Are corneal nerve and dendritic cell parameters assessed via corneal confocal microscopy good markers for multiple sclerosis? - A systematic review and meta-analysis.

Objective: The current study evaluated corneal nerve and dendritic cell changes in multiple sclerosis (MS) compared to healthy controls.

Methods: The study was registered with PROSPERO (ID: CRD42024606762) and adhered to the PRISMA guidelines. PubMed, Scopus, and Web of Science databases were searched. Mean difference (MD), with a 95 % confidence interval, was used to assess outcomes. The quality of evidence was assessed using the GRADE system.

Results: 12 cross-sectional comparative studies (n = 485 MS patients, n = 319 controls) met the inclusion criteria. Corneal nerve fiber density (MD = -8.35 fibers/mm, 95 % CI: -11.90 to -4.79; number of studies = 6), corneal nerve fiber length (MD = -4.05 mm/mm, 95 % CI: -5.74 to -2.36; number of studies = 9) and corneal nerve branch density (MD = -18.76 branches/mm, 95 % CI: -21.51 to -16.02; number of studies = 6) were significantly lower in MS compared to healthy controls. Heterogeneity was significant for corneal nerve fiber density and corneal nerve fiber length, but insignificant for corneal nerve branch density. No significant difference was found in corneal dendritic cell density; however, in the subgroup with disease duration ≤8 years, multiple sclerosis patients had significantly higher dendritic cell density (MD = 17.36 cells/mm, 95 % CI: 4.17 to 30.56; number of studies = 3).

Conclusion: Corneal nerve degeneration and dendritic cell changes assessment with corneal confocal microscopy may be an emerging tool with potential for disease monitoring. Further longitudinal studies are needed to validate these findings and clarify their correlation with MS progression and severity.