# Quantitative assessment of glaucomatous conventional outflow dynamics

> **NIH NIH R01** · DUKE UNIVERSITY · 2024 · $719,160

## Abstract

PROJECT SUMMARY/ABSTRACT
Glaucoma, a leading cause of blindness worldwide, is clinically treated by lowering intraocular pressure (IOP)
which can delay or prevent vision loss. However, first-line standard-of-care treatments for primary open-angle
glaucoma (POAG), the most common form, do not target the conventional outflow pathway (COP) where IOP is
tightly regulated and pathology causes elevated IOP. Moreover, much of our knowledge about COP anatomy
was derived from histological samples that are subject to artifacts from long-term glaucoma therapy that alters
physiologic outflow. Unfortunately, these samples represent only a snapshot in time and space of the dynamic,
spatially heterogeneous COP tissues (causing a “restricted field of view” problem) that is particularly worrisome
because spatial heterogeneity is worse in glaucoma patients, and is thought to contribute to ocular hypertension.
In our previous highly-productive funding period, we pioneered techniques using near-infrared (NIR) optical
coherence tomography (OCT) to image the COP in living mice, known to be anatomically, physiologically, and
pharmacologically very similar to the human COP. Further, we developed AI-driven software to automatically
segment OCT images, observing functional changes in COP tissues in response to drugs, disease, and age. We
then used these images to estimate stiffness/fibrosis of the trabecular meshwork (TM) in vivo. While we made
tremendous progress, we suffered from the “restricted field of view” problem and less-than-desired spatial
resolution. In the upcoming funding period, we will overcome these obstacles by using two exciting, cutting-edge
imaging technologies: (i) robotically-positioned (r) visible light (vis) OCT (denoted “r-vis-OCT”), and (ii) optical
coherence refraction tomography (OCRT), enabling ultra-high-resolution visualization and segmentation of the
3D, spatially heterogeneous architecture of COP tissues around the eye’s circumference. This integrated, whole-
system view will allow us to understand the inherently spatially distributed physiology of IOP (dys)regulation. Our
overarching hypothesis is that r-vis-OCT/OCRT can be used to accurately quantify spatial and temporal changes
in conventional outflow function with age, disease, and drugs. To test this hypothesis, we propose 3 specific
aims (SAs): Aim 1: Use r-vis-OCT in living mice to monitor dynamic, spatially-heterogeneous COP anatomic and
functional responses to drugs and age. Aim 2: Use r-vis-OCT in mice to monitor dynamic, spatially-
heterogeneous COP anatomy and function in 2 relevant disease models. Aim 3: Develop r-vis-OCRT for ultra-
high-resolution monitoring of COP behavior in living mice. Successful completion of our aims will provide
fundamental information about the dynamic processes that maintain conventional outflow in the face of transient
challenges such as pigment showers, IOP spikes or changes in preferential flow pathways. Further, we will learn
about the homeostat...

## Key facts

- **NIH application ID:** 10978370
- **Project number:** 2R01EY030124-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** C ROSS ETHIER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $719,160
- **Award type:** 2
- **Project period:** 2019-05-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978370

## Citation

> US National Institutes of Health, RePORTER application 10978370, Quantitative assessment of glaucomatous conventional outflow dynamics (2R01EY030124-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10978370. Licensed CC0.

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