Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study

Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) ( n = 45) or secondary progressive MS (SPMS) ( n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm 2 ) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls ( n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP ( p < 0.001 and p < 0.001, respectively) and DCF ( p < 0.001 and p = 0.005) were higher and NCF ( p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP ( p = 0.01) was significantly reduced, and NCP ( p = 0.004) and NCF ( p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher ( p = 0.04–0.05) in patients who switched disease-modifying treatment, and baseline NCP ( p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS