Abstract
BACKGROUND: Hyperreflective retinal foci (HRF) visualized by optical coherence tomography (OCT) potentially represent clusters of microglia. We compared HRF frequencies and their association with retinal neurodegeneration between people with clinically isolated syndrome (pwCIS), multiple sclerosis (pwMS), aquaporin 4-IgG positive neuromyelitis optica spectrum disorder (pwNMOSD), and healthy controls (HC)-as well as between eyes with (ON(+)eyes) and without a history of optic neuritis (ON(-)eyes). METHODS: Cross-sectional data of pwCIS, pwMS, and pwNMOSD with previous ON and HC were acquired at Charité-Universitätsmedizin Berlin. HRF analysis was performed manually on the central macular OCT scan. Semi-manual OCT segmentation was performed to acquire the combined ganglion cell and inner plexiform layer (GCIPL), inner nuclear layer (INL), and peripapillary retinal nerve fiber layer (pRNFL) thickness. Group comparisons were performed by linear mixed models. RESULTS: In total, 227 eyes from 88 patients (21 pwCIS, 32 pwMS, and 35 pwNMOSD) and 35 HCs were included. HRF in GCIPL and INL were more frequently detected in pwCIS, pwMS, and pwNMOSD than HCs (p < 0.001 for all comparisons) with pwCIS exhibiting the greatest numbers. ON(+)eyes of pwMS had less HRF in GCIPL than ON(-)eyes (p = 0.036), but no difference was seen in pwCIS and pwNMOSD. HRF GCIPL were correlated to GCIPL thickness in ON(+)eyes in pwMS (p = 0.040) and pwNMOSD (p = 0.031). CONCLUSION: HRF occur in ON(+)eyes and ON(-)eyes across neuroinflammatory diseases. In pwMS and pwNMOSD, HRF frequency was positively associated with GCIPL thickness indicating that HRF formation might be dependent on retinal ganglion cells.