Dynamics of Hyper-Reflective Foci and Hard Exudates in Diabetic Macular Edema Treated with Faricimab

Background/Objectives: Diabetic macular edema is caused by disruptions in the blood-retinal barrier, resulting in leakage and inflammation, appearing in optical coherence tomography as retinal fluid, hard exudates, and hyper-reflective foci. This study aimed to assess volumetric changes in hyper-reflective foci and hard exudates in faricimab-treated diabetic macular edema in real-world practice. Methods: This retrospective longitudinal study included forty-four eyes with faricimab-treated diabetic macular edema and follow-up of ≥40 weeks. Optical coherence tomography scans were analyzed at baseline, post-loading, 6 months and 1 year. Hyper-reflective foci and hard exudates were quantified across macular subfields using a machine-learning algorithm with manual correction. Outcomes included volumetric changes, best-corrected visual acuity, and central subfield thickness. Early morphologic responders were defined post-loading by ≥20% central subfield thickness reduction and/or central subfield thickness below 280 µm. Results: At 1 year, hyper-reflective foci and hard exudate volumes significantly decreased in the central subfield (median differences: -0.025 nL, p = 0.00028; -0.119 nL, p = 0.00025) and outer ring (-0.178 nL, p = 0.00041; -0.612 nL, p = 0.014). Hard exudate volume significantly decreased in the inner ring (-0.740 nL, p < 0.0001). Best-corrected visual acuity and central subfield thickness improved significantly (-0.10 logarithm of the minimum angle of resolution (logMAR), p = 0.0018; -48 µm, p < 0.0001). Total hyper-reflective foci volumes were similar between responders and non-responders. In contrast, hard exudate burden remained numerically higher in non-responders. Conclusions: During the year following the switch to faricimab, HRF and HE burden decreased alongside visual and anatomical improvement. HRF volumes were descriptively similar between early CST responders and non-responders, whereas HE burden remained numerically higher in non-responders.