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Flowchart of Pathogenesis of diebetic retinopaty . Take reference from datta , zia & khurana

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pathogenesis diabetic retinopathy mechanisms Datta Khurana Zia

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diabetic retinopathy biochemical pathways polyol pathway PKC VEGF pericyte loss

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Pathogenesis of Diabetic Retinopathy Flowchart

Pathogenesis of Diabetic Retinopathy

Here is a structured breakdown of the flowchart, referenced from Datta, Zia (Eye Care of the Patient with Diabetes Mellitus, p. 34), and Khurana:

🔴 Starting Point: Chronic Hyperglycemia

1️⃣ Four Key Biochemical Pathways (Parallel)

PathwayMechanismEffect
Sorbitol / Polyol PathwayExcess glucose → Sorbitol via Aldose ReductaseOsmotic stress, NADPH depletion, oxidative damage
Advanced Glycation End-products (AGEs)Non-enzymatic glycation of proteinsBM thickening, crosslinking, pericyte dysfunction
Protein Kinase C (PKC) ActivationDiacylglycerol accumulation activates PKC↑ Vascular permeability, VEGF upregulation
Oxidative StressFree radical overproductionEndothelial cell injury, mitochondrial dysfunction

2️⃣ Retinal Microvascular Changes

  • Pericyte loss (earliest histological change)
  • Basement membrane thickening
  • Endothelial cell damage
  • Breakdown of the Blood-Retinal Barrier (BRB)
  • Increased vascular permeability

3️⃣ Non-Proliferative Diabetic Retinopathy (NPDR)

  • Microaneurysms (earliest clinical sign)
  • Dot & blot hemorrhages
  • Hard exudates (lipid leakage)
  • Cotton-wool spots (nerve fiber layer infarcts)
  • Venous beading
  • IRMA (Intraretinal Microvascular Abnormalities)

4️⃣ Retinal Ischemia → VEGF Release

  • Capillary non-perfusion → retinal hypoxia
  • VEGF secreted → drives neovascularization

5️⃣ Proliferative Diabetic Retinopathy (PDR)

  • NVD (Neovascularization at Disc) / NVE (elsewhere)
  • Vitreous hemorrhage
  • Tractional retinal detachment
  • Rubeosis iridis (iris neovascularization) → Neovascular glaucoma

6️⃣ Diabetic Macular Edema (DME) (Can occur at any stage)

  • BRB breakdown → fluid accumulation in macula
  • Macular thickening → central visual loss
References: Khurana AK – Comprehensive Ophthalmology; Datta & Zia – Eye Care of the Patient with Diabetes Mellitus (p. 34); supported by established biochemical pathway literature (sorbitol pathway, AGEs, PKC, VEGF).
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