F. G. Holz R. F. Spaide Editors

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1 Essentials in Ophthalmology Medical Retina F. G. Holz R. F. Spaide Editors

2 Essentials in Ophthalmology G. K. Krieglstein R. N. Weinreb Series Editors Glaucoma Cataract and Refractive Surgery Uveitis and Immunological Disorders Vitreo-retinal Surgery Medical Retina Oculoplastics and Orbit Pediatric Ophthalmology, Neuro-Ophthalmology, Genetics Cornea and External Eye Disease

3 Editors Frank G. Holz RichardF.Spaide Medical Retina With 91 Figures, Mostly in Colour and 13 Tables 123

4 Series Editors Günter K. Krieglstein, MD Professor and Chairman University of Cologne Kerpener Straße Cologne Robert N. Weinreb, MD Professor and Director Hamilton Glaucoma Center University of California at San Diego 9500 Gilman Drive La Jolla, CA Volume Editors Frank G. Holz, MD Professor and Chairman University of Bonn Ernst-Abbe-Straße Bonn Richard F. Spaide, MD Assistant Clinical Professor Vitreous, Retina, and Macula Consultants of New York, and LuEsther T. Mertz Retinal Research Center Manhattan Eye, Ear, and Throat Hospital 460 Park Avenue New York, NY ISBN Springer Berlin Heidelberg NewYork ISSN Library of Congress Control Number: This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer- Verlag. Violations are liable for prosecution under the German Copyright Law. Springer is a part of Springer Science + Business Media springer.com Springer-Verlag Berlin Heidelberg 2007 The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Editor: Marion Philipp, Heidelberg, Desk Editor: Martina Himberger, Heidelberg, Production: LE-TeX Jelonek, Schmidt & Vöckler GbR, Leipzig, Cover Design: WMXDesign GmbH, Heidelberg, Printed on acid-free paper 24/3180Wa

5 Foreword The series Essentials in Ophthalmology was initiated two years ago to expedite the timely transfer of new information in vision science and evidence-based medicine into clinical practice. We thought that this prospicient idea would be moved and guided by a resolute commitment to excellence. It is reasonable to now update our readers with what has been achieved. The immediate goal was to transfer information through a high quality quarterly publication in which ophthalmology would be represented by eight subspecialties. In this regard, each issue has had a subspecialty theme and has been overseen by two internationally recognized volume editors, who in turn have invited a bevy of experts to discuss clinically relevant and appropriate topics. Summaries of clinically relevant information have been provided throughout each chapter. Each subspecialty area now has been covered once, and the response to the first eight volumes in the series has been enthusiastically positive. With the start of the second cycle of subspecialty coverage, the dissemination of practical information will be continued as we learn more about the emerging advances in various ophthalmic subspecialties that can be applied to obtain the best possible care of our patients. Moreover, we will continue to highlight clinically relevant information and maintain our commitment to excellence. G. K. Krieglstein R. N.Weinreb Series Editors

6 Preface Clinicians and basic scientists from the fields of ophthalmology and vision research have made tremendous progress in understanding the pathogenesis of retinal diseases, developing novel diagnostic techniques, and instituting new treatments for retinal conditions. This multi-authored volume provides concise updates on the relevant and most challenging topics in medical retina. It is a practical and useful publication that will help all ophthalmologists, whether in training or in practice, to manage patients with retinal diseases. The first two chapters on microperimetry and scanning laser fundus imaging highlight the advances in diagnostic technology that have contributed significantly to our understanding of the pathophysiology and treatment of various diseases. The following chapters address the latest developments in the area of age-related macular degeneration including an update on genetic factors, current management strategies using anti-vegf therapy, the role of combination treatments, and nutritional supplementation. The atrophic form of late AMD, i.e., geographic atrophy, is also addressed. Furthermore, current treatment approaches to diabetic macular edema and retinal vein occlusions are described. Finally, there is a discussion of the novel insights into Stargardt s disease and idiopathic macular teleangiectasia, as well as perspectives on the expanding field of artificial vision. Time and effort have been generously given by the contributing authors, to whom we, as editors, are extremely grateful. We are indebted to the editorial and production staff at Springer for their commitment to a timely publication in this rapidly moving field. Frank G. Holz Richard F. Spaide

7 Contents Chapter 1 Microperimetry in Macular Disease Klaus Rohrschneider 1.1 Introduction Instruments Scanning Laser Ophthalmoscope Fundus Perimetry (Microperimetry) Micro Perimeter Static Threshold Fundus Perimetry Kinetic Fundus Perimetry Comparison Between SLO Perimetry and MP Accuracy of Fundus Perimetry Static Threshold Perimetry Kinetic Perimetry Fundus-related Perimetry Versus Cupola Perimetry Clinical Implementation Macular Holes Age-related Macular Degeneration Geographic Atrophy of the RPE Choroidal Neovascularization in AMD Diabetic Retinopathy Central Serous Chorioretinopathy Stargardt s Disease Vitelliform Macular Dystrophy (Best s Disease) Conclusion Chapter 2 New Developments in cslo Fundus Imaging Giovanni Staurenghi, Grazia Levi, Silvia Pedenovi, Chiara Veronese 2.1 Introduction Near Infrared Imaging Introduction The Effect of Wavelength on Imaging in the Human Fundus Comparison of Light Tissue Interactions for Visible and Near Infrared Wavelengths Using SLO Mode of Imaging Contrast of the Fundus Fundus Features Imaging of Pathological Features in Direct and Indirect Mode Blue Autofluorescence Imaging Autofluorescence and the Eye Fluorescence of the Retinal Pigment Epithelium How to Evaluate RPE Autofluorescence Fundus Autofluorescence Changes in Early AMD Fundus Autofluorescence Changes in Choroidal Neovascularization in AMD Fundus Autofluorescence Changes in Geographic Atrophy in AMD Fundus Autofluorescence in Acute and Chronic Recurrent Central Serous Chorioretinopathy... 27

8 X Contents Fundus Autofluorescence in Stargardt s Macular Dystrophy-Fundus Flavimaculatus Fundus Autofluorescence in Patients with Macular Holes Wide-Field Contact Lens System Introduction Materials and Methods Structure of a Wide-Field Contact Lens System Limit and Advantage of a Wide-Field Contact Lens System Technique for Performing the Examination Other Techniques of Execution of Wide-field Fluorescein Angiograms Clinical Application Chapter 3 Genetics of Age-Related Macular Degeneration: Update Hendrik P.N. Scholl, Monika Fleckenstein, Peter Charbel Issa, Claudia Keilhauer, Frank G. Holz, Bernhard H.F. Weber 3.1 Introduction: Genetic Influence on AMD Analysis of Candidate Genes for AMD Linkage and Association Studies in AMD Complement Factor H Gene LOC Factor B Gene Gene and Gene Environment Interaction in AMD Conclusions Chapter 4 Anti-VEGF Treatment for Age- Related Macular Degeneration Todd R. Klesert, Jennifer I. Lim 4.1 Basic Science Historical Perspective VEGF Isoforms VEGF Expression VEGF Receptors VEGF Activity Current Anti-VEGF Therapies Aptamers: Pegaptanib Sodium (Macugen) Monoclonal Antibodies: Ranibizumab (Lucentis) Monoclonal Antibodies: Bevacizumab (Avastin) Anti-VEGF Therapy: Practical Considerations Intravitreal Injection Technique Safety Considerations Bevacizumab (Avastin) Preparation: Compounding Pharmacies Future Anti-VEGF Therapies VEGF Trap Small Interfering RNAs Receptor Tyrosine Kinase Inhibitors Conclusion Chapter 5 Intravitreal Injections: Techniques and Sequelae Heinrich Heimann 5.1 Introduction Complications of Intravitreal Injections Methodology Perioperative Complications Conjunctival Hemorrhage Conjunctival Scarring Pain Punctate Keratitis and Corneal Edema Vitreous Reflux Traumatic Cataract Cataract Progression Retinal Perforation Vitreous Floaters Vitreous Hemorrhage Retinal Toxicity Intraocular Inflammation... 74

9 Contents XI Uveitis and Pseudoendophthalmitis Endophthalmitis Retinal Artery and Vein Occlusion Retinal Detachment Acute Rise in Intraocular Pressure Ocular Hypertension and Glaucoma Surgical Technique for Intravitreal Injection Guidelines and Preferred Practice Survey Preoperative Assessment and Preparation Concomitant Eye Diseases Preoperative Assessment Preoperative Medication Location Preparation of the Eye and Ocular Adnexa Preparation of the Surgeon Preparation of the Drug Injection Syringe and Needle Position of the Injection Entry Path Advancement of Needle and Injection Postoperative Assessment Assessment Immediately Following the Injection Topical Therapy Follow-up Examinations Chapter 6 Combination Therapies for Choroidal Neovascularization Richard F. Spaide 6.1 Introduction Angiogenesis Development of CNV Cancer and Angiogenesis Normalization of Tumor Vasculature Two-Component Model of CNV Two-Component Model and Therapy Are There Cytokines to Block Other Than VEGF? Combination Therapies Anti-VEGF Biologics and Photodynamic Therapy Anecortave Acetate and Photodynamic Therapy Intravitreal Triamcinolone and Photodynamic Therapy Triamcinolone and Anti- VEGF Therapy Triamcinolone and Anecortave Acetate Conclusion Chapter 7 Nutritional Supplementation in Agerelated Macular Degeneration Hanna R. Coleman, Emily Y. Chew 7.1 Introduction Risk Factors Age-Related Eye Disease Study Lutein/Zeaxanthin Zinc Vitamin E Dietary Fat Intake Age-Related Eye Disease Study Conclusion Chapter 8 New Perspectives in Geographic Atrophy Associated with AMD Steffen Schmitz-Valckenberg, Monika Fleckenstein, Hendrik P.N. Scholl, Frank G. Holz 8.1 Introduction Basics Development and Spread of Atrophy Fundus Autofluorescence Imaging in Geographic Atrophy Quantification of Atrophy Progression

10 XII Contents 8.4 Risk Factors Genetic Factors Systemic Risk Factors Ocular Risk Factors Development of CNV in Eyes with GA Visual Function in GA Patients Measurement of Visual Acuity Contrast Sensitivity Reading Speed Fundus Perimetry Chapter 9 Diabetic Macular Edema: Current Treatments Florian K.P. Sutter, Mark C. Gillies, Horst Helbig 9.1 Introduction Epidemiology Pathophysiology Diabetic Macular Edema and Laboratory Science Quality of Life Diagnosis and Screening Types of Diabetic Macular Edema Clinically Significant Macular Edema Focal Diabetic Macular Edema Diffuse Diabetic Macular Edema Cystoid Macular Edema Ischemic Macular Edema OCT Patterns of Diabetic Macular Edema Treatment Systemic Treatment Glycemic Control Blood Pressure Control Reducing Levels of Blood Lipids Treatment of Renal Dysfunction and Anemia Smoking Systemic Pharmacotherapy PKC-ß Inhibitors Aldose Reductase and AGE Inhibitors Antioxidants A Team Approach to the Prevention of Loss of Vision in People with Diabetes Local Ophthalmic Treatment Focal Macular Laser Grid Macular Laser Recent Trends in Macular Laser Therapy Micropulsed, Sub-threshold Selective Laser Therapy Vitrectomy Intravitreal Steroids Periocular Steroids Intravitreal Anti-VEGF Antibodies Cataract Surgery Current Clinical Practice/ Recommendations Chapter 10 Treatment of Retinal Vein Occlusions Rajeev S. Ramchandran, R. Keith Shuler, Sharon Fekrat 10.1 Introduction Pathophysiology Branch and Central Vein Occlusion Studies Background Branch Vein Occlusion Study Central Vein Occlusion Study Systemic Pharmacologic Treatments Targeting Macular Edema Intravitreal Pharmacotherapy Background Intravitreal Triamcinolone: BRVO Intravitreal Triamcinolone: CRVO Fluocinolone Acetonide Intravitreal Implant

11 Contents XIII Standard of Care vs. Corticosteroid for Retinal Vein Occlusion Study Intravitreal Anti-VEGF Therapy Surgical Treatments BRVO CRVO Laser-Induced Venous Chorioretinal Anastomosis Recombinant Tissue Plasminogen Activator Radial Optic Neurotomy Intravitreal Triamcinolone: As Adjunctive Therapy Prevention Systemic Factor Control Conclusion Chapter 11 New Perspectives in Stargardt s Disease Noemi Lois 11.1 Introduction Epidemiology and Clinical Findings Imaging Studies Fluorescein Angiography Indocyanine Green Angiography Fundus Autofluorescence Optical Coherence Tomography Electrophysiology and Psychophysics Histopathology Differential Diagnosis Genetics and Molecular Biology Animal Models of STGD- FFM Current and Future Treatments Chapter 12 Idiopathic Macular Telangiectasia Peter Charbel Issa, Hendrik P.N. Scholl, Hans-Martin Helb, Frank G. Holz 12.1 Introduction Type 1 Idiopathic Macular Telangiectasia Epidemiology Diagnostic Approach and Clinical Findings Functional Implications Pathophysiological Considerations Therapy Type 2 Idiopathic Macular Telangiectasia Epidemiology Diagnostic Approach and Clinical Findings Functional Implications Associated Diseases Pathophysiological Considerations Therapeutic Approaches Type 3: Idiopathic Macular Telangiectasia Perspectives Chapter 13 Artificial Vision Peter Walter 13.1 Introduction Current Concepts for Restoring Vision Using Electrical Stimulation Interfacing the Neurons Epiretinal Stimulation Subretinal Approach Transchoroidal, Transscleral, and Suprachoroidal Stimulation Optic Nerve Approach Cortical Prosthesis Pixel Vision and Filters Outlook Conclusion Subject Index

12 Contributors Peter Charbel Issa, Dr. University of Bonn Ernst-Abbe-Straße Bonn Emily Y. Chew, MD National Eye Institute/National Institutes of Health 10 Center Drive Bethesda, MD Hanna R. Coleman, MD National Eye Institute/National Institutes of Health 10 Center Drive Bethesda, MD Sharon Fekrat, MD, FACS Duke University Medical Center Durham, NC Monika Fleckenstein, Dr. University of Bonn Ernst-Abbe-Straße Bonn Mark C. Gillies, MD Save Sight Institute P. O. Box 4337 Sydney NSW 2001 Australia Heinrich Heimann, Priv.-Doz. Dr. Consultant Ophthalmic Surgeon St. Paul s Eye Unit, Royal Liverpool University Hospital Prescot Street Liverpool, L7 8XP UK Hans-Martin Helb, Dr. University of Bonn Ernst-Abbe-Straße Bonn Horst Helbig, Prof. Dr. University of Regensburg Franz-Josef-Strauß-Allee Regensburg Frank G. Holz, Prof. Dr. University of Bonn Ernst-Abbe-Straße Bonn Claudia Keilhauer, Dr. University of Würzburg Josef-Schneider-Straße Würzburg Todd R. Klesert, MD, PhD Doheny Retina Institute of the Doheny Eye Institute USC Keck School of Medicine 1450 San Pablo Street Los Angeles, CA 90027

13 XVI Contributors Grazia Levi, MD II Scuola di Specialità in Oftalmologia Università degli studi di Milano Facoltà di Medicina e Chirurgia Dipartimento di Scienze Cliniche Luigi Sacco Via G.B. Grassi, Milano Italy Jennifer I. Lim, MD Doheny Eye Institute USC Keck School of Medicine 1450 San Pablo Street Los Angeles, CA Noemi Lois, MD, PhD Aberdeen Royal Infirmary University Hospital Foresterhill Aberdeen AB25 2ZN UK Silvia Pedenovi, MD II Scuola di Specialità in Oftalmologia Università degli studi di Milano Facoltà di Medicina e Chirurgia Dipartimento di Scienze Cliniche Luigi Sacco Via G.B. Grassi, Milano Italy Rajeev S. Ramchandran, MD Duke University Medical Center Durham, NC Klaus Rohrschneider, Prof. Dr. University of Heidelberg Im Neuenheimer Feld Heidelberg Steffen Schmitz-Valckenberg, Dr. University of Bonn Ernst-Abbe-Straße Bonn Hendrik P.N. Scholl, Priv.-Doz. Dr. University of Bonn Ernst-Abbe-Straße Bonn R. Keith Shuler, MD Duke University Medical Center Durham, NC Richard F. Spaide, MD, Prof. Vitreous, Retina, and Macula Consultants of New York, and LuEsther T. Mertz Retinal Research Center, Manhattan Eye, Ear, and Throat Hospital 460 Park Avenue New York, NY Giovanni Staurenghi, MD, Prof. Cattedra di Clinica Oculistica II Scuola di Specialità in Oftalmologia Università degli studi di Milano Facoltà di Medicina e Chirurgia Dipartimento di Scienze Cliniche Luigi Sacco Via G.B. Grassi, Milano Italy Florian K.P. Sutter, Priv.-Doz. Dr. University of Zurich Rämistraße Zurich Switzerland

14 Contributors XVII Chiara Veronese, MD II Scuola di Specialità in Oftalmologia Università degli studi di Milano Facoltà di Medicina e Chirurgia Dipartimento di Scienze Cliniche Luigi Sacco Via G.B. Grassi, Milano Italy Bernhard H.F. Weber, Prof. Dr. Institute for Human Genetics University of Regensburg Franz-Josef-Strauß-Allee Regensburg Peter Walter, Prof. Dr. RWTH Aachen University Pauwelsstraße Aachen

Editors Frank G.Holz Richard F. Spaide. Medical Retina. With 91 Figures, Mostly in Colour and13tables. Springer

Editors Frank G.Holz Richard F. Spaide Medical Retina With 91 Figures, Mostly in Colour and13tables Springer ääm mm.m iiiii HHHHHMmi Chapter1 Microperimetry in Macular Disease Klaus Rohrschneider 1.1 Introduction