Diabetic Retinopathy (eBook)

Dr. Browning is Retina Specialist at Charlotte Eye Ear Nose and Throat Associates in Charlotte, North Carolina, USA, and is involved with the Diabetic Retinopathy Clinical Research network.

Preface 8
Acknowledgments 10
Contents 12
Contributors 14
Pathophysiology of Diabetic Retinopathy 15
1.1 Retinal Anatomy 15
1.1.1 History 15
1.1.2 Anatomy 15
1.1.3 Microanatomy of the Retina Neurons 19
1.1.4 Intercellular Spaces 20
1.1.5 Internal Limiting Membrane 21
1.1.6 Circulation 21
1.1.7 Arteries 21
1.1.8 Veins 22
1.1.9 Capillaries 22
1.2 Hemodynamics, Macular Edema, and Starling’s Law 22
1.3 Biochemical Basis for Diabetic Retinopathy 24
1.3.1 Increased Polyol Pathway Flux 25
1.3.2 Advanced Glycation End Products (AGEs) 26
1.3.3 Activation of Protein Kinase C (PKC) 27
1.3.4 Increased Hexosamine Pathway Flux 28
1.4 Macular Edema 29
1.4.1 Blood-Retinal Barrier 31
1.4.2 Mechanism of Blood-Retinal Barrier Breakdown 33
1.4.3 Renin-Angiotensin System 37
1.5 Development of Proliferative Diabetic Retinopathy 38
1.6 Summary of Key Points 39
1.7 Future Directions 39
References 39
Genetics and Diabetic Retinopathy 45
2.1 Background for Clinical Genetics 45
2.2 The Role of Polymorphisms in Genetic Studies 46
2.3 Types of Genetic Study Design 49
2.4 Studies of the Genetics of Diabetic Retinopathy 53
2.4.1 Clinical Studies 53
2.4.2 Molecular Genetic Studies 54
2.4.3 EPO Promoter 54
2.4.4 Aldose Reductase Gene 54
2.4.5 VEGF Gene 54
2.4.6 IGF-1 59
2.5 Genes in or Near the HLA Locus 59
2.6 Receptor for Advanced Glycation End Products (RAGE) Genes 59
2.7 Endothelial NOS2 and NOS3 Genes 60
2.8 Renin-Angiotensin System-Associated Genes 60
2.9 Solute Carrier Family 2 (Facilitated Glucose Transporter), Member 1 Gene (SLC2A1) 60
2.10 Gene-Environment Interaction 60
2.11 Potential Value of Identifying Genetic Associations with Diabetic Retinopathy 60
2.12 Summary of Key Points 61
2.13 Future Directions 61
Glossary 61
References 63
Epidemiology of Diabetic Retinopathy 67
3.1 Introduction and Definitions 67
3.2 Epidemiology of Diabetes Mellitus 70
3.3 Factors Influencing the Prevalence of Diabetes Mellitus 71
3.4 Epidemiology of Diabetic Retinopathy 73
3.5 Diabetes and Visual Loss 73
3.6 Prevalence and Incidence of Diabetic Retinopathy 74
3.7 By Diabetes Type 75
3.8 By Insulin Use 75
3.9 By Age 76
3.10 By Duration of Diabetes Mellitus 76
3.11 By Ethnicity 77
3.12 Gender 78
3.13 Age at Onset of Diabetes 79
3.14 Socioeconomic Status and Educational Level 79
3.15 Family History of Diabetes 79
3.16 Changes Over Time 79
3.17 Epidemiology of Diabetic Macular Edema (DME) 80
3.18 Epidemiology of Proliferative Diabetic Retinopathy (PDR) 83
3.19 Socioeconomic Impact of Diabetes 83
3.20 Socioeconomic Impact of Diabetic Retinopathy 85
3.21 Summary of Key Points 85
3.22 Future Directions 86
References 86
Systemic and Ocular Factors Influencing Diabetic Retinopathy 90
4.1 Introduction 90
4.2 Systemic Factors 90
4.2.1 Glycemic Control 90
4.2.1.1 Type 1 Diabetes Mellitus 91
4.2.1.2 Type 2 Diabetes Mellitus 95
4.2.1.3 Rapidity of Improvement in Glycemic Control 97
4.2.2 Glycemic Variability 99
4.2.3 Insulin Use in Type 2 Diabetes 99
4.2.4 Pancreas and Pancreas-Renal Transplantation 99
4.2.5 Blood Pressure 99
4.2.6 Serum Lipids 101
4.2.7 Anemia 102
4.2.8 Nephropathy 102
4.2.9 Pregnancy 102
4.2.10 Other Systemic Factors 104
4.2.11 Influence on Visual Loss 104
4.3 Effects of Systemic Drugs 105
4.3.1 Diuretics 105
4.3.2 Renin-Angiotensin System Drugs 105
4.3.3 Aldose Reductase Inhibitors 106
4.3.4 Drugs That Target Platelets 106
4.3.5 Statins 107
4.3.6 Protein Kinase C Inhibitors 107
4.3.7 Thiazolidinediones (Glitazones) 107
4.3.8 Miscellaneous Drugs 107
4.4 Ocular Factors Influencing Diabetic Retinopathy 107
4.5 Diabetic Retinopathy and Associated Comorbidity 109
4.6 Economic Consequences 109
4.7 Summary of Key Points 110
4.8 Future Directions 110
References 110
Defining Diabetic Retinopathy Severity 117
5.1 Summary of Key Points 126
5.2 Future Directions 126
5.3 Practice Exercises 126
References 131
Diagnostic Techniques in Clinical Practice - OCT, FA, Ultrasound 133
6.1 Optical Coherence Tomography (OCT) 133
6.2 Heidelberg Retinal Tomograph (HRT) 140
6.3 Retinal Thickness Analyzer (RTA) 141
6.4 Microperimetry 141
6.5 Color Fundus Photography 141
6.6 Fluorescein Angiography 141
6.7 Ultrasonography 145
6.8 Multifocal ERG 145
6.9 Miscellaneous Modalities 145
6.10 Summary of Key Points 146
6.11 Future Directions 146
6.12 Practice Exercises 146
References 148
Diabetic Macular Edema 152
7.1 Epidemiology and Risk Factors 152
7.2 Pathophysiology and Pathoanatomy 153
7.2.1 Anatomy 153
7.3 Physiology 158
7.4 Clinical Definitions 163
7.5 Focal and Diffuse Diabetic Macular Edema 165
7.6 Subclinical Diabetic Macular Edema 168
7.7 Refractory Diabetic Macular Edema 168
7.8 Regressed Diabetic Macular Edema 169
7.9 Recurrent Diabetic Macular Edema 169
7.10 Methods of Detection of Diabetic Macular Edema 169
7.11 Case Report 1 171
7.12 Case Report 2 173
7.13 Other Ancillary Studies in Diabetic Macular Edema 178
7.14 Natural History 178
7.15 Treatments 179
7.15.1 Metabolic Control and Effects of Drugs 179
7.16 Focal/Grid Laser Photocoagulation 180
7.16.1 ETDRS Treatment of CSME 180
7.17 Evolution in Focal/Grid Laser Treatment Since the ETDRS 184
7.18 Macular Thickness Outcomes After Focal/Grid Photocoagulation 185
7.19 Resolution of Lipid Exudates After Focal/Grid Laser Photocoagulation 186
7.20 Inconsistency in Defining Refractory Diabetic Macular Edema 187
7.21 Alternative Forms of Laser Treatment for Diabetic Macular Edema 187
7.22 Peribulbar Triamcinolone Injection 188
7.23 Intravitreal Triamcinolone Injection 188
7.24 Intravitreal Dexamethasone Delivery System 189
7.25 Intravitreal Injections of Anti-VEGF Drugs 189
7.26 Combined Intravitreal Anti-VEGF Drugs and Triamcinolone 190
7.27 Combined Intravitreal and Peribulbar Triamcinolone and Focal Laser Therapy 190
7.28 Vitrectomy 190
7.29 Supplemental Oxygen and Hyperbaric Oxygenation 196
7.30 Resection of Subfoveal Hard Exudates 196
7.31 Subclinical Diabetic Macular Edema 196
7.32 Cases with Simultaneous Indications for Focal and Scatter Laser Photocoagulation 198
7.33 Exacerbation of Diabetic Macular Edema by Scatter Photocoagulation 198
7.34 Factors Influencing Treatment of Diabetic Macular Edema 199
7.35 Sequence of Therapy 199
7.36 Interaction of Cataract Surgery and Diabetic Macular Edema 201
7.37 Summary of Key Points 201
7.38 Future Directions 202
References 202
Diabetic Macular Ischemia 214
8.1 Introduction 214
8.2 Pathogenesis, Anatomy, and Physiology 214
8.3 Natural History 218
8.4 Clinical Evaluation 219
8.5 Clinical Significance of Diabetic Macular Ischemia 226
8.6 Controversies and Conundrums 227
8.7 Summary of Key Points 228
8.8 Future Directions 229
References 229
Treatment of Proliferative Diabetic Retinopathy 237
9.1 Introduction 237
9.2 Laser Photocoagulation 239
9.2.1 Indications 243
9.2.2 PRP Technique 246
9.2.3 Complications 253
9.2.4 Outcome 254
9.3 Intraocular Pharmacological Therapy 254
9.4 Vitreoretinal Surgery 256
9.4.1 Indications 256
9.4.2 Preoperative Management 266
9.4.3 Instrumentation 267
9.4.4 Techniques 269
9.4.5 Postoperative Management 277
9.4.6 Complications 278
9.4.7 General Outcome 283
9.5 Follow-Up Considerations in PDR 284
9.6 Case Management: Decision-Making in Complicated Cases 284
9.6.1 Cataract and PDR 284
9.6.2 Dense Vitreous Hemorrhage and Untreated PDR 286
9.6.3 Untreated PDR with Diabetic Macular Edema 286
9.6.4 PDR with Severe Fibrovascular Proliferation/Traction Retinal Detachment 287
9.6.5 PDR with Neovascular Glaucoma 287
9.6.6 Conditions Altering the Clinical Course of PDR 287
9.7 Summary of Key Points 290
9.8 Future Directions 291
References 292
Cataract Surgery and Diabetic Retinopathy 315
10.1 Scope of the Problem of Diabetic Retinopathy Concomitant with Surgical Cataract 315
10.2 Visual Outcomes After Cataract Surgery in Patients with Diabetic Retinopathy 315
10.3 Postoperative Course and Special Considerations After Cataract Surgery in Patients with Diabetic Retinopathy 315
10.4 The Influence of Cataract Surgery on Diabetic Retinopathy 317
10.5 The Role of Ancillary Testing in Managing Cataract Surgery in Eyes with Diabetic Retinopathy 322
10.6 Candidate Risk and Protective Factors for Diabetic Macular Edema Induction or Exacerbation Following Cataract Surgery and Suggested Management Actions 322
10.7 The Problem of Adherence to Preferred Practice Guidelines 323
10.8 Management of the Diabetic Eye Without Macular Edema About to Undergo Cataract Surgery 323
10.9 Treatment of Diabetic Macular Edema Detected Before Cataract Surgery When the Macular View Is Clear 324
10.10 Management When Cataract Sufficient to Obscure the Macular View and DME Coexist or When Refractory DME and Cataract Coexist 325
10.11 Patients with Simultaneous Indications for Panretinal Photocoagulation and Cataract Surgery 325
10.12 Management of Cataract in Patients with Diabetic Retinopathy Undergoing Vitrectomy 326
10.13 Influence of Vitrectomy Surgery on Cataract Formation 326
10.14 Summary Flow Chart of Management Principles and Estimated Outcomes for Diabetic Eyes Facing Cataract Surgery 327
10.15 Postoperative Endophthalmitis in Patients with Diabetic Retinopathy 328
10.16 Summary of Key Points 328
10.17 Future Directions 329
References 329
The Relationship of Diabetic Retinopathy and Glaucoma 334
11.1 Interaction of Diabetes and Glaucoma 334
11.2 Iris and Angle Neovascularization Pathoanatomy and Pathophysiology 335
11.3 Epidemiology 337
11.4 Clinical Detection 338
11.5 Classification 341
11.6 Risk Factors for Iris Neovascularization 341
11.7 Entry Site Neovascularization After Pars Plana Vitrectomy 343
11.8 Anterior Hyaloidal Fibrovascular Proliferation 344
11.9 Treatments for Iris Neovascularization 344
11.10 Modifiers of Behavior of Iris Neovascularization 345
11.11 Management of Neovascular Glaucoma 346
11.12 Summary of Key Points 350
11.13 Future Directions 350
References 350
The Cornea in Diabetes Mellitus 356
12.1 Introduction 356
12.2 Pathophysiology 356
12.3 Anatomy and Morphological Changes 357
12.4 Clinical Manifestations 358
12.5 Ocular Surgery 359
12.6 Treatment of Corneal Disease in Diabetes Mellitus 360
12.7 Conclusion 360
12.8 Summary of Key Points 360
12.9 Future Directions 361
References 361
Optic Nerve Disease in Diabetes Mellitus 365
13.1 Relevant Normal Optic Nerve Anatomy and Physiology 365
13.2 The Effect of Diabetes on the Optic Nerve 366
13.3 Nonarteritic Anterior Ischemic Optic Neuropathy and Diabetes 367
13.4 Diabetic Papillopathy 369
13.5 Disk Edema Associated with Vitreous Traction 370
13.6 Superior Segmental Optic Hypoplasia (Topless Optic Disk Syndrome) 370
13.7 Wolfram Syndrome 371
13.8 Summary of Key Points 372
13.9 Future Directions 373
References 373
Screening for Diabetic Retinopathy 377
14.1 Introduction 377
14.2 Who Does Not Need to Be Screened 378
14.3 Screening for Diabetic Retinopathy by Adjunctive or Stand-Alone Visual Acuity Testing 378
14.4 Screening with Undilated Direct Ophthalmoscopy by Non-eye Care Professionals 378
14.5 Screening with Dilated Ophthalmoscopy by Ophthalmic Technicians or Optometrists 379
14.6 Screening with Dilated Ophthalmoscopy by Ophthalmologists 379
14.7 Screening with Dilated Ophthalmoscopy by Retina Specialists 380
14.8 Photographic Screening 381
14.9 Nonmydriatic Photography 383
14.10 Mydriatic Photography 384
14.11 Risk Factors for Ungradable Photographs 384
14.12 Number of Photographic Fields 384
14.13 Criteria for Referral 384
14.14 Obstacles to the Use of Teleophthalmic Screening Methods 385
14.15 Combination Methods of Screening 385
14.16 Case Yield Rates 385
14.17 Compliance with Recommendation to Be Seen by an Ophthalmologist 386
14.18 Intravenous Fluorescein Angiography and Oral Fluorescein Angioscopy 386
14.19 Automated Fundus Image Interpretation 387
14.20 Subgroups Needing Enhanced Screening Efforts 387
14.21 Screening in Pregnancy 387
14.22 Economic Considerations 387
14.23 Comparisons of the Screening Methods 388
14.24 Accountability of Screening Programs 390
14.25 Summary of Key Points 390
14.26 Future Directions 390
References 391
Practical Concerns with Ethical Dimensions in the Management of Diabetic Retinopathy 394
15.1 Incorporating Ancillary Testing in the Management of Patients with Diabetic Retinopathy 394
15.2 Patients with Sight-Threatening Diabetic Retinopathy and Insufficient or No Ability to Address Medical Bills 399
15.2.1 Case 1 399
15.2.2 Case 2 401
15.3 Communications with Primary-Care Physicians 402
15.4 Working in a Managed Care Environment (Capitation) 402
15.5 Interactions with Medical Industry 403
15.6 Interactions with Ambulatory Surgery Centers 406
15.7 Comanagement of Patients 406
15.8 Relationships with Investment Firms 406
15.9 Summary of Key Points 406
15.10 Future Directions 406
References 407
Clinical Examples in Managing Diabetic Retinopathy 409
16.1 Case 1: Proliferative Diabetic Retinopathy with Dense Premacular Hemorrhage in a Patient on Coumadin 409
16.1.1 Discussion 409
16.2 Case 2: Bilateral Proliferative Diabetic Retinopathy with Acute Vitreous Hemorrhage in One Eye and a Chronic Traction Retinal Detachment in the Other Eye 411
16.2.1 Discussion 412
16.2.2 Opinion 1 413
16.2.3 Opinion 2 414
16.2.4 Opinion 3 414
16.3 Case 3: Sight Threatening Diabetic Retinopathy in a Patient with Concomitant Medical and Socioeconomic Problems 415
16.3.1 Discussion 415
16.4 Case 4: Asymptomatic Retinal Detachment Following Vitrectomy in a Patient Who Has Had Panretinal Laser Photocoagulation 416
16.4.1 Discussion 417
16.5 Case 5: Management of Progressive Vitreous Hemorrhage Following Scatter Photocoagulation for Proliferative Diabetic Retinopathy 417
16.5.1 Discussion 418
16.6 Case 6: Post-surgical, Inflammatory Macular Edema, or Diabetic Macular Edema? 419
16.6.1 Discussion 420
16.7 Case 7: Proliferative Diabetic Retinopathy with Macular Traction and Ischemia 421
16.7.1 Discussion 421
16.8 Case 8: What Is Maximal Focal/Grid Laser Photocoagulation for Diabetic Macular Edema? 425
16.8.1 Definition of the Problem 425
16.8.2 Discussion 426
16.9 Case 9: What Independent Information Does Macular Perfusion Add to Patient Management in Diabetic Retinopathy? 429
16.9.1 Discussion 429
16.10 Case 10: Macular Edema Following Panretinal Photocoagulation for Proliferative Diabetic Retinopathy 431
16.10.1 Discussion 431
16.11 Case 11: Diabetic Macular Edema with a Subfoveal Scar 433
16.11.1 Discussion 433
16.12 Case 12: How Does the Severity of Diabetic Macular Edema Affect the Therapeutic Approach? 434
16.12.1 Definition of the Problem 434
16.12.2 Discussion 436
16.13 Case 13: Management Options for a Complicated Case of Proliferative Diabetic Retinopathy with Severe Fibrovascular Proliferation, Sub-clinical Macular Edema, and Recent Vitreous Hemorrhage 438
16.13.1 Definition of the Problem 438
16.13.2 Discussion 438
16.14 Case 14: How Is Diabetic Macular Ischemia Related to Visual Acuity? 440
16.14.1 Definition of the Problem 440
16.14.2 Discussion 441
References 442
Subject Index 446