Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis

• Published in: Scientific reports Vol. 11; no. 1; p. 21688
• Main Authors: Petropoulos, Ioannis N., Fitzgerald, Kathryn C., Oakley, Jonathan, Ponirakis, Georgios, Khan, Adnan, Gad, Hoda, George, Pooja, Deleu, Dirk, Canibano, Beatriz G., Akhtar, Naveed, Shuaib, Ashfaq, Own, Ahmed, Malik, Taimur, Russakoff, Daniel B., Mankowski, Joseph L., Misra, Stuti L., McGhee, Charles N. J., Calabresi, Peter, Saidha, Shiv, Kamran, Saadat, Malik, Rayaz A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.11.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 692/53; 692/53/2421; 692/617; Adult; Algorithms; Autoimmune diseases; Axons - physiology; Biomarkers; Confocal microscopy; Cornea; Cornea - diagnostic imaging; Cornea - innervation; Cornea - metabolism; Disease Progression; Female; Fibers; Humanities and Social Sciences; Humans; Male; Microscopy; Microscopy, Confocal - methods; Middle Aged; multidisciplinary; Multiple sclerosis; Multiple Sclerosis - metabolism; Multiple Sclerosis - physiopathology; Nerve Fibers; Reproducibility of Results; Science; Science (multidisciplinary); Segmentation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-01226-1

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/mm 2 , 95% CI − 18.24 to − 11.59, P  < .0001), CNFL [for ACCMetrics: 19.75 ± 2.39 vs. 12.40 ± 3.30 mm/mm 2 , 95% CI − 8.94 to − 5.77, P  < .0001; for deepNerve: 21.98 ± 2.76 vs. 14.40 ± 4.17 mm/mm 2 , 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.