{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:05:36Z","timestamp":1789445136895,"version":"build-2803163510"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T00:00:00Z","timestamp":1789344000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"abstract":"ABSTRACT<\/jats:title>\n \n Introduction\/Aims<\/jats:title>\n Small fiber involvement in Charcot\u2013Marie\u2013Tooth disease (CMT) is incompletely characterized. We evaluated corneal small fiber parameters and immune cell density in common CMT subtypes, which are predominantly demyelinating neuropathies, using in\u00a0vivo corneal confocal microscopy (IVCCM).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Sixteen patients with genetically confirmed hereditary demyelinating neuropathies (\n PMP22<\/jats:italic>\n \u2010related CMT1A\/HNPP and CMTX1) and 32 healthy controls underwent IVCCM. Corneal nerve fiber density (CNFD), length (CNFL), branch density (CNBD), tortuosity (CNFT), and Langerhans cell density were quantified. Clinical severity was assessed with the Charcot\u2013Marie\u2013Tooth Neuropathy Score (CMTNS). Neuropathic pain was defined as painDETECT \u2265\u200919 or ongoing treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients showed reduced CNFD compared with controls (20.8\u2009\u00b1\u200910.7 vs. 26.1\u2009\u00b1\u20095.3\u2009fibers\/mm\n 2<\/jats:sup>\n ;\n p<\/jats:italic>\n \u2009=\u20090.024). Subgroup analysis demonstrated significant reductions in CNFD (\n p<\/jats:italic>\n \u2009=\u20090.001), CNFL (\n p<\/jats:italic>\n \u2009=\u20090.006), and CNBD (\n p<\/jats:italic>\n \u2009=\u20090.040) in\n PMP22<\/jats:italic>\n \u2010related neuropathies, whereas CMTX1 patients did not differ from controls. CNFD, CNFL, and CNBD correlated inversely with CMTNS. Patients with neuropathic pain exhibited lower CNFD (10.5\u2009\u00b1\u20098.8 vs. 25.4\u2009\u00b1\u20097.9 fibers\/mm\n 2<\/jats:sup>\n ,\n p<\/jats:italic>\n \u2009=\u20090.009), CNFL (9.8\u2009\u00b1\u20093.9 vs. 16.2\u2009\u00b1\u20092.8\u2009mm\/mm\n 2<\/jats:sup>\n ,\n p<\/jats:italic>\n \u2009=\u20090.002), and CNBD (9.9\u2009\u00b1\u200911.8 vs. 32.7\u2009\u00b1\u200919.2 branches\/mm\n 2<\/jats:sup>\n ,\n p<\/jats:italic>\n \u2009=\u20090.030) than painless patients. Langerhans cell density did not differ between groups.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n \n PMP22<\/jats:italic>\n \u2010related neuropathies demonstrate significant corneal small fiber loss without increased Langerhans cell density, suggesting a predominantly structural phenotype without evidence of increased corneal immune activation. IVCCM may serve as a noninvasive biomarker of small fiber involvement and disease severity.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mus.70405","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:50:01Z","timestamp":1789444201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Corneal Confocal Microscopy in Hereditary Demyelinating Neuropathies: Small Fiber Involvement in Charcot\u2013Marie\u2013Tooth Disease"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6923-2235","authenticated-orcid":false,"given":"Ezgi","family":"Keskiner\u2010Ozturk","sequence":"first","affiliation":[{"name":"Department of Neurology Marmara University School of Medicine Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8322-1842","authenticated-orcid":false,"given":"Semra","family":"Akkaya\u2010Turhan","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Marmara University School of Medicine Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6132-2300","authenticated-orcid":false,"given":"Kayihan","family":"Uluc","sequence":"additional","affiliation":[{"name":"Department of Neurology Marmara University School of Medicine Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8530-4382","authenticated-orcid":false,"given":"Hande","family":"Alibas","sequence":"additional","affiliation":[{"name":"Department of Neurology Marmara University School of Medicine Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-2187","authenticated-orcid":false,"given":"Pinar","family":"Kahraman\u2010Koytak","sequence":"additional","affiliation":[{"name":"Department of Neurology Marmara University School of Medicine Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,14]]},"reference":[{"issue":"1","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/s41572-025-00679-2","article-title":"Charcot\u2010Marie\u2010Tooth Disease and Related Neuropathies","volume":"12","author":"Burns J.","year":"2026","journal-title":"Nature Reviews. Disease Primers"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.neulet.2015.01.059","article-title":"Demyelinating CMT\u2014What's Known, What's New and What's in Store?","volume":"596","author":"Brennan K. M.","year":"2015","journal-title":"Neuroscience Letters"},{"key":"e_1_2_12_4_1","first-page":"817","volume-title":"Peripheral Nerve Disorders","author":"Pareyson D.","year":"2013"},{"key":"e_1_2_12_5_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/1750-1172-9-38","article-title":"PMP22 Related Neuropathies: Charcot\u2010Marie\u2010Tooth Disease Type 1A and Hereditary Neuropathy With Liability to Pressure Palsies","volume":"9","author":"Paassen B. W.","year":"2014","journal-title":"Orphanet Journal of Rare Diseases"},{"issue":"1","key":"e_1_2_12_6_1","doi-asserted-by":"crossref","DOI":"10.1111\/ene.16523","article-title":"Phenotype\u2010Genotype Correlation in X\u2010Linked Charcot\u2010Marie\u2010Tooth Disease: A French Cohort Study","volume":"32","author":"Barbat du Closel L.","year":"2025","journal-title":"European Journal of Neurology"},{"issue":"3","key":"e_1_2_12_7_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1111\/j.1529-8027.2012.00424.x","article-title":"X\u2010Linked Charcot\u2010Marie\u2010Tooth Disease","volume":"17","author":"Scherer S. 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A.","year":"2018","journal-title":"Diabetologia"},{"issue":"9","key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1016\/j.clinthera.2021.04.003","article-title":"Corneal Confocal Microscopy: A Biomarker for Diabetic Peripheral Neuropathy","volume":"43","author":"Petropoulos I. 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R.","year":"2021","journal-title":"Neuroscience Letters"}],"container-title":["Muscle & Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70405","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.70405","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70405","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T03:50:05Z","timestamp":1789444205000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70405"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,14]]},"references-count":33,"alternative-id":["10.1002\/mus.70405"],"URL":"https:\/\/doi.org\/10.1002\/mus.70405","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,14]]},"assertion":[{"value":"2026-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-07","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"mus.70405"}}