Multimodal imaging biomarkers associated with recurrence of diabetic macular edema during aflibercept treat-and-extend therapy

This prospective, non-randomized study aimed to identify multimodal imaging biomarkers predictive of treatment response in diabetic macular edema (DME) patients undergoing intravitreal aflibercept therapy using a treat-and-extend (T&E) regimen. Twenty-eight eyes with center-involved DME received five monthly aflibercept injections followed by an 18-month T&E phase. Imaging biomarkers included hyperreflective foci (HRF) and choroidal vascular index (CVI) on OCT, leakage area and microaneurysm count on fluorescein angiography (FA), and intraretinal microvascular abnormalities (IRMA) on OCT angiography (OCTA). During the T&E phase, treatment intervals were shortened in 39.3% of eyes and maximally extended in 60.7%, with complete macular dryness maintained in 22.6%. The completely dry group showed significant reductions in HRF, CVI, leakage area (84.4%), and microaneurysm count (57.7%). Minimal leakage (< 1 mm²) was observed in 85.7% of the dry group compared with 10-23.5% of other groups. OCTA revealed greater IRMA regression in the dry group (75.0%) than in the shortened interval group (10.3%). Logistic regression identified IRMA regression as a significant predictor of treatment interval extension. Multimodal imaging, particularly OCTA-derived IRMA regression, may serve as a valuable biomarker for optimizing individualized T&E management in DME.