Diagnosis & Diagnosis & Management of Management of

Diabetic Eye DiseaseDiabetic Eye Disease

A. Paul Chous, M.A., O.D., F.A.A.O.A. Paul Chous, M.A., O.D., F.A.A.O.

Tacoma, WATacoma, WASpecializing in Diabetes Eye Care & EducationSpecializing in Diabetes Eye Care & Education

Part 2Part 2

Biochemical InfluencesBiochemical Influences In large vessels: In large vessels:

Free fatty acids (FFAs) cause Free fatty acids (FFAs) cause inflammation, dyslipidemia, and inflammation, dyslipidemia, and atherosclerosis atherosclerosis

Small, dense LDLSmall, dense LDL Increased blood viscosity & vessel Increased blood viscosity & vessel

rigidity causes HTNrigidity causes HTN Increased platelet adhesionIncreased platelet adhesion

Visceral Adipose Visceral Adipose TissueTissue

Visceral fat releases substances Visceral fat releases substances that cause insulin resistance that cause insulin resistance and mobilize non-esterified and mobilize non-esterified fatty acids (Free Fatty Acids)fatty acids (Free Fatty Acids)

Insulin resistance Insulin resistance HyperglycemiaHyperglycemia

FFAs are oxidized by vascular FFAs are oxidized by vascular endothelium endothelium inflammatory inflammatory cytokines (PAI-1, CRP & more)cytokines (PAI-1, CRP & more)

Large vessel

A Unifying Mechanism for A Unifying Mechanism for Microvascular and Macrovascular Microvascular and Macrovascular Diabetes ComplicationsDiabetes Complications

FFAs GluPolyolHexosaminePKCAGEs

Adapted source: Michael Brownlee, M.D.

Small vessel

Hemodynamic InfluencesHemodynamic Influences

Conditions that increase retinal blood Conditions that increase retinal blood flow increase the risk of severe DRTflow increase the risk of severe DRT– HyperglycemiaHyperglycemia– Systemic hypertensionSystemic hypertension– PregnancyPregnancy– Ocular hypotensionOcular hypotension

Other InfluencesOther Influences

Genetic SusceptibilitiesGenetic Susceptibilities HaptoglobinHaptoglobin Lipid SNPsLipid SNPs

Endocrine factorsEndocrine factors Growth hormone (GH) and Growth hormone (GH) and

Insulin-like growth factors (IGF)Insulin-like growth factors (IGF)

Diabetic Eye Disease

Diabetes Epidemic

Microvascular BiochemistryPKC, AGEs, Polyol Flux, Hexosamine

Macrovascular BiochemistryGlycated LDL, sticky platelets, CRPCAMs/leukocyte adhesion, 4 pathways

Increased Blood Flow:Shear Stress

Shunting

Factors Contributing to Diabetic Eye Disease

Hypertension

Pericyte Damage

Pericyte Damage

Hormonal Factors & Individual Genetic Susceptibility

It’s Not Just The Eye…..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)

Diagnosis & Management of Diagnosis & Management of Distinct EntitiesDistinct Entities

““Diabetic Eye Disease” refers to ocular Diabetic Eye Disease” refers to ocular pathologies more commonly seen in pathologies more commonly seen in patients with diabetespatients with diabetes

All of these conditions are attributable, All of these conditions are attributable, at least in part, to chronic at least in part, to chronic hyperglycemiahyperglycemia

Ocular Diseases Ocular Diseases Associated With DiabetesAssociated With Diabetes

CataractCataract KeratopathyKeratopathy Efferent Cranial NeuropathyEfferent Cranial Neuropathy GlaucomaGlaucoma Ischemic Optic NeuropathyIschemic Optic Neuropathy Retinal Vascular OcclusionRetinal Vascular Occlusion Diabetic RetinopathyDiabetic Retinopathy