Baseline Deep Capillary Plexus Ischemia Predicts Earlier Diabetic Retinopathy Complications Than Foveal Avascular Enlargement.

Abstract

Purpose: To evaluate whether diabetic macular ischemia metrics-deep capillary plexus baseline geometric perfusion deficit (GPDd) and foveal avascular zone enlargement (FAZe)-predict the risk and timing of diabetic retinopathy (DR) complications in a 2-year period.

Design: A prospective observational cohort study.

Participants: A total of 265 eyes (175 patients) across the DR severity spectrum.

Methods: Patients underwent baseline and follow-up ophthalmic evaluations. GPDd was quantified as the percentage of retinal tissue ≥30 µm from the nearest perfused capillary on 3 × 3-mm optical coherence tomography angiography (OCTA) images of the deep capillary plexus. FAZe was calculated as the difference between the structural FAZ area measured on en face OCT and the functional FAZ area measured on OCTA. Time-to-complication analysis was conducted using Cox regression models adjusted for age, sex, glycated hemoglobin, diabetes duration, and hypertension; because of its collinearity with OCTA metrics, DR severity was excluded from the primary analysis. Restricted mean survival time (RMST) quantified the differences in complication-free survival time (days). Kaplan-Meier curves compared survival profiles between high- and low-biomarker groups, defined using the optimal Youden's J-index cutoff for referable DR.

Main outcome measures: Baseline GPDd and FAZe levels, occurrence of DR complications, and time to the first complication. DR complications were defined as a loss of ≥10-letter best-corrected visual acuity, DR severity progression, vitreous hemorrhage, initiation of an anti-VEGF therapy, or panretinal photocoagulation.

Results: Higher baseline GPDd level was associated with both an increased hazard and earlier onset of DR complications. In restricted mean survival time analysis, a +1 SD increase in GPDd corresponded to a 70-day reduction in complication-free survival (95% CI, -103.9 to -36.0; P < .001). When dichotomized into high and low GPDd groups, eyes with high GPDd level developed complications 117.2 days (∼4 months) earlier than those with low GPDd level (95% CI, -187.7 to -46.8; P = .001). In multivariable Cox regression, each 1-SD increase in GPDd (3.62%) was associated with a 77% higher hazard of complications (P < .001). By contrast, FAZe was not significantly associated with an increased hazard or earlier complication onset after adjustment for GPDd.

Conclusions: Elevated GPDd level, but not FAZe, independently predicted an increased complication risk and shorter complication-free survival. GPDd is a robust, time-sensitive biomarker for patients who may benefit from closer monitoring.