# Biomarkers of Systemic Inflammation in Intermediate Age-Related Macular Degeneration

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $394,343

## Abstract

PROJECT SUMMARY/ABSTRACT
Age-related macular degeneration (AMD), a chronic multifactorial disease primarily affecting the macula region
of the retina, is a leading cause of vision loss in the elderly. AMD is a disease of the photoreceptor support
system linked with local inflammatory events and complement activation-promotion genes. Apart from a small
number of studies in advanced AMD, the significance of systemically assessed inflammation in AMD has not
been adequately addressed. This is especially true for patients with intermediate AMD (iAMD), an early form of
AMD, where we suggest that the presence of systemic inflammation may be a risk factor for iAMD progression
to the visually threatening forms of advanced AMD. To address this knowledge gap, we conducted pilot studies
to evaluate profiles of circulating inflammatory markers including complement, cytokines, chemokines, and
high-sensitivity C-reactive protein (hsCRP) in patients with iAMD recruited into our Colorado AMD registry. We
found compelling evidence that certain inflammatory biomarkers distinguished patients with and without iAMD,
and most importantly patients with iAMD who progressed to advanced AMD. Furthermore, we found in iAMD
patients a significant link between systemic levels of hsCRP, and choroidal thinning on optical coherence
tomography (OCT), a finding which is one of the pathological events linked with AMD. In aggregate, these
findings suggest that studying iAMD as we propose, can provide insights into early pathologic events in AMD
and also allow one to identify those at highest risk for severe AMD and progressive visual loss. The purpose of
the proposed study is to corroborate and expand on the findings from our novel pilot data in an adequately
powered iAMD cohort and explore our hypothesis that among patients with iAMD an inflammatory biomarker
profile will identify patients who will convert to advanced AMD. We will leverage our cohort's existing
longitudinal blood samples linked to demographic and epidemiology data as well as DNA, multimodal image,
and outcome data. We will address this hypothesis with two specific aims. In Aim 1 we will follow an iAMD
cohort over time and, a) Identify the profile of inflammatory biomarkers that best distinguishes patients with
iAMD who progress to advanced AMD, and b) Develop a dynamic risk score for AMD progression that
combines AMD epidemiological, newly defined inflammatory profiles, and genetic risk factors. In Aim 2, we will
focus on OCT imaging biomarkers previously established as risk factors for AMD progression. We will
determine the relationships between circulating inflammatory biomarkers and both qualitative (e.g., reticular
pseudodrusen) and quantitative (e.g., drusen volume and choroidal thickness) measures. We expect our study
will show an important role for systemic inflammation in iAMD. This study will present an opportunity to better
understand iAMD pathogenesis as well as for early identification of a high-risk gro...

## Key facts

- **NIH application ID:** 10828736
- **Project number:** 5R01EY032456-04
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** ANNE M. LYNCH
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $394,343
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10828736

## Citation

> US National Institutes of Health, RePORTER application 10828736, Biomarkers of Systemic Inflammation in Intermediate Age-Related Macular Degeneration (5R01EY032456-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10828736. Licensed CC0.

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