# Structural and functional tests of ganglion cell damage in glaucoma

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $499,625

## Abstract

This project will use a combination of structural and functional measurements to test the hypothesis that early-
stage damage in human glaucoma occurs first in the inner plexiform layer (IPL) of the retina – especially its OFF
sub-lamina – as suggested by murine glaucoma models. In the first Aim, we will use a novel visible-light optical
coherence tomograph (VIS OCT) to study structural changes in the retina of glaucoma patients. The newly
developed VIS OCT has sufficient image contrast and resolution to segment the IPL boundaries and to define
sub-lamination in volumetric OCT data, something not currently possible with existing near-infrared OCT
instruments. We will make comparative measurements within the IPL and between the IPL, the ganglion cell
layer (GCL) and the retinal nerve fiber layer (RNFL). Because data from mouse models of glaucoma suggests
that early damage occurs preferentially within the OFF sub-lamina of the IPL, we will make separate VIS OCT
measurements biased for the OFF- and ON-sublaminae of the IPL and use machine learning approaches to
determine whether a similar damage process can be demonstrated in human. To test whether OFF-pathway
function is preferentially lost in glaucoma, we will use a novel Steady-State Visual Evoked Potential (SSVEP)
paradigm that employs sawtooth increments and decrements to bias the measurement to ON vs OFF pathways,
respectively, a paradigm our data suggests discriminates glaucoma from control patients. The second Aim will
optimize this SSVEP measurement for testing localized areas of the visual field. The third Aim will make
comparative measurements of visual-field, VIS OCT and SSVEP loss patterns in a large sample of glaucoma
patients and in age- and sex-matched controls. Thickness and interface reflectivity amplitude maps derived from
VIS OCT imaging of the RNFL, GCL and IPL including sublaminae will be correlated topographically with visual
field defects to assess the relative sensitivity of our structural biomarkers at and near visual field locations with
demonstrable losses on conventional (Humphrey) perimetry. Similarly, SSVEP responses from different
locations in the visual field will be correlated topographically with visual field loss patterns and to VIS OCT losses,
with special emphasis on correlating structural damage in OFF vs ON sub-laminae of the IPL with the functional
correlates derived from regional decremental and incremental SSVEPs. Separately and in combination, our
structural and functional measurements are designed to provide strong tests of the biological hypothesis that the
OFF pathway is preferentially damaged in human glaucoma, and to reveal new biomarkers for the disease.

## Key facts

- **NIH application ID:** 10150874
- **Project number:** 5R01EY030361-03
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jeffrey L Goldberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $499,625
- **Award type:** 5
- **Project period:** 2019-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150874

## Citation

> US National Institutes of Health, RePORTER application 10150874, Structural and functional tests of ganglion cell damage in glaucoma (5R01EY030361-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10150874. Licensed CC0.

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