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Original Investigation
June 1, 2017

Use of Corneal Confocal Microscopy to Detect Corneal Nerve Loss and Increased Dendritic Cells in Patients With Multiple Sclerosis

Author Affiliations
  • 1Department of Ophthalmology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
  • 2Department of Neurology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
  • 3Weill Cornell Medicine-Qatar, Education City, Doha, Qatar
  • 4Central Manchester University Teaching Hospitals Foundation Trust, University of Manchester, Manchester, England
JAMA Ophthalmol. Published online June 1, 2017. doi:10.1001/jamaophthalmol.2017.1590
Key Points

Question  Can in vivo confocal microscopy detect axonal loss in patients with multiple sclerosis?

Findings  In this cross-sectional comparative study of 57 patients with multiple sclerosis and 30 healthy individuals, in vivo corneal confocal microscopy demonstrated reduced corneal nerve measures and increased dendritic cell density in patients with multiple sclerosis.

Meaning  Corneal confocal microscopy may be used as an imaging biomarker for identifying axonal loss in patients with multiple sclerosis.


Importance  Multiple sclerosis (MS) is characterized by demyelination, axonal degeneration, and inflammation. Corneal confocal microscopy has been used to identify axonal degeneration in several peripheral neuropathies.

Objective  To assess corneal subbasal nerve plexus morphologic features, corneal dendritic cell (DC) density, and peripapillary retinal nerve fiber layer (RNFL) thickness in patients with MS.

Design, Setting, and Participants  This single-center, cross-sectional comparative study was conducted at a tertiary referral university hospital between May 27, 2016, and January 30, 2017. Fifty-seven consecutive patients with relapsing-remitting MS and 30 healthy, age-matched control participants were enrolled in the study. Corneal subbasal nerve plexus measures and DC density were quantified in images acquired with the laser scanning in vivo corneal confocal microscope, and peripapillary RNFL thickness was measured with spectral-domain optical coherence tomography.

Main Outcomes and Measures  Corneal nerve fiber density, nerve branch density, nerve fiber length, DC density, peripapillary RNFL thickness, and association with the severity of neurologic disability as assessed by the Kurtzke Expanded Disability Status Scale (score range, 0-10; higher scores indicate greater disability) and Multiple Sclerosis Severity Score (score range, 0.01-9.99; higher scores indicate greater severity).

Results  Of the 57 participants with MS, 42 (74%) were female and the mean (SD) age was 35.4 (8.9) years; of the 30 healthy controls, 19 (63%) were female and the mean (SD) age was 34.8 (10.2) years. Corneal nerve fiber density (mean [SE] difference, −6.78 [2.14] fibers/mm2; 95% CI, −11.04 to −2.52; P = .002), nerve branch density (mean [SE] difference, −17.94 [5.45] branches/mm2; 95% CI, −28.77 to −7.10; P = .001), nerve fiber length (mean [SE] difference, −3.03 [0.89] mm/mm2; 95% CI, −4.81 to −1.25; P = .001), and the mean peripapillary RNFL thickness (mean [SE] difference, −17.06 [3.14] μm; 95% CI, −23.29 to −10.82; P < .001) were reduced in patients with MS compared with healthy controls. The DC density was increased (median [interquartile range], 27.7 [12.4-66.8] vs 17.3 [0-28.2] cells/mm2; P = .03), independent of a patient’s history of optic neuritis. Nerve fiber density and RNFL thickness showed inverse associations with the Expanded Disability Status Scale (ρ = −0.295; P = .03 for nerve fiber density and ρ = −0.374; P = .004 for RNFL thickness) and the Multiple Sclerosis Severity Score (R = −0.354; P = .007 for nerve fiber density and R = −0.283; P = .03 for RNFL thickness), whereas other study measures did not.

Conclusions and Relevance  These data suggest that corneal confocal microscopy demonstrates axonal loss and increased DC density in patients with MS. Additional longitudinal studies are needed to confirm the use of corneal confocal microscopy as an imaging biomarker in patients with MS.