title: Corneal confocal microscopy: a novel noninvasive test to diagnose and stratify the severity of human diabetic neuropathy.
abstract: OBJECTIVE
  The accurate quantification of human diabetic neuropathy is important to define at-risk patients, anticipate deterioration, and assess new therapies.
  
  
  METHODS
  A total of 101 diabetic patients and 17 age-matched control subjects underwent neurological evaluation, neurophysiology tests, quantitative sensory testing, and evaluation of corneal sensation and corneal nerve morphology using corneal confocal microscopy (CCM).
  
  
  RESULTS
  Corneal sensation decreased significantly (P = 0.0001) with increasing neuropathic severity and correlated with the neuropathy disability score (NDS) (r = 0.441, P < 0.0001). Corneal nerve fiber density (NFD) (P < 0.0001), nerve fiber length (NFL), (P < 0.0001), and nerve branch density (NBD) (P < 0.0001) decreased significantly with increasing neuropathic severity and correlated with NDS (NFD r = -0.475, P < 0.0001; NBD r = -0.511, P < 0.0001; and NFL r = -0.581, P < 0.0001). NBD and NFL demonstrated a significant and progressive reduction with worsening heat pain thresholds (P = 0.01). Receiver operating characteristic curve analysis for the diagnosis of neuropathy (NDS >3) defined an NFD of <27.8/mm(2) with a sensitivity of 0.82 (95% CI 0.68-0.92) and specificity of 0.52 (0.40-0.64) and for detecting patients at risk of foot ulceration (NDS >6) defined a NFD cutoff of <20.8/mm(2) with a sensitivity of 0.71 (0.42-0.92) and specificity of 0.64 (0.54-0.74).
  
  
  CONCLUSIONS
  CCM is a noninvasive clinical technique that may be used to detect early nerve damage and stratify diabetic patients with increasing neuropathic severity.
authors.affiliation: Division of Cardiovascular Medicine, University of Manchester and Central Manchester Foundation Trust, Manchester, U.K
authors.forename: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.forename: Cristian
authors.initials: C
authors.lastname: Quattrini
authors.forename: Caroline
authors.initials: C
authors.lastname: Abbott
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Kallinikos
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.forename: Joanne
authors.initials: J
authors.lastname: Finnigan
authors.forename: Philip
authors.initials: P
authors.lastname: Morgan
authors.forename: Nathan
authors.initials: N
authors.lastname: Efron
authors.forename: Andrew J M
authors.initials: AJ
authors.lastname: Boulton
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
mesh_terms: D003315:Cornea / Q000294:innervation* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000175:diagnosis*; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008875:Middle Aged