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Scott M. Whitcup Dimitri T. Azar Editors Pharmacologic Therapy of Ocular Disease Handbook of Experimental Pharmacology

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Scott M. Whitcup Dimitri T. Azar Editors Pharmacologic Therapy of Ocular Disease Handbook of Experimental Pharmacology Handbook of Experimental Pharmacology 242 Scott M. Whitcup Dimitri T. Azar Editors Pharmacologic Therapy of Ocular Disease Handbook of Experimental Pharmacology Volume 242 Editor-in-Chief J.E. Barrett, Philadelphia Editorial Board V. Flockerzi, Homburg M.A. Frohman, Stony Brook, NY P. Geppetti, Florence F.B. Hofmann, Mu¨nchen M.C. Michel, Mainz C.P. Page, London W. Rosenthal, Jena K. Wang, Beijing More information about this series at http://www.springer.com/series/164 Scott M. Whitcup • Dimitri T. Azar Editors Pharmacologic Therapy of Ocular Disease Editors Scott M. Whitcup Dimitri T. Azar Akrivista and Whitecap Biosciences Illinois Eye and Ear Infirmary Mission Viejo, California University of Illinois at Chicago USA College of Medicine Chicago, Illinois Jules Stein Eye Institute USA David Geffen School of Medicine at UCLA Los Angeles, California USA ISSN 0171-2004 ISSN 1865-0325 (electronic) Handbook of Experimental Pharmacology ISBN 978-3-319-58288-7 ISBN 978-3-319-58290-0 (eBook) DOI 10.1007/978-3-319-58290-0 Library of Congress Control Number: 2017941200 # Springer International Publishing AG 2017 This work is subject to copyright. All rights are reserved by the Publisher, 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 physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, 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. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Preface Louis Pasteur said, “There are no such things as applied sciences, only applications of science.” The application of scientific advancements over the last two decades has led to a plethora of new sight-saving therapies. It is both illuminating and encouraging to compare the last volume of the Handbook of Experimental Phar- macology devoted to the Pharmacology of the Eye published in 1984 to the current volume. The 1984 version, edited by Marvin Sears, provided a sound physiologic and pharmacologic foundation to guide ophthalmic therapy. The medications that were discussed focused on glaucoma, ocular infections, and ocular inflammatory disease. There was little discussion of therapies for retinal diseases or dry eye, and topics such as sustained-release drug delivery were not discussed. The goal of the current volume is to present the science that can further catalyze the progress in ocular pharmacology as well as to review the resulting new therapies available today and in future trials. Chapters on ocular pharmacology and ocular pharmacokinetics are presented at the start of the book and provide the principles forming the basis of the subsequent disease-focused chapters spanning the tear film to the optic nerve and tissues in between. Some of the new therapies discussed in this volume include new classes of drugs to treat ocular hypertension and glaucoma, anti-VEGF therapy for retinal disease, and the use of biologic agents to manage ocular inflammatory diseases. A chapter on drug delivery has been included since extendedrelease of medications will be required to improve patient care and allow the practicaladministration of certain compounds to the eye. Discussion of gene therapy for diseases such as retinitis pigmentosa and neuroprotection for diseases of the optic nerve are also recent additions. Winston Churchill suggested that, “if you have knowledge, let others light their candles with it.” It is our hope that this book will serve not only to summarize the current state of the science of ocular pharmacology and therapeutics, but also to stimulate and support further advances that will benefit patients. We would like to thank the authors for their excellent contributions and for their dedications. Our thanks also go to Sumathy Thanigaivelu, Suzanne Dathe, and Balamurugan Elumalai at Springer, and to Dr. Joelle Hallak for their tireless efforts v vi Preface in making this project possible. Finally, we would like to dedicate this book to Dr. Robert Nussenblatt, who contributed to both this edition and the volume published in 1984. Bob was a teacher, mentor, and friend, and worked throughout his career to improve patient care. Mission Viejo, CA, USA Scott M. Whitcup Chicago, IL, USA Dimitri T. Azar Contents Part I General Principles Principles of Ocular Pharmacology ............................ 3 Yong Park, Dorette Ellis, Brett Mueller, Dorota Stankowska, and Thomas Yorio Ocular Pharmacokinetics .................................... 31 Chandrasekar Durairaj Ocular Drug Delivery ....................................... 57 Burcin Yavuz and Uday B. Kompella Part II Anterior Segment and Tear Film Ocular Pharmacology of Tear Film, Dry Eye, and Allergic Conjunctivitis ............................................. 97 Shilpa Gulati and Sandeep Jain Anti-Infective and Anti-Inflammatory Pharmacotherapies .......... 119 Mark I. Rosenblatt Keratoconus and Other Corneal Diseases: Pharmacologic Cross-Linking and Future Therapy ............................ 137 Kimberly M. Hsu and Joel Sugar Lens: Management of Cataract Surgery, Cataract Prevention, and Floppy Iris Syndrome ................................... 163 Joao Crispim and Wallace Chamon Part III Trabecular Meshworkand Uvea Glaucoma-Intraocular Pressure Reduction ...................... 181 Alex S. Huang, Lilit Minasyan, and Robert N. Weinreb Translational Pharmacology in Glaucoma Neuroprotection .......... 209 Leonard A. Levin vii viii Contents Pharmacologic Treatment of Noninfectious Uveitis ................ 231 Jared E. Knickelbein, Karen R. Armbrust, Meredith Kim, H. Nida Sen, and Robert B. Nussenblatt Part IV Posterior Segment and Optic Nerve Anti-angiogenic Therapy for Retinal Disease ..................... 271 Yannis M. Paulus and Akrit Sodhi Corticosteroids and Anti-Complement Therapy in Retinal Diseases ... 309 Raja Narayanan and Baruch D. Kuppermann Dry Age-Related Macular Degeneration Pharmacology ............. 321 Charles B. Wright and Jayakrishna Ambati Hereditary Retinal Dystrophy ................................ 337 Thomas C. Hohman Optic Nerve .............................................. 369 Lynn K. Gordon Index ................................................... 387 Principles of Ocular Pharmacology Yong Park, Dorette Ellis, Brett Mueller, Dorota Stankowska, and Thomas Yorio Contents 1 Introduction ................................................................................... 4 2 Receptor Profile ............................................................................... 7 2.1 Ligand-Gated Ion Channels ............................................................ 7 2.2 G Protein-Coupled Receptors .......................................................... 9 2.3 Kinase-Linked Receptors ............................................................... 10 2.4 Nuclear Receptors ...................................................................... 11 3 Drug Receptor Targets as Modulators of Ocular Function . .. .. .. .. .. .. .. .. .. .. .. .. .. .. .. 12 3.1 Ion Channel ............................................................................. 12 3.2 Alpha-Adrenergic Receptors ........................................................... 13 3.3 Beta-Adrenergic Receptors ............................................................. 13 3.4 Histamine Receptors .................................................................... 14 3.5 Prostaglandin Receptors ................................................................ 15 3.6 Kinase-Linked Receptors ............................................................... 16 4 Drug Interaction and Ocular Therapy ........................................................ 17 4.1 Cornea ................................................................................... 17 4.2 Uvea ..................................................................................... 19 4.3 Retina/Anterior Eye Segment .......................................................... 19 4.4 Other Regulators of IOP ................................................................ 21 References ........................................................................................ 23 Abstract Recently, in a poll by Research America, a significant number of individuals placed losing their eyesight as having the greatest impact on their lives more so than other conditions, such as limb loss or memory loss. When they were also Y. Park • D. Ellis • D. Stankowska • T. Yorio (*) North Texas Eye Research Institute, University of North Texas Health
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