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Cited by 66Fibromyalgia and Chronic Fatigue Syndrome ResearchPain Mechanisms and TreatmentsPsychosomatic Disorders and Their Treatments

Cornea nerve fiber quantification and construction of phenotypes in patients with fibromyalgia

Open access
Oudejans, Linda, He, Xuan, Niesters, Marieke, Dahan, Albert, Brines, Michael, van Velzen, Monique·2016·Scientific Reports
DOI 10.1038/srep23573PMC PMC4804273
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Abstract

Cornea confocal microscopy (CCM) is a novel non-invasive method to detect small nerve fiber pathology. CCM generally correlates with outcomes of skin biopsies in patients with small fiber pathology. The aim of this study was to quantify the morphology of small nerve fibers of the cornea of patients with fibromyalgia in terms of density, length and branching and further phenotype these patients using standardized quantitative sensory testing (QST). Small fiber pathology was detected in the cornea of 51% of patients: nerve fiber length was significantly decreased in 44% of patients compared to age- and sex-matched reference values; nerve fiber density and branching were significantly decreased in 10% and 28% of patients. The combination of the CCM parameters and sensory tests for central sensitization, (cold pain threshold, mechanical pain threshold, mechanical pain sensitivity, allodynia and/or windup), yielded four phenotypes of fibromyalgia patients in a subgroup analysis: one group with normal cornea morphology without and with signs of central sensitization and a group with abnormal cornea morphology parameters without and with signs of central sensitization. In conclusion, half of the tested fibromyalgia population demonstrates signs of small fiber pathology as measured by CCM. The four distinct phenotypes suggest possible differences in disease mechanisms and may require different treatment approaches.

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  • The lack of correlation between quantitative small fiber reduction and dysfunction in QST, pleasant touch test, and questionnaire data was also reported.

    “The lack of correlation between quantitative small fiber reduction and dysfunction in the remaining small fiber tests, namely QST and pleasant touch test, as well as questionnaire data was also reported.15,27,33”

    From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [33]

    The Results section ('Correlations and subgroup analysis'; page unavailable) reports no significant correlations between corneal nerve morphology and QST or questionnaire scores. The paper does not report a pleasant-touch test or a correlation involving one, so that part of the attributed claim is unsupported. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • An earlier CCM study in a predominantly female FMS cohort showed loss of corneal nerve fibers but no correlation between abnormal corneal morphology and QST, WPI, and disease duration.

    “This confirms the findings of an earlier study using CCM to construct phenotypes in a cohort of predominantly female patients with FMS,33 where the authors showed a loss of corneal nerve fibers but no correlation between abnormal corneal morphology and QST, WPI, and disease duration.”

    From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [33]

  • In previous studies, FMS subgroups have been defined based on extent of alterations in small fibers in skin and cornea, but hardly any male patients were included.

    “In previous studies, FMS subgroups have been defined based on the extent of alterations in small fibers in skin and cornea33; however, hardly any male patients were included.”

    From Pain and small fiber pathology in men with fibromyalgia syndrome (2024) · cites this paper as [33]

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Cited by

Sorted by citations

Authors
Oudejans, L., He, X., Niesters, M., Dahan, A., Brines, M., & van Velzen, M.
Affiliations
  • Leiden University Medical Center (NL)
  • Araim Pharmaceuticals (United States) (US)
Corresponding author
Dahan, Albert
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2016-03-23
Volume
6
Issue
1
Pages
23573-23573
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/srep23573
PMC
PMC4804273
OpenAlex
W2329592746
Cited by
66
References
3
Citations by year
2026: 5 · 2025: 11 · 2024: 3 · 2023: 6 · 2022: 8 · 2021: 5 · 2020: 11 · 2019: 7 · 2018: 4 · 2017: 5 · 2016: 1
FWCI
5.04
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
  • Leiden Repository (Leiden University) (submittedVersion)
Funders
University of Manchester
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Fibromyalgia and Chronic Fatigue Syndrome Research
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Psychosomatic Disorders and Their Treatments
Keywords
fibromyalgia, corneal nerve fiber density, central sensitization, quantitative sensory testing, phenotypes, allodynia, cold pain threshold, mechanical pain sensitivity, wind-up
MeSH terms
Adult, Cornea, Female, Fibromyalgia, Humans, Male, Middle Aged, Nerve Fibers, Microscopy, Confocal, Young Adult

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