Using a theoretical model to assess the impact of retinal capillary loss and autoregulation capacity in glaucoma

Abstract

Purpose : A theoretical model of the retina is used to predict retinal blood flow and oxyhemoglobin saturation at differing levels of capillary density (CD) and autoregulation capacity (AC) as intraluminal pressure (P_a) is varied.

Methods : A theoretical model was designed to account for vascular heterogeneity, flow regulation, and oxygen transport mechanisms. Capillary loss ranging from 10% (early glaucoma) to 30-50% (advanced glaucoma) is simulated. AC is varied between 0 (totally impaired) and 1 (totally functional) to simulate the impact of different impairments to a patient’s ability to regulate blood flow.

Results : Under baseline conditions of CD = 500 mm^-2 and AC = 1, an autoregulation plateau is predicted for P_a = 32 - 40 mmHg in Fig. 1 (dark green). The impact of decreasing CD by 10% (450 mm^-2, black), 30% (350 mm^-2, red), and 50% (250 mm^-2, blue) on the autoregulation plateau is also shown. As CD is decreased, the plateau is translated to higher pressure values, and flow levels are increased. Thus, decreased CD leads to a loss in the autoregulation plateau for P_a = 32 - 40 mmHg. If a patient has no ability to regulate flow (AC = 0), the autoregulation plateau disappears entirely. Fig. 2 (left) shows that the model predicts a large change in mean oxyhemoglobin saturation downstream of the capillaries if AC = 0 (blue). In Fig. 2 (right), when AC = 1, the model predicts small changes in saturation when P_a is decreased from 40 to 32 mmHg for CD = 500 mm^-2 (3.7%) and 450 mm^-2 (4.7%), but much larger changes when CD = 350 mm^-2 (19.3%) and 250 mm^-2 (51.9%).

Conclusions : Model predictions indicate that the inability to autoregulate for P_a = 32 - 40 mmHg when CD is decreased by 30-50% causes a significant decrease in oxygenation, which could partially explain the loss of vision function in advanced glaucoma patients.

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

 

Figure 1. Normalized flow as a function of P_a is shown for CD = 500 mm^-2 (dark green), 450 mm^-2 (black), 350 mm^-2 (red), and 250 mm^-2 (blue). Three levels of AC are shown: 0 (dotted), 0.5 (dash-dot), and 1 (solid).

 

Figure 2. (Left) Average saturation downstream of the capillaries given as a function of intraluminal pressure (P_a) for CD = 500 mm^-1 when autoregulation capacity (AC) = 1 (red) and 0 (blue). (Right) Average saturation as a function of P_a for AC = 1 and capillary density (CD) = 500 mm^-2 (green), 450 mm^-2 (black), 350 mm^-2 (red), and 250 mm^-2 (blue).