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Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis

Eye volume 37, pages 2950–2955 (2023)Cite this article

Subjects

Abstract

Background/Objectives

Rheumatoid arthritis (RA) is a multisystem autoimmune disorder characterized by articular and extra-articular manifestations. Neuropathy is a poorly studied manifestation of RA. The aim of this study was to utilize the rapid non-invasive ophthalmic imaging technique of corneal confocal microscopy to identify whether there is evidence of small nerve fibre injury and immune cell activation in patients with RA.

Subjects/Methods

Fifty consecutive patients with RA and 35 healthy control participants were enrolled in this single-centre, cross-sectional study conducted at a university hospital. Disease activity was assessed with the 28-Joint Disease Activity Score and erythrocyte sedimentation rate (DAS28-ESR). Central corneal sensitivity was measured with a Cochet-Bonnet contact corneal esthesiometer. A laser scanning in vivo corneal confocal microscope was used to quantify corneal nerve fibre density (CNFD), nerve branch density (CNBD), nerve fibre length (CNFL), and Langerhans cell (LC) density.

Results

Corneal sensitivity (P = 0.01), CNFD (P = 0.02), CNBD (P < 0.001), and CNFL (P < 0.001) were lower, and mature (P = 0.001) and immature LC densities (P = 0.011) were higher in patients with RA compared to control subjects. CNFD (P = 0.016) and CNFL (P = 0.028) were significantly lower in patients with moderate to high (DAS28-ESR > 3.2) compared to mild (DAS28-ESR ≤ 3.2) disease activity. Furthermore, the DAS28-ESR score correlated with CNFD (r = −0.425; P = 0.002), CNBD (ρ = −0.362; P = 0.010), CNFL (r = −0.464; P = 0.001), total LC density (ρ = 0.362; P = 0.010) and immature LC density (ρ = 0.343; P = 0.015).

Conclusions

This study demonstrates reduced corneal sensitivity, corneal nerve fibre loss and increased LCs which were associated with the severity of disease activity in patients with RA.

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Fig. 1: Representative corneal confocal microscopy images.
Fig. 2: Corneal nerve fibre parameters and Langerhans cell (LC) density in patients with rheumatoid arthritis (RA) and healthy control participants, showing significantly lower corneal nerve fibre density (CNFD), corneal nerve branch density (CNBD) and corneal nerve fibre length (CNFL), and higher LC density in patients with RA.

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Data availability

All anonymized data that support the findings of this study are available to any qualified researcher upon reasonable request to the corresponding author (ORCID: 0000-0002-0509-5649).

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Funding

Funding

This work was supported by The Scientific Research Coordination Center of Necmettin Erbakan University (Project ID: 201218001). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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Authors and Affiliations

  1. Department of Ophthalmology, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey

    Gulfidan Bitirgen & Gunhal Satirtav

  2. Division of Rheumatology, Department of Internal Medicine, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey

    Adem Kucuk & Mustafa Cagri Ergun

  3. Weill Cornell Medicine-Qatar, Research Division, Qatar Foundation, Doha, Qatar

    Rayaz A. Malik

  4. Institute of Cardiovascular Sciences, Cardiac Centre, Faculty of Medical and Human Sciences, University of Manchester and NIHR Clinical Research Facility, Manchester, UK

    Rayaz A. Malik

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  1. Gulfidan Bitirgen
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Contributions

GB, AK, and RAM contributed to the conception and design of the study; GB, AK, MCE, GS, and RAM contributed to acquisition and analysis of data; GB, MCE and GS drafted the text and prepared the figures; AK and RAM reviewed the draft, provided suggestions and improvements.

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Correspondence to Gulfidan Bitirgen.

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Bitirgen, G., Kucuk, A., Ergun, M.C. et al. Corneal nerve loss and increased Langerhans cells are associated with disease severity in patients with rheumatoid arthritis. Eye 37, 2950–2955 (2023). https://doi.org/10.1038/s41433-023-02447-6

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