Purpose To identify optical coherence tomography angiography (OCTA)-derived biomarkers correlating with diabetic retinopathy (DR) severity and characterize longitudinal retinal microvascular changes across DR stages.

Methods In this 3-year prospective study, we analyzed OCTA images from 328 eyes of 164 adults with type II diabetes and 33 eyes from 17 healthy controls. Patients were categorized as no DR, mild, moderate, or severe nonproliferative DR (NPDR), or proliferative DR (PDR) at baseline. Bilateral OCTA scans were obtained at each visit and processed with a validated pipeline to extract seven microvascular indices from the superficial and deep capillary plexuses: vessel density, skeleton density, acircularity index, average vessel caliber, foveal avascular zone (FAZ) area, FAZ perimeter, and fractal dimensions. Linear regression quantified changes over time, and intergroup comparisons were made using ANOVA and post-hoc testing.

Results Patients with severe NPDR showed a significant annual decrease in vessel density and skeleton density in the deep capillary plexus compared to healthy controls, indicating progressive ischemia. Acircularity index increased significantly in severe NPDR compared to mild NPDR, suggesting worsening macular ischemia. In the superficial plexus, severe NPDR patients exhibited significantly greater annual vessel caliber narrowing than mild NPDR. Conversely, skeleton density in PDR increased relative to severe NPDR, possibly reflecting neovascular remodeling.

Conclusions Longitudinal OCTA analysis reveals stage-specific microvascular changes in DR. These dynamic biomarkers may provide early indicators of DR progression and offer a quantitative foundation for individualized monitoring and timely intervention strategies.

Translational Relevance OCTA-derived biomarkers offer a noninvasive tool for detecting early DR changes and guiding personalized care strategies.

The authors have declared no competing interest.

NCT04505566

This study was funded by the National Eye Institute (R01-EY031315).

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Vanderbilt University Medical Center gave ethical approval for this work.

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All data produced in the present study are available upon reasonable request to the authors.