The Vitreous
'Nature Unveiling Before Science', E. Barias, 1902; CAncienne Faculte de Meaecine Rene De cartes, Paris, France. (Photograph by Lionel LeChevalier.)
]. Sebag The Vitreous Structure, Function, and Pathobiology Foreword by C.L. Schepens With 56 Illustrations, 7 in Color Springer-Verlag New York Berlin Heidelberg London Paris Tokyo Hong Kong
J. SEBAG, M.D. Eye Research Institute of Retina Foundation Harvard Medical School Boston, Massachusetts, USA Current address 8th Floor Suite Pacifica Tower 18800 Delaware Sb eet Huntington Beach, California 92648, USA Cover: Whole human vitreous dissected of the sclera, choroid, and retina (see Fig. IV.l.A, p. 37). Library of Congress Cataloging-in-Publication Data Sebag, J. The vitreous: structure, function, and pathobiology/j. Sebag: foreword by C.L. Schepens. p. cm. Includes bibliographies and index. l. Vitreous body. 2. Vitreous body-pathophysiology. I. Title. [DNLM: l. Eye Diseases-physiopathology. 2. Vitreous Bodyanatomy & histology. 3.Vitreous Body-physiopathology. WW 250 S443v] RE501.S43 1989 617.7'46-dc20 DNLM-DLC for Library of Congress 89-11402 1989/by Springer-Verlag New York Inc. Softcover reprint of the hardcover I st edition 1989 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer-Verlag, 175 Fifth Avenue, New York, NY 1O0lO, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use of general descriptive names, trade names, trademarks, etc. in this publication, even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely by anyone. While the advice and information in this book are believed to be true and accurate at the date of going to press, neither the author nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Typeset by TCSystems, Inc., Shippensburg, Pennsylvania. Printed and bound by Arcata Graphics/Halliday, West Hanover, Massachusetts. 9 8 7 6 5 4 3 2 1 ISBN-13: 978-1-4613-8910-1 e-isbn-13: 978-1-4613-8908-8 DOl: 10.1007/978-1-4613-8908-8
Foreword The vitreous body long has been the most mysterious of all ocular structures, owing perhaps to its seeming simplicity. There have been few concerted, sustained efforts to unravel the mysteries of how the vitreous is composed and what role it plays in normal physiology. Over the years, however, many studies have produced independent findings concerning vitreous biochemistry, structure, and physiology. The Vitreous organizes these findings into a well-constructed compendium that not only addresses the most current scientific knowledge, but also reviews historical perspectives in a manner that lends richness to the scope of the book. The first few chapters present an exhaustive, yet readable, review of the body of scientific data that have come from laboratories and researchers throughout the world. Extensive bibliographies direct interested readers further into specific aspects of the basic science of the vitreous. Chapter II: "Embryology" and Chapter IV: "Structure" present a novel organizational approach to assembling and presenting data in an integrated manner. Chapter V: "Functions" and Chapter VI: "Development and Aging" introduce fresh perspectives on the importance of the vitreous as something more than a vestigial space filler within the eye. In Chapter VII: "Pathobiology," Dr. Sebag presents an analysis of the pathology of the vitreous in terms of abnormal human biology. The usual clinical descriptions of syndromes often found in ophthalmic texts are avoided. Instead, the various disease states of the vitreous are considered in terms of molecular, structural, and cellular events. Thus, different diseases are grouped according to the basic pathophysiology they share, for example, cellular proliferation. In this way knowledge about the mechanisms at play in one disease can further our understanding of another disease. Frequent references to earlier sections, where the scientific foundation was established, build upon basic information to demonstrate how derangements in the "normal" state lead to various diseases. A novel approach, used in Chapter VII, is the consideration of how the effects of diabetes mellitus on connective tissues elsewhere in the body furthers understanding about the effects of diabetes on the vitreous and thus about diabetic retinopathy.
vi Foreword The Vitreous, which was written by a single author, achieves its cohesiveness through extensive cross-referencing. However, Dr. Sebag avoids the risk of presenting only one point of view by outlining competing and contrasting perspectives. Although a most interesting section of Chapter VII addresses the effects of various surgical interventions, The Vitreous is not a surgical manual. Rather, it is an attempt to integrate for clinicians and scientists the basic scientific knowledge of biochemistry, structure, and physiology of the vitreous with clinical concepts of function and the pathophysiology of vitreoretinal disease. I applaud this successful attempt. Boston, Massachusetts CHARLES L. SCHEPENS
Acknowledgements I am indebted to Dr. Endre A. Balazs who first stimulated my interest in the vitreous. Some of the investigations reported in this book were begun in the Matrix Biology Laboratory of the Edward S. Harkness Eye Research Institute, College of Physicians and Surgeons, Columbia University, New York. I am greatly indebted to Dr. Charles L. Schepens who during many years has promoted and supported my continued investigations at the Eye Research Institute of Retina Foundation, Harvard Medical School, Boston, Massachusetts. The New York Bank for Sight Restoration and the New England Eye Bank kindly provided the material for investigations on vitreous structure. Lynda Morgan of Huntington Beach, California, and Rose Davis of Boston, Massachusetts, provided expert clerical assistance in the preparation of this book. J. SEBAG
Contents Foreword. CHARLES L. SCHEPENS... Acknowledgements....................... v vii I Introduction... 1 A. General Background.................................. 1 B. Historical Perspective...................... 1 1. Vitreous Structure................................ 1 2. Vitreous Biochemistry............................. 3 References............................................... 4 II Embryology of the Vitreous............................... 7 A. Structural Development............................... 7 1. Primary Vitreous.................................. 7 2. Secondary Vitreous............................... 9 3. Zonular System................................... 11 B. Cellular Development................................ 11 1. Hyalocytes... 12 2. Fibroblasts... 12 C. Molecular Development............................. 12 1. Collagen... 12 2. Hyaluronic Acid.................................. 13 3. Other Molecular Components..................... 14 References............................................... 14 III Biochemistry... 17 A. Collagen... 17 B. Hyaluronic Acid (HA)... 19 C. Collagen-HA Interaction.............................. 21 D. Noncollagenous Proteins.............................. 24 E. Glycoproteins... ".'................ 25 F. Low-Molecular-Weight Substances.................... 25 1. Sodium... 26 2. Potassium... ~.......... 26 3. Chloride... 26
x Contents 4. Calcium... 26 5. Phosphates... 26 6. Bicarbonate... 26 G. Miscellaneous Compounds............................ 26 1. Ascorbic Acid............ 26 2. Lactic Acid....................................... 27 3. Amino Acids... 27 4. Lipids... 27 H. Species Variations.................................... 27 1. Glycosaminoglycans... 28 2. Collagen... 28 3. Protein... 29 4. Glycoproteins... 29 5. Lipids...'... 29 6. Miscellaneous... 29 References............................................... 29 IV Structure of the Vitreous.................................. 35 A. Organization and Distribution of Molecular Components............................... 35 B. Vitreous Body........................................ 36 C. Vitreous Base........................................ 39 D. Vitreous Cortex... 40 1. Hyalocytes... 43 2. Fibroblasts... 46 E. Basal Laminae and Vitreoretinal Interface.............. 47 F. Zonules... 54 References............................................... 54 V Functions of the Vitreous................................. 59 A. Developmental... 59 B. Optical... 60 1. Media Transparency.............................. 60 2. Accommodation... 61 C. Mechanical... 63 D. Physiology and Metabolism........................... 64 References............................................... 67 VI Development and Aging of the Vitreous.................... 73 A. Development to the Adult............................ 73 1. Structural Development........................... 73 2. Molecular Development........................... 73 3. Morphologic Changes During Development........ 75 B. Aging... :... 80 1. Rheology... 80 2. Biochemistry........................... 82 3. Morphology... 83 C. Posterior Vitreous Detachment........................ 84 1. Definition... 84 2. Epidemiology... 87
Contents xi 3. Pathogenesis.... 87 4. Sequelae.... 90 References.... 92 VII Pathobiology of the Vitreous.... 97 A. Developmental and Inherited Disorders.... 97 1. Hyaloid Vascular System.... 97 2. Dominant Exudative Vitreoretinopathy.... 98 3. Retinopathy of Prematurity.... 99 4. Wagner's Disease.... 101 5. Vitreoretinal Dystrophy of Goldmann-Favre.... 102 B. Connective-Tissue Disorders.... 102 1. Marfan's Syndrome.... 103 2. Ehlers-Danlos Syndrome.... 103 3. Stickler Syndrome.... 103 C. Diabetes Mellitus.... 105 1. Biochemical Effects.... 105 2. Vitreous Effects.... 106 D. Cell Invasion.... 107 1. Cell Proliferation at the Vitreoretinal Interface.... 108 2. Trauma.... 113 3. Inflammation.... 115 4. Neoplasia.... 120 E. Vascular Invasion and Effects of Vitreous Hemorrhage.. 120 1. Role of Vitreous in Neovascularization.... 120 2. Effects of Hemorrhage on the Vitreous.... 123 F. Vitreoretinal Traction.... 124 1. Peripheral Traction.... 125 2. Traction on Retinal Blood Vessels.... 128 3. Posterior Pole Traction.... 132 G. Miscellaneous Conditions of the Vitreous.... 133 1. Myopia.... 133 2. Aphakia.... 135 3. Retinitis Pigmentosa.... 138 4. Vitreous Opacities.... 139 H. Effects of Surgical Intervention.... 142 1. Vitrectomy.... 142 2. Photocoagulation.... 144 3. Cryopexy.... 145 4. Intravitreal Injections.... 146 References.... 147 Color Plates.... 161 Index.... 167
The Vitreous