pathogenesis of diabetic retinopathy

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  • genetic studies, suggest that diabetic retinopathy is an interactions between
    • environmental factors, especially hyperglycaemia (1,2,3), and
    • several genetic factors
      • associated genes under study are aldose receptor, advanced glycation end products receptor, vascular endothelial growth factor, intercellular adhesion molecule 1, beta3-adrenergic receptor gene, hemochromatosis, and alpha2beta1 integrin (2)
  • the retinopathy in diabetes result from five fundamental processes (3)
    • retinal capillary microaneurysms
    • excessive vascular permeability
    • vascular occlusion
    • proliferation of new blood vessels and accompanying fibrous tissue
    • contraction of fibrovascular proliferations and vitreous
  • duration of diabetes and severity of hyperglycemia are the major risk factors for developing retinopathy (3)
  • severity of hyperglycemia is the key alterable risk factor (1)
  • increased retinal blood flow results in microaneurysm formation in capillaries, precapillary arterioles and venules, leading to occlusion and transudation of fluid and lipid. Hyperglycaemia is the cause of high retinal blood flow. Other factors such as pregnancy and high blood pressure will also lead to an increase in retinal blood flow
  • occlusion of capillaries results in retinal ischaemia with compensatory neovascularisation on the retina, iris, and optic disc (proliferative retinopathy)
  • ischaemic retina may express an unknown vasoproliferative substance leading to new vessel formation
  • vitreous haemorrhage may occur as a result of bleeding from new vessels
  • fibrous tissue is carried along with the new vessels; there is an increased risk of retinal detachment as a result of retraction of this tissue
  • cotton wool spots occur secondary to occlusion and represent retinal microinfarcts
  • retinal thickening (1), oedema and hard exudates occur as a result of leakage from capillaries; hard exudates are composed of lipoprotein and lipid filled macrophages
  • flameshaped haemorrhages occur when the rupture of microaneurysms occurs at nerve level
  • blot haemorrhages occur if rupture of microaneurysms occur deep in the retina


  1. Uhlmann K, et al. Genetics of diabetic retinopathy. Exp Clin Endocrinol Diabetes. 2006 Jun;114(6):275-94
  2. Ferris FL et al. Treatment of Diabetic Retinopathy. N Engl J Med 1999;341:667
  3. American Academy of Ophthalmology Retina Panel (2003). Diabetic Retinopathy,Preferred Practice Pattern® Guideline.

Last reviewed 01/2018