Association of epiretinal membranes with disability in people with multiple sclerosis

Background: Epiretinal membranes (ERMs) consist of glial and fibrocellular tissue, potentially arising from pathologic microgliosis, macrogliosis, and/or retinal pigment epithelium (RPE) cell migration. The clinical relevance of ERMs in people with multiple sclerosis (PwMS) remains largely unstudied. Objectives: To investigate ERM prevalence and their associations with retinal layer thicknesses and disability measures in PwMS. Methods: PwMS exhibiting ERMs (ERM+) were matched 1:1 with PwMS without ERMs (ERM−) by optic neuritis (ON) history, multiple sclerosis (MS) subtype, age, sex, and race. Disability assessments included high-contrast/low-contrast letter acuity (HC-/LCLA), Expanded Disability Status Scale (EDSS), walking speed test (WST), manual dexterity test (MDT), and processing speed test (PST) scores. Results: Among 1264 participants screened (1120 PwMS and 144 healthy controls [HCs]), ERMs were observed in 206 PwMS (18.4%) and 17 HCs (11.8%). ERM+ PwMS exhibited higher EDSS (1.0 ± 0.3, p = 0.002), longer WST (0.8 ± 0.2 seconds, p < 0.001), longer MDT (2.2 ± 0.5 seconds, p < 0.001), lower PST (−3.0 ± 1.4, p = 0.08), lower LCLA (−4.2 ± 1.1 letters, p < 0.001), and lower ganglion cell-inner plexiform layer (−1.8 ± 0.8 µm, p = 0.03), inner nuclear layer (−0.8 ± 0.3 µm, p = 0.01), outer nuclear layer (−1.6 ± 0.6 µm, p = 0.01), and RPE (−0.5 ± 0.1 µm, p < 0.001) thicknesses. Higher ERM stage correlated with greater disability. Conclusion: ERMs may identify a distinct MS phenotype, potentially characterized by pathological microglial and/or macroglial activity. ERMs may be a marker of similar global processes throughout the central nervous system that potentially contribute to greater overall disability.