Predicting the impact of retinal vessel density on retinal vessel and tissue oxygenation using a theoretical model

Vascular impairments, including compromised flow regulation, have been identified as significant contributors to glaucomatous disease. Recent studies have shown glaucoma patients with significantly reduced peripapillary, macular, and optic nerve head vessel densities occurring with early glaucomatous structural changes prior to detectable visual field loss. This study aims to quantify the potential impact of decreased vessel densities on retinal perfusion and oxygen metabolism. In our clinical observations, pre-perimetric glaucoma patients exhibited a 10-13 % reduction in vessel density compared to healthy individuals. Our theoretical model of the retinal vasculature is adapted in this study to assess the potential impact of this reduction in vessel density on retinal oxygenation. The model predicts a 1 % and 38 % decrease in mean oxygen saturation in retinal vessels immediately downstream of the capillaries when vessel density is decreased from its reference value by 10 % and 50 %, respectively. The impact of capillary loss on oxygen extraction fraction and the partial pressure of oxygen in retinal tissue is also predicted. Reductions in vessel density are simulated in combination with impaired flow regulation, and the resulting effects on saturation and flow are predicted. The model results showed a nonlinear relationship between vessel density and downstream saturation, indicating that larger decreases in the density of capillaries have a disproportionate impact on oxygenation. The model further demonstrates that the detrimental effects of minor vessel density reductions are exacerbated when combined with other vascular impairments.