Anatomical and systemic predictors of early response to subthreshold micropulse laser in diabetic macular edema: a retrospective cohort study

Background/Objectives: The aim of this study was to identify anatomical and systemic predictors of early (≤2 months) response to subthreshold micropulse laser (SMPL) in center-involving diabetic macular edema (DME) using automated AI-based OCT biomarker quantification. Methods: Retrospective observational study of 65 eyes. Spectral-domain optical coherence tomography (SD-OCT) volumes were analyzed with a CE-marked software (Ophthal v1.0; Mr. Doc s.r.l., Rome, Italy) to quantify intraretinal fluid (IRF) and subretinal fluid (SRF) volumes and outer retinal integrity (external limiting membrane, ELM; ellipsoid zone, EZ). SMPL (577 nm; 5% duty cycle; 200 ms; 150 µm; 250 mW) was applied in a high-density macular grid, sparing the foveal avascular zone. The primary endpoint was absolute and percentage change in IRF volume from baseline to follow-up; predictors of %IRF reduction were assessed by multivariable linear regression. Results: At 52 days (IQR 41–60), best-corrected visual acuity improved from 0.22 to 0.15 logMAR (p < 0.001). IRF volume decreased (median −0.045 mm3; p = 0.034) despite stable central subfield thickness. All eyes with baseline SRF (n = 5; median 0.026 mm3 [0.020–0.046]) achieved complete SRF resolution. Treatment-naïve eyes had greater %IRF reduction than pretreated eyes (59.6% vs. 11.5%; p = 0.029). High responders showed shorter diabetes duration than low responders (14.5 vs. 17 years; p = 0.025); however, treatment-naïve status was the strongest independent predictor of %IRF reduction (p = 0.028). Conclusions: AI-derived fluid volumetrics capture early SMPL response despite unchanged thickness. Treatment-naïve status and shorter diabetes duration may define a metabolic window for optimal early response in DME.