Pathogenesis of Diabetic Retinopathy
Although the primary cause of diabetic microvascular disease remains poorly understood, exposure to hyperglycemia over an extended period results in biochemical and molecular pathway changes, including increases in inflammatory oxidative stress, advanced glycation end products, and protein kinase C pathways that ultimately cause endothelial damage and pericyte loss. Numerous hematologic abnormalities are also associated with the onset and progression of retinopathy, including increased platelet adhesion, increased erythrocyte aggregation, and defective fibrinolysis. However, the precise role of each of these abnormalities in the pathogenesis of retinopathy—individually or in combination—is not well defined.
Over time, retinal capillary changes such as basement membrane thickening and selective loss of pericytes lead to capillary occlusion and retinal nonperfusion. High-resolution imaging of the retinal vasculature, now available through OCT angiography (OCTA) and adaptive optics scanning laser ophthalmoscopy, often reveals areas of vascular remodeling even in eyes with clinically mild diabetic retinopathy. Vascular abnormalities occur in both the superficial and deeper retinal capillary plexuses. These changes worsen with increasing levels of diabetic retinopathy severity (Fig 5-1). In addition, endothelial barrier decompensation leads to serum leakage and retinal edema. In late stages of the disease, retinal neovascularization develops in response to increases in intraocular vascular endothelial growth factor (VEGF), which is produced by ischemic retinal tissue.
Excerpted from BCSC 2020-2021 series: Section 10 - Glaucoma. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.