# Structure-Function Relationships in Stargardt Disease.

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $245,625

## Abstract

Project Summary/Abstract
 ABCA4 gene related Stargardt disease (STGD1) is the most common juvenile macular
dystrophy and can affect both children and adults. It is inherited as an autosomal-recessive trait
associated with mutations in the ABCA4 gene. Patients experience a slow progressive loss of visual
function, especially central vision, and can reach legal blindness in decades. Currently there is no
approved treatment for STGD1. Potential treatment options include pharmacologic, gene replacement
and stem-cell transplantation approaches. Success of future STGD1 treatment trials will depend on
appropriately selected trial endpoints. Regulatory agencies prefer visual function outcomes which
however can be inefficient for STGD1 trials because of the slow rates of visual function loss in the
disease natural history. Retinal structural parameters (SP) measured by fundus autofluorescence (FAF)
and optical coherence tomography (OCT) imaging are widely used clinically to track disease
progression. However, before accepting an SP as a trial endpoint, regulatory agencies require evidence
of significant relationships between the SP and functional outcomes, including both cross-sectional
relationships and also longitudinal associations between structural changes and “a future clinically
significant outcome”. Such evidence (or lack of) has not been well demonstrated for STGD1. The
Progression of Atrophy Secondary to Stargardt Disease (ProgStar) prospective study, including its
ancillary Scotopic Microperimetric Assessment of Rod Function in Stargardt Disease (SMART) study, is
a multi-center international study of 259 molecularly confirmed STGD1 patients to generate natural
history data over 2 years of follow-up. Leveraging data from these studies, our aims are: First, to
assess cross-sectional and longitudinal associations of FAF derived parameters on atrophic lesion size
with functional outcomes of best corrected visual acuity (BCVA) and macula sensitivities from photopic
and scotopic microperimetry tests. Second, to assess cross-sectional and longitudinal associations of
OCT derived parameters on retinal integrity, including thicknesses and intact areas of the inner and
outer retinal layers, with functional outcomes of BCVA and photopic and scotopic macula sensitivities.
Generalized linear models with generalized estimating equation will be used. The knowledge learned
will demonstrate what FAF and OCT derived SPs, at what magnitudes, and under what phenotypic
conditions, are associated with loss of visual functions, thus leading to a better understanding of the
disease pathophysiology. The knowledge will inform choices of endpoints and enrollment criteria for
forthcoming STGD1 treatment trials.

## Key facts

- **NIH application ID:** 10288617
- **Project number:** 1R21EY032955-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Xiangrong Kong
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $245,625
- **Award type:** 1
- **Project period:** 2021-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288617

## Citation

> US National Institutes of Health, RePORTER application 10288617, Structure-Function Relationships in Stargardt Disease. (1R21EY032955-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10288617. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*