In Vivo Corneal Confocal Microscopy in Multiple Sclerosis: Can it Differentiate Disease Relapse in Multiple Sclerosis?

Abstract

Purpose: This study aims to investigate the role of in vivo corneal confocal microscopy (IVCCM) in the detection of corneal inflammatory activity and subbasal nerve alterations in patients with multiple sclerosis (MS) and to further determine whether IVCCM can be used to detect (acute) disease relapse.

Design: Prospective cross-sectional study, with a subgroup follow-up.

Methods: This single-center study included 58 patients with MS (MS-Relapse group [n = 27] and MS-Remission group [n = 31]), and 30 age- and sex-matched healthy control subjects. Patients with a history of optic neuritis or trigeminal symptoms were excluded. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL), and dendritic cell (DC) density were evaluated in all patients with MS and control subjects by IVCCM. Patients in the MS-Relapse group who were in remission for ≥6 months after the MS incident underwent a repeat IVCCM.

Results: No statistical difference was observed between the MS-Relapse and MS-Remission groups regarding age, sex, MS duration, and the number of relapses (P > .05). Compared with healthy control subjects, all subbasal nerve parameters were significantly lower (CNFD: P < .001, CNFL: P < .001, CNBD: P < .001), and the DC density was significantly higher (P = .023) in patients with MS. However, no significant difference was observed between MS-Relapse and MS-Remission groups in terms of CNFD (mean [SE] difference -2.05 [1.69] fibers/mm² [95% confidence interval {CI} -1.32 to 5.43]; P < .227), CNFL (mean [SE] difference -1.10 [0.83] mm/mm² [95% CI -0.56 to 2.75]; P < .190), CNBD (mean [SE] difference -3.91 [2.48] branches/mm² [95% CI -1.05 to 8.87]; P < .120), and DC density (median [IQR], 59.38 [43.75-85.0] vs 75.0 [31.25-128.75]; P = .596). The repeat IVCCM in relapse patients (n = 16 [59.3%]) showed a significant increase in CNFD (P = .036) and CNBD (P = .018), but no change was observed in CNFL (P = .075) and DC density (P = .469).

Conclusion: Although increased inflammation and neurodegeneration can be demonstrated in patients with MS compared with healthy control subjects, a single time point evaluation of IVCCM does not seem to be sufficient to confirm the occurrence of relapse in patients with MS. However, IVCCM holds promise for demonstrating early neuroregeneration in patients with MS.

Keywords: In vivo corneal confocal microscopy; Inflammation; Multiple sclerosis; Neurodegeneration; Neuroregeneration; Relapse.