TY - JOUR
T1 - Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
AU - Petropoulos, Ioannis N.
AU - Fitzgerald, Kathryn C.
AU - Oakley, Jonathan
AU - Ponirakis, Georgios
AU - Khan, Adnan
AU - Gad, Hoda
AU - George, Pooja
AU - Deleu, Dirk
AU - Canibano, Beatriz G.
AU - Akhtar, Naveed
AU - Shuaib, Ashfaq
AU - Own, Ahmed
AU - Malik, Taimur
AU - Russakoff, Daniel B.
AU - Mankowski, Joseph L.
AU - Misra, Stuti L.
AU - McGhee, Charles N.J.
AU - Calabresi, Peter
AU - Saidha, Shiv
AU - Kamran, Saadat
AU - Malik, Rayaz A.
N1 - Funding Information:
Drs. Ioannis N. Petropoulos, Kathryn C. Fitzgerald, Georgios Ponirakis, Adnan Khan, Hoda Gad, Pooja George, Dirk Deleu, Beatriz Canibano, Naveed Akhtar, Ashfaq Shuaib, Ahmed Own, Stuti L. Misra, Charles N.J. McGhee and Saadat Kamran report no financial disclosures. Dr. Jonathan Oakley is an employee of Voxeleron LLC and holds a patent application relating to aspects of the algorithm’s implementation (Voxeleron deepNerve). Dr. Taimur M. Malik owns stock in Pfizer, Cymba Therapeutics, Moderna, Boston Scientific and Walgreens. Dr. Daniel B Russakoff is an employee of Voxeleron LLC and holds a patent application relating to aspects of the algorithm’s implementation (Voxeleron deepNerve). Dr. Joseph L Mankowski holds a patent application relating to aspects of the algorithm’s implementation (Voxeleron deepNerve). Dr. Peter Calabresi is PI on grants to Johns Hopkins from Annexon and Biogen and has received consulting honoraria from Biogen and Disarm Therapeutics for serving on scientific advisory boards. Dr. Shiv Saidha has received consulting fees from Medical Logix for the development of CME programs in neurology, and has served on scientific advisory boards for Biogen, Genzyme, Genentech Corporation, EMD Serono, and Celgene. He is the PI of investigator-initiated studies funded by Genentech and Biogen, was the site investigator of a trial sponsored by MedDay Pharmaceuticals and received support from the Race to Erase MS foundation. He has received equity compensation for consulting from JuneBrain LLC, a retinal imaging device developer. Dr. Rayaz A. Malik is a PI on grants from Proctor and Gamble and Pfizer and has received consulting honoraria for serving on advisory boards for Novo Nordisk, Aventis Pharma and Proctor and Gamble.
Funding Information:
This work was kindly supported by Qatar National Research Fund (Grant Number BMRP 20038654), a Merck Grant for Multiple Sclerosis Innovation (Grant Number 201701.10249.POT) and the Blaustein Pain Research Fund, Johns Hopkins University School of Medicine (Joseph L. Mankowski). Dr. Stuti L. Misra was supported by a Fulbright New Zealand Travel Award.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-021-01226-1
DO - 10.1038/s41598-021-01226-1
M3 - Article
C2 - 34737384
AN - SCOPUS:85118607677
SN - 2045-2322
VL - 11
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 21688
ER -