11830 Westline Industrial Drive St.Louis,Missouri 63146 CLINICAL OCULAR PHARMACOLOGY,FIFTH EDITION ISBN:978-0-7506-7576-5 Copyright © 2008 by Butterworth-Heinemann, an imprint of Elsevier Inc. All rights reserved.No part of this publication may be reproduced or transmitted in any form or by any means,electronic or mechanical,including photocopying,recording,or any information storage and retrieval system,without permission in writing from the publisher.Permissions may be sought directly from Elsevier's Rights Department: phone:(+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax (+44) 1865 853333;e-mail:[email protected] may also complete your request on- line via the Elsevier website at http://www.elsevier.com/permissions. Notice Knowledge and best practice in this field are constantly changing.As new research and experience broaden our knowledge,changes in practice,treatment and drug therapy may become necessary or appropriate.Readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered,to verify the recommended dose or formula,the method and duration of administration,and contraindications.It is the responsibility of the practitioner,relying on their own experience and knowledge of the patient, to make diagnoses,to determine dosages and the best treatment for each individual patient,and to take all appropriate safety precautions.To the fullest extent of the law,neither the Publisher nor the Editors assume any liability for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this book. The Publisher Library of Congress Control Number: 2007932736 Vice President and Publisher:Linda Duncan Senior Editor:Kathy Falk Senior Developmental Editor:Christie M.Hart Publishing Services Manager:Melissa Lastarria Senior Project Manager:Joy Moore Design Direction:Julia Dummitt Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 1 To Cindy,Andrew, Kenton, and Harrison, who have taught me about love and family, and to my parents, who taught me about the value of hard work. J.D.B. To Jaak, Maire, and Ilomai and her family with more love and thanks than life and time can hold. S.D.J. Contributors Diane T. Adamczyk, OD David D. Castells, OD Director of Residency Education and Externships Associate Professor State University of New York Illinois College of Optometry State College of Optometry Chicago,Illinois New York,New York John G. Classé, OD, JD John F. Amos, OD Professor Dean School of Optometry School of Optometry University of Alabama at Birmingham University of Alabama at Birmingham Member of the Alabama Bar Birmingham,Alabama Birmingham,Alabama Howard Barnebey, MD Rachel A. Coulter, OD Specialty Eyecare Centre Associate Professor Bellevue,Washington College of Optometry Former Clinical Associate Professor Nova Southeastern University Department of Ophthalmology Fort Lauderdale,Florida University of Washington Seattle,Washington Timothy R. Covington, MS, PharmD President and CEO Jimmy D. Bartlett, OD, DOS, ScD Covington Healthcare Associates,LLC Professor of Optometry Birmingham,Alabama School of Optometry Professor of Pharmacy Practice University of Alabama at Birmingham Harrison School of Pharmacy Professor of Pharmacology Auburn University University of Alabama School of Medicine Auburn,Alabama Birmingham,Alabama Mitchell W. Dul, OD, MS David C. Bright, OD Associate Professor Professor Chairman,Department of Clinical Sciences Southern California College of Optometry Director,Glaucoma Institute of the University Fullerton,California Optometric Center Chief,Optometry Section State University of New York Greater Los Angeles Healthcare System (VHA) State College of Optometry Los Angeles,California New York,New York Private Practice Linda Casser, OD, FAAO Peekskill,New York Director of Clinical Examinations National Board of Examiners in Optometry Charlotte,North Carolina vii viii CONTRIBUTORS Arthur B. Epstein, OD, FAAO Kimberly A. Lambreghts, RN, OD Clinical Adjunct Assistant Professor Associate Clinical Professor Northeastern State University College of Optometry University of Houston Tahlequah,Oklahoma College of Optometry Private Practice Houston,Texas North Shore Contact Lens & Vision Consultants,PC Roslyn Heights,New York Nada Lingel, OD, MS Distinguished Professor of Optometry Richard G. Fiscella, RPh MPH Pacific University College of Optometry Clinical Professor Forest Grove,Oregon Department of Pharmacy Practice Robert W. Lingua, MD Adjunct Assistant Professor Lingua Vision Surgical Group Department of Ophthalmology Fullerton,California University of Illinois at Chicago Chicago,Illinois Blair B. Lonsberry, MS, OD, MEd, FAAO Associate Professor Marcela Frazier, OD, MPH Clinic Director,Portland Vision Center Assistant Professor Pacific University College of Optometry School of Optometry Portland,Oregon University of Alabama at Birmingham Birmingham,Alabama Gerald G. Melore, OD, MPH Assistant Clinical Professor Denise Goodwin, OD, FAAO Pacific University Associate Professor College of Optometry Pacific University College of Optometry Forest Grove,Oregon Forest Grove,Oregon Cynthia Ann Murrill, OD, MPH Susan P. Haesaert, OD Adjunct Faculty Attending Optometrist Pacific University College of Optometry Boston Veterans Administration Healthcare System Forest Grove,Oregon Associate Professor of Optometry Pacific Cataract and Laser Institute New England College of Optometry Tacoma,Washington Boston,Massachusetts Jerry R. Paugh, OD, PhD Nicky R. Holdeman, OD, MD Associate Professor and Associate Dean for Research Professor and Associate Dean for Clinical Education Southern California College of Optometry Executive Director,University Eye Institute Fullerton,California Chief of Medical Services C. Denise Pensyl, OD, MS, FAAO University Eye Institute Chief,Optometry University of Houston Bakersfield VA Outpatient Clinic Houston,Texas Greater Los Angeles VA Healthcare System Bakersfield,California Siret D. Jaanus, PhD, LHD Professor Joan K. Portello, OD, MPH, FAAO Southern California College of Optometry Associate Professor Fullerton,California State University of NewYork State College of Optometry Alan G. Kabat, OD, FAAO New York,New York Associate Professor Nova Southeastern University,College of Optometry C. Lisa Prokopich, OD, BSc Fort Lauderdale,Florida Lecturer Head,Ocular Health Clinic,Optometry David M. Krumholz, OD, FAAO School of Optometry Associate Professor University of Waterloo State University of New York Waterloo,Ontario,Canada State College of Optometry Head,Freeport Hospital Vision Centre New York,New York Kitchener,Ontario,Canada CONTRIBUTORS ix Christopher J. Quinn, OD, FAAO Michael E. Stern, PhD President Vice President,Inflammation Research Program Omni Eye Services Allergan,Inc. Iselin,New Jersey Irvine,California Kimberly K. Reed, OD, FAAO Tammy Pifer Than, MS, OD, FAAO Associate Professor Adjunct Associate Professor Nova Southeastern University School of Optometry College of Optometry University of Alabama at Birmingham Fort Lauderdale,Florida Birmingham,Alabama Adjunct Faculty Leo Paul Semes, OD Mercer University School of Medicine Professor Macon,Georgia School of Optometry Staff Optometrist University of Alabama at Birmingham Carl Vinson VAMC University Optometric Group Dublin,Georgia Birmingham,Alabama Michael D. VanBrocklin, OD David P. Sendrowski, OD, FAAO Adjunct Faculty Professor Pacific University College of Optometry Southern California College of Optometry Forest Grove,Oregon Fullerton,California Pacific Cataract and Laser Institute Tacoma,Washington Leonid Skorin, Jr., OD, DO, FAAO, FAOCO Senior Staff Ophthalmologist Erik Weissberg, OD Albert Lea Eye Clinic–Mayo Health System Associate Professor Albert Lea,Minnesota New England College of Optometry Clinical Assistant Professor of Ophthalmology Boston,Massachusetts Department of Surgery Chicago College of Osteopathic Medicine Suzanne M. Wickum, OD Midwestern University Clinical Associate Professor Downers Grove,Illinois University of Houston Clinical Assistant Professor College of Optometry Department of Neurology and Ophthalmology Houston,Texas College of Osteopathic Medicine Michigan State University Elizabeth Wyles, OD East Lansing,Michigan Assistant Professor Clinical Assistant Professor of Ophthalmology and Visual Illinois College of Optometry Sciences Chicago,Illinois University of Illinois Eye & Ear Infirmary Chicago,Illinois Kathy Yang-Williams, OD, FAAO Adjunct Professor Northwest Eye Surgeons,PC College of Optometry Seattle,Washington Pacific University Forest Grove,Oregon Diane P. Yolton, PhD, OD Professor Emeritus David L. Standfield, OD Pacific University Adjunct Faculty College of Optometry Pacific University College of Optometry Forest Grove,Oregon Forest Grove,Oregon Pacific Cataract and Laser Institute Chehalis,Washington Condit F. Steil, PharmD, FAPhA, CDE Associate Professor of Pharmacy Practice McWhorter School of Pharmacy Samford University Birmingham,Alabama Preface There continues to be an explosion of research on issues that chapter content is “evidence based.”In this edition, of pharmacologic relevance to primary eye care delivery. each contributing author has been carefully instructed to New ophthalmic formulations are being developed,new ensure that evidence-based material is the cornerstone of diagnostic methods introduced,and new medications and every chapter.This is consistent with past editions of this delivery systems are available that were unheard of a book.However,because reference sources are so easily decade ago.It is important that these new concepts be retrieved today through the internet and other electronic introduced to students and practitioners alike.This new sources,we have elected in this edition to simply provide fifth edition of Clinical Ocular Pharmacologyaddresses selected bibliographies rather than detailed annotated these new concepts and provides “one-stop shopping”for references.The bibliographies are current and concise, students,residents,and practicing clinicians who need a direct the reader to the most relevant source material,and ready source of information regarding both the basic consist of salient major review articles,as well as impor- pharmacology of ophthalmic drugs,as well as their utiliza- tant classic literature.Our intent,as in previous editions, tion in clinical practice.In this edition,readers will find is to recognize the work of those individuals who have that every chapter has been substantially updated from contributed to the knowledge base in ocular pharma- our previous work, and several chapters have been cology and to ensure that our readers receive the most completely rewritten. contemporary thought regarding pharmacologic concepts New topics not previously discussed include several for both the diagnosis and therapeutic intervention in novel drug delivery systems;the pharmacologic treatment primary eye care. of retinal diseases,including age-related macular degenera- The updated book design elements you see in these tion and diabetic retinopathy; and nutritional agents pages,together with the concise writing of our contribut- relevant to ocular therapy.We have expanded coverage of ing authors and their streamlined reference formatting, medications used to treat infections, allergies, and dry have resulted in a book that,although visibly smaller and eyes.New information on ocular hypotensive drugs and more portable,retains its goal of providing the most clin- an entirely new chapter on the contemporary medical ically relevant material and guidance to optometrists and management of glaucoma offer new insights on treatment ophthalmologists who care for primary eye care patients. of these extremely important diseases. One of the most challenging tasks facing authors of Jimmy D. Bartlett, OD, DOS, ScD contemporary medical and scientific books is to ensure Siret D. Jaanus, PhD, LHD xi Acknowledgments We are deeply grateful for our contributing authors,both fourth edition,these editors skillfully guided the develop- those who are new to this edition and those who have ment,organization,and presentation of their respective contributed to previous editions.Without their enthusi- chapters.Their work has clearly improved the readability, asm,commitment,and expert contributions,the prepara- accuracy, and conciseness of virtually all the material tion of this book would have been impossible.The helpful represented in this edition. suggestions from our colleagues and the expert advice Our editor,Christie Hart,Senior Developmental Editor from peer referees, who offered insightful and useful at Elsevier,was steadfast in her commitment to this proj- comments regarding each revised chapter, have clearly ect and in her efforts to coordinate and to ensure timely improved the presentation and accuracy of the text.We contributions from all the authors and section editors. are most appreciative of our administrative associates, We are extremely grateful to her for her tireless efforts Debi Honeycutt, Donna Scott, and Karen Beeching, for on behalf of this edition. their expert technical skills in preparing the voluminous Most of all,we must also thank our readers,who have manuscript.We are extremely grateful for our section continually given us positive feedback regarding the useful- editors—Richard Fiscella, Nicky Holdeman, and Lisa ness of this book.Our students,residents,and clinicians Prokopich—who spent enumerable hours reviewing from many countries have offered insightful comments draft manuscript and corresponding with authors and and positive encouragement that have led to the develop- reviewers to achieve the desired end result.As in the ment of this new edition. xiii SECTION I Fundamental Concepts in Ocular Pharmacology There is no great danger in our mistaking the height of the sun,or the fraction of some astronomical computation;but here where our whole being is concerned,’tis not wisdom to abandon ourselves to the mercy of the agitation of so many contrary winds. Hippocrates 1 1 Pharmacotherapy of the Ophthalmic Patient Rachel A. Coulter, Jimmy D. Bartlett, and Richard G. Fiscella Pharmacotherapyof the ophthalmic patient refers to the socioeconomic levels not covered by health insurance, use of diagnostic drugs to facilitate the examination and obtaining prescribed medications may not be feasible. diagnosis of patients undergoing comprehensive assess- This can result in the progression of chronic eye condi- ment and to the use of therapeutic drugs for the treat- tions such as glaucoma.To control medication costs and ment of patients with eye or vision problems. Patients to increase compliance with drug usage,patients should requiring ophthalmic pharmacotherapy are individuals. be encouraged to comparison shop among pharmacies, Individuals with eye problems may have unique medical especially for medications used for prolonged periods of histories that can include any range or combination of time.Several studies have documented that prescription systemic conditions from the common cold or asthma to drug prices vary considerably among pharmacies. rheumatoid arthritis or diabetes. Individuals may take Patients may need guidance in choosing community phar- medications that can interact with administered or macies that combine reasonable prices with necessary prescribed ocular drugs.Individuals vary in their desire or services. Prescribing generic drugs when feasible may need to overcome health problems.Some individuals may help to control the costs of therapy,especially for chronic have socioeconomic disadvantages that make prescribed diseases such as glaucoma. medications unaffordable.This chapter discusses funda- Studies have investigated the pharmacoeconomics of mental issues that must be addressed if each ophthalmic drug therapy.The drug price may reflect only part of the patient is to benefit fully from pharmacotherapy. medication “cost.”Other costs,such as those associated with adverse drug effects,additional laboratory tests,and office visits, may more realistically reflect the pharma- INITIATING AND MONITORING OCULAR coeconomics of therapy.For ophthalmic medications,the PHARMACOTHERAPY daily cost of medications also depends on the volume of The decision to use or refrain from using drugs for diagno- the medication, the drop size, dosing regimen, compli- sis or treatment is often straightforward.Topical anesthet- ance,and other factors.Publications have reviewed glau- ics must be used for applanation tonometry.Mydriatics are coma and topical corticosteroid therapy and described required for stereoscopic ophthalmoscopic examinations. more cost-effective treatment options not based solely on Pharmacologic intervention is needed for patients who the actual medication cost. have glaucoma. Other situations are less clear. Patients Long-term management of chronic eye conditions with mild blepharitis may not need antibiotics. Patients depends on patient adherence to therapy. This involves with dry eye syndrome who have intermittent symptoms an understanding of the ocular condition and a budgeted but lack ocular surface abnormalities may not require medical care plan.Clinicians’best intentions and efforts pharmacotherapeutic intervention. Simple reassurance toward therapy are unsuccessful if the medical and phar- can be sufficient for some patients, the disease process macotherapeutic plan is not practical and reasonable to may be left to run its natural course.The decision to use that particular patient. diagnostic or therapeutic pharmaceutical agents should Patient education can impact the ability or willingness be based on several factors:symptoms,signs,knowledge of patients to use prescribed medications. Studies of of the natural history of the disease process,potential for patient preferences for eyedrop characteristics have morbidity,and identification of any underlying ocular or determined that patients differ in how they value various general medical contraindications. drop characteristics and are willing to pay or undergo A frequently overlooked factor in prescribing drugs inconvenience for some attributes but not for others.A frank for ophthalmic patients is affordability. Managed health discussion should include possible side effects, dosage, care coverage has limitations. For patients at lower and cost to determine patient preference and achieve 3