Macular Optical Coherence Tomography Angiography Biomarkers Predict Regional Retinal Nonperfusion Patterns on Ultrawidefield Angiography in Diabetes

Summary

Diabetic macular OCTA DCP perfusion defects biomarker for ischemia in all retinal regions on UWF FA. Increased FAZ reflected posterior ischemia. Prospective — 159 eyes.

Abstract

Objective: To determine whether foveal avascular zone (FAZ) enlargement and geometric perfusion deficits in the deep capillary plexus (GPDd) are independently associated with retinal nonperfusion in different regions of ultrawidefield fluorescein angiography (UWF-FA) in diabetes.

Design: Prospective cross-sectional observational study.

Participants: A total of 159 eyes from 112 patients with diabetes, and without center-involving diabetic macular edema, across the spectrum of diabetic retinopathy severity.

Methods: Nonperfusion in the posterior, peripheral (inside and outside ETDRS 7-fields, respectively), and total retina were quantified on UWF-FA. Averaged 3 × 3 mm en-face optical coherence tomography (OCT) and OCT angiography (OCTA) were used to measure the structural and functional FAZ areas, respectively, and the discrepancy between them defined as FAZ enlargement. GPDd was defined as the proportion of retinal areas located ≥30 µm from the nearest perfused capillary on OCTA in the deep capillary plexus. Linear mixed-effects models adjusted for key covariates were applied, and model fit was evaluated using likelihood ratio tests and information criteria.

Main outcome measures: Standardized associations (β) and improvements in model fit for FAZ enlargement and GPDd in predicting posterior, peripheral, and total nonperfusion.

Results: Posterior nonperfusion was significantly associated with GPDd (β = 0.216, P < .001), FAZ enlargement (β = 0.128, P = .016), and hemoglobin A1c (β = 0.240, P = .008). Both peripheral and total nonperfusion were associated with GPDd (β = 0.216 and 0.237; P = .008 and 0.001, respectively) and diabetes duration (β = 0.214 for both; P = .046 and 0.040), but not with FAZ enlargement. Model comparisons further confirmed the added value of GPDd across all regions (P ≤ .009), whereas FAZ enlargement improved model fit only for posterior nonperfusion (P ≤ .018).

Conclusions: Our findings suggest that GPDd is a robust biomarker of ischemic burden across all retinal regions, significantly improving model fit in predicting retinal nonperfusion on UWF-FA. On the other hand, FAZ enlargement reflected posterior ischemia but did not improve model performance outside that region. These findings highlight the complementary contributions of OCTA-derived metrics for regional characterization of retinal ischemia in diabetes, with implications for OCTA biomarker-based stratification.