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Multicenter Study
. 2021 Apr 8;18(1):89.
doi: 10.1186/s12974-021-02130-1.

Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy

Michael Fleischer  1 , Inn Lee  2 , Friedrich Erdlenbruch  1 , Lena Hinrichs  3 , Ioannis N Petropoulos  4   5 , Rayaz A Malik  4   5 , Hans-Peter Hartung  2   6   7   8 , Bernd C Kieseier  2 , Christoph Kleinschnitz  1 , Mark Stettner  9
Affiliations
Multicenter Study

Corneal confocal microscopy differentiates inflammatory from diabetic neuropathy

Michael Fleischer et al. J Neuroinflammation. .

Abstract

Background: Immune-mediated neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP) are treatable neuropathies. Among individuals with diabetic neuropathy, it remains a challenge to identify those individuals who develop CIDP. Corneal confocal microscopy (CCM) has been shown to detect corneal nerve fiber loss and cellular infiltrates in the sub-basal layer of the cornea. The objective of the study was to determine whether CCM can distinguish diabetic neuropathy from CIDP and whether CCM can detect CIDP in persons with coexisting diabetes.

Methods: In this multicenter, case-control study, participants with CIDP (n = 55) with (n = 10) and without (n = 45) diabetes; participants with diabetes (n = 58) with (n = 28) and without (n = 30) diabetic neuropathy, and healthy controls (n = 58) underwent CCM. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), corneal nerve branch density (CNBD), and dendritic and non-dendritic cell density, with or without nerve fiber contact were quantified.

Results: Dendritic cell density in proximity to corneal nerve fibers was significantly higher in participants with CIDP with and without diabetes compared to participants with diabetic neuropathy and controls. CNFD, CNFL, and CNBD were equally reduced in participants with CIDP, diabetic neuropathy, and CIDP with diabetes.

Conclusions: An increase in dendritic cell density identifies persons with CIDP. CCM may, therefore, be useful to differentiate inflammatory from non-inflammatory diabetic neuropathy.

Keywords: Chronic inflammatory demyelinating neuropathy; Diabetes mellitus; corneal confocal microscopy.

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Conflict of interest statement

Fleischer (none), Lee (none), Hinrichs (none), Petropoulos (none), Erdlenbruch (none), Malik served on the scientific advisory board and/or received speaker honoraria or travel funding from Biogen Idec, Merck, Pfizer, Novo Nordisk. Hartung received personal fees for consulting, serving on steering, and data monitoring committees from Bayer Healthcare, Biogen, Celgene Receptos, CSL Behring, GeNeuro, MedImmune, Merck, Novartis, Octapharma, Roche, Sanofi Genzyme, and Teva. Kieseier (none). Kleinschnitz (none), Stettner: served on the scientific advisory and/or received speaker honoraria or travel funding from UCB, Biogen Idec; Grifols, Genzyme, Roche, Merck, Novartis, Octapharma, CSL Behring, Sanofi-Aventis, TEVA, and Bayer.

Figures

Fig. 1
Fig. 1
Corneal infiltrating cells and nerve fiber parameters in participants with chronic inflammatory demyelinating polyneuropathy (CIDP) or diabetes. Corneal cellular infiltrates were classified as dendritic cells (without [DCP] or with [DCF] fiber contact) or non-dendritic cells (without [NCP] or with [NCF] fiber contact) in participants with CIDP, diabetes and control participants a–d. Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified e–g. The number of infiltrating cells with proximity to nerve fibers h, the number of cells without nerve fiber contact i, and the total corneal cell count j were determined. Mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001, ns indicates not significant
Fig. 2
Fig. 2
Corneal infiltrating cells and nerve fiber parameters in participants with chronic inflammatory demyelinating polyneuropathy (CIDP) and diabetic neuropathy. Corneal confocal microscopy was used to classify corneal cellular infiltrates as dendritic cells (without [DCP] or with [DCF] fiber contact) or non-dendritic cells (without [NCP] or with [NCF] fiber contact) and to assess corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) in participants with diabetes who fulfilled (+to) or did not fulfill (−to) the Toronto criteria for large fiber neuropathy, in participants with diabetes and in healthy individuals (control) a–g. Participants with CIDP were further subdivided into those with (+) or without (−) diabetes h–k. Mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001, ns indicates not significant
Fig. 3
Fig. 3
Corneal infiltrating cells and nerve fiber parameters in participants with chronic inflammatory demyelinating polyneuropathy (CIDP) with (+), or without (−) monoclonal gammopathy of undetermined significance (MGUS). Corneal confocal microscopy was used to classify corneal cellular infiltrates as dendritic cells (without [DCP] or with [DCF] fiber contact) or non-dendritic cells (without [NCP] or with [NCF] fiber contact) in participants with CIDP with (+) or without (−) MGUS, in participants with diabetes, and control individuals a–d. Corneal nerve fiber density (CNFD), corneal nerve fiber length (CNFL), and corneal nerve branch density (CNBD) were quantified e–g. Mean ± SEM, **P < 0.01, ***P < 0.001, ns indicates not significant
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