Using a Theoretical Model to Assess the Impact of Vascular Risk Factors on Autoregulation in the Retina.

Purpose: Vascular impairments, including reduced capillary density (CD), impaired autoregulation capacity (Reg), and elevated intraocular pressure (IOP), have been identified as significant contributors to glaucomatous disease. This study implemented a theoretical model to quantify the impact of these impairments on retinal blood flow and oxygenation as intraluminal pressure (Pa) is varied. Methods: A theoretical model of the retinal vasculature was used to simulate reductions in CD by 10% (early glaucoma) and 30% to 50% (advanced glaucoma), a range in autoregulation capacity from 0% (totally impaired) to 100% (totally functional), and normal (15 mm Hg) and elevated (25 mm Hg) levels of IOP. Results: Under baseline conditions of CD = 500 mm-2, Reg = 100%, and IOP = 15 mm Hg, an autoregulation plateau was predicted for Pa = 28 to 44 mm Hg. Decreased CD, impaired flow regulation mechanisms, and increased IOP all cause a loss of the autoregulation plateau and a corresponding decrease in tissue oxygenation in this pressure range. Although the detrimental effects of small decreases in CD or elevations in IOP are mostly offset by functional flow regulation, larger changes and/or combinations of vascular impairments lead to a significant drop in retinal oxygenation. Conclusions: Model predictions indicate that isolated or combined vascular impairments in CD, flow regulation, and IOP contribute to poor retinal tissue oxygenation, which could lead to vision loss in advanced glaucoma patients. This study motivates early identification of vascular changes to prevent a substantially worse effect of these factors on retinal oxygenation during the progression of glaucoma.