Corneal Confocal Microscopy Identifies and Differentiates Patients With Multiple Sclerosis and Epilepsy.

Purpose: To assess whether corneal nerve analysis can identify and differentiate patients with multiple sclerosis (MS) from those with epilepsy.

Methods: Participants with MS (n = 83), participants with epilepsy (n = 50), and healthy controls (HCs) (n = 20) underwent corneal confocal microscopy (CCM) and quantification of automated corneal nerve fiber length (ACNFL), automated corneal nerve fractal dimension (ACNFrD), and ACNFrD/ACNFL ratio of the subbasal nerve plexus.

Results: ACNFL (MS: P < 0.0001; epilepsy: P = 0.002) and ACNFrD (MS: P < 0.0001; epilepsy: P = 0.025) were significantly lower and the ACNFrD/ACNFL ratio (MS: P < 0.0001; epilepsy: P = 0.018) was significantly higher compared to HCs. ACNFL (P = 0.001), ACNFrD (P = 0.0003), and ACNFrD/ACNFL ratio (P = 0.006) were significantly lower in patients with MS compared to those with epilepsy. ACNFL had the highest diagnostic utility for identifying patients with MS (sensitivity/specificity 0.86/0.85, area under the curve [AUC] 0.90, P < 0.0001), and ACNFrD had the highest diagnostic utility for identifying patients with epilepsy (sensitivity/specificity 0.78/0.75, AUC 0.76, P = 0.0008). ACNFrD had the highest diagnostic utility for differentiating patients with MS from epilepsy (sensitivity/specificity 0.66/0.65, AUC 0.70, <0.0001).

Conclusions: Corneal neurodegeneration occurs in and is characterized by a distinct pattern that differentiates patients with MS and epilepsy.

Translational Relevance: CCM identifies and differentiates patients with MS and epilepsy, albeit with moderate performance. Further validation, with a larger sample size, is needed.