# Predictive markers for diabetic retinopathy via quantitative imaging of retinal capillary functions

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $489,205

## Abstract

PROJECT SUMMARY
Diabetic retinopathy (DR) remains the leading cause of blindness, affecting over 4 million Americans. The
prediction of DR progression and treatment outcome holds the key in the care for DR and the prevention of
vision-threating conditions. However, clinicians are now faced with the challenge of limited established
predictors for the development of DR and treatment response. Our hypothesis is that capillary dysfunction, as
the central crux of the DR pathology, is a sensitive predictor of DR progression and treatment outcome. In
diabetic eyes, hyperglycemia leads to capillary dysfunction which leads to a breakdown of the blood retinal
barrier (BRB) resulting in capillary leakage. This capillary dysfunction further leads to capillary loss and non-
perfusion, which causes ischemic hypoxia. The combined effects of capillary leakage and hypoxia results in
neovascularization and retinal hemorrhage, signifying the onset of proliferative DR. In this pathogenic process,
capillary leakage, oxygenation, and capillary blood flow are three key aspects of capillary function, and
therefore have become our targets of imaging and quantification. We have developed visible light optical
coherence tomography (OCTA) to non-invasively quantify blood oxygenation at the capillary level. We have
also shown that measuring the dynamics of near infrared OCTA allows quantification of the flow dynamics of
capillary flow. The quantification of both oxygenation and flow dynamics provides measurement of capillary
perfusions. In addition, we have developed a novel multimodal 3D imaging technique, oblique scanning laser
ophthalmology (oSLO), which unprecedentedly enables wide-field 3D fluorescence imaging in the retina. Since
the administration of fluorescein dye is a component of the standard of care and fluorescein angiography (FA)
is the gold standard for diagnosing DR, the 3D imaging capability of oSLO can uniquely provide sensitive
detection of dye leakage. Taken altogether, we will explore three specific aims. 1) To develop a multimodal
oSLO/OCT system to quantify capillary blood oxygenation, flow dynamics, and leakage, with large field of view,
high resolution and high speed. 2) To conduct a pilot clinical study to assess the correlation of DR severity to
retinal capillary function in humans. 3) To explore the prognostic value of imaging markers for capillary
functions that can predict anti-VEGF treatment response. IMPACT ON PUBLIC HEALTH: 1) The success of
this project will lead to a groundbreaking new imaging device that is currently not available. 2) The validity of
the imaging method could also lead to further clinical studies on predictive imaging markers on DR progression
and treatment response. 3) The multiple measurements of capillary functions will provide further insight into the
pathophysiology and new treatment strategies for this debilitating eye disease.

## Key facts

- **NIH application ID:** 10220441
- **Project number:** 7R01NS108464-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Ji Yi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $489,205
- **Award type:** 7
- **Project period:** 2018-09-30 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10220441

## Citation

> US National Institutes of Health, RePORTER application 10220441, Predictive markers for diabetic retinopathy via quantitative imaging of retinal capillary functions (7R01NS108464-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10220441. Licensed CC0.

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