Release of angiogenic factors in response to the ischaemic retina is currently the most favoured hypothesis for the pathogenesis of proliferative
diabetic retinopathy. Reducing the stimulus for angiogenesis by destroying the ischaemic retina also forms the basis of the most effective treatment of
diabetic retinopathy by
photocoagulation. Though ischaemia is undoubtedly important for neovascularization, there is recent evidence which cast doubts on
ischemia being the sole mechanism for
diabetic retinopathy. Many clinical observations viz. the protective effects of
glaucoma,
myopia, unilateral
carotid stenosis on
diabetic retinopathy; and its worsening after
cataract extraction are not adequately explained by the present hypothesis. Moreover, the recent in vitro culture studies on
retinal pigment epithelial cells have suggested an alternative explanation for the effectiveness of
photocoagulation in proliferative
diabetic retinopathy. Furthermore,
hyperglycemia has been strongly correlated with the incidence and progression of
diabetic retinopathy, but has only been indirectly indicted in its pathogenesis. These facts can be integrated into a more plausible hypothesis for the pathogenesis of
diabetic retinopathy. It is hypothesized that a relative reduction in intra-ocular pressure caused by persistent or intermittent
hyperglycemia may be the missing link that induces certain morphological changes in the retinal pigment epithelium. These changes, in addition to the ischaemic retina, may be important for the pathogenesis of
diabetic retinopathy. Such a hypothesis also explains most of the hitherto unexplained features of
diabetic retinopathy.