Macrophage-Like Cell Density and Distribution in Relation to Vascular Leakage in Diabetes.

Purpose: To investigate the relationship between macrophage-like cell (MLC) density and vascular leakage in the macula, an indicator of blood-retinal barrier (BRB) breakdown, in diabetic retinopathy (DR), and to understand whether MLCs cluster within areas of vascular leakage. Design: Cross-sectional imaging analysis. Subjects: A total of 161 eyes from 152 diabetic participants with various stages of DR. Methods: Fluorescein angiography (FA) was used to delineate and quantify macular leakage and OCT angiography was used to visualize MLCs using an averaged 3-μm OCT slab above the vitreoretinal interface. In a subgroup of 36 eyes, MLC density maps were overlaid onto FA images to assess the spatial distribution of MLCs relative to leakage zones and their perimeter. Main Outcome Measures: Correlation between MLC density and macular leakage, and the spatial distribution of MLCs in relation to leakage zones. Results: A nonlinear relationship was observed between MLC density and macular leakage, captured by a quadratic model (r2 = 0.246, P < 0.001). Macrophage-like cell density increased with leakage, peaking between 50% and 60%, but then declined in eyes with more extensive leakage (>60%). Macrophage-like cells were more likely to cluster near leakage boundaries (P < 0.01), without difference in MLC density inside- versus outside-leakage areas (P = 0.08). Conclusions: The nonlinear relationship between MLC density and macular leakage in DR, along with MLC accumulation around the borders of leakage, suggest a nuanced role for these cells in DR and BRB breakdown. These findings also suggest a complex interplay among different macrophage populations and may reflect changes in MLC function or migration to deeper retinal layers with advancing leakage. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.