# Functional Imaging in Hypoxic-Ischemic Retinal Disease

> **NIH NIH K08** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2020 · $53,290

## Abstract

Project Summary
Ischemia and hypoxia play critical roles in the pathophysiology of common blinding diseases
such as diabetic retinopathy (DR) and retinal vein occlusions (RVO). Unfortunately, the
correlation between impaired capillary perfusion, often called ischemia or “nonperfusion,” and
hypoxia is largely unknown in a clinical setting because of limited imaging methodologies.
Impaired capillary perfusion is almost exclusively demonstrated in clinic by fluorescein
angiography (FA) but histological studies show that FA underestimates capillary density as
much as 30-40% thereby under-diagnosing “nonperfusion.” Indirect clinical evidence and animal
studies suggest that hypoxia underlies sequelae of DR and RVO. For example, contrast
sensitivity deficits and retinal thickening are reversed in diabetic subjects breathing oxygen.
However, there is little direct evidence of retinal hypoxia in humans because of the invasive
methods needed to measure intraretinal oxygen levels. Since there is no direct clinical measure
for mild-moderate hypoxia and only limited assessments of impaired capillary perfusion
(ischemia), current treatments for DR and RVO presume a direct and static relationship
between these two. However, abundant clinical evidence suggests that ischemia and hypoxia
are not directly correlated. These observations confirm that the correlation between ischemia,
hypoxia and sequelae of retinal vascular diseases are incompletely understood. I hypothesize
that the relationship between microvascular hypoxia and ischemia is not static nor necessarily
direct; and I suggest that this underlies limitations in current treatments and therapeutic failures.
I propose basic and clinical studies that correlate real time intraocular pO2 measurements in
animal models of ischemia with non-invasive imaging methods such as optical coherence
tomography angiography (OCTA) to assess retinal capillary perfusion and hyperspectral
computed tomographic imaging spectroscopy (HCTIS) to assess tissue hypoxia. These
methods are then translated to the clinic where they are already shown to be safe and effective
imaging modalities in pilot studies I have performed. The combination of these approaches
leverages the gold standard intraocular pO2 measurements to validate and calibrate non-
invasive methods that can be used safely and effectively in human subjects. Lastly, I propose
to use OCTA and HCTIS to correlate the extent and duration of ischemia and hypoxia in human
subjects with vision loss from DR and RVO.

## Key facts

- **NIH application ID:** 9979875
- **Project number:** 5K08EY027006-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Amir H Kashani
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $53,290
- **Award type:** 5
- **Project period:** 2016-08-01 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979875

## Citation

> US National Institutes of Health, RePORTER application 9979875, Functional Imaging in Hypoxic-Ischemic Retinal Disease (5K08EY027006-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9979875. Licensed CC0.

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