Microaneurysm Reflectivity as a Prognostic Biomarker for Intravitreal Treatment Response in Diabetic Retinopathy

Am J Ophthalmol. 2026 May:285:39-48. doi:10.1016/j.ajo.2026.01.027.

Summary

DME Anti-VEGF Microaneurysm: Complete fluid resolution in 51% of OCT hyperreflective MA phenotype vs 7% hyporeflective MA phenotype. Retrospective, 66 treatment-naive patients.

Abstract

Purpose: To investigate whether baseline reflectivity patterns of diabetic microaneurysms (MAs) on spectral-domain optical coherence tomography (SD-OCT) predict treatment response in diabetic macular edema (DME).

Design: Retrospective clinical cohort study.

Methods: Sixty-six patients with treatment-naive DME were analyzed. All microaneurysms within the central 3 mm ETDRS area were identified and classified based on internal reflectivity on SD-OCT. Patients were categorized into 2 phenotypic groups based on the predominant reflectivity pattern: predominantly hyperreflective phenotype (>50% hyperreflective MAs) or predominantly hyporeflective phenotype (>50% hyporeflective MAs). Patients received intravitreal anti-VEGF therapy or dexamethasone implants over 12 months. The primary outcome was complete intraretinal fluid resolution at 12-month follow-up.

Results: Thirty-nine patients (59.1%) were classified as hyperreflective phenotype and 27 (40.9%) as hyporeflective phenotype at baseline. Complete fluid resolution was achieved in 20 of 39 hyperreflective phenotype patients (51.3%) compared to 2 of 27 hyporeflective phenotype patients (7.4%, P < .001). Multivariate logistic regression confirmed phenotype classification as the only independent predictor of treatment response (OR 13.50, 95% CI 2.87-63.51, p < .001).

Conclusions: Microaneurysm reflectivity phenotype on SD-OCT may serve as a useful predictor of treatment response in DME. Hyperreflective phenotype demonstrated significantly higher rates of fluid resolution compared to hyporeflective phenotype, independent of patient characteristics and treatment modality.