title: Rapid automated diagnosis of diabetic peripheral neuropathy with in vivo corneal confocal microscopy.
abstract: OBJECTIVE
  To assess the diagnostic validity of a fully automated image analysis algorithm of in vivo confocal microscopy images in quantifying corneal subbasal nerves to diagnose diabetic neuropathy.
  
  
  METHODS
  One hundred eighty-six patients with type 1 and type 2 diabetes mellitus (T1/T2DM) and 55 age-matched controls underwent assessment of neuropathy and bilateral in vivo corneal confocal microscopy (IVCCM). Corneal nerve fiber density (CNFD), branch density (CNBD), and length (CNFL) were quantified with expert, manual, and fully-automated analysis. The areas under the curve (AUC), odds ratios (OR), and optimal thresholds to rule out neuropathy were estimated for both analysis methods.
  
  
  RESULTS
  Neuropathy was detected in 53% of patients with diabetes. A significant reduction in manual and automated CNBD (P < 0.001) and CNFD (P < 0.0001), and CNFL (P < 0.0001) occurred with increasing neuropathic severity. Manual and automated analysis methods were highly correlated for CNFD (r = 0.9, P < 0.0001), CNFL (r = 0.89, P < 0.0001), and CNBD (r = 0.75, P < 0.0001). Manual CNFD and automated CNFL were associated with the highest AUC, sensitivity/specificity and OR to rule out neuropathy.
  
  
  CONCLUSIONS
  Diabetic peripheral neuropathy is associated with significant corneal nerve loss detected with IVCCM. Fully automated corneal nerve quantification provides an objective and reproducible means to detect human diabetic neuropathy.
authors.affiliation: School of Medicine, Institute of Human Development, Centre for Endocrinology and Diabetes, Manchester Academic Health Science Centre, Manchester, United Kingdom.
authors.forename: Ioannis N
authors.initials: IN
authors.lastname: Petropoulos
authors.forename: Uazman
authors.initials: U
authors.lastname: Alam
authors.forename: Hassan
authors.initials: H
authors.lastname: Fadavi
authors.forename: Andrew
authors.initials: A
authors.lastname: Marshall
authors.forename: Omar
authors.initials: O
authors.lastname: Asghar
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Dabbah
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: James
authors.initials: J
authors.lastname: Graham
authors.forename: Georgios
authors.initials: G
authors.lastname: Ponirakis
authors.forename: Andrew J M
authors.initials: AJ
authors.lastname: Boulton
authors.forename: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
mesh_terms: D003315:Cornea / Q000294:innervation* / Q000473:pathology; D003929:Diabetic Neuropathies / Q000175:diagnosis*; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009900:Optic Nerve / Q000473:pathology*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012720:Severity of Illness Index
keywords: corneal confocal microscopy; diabetes; diabetic neuropathy