Longitudinal Changes in Anatomic Biomarkers on Optical Coherence Tomography Angiography in Diabetic Retinopathy

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.

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.

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.

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. Competing Interest Statement The authors have declared no competing interest. Clinical Trial NCT04505566 Funding Statement This study was funded by the National Eye Institute (R01-EY031315). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes 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. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors.