Foreword

During the past 25 years, our understanding of the molecular mechanisms of ocular diseases has greatly increased. As particular molecules have been implicated in disease processes, treatments that specifically target those molecules have been developed. Some recent successes have fueled research aimed at further elucidating molecular pathogenesis of ocular diseases and translational research aimed at converting recent findings into treatments. Those successes have also awakened the pharmaceutical industry to the unmet needs and potential opportunities related to ocular diseases. Thus, it is likely that new pharmacotherapies for retinal and uveal diseases will continue to become available for the foreseeable future.

In Retinal Pharmacotherapy, the editors, Quan Dong Nguyen, Eduardo Büchele Rodrigues, Michel Eid Farah, and William F. Mieler, and the authors have compiled a valuable resource that describes numerous pharmacologic agents that are currently available to treat retinal and posterior uveitic diseases. The Book is organized into six sections. Section 1 is devoted to the basic understanding of the molecular pathogenesis of retinal diseases. Section 2 describes animal models of retinal diseases that are useful for preclinical testing of drugs given by various routes of administration. Clinical features of retinal and

posterior uveitic diseases that may be amendable to pharmacotherapy are discussed in Section 3. In Section 4, the appropriate uses of several drugs that have been shown to have therapeutic benefits for retinal diseases are reviewed. Section 5 covers topics that combine pharmacotherapy and surgery for treatment of retinal and posterior uveal diseases. Section 6 discusses value-based medicine, pharmacoeconomics, and the impact of regulatory bodies such as the FDA in the development of pharmacotherapy for retinal diseases.

Retinal Pharmacotherapy contains 53 chapters with contributions from over 120 authors from North America, South America, Europe, Asia, and Australia, many of whom are recognized authorities in the field. It will serve as an important resource for retina specialists, uveitis specialists, and comprehensive ophthalmologists.

Peter A. Campochiaro, MD

George and Dolores Eccles Professor of Ophthalmology Wilmer Eye Institute

Johns Hopkins University 2009

Anthony P Adamis MD

Adjunct Professor

Department of Ophthalmology and Visual

Sciences

University of Illinois College of Medicine

Chicago, IL, USA

Madeleine KM Adams MB ChB

BSc (Hons) MRCOphth

Honorary Research Fellow University of Melbourne

Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital East Melbourne, VIC, Australia

Thomas A Albini MD

Assistant Professor of Clinical

Ophthalmology

Bascom Palmer Eye Institute

Miami, FL, USA

Jayakrishna Ambati MD

Professor and Vice Chair

Ophthalmology and Visual Sciences

Professor of Physiology

Dr. E. Vernon Smith and Eloise C. Smith

Endowed Chair

University of Kentucky

Doris Duke Distinguished Clinical

Scientist

Burroughs Wellcome Translational

Research Clinical Scientist

Lexington, KY, USA

Luis Amselem MD

Consultant, Institut de la Mácula i de la Retina

Consultant, Department of Ophthalmology and Visual Sciences Retinal and Vitreous Surgery Ocular Oncology

2nd Mayo Hospital Barcelona, Spain

J Fernando Arévalo MD, FACS

Professor of Ophthalmology

Clinica Oftalmologica Centro Caracas and University of Los Andes

The Arévalo-Coutinho Foundation for Research in Ophthalmology Caracas, Venezuela

Lluis Arias MD

Consultant

Institut de la Mácula i de la Retina Centro Médico Teknon Barcelona, Spain

Helen Dede Ayertey MD

Doctor of Medicine Center of Ophthalmology University of Cologne Cologne, Germany

Paul N Baird BSc (Hons) PhD

Associate Professor of Ophthalmology University of Melbourne

Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital East Melbourne, VIC, Australia

Susanne Binder MD

Professor and Chairman Department of Ophthalmology The Ludwig Boltzmann Institute for

Retinology and Biomicroscopic Laser Surgery

Vienna, Austria

Fabio Bom Aggio MD

Vision Institute, Department of Ophthalmology

Federal University of São Paulo São Paulo, Brazil

Melissa M Brown MD, MN, MBA

Director, Center for Value-Based Medicine; Adjunct Senior Fellow, Leonard Davis Institute

Center for Value-Based Medicine Flourtown, PA, USA

Gary C Brown MD, MBA

Attending Surgeon Retina Service Wills Eye Institute

Chief Medical Officer

Center for Value-Based Medicine Wyndmoor, PA, USA

Richard Brunner MD

Professor of Ophthalmology

Center of Ophthalmology

University of Cologne

Cologne, Germany

J Peter Campbell MD, MPH

Resident in Ophthalmology

Wilmer Eye Institute

Johns Hopkins University School of

Medicine

Baltimore, MD, USA

Jose A Cardillo MD

Department of Ophthalmology

Federal University of São Paulo

UNIFESP-EPM

São Paulo, Brazil

Chi-Chao Chan MD

Chief, Section of Immunopathology

Laboratory of Immunology

Chief, Histology Core

National Eye Institute

National Institutes of Health

Bethesda, MD, USA

Pik Sha Chan MD

Attending Physician

Retina and Pediatric Ophthalmology

Service

Asian Eye Institute

Makati City, Philippines

Aimee v Chappelow MD

Cole Eye Institute

Cleveland Clinic Foundation

Cleveland, OH, USA

contributors of List

Emily Y Chew MD

Deputy Director

Division of Epidemiology and Clinical

Applications

National Eye Institute

National Institutes of Health

Bethesda, MD, USA

Victor Chong MD

Consultant Ophthalmic Surgeon

University of Oxford

Oxford Eye Hospital

Oxford, UK

Hanna R Coleman MD

Staff Clinician, New York Presbyterian

Hospital, Columbia

Department of Ophthalmology

Columbia University Medical Center

NY, USA

Gabriel J Coscas MD

Emeritus Professor of Clinical

Ophthalmology

Department of Ophthalmology

University of Paris XII

Créteil, France

Yongping Crawford MD PhD

ES Cell Culture

Genentech, Inc.

San Francisco, CA, USA

Emmett T Cunningham Jr

MD PhD MPH

Director, The Uveitis Service

California Pacific Medical Center

Adjunct Clinical Professor of

Ophthalmology

Stanford University School of Medicine

San Francisco, CA, USA

Hajir Dadgostar MD

Cole Eye Institute

Cleveland Clinic Foundation

Cleveland, OH, USA

Taraprasad Das MD FRCS

Director

LV Prasad Eye Institute

Patia

Bhubaneswar, India

Janet l Davis MD MA

Professor of Ophthalmology

Department of Ophthalmology

Bascom Palmer Eye Institute

University of Miami

Miami, FL, USA

Heidrun L Deissler Dipl-Chem

Head of Research Laboratory

Department of Ophthalmology

University Eye Hospital Ulm

Ulm, Germany

Diana V Do MD

Assistant Professor of Ophthalmology

the Wilmer Eye Institute

the Johns Hopkins University School of

Medicine

Baltimore, MD, USA

Michel Eid Farah MD

Professor of Ophthalmology and

Vice-chairman

Retina and Vitreous Department

Federal University of São Paulo

Vision Institute

São Paulo, Brazil

Napoleone Ferrara MD

Genentech Fellow

Genentech, Inc.

San Francisco, CA, USA

Robert P Finger MD MIH

Department of Ophthalmology

University of Bonn

Bonn, Germany

Harry W Flynn, Jr. MD

The J Donald M Gass Distinguished

Chair in Ophthalmology

Professor of Ophthalmology

Bascom Palmer Eye Institute

University of Miami Miller School of

Medicine

Naples, FL, USA

Gildo y Fujii MD PhD

Professor of Ophthalmology

Londrina State University

Fujii Institute of Ophthalmology

Londrina, Brazil

Gerardo García-Aguirre MD

Assistant Staff Retina Department

Hospital “Dr. Luis Sánchez Bulnes” Asociación para Evitar la Ceguera en México (APEC)

Mexico City, Mexico

Thomas W Gardner MD MS

Jack and Nancy Turner Professor

of Ophthalmology and Cellular and

Molecular Physiology

Department of Ophthalmology

Penn State College of Medicine

Hershey, PA, USA

Gerhard Garhöfer MD

Department of Clinical Pharmacology

Medical University of Vienna

Vienna, Austria

Mauro Goldbaum MD

Executive Director

Eyetech, Inc

São Paulo, Brazil

David T Goldenberg MD

Private Practice

Retinal Consultants of Arizona

Phoenix, AZ, USA

Sandeep Grover MD

Assistant Professor

Director, Inherited Retinal Diseases and

Electrophysiology

Department of Ophthalmology

University of Florida

Jacksonville, FL, USA

Robyn H Guymer MBBS PhD FRANZCO

Professor of Ophthalmology University of Melbourne

Centre for Eye Research Australia Royal Victorian Eye and Ear Hospital East Melbourne, VIC, Australia

Zohar Habot-Wilner MD

Doctor of Medicine

Department of Ophthalmology

Tel-Aviv Medical Center

Tel-Aviv, Israel

Seenu M Hariprasad MD

Associate Professor of Surgery

Section of Ophthalmology and Visual

Science

Chief, Vitreoretinal Service

Director of Clinical Research and

Vitreoretinal Fellowship Program

University of Chicago

Chicago, IL, USA

Jeffrey S Heier MD

Vitreoretinal Specialist

Ophthalmic Consultants of Boston

Boston, MA, USA

Rocío Herrero-Vanrell PhD

Professor of Pharmaceutical Technology

Department of Pharmacy and

Pharmaceutical Technology

School of Pharmacy

Universidad Complutense

Madrid, Spain

Alexandra A Herzlich MD

National Institute of Health

Bethesda, MD, USA

Frank G Holz MD

Ophthalmologist, University Eye Hospital

Director

Department of Ophthalmology

University of Bonn

Bonn, Germany

John j Huang MD

Assistant Professor

Director of Ocular Immunology and

Uveitis

Faculty of Vitreo-Retina

Director of Clinical Trials and

Translational Research

Department of Ophthalmology

Yale University

New Haven, CT, USA

Mohamed Ibrahim MD

Research Fellow

Wilmer Eye Institute

Johns Hopkins University School of

Medicine

Baltimore, MD, USA

Hisanori Imai MD

Department of Ophthalmology

Kobe University School of Medicine

Kobe, Japan

Peter Charbel Issa MD FEBO

Department of Ophthalmology

University of Bonn

Bonn, Germany

Peter K Kaiser MD

Professor of Ophthalmology

Cleveland Clinic Lerner College of

Medicine

Director, Digital OCT Reading Center

Cole Eye Institute

Cleveland, OH, USA

Jennifer J Kang-Mieler PhD

Associate Professor of Biomedical

Engineering

Department of Ophthalmology and Visual

Sciences

Illinois Institute of Technology

Chicago, IL, USA

Ravi Keshavamurthy MD

Retina Fellow

Department of Ophthalmology

University of Florida

Jacksonville, FL, USA

Bernd Kirchhof MD

Department of Vitreo-Retinal Surgery

Center of Ophthalmology

University of Cologne

Cologne, Germany

Ainat Klein MD

Medical Doctor

Department of Ophthalmology

Tel-Aviv Medical Center, Sackler Faculty

of Medicine

Tel-Aviv University

Tel-Aviv, Israel

Mark E Kleinman MD

Resident in Ophthalmology

Department of Ophthalmology and Visual

Sciences

University of Kentucky

Lexington, KY, USA

Tim U Krohne MD FEBO

Ophthalmologist

University Eye Hospital

Bonn, Germany

Baruch D Kuppermann MD PhD

Professor of Ophthalmology

University of California Irvine

Irvine, CA, USA

Malaika M Kurz-Levin MD

University Hospital

Department of Ophthalmology

Medical Retina

Zurich, Switzerland

Oh Woong Kwon MD PhD

Director

The Retina Center

Nune Eye Hospital

Seoul, South Korea

Gabriele E Lang MD

Professor of Ophthalmology

Head of the Division of Medical Retina

and Laser Surgery

Department of Ophthalmology

University Eye Hospital Ulm

Ulm, Germany

Susan Lightman PhD FRCP FRCOphth

Professor of Clinical Ophthalmology

Department of Clinical Opthalmology

Institute of Ophthalmology

Moorfields Eye Hospital

London, UK

Richard C Lin MD PhD

Clinical Assistant Professor

Stanford University

Palo Alto Veterans Hospital

Palo Alto, CA, USA

Anat Loewenstein MD

Professor of Ophthalmology

Department of Ophthalmology

Tel Aviv Medical Center

Tel Aviv, Israel

Thorsteinn Loftsson MSPharm PhD

Professor

Faculties of Medicine and Pharmacy

University of Iceland

Reykjavik, Iceland

Tao Lu Lowe PhD

Associate Professor of Pharmaceutical

Sciences

School of Pharmacy

Thomas Jefferson University

Philadelphia, PA, USA

Maurício Maia MD PhD

Professor of Vitreoretinal Surgery

Department of Ophthalmology

Federal University of São Paulo

São Paulo, Brazil

Juliana Mantovani Bottós MD

Vision Institute, Department of

Ophthalmology

Federal University of São Paulo

São Paulo, Brazil

Mariana Martínez-Castellanos

MD

Retina Department

Hospital “Dr. Luis Sánchez Bulnes”

Mexico City, Mexico

contributors of List

contributors of List

Trevor J McFarland BS

Senior Research Assistant

Casey Eye Institute

Oregon Health and Science University

Portland, OR, USA

Gustavo B Melo MD

Vision Institute, Department of

Ophthalmology

Federal University of São Paulo

São Paulo, Brazil

Carsten H Meyer MD

Ophthalmologist

University Eye Hospital

Bonn, Germany

Stephan Michels MD MBA

Assistant Professor of Medical Retina

Department of Ophthalmology

Triemli Hospital Zurich

Zurich, Switzerland

William F Mieler MD

Professor and Vice-Chairman

Department of Ophthalmology and Visual

Sciences

University of Illinois at Chicago

Chicago, IL, USA

Gauri P Misra MD

Department of Pharmaceutical Sciences

School of Pharmacy

Thomas Jefferson University

Philadelphia, PA, USA

Jordi M Monés MD

Director

Institut de la Mácula i de la retina Centro Médico Teknon Barcelona, Spain

Raja Narayanan MD

Consultant

Kanuri Santhamma Vitreoretinal Service

LV Prasad Eye Institute

Hyderabad, India

Jackie K Nguyen MD

Vitreoretinal Surgeon

Private Practice

Eyecare Medical Group

Portland, ME, USA

Quan Dong Nguyen MD MSc

Associate Professor of Ophthalmology

Diseases of the Retina and Vitreous, and

Uveitis

Wilmer Eye Institute

Johns Hopkins University School of

Medicine

Baltimore, MD, USA

Robert B Nussenblatt MD MPH

Chief

Laboratory of Immunology

National Eye Institute

National Institutes of Health

Bethesda, MD, USA

Masahito Ohji MD

Professor and Chairman

Department of Ophthalmology

Shiga University of Medical Science

Otsu, Shiga, Japan

Timothy W Olsen MD

F Phinizy Calhoun Sr Professor and

Chairman

Department of Ophthalmology

Emory University

Director, Emory Eye Center

Atlanta, GA, USA

Mrinali Patel MD

Postgraduate Student (PGY-1)

Memorial Sloan Kettering Cancer Center

NY, USA

Fernando M Penha MD PhD

Postdoctoral Associate,

Bascom Palmer Eye Institute, University

of Miami,

Miami, FL, USA

Postdoctoral Associate

Department of Ophthalmology

Federal University of São Paulo

São Paulo, Brazil

Hugo Quiroz-Mercado MD

Professor

Rocky Mountain Lions Eye Institute

University of Colorado Hospital

Aurora, CO, USA

Eduardo Büchele Rodrigues MD

Vision Institute, Department of

Ophthalmology

Federal University of São Paulo

São Paulo, Brazil

Mi In Roh MD

Opththalmology Research Fellow

Department of Ophthalmology

Harvard Medical School

Massachusetts Eye and Ear Infirmary

Boston, MA, USA

Juliana V Rossi MD

Retina and Vitreous Vision Institute

Department of Ophthalmology

Federal University of São Paulo

São Paulo, Brazil

Theodor Charles Sauer BS

Duke Medical School

Duke University

Durham, NC, USA

Osamu Sawada MD

Assistant Professor

Department of Ophthalmology

Shiga University of Medical Science

Otsu, Shiga, Japan

Andrew P Schachat MD

Professor of Ophthalmology, Lerner

College of Medicine

Vice Chairman

Cole Eye Institute

Cleveland Clinic Foundation

Cleveland, OH, USA

Ursula Schmidt-Erfurth MD

Professor and Chair

Department of Ophthalmology and

Optometry

Medical University of Vienna

Vienna, Austria

Hendrik P N Scholl MD MA

Consultant Ophthalmologist

Department of Ophthalmology

University of Bonn

Bonn, Germany

Stephen G Schwartz MD Mba

Associate Professor of Clinical

Ophthalmology

Medical Director, Bascom Palmer Eye

Institute at Naples

Naples, FL, USA

Syed Mahmood Shah Mbbs

Research Scientist

Wilmer Eye Institute

Johns Hopkins University School of

Medicine

Baltimore, MD, USA

Chirag Pradip Shah MD MPH

Vitreoretinal Surgery Fellow

Wills Eye Institute

Retina Service

Philadelphia, PA, USA

Carol L Shields MD

Professor of Ophthalmology

Ocular Oncology Service

Wills Eye Hospital

Philadelphia, PA, USA

Jerry A Shields MD

Professor of Ophthalmology

Thomas Jefferson University

Director, Oncology Services

Wills Eye Hospital

Philadelphia, PA, USA

Ravi J Singh MD

Department of Ophthalmology

Penn State College of Medicine

Hershey, PA, USA

Sobha Sivaprasad DM MS DNB FRCS

Consultant Ophthalmologist and Senior

Lecturer

Laser and Retinal Research Unit

Kings College Hospital

London, UK

Ricardo Luiz Smith MD PhD

Professor of Anatomy

Department of Morphology and Genetics

Federal University of São Paulo

São Paulo, Brazil

Ji Hun Song MD

Assistant Professor

Department of Ophthalmology

Ajou University School of Medicine

Suwon, South Korea

Gisèle Soubrane MD PhD

Professor and Chair of Ophthalmology Université de Paris Val de Marne Créteil, France

Boris V Stanzel MD

Resident in Ophthalmology

University Eye Hospital

Bonn, Germany

Einar Stefánsson MD PhD

Professor and Chairman

Department of Ophthalmology

Landspitali University Hospital

Reykjavik, Iceland

Glenn L Stoller MD

Private Practice

Ophthalmic Consultants of Long Island

Lynbrook, NY, USA

J Timothy Stout MD PhD MBA

Vice President, Oregon Health and

Science University

Professor of Genetics, Retina and

Vitreous Diseases

Casey Eye Institute

Portland, OR, USA

R C Andrew Symons MB BS PhD

FRANZCO

Assistant Professor of

Ophthalmology

Department of Ophthalmology

University of Kansas

Prairie Village, KS, USA

John T Thompson MD

Assistant Professor

Wilmer Eye Institute

Johns Hopkins University

Baltimore, MD, USA

Michael T Trese MD

Clinical Professor of Biomedical

Sciences, Oakland University, Rochester

Chief Pediatric and Adult Vitreoretinal

Surgery, Wm. Beaumont Hospital

Royal Oak, MI, USA

Harvey Siy Uy MD DPBO

Director for Research and Chief, Uveitis Service, Asian Eye Institute

Clinical Associate Professor of Ophthalmology

Jose Rizal Ophthalmology Center University of the Philippines Philippine General Hospital Makati City, Philippines

Monika Voigt MD PhD

Department of Ophthalmology of Créteil

University Paris XII

Créteil, France

Shawn Wilker MD

Assistant Professor of Ophthalmology

Case Western Reserve University

School of Medicine

Cleveland, OH, USA

George A Williams MD

Chair, Department of Ophthalmology

Clinical Professor

Beaumont School of Medicine

Oakland University

Beaumont Eye Institute

Royal Oak, MI, USA

Steven Yeh MD

Vitreoretinal Fellow

Casey Eye Institute

Portland, OR, USA

Ellen Yu-Keh MD

Asian Eye Institute

Makati City, Philippines

Donald J Zack MD PhD

Guerrieri Professor of Genetic

Engineering and Molecular

Ophthalmology

Johns Hopkins Medical School

Baltimore, MD, USA

David G. Zeballos MD

Retina and Vitreous Service

Clinica Oftalmológica Centro Caracas

Caracas, Venezuela

contributors of List