Contents -- Preface -- List of Contributors -- Chapter 1 Standards of Medical Care in Diabetes - 2009 American Diabetes Association -- 1.1. Classification and Diagnosis -- 1.1.1. Classification -- 1.1.2. Diagnosis of Diabetes -- 1.1.3. Diagnosis of Prediabetes -- 1.2. Testing for Prediabetes and Diabetes in Asymptomatic Patients -- 1.2.1. Testing for Prediabetes and Type 2 Diabetes in Adults -- 1.2.2. Testing for Type 2 Diabetes in Children -- 1.2.3. Screening for Type 1 Diabetes -- 1.3. Detection and Diagnosis of GDM -- 1.4. Prevention/Delay of Type 2 Diabetes -- 1.5. Diabetes Care -- 1.5.1. Initial Evaluation -- 1.5.2. Management -- 1.5.3. Glycemic Control -- 1.5.3.1. Assessment of glycemic control -- 1.5.3.2. Glycemic goals in adults -- 1.6. Prevention and Management of Diabetes Complications -- 1.6.1. CVD -- 1.6.1.1. Hypertension/blood pressure control -- 1.6.1.2. Dyslipidemia/lipid management -- 1.6.1.3. Antiplatelet agents -- 1.6.1.4. Smoking cessation -- 1.6.2. Retinopathy Screening and Treatment -- References -- Chapter 2 Clinical Presentation of Retinopathy José Cunha-Vaz -- 2.1. Preclinical Stage -- 2.2. Nonproliferative Diabetic Retinopathy -- 2.3. Complications of Diabetic Retinal Disease -- 2.3.1. Diabetic Macular Edema -- 2.3.2. Preproliferative and Proliferative Diabetic Retinopathy -- References -- Chapter 3 Clinical Diagnostic Methodologies -- 3.1. Fundus Photography and Fluorescein Angiography Lilianne Duarte and José Cunha-Vaz -- 3.1.1. Mild Nonproliferative Retinopathy -- 3.1.2. Moderate Nonproliferative Retinopathy Without Macular Edema -- 3.1.3. Nonproliferative Retinopathy with Clinically Significant Macular Edema -- 3.1.4. Severe Nonproliferative Retinopathy -- 3.1.5. Diabetic Retinopathy Screening.

3.1.6. Grading Diabetic Retinopathy from Stereoscopic Color Fundus Photographs-an Extension of the Modified Airlie House Classification. ETDRS Report Number 10 -- References -- 3.2. Measurements of Retinal Thickness João Figueira, Rui Bernardes and José Cunha-Vaz -- 3.2.1. Retinal Thickness Analyzer (RTA) -- 3.2.2. Optical Coherence Tomography (OCT) -- 3.2.3. Retinal Thickness Measurements -- 3.2.4. Macular Edema -- References -- 3.3. Vitreous Fluorometry and Retinal Leakage Measurements José Cunha-Vaz and Conceição Lobo -- 3.3.1. Basic Principles of Ocular Fluorometry -- 3.3.1.1. Quantitative Measurement of Fluorescein -- 3.3.1.2. Instrumentation and Measurement -- 3.3.1.3. Evaluation of Blood-retinal Barrier Permeability -- 3.3.2. Retinal Leakage Analyzer -- 3.3.3. Experimental Studies -- 3.3.4. Clinical Studies -- 3.3.5. Prognostic Value of Leakage Measurements -- References -- 3.4. Blood Flow José Cunha-Vaz -- 3.4.1. General Hemodynamic Principles -- 3.4.2. Pressure-Volume Relationships -- 3.4.3. Retinal Blood Volume -- 3.4.4. Pressure-Flow Relationships -- 3.4.5. Biophysical Factors Affecting Retinal Capillary Flow -- 3.4.6. Velocity and Intermittence of Retinal Capillary Flow -- 3.4.7. Regulation of Retinal Capillary Blood Flow -- 3.4.8. Autoregulation of Retinal Blood Flow -- 3.4.9. Measurement of Blood Flow -- 3.4.10. Retinal Blood Flow in Diabetes -- References -- 3.5. Retinal Neural Impairment Miguel Castelo-Branco -- 3.5.1. New Psychophysical Techniques to Assess Retinal Neural Impairment in Diabetic Retinopathy -- 3.5.2. Classical Electrophysiological Findings in Diabetic Retinopathy -- 3.5.3. Oscillatory Potentials (OPs) -- 3.5.4. Pattern ERG -- 3.5.5. Multifocal Electrophysiology -- 3.5.6. Future Directions -- References -- Abbreviations -- 3.6. Multimodal Macula Mapping Rui Bernardes, Conceição Lobo and José Cunha-Vaz.

3.6.1. Imaging Systems -- 3.6.2. Multimodal Macula Mapping. Integration of Information and Representation -- 3.6.3. Multimodal Macula Mapping -- 3.6.4. Contribution to the Evaluation of Diabetic Retinopathy -- References -- Chapter 4 Pathogenesis -- 4.1. Molecular Mechanisms Paulo Pereira -- 4.1.1. Glucose Transport in the Retina -- 4.1.2. Aldose Reductase and Polyol Pathway -- 4.1.3. Protein Glycation -- 4.1.4. VEGF and Angiogenesis -- 4.1.5. Activation of Protein Kinase C -- 4.1.6. Oxidative Stress -- 4.1.7. Hyperglycemia and Oxidative Damage: A Unifying Hypothesis -- 4.1.8. Hyperglycemia and Production of Superoxide -- 4.1.9. Activation of Hexosamine Pathway -- 4.1.10. Activation of PKC -- 4.1.11. Formation of AGEs -- 4.1.12. Production of Nitric Oxide -- 4.1.13. Animal Models -- 4.1.14. Genetic Factors -- References -- 4.2. Cell Factors António Francisco Ambrósio -- 4.2.1. Cell Changes Relevant to Blood-Retinal Barrier Breakdown -- 4.2.2. Tight Junctions -- 4.2.3. Alterations in Tight Junctions Expression and Phosphorylation -- 4.2.4. Microvascular Cell Death -- 4.2.5. Neuronal Dysfunction and Death -- 4.2.6. Glial Cells Reactivity and Changes -- 4.2.7. Glutamate Excitotoxicity in Diabetic Retinopathy: Involvement of Neurons and Glial Cells -- 4.2.8. Microglia -- 4.2.9. The Outsiders: Leukocytes and Platelets -- 4.2.10. Low-Grade Chronic Inflammation -- 4.2.11. Microthrombosis -- 4.2.12. Concluding Remarks -- References -- 4.3. Neovascularization in Diabetic Retinopathy Ermelindo Leal and António Francisco Ambrósio -- 4.3.1. Ischemia and Neovascularization in Diabetic Retinopathy -- 4.3.2. Growth Factors -- 4.3.3. Basic Fibroblast Growth Factor (bFGF) -- 4.3.4. Insulin-Like Growth Factors (IGF) -- 4.3.5. Platelet-Derived Growth Factor (PDGF) -- 4.3.6. Vascular Endothelial Growth Factor (VEGF) -- 4.3.7. Conclusions -- References.

4.4. Candidate Genes of Diabetic Retinopathy Alda Ambrósio -- 4.4.1. Molecular Genetics Approaches to Gene Mapping in Complex Human Disease -- 4.4.2. Genetic Susceptibility in Diabetic Retinopathy -- 4.4.3. Candidate Genes in Diabetic Retinopathy -- 4.4.4. Aldose Reductase Gene -- 4.4.5. VEGF Gene -- 4.4.6. RAGE Gene -- 4.4.7. Angiotensin-Converting Enzyme Gene -- 4.4.8. PAI-1 Gene -- 4.4.9. Endothelin Genes -- 4.4.10. Nitric Oxide Synthase Genes -- 4.4.11. Other Candidate Genes -- 4.4.12. Concluding Remarks -- References -- Chapter 5 Epidemiology José Rui Faria Abreu -- 5.1. Prevalence of Visual Impairment -- 5.1.1. Prevalence of Visual Impairment in Diabetic Patients 168 -- 5.1.2. Prevalence of Blindness in Diabetic Patients -- 5.2. Incidence of Visual Impairment -- 5.2.1. Visual Impairment -- 5.2.1.1. Type 1 diabetes -- 5.2.1.2. Type 2 diabetes -- 5.2.2. Blindness -- 5.2.2.1. Type 1 diabetes -- 5.2.2.2. Type 2 diabetes -- 5.3. Risk Factors for Visual Loss -- 5.3.1. Sex -- 5.3.3. Age -- 5.3.4. Duration of Diabetes -- 5.3.5. Severity of Retinopathy -- 5.3.6. Macular Edema -- 5.3.7. Metabolic Control -- 5.3.8. Hypertension -- 5.3.9. Nephropathy -- 5.4. Economic Costs of Visual Impairment and Blindness -- 5.5. Prevalence of Retinopathy -- 5.5.1. Type 1 Diabetes -- 5.5.2. Type 2 Diabetes -- 5.6. Risk Factors of Retinopathy -- 5.6.1. Type 1 Diabetes -- 5.6.1.1. Duration of diabetes -- 5.6.1.2. Age at diagnosis -- 5.6.1.3. Glycemic control -- 5.6.1.4. Blood pressure control -- 5.6.1.5. Pregnancy -- 5.6.1.6. Height, weight and body mass index (BMI) -- 5.6.1.7. Serum lipid levels -- 5.6.1.8. Proteinuria -- 5.6.1.9. Cigarette smoking -- 5.6.1.10. Alcohol -- 5.6.1.11. Physical activity -- 5.6.1.12. Myopia -- 5.6.2. Type 2 Diabetes -- 5.6.2.1. Duration of diabetes -- 5.6.2.2. Age at examination -- 5.6.2.3. Treatment -- 5.6.2.4. Glycemic control.

5.6.2.5. Blood pressure -- 5.6.2.6. Cholesterol and triglycerides -- 5.6.2.7. Renal involvement -- 5.6.2.8. Body mass index (BMI) -- 5.6.2.9. Cigarette smoking and alcohol -- 5.6.2.10. Physical activity -- 5.6.2.11. Cataract extraction -- 5.7. Retinopathy, Comorbidity and Mortality -- 5.7.1. Comorbidity -- 5.7.2. Mortality -- 5.8. Health Care Delivery -- 5.8.1. Economy -- 5.8.1.1. Identification of costs of screening and treatment -- 5.8.1.2. Quality of life -- 5.8.1.3. Health care economic analyses -- 5.8.1.4. Cost-effectiveness in diabetic retinopathy -- References -- Chapter 6 Major Clinical Trials on Treatment for Diabetic Retinopathy Luisa Ribeiro -- Clinical Trials -- 6.1. Photocoagulation -- 6.1.1. Diabetic Retinopathy Study (DRS) -- 6.1.2. Early Treatment Diabetic Retinopathy Study (ETDRS) -- 6.2. Vitrectomy -- 6.2.1. Diabetic Retinopathy Vitrectomy Study (DRVS) -- 6.3. Medical Approaches -- 6.3.1 Diabetes Control and Complications Trial (DCCT) -- 6.3.2 United Kingdom Prospective Diabetes Study (UKPDS) -- References -- Chapter 7 Photocoagulation for Macular Edema and Proliferative Retinopathy Francisco Goméz-Ulla -- 7.1. Rationale and Results of Photocoagulation -- 7.1.1. Diabetic Macular Edema: Results -- 7.1.2. Proliferative Diabetic Retinopathy: Results -- 7.2. Clinical Evaluation and Pre-treatment Options -- 7.2.1. Macular Edema -- 7.2.2. Proliferative Diabetic Retinopathy -- 7.3. Laser Treatment Techniques -- 7.3.1. Macular Edema -- 7.3.2. Proliferative Retinopathy -- 7.4. Post-operative Follow-up and Complications -- 7.4.1. Macular Edema -- 7.4.2. Proliferative Retinopathy -- 7.5. Special Cases -- 7.5.1. Proliferative Retinopathy and Macular Edema -- 7.5.2. Macular Edema and Traction -- 7.5.3. Diabetic Retinopathy and Cataract Surgery -- 7.5.4. Proliferative Retinopathy and Traction on Vitreous Hemorrhage.

7.6. Conclusions and General Guidelines.