# Functionally Validated Structural Endpoints for Early AMD

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2022 · $68,262

## Abstract

ALSTAR2 is a prospective study designed to identify functionally validated structural endpoints on a
progression sequence from aging to early AMD to intermediate AMD. Because ALSTAR2 was designed
to incorporate current concepts of deposit-driven AMD progression and human retinal neuroscience, it
will also reveal and refine pathologic mechanisms during the earliest stages of AMD. Enrollment between
October 2019 and September 2021 resulted in 532 adults ≥ 60 years. We will begin our 3-year follow-up
visit in October 2022. Today we request supplemental funds for a unique opportunity at follow-up that
may support a new clinical trial and dietary recommendations to facilitate AMD prevention. In brief we
wish to measure retinal and serum levels of xanthophyll carotenoids (lutein, L; zeaxanthin; Z, meso-Z)
found in human macula. Reduced risk for choroidal neovascularization due to L and Z supplementation
was previously shown in a secondary analysis of AREDS2. To the funded aims of the original grant
application, we added an objective imaging study of carotenoids to the baseline study, using institutional
funds. Two-wavelength autofluorescence is a modality on the Spectralis OCT instrument that we use for
our other imaging tests. In 2020 our group published the first images of AMD eyes using this technology.
In ALSTAR2 baseline, we also measured serum carotenoids via high-performance liquid
chromatography. The purpose of this add-on to baseline was to probe one aspect of a Center-Surround
model of deposit-driven AMD progression. This model connects the tight foveal centration of high-risk
soft drusen, composition of Bruch’s membrane lipids implicating diet, delivery of xanthophylls from
circulation to foveal cells, and poor rod-mediated dark adaptation in parafovea. Exciting findings from
baseline were presented at the international Brain and Ocular Nutrition Conference in Cambridge UK
(late July 2022). MPOV was positively correlated with serum carotenoid levels (r = 0.49), at levels higher
than in previous literature. This correlation was not impacted by L and Z supplement use. We hypothesize
that transfer of L and Z is related to soft druse formation. Our baseline results are intriguing yet cross-
sectional. Determining change over time in this large sample is critical for understanding the roles of L
and Z in aging and AMD. We thus wish to measure serum L and Z at the 3-year follow-up visit, as well as
objective two-wavelength autofluorescence imaging and MPOV. Because we also hypothesize that the
HDL genes of the AMD GWAS regulate carotenoid bioavailability from gut to fovea, funds for whole
genome sequencing of ALSTAR2 participants are also being sought in parallel from other sources.

## Key facts

- **NIH application ID:** 10691011
- **Project number:** 3R01EY029595-04S2
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Christine A Curcio
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $68,262
- **Award type:** 3
- **Project period:** 2019-05-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10691011

## Citation

> US National Institutes of Health, RePORTER application 10691011, Functionally Validated Structural Endpoints for Early AMD (3R01EY029595-04S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10691011. Licensed CC0.

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