264-71.

14. Wang Yin GH, McAlinden C, Pieri E, Giulardi C, Holweck G, Hoffart L. Surgical treatment of presbyopia with central presbyopic keratomileusis: One-year results. J Cataract Refract Surg. 2016;42:1415-23. 15. Luger MHA, McAlinden C, Buckhurst PJ, Wolffsohn JS, Verma S, Arba-Mosquera S. Presbyopic LASIK using hybrid bi-aspheric micro-monovision ablation profile for presbyopic corneal treatments. Am J Ophthalmol. 2015;160: 493-505. 16. Baudu P, Penin F, Arba Mosquera S. Uncorrected bino­ cular performance after biaspheric ablation profile for presbyopic corneal treatment using AMARIS with the PresbyMAX module. Am J Ophthalmol. 2013;155:636-47, 647.e1. 17. Uthoff D, Pölzl M, Hepper D, Holland D. A new method of cornea modulation with excimer laser for simultaneous correction of presbyopia and ametropia. Graefes Arch Clin Exp Ophthalmol Albrecht Von Graefes Arch Klin Exp Ophthalmol. 2012;250:1649-61. 18. Jackson WB, Tuan K-MA, Mintsioulis G. Aspheric wavefrontguided LASIK to treat hyperopic presbyopia: 12-month results with the VISX platform. J Refract Surg Thorofare NJ. 2011;27:519-9. 19. Ang RET, Cruz EM, Pisig AU, Solis MLPC, Reyes RMM, Youssefi G. Safety and effectiveness of the SUPRACOR presbyopic LASIK algorithm on hyperopic patients. Eye Vis Lond Engl. 2016;3:33. 20. Ryan A, O’Keefe M. Corneal approach to hyperopic pre­ sbyopia treatment: six-month outcomes of a new multifocal excimer laser in situ keratomileusis procedure. J Cataract Refract Surg. 2013;39:1226-33. 21. Soler Tomás JR, Fuentes-Páez G, Burillo S. Symmetrical Versus Asymmetrical PresbyLASIK: Results After 18 Months and Patient Satisfaction. Cornea. 2015;34:651-7. 22. Gifford P, Kang P, Swarbrick H, Versace P. Changes to corneal aberrations and vision after Presbylasik refractive surgery using the MEL 80 platform. J Refract Surg Thorofare NJ. 2014;30:598-603. 23. Reinstein DZ, Archer TJ, Gobbe M. LASIK for Myopic Astigmatism and Presbyopia Using Non-Linear Aspheric Micro-Monovision with the Carl Zeiss Meditec MEL 80 Platform. J Refract Surg Thorofare NJ. 2011;27:23-37. 24. Reinstein DZ, Carp GI, Archer TJ, Gobbe M. LASIK for presbyopia correction in emmetropic patients using aspheric ablation profiles and a micro-monovision protocol with the Carl Zeiss Meditec MEL 80 and VisuMax. J Refract Surg Thorofare NJ. 2012;28:531-41. 25. Evans BJW. Monovision: a review. Ophthalmic Physiol Opt J Br Coll Ophthalmic Opt Optom. 2007;27:417-39. 26. Courtin R, Saad A, Grise-Dulac A, Guilbert E, Gatinel D. Changes to Corneal Aberrations and Vision After Monovision in Patients With Hyperopia After Using a Customized Aspheric Ablation Profile to Increase Corneal Asphericity (Q-factor). J Refract Surg Thorofare NJ. 2016;32:734-41. 27. El Danasoury AM, Gamaly TO, Hantera M. Multizone LASIK with peripheral near zone for correction of presbyopia in myopic and hyperopic eyes: 1-year results. J Refract Surg Thorofare NJ. 2009;25:296-305.

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CHAPTER

21

Corneal Inlays Sana Tinwala, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair

  INTRODUCTION The history of corneal inlays may be traced to 1949 when José Barraquer introduced the prototype polymethyl­ methacrylate inlay to treat high myopia or aphakia. These inlays showed promise in correcting the targeted refractive error; however, the unacceptable rates of implant extrusion and corneal necrosis led to a discontinuation of the technique.1 The introduction of biocompatible materials such as hydrogel revived an interest in corneal inlays.2 Older generation inlays were associated with a high rate of explant due to stromal thinning/melting, corneal haze, and opacification as well as decentration.3 The combination of new biocompatible materials together with advancements in surgical techniques has improved the safety and efficacy of new-generation corneal inlays.4,5 We herein discuss the present-day corneal inlays with their characteristics, outcomes, and limitations.

  CORNEAL INLAYS The new-generation corneal inlays have small diameters, thin design, high permeability to fluids and nutrients, and the possibility to be placed at a relatively deeper level within the stromal tissue without the risk of complications. The improved design has helped to overcome the risks associated with the older generation inlays such as hampering of the natural metabolic functions of the cornea.

At present, there are three types of corneal inlays based on different mechanisms (Table 1): ■■ Small aperture inlays—rely on small-aperture optics to increase the depth of focus, e.g., KAMRA (AcuFocus, Irvine, California). ■■ Refractive inlays—alter the refractive index with a bifocal optic, e.g., Flexivue Microlens (Presbia, Los Angeles), IcoLens (Neoptics AG, Hunenberg, Switzerland). ■■ Corneal reshaping inlays—change the corneal curvature, e.g., Raindrop corneal inlay/PresbyLens (ReVision Optics, Lake Forest, California). The device is typically implanted in the nondomi­ nant eye either beneath a corneal flap or into an intra­ stromal pocket created by femtosecond laser. Pocket is preferred over flap due to lesser transection of anterior collagen lamellae and subepithelial nerve fiber layer, which is associated with enhanced postoperative biomechanical stability and a decreased incidence of dry eyes.5 The postoperative outcomes rely on accurate centration of inlays and even small decentration may adversely impact visual acuity.6

Kamra Corneal Inlay The Kamra Inlay (AcuFocus, Inc., Irvine, California, USA) is an opaque implant made of polyvinylidene fluoride with a central aperture.

TABLE 1: Characteristics of different corneal inlays. Corneal inlay

Diameter

Thickness

Depth of placement

Mechanism

Centration

Material

Kamra

3.8 mm

5 microns

200–250 microns

Pinhole principle— increased depth of focus

Over first Purkinje image

Polyvinylidene fluoride

Flexivue Microlens

3.2 mm

15–20 microns

280–300 microns

Corneal multifocality— plano central zone with midperipheral rings of varying power

Over first Purkinje image

Hydroxyethyl methacrylate and methyl methacrylate

Raindrop

2 mm

32 microns

120–200 microns

Change in shape— increased central corneal curvature

Central over light constricted pupil

Hydrogel

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CHAPTER 21: Corneal Inlays

Principle

Outcomes

The mechanism of action of small aperture inlays is based on increasing the depth of focus by utilizing the “pinhole effect”. It received Food and Drug Administration (FDA) approval in 2015 for the surgical correction of presbyopia.

The safety and efficacy of Kamra inlays have been demons­ trated in various long-term studies.7,8 The procedure being potentially reversible, the inlay can be removed in case of an undesired outcome.

Design The present generation Kamra inlay is 5 microns thick with a 1.6-mm central aperture and an overall outer diameter of 3.8 mm. The opaque peripheral part of the implant has 8,400 laser-drilled holes of 5–11 microns diameter to facilitate corneal nutrition and maintain oxygen permea­bility in the corneal stroma (Fig. 1). The opaque region allows transmission of only 6.7% of the light rays.

Technique The inlay is implanted in the nondominant eye in a femtosecond laser-assisted intrastromal corneal pocket. The depth of placement of this implant ranges from 200 to 250 µm. In eyes with previous laser-assisted in situ kerato­ mileusis (LASIK) surgery, the placement of the inlay is into a pocket, which is created at least 100–110 μm beneath the overlying LASIK flap.

Indications The Kamra inlay has a wide range of applications in pre­ sbyopes with emmetropia, myopia, and hypermetropia, prior history of LASIK or previous cataract surgery with monofocal IOL implantation. It is best suited for presbyopes with low degrees of myopia ranging from −0.75 to −1.0 D. LASIK may be performed with Kamra inlay implantation for correction of coexistent refractive errors, either as a simultaneous or a sequential procedure. In addition, photo­ refractive keratectomy has been performed in conjunction with Kamra inlay implantation, and the combined technique is known as PRKamra.

Visual acuity and quality: Dexl et al. evaluated the longterm outcomes after implan­tation of Kamra inlay in emmetropic presbyopes and observed an improvement in both the uncorrected near and intermediate visual acuities over 5 years of follow-up.9 As expected, a slight decrease in the uncor­rected distance visual acuity (UDVA) was observed in the operated eye; however, 93.5% patients had UDVA of 20/20 or better. Tomita et al. observed the outcomes of Kamra implan­ tation performed after previous LASIK surgery, as well as with simultaneous LASIK.7,8 In patients with previous history of LASIK, the implant was placed in a pocket created at least 80 microns beneath the LASIK flap. The implant had minimal impact on the distance vision and led to significant improvement in intermediate as well as near vision.8 Simultaneous LASIK with Kamra inlay is a viable option for the management of coexistent myopia and hypermetropia.7 An improvement in uncorrected distance as well as near visual acuity is observed with minimal adverse impact on stereoacuity and contrast sensitivity. The near visual acuity improved by seven lines in hyperopes, six lines in emmetropes, and two lines in myopes; in addition, an improvement of three, one, and ten lines was observed for distance vision in hyperopes, emmetropes, and myopes, respectively. Reading performance: Significant improvements in all reading parameters, such as smallest print size that could be read, mean reading acuity, mean reading distance, and mean reading speed, have been observed.10 Safety: Studies in humans have demonstrated good safety with no inflammatory reactions. There have been no cases of ulceration or stromal fibrosis. The endothelial cell count, corneal thickness, and contrast sensitivity have been observed to be stable over 2 years.10,11 No localized changes in the visual field or scotomas have been observed following inlay implantation.10,11 Although refraction may shift, there is generally no loss of best-corrected visual acuity (BCVA).

Post-inlay Examinations and Surgery

Fig. 1: Design of Kamra corneal inlay.

No difficulty is encountered during retinal examination in eyes implanted with this inlay.11 Normal fundus examination and imaging using optical coherence tomography are feasible with Kamra inlays in situ. Patients with inlay implan­tation requiring cataract surgery are now being seen. Uneventful small-incision phacoemulsification with mono­ focal IOLs is an option.

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SECTION 7: Presbyopia

Complications The most common complaints observed after Kamra implant are similar to those after LASIK, including dry eyes, glare, halos, and problems in night vision.7,8,11 An explant may be required in patients unhappy with vision, debilitating dysphotic symptoms, refractive shift, or flaprelated problems. The surgery is potentially reversible; however, residual haze and loss of corrected distance visual acuity (CDVA) have been observed after explant of the Kamra inlay.12 The visual outcomes after inlay implantation are dependent on adequate centration, with minor decentration of even 0.5 mm having a significant adverse impact on the image quality.8 Recentration of small aperture inlays may be performed successfully with visual improvement. A mild hyperopic shift has been observed after implantation of Kamra inlay, which may in part be related to central flattening and annular steepening, and keratometry changes induced due to the wound-healing response with stromal thickening over the inlay.13 In addition, infectious keratitis, epithelial ingrowth, corneal epithelial iron deposits, and corneal haze have been reported.5,11,14

Refractive Optic Inlays The refractive inlays function by creating a multifocal effect by inducing a change in the central refractive index of the cornea. The commercially available refractive optic inlays include the Flexivue Microlens, the Invue Lens, and the Icolens.

Principle Refractive inlays are based on the principle of creating a multifocal cornea by altering the refractive index due to their bifocal optic design. The central part of the inlay is refractive neutral and provides distance vision; it is

surrounded by one or more rings with variable near add to provide intermediate and near vision.4

Design The Flexivue Microlens (Presbia, Los Angeles, CA) is a transparent refractive inlay that is made of a hydrophilic copolymer of hydroxyethyl methacrylate and methyl methacrylate along with ultraviolet blockers. The diameter of the implant is 3.2 mm with a central 0.51 mm aperture to facilitate fluid and oxygen flow and maintain corneal nutrition. The thickness of the implant varies from 15 to 20 microns based on the near add.2,4 The central region is optically neutral and intended for distance vision; the peripheral zone has a higher refractive index than the cornea to provide near add ranging from +1.5 D to +3.5 D (0.25 D steps) (Fig. 2). The clear hydrogel inlay allows 95% of visible light to be transmitted.4 The Icolens (Neoptics, Hunenberg, Switzerland) is another refractive optic inlay made of hydrophilic acrylic hydrogel. Similar to Flexivue Microlens, the diameter of this inlay is 3 mm with a central 150 microns hole to facilitate corneal nutrition and maintain transparency. There is a central 1.8-mm wide zone for distance and peripheral zone for near. Refractive inlays are implanted at a depth of 280– 300 microns in a pocket created using femtosecond laser. The device is centered on the first Purkinje image and does not induce any alterations in corneal surface shape due to its relatively deep placement. The inlay is bioinert and may be easily removed or replaced with higher power inlay as the patient ages. Flexivue Microlens has received CE approval in Europe.

Outcomes Beer et al. reported satisfactory near vision at 1 year after implan­ t ation of the Flexivue Microlens in

Fig. 2: Design of Flexivue Microlens corneal inlay.

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CHAPTER 21: Corneal Inlays emmetropic presbyopes. Of the 31 patients, 90% reported good-to-excellent near vision. Binocular UDVA was maintained with 100% of patients reporting 20/20 binocular vision; however, there was a fall in CDVA of 3 or more lines in 16.1% of operated eyes. There was an increased induction of spherical aberrations, which was associated with the improvement in near vision.15 Similarly, Limnopoulou et al. observed an uncorrected near visual acuity of 20/32 or better in 75% of patients implanted with the Flexivue Microlens.16 There was a significant decrease in the UDVA in the operated eye; in addition, a loss of one line of CDVA was reported by 37% patients. Increased higher order aberrations were observed in the operated eye along with visually disturbing phenomenon such as glare and halos in 12.5% patients. The outcomes of Icolens are similar with 90% of patients satisfied with postoperative near vision. A significant loss of uncorrected and CDVA was observed in the corrected eye, with over 21% patients requiring an explant due to no significant benefit in near vision.17 The loss of CDVA was postulated to be due to an implant related neuro-optical phenomenon.

Space-occupying Corneal Inlays The Raindrop corneal inlay (ReVision Optics, Lake Forest, CA) is a space-occupying corneal reshaping inlay intended for the correction of presbyopia in emmetropes.

Principle The mechanism of Raindrop corneal inlay is increasing the steepness of the central cornea by inducing curvatural changes in the corneal surface. 18 The position of the implant in corneal stroma is relatively superficial as compared to other inlays to allow for modifications in corneal shape. The implant increases the central corneal power by +4 D, with an average increase in steepness and keratometry by +1.7 D. The implant is refractive neutral and does not provide any distance correction; it is intended for use in emmetrope presbyopes with requirement of +1.5 to +2.5 D near add. Constricted pupil enhances the pseudo­ accommodative effect of the implant.

Design The Raindrop inlay is a transparent hydrogel lenticule with 2-mm diameter. The central thickness of the inlay is 32 microns and the peripheral edge thickness is 10 microns (Fig. 3). It is a refractive neutral inlay with a refractive index similar to that of the human cornea. The implant is placed beneath a lamellar corneal flap of 120–200-µm thickness and is centered based on the pupil.

Outcomes The initial studies showed promising results with Raindrop inlay, with an improvement in the near visual acuity without a significant adverse impact on the distance visual acuity.18 The device received FDA approval in 2016; however, a subsequent post-approval study observed the development of corneal haze in 75% patients with 42% having a central haze involving the visual axis. The US FDA revoked the approval in 2018 and issued a class I recall of the device; the inlay is no longer commercially available.19

Advantages The main advantage of corneal inlays is related to the potential reversibility of the procedure. The inlays are tissue additive procedures and do not entail corneal ablation or removal of stromal tissue. They may be safely combined with other corneal refractive procedures for correction of ametropia in addition to presbyopia. The corneal inlays are implanted unilaterally in the nondominant eye, and the reported loss of CDVA in the operated eye usually does not impact the binocular uncorrected vision. The increased margin of safety and pre­ servation of stereoacuity is an advantage of this technique.

Limitations A loss of CDVA in the operated eye is a major roadblock with any refractive procedure and limits the acceptability of the surgery and patient satisfaction. Though the technique is potentially reversible, residual haze and persistent loss of distance visual acuity have been reported.12 In addition, the inlays rely on adequate centration and even mild decentration can significantly worsen the quality of vision.

Fig. 3: Design of Rainbow corneal inlay.

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SECTION 7: Presbyopia Inlays may be associated with decreased ocular surface stability and dry eyes. In addition, dysphotic symptoms including glare and halos, decreased contrast sensitivity, and visual quality may be observed with varying frequency in all kinds of implants. Stromal thinning and melting have been reported after inlays, which may warrant an explant.7,10,11

  CORNEAL ONLAYS In contrast to inlays, which are synthetic lenticules implanted within the corneal stroma, onlays are lenticules implanted underneath the epithelium. The combination of corneal shape modification and inherent refractive index of the onlay provide presbyopic correction. Short-term outcomes of collagen-based onlays appear promising; however, long-term biocompatibility, efficacy, and safety of these implants are yet to be evaluated.

  CONCLUSION Corneal inlays are a promising technique for surgical correction of presbyopia. The present-day implants have a limited application owing to the decrease in CDVA and associated dysphotic symptoms such as glare and halos. Various novel designs of corneal inlays are being evaluated including those based on diffractive designs with an array of micro-holes, and trifocal designs for near, intermediate as well as distance vision. In addition, allogenic inlays utilizing refractive lenticules are being evaluated. Future technological advancements may help to enhance the safety of the procedure and promote its acceptability.

  REFERENCES 1. Barraquer JI. Modification of refraction by means of intracorneal inclusions. Int Ophthalmol Clin. 1966;6:53-78. 2. Papadopoulos PA, Papadopoulos AP. Current management of presbyopia. Middle East Afr J Ophthalmol. 2014;21:10-7. 3. Choyce DP. The present status of intra-cameral and intracorneal implants. Can J Ophthalmol J Can Ophtalmol. 1968;3:295-311. 4. Arlt E, Krall E, Moussa S, Grabner G, Dexl AK. Implantable inlay devices for presbyopia: the evidence to date. Clin Ophthalmol Auckl NZ. 2015;9:129-37. 5. Waring GO, Klyce SD. Corneal inlays for the treatment of presbyopia. Int Ophthalmol Clin. 2011;51:51-62. 6. Seyeddain O, Riha W, Hohensinn M, Nix G, Dexl AK, Grabner G. Refractive surgical correction of presbyopia with the AcuFocus small aperture corneal inlay: two-year follow-up. J Refract Surg Thorofare NJ. 2010;26:707-15. 7. Tomita M, Kanamori T, Waring GO, Yukawa S, Yamamoto T, Sekiya K, et al. Simultaneous corneal inlay implantation

and laser in situ keratomileusis for presbyopia in patients with hyperopia, myopia, or emmetropia: six-month results. J Cataract Refract Surg. 2012;38:495-506. 8. Tomita M, Kanamori T, Waring GO, Nakamura T, Yukawa S. Small-aperture corneal inlay implantation to treat presbyopia after laser in situ keratomileusis. J Cataract Refract Surg. 2013;39:898-905. 9. Dexl AK, Jell G, Strohmaier C, Seyeddain O, Riha W, Rückl T, et al. Long-term outcomes after monocular corneal inlay implantation for the surgical compensation of presbyopia. J Cataract Refract Surg. 2015;41:566-75. 10. Dexl AK, Seyeddain O, Riha W, Rückl T, Bachernegg A, Emesz M, et al. Reading performance and patient satis­ faction after corneal inlay implantation for presbyopia correction: two-year follow-up. J Cataract Refract Surg. 2012; 38:1808-16. 11. Seyeddain O, Hohensinn M, Riha W, Nix G, Rückl T, Grabner G, et al. Small-aperture corneal inlay for the correction of presbyopia: 3-year follow-up. J Cataract Refract Surg. 2012; 38:35-45. 12. Moshirfar M, Skanchy DF, Rosen DB, Heiland MB, Liu HY, Buckner B, et al. Visual Prognosis after Explantation of Small-aperture Corneal Inlays in Presbyopic Eyes: A Case Series. Med Hypothesis Discov Innov Ophthalmol J. 2019;8:129-33. 13. Moshirfar M, Desautels JD, Walker BD, Birdsong OC, Skanchy DF, Quist TS, et al. Long-term changes in kerato­ metry and refraction after small aperture corneal inlay implantation. Clin Ophthalmol Auckl NZ. 2018;12:1931-8. 14. Duignan ES, Farrell S, Treacy MP, Fulcher T, O'Brien P, Power W, et al. Corneal inlay implantation complicated by infectious keratitis. Br J Ophthalmol. 2016;100:269-73. 15. Beer SMC, Santos R, Nakano EM, Hirai F, Nitschke EJ, Francesconi C, et al. One-year Clinical Outcomes of a Corneal Inlay for Presbyopia. Cornea. 2017;36:816-20. 16. Limnopoulou AN, Bouzoukis DI, Kymionis GD, Panagopoulou SI, Plainis S, Pallikaris AI, et al. Visual outcomes and safety of a refractive corneal inlay for presbyopia using femtosecond laser. J Refract Surg Thorofare NJ. 2013;29:12-8. 17. Baily C, Kohnen T, O’Keefe M. Preloaded refractiveaddition corneal inlay to compensate for presbyopia implanted using a femtosecond laser: one-year visual outcomes and safety. J Cataract Refract Surg. 2014;40:1341-8. 18. Garza EB, Gomez S, Chayet A, Dishler J. One-year safety and efficacy results of a hydrogel inlay to improve near vision in patients with emmetropic presbyopia. J Refract Surg Thorofare NJ. 2013;29:166-72. 19. Health C for D and R. (2020). Increased Risk of Corneal Haze Associated with the Raindrop Near Vision Inlay: FDA Safety Communication. FDA 2020. [online] Available from: https:// www.fda.gov/medical-devices/safety-communications/ increased-risk-corneal-haze-associated-raindrop-nearvision-inlay-fda-safety-communication. [Last accessed June, 2021].

SECTION

8

Miscellaneous

22. Bioptics

25. Intrastromal Corneal Ring Segments

23. Corneal Collagen Cross-linking and Refractive Surgeries

26. Incisional Refractive Surgery

Farin Shaikh, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair

Sridevi Nair, Harathy Selvan, Manpreet Kaur, Jeewan S Titiyal

24. Refractive Surgery in Challenging Scenarios Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

Rinky Agarwal, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal Meghal Gagrani, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair

CHAPTER

22

Bioptics Farin Shaikh, Manpreet Kaur, Jeewan S Titiyal, Sridevi Nair

  INTRODUCTION Bioptics is defined as the sequential association of surgical approaches involving two different optical planes (lens and cornea) for correction of high ametropia and postsurgical refractive surprises. The term “Bioptics” was first introduced by Dr Roberto Zaldivar in 1994, when he implanted posterior chamber phakic intraocular lens (IOL) followed by secondary laser-assisted in situ keratomileusis (LASIK) for the correction of extreme myopia.1 In addition to achieving near emmetropia in cases with extremes of refractive error, bioptics aims to refine stability and predictability of refrac­ tive correction, conserve corneal prolate asphericity thus limiting optical aberrations, and maintain large optical zones in order to achieve optimal quality of vision. In cases of extreme ametropia, total correction of refrac­ tive error in a single refractive plane is insufficient and is associated with poor quality of vision due to smaller optical zone and large ablation depth.2 Bioptics provides custo­ mized way of treatment in these patients so as to achieve pre­dictable and reliable postoperative outcomes.3 Presently, it encompasses the use of an intraocular implant followed by a cornea-based procedure for refractive errors that cannot be corrected only by one procedure.4-6

  PATIENT SELECTION AND PREOPERATIVE WORK-UP Adequate patient selection and preoperative work-up is of utmost importance in any refractive surgery to achieve desired outcomes. The patient should be over 18 years of age with stable refractive error and suitable for both component procedures of bioptics. As majority of patients undergoing bioptics are high myopes, regular posterior segment evaluation is advised. Preoperative laser of pathological peripheral retinal degenerations is recom­ mended to reduce the risk of postoperative detachment. The detailed inclusion and exclusion criteria are similar to other refractive surgeries and summarized in Table 1.

TABLE 1: Inclusion and exclusion criteria for bioptics. Inclusion criteria

Exclusion criteria

Age ≥ 18–21 years

Age < 18–21 years

Stable refractive error

Central keratometry > 47.2 D

CCT ≥ 500 microns

Large pupil size (>7 mm)

Iridocorneal angle ≥ 30°

Known case of progressive corneal ectatic disorders

Anterior chamber depth—from endothelium >2.8 mm, 10.8 mm, Severe dry eyes, collagen vascular 34 and 6 D), borderline residual stromal bed thickness (250–330 microns), thin corneas (475–520 microns), increased preoperative astigmatism (>1.5 D), increased percentage tissue altered (PTA > 35%), and borderline high indices such as Belin–Ambrósio devia­ tion index (BAD-D), Corvis biomechanical index (CBI), or tomographic and biomechanical index (TBI) may be considered.4

Regression after corneal refractive surgeries is believed to be a manifestation of biomechanical instability and performing simultaneous corneal cross-linking may be beneficial in patients at higher risk for regression such as hyperopes and high myopes.5

Treatment Protocols Various treatment protocols have been described for performing combined accelerated CXL with corneal refractive surgery based on the riboflavin concentration used, UV irradiation time, UV power, and the total energy delivered (Table 1).

Riboflavin Solution A 0.22–0.25% dextran-free formulation of riboflavin 5-phosphate solution is recommended for intrastromal application, as the lack of dextran allows the solution to permeate faster into the stroma. The formulations are commercially available as VibeX Xtra (0.22%; Avedro), Collagex plus (0.25%; LightMed), and Peschke L (0.23%; Peschke Trade).

UV Energy The UVA energy dose used for “Xtra” procedures in published literature ranges from 0.8–5.4 J/cm2; however, a lower energy has been recommended by most authors, as the indication for CXL in patients undergoing refractive procedures is prophylactic rather than therapeutic. 6 Lower energy and accelerated protocols also lead to less keratometric flattening as compared to conventional CXL while reducing the incidence of complications such as diffuse lamellar keratitis (DLK) and central toxic keratopathy.5

Surgical Technique For performing LASIK Xtra, the most commonly employed technique requires the coating of the stromal bed with riboflavin for about 45–120 seconds after excimer laser treatment. The LASIK flap is then repositioned and the UVA light is applied. Some authors have suggested rinsing

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SECTION 8: Miscellaneous TABLE 1: Studies evaluating the long-term outcomes of simultaneous accelerated corneal collagen cross-linking with corneal refractive surgeries. Follow-up (months)

Riboflavin solution used

UVA power (mW/cm2)

UVA radiation time

Total energy dose (J/cm2)

Celik et al. (2012) •• LASIK—4 •• LASIK Xtra—4 •• Contralateral eye study

12

•• 0.1% solution •• Stromal bed soaked for 90 seconds before flap reposition

30

3 minutes

5.4

•• Long-term UDVA and SE comparable in both groups •• Mild transient stromal haze in LASIK CXL group

Tomita et al. (2014)

•• LASIK—24 •• LASIK Xtra—24

12

•• 0.1% solution •• Stromal bed soaked for 60 seconds before flap reposition

30

1 min

1.8

Refractive and keratometric (p > 0.05) results between the two groups were comparable

Kanellopoulos et al. (2014)

•• LASIK—82 •• LASIK Xtra—73

12

•• 0.1% riboflavin •• Stromal bed soaked for 60 seconds before flap reposition

30

80 seconds

2.4

More eyes (64.4% vs 61%) gained one or more lines in LASIK Xtra group

Kanellopoulos et al. (2015)

•• LASIK—75 •• LASIK Xtra—65

24

•• 0.1% riboflavin •• Stromal bed soaked for 60 seconds before flap reposition

30

80 seconds

2.4

•• Better refractive stability on LASIK Xtra group •• More eyes in the LASIK Xtra group achieved UDVA better than 20/20 (94% vs. 85%) and 20/25 (96% vs. 90%)

Seiler et al. (2015)

•• LASIK—76 •• LASIK Xtra—76

12

•• 0.5% aqueous riboflavin •• Stromal bed soaked for 2 minutes before flap reposition

9

5 minutes

2.7

•• Early postoperative complications such as DLK (stage 1 in 38%; stage 2 in 5%) and epithelial erosions (16%) higher in LASIK Xtra group •• Long-term visual acuity comparable in both groups •• Relifting a flap in LASIK Xtra eyes more difficult

Kohnen et al. (2020)

•• LASIK—26 •• LASIK Xtra—26 (contralateral eye study) •• 23 patients completed 12-month follow-up

12

•• 0.22% riboflavin •• Stromal bed soaked for 90 seconds before flap reposition

30

90 seconds

2.7

•• Myopic regression more in LASIK only group •• BSCVA in the LASIK Xtra group worse in the 1st month; thereafter both groups were comparable

Lim et al. (2020)

LASIK Xtra—163

22.8 months •• 0.22% riboflavin (mean FU) •• Stromal bed soaked for 45 seconds before flap reposition

30

46 seconds

1.4

•• Mild haze in 24 eyes and grade 1 DLK in 2 eyes that resolved within 1 month •• Mild myopic (−0.1 D mean) regression at 3 years

Protocol

Eyes (n)

Outcomes

Myopic LASIK Xtra

Contd…

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CHAPTER 23: Corneal Collagen Cross-linking and Refractive Surgeries Contd…

Protocol

Eyes (n)

Follow-up (months)

Riboflavin solution used

UVA power (mW/cm2)

UVA radiation time

Total energy dose (J/cm2)

1.6

Outcomes

Hyperopic LASIK Xtra Kanellopoulos et al. (2012)

•• Hyperopic LASIK—34 eyes •• Hyperopic LASIK Xtra—34 eyes (contralateral eye study)

24 months

0.1% riboflavin

10

3 minutes

Significantly greater regression observed in eyes without CXL at 2 years (0.72 D vs 0.22 D)

Aslanides et al. (2013)

•• Hyperopic LASIK—5 eyes •• Hyperopic LASIK Xtra—5 eyes

36 (LASIK group) 48 (LASIK Xtra group)

0.1% solution

3

30 minutes 5.4

No regression in LASIK Xtra group versus a trend of regression in LASIK group at 2 years

Lee et al. (2017)

•• tPRK-CXL: 47 •• tPRK: 42

12

•• 0.1% riboflavin •• Stromal bed soaked for 120 seconds after tPRK •• 0.02% MMC for 20 seconds after cross-linking

30

90 seconds 2.7

•• Earlier stabilization of UDVA in tPRKCXL group •• UDVA comparable in both groups at 12 months •• Lower MRSE and SE in tPRK-CXL group at 12 months •• tPRK-CXL group had longer epithelial healing time and one case developed a marginal infiltrate

Sachdeva et al. (2018)

•• PRK: 118 •• PRK-CXL: 109

12

•• 0.25% riboflavin •• Stromal bed soaked for 90 seconds •• No MMC applied

30

90 seconds 2.7

•• Refractive and keratometric outcomes were comparable in both groups •• Grade 1 haze in 9 PRK-CXL eyes— 1/9 eyes lost one line CDVA at 12 months

32 months

•• 0.1% riboflavin •• 0.02% MMC for 30–50 seconds after excimer ablation •• Stromal bed soaked for 20 minutes after MMC washed out

18 mJ/min (365 nm)

5 minutes

Mild (grade 0.5–1) corneal haze during the 1st month was seen in all cases; resolved completely at 6-month follow-up

12

0.25% riboflavin soaked for 60 seconds

45

75 seconds 3.4

•• Good safety and efficacy •• Two eyes developed transient grade 2 haze at 1 month which resolved within 3 months

Myopic PRK Xtra

Mohammadpour PRK-CXL: 17 et al. (2020) (Tehran protocol)

SMILE Xtra Sri Ganesh et al. (2015)

SMILE Xtra: 40

Contd…

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SECTION 8: Miscellaneous Contd… Follow-up (months)

Riboflavin solution used

UVA power (mW/cm2)

UVA radiation time

Total energy dose (J/cm2)

18

3 minutes

3.2

Protocol

Eyes (n)

Osman et al. (2019)

•• SMILE: 30 •• SMILE Xtra: 30

24

0.1% riboflavin soaked for 15 minutes

Liu et al. (2021)

•• SMILE Xtra; 48 eyes •• LASIK Xtra: 90 eyes

12

•• SMILE Xtra: 30 0.25% riboflavin soaked for 90 seconds •• LASIK Xtra: Stromal bed soaked with 0.25% riboflavin for 90 seconds

90 seconds 2.7

Outcomes •• Visual outcomes comparable in both groups •• Significantly higher CRF and densitometry in SMILE Xtra group •• Mild haze in SMILE Xtra group at 1 month; resolved by 3 months Refractive and keratometric outcomes in both groups were comparable

(LASIK: laser-assisted in situ keratomileusis; SMILE: small incision lenticule extraction; PRK: photorefractive keratectomy; tPRK: transepithelial photorefractive keratectomy; CXL: corneal collagen cross-linking; UV: ultraviolet; MMC: mitomycin C; FU: follow-up; UDVA: uncorrected distance visual acuity; SE: spherical equivalent; CRF: corneal resistance factor)

off riboflavin prior to flap repositioning and UVA light application. Soaking the flap in riboflavin solution should be avoided as cross-linking may cause it to shrink and predispose to flap striae.1 SMILE Xtra requires the injection of riboflavin solution into the stromal pocket for about 60 seconds following the lenticule removal. After soaking the stromal bed with riboflavin for several seconds, the interface is washed off and the central cornea is irradiated with UVA light.6 For PRK Xtra, the stromal bed is soaked with riboflavin solution for about 90 seconds after the epithelial removal (mechanical or excimer laser mediated) and excimer laser ablation. The excess riboflavin is rinsed away and UVA light applied over the central cornea, followed by a mitomycin C application and bandage contact lens (BCL) placement.7

Clinical Outcomes The postoperative efficacy, stability, and safety of LASIK Xtra are comparable or superior to LASIK alone for both myopia and hyperopia. LASIK Xtra has also shown better keratometric stability and lesser regression in both myopic and hyperopic eyes, attributed to better biomechanical stabilization and lesser epithelial hyperplasia.8 Photorefractive keratectomy with simultaneous CXL has been reported to be comparable to PRK alone in terms of long-term visual outcomes, refractive predictability, and keratometric stability.9

The long-term efficacy, predictability, and safety of SMILE Xtra are comparable to that of SMILE. A transient haze observed in the immediate post-operative period may lead to a delayed visual rehabilitation in SMILE Xtra patients without affecting the final long-term visual outcomes.10 No endothelial cell damage has been reported on performing CXL simultaneously with corneal refractive surgeries.

Complications Reports of complications with LASIK Xtra are rare and visually insignificant in most cases. Faint stromal haze, DLK, and corneal erosions have been reported in the immediate postoperative period and may be responsible for the delayed visual rehabilitation reported with LASIK Xtra by some authors.11 A single case of postoperative ectasia has been reported to occur 2 years after LASIK Xtra in a hyperopic patient.12 Postoperative complications reported in the immediate postoperative period following PRK Xtra include sterile marginal infiltrates that resolved on topical steroid therapy and toxic keratopathy that caused a large hyperopic shift with deterioration in visual acuity. Transient stromal haze, which minimally impacted the vision and resolved within 6 months, was reported by Sachdeva et al. in their PRK Xtra patients; this could be attributed to authors omitting the use of mitomycin C in this group in contrast to the PRK only group.2,9

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CHAPTER 23: Corneal Collagen Cross-linking and Refractive Surgeries

  CORNEAL COLLAGEN CROSS-LINKING PLUS

depopulation, thus reducing the possibility of stromal haze formation.13

The term “corneal collagen cross-linking plus (CXL plus)” refers to the combination of refractive procedures with corneal cross-linking in patients with corneal ectatic disorders, thereby providing them the dual advantages of improved refractive outcomes as well as disease stabilization. The procedures that have been described as an adjuvant to CXL aim to regularize the cornea, reduce irregular astigmatism and improve the refractive status, and include conductive keratoplasty, PRK, phototherapeutic keratectomy (PTK), intracorneal ring segment implantation, and phakic intraocular lens (IOL) implantation.

Corneal Collagen Cross-linking with Photorefractive Keratectomy Topography-guided PRK was the first procedure to be performed in combination with CXL in patients with corneal ectasia. Though initially performed as a twostep sequential procedure with CXL followed by PRK, a simultaneous approach was adopted thereafter. Corneal surface ablation followed by CXL performed in a single sitting has the advantages of lesser corneal haze, better preservation of cross-linked stromal tissue, and better patient comfort. The primary aim of PRK in this procedure is to regularize the cornea and not the correction of refractive error; however, partial correction of refractive error may be attempted as long as a residual stromal thickness of about 350–400 microns remains after ablation. The application of MMC 0.02% after PRK in order to prevent stromal haze remains a matter of debate. While some authors have recommended its use, others have omitted it citing that cross-linking the ablated stroma leads to keratocyte

Treatment Protocols Various treatment recommendations and protocols have been proposed for PRK-CXL, including the Athens protocol and the Enhanced Athens protocol (Table 2).14 Athens protocol described by Kanellopoulos et al. incorporates sequential excimer laser-mediated epithelial debridement, partial topography-guided excimer laser stromal ablation, and high-fluence UVA accelerated CXL performed in a single session. Correction of about 70% of astigmatism and up to 70% of sphere, as permitted by 50 microns of stromal ablation, is planned. Enhanced Athens protocol combines topography-guided PRK with customized, variable-pattern refractive CXL.

Indications Progressive early keratoconus patients, above 18 years of age, with corneal thickness > 450 microns (residual stromal bed thickness after excimer ablation > 400 microns), predominantly irregular astigmatism and CL intolerance, may be considered for PRK-CXL.

Outcomes Long-term results of studies evaluating PRK combined with CXL have reported a significant improvement in UDVA, flattening of maximum keratometry, and stabilization of disease. 15 There are significant clinical improve­ ments and disease stability in post-LASIK ectasia. Studies comparing simultaneous PRK and CXL with CXL alone in progressive keratoconus observed the combined proce­ dure to produce better visual outcomes including a better

TABLE 2: The indications, treatment protocols, and outcomes of photorefractive keratectomy with corneal collagen cross-linking. Surface ablation protocol

CXL protocol

Outcomes

Athens protocol

•• A 6.5-mm epithelial ablation (50 microns) •• Partial topography-guided PRK (5.5-mm OZ) with a maximum stromal ablation of 50 microns •• 0.02% MMC applied for 20 seconds

High-fluence accelerated CXL with 0.1% riboflavin-5-phosphate solution at 6 mW/cm2 for 15 minutes

•• Long-term results confirm an improvement in UDVA, flattening of maximum keratometry, and stabilization of disease (in 94.4%); with most parameters stabilizing by the first year •• Progressive overcorrection/hyperopic shift may be seen up to 3 years

Enhanced Athens protocol

•• A topography-guided partial PRK (maximum 30 microns) performed initially followed by a 7 mm, 50 microns PTK for epithelial removal •• 0.02% mitomycin C applied for 20 seconds

•• Stroma soaked with 0.1% riboflavin solution (with HPMC) for 5 minutes •• 20 mW/cm2 of UV light fluence delivered uninterrupted in three different concentric patterns: the inner pattern matched to thinnest part of cornea receives a total of 15 J energy, the intermediate 10 J, and the outer 5 J

•• Significantly enhanced refractive effect, and corneal flattening with less tissue removal (30 microns vs 50 microns) •• Improved UDVA and CDVA outcomes

(LASIK: laser-assisted in situ keratomileusis; SMILE: small incision lenticule extraction; PRK: photorefractive keratectomy; CXL: corneal collagen cross-linking; UV: ultraviolet; UDVA: uncorrected distance visual acuity; OZ: optical zone; HPMC: hydroxypropyl methylcellulose)

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SECTION 8: Miscellaneous higher-order aberration (HOA) profile with com­parable disease stability.14

Complications The complications reported with combined CXL and PRK include stromal haze, which may be visually significant in up to 5% cases, corneal edema, stromal scar, and microbial keratitis. Failure to halt disease progression has been observed in about 6% cases.13

Corneal Collagen Cross-linking with Phototherapeutic Keratectomy The combination of CXL with transepithelial PTK (tPTK) has been referred to as the Cretan’s protocol. Transepithelial PTK serves the dual purpose of removing the epithelium for CXL as well as regularizing the corneal surface. The Cretan protocol plus additionally incorporated conventional PRK (performed after PTK) to the Cretan protocol for spherocylindrical correction in patients with sufficient preoperative corneal thickness (Table 3).16

Indications Indications for PTK-CXL are similar to that of PRK-CXL. Furthermore, since the amount of stromal tissue removed is much lower, it may be a feasible alternative in patients with thinner corneas who are not eligible for PRK-CXL.

Outcomes Transepithelial PTK with CXL has been reported to produce a significant improvement in uncorrected distance visual acuity (UVDA), HOAs, and keratometry while maintaining disease stability in keratoconus patients. Kymionis et al. reported an improvement in UDVA from 0.99 to 0.61 logMAR units at a mean follow-up of 33.8 ± 10.82 months with the Cretan protocol. Mean steep keratometry flattened from

53.3 to 49.9 D and the mean stigmatism reduced from 6.2 to 4.5 D. Visually significant stromal haze has been reported in up to 7.3% of cases with the Cretan protocol plus.17

Corneal Collagen Cross-linking with Intracorneal Ring Segment Implantation Intracorneal ring segment (ICRS) implantation in keratoconus patients helps to flatten and regularize the central cornea, thus improving the visual outcomes and contact lens tolerance in these patients. It, however, does not prevent disease progression and combining it with CXL helps to stabilize disease progression. ICRS implantation performed first followed by CXL in the same sitting provides greater flattening of cornea and stabilization of ectasia. CXL when performed first induces a corneal stiffening, which may limit the ability of the ring segments to flatten the cornea.18 While most studies have used the standard Dresden protocol with epithelium off CXL, different techniques of riboflavin application including an epithelium on approach, injection into the intrastromal pockets, and flash cross-linking have been described. A recent study found the treatment efficacy of ICRS implantation and CXL with intratunnel application of riboflavin comparable to that of epithelium off CXL.19

Indications CXL can be combined with ICRS implantation in corneal ectasia patients of mild-to-moderate severity with contact lens intolerance, CDVA < 0.6–0.9 decimal, and corneal thickness > 400 microns at thinnest site and the site of ring implantation.

Outcomes Studies comparing ICRS implantation with CXL vs. ICRS implantation alone have found the former to produce comparable or greater flattening in keratometry, reduction

TABLE 3: The indications, treatment protocols, and outcomes of phototherapeutic keratectomy with corneal collagen cross-linking. Surface ablation protocol

CXL protocol

Outcomes

Cretan protocol

•• Transepithelial PTK ablation performed at 6.5–7.0 mm zone at 50 microns depth •• The deepithelialized area enlarged mechanically to intended 8.0–9.0 mm

•• Stroma soaked with 0.1% riboflavin phosphate solution (with Dextran) for 30 minutes •• CXL performed at 3 mW/cm2 × 30 mins

Significant improvement in visual and keratometric outcome measures

Cretan protocol plus

•• Transepithelial PTK ablation performed at 6.5–7.0-mm zone at 50 microns depth •• The de-epithelialized area enlarged mechanically to intended 8.0–9.0 mm •• Conventional PRK performed with a maximum ablation up to 50 microns and OZ of 5.5 mm •• Minimum estimated corneal thickness after combined transepithelial PTK and PRK should be 350 microns

•• Stroma was soaked with 0.1% riboflavin (isotonic, if CT after ablation > 400 microns; hypotonic, if 400 microns, good spectacle-corrected distance visual acuity (CDVA > 0.3), and moderate-to-high refractive error with a predominantly regular astigmatism and anterior chamber depth > 3 mm are suitable for CXL followed by phakic IOL implantation. Pellucid marginal degeneration patients have a predominantly astigmatic error with fewer HOAs than keratoconus patients, making them suitable candidates for the procedure.13

Outcomes Studies evaluating phakic IOL implantation after CXL in keratoconus patients report good visual outcomes and disease stability over long-term follow-up. While no visually significant complications have been reported, increased inflammatory response with giant cell deposition over IOL optic surface with Artiflex phakic IOL implantation and a transient increase in IOP in the immediate postoperative period with Visian ICL have been reported.20

  CONCLUSION The integration of CXL with refractive procedures has expanded the scope of refractive correction to previously unfeasible scenarios such as borderline thin corneas and corneal ectatic disorders. In fact, the future of refractive surgery may lie in minimally invasive procedures such as photorefractive intrastromal cross-linking (PiXL) for correction of refractive errors including presbyopia.

  REFERENCES 1. Kanellopoulos AJ, Asimellis G, Salvador-Culla B, Chodosh J, Ciolino JB. High-irradiance CXL combined with myopic

LASIK: flap and residual stroma biomechanical properties studied ex-vivo. Br J Ophthalmol. 2015;99(6):870-4. 2. Lee H, Roberts CJ, Ambrósio R, Elsheikh A, Kang DSY, Kim TI. Effect of accelerated corneal crosslinking combined with transepithelial photorefractive keratectomy on dynamic corneal response parameters and biomechanically corrected intraocular pressure measured with a dynamic Scheimpflug analyzer in healthy myopic patients. J Cataract Refract Surg. 2017;43(7):937-45. 3. Randleman JB, Trattler WB, Stulting RD. Validation of the Ectasia Risk Score System for preoperative laser in situ keratomileusis screening. Am J Ophthalmol. 2008; 145(5):813-8. 4. Ma J, Wang Y, Jhanji V. Corneal refractive surgery combined with simultaneous corneal cross-linking—indications, protocols and clinical outcomes: a review. Clin Exp Ophthalmol. 2020;48(1):78-88. 5. Lim EWL, Lim L. Review of Laser Vision Correction (LASIK, PRK and SMILE) with Simultaneous Accelerated Corneal Crosslinking: Long-term Results. Curr Eye Res. 2019;44(11):1171-80. 6. Liu C, Wang Z, Wu D, Luo T, Su Y, Mo J, et al. Comparison of 1-year Outcomes between Small Incision Lenticule Extraction with Prophylactic Cross-linking and Femtosecond Laser-assisted in Situ Keratomileusis with Prophylactic Cross-linking. Cornea. 2021;40(1):12-8. 7. Mohammadpour M, Farhadi B, Mirshahi R, Masoumi A, Mirghorbani M. Simultaneous photorefractive keratectomy and accelerated collagen cross-linking in high-risk refractive surgery (Tehran protocol): 3-year outcomes. Int Ophthalmol. 2020;40(10):2659-66. 8. Kohnen T, Lwowski C, Hemkeppler E, de’Lorenzo N, Petermann K, Forster R, et al. Comparison of Femto-LASIK with Combined Accelerated Cross-linking to Femto-LASIK in High Myopic Eyes: A Prospective Randomized Trial. Am J Ophthalmol. 2020;211:42-55. 9. Sachdev GS, Ramamurthy S, Dandapani R. Comparative analysis of safety and efficacy of photorefractive keratectomy versus photorefractive keratectomy combined with crosslinking. Clin Ophthalmol. 2018;12:783-90. 10. Osman IM, Helaly HA, Abou Shousha M, AbouSamra A, Ahmed I. Corneal Safety and Stability in Cases of Small Incision Lenticule Extraction with Collagen Cross-linking (SMILE Xtra). J Ophthalmol. 2019;2019:6808062. 11. Seiler TG, Fischinger I, Koller T, Derhartunian V, Seiler T. Superficial corneal crosslinking during laser in situ keratomileusis. J Cataract Refract Surg. 2015;41(10):2165-70. 12. Taneri S, Kiessler S, Rost A, Dick HB. Corneal Ectasia after LASIK Combined with Prophylactic Corneal Cross-linking. J Refract Surg. 2017;33(1):50-2. 13. Kankariya VP, Dube AB, Grentzelos MA, Kontadakis GA, Diakonis VF, Petrelli M, et al. Corneal cross-linking (CXL) combined with refractive surgery for the comprehensive management of keratoconus: CXL plus. Indian J Ophthalmol. 2020;68(12):2757-72. 14. Kontadakis GA, Kankariya VP, Tsoulnaras K, Pallikaris AI, Plaka A, Kymionis GD. Long-term Comparison of Simultaneous Topography-guided Photorefractive Keratectomy followed by Corneal Cross-linking versus Corneal Cross-linking Alone. Ophthalmology. 2016;123(5): 974-83.

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SECTION 8: Miscellaneous 15. Kanellopoulos AJ. Ten-year Outcomes of Progressive Keratoconus Management with the Athens Protocol (Topography-Guided Partial-Refraction PRK Combined with CXL). J Refract Surg. 2019;35(8):478-83. 16. Grentzelos MA, Kounis GA, Diakonis VF, Siganos CS, Tsilimbaris MK, Pallikaris IG, et al. Combined trans­ epithelial phototherapeutic keratectomy and conventional photo­ r efractive kerate ctomy follow e d simulta­ neously by corneal crosslinking for keratoconus: cretan protocol plus. J Cataract Refract Surg. 2017;43(10): 1257-62. 17. Zhu AY, Jun AS, Soiberman US. Combined Protocols for Corneal Collagen Cross-linking with Photorefractive Surgery for Refractive Management of Keratoconus: Update on Techniques and Review of Literature. Ophthalmol Ther. 2019;8(Suppl 1):15-31.

18. Hashemi H, Alvani A , Seyedian MA , Yaseri M, Khabazkhoob M, Esfandiari H. Appropriate Sequence of Combined Intracorneal Ring Implantation and Corneal Collagen Cross-linking in Keratoconus: A Systematic Review and Meta-analysis. Cornea. 2018;37(12):1601-7. 19. Hosny M, Nour M, Azzam S, Salem M, El-Mayah E. Simultaneous intratunnel cross-linking with intrastromal corneal ring segment implantation versus simultaneous epithelium-off cross-linking with intrastromal corneal ring segment implantation for keratoconus management. Clin Ophthalmol. 2018;12:147-52. 20. Antonios R, Dirani A, Fadlallah A, Chelala E, Hamade A, Cherfane C, et al. Safety and Visual Outcome of Visian Toric ICL Implantation after Corneal Collagen Cross-linking in Keratoconus: Up to 2 years of Follow-up. J Ophthalmol. 2015;2015:514834.

CHAPTER

24

Refractive Surgery in Challenging Scenarios Sridevi Nair, Manpreet Kaur, Jeewan S Titiyal

  INTRODUCTION The outcomes of modern refractive surgery in normal corneas are fairly accurate and predictable with a high index of safety. Certain clinical scenarios continue to pose a challenge to the refractive surgeon owing to their complex presentation, intraoperative challenges, and less predict­ able visual outcomes. In this chapter, we discuss some of the commonly encountered challenging scenarios in refractive practice including refractive surgery in children, hyperopia, and postkeratoplasty cases.

  REFRACTIVE SURGERY IN PEDIATRIC PATIENTS Pediatric refractive procedures have a limited application due to the inherent lack of refractive stability in these cases. The progressive nature of the pathology makes them prone to the risk of the refractive error reappearing or progressing after the procedure.

Indications and Patient Selection The most common indications for performing pediatric keratorefractive surgery are anisometropic amblyopia and bilateral high-refractive errors in children noncompliant with glasses or contact lens use.1 Children with special needs, facial deformities, and delayed sensory or motor milestones may not tolerate spectacles or contact lens. Kerato­refractive procedures are also used to treat high accommodative esotropia in children.

Preoperative Considerations Age at intervention is an important consideration especially when aimed at treating or preventing amblyopia in the pediatric patients. Anisometropic amblyopia is best managed early, as patients above the age of 10 years are less responsive to treatment. There is no definitive lower limit and both laser-assisted in situ keratomileusis (LASIK) and photorefractive keratectomy (PRK) have been described

for treating anisometropic amblyopia in patients as young as 1 year. Preoperative assessment and screening are similar to any refractive surgery. While the indices used for ectasia screening are the same as described for adult subjects, the red flag signs may not manifest at a young age, thereby increasing the possibility of overlooking cases at risk to develop postoperative corneal ectasia.

Choice of Procedure Among the corneal procedures, surface ablation (photorefractive keratectomy) is preferred to flap-based LASIK, as children are prone to develop flap-related complications subsequent to eye rubbing or trauma. Faster epithelial healing in pediatric patients minimizes post­ operative discomfort following PRK. Stromal disruption is less in surface ablative procedures and may be associated with less pronounced biomechanical weakening and better long-term stability. Small incision lenticule extraction (SMILE) being a flapless procedure may have potential benefit in the pediatric age group.2 Lens-based procedures such as phakic intraocular lens (IOL) implantation, refractive lens exchange, and lensec­ tomy are feasible options for treating severe ametropia wherein laser-based procedures are not feasible. Refractive lens exchange may be consi­dered in cases of very high hypermetropia with a shallow anterior chamber, which precludes phakic IOL implantation. Conditions such as microspherophakia may also require lens extraction for treatment of the refractive error.3

Planning the Target Refraction The target refractive error should be near emmetropic in younger children undergoing surgery for amblyopia. For anisometropia, the target error should match that of the other eye. In adolescent children, it may be preferable to leave the child emmetropic or slightly hyperopic to compensate for the slight myopic shift due to natural ocular growth.

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SECTION 8: Miscellaneous

Operative Considerations and Challenges Younger children often require general anesthesia or sedation during surgery to ensure adequate patient coopera­ tion and comfort. Inhalational anesthetic agents may adversely affect excimer laser function; in addition, they preclude the ability of the patient to fixate on the laser target or the operating light during surgery. Proper positioning of the child is imperative to enable accurate treatment centration. Accurate astigmatic correc­ tion may be challenging in patients under general anesthesia owing to cyclotorsion.4

Clinical Outcomes ■■ Corneal refractive surgeries: PRK and LASIK are effec­

tive modalities for treating anisometropic ametropia in amblyogenic age group. Studies have reported signi­ ficant improvement in postoperative corrected and uncorrected distance visual acuity, binocularity, and stereopsis with a favorable safety profile. Surface ablation is associated with better predictability for treatment of myopic errors.5 Visual improvement is more pronounced in younger children; in addition, favorable outcomes are observed in older children outside the standard age of visual plasticity.6 The main postoperative complica­ tion is visually significant corneal haze that may require repeat ablation. Myopic regression or recurrence has been reported in up to 50% of patients. Rarer complica­ tions include epithelial ingrowth, flap striae, and free flaps.2,7 ■■ Lens-based procedures: Improved refractive outcomes and stereopsis have been observed after phakic IOL implanta­tion and refractive lens exchange for treating anisometropic amblyopia and high bilateral ametropia.8 Long-term studies are required to assess the endothelial cell loss and incidence of cataract formation with phakic IOL implantation in pediatric population.2 Pediatric refrac­ tive lens exchange is associated with a heightened risk of posterior segment complications, posterior capsular opacification, and glaucoma.9

Postoperative Challenges in Pediatric Refractive Surgery General anesthesia may be required for the postoperative evaluation, diagnosis, and treatment of complications such as flap dislocation or microbial keratitis. Corneal wound healing and biomechanical response after a keratorefractive procedure may be heightened in pediatric patients, predisposing them to an increased risk of corneal haze and ectasia. The continual ocular growth may affect the long-term refractive outcomes. Loss of accommodation following the lens-based procedures can have an adverse effect on the visual development of pediatric patients. The frequent incidence of postoperative haze may necessitate a longer course of topical steroids, increasing the risk for

steroid-induced glaucoma or cataract in these patients. Providing appropriate spectacle correction for any residual error and instituting amblyopia therapy if required are crucial for optimizing visual outcomes after refractive surgery in children.

  REFRACTIVE SURGERY FOR HYPEROPIA L’Esperance first proposed the principle of hyperopic ablation involving the removal of a negative meniscus of stromal tissue, thicker at its periphery than the center.10 Refractive surgery for hyperopia is challenging owing to the increased incidence of regression and suboptimal visual quality while treating higher errors. Table 1 details the different refractive procedures for correcting hyperopia including patient selection, operative considerations, visual outcomes, and limitations.

Preoperative Considerations Preoperative factors such as the degree of hyperopia, age of patient, lens status, accommodative ability, keratometry, corneal topography, anterior chamber depth, and endo­ thelial cell status help to determine the right candidate for surgery and the type of procedure to be employed. ■■ Type of procedure: Laser-based keratorefractive proce­ dures have good efficacy till +4 D of refractive error; the predictability and stability are much lower with higher refractive errors. Lens-based procedures are a viable alternative for correcting higher refractive errors; however, hyperopic eyes are inherently smaller with shallow anterior chambers limiting the feasibility of phakic IOLs. The Artisan iris-fixated phakic IOL and the Visian implantable collamer lens (ICL) are available for the correction of hyperopia; however, neither are US FDA approved for the indication. In older patients with cataractous changes, refractive lens exchange with a monofocal or presbyopic IOL may be a suitable option.11 ■■ Latent hyperopia: Assessment of the preoperative refractive error may be difficult in younger patients due to increased accommodative tone and a significant latent component of hyperopia, which may manifest after surgery. A cycloplegic refraction with fogging is mandatory to deter­mine the full refractive error. The treatment may be based on manifest refraction in patients with a 7.5 mm) with •• Optic size— slightly •• Large OZ, with low 6.3–6.7 mm optical larger than that for curvature gradient zone and 2 mm myopes between it and the transition zone •• Peripheral iridotomy transition zone •• Increased duration of mandatory laser application and lenticule dissection •• Centration based on first Purkinje reflex before docking •• No eye tracking

Visual outcomes

•• Visual outcomes less predictable and accurate than myopic LASIK •• Outcomes worse in higher hyperopic errors •• ±1.0 D accuracy ranges from 33–100%

•• Visual outcomes less predictable and accurate than myopic PRK, comparable to hyperopic LASIK •• Outcomes worse in higher hyperopic errors •• ±0.5 D accuracy ranges from 57 to 83.3%

•• ±0.50 D accuracy of •• Good predictability about 53% at 1 year and stability for postoperatively correction of high hyperopia >4 D •• UDVA > 20/40 in 95% •• One line loss in 16% •• 56.4–100% within ±1.0 D

•• Good predictability and stability for correction of high hyperopia >4 D •• ±1.0 D accuracy ranges from 68–100%

Limitations/ complications

•• Refractive regression, more pronounced with older lasers •• Visual disturbances due to HOAs induced by laser treatment, smaller optical zones and steeper postoperative keratometry •• Greater severity of postoperative dry eye

•• Refractive regression, more pronounced with older lasers •• Initial myopic overshoot; reversed by regression •• Slower refractive stabilization •• Midperipheral haze •• Postoperative pain

•• Less understood due to paucity of literature on the subject •• Anticipated to be similar to myopic SMILE

•• Endothelial damage •• Endophthalmitis •• Retinal detachment •• Cystoid macular edema •• Uveal effusion

•• Cataract •• Glaucoma •• Iritis/anterior uveitis/ pigment dispersion •• Endothelial cell loss •• Postoperative glare/ halos •• ICL removal/ repositioning due to pupillary block or upside down placement

Multifocal (EDOF/ trifocal) IOLs may be considered to provide good near and intermediate correction as well

(LASIK: laser-assisted in situ keratomileusis; SMILE: small incision lenticule extraction; PRK: photorefractive keratectomy; ICL: implantable collamer lens; UDVA: uncorrected distance visual acuity; SE: spherical equivalent; EDOF: extended depth of focus; HOAs: higher order aberrations; OZ: optical zone)

for laser ablative procedures, as the hyperopic error is more stable. These patients should be explained that the presbyopic component, if any, would persist after surgery. ■■ Keratometry: Final postoperative keratometry should be limited to 28 microns is recommended to prevent epithelial breakdown.13

Operative Considerations Larger ablation zone is required for hyperopic excimer laser procedure; however, corneal diameters are often smaller in hyperopes and PRK may be preferred in these

cases. Large optical zones and transition zones with a lower curvature gradient are the key for achieving good visual outcomes in hyperopes. The angle kappa in these patients is often large and it is recommended to center the treatment on or close to the coaxially sighted corneal light reflex rather than the pupillary center. Pupil-centered treatment may lead to a decentered treatment with significant induction of higher order aberrations (HOAs).14 Table 2 compares the operative considerations and outcomes with hyperopic and myopic corneal ablative procedures.

Clinical Outcomes Hyperopic Corneal Ablation Refractive predictability and safety of hyperopic LASIK is inferior to myopic LASIK, more so with higher magnitude of hyperopic correction (>4 D). Smaller optical zones lead to corneal irregularity, decentered treatment, and induction

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SECTION 8: Miscellaneous TABLE 2: Comparative evaluation of hyperopic and myopic laser-assisted in situ keratomileusis (LASIK). Myopic LASIK

Hyperopic LASIK

Keratometry

Minimum estimated postoperative keratometry 34 D

Maximum estimated postoperative keratometry 48–50 D

Range of refractive error

−14 DS, 6 DC

+6 DS, 6 DC

Ablation profile

Central cornea ablated to flatten the cornea

Preferential ablation of midperiphery with central steepening

Optical zone

6.5 mm

6–7 mm

Transition zone

1.25–1.5 mm

1.5–2 mm

Ablation zone

8 mm

9 mm

Treatment centration

Pupil centered

Centered on visual axis/first Purkinje reflex

Excimer ablation time

•• Ablation time shorter •• 1.4–2.5 seconds per diopter sphere

•• Ablation time longer •• 3.75–5 seconds per diopter sphere

Flap size

Smaller flap size (7.5–8 mm)

Larger flap size (9–9.2 mm)

Patient selection

Operative considerations

Outcomes with different ablation profiles Wavefront optimized

•• 93% 20/20 or better •• 99% 20/40 or better

•• 67% 20/20 or better •• 95% 20/40 or better

Wavefront guided

•• 93.4% 20/20 or better •• 99.4% 20/40 or better

•• 67% 20/20 or better •• 95% 20/40 or better

Topography guided

•• 94.8% within 0.5 D target •• 92.6% were 20/20 or better

•• 75.5% within 0.5 D target •• 94.4% in ±1.00 D range

Triple A ablation profile (Mel 90)

•• ± 0.50 D in 88% and ± 1.00 D in 100% of eyes •• UDVA 20/20 or better in 92%

•• ±0.50 D in 73% and ±1.00 D in 93% of eyes •• UDVA 20/20 or better in 75%

Postoperative aberrations

Induces positive spherical aberrations and positive secondary astigmatism

More induced aberrations—induce negative spherical aberrations and negative secondary astigmatism

Postoperative regression

•• Rare in low myopic corrections •• In moderate-to-high myopia: 0.74 ± 0.99 D between 3 months—12 years

More common: •• +1.47 D ±1.43 D over 1–16 years •• >0.75 D at 6 months in about 10%

of HOAs, resulting in poor visual quality and high rates of regression. Predictability and safety of hyperopic LASIK have improved over the years with the introduction of more advanced excimer laser systems, better treatment algori­ thms, and changes in surgical protocol such as employing larger optical zones (>6.5 mm) and centering the treatment on the coaxially sighted corneal light reflex.15 Variable predictability is observed with 47–95% of cases within ±0.5 D of target refraction.13 Efficacy varies from 24 to 95.7% and 0 to 6.5% cases lost 2 lines of corrected distance visual acuity (CDVA).13,16,17 Loss of CDVA is partly attributed to the minification effect in the absence of hyperopic glasses.13 Regression after hyperopic LASIK is a postoperative challenge and occurs mostly during the 1st year after surgery. It may be attributed to the unmasking of latent hyperopia after surgery in immediate postoperative period, or epithelial hyperplasia and stromal remodeling in cases with late regression. The progressive physiological increase in the hyperopic error with age may also lead to regression years after surgery.18 Retreatment rates range from 6 to 20.8%; predisposing factors include older age,

higher preoperative refractive error, residual astigmatism, smaller optical zones, and rigid gas permeable contact lens use.13,16,19 Long-term visual outcomes and safety of hyperopic PRK is comparable with LASIK; however, PRK is associated with increased postoperative pain, midperi­pheral haze, and slower refractive stabilization owing to transient initial myopic overcorrection.20

Hyperopic Phakic IOL Phakic IOL implantation is a feasible option particularly in high hyperopes with an adequate AC depth (>3 mm). It is associated with better predictability, stability, and quality of vision than corneal procedures. Endothelial cell loss ranging from 4.5 to 11.7%, iris chafing and pigment release, IOL decentration and postoperative uveitis may be observed with anterior chamber phakic IOLs.21 Phakic IOL removal, repositioning, or replacement may be required in 4.5–7.7% of cases due to residual refractive error, posterior synechiae with small pupils, and misalignment of toric IOL. Post ICL complications include cataract (7.7%, most visually insignificant), glaucoma (13.3%), and endothelial cell loss (1–4.9%). Retinal detachment after

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CHAPTER 24: Refractive Surgery in Challenging Scenarios phakic IOL implan­ta­tion has not been observed in hyperopic patients.22

Refractive Lens Exchange Outcomes of refractive lens exchange in older hyperopic patients with higher errors are promising, especially with the advent of newer presbyopic IOLs, which provide better patient satisfaction and spectacle independence. Endothelial damage secondary to shallow AC and post­ operative uveal effusion may adversely impact visual outcomes.23

Small Incision Lenticule Extraction in Hyperopia Small incision lenticule extraction (SMILE) for treating hyperopia involves the creation of a doughnut-shaped lenticule with a diameter of 7.5 mm or more, that is thinner in the center and thicker in the periphery. Evolution of surgical technique including the expansion of the optical zone and addition of a transition zone to the lenticule diameter has helped to improve the visual outcomes and refractive stability of hyperopic SMILE.

Preoperative and Operative Considerations Preoperative considerations are similar to that of LASIK in hyperopes. Larger treatment zones, optical zones, and smoother transition zones are important for good visual outcomes. The actual optical zone achieved as compared to the programmed optical zone with SMILE is larger than that observed with LASIK, making it a good alternative for patients with smaller corneal diameters.24

Outcomes Visual outcomes of hyperopic SMILE are inferior to myopic SMILE but comparable to hyperopic LASIK. About 53% cases achieve ±0.50D accuracy at 1 year. Regression and refractive stability are higher than myopic SMILE but comparable to that of hyperopic LASIK.25

  REFRACTIVE SURGERY IN POSTKERATOPLASTY PATIENTS Post-operative astigmatism and ametropia are the most common complications observed in postkeratoplasty patients and prevent good postoperative visual outcomes in spite of a clear graft. Up to one-third of patients undergoing PK may develop >8 D astigmatism; majority have signifi­cant irregular astigmatism or aniseikonia.26

Preoperative Considerations ■■ Indications: Refractive procedures should be considered

in patients in whom conventional methods of optical correction have failed or have produced significant aniseikonia.

■■ Timing of surgery: Establishing refractive stabilization

is a prerequisite for performing refractive surgery. Refractive stabilization in post-keratoplasty patients usually takes about 3–6 months after complete suture removal. ■■ Type of surgery: The various refractive surgical proce­ dures described to treat post-keratoplasty refractive error include corneal incisional procedures, corneal laser-based procedures such as LASIK, PRK, or SMILE, and lens-based surgeries such as phakic IOL implan­ tation or phacoemulsification with IOL implantation. Incisional procedures are rarely performed due to their poor predictability and lack of accurate nomograms for treating astigmatism in post-keratoplasty patients. Corneal laser-based procedures may be performed in patients with moderate refractive error and sufficient residual stromal bed thickness. They should be avoided in patients with marked peripheral corneal vascularization, thin host tissue, central graft thickness < 500 microns, graft host junction ectasia, extremely flat (55 D) corneas, a significant graft override, or wound malapposition.27 Phakic IOL implantation may be considered in patients unsuitable for corneal procedures or those with higher refractive errors, provided their AC depth is >3 mm with endothelial cell count >1,500–2,000 cell/mm2. Piggyback IOL implantation can be performed to treat ametropic pseudophakic patients.

Operative Considerations The planned flap size for LASIK should be larger or smaller than the corneal graft in order to prevent flap initiation at the graft-host junction. In case of larger flaps, intersection of flap cut at the graft-host junction may result in free caps or the loss of a crescent-shaped tissue from the host side. A two-step procedure, which entails the creation of flap first followed by ablative treatment at an interval to allow corneal stabilization, has also been described. Flap creation itself may alter the corneal biomechanics and refractive error in post-keratoplasty patients. Performing customized ablation as a second procedure after refractive stabilization may produce more accurate and predictable results.28

Clinical Outcomes Laser-assisted in situ keratomileusis is an effective proce­dure for refractive correction after PK or DALK, with 20–61% cases achieving accuracy within ±0.5 D.29,30 Topography-guided ablation is associated with good outcomes, especially in highly irregular corneas with significant HOAs. Factors such as epithelial hyperplasia and stromal remodeling may pose challenges during the treatment planning.31 Predictability in achieving ±0.5 D accuracy after phakic IOL implanta­ tion in post-PK and DALK eyes ranges from 50–71%, with 33–88% of eyes achieving UCVA of 20/40 or better.32,33

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SECTION 8: Miscellaneous

Complications Flap-related complications including buttonhole or incomplete flaps, decentered ablation, epithelial ingrowth, flap displacement, under correction, and graft rejection have been reported. PRK is associated with less predictable outcomes in post-keratoplasty patients as compared with LASIK; associated complications include delayed visual rehabilitation, increased stromal haze, stromal scar, and regression.27

  REFRACTIVE SURGERY IN PSEUDOPHAKIA Modern-day phacoemulsification is akin to refractive surgery with the patients desirous of perfect refractive outcomes. We have progressed a long way from unsightly aphakic glasses post-cataract surgery to the presentday expectations of 20/20 visual acuity with spectacle independence for near as well. Despite advancements in assessment of preoperative biometry and IOL power calculation, a residual refractive error may be observed in some patients. This may adversely impact patient satisfaction, especially in cases with premium IOL implantation. The management options include corneal ablation, piggyback intraocular lenses, and IOL exchange. Corneal ablative procedures including PRK and LASIK have a higher index of efficacy and safety as compared with other therapeutic modalities, and are the treatment of choice in lower magnitude of refractive errors.34

Indications The primary indication for post-phacoemulsification refractive surgery is a dissatisfied patient with suboptimal visual outcomes. A difference of two or more lines between the postoperative uncorrected and best-corrected distance visual acuity indicates the need for a secondary procedure to correct the residual ametropia. In addition, a residual spherical equivalent of 0.5 D or higher also warrants intervention in an unhappy patient.35 The vision loss should be attributable to the residual refractive error alone and be fully corrected with refraction. Blepharitis, dry eyes, posterior capsular opacification, and retinal pathologies should be ruled out.

Timing of Surgery Refractive stability for at least 3 months after phaco­ emulsification should be documented before undertaking any secondary corneal ablative procedure.35

Choice of Surgical Technique: LASIK versus PRK Both PRK and LASIK are viable alternatives for post­ phacoemulsification enhancement, and the choice of

procedure may be customized as per the surgeon preference and patient profile. PRK is not associated with any flaprelated complications, and has a lesser incidence of postoperative dry eyes. It may be preferred in patients with low magnitude of refractive errors, pre-existing dry eyes, thinner corneas, and irregular astigmatism. Laser-assisted in situ keratomileusis results in rapid visual recovery with minimal postoperative pain or stromal haze. It is associated with a higher patient comfort and may be preferred in cases with relatively larger residual ametropia.

Corneal Ablation after Toric IOL Both LASIK and PRK have been performed to tackle residual ametropia post-toric IOL implantation. Spherical correction is more predictable; however, outcomes of cylindrical correction may be influenced by various factors including patient age, alignment of toric IOL in the eye, as well as magnitude of residual cylinder. Large residual astigmatism after phacoemulsification correlates with poor predictability and suboptimal refractive outcomes after secondary enhancement procedures.36

Corneal Ablation after Multifocal IOL Fine-tuning of refractive outcomes may be more often required after implantation of multifocal IOLs due to high-patient expectations. LASIK/PRK with multifocal IOL in situ is more complex owing to various reasons. Firstly, accurate assessment of ametropia and refraction is more challenging and may change with pupil size and lighting conditions. Similarly, accurate aberrometry and wavefront analysis may not be feasible, especially with diffractive IOLs.37 Wavefront-guided LASIK is efficacious in treating residual ametropia; however, it does not correct the HOAs. In addition, outcomes of wavefront-guided treatments are comparable to conventional corneal ablation. Therefore, conventional wavefront-optimized treatment profiles are preferred in post-multifocal IOL enhancements.38

Outcomes Laser-assisted in situ keratomileusis is more efficacious and has superior predictability than lens-based proce­ dures, including IOL exchange and piggyback IOLs in the correction of post-phacoemulsification ametropia. Fernández–Buenaga et al. observed 100% predictability in achieving ±1 D of target refraction with LASIK for residual ametropia as compared with 62.5% predictability of IOL exchange and 85% of piggyback IOLs.39 In addition, index of safety is higher with LASIK or PRK with no reports of sightthreatening complications; IOL exchange may be associated with retinal and other intraocular complications.40 The benefit of LASIK or PRK over lens-based proce­ dures is more pronounced in cases with residual myopia

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CHAPTER 24: Refractive Surgery in Challenging Scenarios as compared with hyperopia or mixed astigmatism. An uncorrected distance visual acuity of 20/40 or better has been demonstrated in 91.7% myopes and 90.9% hyperopes undergoing refractive enhancement after phaco­ emulsification.41 The outcomes of secondary enhancement may not be at par with that of primary LASIK or PRK in virgin eyes, and patient expectations must be appropriately addressed preoperatively.

  CONCLUSION Refractive surgery in special situations presents a set of challenges that are unique to each clinical scenario. The predictability and accuracy of visual outcomes following refractive surgery in such scenarios have improved over the years owing to the advances in corneal laser technology, improved ablation algorithms, and evolution of customized corneal ablative treatments. Newer techniques of hyperopic refractive correction such as SMILE and allogeneic stromal lenticule implantation may emerge as more efficacious alternatives to LASIK and PRK.

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SECTION 8: Miscellaneous 29. Balestrazzi A, Balestrazzi A, Menicacci F, Cartocci G, Menicacci F, Michieletto P, et al. Femtosecond laser-assisted in situ keratomileusis for the correction of residual ametropia after deep anterior lamellar keratoplasty: a pilot investigation. Eye (Lond). 2017;31(8):1168-75. 30. Imamoglu S, Kaya V, Oral D, Perente I, Basarir B, Yilmaz OF. Corneal wavefront-guided customized laser in situ kerato­ mileusis after penetrating keratoplasty. J Cataract Refract Surg. 2014;40(5):785-92. 31. Bandeira E, Silva F, Hazarbassanov RM, Martines E, Güell JL, Hofling-Lima AL. Visual Outcomes and Aberrometric Changes with Topography-guided Photorefractive Keratec­ tomy Treatment of Irregular Astigmatism after Penetrating Keratoplasty. Cornea. 2018;37(3):283-9. 32. Tiveron MC, Alió Del Barrio JL, Kara-Junior N, Plaza-Puche AB, Abu-Mustafa SK, Zein G, et al. Outcomes of Toric Iris-Claw Phakic Intraocular Lens Implantation after Deep Anterior Lamellar Keratoplasty for Keratoconus. J Refract Surg. 2017; 33(8):538-44. 33. Alfonso JF, Lisa C, Abdelhamid A, Montés-Micó R, Poo-López A, Ferrer-Blasco T. Posterior chamber phakic intraocular lenses after penetrating keratoplasty. J Cataract Refract Surg. 2009;35(7):1166-73. 34. Moshirfar M, McCaughey MV, Santiago-Caban L. Corrective Techniques and Future Directions for Treatment of Residual Refractive Error following Cataract Surgery. Expert Rev Ophthalmol. 2014;9(6):529-37.

35. Ayala MJ, Pérez-Santonja JJ, Artola A, Claramonte P, Alió JL. Laser in situ keratomileusis to correct residual myopia after cataract surgery. J Refract Surg. 2001;17(1):12-6. 36. Fan YY, Sun CC, Chen HC, Ma DHK. Photorefractive keratectomy for correcting residual refractive error following cataract surgery with premium intraocular lens implantation. Taiwan J Ophthalmol. 2018;8(3):149-58. 37. Charman WN, Montés-Micó R, Radhakrishnan H. Problems in the measurement of wavefront aberration for eyes implanted with diffractive bifocal and multifocal intraocular lenses. J Refract Surg. 2008;24(3):280-6. 38. Alfonso JF, Fernández-Vega L, Montés-Micó R, Valcárcel B. Femtosecond laser for residual refractive error correction after refractive lens exchange with multifocal intraocular lens implantation. Am J Ophthalmol. 2008;146(2):244-50. 39. Fernández-Buenaga R, Alió JL, Pérez Ardoy AL, Quesada AL, Pinilla-Cortés L, Pinilla Cortés L, et al. Resolving refractive error after cataract surgery: IOL exchange, piggyback lens, or LASIK. J Refract Surg. 2013;29(10):676-83. 40. Artola A, Ayala MJ, Claramonte P, Pérez-Santonja JJ, Alió JL. Photorefractive keratectomy for residual myopia after cataract surgery. J Cataract Refract Surg. 1999;25(11): 1456-60. 41. Kim P, Briganti EM, Sutton GL, Lawless MA, Rogers CM, Hodge C. Laser in situ keratomileusis for refractive error after cataract surgery. J Cataract Refract Surg. 2005;31(5): 979-86.

CHAPTER

25

Intrastromal Corneal Ring Segments Rinky Agarwal, Manpreet Kaur, Sridevi Nair, Jeewan S Titiyal

  INTRODUCTION Intrastromal corneal ring segments (ICRS) are synthetic polymethylmethacrylate (PMMA) devices implanted in the midperi­pheral cornea to induce corneal flattening and refractive correction. The devices were originally introduced for the surgical correction of mild myopia in patients unsuitable for corneal ablative procedures.1 The initial intracorneal rings (ICR) had a 360° design, which resulted in incision-related complications and delayed wound healing. The design was subsequently modified to consist of two ring segments implanted in intrastromal tunnels (Fig. 1). The present-day indications of ICRS are limited to the treat­ ment of corneal ectatic disorders.2,3 We herein discuss the mechanism of action, devices, indications, and outcomes of ICRS.

  MECHANISM OF ACTION Intracorneal ring segments are based on the Barraquer thickness law, which states that corneal flattening may be induced by either the addition of material to the periphery of

cornea or removal of equal amount of tissue from the center of cornea.4 When implanted in the midperipheral corneal stroma, these segments act as passive spacers and separate the collagen bands leading to a flattening of the cornea along with increased corneal thickness.5 The arc-shortening effect induced by these elements on the anterior corneal surface results in a change in the central corneal geometric shape into a prolate aspheric surface.6 This results in upgraded optical quality of the cornea translating into an improved visual acuity. The flattening effect is reversible on explantation. In normal corneas with orthogonal arrangement of collagen fibers, flattening effect created by these segments is directly proportional to thickness and inversely proportional to the diameter of the implants. 4 However, in ectatic corneas with loss of organized disposition of collagen fibers, the corrective response is unpredictable. Though few authors believe that ICRS implantation may delay or stop progression of keratoconus, implantation of these segments does not increase the biomechanical stability of cornea, and progression of the underlying disorder can occur despite their implantation.5,7,8

Fig. 1: Evolution of intracorneal ring segments.

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SECTION 8: Miscellaneous

  INDICATIONS AND PATIENT SELECTION The ICRS received FDA approval in 1999 for the correction of mild myopia ranging from −1.0 to −3.0 D in patients of 21 years of age or older with a stable refractive error. At present, the main indication is management of corneal ectasia, either primary keratoconus or secondary to refractive surgery to promote visual rehabilitation. The utility of ring seg­ments is also being evaluated in other ectatic disorders including pellucid marginal degeneration, Terrien’s marginal degene­ ration, keratoglobus, as well as advanced keratoconus.9 Indications and selection of appropriate candidates for ICRS implantation are mentioned in Table 1. A minimum corneal thickness of 450 microns should be documented at the site of implantation. In addition, the maximum keratometry should be 21 years •• At least 450 microns thickness at the site of implantation •• No central corneal scarring •• Maximum K ≤ 58 D •• All other modes of visual rehabilitation have failed •• Well-aligned topographic and refractive axis (50 years: Subtract additional 0.02 D per year.

TABLE 4: Femtosecond laser-assisted astigmatic keratotomy nomogram in eyes with low-to-moderate astigmatism. Astigmatism (in Diopters)

Length of arc at 8 mm optical zone (in degrees)

1

30

1.25

40

1.5

50

2

70

2.5

80

Note: •• Single arcuate keratotomy paired with a phacoemulsification incision •• Astigmatic keratotomy incisions centered 180° away from phaco­ emulsification incision along the steep axis.

Price et al. performed a multicenter, prospective evaluation of arcuate keratotomy in 160 eyes with astigmatism ranging from 1.0 to 6.0 D.20 They observed frequent undercorrections and overcorrections, with a residual refractive cylinder of at least 1.0 D in 61% of eyes and at least 2.0 D in 17% of eyes. The predictability of astigmatic keratotomies ranges from 54 to 84%.21 The predictability of these procedures is less for pseudophakic astigmatism than for naturally occurring astigmatism and they are more useful in reducing the magnitude of astigmatism to improve spectacle tole­ rance rather than achieve emmetropia. Titiyal et al. observed comparable astigmatic correction with AK or toric intraocular lenses (IOLs) for moderate astigmatism of 1.25–3.0 D, and 84% of eyes with AK had a residual refractive cylinder of 1.00 D or less. Day et al. performed femtosecond laser-assisted intra­ stromal AK in 196 eyes with a mean preoperative cylinder of 1.21 ± 0.42 D and observed a mean astigmatism correction of 63%.22 A total of 85.7% of eyes had a residual cylinder of 1 D or less, and 32.1% of eyes had residual cylinder of 0.5 D or less. Intrastromal AKs are best suited for astig­matism of 1.5 D or less in cases undergoing concomitant femtosecond laser-assisted cataract surgery.23 Femtosecond laser-assisted AKs have more precise arc length, depth, and location as compared with manual incisions. Moreover, they are associated with a decreased incidence of complications such as corneal perforation, epithelial downgrowth, and infections.23,24

Complications The intraoperative complications include corneal perforation and epithelial drag or tears. One of the most distressing postoperative compli­ cations is dysphotic ocular phenomenon including glare and haloes due to encroachment of the visual axis, which can be avoided by ensuring a clear optical zone of at least 7 mm. Other postoperative complications include undercorrections, overcorrections, regression, irregular astigmatism, epithelial plugs, and keratitis. Anterior gasbubble breakthrough is a unique complication that may be observed in intrastromal femtosecond astigmatic keratotomies.

  CONCLUSION The role of incisional refractive surgeries is limited to the correction of astigmatism during cataract surgery, after keratoplasty, or as an adjunct to treat residual astigmatism

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CHAPTER 26: Incisional Refractive Surgery after other keratorefractive surgeries. Femtosecond laser technology has increased the accuracy, reproducibility, and safety of astigmatic incisions. Development of specific nomograms for use with femtosecond laser-assisted cataract surgery may help to improve the predictability of astigmatic correction by limbal relaxing incisions and arcuate incisions.

  REFERENCES 1. Sato T. Posterior incision of cornea: surgical treatment for conical cornea and astigmatism. Am J Ophthalmol. 1950;33(6):943-8. 2. Choi DM, Thompson RW, Price FW. Incisional refractive surgery. Curr Opin Ophthalmol. 2002;13(4):237-41. 3. Robin JB. Radial keratotomy: procedures. Indian J Ophthalmol. 1990;38(3):103-6. 4. Lindstrom RL. Minimally invasive radial keratotomy: miniRK. J Cataract Refract Surg. 1995;21(1):27-34. 5. Salz J, Lee JS, Jester JV, Steel D, Villasenor RA, Nesburn AB, et al. Radial keratotomy in fresh human cadaver eyes. Ophthalmology. 1981;88(8):742-6. 6. Salz JJ, Villaseñor A, Elander R, Reader AL, Swinger C, Buchbinder M. Four-incision radial keratotomy for low-tomoderate myopia. Ophthalmology. 1986;93(6):727-38. 7. Flanagan GW, Binder PS. Effect of incision direction on refractive outcome after radial keratotomy. J Cataract Refract Surg. 1996;22(7):915-23. 8. Waring GO, Moffitt SD, Gelender H, Laibson PR, Lindstrom RL, Myers WD, et al. Rationale for and design of the National Eye Institute Prospective Evaluation of Radial Keratotomy (PERK) Study. Ophthalmology. 1983;90(1): 40-58. 9. MacRae S, Rich L, Phillips D, Bedrossian R. Diurnal variation in vision after radial keratotomy. Am J Ophthalmol. 1989;107(3):262-7. 10. Kemp JR, Martinez CE, Klyce SD, Coorpender SJ, McDonald MB, Lucci L, et al. Diurnal fluctuations in corneal topography 10 years after radial keratotomy in the Prospective Evaluation of Radial Keratotomy Study. J Cataract Refract Surg. 1999; 25(7):904-10. 11. Chiba K, Oak SS, Tsubota K, Laing RA, Goldstein J, Hecht S. Morphometric analysis of corneal endothelium following radial keratotomy. J Cataract Refract Surg. 1987;13(3): 263-7. 12. Mendez A. Advances in the hyperopia correction with hexagonal keratotomy. Presented at the Symposium on

Cataract, IOL, and Refractive Surgery. Los Angeles, California: 1986. 13. Basuk WL, Zisman M, Waring GO, Wilson LA, Binder PS, Thompson KP, et al. Complications of hexagonal keratotomy. Am J Ophthalmol. 1994;117(1):37-49. 14. McLeod SD, Flowers CW, Lopez PF, Marx J, McDonnell PJ. Endophthalmitis and orbital cellulitis after radial keratotomy. Ophthalmology. 1995;102(12):1902-7. 15. O’Day DM, Feman SS, Elliott JH. Visual impairment following radial keratotomy. A cluster of cases. Ophthalmology. 1986;93(3):319-26. 16. Baharozian CJ, Song C, Hatch KM, Talamo JH. A novel nomo­ gram for the treatment of astigmatism with femtosecondlaser arcuate incisions at the time of cataract surgery. Clin Ophthalmol Auckl NZ. 2017;11:1841-8. 17. Price FW, Grene RB, Marks RG, Gonzales JS. Astigmatism reduction clinical trial: a multicenter prospective evaluation of the predictability of arcuate keratotomy. Evaluation of surgical nomogram predictability. ARC-T Study Group. Arch Ophthalmol Chic Ill. 1995;113(3):277-82. 18. Byun YS, Kim S, Lazo MZ, Choi MH, Kang MJ, Lee JH, et al. Astigmatic correction by intrastromal astigmatic keratotomy during femtosecond laser-assisted cataract surgery: Factors in outcomes. J Cataract Refract Surg. 2018;44(2):202-8. 19. Day AC, Stevens JD. Predictors of femtosecond laser intrastromal astigmatic keratotomy efficacy for astigmatism management in cataract surgery. J Cataract Refract Surg. 2016;42(2):251-7. 20. Price FW, Grene RB, Marks RG, Gonzales JS. Arcuate trans­ verse keratotomy for astigmatism followed by subsequent radial or transverse keratotomy. ARC-T Study Group. Astigmatism Reduction Clinical Trial. J Refract Surg Thorofare NJ. 1996;12(1):68-76. 21. Oshika T, Shimazaki J, Yoshitomi F, Oki K, Sakabe I, Matsuda S, et al. Arcuate keratotomy to treat corneal astigmatism after cataract surgery: a prospective evaluation of predictability and effectiveness. Ophthalmology. 1998; 105(11):2012-2016. 22. Day AC, Lau NM, Stevens JD. Nonpenetrating femto­ second laser intrastromal astigmatic keratotomy in eyes having cataract surgery. J Cataract Refract Surg. 2016;42(1): 102-9. 23. Chang JSM. Femtosecond laser-assisted astigmatic keratotomy: a review. Eye Vis Lond Engl. 2018;5:6. 24. Vickers LA, Gupta PK. Femtosecond laser-assisted keratotomy. Curr Opin Ophthalmol. 2016;27(4):277-84.

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Index Page numbers followed by f refer to figure, fc refer to flowchart, and t refer table.

A Aberration 42 analysis 47 chromatic 42 flap-induced 116 free eye 44 higher-order 42 lower-order 42, 43f, 114 postoperative 224 reveal 44 Aberrometers 42 classification of 46fc sequential ray-tracing 46 Aberrometry and wavefront analysis 42 device, expensive 113 ray-tracing 47f, 47t, 48f, 190f Ablation algorithm 74 decentered 81 deeper 71 depth of 74 ray tracing-based 119 topography guided 118t wavefront-guided 113f, 114, 115 wavefront-optimized 111 Abrasions, peripheral small 141 Abrupt corneal curvature changes 31 Acanthamoeba 102 ACD See Anterior chamber depth Acquired immunodeficiency syndrome 58 Age-related macular degeneration 33 Allergic keratoconjunctivitis 61 Amblyopia 58 Ambrósio relational thickness 31 maximum 61 Ambrósio-enhanced ectasia display 26 Ametropia 225 AMG See Amniotic membrane graft Aminoglycosides 56 Amniotic membrane graft 107 AMO VISX hyperopia 196 Anisometropic amblyopia 221, 222 Anterior chamber air bubbles 97 depth 64, 155-157 Anterior chamber gas bubbles 97 prevention 98 risk factors 97 treatment 98 Anterior corneal curvature 18 keratotomy incisions 3 stroma 213 surface 229 Antiglaucoma medications 104

Anti-inflammatory therapy 107 Aphakia 200 Arc length 237 Arcuate keratotomy 237t ArF excimer laser 90 Argon fluoride 4, 90 laser 90 ARS See Adjustable refractive surgery Artificial intelligence, role of 40 Artiflex toric 153 Artisan iris claw lens 4 Artisan toric 153 ART-MAX See Ambrosio relational thickness maximum Aspheric ablation profile 111 Aspheric shape 111 Astigmatic correction, magnitude of 237 Astigmatic keratotomy 236, 237 incisions 236 indications 237 principle 236 surgical technique 237 Astigmatism 4, 75, 84 low-to-moderate 238t post-operative 225 SMILE for 132 surgically-induced 168 Asymmetrical technique 197 Athens protocol 217 Azar flap technique 73 Azar technique 73

B Bacterial endotoxins 146 BAD-D See Belin ambrosio enhanced ectasia display deviation value Bandage contact lens 78, 79, 94, 99, 101, 232 Barraquer’s technique 4 Basal epithelial cells, elongation of 12 Bausch and Lomb keratometer 18, 19 BCL See Bandage contact lens BCVA See Best-corrected visual acuity Beam profile 91 Beam’s homogeneity 75 Belin-Ambrósio deviation index 31, 213 Belin-Ambrósio enhanced ectasia 29f, 35, 61 display 28t, 31t Best spectacle corrected visual acuity 61, 118, 173, 175, 210 Best-corrected visual acuity 142, 198, 209 Best-fit sphere 23, 23f, 25 concept of 23, 26 enhanced 29f

BFS See Best-fit sphere Bi-aspheric multifocal corneal surface 196 Bioptics 65, 207, 207t classification of surgical techniques of 207 differed 208, 209 reverse 209 surgical approaches in 210t surgical techniques of 208t Black spots 136, 137f clinical significance 137 incidence 136 mechanism 136 predisposing factors 137 prevention 137 Blepharitis 61 Bowman’s layer 188 Brillouin frequency 40 Brillouin microscopy 40 Bruch’s membrane 56 BSCVA See Best spectacle corrected visual acuity

C Camellin technique 73 Cap and side-cut tears 140 incidence 140 management 140 predisposing factors 140 prevention 140 Cap cut 130 Cap diameter 128 Cap edema 138 Cap lenticular adhesion 139f Cap microstriae 142, 143 incidence 143 management 143 pathophysiology 143 predisposing factors 143 Cap parameters 128 Cap side-cut 128, 130 Cap tear 140f Cap thickness 128 Cap-lenticular adhesions 126, 139 Capsular bag 190 Carriazo pendular microkeratome 85 Cataract 65, 163, 164f, 222, 224 development of 164 incidence 163 management 164 morphology 164 pathophysiology 164 predisposing factors 164 secondary 162 surgery 46, 238 Causative organisms 100

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Index CBI See Corvis biomechanical index CDVA See Corrected distance visual acuity Center keratoconus index 26 Central cornea 4 thickness 34, 158, 207 Central islands 82 Central keratometry 23 Central myopic refraction 119 Central presbyLASIK 195 Central toxic keratopathy 100, 104, 105t clinical diagnosis 104 Chemical de-epithelialization 72 Chilled balanced salt solution 78 Choroidal neovascular complex 56 membrane 54-56 Chronic uveitis and inflammation 163, 166 CHRPE See Congenital hypertrophy of retinal pigment epithelium Chung’s swing technique 131 Ciliary body 192 Ciliary muscle, electrostimulation of 199 Ciliary sclerotomy, anterior 192 Circle technique 182 CL See Contact lens Collagen cross-linking 142 fibers 79, 229 lamellae 11 peripheral 187 vascular disorders 235 Confocal microscopy 13, 79, 101 Conic intrastromal relaxing incisions 209 Conjunctival chemosis 95 Conjunctival goblet cells 106 Connective tissue disorder 58, 59 Contact glass 129 Contact lens 101, 119, 129, 187 history of 58, 143 Continuous curvilinear lenticulerrhexis 132 technique 131 Cornea 11, 22, 23, 26, 46, 48f, 62, 85, 95, 119, 192, 218, 219 anatomy of 11, 12f locations of 111 movement of 33 normal 29f, 119, 229 Scheimpflug imaging of 24 Corneal ablation 91f, 111, 112fc, 117, 187, 189, 226 complications of flap-based 94 conventional 194 customized 111, 120 excimer laser platforms for 91t flap-based 71 minimal 196 platforms 114t procedures 69 Corneal ablative procedures, retreatment after 175fc Corneal and intraocular procedures 209 Corneal applanation 55 Corneal astigmatism, irregular 118 Corneal backscattered light 38 Corneal biomechanical assessment 33, 34f, 62 parameter 31 properties 33, 40 response 111 strength 92

Corneal biomechanics 33, 62, 92, 126 Corneal biopsy 101 Corneal carving 4 Corneal collagen 103 cross-linking 65, 101, 210, 211, 213, 217, 217t, 218, 219 plus 217 Xtra 213 efficacy of 108 Corneal curvature, actual 23 Corneal decompensation 163, 166 Corneal deformation 35 stages of 35 Corneal densitometry 38 Corneal diagnostics, advancements in 3, 4 Corneal ectasia 33, 108, 219 management of 230 postoperative 221 Corneal ectatic disorders 61, 219 Corneal endothelial cell density 61 Corneal endothelium 162 Corneal epithelial cells 11 defect 99 Corneal epithelium 11 Corneal flaps 84 create 84, 86t Corneal flattening 229 concept of 3 Corneal haze 76, 78-80, 144 persistent 80 Corneal hysteresis 34 Corneal incision 3, 158 Corneal infiltrates 82 Corneal inlays 188, 200, 200t, 203 advantage of 203 history of 200 Corneal irregularity measure 20 Corneal laser ablation 174t retreatment after 173 based procedures 225 refractive surgery 67f treatment 5 Corneal light reflex 129 Corneal necrosis 200 Corneal nerve fiber, sub-basal 14f regeneration 13 Corneal onlays 204 Corneal pachymetry 62, 71 Corneal power, redistribution of 235 Corneal refractive procedures 203 surgeries 214t, 222 Corneal relaxing incisions 236 Corneal reshaping inlays 200 Corneal resistance factor 34, 216 Corneal rigidity 33 Corneal scrapings 101 Corneal sphere 50 Corneal stability 35 Corneal stroma 34 Corneal suction 55 Corneal surface 85 anterior and posterior 18 application, intraoperative 75f Corneal thickness 31, 156, 218 increased 229 spatial profile 29, 30f

Corneal tissue 195 Corneal topography 18, 62, 108f, 119, 120, 193, 231f accurate 18 Corneal transparency 15 Corneal vertex centration 145 Corneal visualization scheimpflug technology 34, 38 Corneal wavefront, fourier analysis of 50t Corneal wound 13, 14 healing 11, 12fc, 13-15, 222 clinical relevance of 15 comparative evaluation of 15t elements of 12f Corrected distance visual acuity 107, 174, 195, 202 Corticosteroids, prolonged topical 164 Corvis biomechanical index 61, 108, 213 laser vision correction 174 CORVIS-ST See Corneal visualization scheimpflug technology Crystalline lens 4, 156, 158, 168 exchange, bioptics with 211 CT See Corneal thickness CTD See Connective tissue disorder Curvature map anterior 25 axial 18 Custom Q ablations 119 treatments 119, 198 Customized corneal ablation, types of 111, 112t CXL See Corneal collagen cross-linking Cystic retinal tufts 53 Cystoid macular edema 55 Cytokine 16

D DALK See Deep anterior lamellar keratoplasty Decentered treatment 142, 145 incidence 145 management 145 predisposing factors 145 prevention 145 DED See Dry eye disease Descemet’s membrane 188 Deviation index 28 Diabetes mellitus 59, 99, 144 Diffuse lamellar keratitis 12, 16, 65, 78, 89, 90, 98, 100, 101, 103, 103f, 105t, 107, 142, 146, 177 clinical diagnosis 103 development of 146 incidence 146 management 146 pathophysiology 146 predisposing factors 146 prevention 146 risk factors 103 treatment 104 Dilated fundus examination 52, 174 Distance vision 119, 196, 197, 202 Distance visual acuity 146, 159, 192, 222 Distortions 167 DLK See Diffuse lamellar keratitis DM See Diabetes mellitus

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Index Docking 129 Docosahexaenoic acid 16 Dry eye 67, 78, 101, 142 assessment 60 disease 5, 61, 101, 106 pre-existing 61 mild 143 postoperative 5, 16, 82, 135, 143 severe 143 symptoms 16 transient 132 Dynamic corneal response 38t Dysfunctional lens syndrome 193, 193fc Dysphotic symptoms 81, 145

E EBM See Epithelial basement membrane EBMD See Epithelial basement membrane dystrophy ECC See Endothelial cell count ECM See Extracellular matrix Ectasia 67, 68, 82, 101, 142, 146 incidence 146 management 146 pathophysiology 146 postoperative 5, 33, 58 postsurgical 58 preclinical 62 predisposing factors 146 red indicates 29 subclinical 35 Ectatic cornea 26 Ectatic disorders, family history of 58 Ectatic eye 40 EDOF See Extended depth of focus Elastography 40 Elevation maps, anterior and posterior 25 Emerging technologies 40 Endophthalmitis 162, 168 etiology 168 incidence 168 management 168 Endothelial cell 151, 222 count 61, 64, 156, 157 loss 65, 163, 166, 167, 211 Endothelial corneal dystrophies 58 Endothelial decompensation 156 Endothelial perforation 233 Enhanced Athens protocol 217 Epipolis-laser in situ keratomileusis 74, 80 Epiretinal membrane formation 54 Epithelial cells 13, 144 changes 11 debridement 81 drag 238 hyperplasia 14, 216 injury 13 removal, technique of 72, 72t, 78 Epithelial basement membrane 11, 12, 12f, 15 dystrophy 59, 61, 63, 99 regeneration 13 Epithelial defect 141 healing of 15 incidence 141 intraoperative 99 prevention 100 risk factors 99 treatment 100

large central 141 management 141 predisposing factors 141 Epithelial flap 81 related complications 81 Epithelial healing 15 delayed 79, 81 Epithelial ingrowth 87, 101, 105, 142, 144, 144f clinical diagnosis 106 incidence 144 management 144 pathophysiology 144 predisposing factors 144 risk factors 106 risk of 97 treatment 106 Epithelial thickness 223 mapping 175 Epitheliotoxic medication predispose 99 Epithelium peripheral 13 removal, method of 75 Erbium-doped yttrium aluminum garnet 192 Ergonomics 91 Excimer ablation time 224 Excimer laser 90 ablation 74, 90, 187, 193, 219 calibration 74 function 222 monovision 195f platforms 92 evolution of 91f procedures 194fc technology 90 evolution of 90 treatment 213 Extended depth of focus 63f, 64 Extracellular matrix 12, 12f, 15 Extreme ametropia 207 Eye 132, 161 bleed in 99 blurred 197 both 197 deep-set 95 displacements of 92 dominant 196, 197 nondominant 196 optical aberrations of 115 refractive power 18 rubbing 102 symptom 106 tracker 92, 115 conventional 92 response time 91 speed 91 tracking, passive 74

F Facial deformities 221 FECD See Fuchs’ endothelial corneal dystrophy Femtosecond 90 flaps 87 Femtosecond laser 84, 85, 89, 94 application 129 created flaps 89 delivery 98f

flap 89, 96t lentotomy 191 role of 191 platform 85, 86t settings and technique 87 systems 87 technology 4 Femtosecond laser-assisted astigmatic keratotomy 238t nomogram 238t cataract surgery 163f, 165f, 239 corneal ablative 6 flaps 89t flap 55 creation 85, 88f in situ keratomileusis 35, 65 planar flap 89f procedures 209 Femtosecond lenticule extraction 4, 125, 139 Femtosecond technique 232 Ferrara ring 230 Fibroblast 15 growth factor 13 Fixation and eye trackers 74 Flap architecture 87 buttonholes 95 centration of 85 characteristics 89 dislocation 100 incomplete 94 irregular 94 macrostriae 103f recutting 176 related complications 87, 89, 94 stroma, ablation of 175 Flap striae 100, 102 clinical diagnosis 102 prevention 103 risk factors 102 treatment 103 Flap tears 99 prevention 99 risk factors 99 treatment 99 Flapless refractive surgery 93 Flapless surgery 146 Flaporhexis 176 Flatter periphery 18 Flexivue microlens corneal inlay, design of 202f Fluoroquinolones 102 Fortified antibiotics 102 Fourier analysis 50 Fourier transform 115 Free cap 95 Fruste keratoconus 107 FS-LASIK See Femtosecond laser-assisted in situ keratomileusis Fuchs’ endothelial corneal dystrophy 59, 61

G Galilei dual scheimpflug analyzer 24 GAT See Goldmann applanation tonometry Giant cell 219 Giant retinal tear 168

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Index Glaucoma 33, 65, 164, 165, 165t, 224 postoperative 166f secondary 162 steroid-induced 222 Goldmann applanation tonometry 38 Goldmann-correlated intraocular pressure 34 Gonioscopy 60 Good near vision 197 Gram-positive bacteria 102, 146

H Hartmann-Shack aberrometer 44, 115 Haze 67 clinical evaluation of 79 postoperative 15 Heparan sulfate proteoglycans 11 Herpes simplex virus keratitis 82 Hexagonal keratotomy 236 Higher order aberration 42, 43f, 44t, 50, 62, 89, 111, 112, 128, 174, 175, 223 HOA See Higher order aberration Hormone replacement therapy 59 HPMC See Hydroxypropyl methylcellulose Human cornea 33, 111 Human eye, monochromatic aberrations of 42t Hydroexpression 131 Hydrophilic acrylic lens 191 optic 152 Hydroxypropyl methylcellulose 217 Hyperopia 4, 5, 75, 80, 84, 116, 153, 155, 221, 225, 237 bioptics for 211 correction of 5, 222 high 155 refractive surgery for 22, 223t SMILE for 132 Hyperopic corneal ablation 223 principle of 222 profiles 16 Hyperopic correction 223 diopter of 223 Hyperopic shift, mild 202

I ICL See Implantable collamer lens ICRS See Intrastromal corneal ring segments Implantable collamer lens 65, 151, 157, 157t, 158, 161, 165, 209, 211, 222 evolution of 155f hyperopic visian 155 Implantable phakic contact lens 191 Implants, characteristics of 231 Incisional refractive surgery 235 role of 238 Incisions, intersection of 236 Infectious keratitis 82, 100, 105t, 142, 146 causative agents 146 incidence 146 management 147 Infectious keratoconjunctivitis, postoperative 103 Inflammatory cells 146 Initial intracorneal rings 229 Intentional anisometropia, creation of 195f Interface epithelial cell 144f

Interface haze 141, 142 incidence 141 management 143 pathophysiology 141 predisposing factors 141 prevention 143 Interface infiltrates, incidence of 146 Interface irrigation 102 Interpreting videokeratograph maps 18 Intracameral gas bubbles 98f Intracorneal ring segment 229, 231f characteristics of 230t evolution of 229f implantation 218 selection for 230t Intralamellar stromal keratitis 104 pressure-induced 104 Intraocular lens 4, 47, 63, 63f, 64, 187, 193, 209, 210 accommodative 190 dual-optic 190 hyperopic phakic 224 multifocal 226 premium 46 Intraocular pressure 34, 38, 85, 89, 104, 129, 162, 163, 165t accuracy of 33 corneal compensated 34 raised 82, 164 Intraocular procedures 161 Intraocular structures 119, 162 damage to 161 Intrastromal corneal lenticule 125 Intrastromal corneal ring 233 segments 142, 209, 210, 229, 230 complications of 233t Intrastromal femtosecond laser 187 Intrastromal gas 146 Intrastromal refractive 125 Intrastromal small incision lenticule extraction, creation of 129f Intrastromal tunnels 232 Intravitreal antibiotics 168 Invasive radial keratotomy 236 IOL See Intraocular lens IOP See Intraocular pressure Iridectomy, peripheral 157, 164 Iridocorneal angle 162 Iridotomy, peripheral 154, 157, 165 Iris 161, 162 chafing 166f claw 157, 159 lens 152 registration 97 Irregular astigmatism 81, 145 index 23 Irregular topography 142, 145 incidence 145 management 145 predisposing factors 145

J Javal and Schiotz keratometer 18, 19 Jeweler’s forceps 73

K Kamra corneal inlay 200, 201 complications 202 design of 201, 201f

principle 201 technique 201 Keraring 355 230 Keratoconic eyes 35 Keratoconus 21f, 59, 116, 213, 230 bioptics for 211 classification index 23 index 26 mild-to-moderate 119 prediction index 23 progressive 219 severity index 23 subclinical 5 Keratocytes 11 density of 11 Keratometry 18, 128, 223, 224 maximum 217 Keratomileusis, concept of 4 Keratoplasty 217 conductive 187 Keratorefractive procedures 125 surgeries 11, 12fc, 13, 15, 16, 46, 235, 239 Keratoscopy 18

L Lamellar keratoplasty 79, 230 deep anterior 101 Lamellar plane, anterior 130 Lamellar separation, posterior 130 Laser blended vision 193 Laser epithelial keratomileusis 76t, 81 Laser flaps, customization of 87 Laser in situ keratomileusis 46 epithelial 76t Laser keratome 129 Laser presbyopia reversal 192 Laser programming 74 Laser refractive surgery, contraindications for 59t Laser settings 127 Laser subepithelial keratomileusis 71, 73 Laser vision correction 6, 38, 175 Laser-assisted in situ keratomileusis 3f, 4f, 5, 12, 13, 14f, 15t, 58, 63, 63f, 79, 84, 86t, 92-94, 99f, 100t, 114, 117,151, 136, 146, 173, 176, 176t, 179, 188, 193, 195, 196f, 207, 209, 210, 221, 225, 230, 237 complications with 216 flap 85t creation 84 relift 177 multifocal 198 myopic 224t postoperative complications after 100 retreatment after 176 simultaneous 201 surgery 201 thin-flap 180, 181, 181f wavefront-guided 115 Laser-assisted sub-epithelial keratectomy 175 Laser-blended vision 195, 197, 197f principle of 197 Laser-in situ keratomileusis 135 Laser-related complications 5 LASIK See Laser-assisted in situ keratomileusis

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 1st Proof Time/Date: 06:34 PM/10 Aug 21

Index Latent hyperopia 222 Lattice degeneration 53 LBV See Laser blended vision Lens 46, 48f, 156 and cornea 207 based procedures 64, 222 decentered 163, 167 dislocated 163, 167 single-piece 151 Lens-based procedures, history of 4 Lenticular accommodation 115 Lenticular astigmatism 117, 118 Lenticular opacities 5 pre-existing 164 Lenticular side-cut dissection 131 Lenticule cut 129, 130 diameter 128 dissection 130f, 138 and extraction 130 forceful 140 extraction difficult 138, 139 flap-based 125 procedures 6 intrastromal keratoplasty 6 irrigation 131 minimum thickness of 128 planes lower 132 upper 132 side-cut 130 Limbal bleed 98 prevention 98 risk factors 98 treatment 98 Limbal centration 115 Limbal region, peripheral 22 Lindstrom nomogram, modified 237t Lipid layer thickness 62 LK See Lamellar keratoplasty Local anesthesia 55, 157 Low refractive errors 139 Lower energy femtosecond laser platform 86 Lower-frequency excimer lasers 174 LVC See Laser vision correction

M Machine and laser settings 126 Macular diseases 54 Macular hemorrhage 54-56 Macular hole 55, 56 Manifest refraction spherical equivalent 114, 179 MCA See Mutual comparative analysis McDonald technique 73 Mean toric keratometry 22 Medennium phakic lens 154, 157 Meesmann dystrophy 76 Meibomian gland dysfunction 107 function 62 secretions 146 Meniscus sign 130, 139 Merocel sponges 73 Mesopic pupil size, large 167 MFIOL See Multifocal intraocular lens Microbial keratitis 100, 222

Microkeratome 84, 85, 87, 89, 89t, 90, 99 and femtosecond laser flaps complications to 98 creation, comparison of 87 evolution of 84 systems 85t types of 84 Microkeratome flap 4, 87, 89, 102 complications 94, 94t prevention of 96 creation 84, 86f Mid-peripheral laser pulses 119 Minimal dysphotic symptoms 192 Mini-radial keratotomy 236 Mitomycin C 12, 71, 75, 75f, 80, 142, 180, 216 intraoperative 173 MK See Microkeratome MMC See Mitomycin C 79 Modern-day keratometers 18, 19t phacoemulsification 226 Monovision 194, 195 limitations of 194 MPL See Medennium phakic lens MRSE See Manifest refraction spherical equivalent Multifocal cornea 188 ablation 196f Multifocal intraocular lens 63f, 64, 189 implantation 190f Multifocal laser vision correction 194 Multifocal transition profile 194 Multipass technique 75 Mycobacteria, atypical 102 Myofibroblasts 13, 14 Myopes, anterior chamber of 210 Myopia 5, 56, 80, 84, 152, 153, 157, 159, 197 bioptics for 210 correction of high 154 high 75, 200 low-to-moderate 159 mild 230 moderate-to-high 151 reduction of 155 small 152 treatment of 71 moderate-to-high 159 Myopic correction 80 higher 173 Myopic errors, treatment of 222 Myopic eyes 56 Myopic maculopathies 55 Myopic regression 11

N Natural ocular growth 221 NCT See Non-contact tonometry ND:YAG See Neodymium-doped:yttrium aluminum garnet Near vision 190 Neodymium-doped:yttrium aluminum garnet 101, 106, 144, 157 Nerve regeneration 15 Neuroadaptation, postoperative phase of 68 Nidogens 11 Night vision 81 disturbances 46 symptoms 5

Nocardia 100 Nomograms 237 refinement of 173 Non-contact tonometry 38 Non-pupillary block glaucoma 165 Nonsteroidal anti-inflammatory drug 75, 78, 79 Nonvision-threatening complications 66, 67 NSAID See Nonsteroidal anti-inflammatory drug

O OBL See Opaque bubble layer Ocular adnexal assessment 60 biomechanics 33 biometry 61, 62 comorbidities 58 contraindications 59 dominance 61 history 58, 59 response analyzer 33, 34f, 34t structures, iatrogenic damage to 162 Ocular aberration 45t, 114, 115 assessment of 111 Ocular surface 60, 81 assessment 61 disease 235 index 132 staining 61 Ocular wavefront 44, 114 analysis 62 technology 111 Opaque bubble layer 87, 90, 96, 98, 98f, 128, 136, 137, 142 clinical outcomes 138 clinical significance 138 incidence 137 management 98, 138 mechanism 137 predisposing factors 138 prevention 98 risk factors 98 Ophthalmic viscosurgical device 157, 165 Optic diameter 153 Optical aberrations 44, 142, 145 incidence 145 management 145 predisposing factors 145 Optical system 42, 198 Optical zone 74, 174, 175, 217 Oral antiviral prophylaxis 58 Oral doxycycline 105 OZ See Optical zone

P Pachymetry data 28 evaluation 29 map 24, 25 progression index 31 Pain, postoperative 78 Pannus 99 Panoptix lens transmits 189 Paracentral flattening 82 Parachute centering technology 154 Pellucid marginal degeneration 59

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Code: Del-590 Name: Md Iqbal

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Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 1st Proof Time/Date: 06:34 PM/10 Aug 21

Index Penetrating keratoplasty 101, 142, 230 Pentacam maps, evaluating 25 Pentacam random forest index 40 Pentacam topometric index 28 Periodic fundus screening 54 Peripheral cornea exhibits 11 relaxing incisions, nomogram for 238t vascularization 99 Peripheral retinal breaks 53t degeneration 53 types of 53t lesions, types of treatable 53 screening, preoperative 52fc tears 53 Persistent focal tissue 99 Phacoemulsification 189 Phakic eye 151 Phakic intraocular lens 54, 58, 65, 151, 157, 159, 159f, 161, 162f, 165f, 165t, 166f, 167f, 217, 221 angle-supported 151, 152f broken 161 chamber 156, 207 chipped 161 complications of 161 implantation of 65, 157t, 168 iris claw 153t fixated 168f supported 152 surgeries 66f, 163t complications of 161t types of 151 Phoric posture 61 Photoablative de-epithelialization 72 Photorefractive keratectomy 3f, 4, 4f, 11, 12f, 15t, 58, 71, 72f, 72t, 75, 75f, 76t, 80, 80f, 81f, 82, 136, 142, 175, 180, 193, 213, 217, 217t, 230, 237 Phototherapeutic keratectomy 218 Pigment dispersion 163, 166 PIOL See Phakic intraocular lens Piston aberration 43 PKP See Penetrating keratoplasty Placido-based systems 116 Placido-disk system 24 topographer 24 Plasma, rapid expansion of 137 PMD See Pellucid marginal degeneration Polyhydroxyethyl methacrylate 155 Polymethylmethacrylate 151 Polymorphonuclear cells 13 Post-LASIK 53, 105f, 105t, 108f infectious keratitis 101f Post-cataract surgery astigmatism 3 Posterior chamber phakic intraocular lens 153, 154t, 158f, 164f, 167f Posterior corneal astigmatism 117, 118 incisions 3 Posterior polymorphous corneal dystrophy 59 Post-keratoplasty 225 astigmatism 116 cases 221

refractive error 225 surgery in 225 Post-LASIK clinical staging for 106t corneal ectasia 107 clinical diagnosis 107 prevention 108 risk factors 107 treatment 108 development of 33 dry eye 106 clinical diagnosis 106 pathophysiology 106 prevention 107 risk factors 106 treatment 107 ectasia 108, 116, 217 infectious keratitis 89, 100, 104 causative organisms 100 clinical diagnosis 101 risk factors 101 treatment 101 management of 102t, 104t, 107t surface ablation 175 Post-phacoemulsification ametropia 226 refractive surgery 226 Post-phakic IOL endophthalmitis 168 Post-PRK LASIK 177 patients 173 Post-radial keratotomy 25 Post-refractive surgery 15, 16 ectasia 230 evaluation 35 vitreoretinal complications 54 wound healing 11 Post- SMILE infections 146 retreatment 180fc PPCD See Posterior polymorphous corneal dystrophy Preoperative keratorefractive 71 workup 84 PresbyLASIK, peripheral 195 PresbyMAX software 196 Presbyond laser-blended vision 188, 197, 197f Presbyopia 154, 185, 187, 193, 193fc, 195f, 219 correction of 188f, 189, 194fc, 197, 198 corneal approach to 194 laser correction of 194 multifocal approach 196 pathophysiology of 191, 192 procedures for 192 refractive surgery for 187 surgical correction of 187t, 191 treatment 91 Presbyopic corneal ablation 6 techniques of 195t Presbyopic excimer laser ablation techniques 193 Presbyopic laser vision 194 Presbyopic phakic intraocular lens 65, 191, 191f Presbyopic procedures 68 Present-day excimer laser platforms 90 Present-day femtosecond laser platforms 85 Present-day microkeratome systems 84

PRK See Photorefractive keratectomy Promote re-epithelialization 81 Prophylactic laser 56 therapy 54 Prophylactic treatment 54 Pseudomonas 102 Pseudophakia, refractive surgery in 226 Pseudophakic monovision 189 Pseudo-small incision lenticule extraction 125 PTA See Percentage tissue altered PTK See Phototherapeutic keratectomy Pupil 62, 68 and limbus tracking 91 based centration 115 camera, frontal 24 natural 115 ovalization 151, 162, 163 periphery 119 size 115 Pupillary block glaucoma 165 postoperative 157 Pupillary dilation 140 Push-up and push-down technique 131

Q Quadrifocal diffractive technology 189 Quantifying irregular astigmatism 50 Q-value represents 25

R Rabinowitz-McDonnell index, modified 23 Radial corneal incisions 235 Radial keratotomy 3, 107, 230, 235 incisions, mechanism of action of 235f principle 235 prospective evaluation of 236 surgical technique 235 Rainbow corneal inlay, design of 203f Raindrop corneal inlay 200, 203 Rapid strides 6 Refraction, planning target 221 Refractive correction 5, 44, 71, 108, 119, 146 amount of 13 range of 154 Refractive display 27f Refractive error 52, 58, 63, 179, 192 high magnitude of 164 higher 143, 144, 213, 221 low-to-moderate 71 mild-to-moderate 180 range of 224 total correction of 207 type of 15 Refractive index 154 variability 117 Refractive inlays 200, 202 Refractive lens 154 exchange 193, 225 Refractive lenticule extraction 125 Refractive map 20, 22f Refractive optic inlays 202 design 202 principle 202 Refractive outcomes 92 Refractive power 22f map 24

Code: Del-590 Name: Md Iqbal

Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 1st Proof Time/Date: 06:34 PM/10 Aug 21

Index Refractive predictability 216 Refractive procedures 68 complications with 65t lens-based 64fc Refractive regression 15 Refractive stability, lack of 221 Refractive surgeries 3, 3f, 4f, 5, 6, 33, 34, 40, 46, 50t, 55, 60, 63f, 84, 155, 198, 207, 213, 221 adjustable 209 clinical examination of 60t clinical history of 59t complications of 55 cornea-based 55 lens-based 56 contraindications for 54 cornea- and lens-based 55t corneal based 63fc current trends in 5 evaluation of 35 evolution of 3 field of 58 pediatric 222 procedures, cornea-based 187 role of 54 screening 35 technique 50, 211 timing of 54 type of 62 Regression, risk of 133 Regular astigmatism 27f Relifting flap, advantages and limitations of 176t Relifting LASIK flap 176 Residual ametropia 226 Residual error 66, 67 Residual myopic error 210 Residual refractive error 68, 173, 226 Residual spherical equivalent 209 Residual stromal bed thickness 59, 61, 63, 63f, 64, 128, 142, 173, 175, 176, 180 Retained lenticule 139 clinical outcomes 140 fragments 140f, 145 incidence 139 management 140 predisposing factors 139 prevention 139 Retina 45 Retinal breaks 54 development of 54 Retinal complications 55, 168 Retinal detachment 53, 55, 65, 67 unrepaired 54 Retinal lesions, management of treatable 52 Retinal nerve fiber 55 layer changes 55 Retinal phlebitis 55 Retinal pigment epithelium, congenital hypertrophy of 53 Retinal spot diagram 46 Retinal tear and detachment 55 Retinal vein occlusion 55 Retinal vessels 53 Retroillumination techniques 140 Rhegmatogenous retinal detachment 53, 54, 168 Riboflavin solution 213

Rigid gas permeable contact lens 59, 65 RK See Radial keratotomy RLE See Refractive lens exchange Root mean square error 44 values 47f RSBT See Residual stromal bed thickness RSE See Residual spherical equivalent

S Scanning-slit lasers 75 Scheimpflug camera 24 Schirmer’s test 60, 61 Schlemm’s canal 97 Schwind eye-tech-solutions 84 Scleral expansion surgeries 192 Sclerociliary complex 192 Scotopic conditions 81 SE See Spherical equivalent Sequential bioptics 208, 209 Shimmer sign 139 Side cut tears 141f Silicone gel 190 Simultaneous accelerated corneal collagen 214t Simultaneous bioptics 208, 209 Sinskey-hook-assisted dissection 131 Skewed radial axes 23 Slit illumination 140 Slit-lamp assessment 61 evaluation 61 examination 60, 102 Slit-scanning based topography 24 methods 155 Small aperture inlays 200 Small incision lenticule 129 intrastromal keratoplasty 6 Small incision lenticule extraction 3, 3f, 4f, 11, 14, 34, 59, 63, 123, 125, 126, 126f, 128t, 132, 136t, 137f, 138f, 142t, 143f, 144f, 179, 189, 213, 221, 225 circle pattern of 181 complications of 135 contraindications for 126 intraoperative complications in 147 laser parameters of 127t modified techniques for 131 retreatment after 179, 180t surgical technique of 131t techniques for 131t Small palpebral fissure 95 SMILE See Small incision lenticule extraction Snail track degeneration 54 Snell’s law 22f Snellen’s visual acuity 145 Sodium citrate drops 105 Space-occupying corneal inlays 203 design 203 principle 203 Specular microscopy 156 Spherical aberration 44, 111, 112, 196 Spherical equivalent 90, 117, 132, 223 Spherocylindrical correction, amount of 232 Spherocylindrical error 119 Staar foam tip 158

Staphylococcal species 146 Staphylococci 82 Staphylococcus 100, 168 aureus 82 epidermidis 168 Starbursts 46 Steep keratometry 95 Steeper keratometric axis 231 Steeper preoperative keratometry 173 Sterile corneal infiltrates 82 Steroids, discontinuation of 165 Streptococcal species 146 Streptococcus 100, 168 species 82 Streptomyces caespitosus 75 Stroma 132 anterior one-third of 11 changes 13 dystrophies 61 fibrosis 201 healing 15 hypercellularity 15 keratitis 100 keratocytes 11, 13 nerve bundles 14 pocket 6, 87 tissue 4, 5 Stromal ablation, deeper 11 Stromal keratitis, pressure-induced 100, 104f Stromal placement, depth of 231 Stromal tunnel/pockets, creation of 232 Sub-basal nerve plexus 143 Sub-cap lenticule extraction 182, 182f Subepithelial nerve fiber 125 Submacular hemorrhage 168 Suboptimal visual gain 144 Suction loss 96, 135 incidence 135 intraoperative 136f management of 137fc management 135 pathophysiology 135 predisposing factors 135 prevention 97, 135 risk factors 96, 97 treatment 97 Supracor 196 Surface ablation 71, 175, 177 complications of 78 indications of 71f procedures 78 techniques 71 with LASIK, comparison of 76 Surface asymmetry index 23 Surface regularity index 23 Surgical technique 129, 226, 231 Synthetic polymethylmethacrylate 229 Systemic disorders 58 Systemic medications 59

T Tangential map 18 TBI See Tomographic biomechanical index Tear 238 film 81 osmolarity 61 Terrien’s marginal degeneration 230

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Code: Del-590 Name: Md Iqbal

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Title: Refractive Surgery—Decision Making and Surgical Techniques Author: Jeewan Titiyal and Manpreet Kaur

Stage: 1st Proof Time/Date: 06:34 PM/10 Aug 21

Index Theoretical eye models 111 Therapeutic keratoplasty 102 Thermal keratoplasty 4 Tissue elastic properties 40 TLSS See Transient light sensitivity syndrome TMR See Topography-modified refraction Tomographic biomechanical index 61 Topical anesthetics 78 Topical brimonidine tartrate 81 Topical corticosteroids 146 Topical steroids 143, 222 Topography systems 31 Topography systems, elevation-based 23 Topography-guided ablation 5, 116, 117, 117fc, 118, 119 platforms 114 profile 116f Topography-modified refraction 117 Topometric display 26 Toric intraocular lens 226 Torsional alignment 115 Trabecular meshwork 97 Trabeculectomy 165 Tractional tears, risk factors for 54 Transient light sensitivity syndrome 89 Traumatic choroidal ruptures 54 Trigeminal nerve 11 True corneal ectasia 27f True optical aberration 42 Tscherning aberrometers 45, 115

U UCVA See Uncorrected visual acuity UDVA See Uncorrected distance visual acuity

Unclean contact lens 137 Uncorrected distance visual acuity 216-218, 223 Uncorrected visual acuity 61, 65, 76, 117, 118, 174, 175, 196, 210, 211, 218 Uveitis 33 Uveitis-glaucoma-hyphema syndrome 151, 163

V VA See Visual acuity Vannas scissors 73 Vertical asymmetry, index of 26 Vertical gas breakthrough 97 prevention 97 treatment 97 Videokeratograph 18 Vinciguerra butterfly technique 73 screening report 37f Virgin eyes 5 treatment of 117 Vision 211 and ocular motility assessment 60 non-improvement of 145 optimal quality of 207 quality of 76, 92 threatening complications 66, 67 Visual acuity 65, 68, 102, 112, 175 and quality 201, 211 Visual disturbances 102 Visual gain 232 Visual outcomes 90, 113 efficacy of 4

Visual quality 76, 111 Visual recovery 92 delayed 67, 135 Visual symptoms 145 Visually disturbing optical phenomena 167 VisuMax femtosecond laser 129 system 128t components of 127t VisuMax laser 140, 182f platform 126f system 130 Vitamin C 105 Vitreoretinal pathologic conditions 56 Vitreous detachments, posterior 52

W Wavescan system 115 White ring sign 139 White without pressure 53 Wound healing fibroblasts 14 severe 15 WWOP See White without pressure

X Xenon dimer gas 90

Z Zernike coefficient 45 Zernike polynomials 44, 45f, 45t, 50, 115 descriptions 50 Zonular traction tufts 53