Predicting the impact of blood flow autoregulation capacity on retinal oxygenation in early and advanced glaucoma using a theoretical model

Abstract

Purpose : A theoretical model of the human retina is used to predict the partial pressure of oxygen (PO₂) in retinal tissue as the capacity for autoregulation is varied between 0 and 1 for healthy patients, early glaucoma patients (10% decrease in capillary density (CD)), and advanced glaucoma patients (30-50% decrease in CD).

Methods : In the published theoretical model used here, oxygen transport is modeled using both Green’s function and the Krogh cylinder model. It incorporates flow regulation mechanisms responsive to changes in pressure, shear stress, and metabolism. Autoregulation capacity is defined as a fraction that is varied between 0 and 1 to simulate the impact of different impairments to a patient’s ability to regulate flow (1 indicates fully functional regulation and 0 indicates total impairment).

Results : In our clinical observations, early glaucoma patients are shown to exhibit ~10% reduction in CD compared to healthy individuals, with advanced glaucoma patients experiencing significant further reductions. Figure 1 demonstrates the impact of CD on mean tissue PO₂ levels downstream of the capillaries for autoregulation capacities of 0, 0.5, and 1. A 10% decrease in CD (from 500 mm^-2 to 450 mm^-2) yields a 5% decrease in tissue PO₂, whereas total impairment of regulation when CD = 450 mm^-2 yields an 8% decrease in tissue PO₂. If both CD is reduced by 10% and regulation is impaired, PO₂ in the tissue is decreased by 12.4%. For larger decreases in CD, the gap in oxygenation widens between cases with full and impaired regulatory capacity.

Conclusions : By varying two known vascular phenomena of glaucoma, the model demonstrates a more detrimental effect on retinal oxygenation when capillary loss and autoregulation impairment occur in combination. The model predictions motivate early identification of vascular changes as important for preventing a substantially worse effect of these factors on retinal oxygenation in the later stages of glaucoma.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Figure 1. Tissue partial pressure of oxygen (PO₂) levels downstream of the capillaries as capillary density is varied. Three levels of autoregulation capacity (AC) are shown: 0 (red, fully impaired), 0.5 (black), and 1 (blue, fully functional). These simulations assume an intraocular pressure (IOP) = 15 mmHg and oxygen demand of 1 cm³ O₂/100 cm³/min.