Abstract
It is well accepted that only a subset of individuals with diabetes is expected to progress to advanced retinopathy and is at risk of losing functional vision. It is, therefore, of major relevance to identify this subset of patients and when they enter into rapid progression. The Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale is the classic gold standard for grading diabetic retinopathy progression. The fundus abnormalities seen in Diabetic Retinopathy can conceptually be split into three main phenotypes. Those resulting from retinal neurodegeneration, those related to an alteration of the Blood-Retinal Barrier and, finally, those resulting from ischemia. In eyes showing the ischemic phenotype, disease progression is characterized by an initial stage of increasing hypoperfusion involving initially the superficial capillary plexus with progressive involvement of the deep capillary plexus followed by an hyperperfusion response consisting of dilated shunt vessels and intraretinal microvascular abnormalities. Visual acuity is generally maintained as the retinopathy progresses to loss of visual acuity as a result of either clinically significant macular oedema (CSMO) or proliferative diabetic retinopathy (PDR). It is the microvascular changes that occur in response to the progressive capillary closure and the hyperperfusion response characterized by abnormally dilated shunt vessels that create the conditions for CSMO and PDR. Our present understanding of the progress of diabetic retinal disease indicates that prevention of the major vision-threatening complications, may be addressed by either halting the progressive ischemia which characterises the initial hypoperfusion stage or by targeting the angiogenic and inflammatory response that follows.