Intraocular Drug Delivery / Edition 1

by Glenn J. Jaffe, Paul Ashton, P. Andrew Pearson

Overview

This reference studies the most recent advances in the development of ocular drug delivery systems. Covering methods to treat or prevent ocular inflammation, retinal vascular disease, retinal degeneration, and proliferative eye disease, this source covers breakthroughs in the management of endophthalmitis, uveitis, diabetic macular edema, and age-related macular degeneration.

Product Details

ISBN-13:	9780367453817
Publisher:	CRC Press
Publication date:	11/11/2019
Pages:	384
Product dimensions:	7.00(w) x 10.00(h) x (d)

About the Author

Glenn J. Jaffe Paul Ashton P. Andrew Pearson

Table of Contents

Preface iii

Contributors xiii

Part I General

1 Retinal Drug Delivery Paul Ashton 1

Basic Principles of Drug Delivery 1

Drug Delivery to the Posterior Segment of the Eye 8

Drug Elimination Mechanisms 12

Posterior Delivery in Disease States 14

Photodynamic Therapy 18

Future Opportunities and Challenges 19

References 19

2 Blood-Retinal Barrier David A. Antonetti Thomas W. Gardner Alistair J. Barber 27

Introduction 27

Function of the Blood-Retinal Barrier 27

Formation of the Blood-Neural Barrier 28

Ocular Disease and Loss of the Blood-Retinal Barrier 29

Molecular Architecture of the Blood-Retinal Barrier 30

Claudins 30

Occludin 31

Restoring Barrier Properties 33

References 34

3 Neuroprotection Dennis W. Rickman Melissa J. Mahoney 41

Introduction 41

Excitotoxicity as a Stimulus for Neuronal Cell Death 41

Intracellular Effectors of Cell Death 43

Oxidative Stress and the Generation of Free Radicals 45

Neurotrophic and Neurotrophin Deprivation as a Stimulus for Retinal Cell Death 46

Neurotrophins Support the Development and Maintenance of Retinal Ganglion Cells 46

Neurotrophins Support the Development of Inner Retinal Circuitry 47

Models of Photoreceptor Degeneration and Strategies for Their Treatment 47

Neurotrophin Delivery to CNS Tissue 48

Summary 50

References 51

4 Regulatory Issues in Drug Delivery to the Eye Lewis J. Gryziewicz Scott M. Whitcup 59

Introduction 59

Drug Development in the United States 60

References 69

Part II Specific Delivery Systems

5 Antiangiogenic Agents: Intravitreal Injection Sophie J. Bakri Peter K. Kaiser 71

Introduction 71

Intravitreal Injection 72

Technique for Intravitreal Injection 72

VEGF 73

References 81

6 Intravitreal Antimicrobials Travis A. Meredith 85

Introduction 85

Basic Pharmacokinetics 85

Intravitreal Injections 87

Therapeutic Concentration Range 89

Toxicity 89

Characteristics of Selected Antimicrobials 91

References 93

7 Pharmacologic Retinal Reattachment with INS37217 (Denufosol Tetrasodium), a Nucleotide P2Y₂ Receptor Agonist Ward M. Peterson 97

Description of Drug Delivery System 97

Spectrum of Diseases 97

Mechanism of Action 99

Animal Models of Disease Used 100

Results of Animal Model Studies 101

Drug Delivery and Distribution 105

Clinical Study 107

Future Horizons 108

References 109

8 Cell-Based Delivery Systems: Development of Encapsulated Cell Technology for Ophthalmic Applications Weng Tao Rong Wen Alan Laties Gustavo D. Aguirre 111

Description of Encapsulated Cell Technology 111

Spectrum of Diseases for Which This Delivery System Might Be Appropriate 116

Animal Models Used to Investigate the Applicability of this Delivery System for the Diseases Mentioned 118

Pharmacokinetic and Pharmacodynamic Studies Using the Delivery System 120

Results of Animal Model Studies 120

Techniques for Implanting or Placing the Implant in Humans 124

Future Horizons 126

References 126

9 Photodynamic Therapy Ivana K. Kim Joan W. Miller 129

Introduction 129

Preclinical Studies of Verteporfin for Experimental CNV 130

Other Photosensitizers 136

Future Directions 137

References 139

10 Thermal-Sensitive Liposomes Sanjay Asrani Morton F. Goldberg Ran Zeimer 143

Introduction 143

Methodology of Laser-Targeted Drug Delivery 144

Potential Therapeutic Applications of LTD 147

Diagnostic Applications 149

Safety of Light-Targeted Drug Delivery 152

Limitations 153

Conclusion 153

Disclosure of Financial Interest 154

References 154

11 Gene Therapy for Retinal Disease Albert M. Maguire Jean Bennett 157

Description of Drug Delivery System 157

Spectrum of Diseases for Which This Delivery System Might Be Appropriate 160

Animal Models Used to Investigate the Applicability of This Delivery System for the Diseases Mentioned Above 162

Pharmacokinetic Studies Using the Delivery System 163

Results of Animal Model Studies 163

Techniques for Implanting or Placing the Implant in Humans (If Done) 167

Future Horizons 168

References 169

12 Biodegradable Systems Hideya Kimura Yuichiro Ogura 175

Fundamentals of Biodegradable Polymeric Devices 175

Spectrum of Diseases for Which Biodegradable Systems May Be Useful 179

Animal Models Used to Test Biodegradable Drug Delivery Systems 180

Results of Efficacy Studies 181

Pharmacokinetic and Pharmacodynamic Studies 183

Summary and Future Horizons 189

References 189

13 Transscleral Drug Delivery to the Retina and Choroid Jayakrishna Ambati 193

Introduction 193

Scleral Anatomy 193

In Vitro Studies of Scleral Permeability 194

In Vivo Studies of Scleral Permeability 196

Future Directions 198

References 199

14 Nondegradable Intraocular Sustained-Release Drug Delivery Devices Mark T. Cahill Glenn J. Jaffe 203

Implanted Nondegradable Sustained-Release Devices 203

Implanted Microanalysis Probes as Sustained-Release Drug Delivery Systems 216

Microelectromechanical Systems Drug Delivery Devices 219

References 222

Part III Local Drug Delivery Approach to Specific Clinical Diseases

15 Photodynamic Therapy in Human Clinical Studies: Age-Related Macular Degeneration Ivana K. Kim Joan W. Miller 227

Introduction 227

Phase I/II Design and Methodology 227

Phase I/II Results 231

Phase III Design/Methodology 234

Conclusions 244

References 245

16 Age-Related Macular Degeneration Drug Delivery Kourous A. Rezaei Sophie J. Bakri Peter K. Kaiser 249

Treatment Modalities for Neovascular AMD 249

Clinical Trials of Drug Delivery Devices for the Treatment of Neovascular AMD 250

References 259

17 Intraocular Sustained-Release Drug Delivery in Uveitis Mark T. Cahill Glenn J. Jaffe 265

Introduction 265

Corticosteroid Devices 266

Cyclosporine Devices 275

Conclusions 276

References 277

18 Drug Delivery for Proliferative Vitreoretinopathy: Prevention and Treatment Stephen J. Phillips Glenn J. Jaffe 279

Retinal Detachment/Proliferative Vitreoretinopathy 279

Systemic 282

Local Delivery 283

Direct Injection-Subconjunctival or Intravitreal 283

Sustained Delivery and Co-Drugs 286

References 287

19 Pharmacologic Treatment in Diabetic Macular Edema Zeshan A. Rana P. Andrew Pearson 291

Introduction 291

Treatment 292

Corticosteroids 292

Intravitreal Triamcinolone Acetonide (Kenalog) Injection 293

Intravitreal Fluocinolone Acetonide Implant (Retisert) 294

Dexamethasone Implant (Posurdex®) 295

Protein Kinase C Inhibition 296

VEGF Inhibition 297

New Agents on the Horizon 297

References 298

20 Retinal Vein Occlusion Michael M. Altaweel Michael S. Ip 301

Local Drug Delivery Approach: Retinal Vein Occlusion 301

Other Treatments 309

Summary 319

References 320

21 Cytomegalovirus Retinitis Caroline R. Baumal 325

Introduction 325

Virology and Epidemiology of CMV Infection 325

CMV Retinitis in the Era of HAART 327

Clinical Features of CMV Retinitis 328

Diagnosis of CMV Retinitis 330

Treatment of CMV Retinitis 330

Systemic Anti-CMV Therapy 331

Local Modes of Intraocular Drug Delivery 333

Intravitreal Drug Injection 334

The Ganciclovir Intraocular Implant 335

Indications for the Ganciclovir Implant 339

Replacement of the Ganciclovir Implant 340

Complications of the Ganciclovir Implant 341

Summary 342

References 343

22 Endophthalmitis Travis A. Meredith 349

Overview 349

Presentation 349

Predisposing Factors 349

Bacterial Spectrum 350

Antimicrobial Therapy 350

Injection of Intraocular Corticosteroids 352

Prognosis 353

Summary 353

References 353

Index 357

Editorial Reviews

Reviewer: Nicholas N. Volpe, MD (Northwestern University Feinberg School of Medicine)
Description: This is a unique text, representing a "snapshot" in time, describing a wide variety of ocular disorders, exhaustively discussing the newest methods of intraocular drug delivery and providing important incite into the process of drug development and delivery methods, as well as regulatory issues. It is organized in chapters, multi-authored by authorities in the field ophthalmic drug delivery. The full range of therapies and the disorders that they treat are discussed from intravitreal injections to gene therapy.
Purpose: The purpose of the book is to provide the reader with an understanding of the factors influencing drug delivery to the eye and the various methods that have been used successfully to accomplish these modern treatments for various eye diseases. The book clearly meets these objectives providing an up to date summary of the currently available and developing methods of intracoular drug delivery. The authors have chosen a unique theme of drug delivery to cover a wide variety of diseases and treatments and both the casual reader and the scientist in search of new methods and ideas will find this text helpful.
Audience: The authors of the text and the individual chapters are all authorities in their fields and experts on their topics. The book will provide useful information to practitioners interested in the state of the art and what is coming down the road, as well as, the sub-specialist or researcher who is interested in the latest ideas and methods that are used to treat eye disease.
Features: The book includes chapters that range from the most basic topics such as the blood retinal barrier and neuroprotection, to practical clinical chapters on intravitreal antimicrobials and current treatments of macular degeneration. There is a very well written section on regulatory issues as well. Specific methods of drug delivery are discussed in detail. The chapters on gene therapy, photodynamic therapy and sustained release drugs in uveitis are excellent. Unfortunately only ten color figures are included in a separate section on glossy pages. The index is marginal in its usefulness although this might just be a result of some many different topics covered in different ways by different authors.
Assessment: The authors are to be commended. This text is highly recommended, not so much for the causal reader of ophthalmology but more the reader looking for a single resource that updates this very new and important area in ophthalmology. The information is current and reflects both practical clinical information and newer methodologies under development. The reader is certain to gain knowledge and incite into new, complex methods of treatment that are continuing to become more commonplace in ophthalmology for treating a variety of disorders. This book is unique. There is no other book like this one describing so many different methods of treating a wide range of ophthalmic disorders. It is packed with fascinating science and clinical pearls.

Doody's Review Service