Pathogenesis of diabetic retinopathy

• 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.

Reference:

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.