# Measures of Human Receptor and Post Receptor Activity

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 2020 · $636,552

## Abstract

Our long-term objective has been to develop noninvasive techniques for studying the human retina for
both basic science and clinical purposes. By applying current theories of phototransduction to the full-field
electroretinogram (ERG), we successfully developed widely used techniques for studying the global activity of
the rod and cone receptors, as well as the rod bipolar cells. These indices of objective retinal function are
appropriate outcome measures for treatment trials with systemically administered agents. However, many
ongoing and anticipated clinical trials involving diseases of the photoreceptors require localized measures of
retinal function, such as the multifocal electroretinogram (mfERG), static automated perimetry (SAP), and rod
and cone-mediated fundus tracking perimetry, for evaluating treatment efficacy. With recent developments in
retinal imaging, we can relate localized measures of visual function to the underlying structure. We have
focused on frequency domain optical coherence tomography (fdOCT) and fundus autofluorescence (FAF). This
work, supported by the current grant, has benefitted from our novel quantitative approaches for relating the
thickness of retinal layers seen on fdOCT to other structural and functional measures. The upcoming focus will
be on patients having Inherited Retinal Degenerations (IRDs), including STGD1, with identified genetic
mutations. A primary goal is to provide insights into the pathophysiology and rates of progression in
molecularly characterized patients with our novel imaging and functional measures.
 Present outcome measures in RP (primarily SAP and ERGs), and STGD1 (primarily visual acuity and
FAF) are incapable of assessing change with modest sample sizes over a relatively short time interval,
resulting in expensive and lengthy clinical trials. Our recent work with en face slab OCT represents a radical
change in translational research in RP and STGD1. Our work in RP is virtually unique in the steps we are
taking to establish quantitative OCT as a viable clinical trial outcome measure. As evidenced at the NEI-FDA
endpoints workshop (NIH, Nov 9, 2016), there is considerable enthusiasm for an “anatomical” endpoint for
IRDs. Nevertheless, there is still much to be done to expand the measures to EZ area and to establish the
relationship between outer retinal structural alterations (i.e. EZ area) and functional loss. Planned experiments
will determine the extent, nature and progression of receptor loss by developing and evaluating novel en face
slab methods for quantifying the receptor regions on wide-field OCT scans, relating OCT parameters to rod
and cone SAP, developing models relating rod and cone sensitivity to quantitative measures of inner and outer
segment length, outer nuclear layer thickness, and inner nuclear layer thickness, and using multimodal imaging
methods including OCT, infrared (IR) reflectance and FAF to test hypotheses about disease mechanisms and
models of disease progress...

## Key facts

- **NIH application ID:** 9997943
- **Project number:** 5R01EY009076-27
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **Principal Investigator:** DAVID G BIRCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $636,552
- **Award type:** 5
- **Project period:** 1991-05-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9997943

## Citation

> US National Institutes of Health, RePORTER application 9997943, Measures of Human Receptor and Post Receptor Activity (5R01EY009076-27). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9997943. Licensed CC0.

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