Ocular perfusion abnormalities in diabetes

Abstract

ABSTRACT.Purpose: To review the role of ocular perfusion in the pathophysiology of diabetic retinopathy, one of the leading causes of irreversible blindness in the industrialized world. Methods: We carried out a Medline search of the literature published in English or with English abstracts from 1966 to 2000 using various combinations of relevant key words. Results: Hyperglycaemia leads to a wide variety of vascular abnormalities at the microvascular and macrovascular levels, including abnormal autoregulation. Conclusion: Three major aspects of ocular perfusion in diabetic retinopathy require additional investigation. Firstly, the precise mechanisms that link elevated glucose to dysfunction of retinal vascular cells need to be identified. Secondly, those factors that lead to both capillary dropout and to angiogenesis, twin processes that are linked to tissue hypoxia and lead to excess perfusion, increased risk of extravascular leakage and frank haemorrhage, must be carefully delineated. Finally, once specific knowledge of disease fundamentals has been amassed, tests of therapies to reverse or prevent these pathological processes can move forward.

Treatment strategies for refractory diabetic macular edema: switching anti-VEGF treatments, adopting corticosteroid-based treatments, and combination therapy

“…Damage to endothelial cells that are responsible for maintaining the blood-retinal barrier allows for accumulation of extracellular fluid in the macula. There is also thickening of the capillary basement membrane and increased deposition of extracellular matrix components [1,14,15]. Over time, continued retinal microvasculature damage results in capillary nonperfusion and retinal ischemia, resulting in upregulation of angiogenic factors, such as vascular endothelial growth factor (VEGF) [5].…”

“…Early on, there is damage to the pericytes that are responsible for regulating capillary perfusion, which results in microaneurysm formation and impaired regulation of retinal blood flow [14]. Damage to endothelial cells that are responsible for maintaining the blood-retinal barrier allows for accumulation of extracellular fluid in the macula.…”

Biomarkers in Diabetic Retinopathy

“…Using more modern techniques, such as Doppler flow velocity waveform analysis, even earlier changes in blood flow have been identified, prior to the onset of clinically overt retinopathy, and even in prediabetic (impaired glucose tolerance) subjects [96]. Decreased total retinal blood flow and arteriolar vasoconstriction have been confirmed by several other groups [97][98][99]. Later in the retinal disease process, retinal arterioles dilate, which causes increased blood flow [98,100] and accelerated progression to diabetic macular edema (DME) and PDR [101].…”

“…Decreased total retinal blood flow and arteriolar vasoconstriction have been confirmed by several other groups [97][98][99]. Later in the retinal disease process, retinal arterioles dilate, which causes increased blood flow [98,100] and accelerated progression to diabetic macular edema (DME) and PDR [101]. Increased blood pressure induced by exercise, acute hyperinsulinemia, and the degree of diabetic retinopathy present can alter retinal vessel vasodilatory capacity, which can be measured at rest or after exercise [102][103][104].…”

Inflammation and Angiogenesis in Diabetic Retinopathy

“…In early stages of DME, breakdown of the inner blood-retinal barrier may occur, resulting in accumulation of extracellular fluid in the macula 4,5 .Pericytes are essential cellular components in the regulation of retinal capillary perfusion, and damage to these cells in diabetes leads to altered retinal hemodynamics, including abnormal autoregulation of retinal blood flow 6 . Loss of retinal pericytes represents another early microaneurysm formation [7][8][9] .…”