# Total outflow facility before and after goniotomy in ex vivo perfusion models for aqueous humor dynamics: effect of periocular tissue

## TL;DR

This study shows that removing periocular tissue affects the measurement of eye fluid outflow, which could explain why lab tests on glaucoma treatments don't always match real-world results.

## Contribution

The study demonstrates that tissue preparation affects total outflow facility measurements in ex vivo eye models.

## Key findings

- Preserved periorbital tissue significantly lowers total outflow facility compared to trimmed tissue.
- Goniotomy increases outflow facility more in eyes with preserved tissue than in trimmed ones.
- Distal outflow pathways contribute to resistance even with intact trabecular meshwork.

## Abstract

Ex vivo perfusion models to simulate aqueous humor dynamics are commonly used to test interventions for glaucoma treatment. Many models, however, overestimate the effect of surgical interventions. Periorbital tissue is routinely removed during the experimental preparation. Evidence suggests that up to 50% of total outflow resistance is attributable to the distal outflow pathways. It is currently unclear if varying degrees of tissue removal alone elicit changes in total outflow facility (Ctot). We compared Ctot in whole globes with and without preserved periorbital tissue with intact trabecular meshwork (TM) and with surgical TM bypass in an ex vivo perfusion model.

A total of 33 post-mortem porcine eyes with intact surrounding tissue were either trimmed (TISS−, n = 17) or left unchanged (TISS+, n = 16). Constant-flow perfusion at 4.5 μL/min and IOP measurement in the anterior chamber were performed. In a subgroup of 13 globes, a 5 mm goniotomy was performed before perfusion (7 TISS+, 6 TISS−). Ctot was analyzed once a stable equilibrium was reached.

Ctot was 0.27 ± 0.06 with intact TM and 0.36 ± 0.11 μL/mmHg/min with goniotomy in TISS+ globes, as well as 0.36 ± 0.12 and 0.47 ± 0.02 μL/mmHg/min in TISS− globes. Both comparisons (TM intact/ goniotomy) between TISS+ and TISS− globes were statistically significant (TM intact: p = 0.044, goniotomy: p = 0.031).

This study demonstrates the influence of distal outflow pathways on Ctot with intact TM and after goniotomy. Thus, tissue preparation is a potential confounder in ex vivo AHO perfusion setups and may contribute to the different effect sizes of TM bypass surgery between ex vivo and in vivo studies.