Using mathematics and experiments to identify regional tissue hypoxia masked by mean global retinal oxygenation

Abstract

Purpose : Local tissue ischemia has been shown to cause retinal ganglion cell death, but the translation of vascular biomarkers into predictors of open angle glaucoma (OAG) has been challenging. Oximetry and hemodynamics data were collected in OAG and healthy subjects to identify correlations between biomarkers of blood flow and visual function. Mathematical modeling of blood flow and oxygen transport was used to reveal differences in localized tissue oxygenation despite similar measured levels of arteriolar and venous saturation.

Methods : Clinical data from a prospective cross-sectional study included matched examples of healthy and OAG individuals with evaluations of: IOP, blood pressure, visual field (VF) mean defect (MD), pattern standard deviation (PSD), visual field index (VFI), and retinal oxygenation via retinal photographic oximetry. Our mathematical model of the human retinal vasculature was used to predict the arteriolar tissue oxygenation in one quadrant of the eye given an assumed pressure drop across the retinal vasculature of 25 mmHg and an intraocular pressure (IOP) of 15 mmHg.

Results : Healthy (VFI: 99%; MD: 0.29 decibel; PSD: 1.62 decibel) and OAG (VFI: 90%; MD: -5.47 decibel; PSD: 4.83 decibel) samples (both male and Hispanic) exhibited similar IOP and arterial saturations yet had very different clinical outcomes. The model predicted similar disparate outcomes; the two red stars in Fig. 1A highlight two tissue positions where PO₂ = 62 mmHg and PO₂ = 45 mmHg despite identical arterial saturation entering that retinal branch. The histogram in Fig. 1B gives the predicted values of all tissue PO₂, ranging from 35 to 70 mmHg.

Conclusions : This analysis demonstrated that average values frequently reported as mean global values obscure the possibility of regional hypoxia and/or ischemia in some individuals. Developing methodology to discriminate localized tissue metabolic disturbances from global averages may improve translational use of vascular biomarkers in glaucoma and identify patients at elevated risk for progression.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

 

Figure 1. A. Arteriolar tissue PO₂ levels predicted by our theoretical model for a moderate level of tissue demand and IOP = 15 mmHg. The red stars indicate two regions in the arteriolar tissue with significantly different PO₂ values. B. Histogram summarizing the range of tissue PO₂ levels predicted by the theoretical model.