title: Small fiber peripheral neuropathy in Wilson disease: an in vivo documentation by corneal confocal microscopy.
abstract: OBJECTIVE
  Wilson disease (WD) is a disorder of hepatic copper metabolism leading to copper accumulation in hepatocytes and in extrahepatic organs, as the brain and cornea. The aim of this study was to investigate central corneal changes and in particular to assess the parameters of corneal subbasal nerve plexus (SBNP) in patients affected by WD, using corneal confocal microscopy (CCM).
  
  
  METHODS
  A total of 24 patients affected by WD and 24 healthy control subjects were included in this cross-sectional comparative study. One eye of each subject was examined to quantify different corneal parameters. Mean cell diameter and mean cell density of the epithelium; number of fibers (NF), nerve fiber length density (NFLD), number of branchings (NBr), number of beadings (NBe), and fiber tortuosity (FT) of the SBNP; mean cell density of keratocytes of the anterior, medium, and posterior stroma; and mean cell density, polimegatism, and pleomorphism of the endothelium, and central corneal sensitivity were analyzed.
  
  
  RESULTS
  Wilson disease induced significant alterations in SBNP, and corneal epithelium. The NFLD (P < 0.0001), NF (P = 0.001), NBe (P = 0.025), and NBr (P < 0.0001) were significantly lower, whereas FT (P < 0.0001) was significantly higher in WD subjects compared to controls. Moreover mean epithelial cell diameter (P < 0.0001) and mean epithelial cell density (P < 0.0001) were significantly higher and lower compared to controls, respectively.
  
  
  CONCLUSIONS
  The CCM showed significant corneal changes in SBNP, with concomitant corneal epithelium changes in WD, demonstrating the presence of small fiber peripheral neuropathy in these patients. The CCM may contribute to diagnosis and monitoring of the peripheral nervous system involvement in WD.
authors.affiliation: Department of Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Giacomo Carlo
authors.initials: GC
authors.lastname: Sturniolo
authors.affiliation: Department of Ophthalmology, University of Padova, Padova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Lazzarini
authors.affiliation: Department of Gastroenterology, University of Padova, Padova, Italy.
authors.forename: Ottavia
authors.initials: O
authors.lastname: Bartolo
authors.affiliation: Department of Ophthalmology, University of Padova, Padova, Italy.
authors.forename: Marianna
authors.initials: M
authors.lastname: Berton
authors.affiliation: Department of Ophthalmology, University of Padova, Padova, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Leonardi
authors.affiliation: Department of Ophthalmology, University of Padova, Padova, Italy.
authors.forename: Iva Angela
authors.initials: IA
authors.lastname: Fregona
authors.affiliation: Ocular Oncology and Toxicology Research Unit, G.B. Bietti Foundation, IRCCS, Roma, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Parrozzani
authors.affiliation: Department of Ophthalmology, University of Padova, Padova, Italy Ocular Oncology and Toxicology Research Unit, G.B. Bietti Foundation, IRCCS, Roma, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Midena
mesh_terms: D000293:Adolescent; D000328:Adult; D002452:Cell Count; D003315:Cornea / Q000473:pathology*; D003316:Corneal Diseases / Q000175:diagnosis* / Q000209:etiology; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006527:Hepatolenticular Degeneration / Q000150:complications / Q000175:diagnosis*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D012189:Retrospective Studies; D055815:Young Adult
keywords: Wilson disease; corneal confocal microscopy; subbasal nerve plexus