title: Increased Langerhan cell density and corneal nerve damage in diabetic patients: role of immune mechanisms in human diabetic neuropathy.
abstract: OBJECTIVE
  Immune mechanisms have been proposed to play a role in the development of diabetic neuropathy. We employed in vivo corneal confocal microscopy (CCM) to quantify the presence and density of Langerhans cells (LCs) in relation to the extent of corneal nerve damage in Bowman's layer of the cornea in diabetic patients.
  
  
  METHODS
  128 diabetic patients aged 58 ± 1 yrs with a differing severity of neuropathy based on Neuropathy Deficit Score (NDS-4.7 ± 0.28) and 26 control subjects aged 53 ± 3 yrs were examined. Subjects underwent a full neurological evaluation, evaluation of corneal sensation with non-contact corneal aesthesiometry (NCCA) and corneal nerve morphology using corneal confocal microscopy (CCM).
  
  
  RESULTS
  The proportion of individuals with LCs was significantly increased in diabetic patients (73.8%) compared to control subjects (46.1%), P = 0.001. Furthermore, LC density (no/mm(2)) was significantly increased in diabetic patients (17.73 ± 1.45) compared to control subjects (6.94 ± 1.58), P = 0.001 and there was a significant correlation with age (r = 0.162, P = 0.047) and severity of neuropathy (r = -0.202, P = 0.02). There was a progressive decrease in corneal sensation with increasing severity of neuropathy assessed using NDS in the diabetic patients (r = 0.414, P = 0.000). Corneal nerve fibre density (P < 0.001), branch density (P < 0.001) and length (P < 0.001) were significantly decreased whilst tortuosity (P < 0.01) was increased in diabetic patients with increasing severity of diabetic neuropathy.
  
  
  CONCLUSIONS
  Utilising in vivo corneal confocal microscopy we have demonstrated increased LCs in diabetic patients particularly in the earlier phases of corneal nerve damage suggestive of an immune mediated contribution to corneal nerve damage in diabetes.
authors.affiliation: Division of Cardiovascular Medicine, University of Manchester and Manchester Royal Infirmary, Manchester, M13 9NT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Tavakoli
authors.forename: A J M
authors.initials: AJ
authors.lastname: Boulton
authors.forename: N
authors.initials: N
authors.lastname: Efron
authors.forename: R A
authors.initials: RA
authors.lastname: Malik
mesh_terms: D002452:Cell Count; D003315:Cornea / Q000276:immunology* / Q000294:innervation* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000276:immunology* / Q000473:pathology*; D005260:Female; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology* / Q000473:pathology*; D008297:Male; D008875:Middle Aged