1. Diagnosis & Management of Diabetic Eye Disease A. Paul Chous, M.A., O.D., F.A.A.O. Tacoma, WA Specializing in Diabetes Eye Care & Education Part 2

2. Biochemical Influences In large vessels: In large vessels: Free fatty acids (FFAs) cause inflammation, dyslipidemia, and atherosclerosis Free fatty acids (FFAs) cause inflammation, dyslipidemia, and atherosclerosis Small, dense LDL Small, dense LDL Increased blood viscosity & vessel rigidity causes HTN Increased blood viscosity & vessel rigidity causes HTN Increased platelet adhesion Increased platelet adhesion

3. Visceral Adipose Tissue Visceral fat releases substances that cause insulin resistance and mobilize non-esterified fatty acids (Free Fatty Acids) Visceral fat releases substances that cause insulin resistance and mobilize non-esterified fatty acids (Free Fatty Acids) Insulin resistance  Hyperglycemia Insulin resistance  Hyperglycemia FFAs are oxidized by vascular endothelium  inflammatory cytokines (PAI-1, CRP & more) FFAs are oxidized by vascular endothelium  inflammatory cytokines (PAI-1, CRP & more)

4. Large vessel A Unifying Mechanism for Microvascular and Macrovascular Diabetes Complications  FFAs  Glu Polyol Hexosamine PKC AGEs Adapted source: Michael Brownlee, M.D. Small vessel

5. Hemodynamic Influences Conditions that increase retinal blood flow increase the risk of severe DRT –H–H–H–Hyperglycemia –S–S–S–Systemic hypertension –P–P–P–Pregnancy –O–O–O–Ocular hypotension

6. Other Influences Genetic Susceptibilities Genetic Susceptibilities Haptoglobin Haptoglobin Lipid SNPs Lipid SNPs Endocrine factors Endocrine factors Growth hormone (GH) and Insulin-like growth factors (IGF) Growth hormone (GH) and Insulin-like growth factors (IGF)

7. Diabetic Eye Disease Diabetes Epidemic Microvascular Biochemistry PKC, AGEs, Polyol Flux, Hexosamine Macrovascular Biochemistry Glycated LDL, sticky platelets, CRP CAMs/leukocyte adhesion, 4 pathways Increased Blood Flow: Shear Stress Shunting Factors Contributing to Diabetic Eye Disease Hypertension Pericyte Damage Hormonal Factors & Individual Genetic Susceptibility

8. It’s Not Just The Eye….. PDR Doubled the Risk of Cardiovascular Death in T1DM Over 8 Years (EURODIAB Complications Study, 2005) In T2DM, NPDR Conferred 1.3 -1.7 X Increased Risk of Death & PDR Increased Risk of Death 3-5 Fold Over 18 years (Diabetes Care 2007 Feb)

9. Diagnosis & Management of Distinct Entities “Diabetic Eye Disease” refers to ocular pathologies more commonly seen in patients with diabetes “Diabetic Eye Disease” refers to ocular pathologies more commonly seen in patients with diabetes All of these conditions are attributable, at least in part, to chronic hyperglycemia All of these conditions are attributable, at least in part, to chronic hyperglycemia

10. Ocular Diseases Associated With Diabetes Cataract Cataract Keratopathy Keratopathy Efferent Cranial Neuropathy Efferent Cranial Neuropathy Glaucoma Glaucoma Ischemic Optic Neuropathy Ischemic Optic Neuropathy Retinal Vascular Occlusion Retinal Vascular Occlusion Diabetic Retinopathy Diabetic Retinopathy