title: Variance components in confocal scanning laser tomography measurements of neuro-retinal rim area and the effect of repeated measurements on the power to detect loss over time.
abstract: OBJECTIVE
  To estimate the variation in measurements of neuro-retinal rim area (NRA) determined by confocal scanning laser tomography and consequences for clinical follow-up.
  
  
  METHODS
  Altogether, 24 healthy subjects were randomized on -320 μm, Moorfields and Standard NRA plane strategies. Additionally, NRA was measured in 32 glaucoma subjects. Variance components for subjects, visits and measurements were estimated with analysis of variance. Sample sizes required to detect a 6.0 × 10-2mm2NRA change were estimated assuming a significance level of 0.05 and a power of 0.8. Consequences for independent group, and paired comparison design, respectively, were analysed. Further, precision in estimates within subjects over time was investigated.
  
  
  RESULTS
  The variation of NRA among subjects was considerably larger than the variation among visits and measurements. For glaucoma subjects, the variation among visits and measurements were of the same order but larger than in healthy subjects. It was found that independent group comparisons require inconveniently large sample sizes. Within-subject paired comparisons over time require sample sizes of below 15 subjects. The estimated variations for glaucoma subjects imply that 54 months of follow-up is required for detection of change from baseline.
  
  
  CONCLUSIONS
  The variance for subjects is substantial in relation to those for visits and measurements. Cross-sectional independent group comparisons of levels of NRA are unsuitable, due to considerable subject variation. Levels of NRA differences within subjects between visits can be estimated with acceptable precision. Neuro-retinal rim area (NRA) measurement can be used for long-term follow-up of glaucoma progression.
authors.affiliation: Gullstrand lab. Ophthalmology, Department of Neuroscience, Uppsala University, Uppsala, Sweden. camilla.sandberg.melin@neuro.uu.se.|Centre for Research and Development, Uppsala University/Region Gävleborg, Gävle, Sweden. camilla.sandberg.melin@neuro.uu.se.
authors.forename: Camilla
authors.identifier: http://orcid.org/0000-0001-6649-3088
authors.initials: C
authors.lastname: Sandberg Melin
authors.affiliation: Gullstrand lab. Ophthalmology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Nuija
authors.affiliation: Gullstrand lab. Ophthalmology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Albert
authors.initials: A
authors.lastname: Alm
authors.affiliation: Gullstrand lab. Ophthalmology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Zhaohua
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Gullstrand lab. Ophthalmology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Per G
authors.initials: PG
authors.lastname: Söderberg
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005500:Follow-Up Studies; D005901:Glaucoma / Q000175:diagnosis*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology*; D011446:Prospective Studies; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000473:pathology*; D012189:Retrospective Studies; D057109:Scanning Laser Polarimetry / Q000592:standards*; D014054:Tomography / Q000592:standards
keywords: confocal scanning laser tomography; glaucoma; neuro-retinal rim area; variation