# Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced vision loss

> **NIH NIH R01** · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · 2024 · $316,351

## Abstract

At least 50% of patients treated with 1251 brachytherapy for uveal melanoma experience significant vision loss
within 3-5 years after therapy. Extensive vascular pathology has been reported in the normal retina
surrounding the melanoma after 2 years or more. These findings are in line with the accepted, but
incompletely tested, concept that microangiopathy causes radiation-related vision loss due to injury of the
microvascular endothelium during radiation. This leads to progressive capillary loss after a lag period of
several years. 1f this hypothesis is correct, preventing the development of, or treating, radiation-induced
endothelial damage in retinal microvessels will reduce capillary loss and save vision. However, this approach
has been difficult to test because early indicators of microvascular endothelial dysfunction have yet to be
established.
The objectives of the proposed project are to: facilitate earlier detection, treatment and prevention of
radiation- associated vision loss. Specifically, we expect to 1. detect early endothelial dysfunction based on
reduced blood flow and response to light flicker 2. determine whether it is predictive of subsequent capillary
loss and 3. identify molecular mechanisms of radiation-induced endothelial dysfunction. We will apply laser
speckle flowgraphy (LSFG) for noninvasive, real-time imaging and measurement of ocular blood flow, in
human subjects and mice to test our central hypothesis, that post-radiation endothelial dysfunction is
driven by mitochondrial oxidative stress, and is predictive of the severity of subsequent capillary
dropout and vision loss. We will test our hypothesis in two aims: Aim 1: Establish whether early impairment
of the microvascular endothelial function will predict microvessel drop-out and vision loss in humans after 1251
brachytherapy. For this purpose, LSFG, optical coherence tomography (OCT) and OCT-angiography (OCT-
A) and tests of visual function will be performed in a prospective cohort of patients undergoing 1251
brachytherapy for choroidal melanoma. We will test whether early impairment of ocular blood flow and flicker
light-induced vasodilation by LSFG correlate with subsequent vision loss and capillary drop-out (as detected
by OCT-A). Aim 2: Test whether selective inhibition of mitoROS production in endothelium prevents the early
reduction of blood flow and subsequent loss of capillaries after radiation. 1n this aim, genetic mouse models
in which key regulators of mitochondrial superoxide production are inhibited or overexpressed will be used to
test whether inhibition of mitochondrial ROS in the endothelium protects from early impairment of retinal
blood flow, endothelial dysfunction and subsequent capillary dropout.
The expected outcomes of the proposed studies are knowledge of biomarkers of early radiation retinopathy
and insights into the role of endothelial-cell mitochondrial dysfunction in radiation retinopathy. Our studies
have the potential to facilitate the...

## Key facts

- **NIH application ID:** 11443562
- **Project number:** 7R01EY031544-06
- **Recipient organization:** UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
- **Principal Investigator:** Isabella Maria Grumbach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $316,351
- **Award type:** 7
- **Project period:** 2020-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11443562

## Citation

> US National Institutes of Health, RePORTER application 11443562, Laser speckle flowgraphy as early indicator of microvasculopathy in radiation-induced vision loss (7R01EY031544-06). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/11443562. Licensed CC0.

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