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

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....

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Main Authors: Ioannis N. Petropoulos, Kathryn C. Fitzgerald, Jonathan Oakley, Georgios Ponirakis, Adnan Khan, Hoda Gad, Pooja George, Dirk Deleu, Beatriz G. Canibano, Naveed Akhtar, Ashfaq Shuaib, Ahmed Own, Taimur Malik, Daniel B. Russakoff, Joseph L. Mankowski, Stuti L. Misra, Charles N. J. McGhee, Peter Calabresi, Shiv Saidha, Saadat Kamran, Rayaz A. Malik
Format: Article
Language:English
Published: Nature Portfolio 2021-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-021-01226-1
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author Ioannis N. Petropoulos
Kathryn C. Fitzgerald
Jonathan Oakley
Georgios Ponirakis
Adnan Khan
Hoda Gad
Pooja George
Dirk Deleu
Beatriz G. Canibano
Naveed Akhtar
Ashfaq Shuaib
Ahmed Own
Taimur Malik
Daniel B. Russakoff
Joseph L. Mankowski
Stuti L. Misra
Charles N. J. McGhee
Peter Calabresi
Shiv Saidha
Saadat Kamran
Rayaz A. Malik
author_facet Ioannis N. Petropoulos
Kathryn C. Fitzgerald
Jonathan Oakley
Georgios Ponirakis
Adnan Khan
Hoda Gad
Pooja George
Dirk Deleu
Beatriz G. Canibano
Naveed Akhtar
Ashfaq Shuaib
Ahmed Own
Taimur Malik
Daniel B. Russakoff
Joseph L. Mankowski
Stuti L. Misra
Charles N. J. McGhee
Peter Calabresi
Shiv Saidha
Saadat Kamran
Rayaz A. Malik
author_sort Ioannis N. Petropoulos
collection DOAJ
description 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.
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spelling doaj.art-9d7dac5ed8594004baea67b426f557e92022-12-21T19:52:57ZengNature PortfolioScientific Reports2045-23222021-11-011111910.1038/s41598-021-01226-1Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosisIoannis N. Petropoulos0Kathryn C. Fitzgerald1Jonathan Oakley2Georgios Ponirakis3Adnan Khan4Hoda Gad5Pooja George6Dirk Deleu7Beatriz G. Canibano8Naveed Akhtar9Ashfaq Shuaib10Ahmed Own11Taimur Malik12Daniel B. Russakoff13Joseph L. Mankowski14Stuti L. Misra15Charles N. J. McGhee16Peter Calabresi17Shiv Saidha18Saadat Kamran19Rayaz A. Malik20Research Division, Qatar Foundation, Weill Cornell Medicine-Qatar of Cornell UniversityDepartment of Neurology, Johns Hopkins University School of MedicineVoxeleron LLCResearch Division, Qatar Foundation, Weill Cornell Medicine-Qatar of Cornell UniversityResearch Division, Qatar Foundation, Weill Cornell Medicine-Qatar of Cornell UniversityResearch Division, Qatar Foundation, Weill Cornell Medicine-Qatar of Cornell UniversityNeuroscience Institute, Hamad General HospitalNeuroscience Institute, Hamad General HospitalNeuroscience Institute, Hamad General HospitalNeuroscience Institute, Hamad General HospitalNeuroscience Institute, Hamad General HospitalNeuroscience Institute, Hamad General HospitalDepartment of Neurology, Johns Hopkins University School of MedicineVoxeleron LLCDepartment of Neurology, Johns Hopkins University School of MedicineDepartment of Ophthalmology, New Zealand National Eye Centre, University of AucklandDepartment of Ophthalmology, New Zealand National Eye Centre, University of AucklandDepartment of Neurology, Johns Hopkins University School of MedicineDepartment of Neurology, Johns Hopkins University School of MedicineNeuroscience Institute, Hamad General HospitalResearch Division, Qatar Foundation, Weill Cornell Medicine-Qatar of Cornell UniversityAbstract 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.https://doi.org/10.1038/s41598-021-01226-1
spellingShingle Ioannis N. Petropoulos
Kathryn C. Fitzgerald
Jonathan Oakley
Georgios Ponirakis
Adnan Khan
Hoda Gad
Pooja George
Dirk Deleu
Beatriz G. Canibano
Naveed Akhtar
Ashfaq Shuaib
Ahmed Own
Taimur Malik
Daniel B. Russakoff
Joseph L. Mankowski
Stuti L. Misra
Charles N. J. McGhee
Peter Calabresi
Shiv Saidha
Saadat Kamran
Rayaz A. Malik
Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
Scientific Reports
title Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
title_full Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
title_fullStr Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
title_full_unstemmed Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
title_short Corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
title_sort corneal confocal microscopy demonstrates axonal loss in different courses of multiple sclerosis
url https://doi.org/10.1038/s41598-021-01226-1
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