- •Diabetic Retinopathy
- •Preface
- •Acknowledgments
- •Contents
- •Contributors
- •Pathophysiology of Diabetic Retinopathy
- •1.1 Retinal Anatomy
- •1.1.1 History
- •1.1.2 Anatomy
- •1.1.3 Microanatomy of the Retina Neurons
- •1.1.4 Intercellular Spaces
- •1.1.5 Internal Limiting Membrane
- •1.1.6 Circulation
- •1.1.7 Arteries
- •1.1.8 Veins
- •1.1.9 Capillaries
- •1.2 Hemodynamics, Macular Edema, and Starling’s Law
- •1.3 Biochemical Basis for Diabetic Retinopathy
- •1.3.1 Increased Polyol Pathway Flux
- •1.3.2 Advanced Glycation End Products (AGEs)
- •1.3.3 Activation of Protein Kinase C (PKC)
- •1.3.4 Increased Hexosamine Pathway Flux
- •1.4 Macular Edema
- •1.5 Development of Proliferative Diabetic Retinopathy
- •1.6 Summary of Key Points
- •1.7 Future Directions
- •References
- •Genetics and Diabetic Retinopathy
- •2.1 Background for Clinical Genetics
- •2.2 The Role of Polymorphisms in Genetic Studies
- •2.3 Types of Genetic Study Design
- •2.4 Studies of the Genetics of Diabetic Retinopathy
- •2.4.1 Clinical Studies
- •2.4.2 Molecular Genetic Studies
- •2.4.3 EPO Promoter
- •2.4.4 Aldose Reductase Gene
- •2.4.5 VEGF Gene
- •2.5 Genes in or Near the HLA Locus
- •2.6 Receptor for Advanced Glycation End Products (RAGE) Genes
- •2.7 Endothelial NOS2 and NOS3 Genes
- •2.9 Solute Carrier Family 2 (Facilitated Glucose Transporter), Member 1 Gene (SLC2A1)
- •2.11 Potential Value of Identifying Genetic Associations with Diabetic Retinopathy
- •2.12 Summary of Key Points
- •2.13 Future Directions
- •Glossary
- •References
- •Epidemiology of Diabetic Retinopathy
- •3.1 Introduction and Definitions
- •3.2 Epidemiology of Diabetes Mellitus
- •3.3 Factors Influencing the Prevalence of Diabetes Mellitus
- •3.4 Epidemiology of Diabetic Retinopathy
- •3.5 Diabetes and Visual Loss
- •3.6 Prevalence and Incidence of Diabetic Retinopathy
- •3.7 By Diabetes Type
- •3.8 By Insulin Use
- •3.10 By Duration of Diabetes Mellitus
- •3.11 By Ethnicity
- •3.12 Gender
- •3.13 Age at Onset of Diabetes
- •3.14 Socioeconomic Status and Educational Level
- •3.15 Family History of Diabetes
- •3.16 Changes Over Time
- •3.17 Epidemiology of Diabetic Macular Edema (DME)
- •3.18 Epidemiology of Proliferative Diabetic Retinopathy (PDR)
- •3.19 Socioeconomic Impact of Diabetes
- •3.20 Socioeconomic Impact of Diabetic Retinopathy
- •3.21 Summary of Key Points
- •3.22 Future Directions
- •References
- •Systemic and Ocular Factors Influencing Diabetic Retinopathy
- •4.1 Introduction
- •4.2 Systemic Factors
- •4.2.1 Glycemic Control
- •4.2.1.1 Type 1 Diabetes Mellitus
- •4.2.1.2 Type 2 Diabetes Mellitus
- •4.2.1.3 Rapidity of Improvement in Glycemic Control
- •4.2.2 Glycemic Variability
- •4.2.3 Insulin Use in Type 2 Diabetes
- •4.2.5 Blood Pressure
- •4.2.6 Serum Lipids
- •4.2.7 Anemia
- •4.2.8 Nephropathy
- •4.2.9 Pregnancy
- •4.2.10 Other Systemic Factors
- •4.2.11 Influence on Visual Loss
- •4.3 Effects of Systemic Drugs
- •4.3.1 Diuretics
- •4.3.3 Aldose Reductase Inhibitors
- •4.3.4 Drugs That Target Platelets
- •4.3.5 Statins
- •4.3.6 Protein Kinase C Inhibitors
- •4.3.7 Thiazolidinediones (Glitazones)
- •4.3.8 Miscellaneous Drugs
- •4.4 Ocular Factors Influencing Diabetic Retinopathy
- •4.6 Economic Consequences
- •4.7 Summary of Key Points
- •4.8 Future Directions
- •References
- •Defining Diabetic Retinopathy Severity
- •5.1 Summary of Key Points
- •5.2 Future Directions
- •5.3 Practice Exercises
- •References
- •6.1 Optical Coherence Tomography (OCT)
- •6.2 Heidelberg Retinal Tomograph (HRT)
- •6.3 Retinal Thickness Analyzer (RTA)
- •6.4 Microperimetry
- •6.5 Color Fundus Photography
- •6.6 Fluorescein Angiography
- •6.7 Ultrasonography
- •6.8 Multifocal ERG
- •6.9 Miscellaneous Modalities
- •6.10 Summary of Key Points
- •6.11 Future Directions
- •6.12 Practice Exercises
- •References
- •Diabetic Macular Edema
- •7.1 Epidemiology and Risk Factors
- •7.2 Pathophysiology and Pathoanatomy
- •7.2.1 Anatomy
- •7.3 Physiology
- •7.4 Clinical Definitions
- •7.5 Focal and Diffuse Diabetic Macular Edema
- •7.6 Subclinical Diabetic Macular Edema
- •7.7 Refractory Diabetic Macular Edema
- •7.8 Regressed Diabetic Macular Edema
- •7.9 Recurrent Diabetic Macular Edema
- •7.10 Methods of Detection of Diabetic Macular Edema
- •7.11 Case Report 1
- •7.12 Case Report 2
- •7.13 Other Ancillary Studies in Diabetic Macular Edema
- •7.14 Natural History
- •7.15 Treatments
- •7.15.1 Metabolic Control and Effects of Drugs
- •7.16 Focal/Grid Laser Photocoagulation
- •7.16.1 ETDRS Treatment of CSME
- •7.17 Evolution in Focal/Grid Laser Treatment Since the ETDRS
- •7.18 Macular Thickness Outcomes After Focal/Grid Photocoagulation
- •7.19 Resolution of Lipid Exudates After Focal/Grid Laser Photocoagulation
- •7.20 Inconsistency in Defining Refractory Diabetic Macular Edema
- •7.21 Alternative Forms of Laser Treatment for Diabetic Macular Edema
- •7.22 Peribulbar Triamcinolone Injection
- •7.23 Intravitreal Triamcinolone Injection
- •7.24 Intravitreal Dexamethasone Delivery System
- •7.27 Combined Intravitreal and Peribulbar Triamcinolone and Focal Laser Therapy
- •7.28 Vitrectomy
- •7.29 Supplemental Oxygen and Hyperbaric Oxygenation
- •7.30 Resection of Subfoveal Hard Exudates
- •7.31 Subclinical Diabetic Macular Edema
- •7.32 Cases with Simultaneous Indications for Focal and Scatter Laser Photocoagulation
- •7.34 Factors Influencing Treatment of Diabetic Macular Edema
- •7.35 Sequence of Therapy
- •7.36 Interaction of Cataract Surgery and Diabetic Macular Edema
- •7.37 Summary of Key Points
- •7.38 Future Directions
- •References
- •Diabetic Macular Ischemia
- •8.1 Introduction
- •8.2 Pathogenesis, Anatomy, and Physiology
- •8.3 Natural History
- •8.4 Clinical Evaluation
- •8.5 Clinical Significance of Diabetic Macular Ischemia
- •8.6 Controversies and Conundrums
- •8.7 Summary of Key Points
- •8.8 Future Directions
- •References
- •Treatment of Proliferative Diabetic Retinopathy
- •9.1 Introduction
- •9.2 Laser Photocoagulation
- •9.2.1 Indications
- •9.2.2 PRP Technique
- •9.2.3 Complications
- •9.2.4 Outcome
- •9.3 Intraocular Pharmacological Therapy
- •9.4 Vitreoretinal Surgery
- •9.4.1 Indications
- •9.4.2 Preoperative Management
- •9.4.3 Instrumentation
- •9.4.4 Techniques
- •9.4.5 Postoperative Management
- •9.4.6 Complications
- •9.4.7 General Outcome
- •9.5 Follow-Up Considerations in PDR
- •9.6.1 Cataract and PDR
- •9.6.2 Dense Vitreous Hemorrhage and Untreated PDR
- •9.6.3 Untreated PDR with Diabetic Macular Edema
- •9.6.4 PDR with Severe Fibrovascular Proliferation/Traction Retinal Detachment
- •9.6.5 PDR with Neovascular Glaucoma
- •9.6.6 Conditions Altering the Clinical Course of PDR
- •9.7 Summary of Key Points
- •9.8 Future Directions
- •References
- •Cataract Surgery and Diabetic Retinopathy
- •10.1 Scope of the Problem of Diabetic Retinopathy Concomitant with Surgical Cataract
- •10.2 Visual Outcomes After Cataract Surgery in Patients with Diabetic Retinopathy
- •10.3 Postoperative Course and Special Considerations After Cataract Surgery in Patients with Diabetic Retinopathy
- •10.4 The Influence of Cataract Surgery on Diabetic Retinopathy
- •10.5 The Role of Ancillary Testing in Managing Cataract Surgery in Eyes with Diabetic Retinopathy
- •10.6 Candidate Risk and Protective Factors for Diabetic Macular Edema Induction or Exacerbation Following Cataract Surgery and Suggested Management Actions
- •10.7 The Problem of Adherence to Preferred Practice Guidelines
- •10.8 Management of the Diabetic Eye Without Macular Edema About to Undergo Cataract Surgery
- •10.9 Treatment of Diabetic Macular Edema Detected Before Cataract Surgery When the Macular View Is Clear
- •10.10 Management When Cataract Sufficient to Obscure the Macular View and DME Coexist or When Refractory DME and Cataract Coexist
- •10.11 Patients with Simultaneous Indications for Panretinal Photocoagulation and Cataract Surgery
- •10.12 Management of Cataract in Patients with Diabetic Retinopathy Undergoing Vitrectomy
- •10.13 Influence of Vitrectomy Surgery on Cataract Formation
- •10.15 Postoperative Endophthalmitis in Patients with Diabetic Retinopathy
- •10.16 Summary of Key Points
- •10.17 Future Directions
- •References
- •The Relationship of Diabetic Retinopathy and Glaucoma
- •11.1 Interaction of Diabetes and Glaucoma
- •11.2 Iris and Angle Neovascularization Pathoanatomy and Pathophysiology
- •11.3 Epidemiology
- •11.4 Clinical Detection
- •11.5 Classification
- •11.6 Risk Factors for Iris Neovascularization
- •11.7 Entry Site Neovascularization After Pars Plana Vitrectomy
- •11.8 Anterior Hyaloidal Fibrovascular Proliferation
- •11.9 Treatments for Iris Neovascularization
- •11.10 Modifiers of Behavior of Iris Neovascularization
- •11.11 Management of Neovascular Glaucoma
- •11.12 Summary of Key Points
- •11.13 Future Directions
- •References
- •The Cornea in Diabetes Mellitus
- •12.1 Introduction
- •12.2 Pathophysiology
- •12.3 Anatomy and Morphological Changes
- •12.4 Clinical Manifestations
- •12.5 Ocular Surgery
- •12.6 Treatment of Corneal Disease in Diabetes Mellitus
- •12.7 Conclusion
- •12.8 Summary of Key Points
- •12.9 Future Directions
- •References
- •Optic Nerve Disease in Diabetes Mellitus
- •13.1 Relevant Normal Optic Nerve Anatomy and Physiology
- •13.2 The Effect of Diabetes on the Optic Nerve
- •13.3 Nonarteritic Anterior Ischemic Optic Neuropathy and Diabetes
- •13.4 Diabetic Papillopathy
- •13.5 Disk Edema Associated with Vitreous Traction
- •13.6 Superior Segmental Optic Hypoplasia (Topless Optic Disk Syndrome)
- •13.7 Wolfram Syndrome
- •13.8 Summary of Key Points
- •13.9 Future Directions
- •References
- •Screening for Diabetic Retinopathy
- •14.1 Introduction
- •14.2 Who Does Not Need to Be Screened
- •14.5 Screening with Dilated Ophthalmoscopy by Ophthalmic Technicians or Optometrists
- •14.6 Screening with Dilated Ophthalmoscopy by Ophthalmologists
- •14.7 Screening with Dilated Ophthalmoscopy by Retina Specialists
- •14.8 Photographic Screening
- •14.9 Nonmydriatic Photography
- •14.10 Mydriatic Photography
- •14.11 Risk Factors for Ungradable Photographs
- •14.12 Number of Photographic Fields
- •14.13 Criteria for Referral
- •14.14 Obstacles to the Use of Teleophthalmic Screening Methods
- •14.15 Combination Methods of Screening
- •14.16 Case Yield Rates
- •14.17 Compliance with Recommendation to Be Seen by an Ophthalmologist
- •14.18 Intravenous Fluorescein Angiography and Oral Fluorescein Angioscopy
- •14.19 Automated Fundus Image Interpretation
- •14.20 Subgroups Needing Enhanced Screening Efforts
- •14.21 Screening in Pregnancy
- •14.22 Economic Considerations
- •14.23 Comparisons of the Screening Methods
- •14.24 Accountability of Screening Programs
- •14.25 Summary of Key Points
- •14.26 Future Directions
- •References
- •Practical Concerns with Ethical Dimensions in the Management of Diabetic Retinopathy
- •15.1 Incorporating Ancillary Testing in the Management of Patients with Diabetic Retinopathy
- •15.2.1 Case 1
- •15.2.2 Case 2
- •15.4 Working in a Managed Care Environment (Capitation)
- •15.5 Interactions with Medical Industry
- •15.7 Comanagement of Patients
- •15.9 Summary of Key Points
- •15.10 Future Directions
- •References
- •Clinical Examples in Managing Diabetic Retinopathy
- •16.1.1 Discussion
- •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
- •16.2.1 Discussion
- •16.2.2 Opinion 1
- •16.2.3 Opinion 2
- •16.2.4 Opinion 3
- •16.3 Case 3: Sight Threatening Diabetic Retinopathy in a Patient with Concomitant Medical and Socioeconomic Problems
- •16.3.1 Discussion
- •16.4 Case 4: Asymptomatic Retinal Detachment Following Vitrectomy in a Patient Who Has Had Panretinal Laser Photocoagulation
- •16.4.1 Discussion
- •16.5 Case 5: Management of Progressive Vitreous Hemorrhage Following Scatter Photocoagulation for Proliferative Diabetic Retinopathy
- •16.5.1 Discussion
- •16.6.1 Discussion
- •16.7 Case 7: Proliferative Diabetic Retinopathy with Macular Traction and Ischemia
- •16.7.1 Discussion
- •16.8 Case 8: What Is Maximal Focal/Grid Laser Photocoagulation for Diabetic Macular Edema?
- •16.8.1 Definition of the Problem
- •16.8.2 Discussion
- •16.9 Case 9: What Independent Information Does Macular Perfusion Add to Patient Management in Diabetic Retinopathy?
- •16.9.1 Discussion
- •16.10 Case 10: Macular Edema Following Panretinal Photocoagulation for Proliferative Diabetic Retinopathy
- •16.10.1 Discussion
- •16.11 Case 11: Diabetic Macular Edema with a Subfoveal Scar
- •16.11.1 Discussion
- •16.12.1 Definition of the Problem
- •16.12.2 Discussion
- •16.13.1 Definition of the Problem
- •16.13.2 Discussion
- •16.14 Case 14: How Is Diabetic Macular Ischemia Related to Visual Acuity?
- •16.14.1 Definition of the Problem
- •16.14.2 Discussion
- •References
- •Subject Index
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found on chromosome 4 causing optic atrophy, diabetes mellitus, and other neurological and endocrinologic signs.
13.9 Future Directions
The absence of effective therapy for NAION and of prophylactic treatment of proven efficacy for the fellow eye is potentially superable. Geographically widespread networks such as the Diabetic Retinopathy Clinical Research Network may provide the infrastructure to address potential therapies requiring large sample sizes for proper evaluation. Potentially promising therapies will probably arise from a better understanding of the physiology of the vascular supply to the anterior optic nerve. In particular, the hypothesis that central venous insufficiency in the setting of a small optic disk cup may be the causative insult is worthy of further exploration.26 Anti-vascular endothelial growth factor drugs given intravitreally may be a way to test this hypothesis, because it has been shown that they decrease venous congestion and disk edema in central retinal vein occlusion.99 These drugs may be able to abort the vicious cycle of disk edema, increased compression of capillaries, worsened ischemia, and further edema in a confined space.
It has been proposed that laser panretinal photocoagulation might cause optic atrophy and decompress the crowded scleral canal of patients who have had an episode of NAION in one eye.29 This hypothesis could be tested in a randomized clinical trial.
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