pathogenesis of diabetic retinopathy

Last edited 05/2023

  • Genetic studies, suggest that diabetic retinopathy is an interaction between
    • environmental factors, especially hyperglycaemia (1,2), 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 (1).
  • The retinopathy in diabetes result from five fundamental processes (2):
    • 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 (2).
  • Severity of hyperglycemia is the key alterable risk factor.
  • 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 include  pregnancy and high blood pressure.
  • 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, oedema and hard exudates occur as a result of leakage from capillaries; hard exudates are composed of lipoprotein and lipid filled macrophages.
  • Flame-shaped haemorrhages occur when rupture of microaneurysms occurs at nerve level.
  • Blot haemorrhages occur if rupture of microaneurysms occur deep in the retina.


  1. Ferris FL 3rd, Davis MD, Aiello LM. Treatment of diabetic retinopathy. N Engl J Med. 1999 Aug 26;341(9):667-78. doi: 10.1056/NEJM199908263410907.
  2. American Academy of Ophthalmology (AAO) 2019. Preferred Practice Pattern guidelines. Diabetic retinopathy.