Quantitative Volumetric Analysis of Retinal Ischemia with an Oxygen Diffusion Model and OCT Angiography

Purpose

Retinal ischemia is a major feature of diabetic retinopathy (DR). Traditional nonperfused areas measured by OCT angiography (OCTA) measure blood supply but not ischemia. We propose a novel 3-dimensional (3D) quantitative method to derive ischemia measurements from OCTA data.

Design

Cross-sectional study.

Participants

We acquired 223 macular OCTA volumes from 33 healthy eyes, 33 diabetic eyes without retinopathy, 7 eyes with nonreferable DR, 17 eyes with referable but nonvision-threatening DR, and 133 eyes with vision-threatening DR.

Methods

Each eye was scanned using a spectral-domain OCTA system (Avanti RTVue-XR, Visionix/Optovue, Inc) with 1.6-mm scan depth in a 3 × 3-mm region (640 × 304 × 304 voxels) centered on the fovea. For each scanned OCTA volume, a custom algorithm removed flow projection artifacts. We then enhanced, binarized, and skeletonized the vasculature in each OCTA volume and generated a 3D oxygen tension map using a zero-order kinetics oxygen diffusion model. Each volume was scaled to the average retina thickness in healthy controls after foveal registration and flattening of the Bruch's membrane. Finally, we extracted 3D ischemia maps by comparison with a reference map established from scans of healthy eyes using the same processing. To assess the ability of the ischemia maps to grade DR severity, we constructed receiver operating characteristic curves for diagnosing diabetes, referable DR, and vision-threatening DR.

Main Outcome Measures

Spearman correlation coefficient and area under receiver operating characteristic curve (AUC) were used to quantify the ability of the ischemia maps to DR.

Results

The ischemia maps showed that the ischemic tissues were at or near pathologically nonperfused areas, but not the normally nonvascular tissue, such as the foveal avascular zone. We found multiple novel metrics, including inferred 3D-oxygen tension, ischemia index, and ischemic volume ratio, were strongly correlated with DR severity. The AUCs of ischemia index measured were 0.94 for diabetes, 0.89 for DR, 0.88 for referable DR, and 0.85 for vision-threatening DR.

Conclusions

A quantitative method to infer 3D oxygen tension and ischemia using OCTA in diabetic eyes can identify ischemic tissue that are more specific to pathologic changes in DR.

Financial Disclosures

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.