This study aims to explore the role of corneal confocal microscopy (CCM) in detecting axonal degeneration in MS and evaluate correlation with the Multiple Sclerosis Severity Score (MSSS) and Extended Disability Severity Score (EDSS). 

A literature search was conducted across PubMed, Scopus and Google Scholar. The differences in corneal nerve fiber measurements, including corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), between pwMS and healthy controls were quantified using risk ratio (RR) and estimated using random effects models due to high observed heterogeneity. Random-effects meta-regression was utilized to evaluate the relationship between mean EDSS and MSSS with CCM measurements.

A total of 8 studies were included in this meta-analysis with a total of 351 pwMS. CNFD and CNFL were significantly lower in pwMS compared to controls (Hedge’s G Effect Size = -1.53, 95% CI: -2.62, -0.44, p = .01). Meta-regression analysis showed that CNFD (Mean b = -1.93, 95% CI (-3.32, -0.55), p = .01), CNBD (Mean b = -33.36, 95% CI (-48.90, -17.82), p < .01) and CNFL (Mean b = -2.31, 95% CI (-2.94, -1.68) p < .01) had statistically significant associations with MSSS but not with EDSS.

This meta-analysis indicates that corneal nerve fibers measurements via CCM, namely CNFD and CNFL, are reliable and non-invasive biomarkers of axonal degeneration in MS. Additionally, our study highlights that MSSS, which had clear inverse associations with CNFD, CNFL and CNBD, may be a more reliable measure of axonal loss than EDSS.