title: The effects of study design and spectrum bias on the evaluation of diagnostic accuracy of confocal scanning laser ophthalmoscopy in glaucoma.
abstract: OBJECTIVE
  To assess the effects of study design and spectrum bias on the evaluation of diagnostic accuracy of confocal scanning laser ophthalmoscopy (CSLO) in glaucoma.
  
  
  METHODS
  Analysis 1 included 67 eyes with glaucomatous visual field loss and 56 eyes of normal volunteers. Estimates of diagnostic accuracy in this analysis were compared to those obtained from analysis 2, which included a cohort of patients with suspected glaucoma, but without visual field loss at the time of CSLO imaging. For analysis 2, 40 eyes with progressive glaucomatous optic disc change were included in the glaucoma group and 43 eyes without any evidence of progressive damage to the optic nerve that were observed untreated for an average time of 9.01 +/- 3.09 years were included in the normal group. Areas under the receiver operating characteristic (ROC) curves (AUC) were used to evaluate diagnostic accuracy of CSLO parameters.
  
  
  RESULTS
  There was a statistically significant difference between the performance of the parameter with largest AUC, discriminant function Bathija, in analysis 1 (AUC = 0.91) compared with its performance in analysis 2 (AUC = 0.71; P = 0.002). For the contour-line-independent parameter glaucoma probability score, a statistically significant difference was also observed in the performance obtained in analysis 1 (AUC = 0.89) compared with analysis 2 (AUC = 0.65; P < 0.001).
  
  
  CONCLUSIONS
  Estimates of diagnostic accuracy of CSLO in glaucoma can be largely different depending on the population studied and the reference standard used to define disease. Diagnostic accuracy estimates obtained from case-control studies including well-defined groups of subjects with or without disease may not be applicable to the clinically relevant population.
authors.affiliation: Hamilton Glaucoma Center, University of California at San Diego, La Jolla, CA 92093-0946, USA. fmedeiros@eyecenter.ucsd.edu
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Medeiros
authors.forename: Diana
authors.initials: D
authors.lastname: Ng
authors.forename: Linda M
authors.initials: LM
authors.lastname: Zangwill
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Sample
authors.forename: Christopher
authors.initials: C
authors.lastname: Bowd
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D016022:Case-Control Studies; D005901:Glaucoma / Q000175:diagnosis*; D006801:Humans; D007834:Lasers; D008137:Longitudinal Studies; D008875:Middle Aged; D009887:Ophthalmoscopy / Q000379:methods*; D009898:Optic Disk / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000175:diagnosis*; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014786:Vision Disorders / Q000175:diagnosis; D014794:Visual Fields