Moderately elevated IOP may alter optic nerve head hemodynamics enough to cause mild hypoxia over a substantial part of the lamina cribrosa

Abstract

Purpose : Our goal was to evaluate how lamina cribrosa (LC) oxygenation is affected by the tissue distortions resulting from elevated IOP. Specifically, we hypothesized that even moderately elevated IOP may adversely affect blood flow enough to cause mild hypoxia within the LC. Since measurement of LC oxygenation in-vivo is not yet possible, we used 3D eye-specific numerical models of the LC vasculature which we subjected to experimentally-derived tissue deformations.

Methods : We reconstructed detailed 3D models of the LC vessel networks of 3 healthy monkey eyes using histological sections, as described elsewhere (Lee et al., 2022). We also obtained in-vivo IOP-induced LC deformations from a healthy monkey using OCT images and analysis techniques while IOP was controlled, as reported before (Zhong et at., 2022). A biomechanics-based technique was used to map the OCT-derived tissue strains to local LC vessel distortions. The hemodynamics of the three vessel networks were simulated under deformations from various IOP increases (Fig 1). The results were used to determine the effects of IOP on LC oxygenation (PO2), classifying the tissue in one of three levels based on the oxygenation: normoxia (PO2>38mmHg), mild hypoxia (38mmHg>PO2>8mmHg) and severe hypoxia (8mmHg>PO2).

Results : IOP-induced deformations reduced LC oxygenation significantly (p<1e-5, Fig 2). For moderate IOP elevation (20~30 mmHg), the region of severe hypoxia was small, but the mild hypoxia region increased significantly (p<0.05). About 40% of LC tissue suffered from mild hypoxia when IOP reached 30 mmHg. Extreme IOP increases (>50mmHg) led to large severe hypoxia regions.

Conclusions : Our models predicted that moderately elevated IOP can lead to mild hypoxia in a substantial part of the LC, which, if sustained chronically, may contribute to neural tissue damage. For extreme IOP elevations, severe hypoxia was predicted, which would potentially cause more immediate damage. Our findings point to the need to advance experimental tools with the ability to determine in-vivo LC oxygenation to better glaucoma.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

Schematic of our analysis process. Three ONH vasculatures were studied under in-vivo IOP-induced deformations.

 

(left) LC oxygenation levels for Eye 1 at six IOPs. (right) Results varied slightly between eyes but overall LC tissue fractions at mild and severe hypoxia increased with IOP.