Ultra-Widefield OCTA Mapping of Epiretinal Macrophage-Like Cells in Patients With Retinal Vein Occlusion

Purpose: To characterize the ultra-widefield distribution and morphology of epiretinal macrophage-like cells (eMLCs) in retinal vein occlusion (RVO) and assess their associations with retinal ischemia and macular edema. Methods: This cross-sectional study included 68 eyes with unilateral branch or central RVO and 68 unaffected fellow eyes as controls. All eyes underwent 24 × 20 mm ultra-widefield swept-source optical coherence tomography angiography (OCTA). The eMLC density and morphology were quantified using a machine-learning-based pipeline. Foveal avascular zone (FAZ) metrics, central subfield thickness (CST), and nonperfusion areas (NPAs) were analyzed. Exploratory duration-based subgroup analyses were also performed. Results: Compared with fellow eyes, RVO eyes showed higher eMLC density (3.69 [2.43] vs. 2.24 [1.12] cells/mm²), greater total eMLCs area (5.31 [3.83] vs. 2.87 [1.74] mm²), greater CST (411.50 [374.75] vs. 290.50 [35.00] µm), and larger FAZ area (0.360 [0.375] vs. 0.220 [0.165] mm²; all P < 0.001). Within-eye regional analyses showed lower eMLC density in the macular region than in the remaining retina (3.09 [1.57] vs. 4.06 [2.82] cells/mm²) and in NPAs than in the remaining retinal regions of the same image (2.39 [1.67] vs. 4.16 [1.89] cells/mm²; both P < 0.001). In RVO eyes, eMLC count was independently associated with disease duration, prior anti-VEGF injection number, and ischemic status. Conclusions: EMLCs are increased in RVO and show a spatially heterogeneous distribution pattern. In RVO eyes, eMLC count was associated with disease duration, prior anti-VEGF exposure, and ischemic status, whereas duration-based subgroup findings should be interpreted as exploratory. Translational Relevance: Ultra-widefield OCTA-based eMLCs quantification may provide a clinically accessible imaging biomarker for inflammatory involvement in RVO.