Inflammatory Hyperreflective Retinal Foci: An OCT Biomarker of Neuroinflammation in Geographic Atrophy

<b>Background</b>: Inflammatory hyperreflective retinal foci (I-HRF) have been recognized as an optical coherence tomography (OCT) biomarker of aggregates of activated microglial cells. Microglia, the principal resident immune cells, are key players in geographic atrophy (GA) development and progression. <b>Objective</b>: To quantify I-HRF distribution across inner (IR) and outer (OR) retinal layers in GA compared with healthy controls. <b>Methods</b>: Retrospective observational study including patients aged ≥50 years with GA lesion area >1.25 mm² and age-matched healthy subjects. GA eyes were classified as bilateral GA (B-GA) or unilateral GA (U-GA; fellow eye with macular neovascularization). Using Spectralis OCT, I-HRF (≤30 μm; RNFL-like reflectivity; no posterior shadowing) were identified and counted across IR and OR. <b>Results</b>: Sixty-eight eyes from 46 patients with GA (B-GA: 49 eyes; U-GA: 19 eyes) and 19 control eyes were studied. I-HRF were higher in IR than in OR in all groups (<i>p</i> < 0.001). I-HRF were higher in GA eyes in both layers compared with controls (<i>p</i> < 0.05). U-GA exhibited higher I-HRF than B-GA in IR (44.32 ± 8.47 vs. 30.10 ± 7.62; <i>p</i> < 0.001), while I-HRF were not significantly different in OR (9.58 ± 3.04 vs. 8.02 ± 3.33; <i>p</i> = 0.081). <b>Conclusions</b>: I-HRF are increased in GA. They are more numerous in IR, consistent with their proposed inflammatory origin. These findings further support the role microglia may play in GA pathology. I-HRF may become an OCT biomarker to track GA-associated neuroinflammation in different GA phenotypes. Longitudinal studies are needed to clarify I-HRF significance in GA progression.