Small Fiber Peripheral Neuropathy in Wilson Disease: An In Vivo Documentation by Corneal Confocal Microscopy

PURPOSE. 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.