Longitudinal Optical Coherence Tomography Imaging Reveals Hyperreflective Foci Characteristics in Relapsing–Remitting Multiple Sclerosis Patients

<b>Background/Objectives:</b> Retinal hyperreflective foci, 25-50 µm in diameter, that can be imaged by noninvasive optical coherence tomography (OCT) may represent microglial activity related to inflammation. This study aimed to detect hyperreflective foci in the OCT-hyporeflective avascular outer nuclear layer of the retina in relapsing-remitting MS (RRMS) patients without ongoing eye or optic nerve disease. <b>Methods:</b> A cohort of 13 RRMS patients (8 eyes with and 18 eyes without prior optic neuritis) underwent retinal OCT at baseline, after 1 month, after 6 months, and then every 6 months for 3 years. The data were compared with single-examination data from 106 eyes in 53 age-matched healthy subjects. <b>Results:</b> The prevalence of hyperreflective foci at baseline was higher in RRMS patients than in healthy subjects (46.2% vs. 1.8%, <i>p</i> < 0.005). Patients with optic neuritis had much more foci than those without (<i>p</i> < 0.001). Hyperreflective foci recurred in 23.1% of RRMS patients, bilaterally in one with prior optic neuritis and unilaterally in two without. <b>Conclusions:</b> Patients with RRMS, notably those with prior optic neuritis, had elevated rates of retinal infiltration in the absence of retinal disease, suggesting that the phenomenon may represent elevated activity of an immune surveillance or housekeeping mechanism rather than retinal disease.