title: Repeatability of in vivo corneal confocal microscopy to quantify corneal nerve morphology.
abstract: OBJECTIVE
  To establish intraobserver and interobserver repeatability, agreement, and symmetry of corneal nerve fiber (NF) morphology in healthy subjects using in vivo corneal confocal microscopy.
  
  
  METHODS
  Nineteen subjects underwent in vivo corneal confocal microscopy (Heidelberg Retinal Tomograph III Rostock Cornea Module) at baseline and 7 days apart. Bland-Altman plots were generated to assess agreement, and the intraclass correlation coefficient and coefficient of repeatability were calculated to estimate intraobserver and interobserver repeatability for corneal NF density (numbers per square millimeter), nerve branch density (NBD; numbers per square millimeter), NF length (millimeters per square millimeter), and NF tortuosity coefficient. Symmetry between the right and left eyes was also assessed.
  
  
  RESULTS
  Intraclass correlation coefficient and coefficient of repeatability for intraobserver repeatability were 0.66 to 0.74 and 0.17 to 0.64, for interobserver repeatability 0.54 to 0.93 and 0.15 to 0.85, and for symmetry 0.34 to 0.77 and 0.17 to 0.63, respectively. NBD demonstrated low repeatability.
  
  
  CONCLUSIONS
  This study demonstrates good repeatability for the manual assessment of all major corneal NF parameters with the exception of NBD, which highlights the difficulty in defining nerve branches and suggests the need for experienced observers or automated image analysis to ensure optimal repeatability.
authors.affiliation: Centre for Endocrinology and Diabetes, Institute of Human Development, Faculty of Medical and Human Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Ioannis N
authors.initials: IN
authors.lastname: Petropoulos
authors.forename: Tauseef
authors.initials: T
authors.lastname: Manzoor
authors.forename: Philip
authors.initials: P
authors.lastname: Morgan
authors.forename: Hassan
authors.initials: H
authors.lastname: Fadavi
authors.forename: Omar
authors.initials: O
authors.lastname: Asghar
authors.forename: Uazman
authors.initials: U
authors.lastname: Alam
authors.forename: Georgios
authors.initials: G
authors.lastname: Ponirakis
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: Mitra
authors.initials: M
authors.lastname: Tavakoli
authors.forename: Rayaz A
authors.initials: RA
authors.lastname: Malik
mesh_terms: D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003315:Cornea / Q000294:innervation*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D015588:Observer Variation; D009882:Ophthalmic Nerve / Q000033:anatomy & histology*; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D002784:Cholesterol; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human