title: Small-Fiber Neuropathy Is Associated With Corneal Nerve and Dendritic Cell Alterations: An In Vivo Confocal Microscopy Study.
abstract: OBJECTIVE
  In patients with small-fiber neuropathy (SFN), noninvasive diagnostic tests that allow accurate monitoring of disease progression are urgently needed. The aim of this study was to assess corneal trigeminal small sensory nerves and immune cells by in vivo corneal confocal microscopy (CCM) in SFN.
  
  
  METHODS
  In this prospective single-center study, 14 patients with histologically confirmed SFN were analyzed. CCM parameters [corneal nerve fiber density (NFD); the total number of nerves, main trunks, and branches; nerve tortuosity; and dendritic cell density] were compared with 14 age-matched healthy controls and correlated with clinical symptoms, disease course, and histopathological findings.
  
  
  RESULTS
  Corneal NFD (15,489.3 ± 5927.6 μm/mm² vs. 22,687.1 ± 4328.7 μm/mm²; P = 0.001) and the total number of nerves (10.4 ± 4.6/frame vs. 18.5 ± 4.8/frame; P < 0.0001) were significantly reduced in patients with SFN. In contrast, nerve tortuosity was significantly increased (2.2 ± 0.3 vs. 1.7 ± 0.5; P = 0.02). Corneal NFD did not correlate with intraepidermal NFD (ρ = -0.158; P = 0.5) or clinical symptoms (cold P = 0.1; prickling P = 0.2; burning P = 0.8; formication P = 0.7; stabbing P = 0.4; rubbing 0.1; pressure P = 0.1). The average dendritic cell density was increased in SFN (33.5 ± 57.5 cells/mm² vs. 16.1 ± 13.7 cells/mm²) but did not reach significance (P = 0.7).
  
  
  CONCLUSIONS
  CCM provides parameters that reliably indicate injury to sensory afferents of the trigeminal nerve in patients with SFN. Our data suggest that CCM may serve both as a noninvasive diagnostic test and as a surrogate marker in SFN.
authors.affiliation: Departments of *Ophthalmology, †Neurology, and ‡Neuropathology, University Hospital Cologne, Cologne, Germany; and §Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Bucher
authors.forename: Christian
authors.initials: C
authors.lastname: Schneider
authors.forename: Tobias
authors.initials: T
authors.lastname: Blau
authors.forename: Claus
authors.initials: C
authors.lastname: Cursiefen
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.forename: Helmar C
authors.initials: HC
authors.lastname: Lehmann
authors.forename: Ludwig M
authors.initials: LM
authors.lastname: Heindl
mesh_terms: D000200:Action Potentials; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003315:Cornea / Q000294:innervation*; D003713:Dendritic Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D011446:Prospective Studies; D011795:Surveys and Questionnaires; D014276:Trigeminal Nerve / Q000473:pathology*; D020433:Trigeminal Nerve Diseases / Q000175:diagnosis*