Corneal Subbasal Nerve Plexus Evaluation by <i>in Vivo</i> Confocal Microscopy in Multiple Sclerosis: A Potential New Biomarker

Fernandes, Diogo Hipólito; Luís, Maria Elisa; Cardigos, Joana; Xavier, Catarina; Alves, Marta; Papoila, Ana Luísa; Cunha, João Paulo; Ferreira, Joana

doi:10.1080/02713683.2021.1904509

Cited by 10 publications

(6 citation statements)

References 44 publications

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“…We and others have also demonstrated corneal nerve loss in patients with MS, 21 – 26 Parkinson’s disease 27 and dementia. 28 In our recent study of a cohort of patients with relapsing-remitting MS (RRMS), followed over 2 years, we showed that progressive corneal nerve loss was associated with increasing disability.…”

Section: Introductionsupporting

confidence: 65%

“…39 CCM is a non-invasive imaging modality for rapid quantification of small fibres in diabetic 13 and other neuropathies, 14,15 and predicts incident diabetic neuropathy. 17 We and others have also shown significant corneal axonal loss in RRMS, [21][22][23][24][25][26] which was associated with neurological disability. In the present study, we show significant progressive corneal nerve loss and RNFL thinning in both RRMS and SPMS and higher CNBD in patients with RRMS.…”

Section: Discussionmentioning

confidence: 86%

“…No association has been previously reported between ON history and corneal nerve density. [21][22][23][24][25] Previous studies have reported an association between CCM measures and neurological disability [21][22][23][24]29 with the strength of the relationship increasing for greater EDSS. 25 In the present study, ΔCNBD was associated with the number of relapses and disability at baseline and follow-up, and ΔCNFL was associated with ΔEDSS and ΔMSSS.…”

Section: Discussionmentioning

confidence: 97%

“…[21][22][23][24][25] Previous studies have reported an association between CCM measures and neurological disability [21][22][23][24]29 with the strength of the relationship increasing for greater EDSS. 25 In the present study, ΔCNBD was associated with the number of relapses and disability at baseline and follow-up, and ΔCNFL was associated with ΔEDSS and ΔMSSS. It has been postulated that neurodegeneration in MS may initially be detectable only on highly sensitive techniques, before it becomes diffuse and irreversible with progressive disability.…”

Section: Discussionmentioning

confidence: 97%

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Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study

Petropoulos

Al-Shibani

Bitirgen

et al. 2023

Ther Adv Neurol Disord

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Background: Resourceful endpoints of axonal loss are needed to predict the course of multiple sclerosis (MS). Corneal confocal microscopy (CCM) can detect axonal loss in patients with clinically isolated syndrome and established MS, which relates to neurological disability. Objective: To assess corneal axonal loss over time in relation to retinal atrophy, and neurological and radiological abnormalities in MS. Methods: Patients with relapsing-remitting (RRMS) ( n = 68) or secondary progressive MS (SPMS) ( n = 15) underwent CCM and optical coherence tomography. Corneal nerve fibre density (CNFD-fibres/mm2), corneal nerve branch density (CNBD-branches/mm2), corneal nerve fibre length (CNFL-mm/mm2) and retinal nerve fibre layer (RNFL-μm) thickness were quantified along with neurological and radiological assessments at baseline and after 2 years of follow-up. Age-matched, healthy controls ( n = 20) were also assessed. Results: In patients with RRMS compared with controls at baseline, CNFD ( p = 0.004) and RNFL thickness ( p < 0.001) were lower, and CNBD ( p = 0.003) was higher. In patients with SPMS compared with controls, CNFD ( p < 0.001), CNFL ( p = 0.04) and RNFL thickness ( p < 0.001) were lower. For identifying RRMS, CNBD had the highest area under the receiver operating characteristic (AUROC) curve (0.99); and for SPMS, CNFD had the highest AUROC (0.95). At follow-up, there was a further significant decrease in CNFD ( p = 0.04), CNBD ( p = 0.001), CNFL ( p = 0.008) and RNFL ( p = 0.002) in RRMS; in CNFD ( p = 0.04) and CNBD ( p = 0.002) in SPMS; and in CNBD ( p = 0.01) in SPMS compared with RRMS. Follow-up corneal nerve loss was greater in patients with new enhancing lesions and optic neuritis history. Conclusion: Progressive corneal and retinal axonal loss was identified in patients with MS, especially those with more active disease. CCM may serve as an imaging biomarker of axonal loss in MS.

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Section: Introductionsupporting

confidence: 65%

Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

See 2 more Smart Citations

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study

Petropoulos

Al-Shibani

Bitirgen

et al. 2023

Ther Adv Neurol Disord

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show abstract

“…Optical coherence tomography (OCT) has shown retinal nerve fiber layer (RNFL) thinning in MS, but this may be attenuated during acute optic neuritis (ON). 14 We and others have used corneal confocal microscopy (CCM) to show a corneal axonal loss, independent of ON and related it to the severity of MS. [15][16][17][18][19][20][21] Corneal plasmacytoid dendritic immune cells (ICs) are bone marrow-derived antigen-presenting cells responsible for inducing primary immune responses and establishing immunologic memory via antigen capture and T-cell stimulation, respectively. 22 Recent experimental evidence has shown that corneal IC plays an important role in corneal nerve degeneration.…”

Section: Corneal Immune Cells As a Biomarker Of Inflammation In Multi...mentioning

confidence: 99%

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study

Petropoulos,

John,

Al-Shibani

et al. 2023

Ther Adv Neurol Disord

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Background: Corneal immune cells (ICs) are antigen-presenting cells that are known to increase ocular and systemic inflammatory conditions. Objective: We aimed to assess longitudinal changes in corneal IC in patients with multiple sclerosis (MS) and relation to disability and ongoing treatment. Design: Prospective observational study conducted between September 2016 and February 2020. Methods: Patients with relapsing-remitting MS (RRMS) ( n = 45) or secondary progressive MS (SPMS) ( n = 15) underwent corneal confocal microscopy (CCM) at baseline and 2-year follow-up for estimation of corneal IC density [dendritic cells with (DCF) (cells/mm2) or without nerve fiber contact (DCP); and non-dendritic cells with (NCF) or without nerve fiber contact (NCP)]. Optical coherence tomography, neuroimaging, and disability assessments were additionally performed. Healthy controls ( n = 20) were assessed at baseline. Results: In both RRMS and SPMS compared to controls, DCP ( p < 0.001 and p < 0.001, respectively) and DCF ( p < 0.001 and p = 0.005) were higher and NCF ( p = 0.007 and p = 0.02) was lower at baseline. DCP showed excellent performance in identifying patients with MS (sensitivity/specificity = 0.88/0.90) followed by DCF (0.80/0.75) and NCF (0.80/0.85). At follow-up compared to baseline, DCP ( p = 0.01) was significantly reduced, and NCP ( p = 0.004) and NCF ( p = 0.04) were increased. Subgroup analysis showed that baseline NCP and NCF were significantly higher ( p = 0.04–0.05) in patients who switched disease-modifying treatment, and baseline NCP ( p = 0.05) was higher in patients on interferon. Conclusion: Baseline and change in corneal IC were related to axonal degeneration and treatment status. Evaluation of corneal IC using CCM may allow an assessment of ongoing inflammation, disease progression, and the effect of treatment in MS.

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Corneal Nerves

Petropoulos

Malik

2022

In Vivo Confocal Microscopy in Eye Disease

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Corneal Subbasal Nerve Plexus Evaluation by in Vivo Confocal Microscopy in Multiple Sclerosis: A Potential New Biomarker

Cited by 10 publications

References 44 publications

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study

Corneal axonal loss as an imaging biomarker of neurodegeneration in multiple sclerosis: a longitudinal study

Corneal immune cells as a biomarker of inflammation in multiple sclerosis: a longitudinal study

Corneal Nerves

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