Abstract
PURPOSE: To determine longitudinal alterations in corneal nerve fiber morphology, dendritic cell (DC) density, and retinal nerve fiber layer (RNFL) thickness over 2 years in patients with multiple sclerosis (MS). METHODS: Thirty-one consecutive patients with relapsing-remitting MS (RRMS) underwent assessment of the Kurtzke Expanded Disability Status Scale (EDSS), Multiple Sclerosis Severity Score (MSSS), corneal confocal microscopy to quantify corneal subbasal nerve morphology and DC density, and spectral-domain optical coherence tomography to quantify RNFL thickness at baseline and after 2 years. RESULTS: There was a significant reduction in corneal nerve fiber area (CNFA) (P = 0.003), nerve fiber width (CNFW) (P = 0.005), and RNFL thickness (P = 0.004) with an increase in EDSS (P = 0.01) over 2 years. The change in corneal nerve fiber density (CNFD) correlated with the change in EDSS (ρ = -0.468; P = 0.008), MSSS (ρ = -0.442; P = 0.01), DC density (ρ = -0.550; P = 0.001), and RNFL (ρ = 0.472; P = 0.007). The change in corneal nerve fiber length (CNFL) correlated with the change in EDSS (ρ = -0.445; P = 0.01) and MSSS (ρ = -0.490; P = 0.005). Furthermore, there was a significant decrease in CNFL (P < 0.001), CNFA (P = 0.02), CNFW (P = 0.04), corneal total branch density (P = 0.01), and RNFL thickness (P = 0.02) and a significant increase in DC density (P = 0.04) in patients with worsening EDSS (n = 15). CONCLUSIONS: Corneal confocal microscopy can be used to detect progressive corneal nerve fiber loss that relates to a progression of disability in patients with RRMS. TRANSLATIONAL RELEVANCE: Corneal confocal microscopy acts as a sensitive imaging biomarker for progressive nerve degeneration in patients with MS.