Abstract
Axonal loss is the main determinant of disease progression in multiple sclerosis (MS). This study aimed to assess the utility of corneal confocal microscopy (CCM) in detecting corneal axonal loss in different courses of MS. The results were confirmed by two independent segmentation methods. 72 subjects (144 eyes) [(clinically isolated syndrome (n = 9); relapsing–remitting MS (n = 20); secondary-progressive MS (n = 22); and age-matched, healthy controls (n = 21)] underwent CCM and assessment of their disability status. Two independent algorithms (ACCMetrics; and Voxeleron deepNerve) were used to quantify corneal nerve fiber density (CNFD) (ACCMetrics only), corneal nerve fiber length (CNFL) and corneal nerve fractal dimension (CNFrD). Data are expressed as mean ± standard deviation with 95% confidence interval (CI). Compared to controls, patients with MS had significantly lower CNFD (34.76 ± 5.57 vs. 19.85 ± 6.75 fibers/mm2, 95% CI − 18.24 to − 11.59, P < .0001), CNFL [for ACCMetrics: 19.75 ± 2.39 vs. 12.40 ± 3.30 mm/mm2, 95% CI − 8.94 to − 5.77, P < .0001; for deepNerve: 21.98 ± 2.76 vs. 14.40 ± 4.17 mm/mm2, 95% CI − 9.55 to − 5.6, P < .0001] and CNFrD [for ACCMetrics: 1.52 ± 0.02 vs. 1.45 ± 0.04, 95% CI − 0.09 to − 0.05, P < .0001; for deepNerve: 1.29 ± 0.03 vs. 1.19 ± 0.07, 95% − 0.13 to − 0.07, P < .0001]. Corneal nerve parameters were comparably reduced in different courses of MS. There was excellent reproducibility between the algorithms. Significant corneal axonal loss is detected in different courses of MS including patients with clinically isolated syndrome.
Highlights
Multiple Sclerosis (MS) is characterized by inflammation and neurodegeneration with cumulative axonal loss being the main determinant of disease progression[1]
Studies of smaller patient cohorts with predominantly relapsing–remitting MS (RRMS) have demonstrated corneal axonal loss and related it to clinical disability[19,20,21,22,23], retinal nerve fiber layer thinning[22] and an increase in corneal immune cell density[19,24]. It is not known if corneal axonal loss occurs in patients with clinically isolated syndrome (CIS) and whether it differs from RRMS and secondary progressive MS (SPMS)
Patients with SPMS had a significantly higher expanded disability status scale (EDSS) score compared to CIS (4.09 ± 2.29 vs. 0.67 ± 0.66, 95% CI − 5.0 to − 1.8, P < 0.0001) and RRMS with no significant difference between CIS and RRMS
Summary
Multiple Sclerosis (MS) is characterized by inflammation and neurodegeneration with cumulative axonal loss being the main determinant of disease progression[1]. Studies of smaller patient cohorts with predominantly relapsing–remitting MS (RRMS) have demonstrated corneal axonal loss and related it to clinical disability[19,20,21,22,23], retinal nerve fiber layer thinning[22] and an increase in corneal immune cell density[19,24]. The corneal subbasal nerve plexus is comprised of unmyelinated sensory nerve fibers derived from pseudo-unipolar neurons located in the trigeminal ganglion, which project centrally into the brainstem; and trigeminal lesions have been demonstrated in-vivo[25] and in pathological s pecimens[26] from patients with MS These findings argue that corneal nerve loss may act as a surrogate marker for central neurodegeneration and underpin the potential of CCM as a rapid, non-invasive surrogate marker for neurodegeneration in MS
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