# Retinal microvasculature as a predictor of neurodegeneration in multiple sclerosis

> **NIH VA IK2** · PORTLAND VA MEDICAL CENTER · 2022 · —

## Abstract

Objectives: Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative illness that affects nearly
1 million people in the United States. Currently, there are no FDA-approved treatments that directly address
neurodegeneration and its associated clinical impairment. Systemic vascular disease comorbidities, including
hypertension, hyperlipidemia, and obesity, independently worsen MS-related walking limitations. In addition, MS
pathology demonstrates microvascular dysfunction in the central nervous system (CNS). Our working model is
that CNS vascular dysfunction accelerates neurodegeneration and thus limitations in activity and health-related
quality of life. The purpose of this study is to quantify CNS vasculopathy in people with MS through
microvascular changes in the retina as a first step to identify treatable modifiers of neurodegeneration.
The overall study hypothesis is that retinal microvascular changes, measured by optical coherence tomography
angiography (OCTA), in people with MS will correlate with patient-reported and objective measures of
neurodegeneration. The long-term goal is to use OCTA as a surrogate of vascular dysfunction in trials of
neuroprotective therapies.
Plan: This is an observational study. The study procedures include a standard battery of neurologic and visual
clinical exams to assess participant function, questionnaires to assess participant quality of life, and OCTA to
assess CNS vasculature through the retina.
Methods: This 2-year prospective cohort study features cross-sectional and longitudinal analyses to compare
the impact of vascular comorbidities on retinal vascular density, determined by OCTA, as a measure of
neuronal structural and functional integrity. Study MRI data will be collected at baseline and 2 years. We will
enroll 44 subjects (accounting for 25% drop out for longitudinal aims) with a goal of 34 MS subjects with and
without vascular comorbidities (V+, V- respectively). Data from an additional 22 healthy controls has already
been collected and will be included for analysis. Subjects will be aged 30-70 and will be matched by age,
gender, and use of disease modifying therapies. The primary outcome is to compare retinal vascular density in
V+ and V- Veterans through cross-sectional analysis (Specific Aim 1). We will also explore if retinal vascular
density correlates with increased rate of brain atrophy in V+ compared to V- Veterans (Specific Aim 2).
Importantly, we will also determine if clinical impairment and quality of life deteriorates faster in V+ versus V-
Veterans (Specific Aim 3).
Relevance to VA’s Mission: The proposed study will have a profound impact on our Veteran population: of
the 28,000 Veterans receiving care for MS within the VA system, approximately 50% have at least one
vascular disease comorbidity. Since many of these comorbidities are modifiable, early identification of vascular
dysfunction provides a window of opportunity for early interventions to optimize activity, ...

## Key facts

- **NIH application ID:** 10469365
- **Project number:** 5IK2RX003407-03
- **Recipient organization:** PORTLAND VA MEDICAL CENTER
- **Principal Investigator:** Elizabeth Silbermann
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-10-01 → 2025-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10469365

## Citation

> US National Institutes of Health, RePORTER application 10469365, Retinal microvasculature as a predictor of neurodegeneration in multiple sclerosis (5IK2RX003407-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10469365. Licensed CC0.

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