Lessons from our Pupils: A Reflection [Podcast Episode 151]
Dr. Thomas Gardner joined Jay for Episode 151 (LINK) to discuss the mechanisms of visual loss in diabetic retinopathy and the current limitations of the management of diabetic retinopathy. Today we are going to review how diabetes affects the cells of the retina and how these changes present on an exam.
Diabetic retinopathy is a microvascular disease that occurs as a complication of diabetes mellitus. This is a disease that affects the retinal neurovascular unit, which refers to neurons, glia, and vasculature that work together to regulate normal retinal function. Throughout the course of DR, the different components of this unit can become affected. A critical feature of DR is vascular dysfunction and capillary loss, but evidence has shown that neuropathy can appear first, as some patients present with loss of color vision and contrast sensitivity before microvascular changes can be observed. Furthermore, observational studies are now showing that damage to the neuronal layer can promote microangiopathy. Glial cells are also impacted in diabetes. There is an alteration in the homeostatic function of glial cells, which impacts its ability to regulate retinal blood flow, water balance, and the maintenance of barrier function. Microglial cells are also affected in the progression of diabetes, which causes chronic and subclinical inflammation in the retina. As immune cells become activated in DR, there is enhanced leukocyte-endothelial interaction which causes leukostasis and can lead to damage of the retinal vascular endothelium and surrounding tissue. This can happen due to physical obstruction of the capillaries and through the release of pro-inflammatory cytokines, including VEGF. Lastly, diabetes also impacts the RPE, specifically disrupting photoreceptor and choroidal integrity. However, the importance of the dysfunction of this layer in the overall progression of DR remains unclear and under study.
Currently, DR is classified based on the microvascular lesions observed. In the earlier stages, there is nonproliferative diabetic retinopathy (NDPR) that then advances to proliferative diabetic retinopathy (PDR). Changes of the retina in NDPR include the appearance of intraretinal hemorrhages, microaneurysms, venous caliber abnormalities, formation of intraretinal microvascular abnormalities, cotton-wool spots from neuronal infarcts, and retinal neovascularization. As the vascular bed experiences a gradual decrease in perfusion, vessel integrity is lost, ultimately leading to occlusion or degeneration of capillaries. This causes decreased oxygenation to the retinal layer, which eventually leads to expression of proangiogenic growth factors and development of PDR. Hypoxia causes formation of new blood vessels that are fragile and can protrude into the preretinal space. Rupture of these vessels can cause vitreous hemorrhage or tractional retinal detachment. Throughout the progression of NPDR and PDR, diabetic macular edema can arise from the breakdown of the blood-retinal barrier. This breakdown causes leakage of proteins and fluid into the retina, which appears as abnormal retinal thickening and even edema of the macula.
