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

2. Dr. Paul Chous received his undergraduate education at Brown University and the University of California at Irvine, where he was elected to Phi Beta Kappa in 1985. He received his Masters Degree in 1986 and his Doctorate of Optometry in 1991, both with highest honors from the University of California at Berkeley. Dr. Chous was selected as the Outstanding Graduating Optometrist in 1991. He has practiced in Renton, Kent, Auburn and Tacoma, Washington for the last 15 years, emphasizing diabetic eye disease and diabetes education. Dr. Chous has been a Type 1 diabetic since 1968. Dr. Chous serves as a consultant to dLife - Your Diabetes Life, Children With Diabetes, the Diabetes Exercise & Sports Association, and the American Diabetes Association, which honored him with its Distinguished Public Service Award in 1998. He is an Adjunct Faculty member at NOVA Southeastern University in Ft. Lauderdale, Florida. Dr. Chous has given numerous invited talks about diabetes and the eye to both patients and other health care professionals, a process which led him to write a unique and extremely important book aimed at diabetic patients, their families and friends: Diabetic Eye Disease: Lessons From A Diabetic Eye Doctor - How To Avoid Blindness and Get Great Eye Care.

3. The Problem of Diabetes & Diabetic Eye Disease Another American is Dx with DM every 24 seconds Another American is Dx with DM every 24 seconds 1.3 million new cases every year 1.3 million new cases every year Another American dies from a complication of diabetes every 2 minutes Another American dies from a complication of diabetes every 2 minutes More than 250,000 deaths each year More than 250,000 deaths each year The Problem

4. Diabetic Eye Disease Another American becomes legally blind from diabetic retinopathy every 30 minutes No independent tracking of irreparable vision loss from other eye diseases commonly associated with diabetes (retinal vascular occlusion, AION, glaucoma) Realistic accounting might increase the toll from 12-24 thousand to 30,000+ cases per year

5. The Pathobiology of Diabetic Eye Disease Biochemical & Hemodynamic Influences

6. Biochemical Influences In small vessels: In small vessels: Hyperglycemia causes mitochondrial over-production of reactive oxygen species (ROS) Hyperglycemia causes mitochondrial over-production of reactive oxygen species (ROS) This drives four major biochemical pathways that cause microvascular disease: This drives four major biochemical pathways that cause microvascular disease: Polyol Polyol Hexosamine Flux Hexosamine Flux Advanced Glycation Endproducts Advanced Glycation Endproducts Protein Kinase C Protein Kinase C

7. Each of these 4 pathways depends upon over-production of reactive oxygen species (Superoxide) by mitochondria Each of these 4 pathways depends upon over-production of reactive oxygen species (Superoxide) by mitochondria Intracellular Glucose & FFAs mitochondria ATP +  Superoxide (O 2 - ) Mitochondrian

8. Glucose Metabolism Glucose Glucose-6-phosphate Fructose-6-phosphate Glyceraldehyde-3-phosphate 1,3 Diphosphoglycerate (harmless metabolite) GAPDH Polyol Pathway Hexosamine Flux Protein Kinase C Advanced Glycation Endproducts ROS

9. Polyol Pathway Polyol Pathway Increased intracellular sorbitol leads to : Diabetic Peripheral Neuropathy, Diabetic Nephropathy, Diabetic Retinopathy, Keratopathy & Cataract

10. Hexosamine Pathway Hexosamine Pathway Increased levels of inflammatory cytokines lead to: Diabetic Nephropathy

11. AGE Pathway AGE Pathway Non-enzymatic glycation of proteins results in advanced glycation endproducts (AGEs) AGEs are a “biological cement” causing altered protein function and increased oxidative stress Retinopathy, Nephropathy, Neuropathy, Alzheimer’s, ED, Pulmonary Fibrosis…..

12. Protein Kinase C Pathway Protein Kinase C Pathway Increased Protein Kinase C (PKC) activates Vascular Endothelial Growth Factor (VEGF) leading to: Diabetic Macular Edema, Proliferative Retinopathy, Diabetic Kidney Disease