Reactive retinal vasodilation may mask capillary loss in eyes without diabetic retinopathy and isolated neurodegeneration

Reactive retinal vasodilation occurs in healthy individuals when the demand for oxygen surpasses the supply that the vascular bed can provide. This phenomenon may also occur in individuals with diabetes who do not have diabetic retinopathy, potentially masking circulation deficiencies caused by early capillary closure. As a result, eyes with reactive retinal vasodilation may show a seemingly normal circulation area, while also displaying other diabetes-related changes such as neurodegeneration. Our hypothesis suggests that in eyes without overt ischemia, which is one of the phenotypes of diabetic retinal disease, neurodegeneration could be the result of undetected ischemia in the presence of reactive retinal vasodilation. We propose methodologies to investigate this hypothesis, including the assessment of retinal capillaries using optical coherence tomography angiography, as well as the measurement of neurodegeneration markers such as retinal sensitivity, electroretinogram amplitude reductions, and retinal layer thinning. Additionally, we outline an approach for estimating the contribution of large retinal vessels to the percentage of circulation within a measured retinal area, using variables such as vessel length density and vessel area density. If our hypothesis is confirmed, it could lead to the early identification of ischemia before the onset of diabetic retinopathy and offer an opportunity to assess interventions when endothelial and neural damage can still be mitigated.