The Importance of Matching Optical Coherence Tomography Angiography Metrics to Diabetic Retinopathy Severity for Detecting Progression.

Purpose: The purpose of this study was to determine which macular optical coherence tomography angiography (OCTA) metric best captures early progression of capillary non-perfusion across diabetic retinopathy (DR) severities. Methods: In this prospective, 1-year observational study, 208 patients with diabetes (320 eyes) underwent 3 × 3 mm macular OCTA at baseline, 6 months, and 12 months. Registered, averaged images yielded geometric perfusion deficits (GPDs), vessel density (VD), vessel length density (VLD) in the superficial and deep capillary plexuses (SCP and DCP), and foveal avascular zone area. Eyes were graded as non-referable or referable. Linear mixed models adjusted for age, sex, diabetes duration, hemoglobin A1c, and hypertension were conducted. Post hoc Dunnett's tests compared follow-ups with baseline within each severity group. Results: A total of 709 eye visits were analyzed by OCTA. Across the cohort, referable DR, longer diabetes duration, and hypertension were independently associated with higher GPD values. In referable eyes, GPD-DCP increased at 6 months (P = 0.036) and 1 year (P = 0.016), whereas no other OCTA metric changed significantly at 6 months. In non-referable eyes, the only significant change was a decrease in VD-SCP at 1 year (P = 0.004). Conclusions: Microvascular progression follows distinct, layer-specific patterns. In non-referable DR, capillary ischemia progresses more slowly and is more prominent in the SCP. In referable DR, GPD-DCP detected the earliest signs of microvascular progression and may serve as a promising biomarker, preceding vessel-based metrics. These findings suggest that the most informative OCTA metric should be tailored not only to the study question or timeline, but also to DR severity.