title: In Vivo Confocal Microscopy of Corneal Nerves: An Ocular Biomarker for Peripheral and Cardiac Autonomic Neuropathy in Type 1 Diabetes Mellitus.
abstract: OBJECTIVE
  We investigated the relationship between corneal subbasal nerve (SBN) plexus density, corneal sensitivity, and peripheral and cardiac autonomic neuropathy in patients with type 1 diabetes mellitus.
  
  
  METHODS
  We recruited 53 patients with type 1 diabetes mellitus and 40 normal control participants. Corneal in vivo confocal microscopy (IVCM) and sensitivity testing were performed on one eye of each subject. Autonomic function testing was done and an overall neuropathy score obtained from a combination of a symptomatic neuropathy score, clinical assessment, biothesiometry, and nerve conduction tests.
  
  
  RESULTS
  The corneal SBN density (P < 0.001) and corneal sensitivity (P < 0.001) were significantly lower in subjects with diabetes compared to controls. A modest negative correlation between total neuropathy score and SBN density was observed (r = -0.33, P = 0.01). A negative correlation between corneal sensitivity and expiration/inspiration component of the autonomic nerve analysis (ANS-EI) also was noted (r = -0.36, P = 0.008). Corneal SBN density was abnormal in 50% of diabetic subjects classified as "Normal" by the clinical and electrophysiological based tests of total neuropathy score.
  
  
  CONCLUSIONS
  The correlation of corneal SBN density with total neuropathy score suggests that reduced corneal nerve density reflects peripheral neuropathy in diabetes. Corneal SBN changes precede other clinical and electrophysiology tests of neuropathy supporting a possible role for corneal IVCM and corneal sensitivity testing as surrogate markers in the assessment of diabetic peripheral and cardiac autonomic neuropathy.
authors.affiliation: Department of Ophthalmology New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Stuti L
authors.initials: SL
authors.lastname: Misra
authors.affiliation: Department of Ophthalmology New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Jennifer P
authors.initials: JP
authors.lastname: Craig
authors.affiliation: Department of Ophthalmology New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Dipika V
authors.initials: DV
authors.lastname: Patel
authors.affiliation: Department of Ophthalmology New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Charles N J
authors.initials: CN
authors.lastname: McGhee
authors.affiliation: Department of Ophthalmology New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand.
authors.forename: Monika
authors.initials: M
authors.lastname: Pradhan
authors.affiliation: Respiratory Physiology, Auckland District Health Board, Greenlane Clinical Centre, Auckland, New Zealand.
authors.forename: Kevin
authors.initials: K
authors.lastname: Ellyett
authors.affiliation: Department of Neurology, Auckland City Hospital, Auckland, New Zealand.
authors.forename: Dean
authors.initials: D
authors.lastname: Kilfoyle
authors.affiliation: Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand.
authors.forename: Geoffrey D
authors.initials: GD
authors.lastname: Braatvedt
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001341:Autonomic Nervous System / Q000473:pathology; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000473:pathology*; D003315:Cornea / Q000294:innervation*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000473:pathology*; D003929:Diabetic Neuropathies / Q000473:pathology*; D005260:Female; D006331:Heart Diseases / Q000209:etiology / Q000473:pathology*; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal / Q000379:methods*; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000209:etiology / Q000473:pathology*; D015203:Reproducibility of Results; D055815:Young Adult