title: Effectiveness of averaging strategies to reduce variance in retinal nerve fibre layer thickness measurements using spectral-domain optical coherence tomography.
abstract: BACKGROUND
  Automated detection of subtle changes in peripapillary retinal nerve fibre layer thickness (RNFLT) over time using optical coherence tomography (OCT) is limited by inherent image quality before layer segmentation, stabilization of the scan on the peripapillary retina and its precise placement on repeated scans. The present study evaluates image quality and reproducibility of spectral domain (SD)-OCT comparing different rates of automatic real-time tracking (ART).
  
  
  METHODS
  Peripapillary RNFLT was measured in 40 healthy eyes on six different days using SD-OCT with an eye-tracking system. Image brightness of OCT with unaveraged single frame B-scans was compared to images using ART of 16 B-scans and 100 averaged frames. Short-term and day-to-day reproducibility was evaluated by calculation of intraindividual coefficients of variation (CV) and intraclass correlation coefficients (ICC) for single measurements as well as for seven repeated measurements per study day.
  
  
  RESULTS
  Image brightness, short-term reproducibility, and day-to-day reproducibility were significantly improved using ART of 100 frames compared to one and 16 frames. Short-term CV was reduced from 0.94 ± 0.31 % and 0.91 ± 0.54 % in scans of one and 16 frames to 0.56 ± 0.42 % in scans of 100 averaged frames (P ≤ 0.003 each). Day-to-day CV was reduced from 0.98 ± 0.86 % and 0.78 ± 0.56 % to 0.53 ± 0.43 % (P ≤ 0.022 each). The range of ICC was 0.94 to 0.99. Sample size calculations for detecting changes of RNFLT over time in the range of 2 to 5 μm were performed based on intraindividual variability.
  
  
  CONCLUSIONS
  Image quality and reproducibility of mean peripapillary RNFLT measurements using SD-OCT is improved by averaging OCT images with eye-tracking compared to unaveraged single frame images. Further improvement is achieved by increasing the amount of frames per measurement, and by averaging values of repeated measurements per session. These strategies may allow a more accurate evaluation of RNFLT reduction in clinical trials observing optic nerve degeneration.
authors.affiliation: Department of Ophthalmology, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria. berthold.pemp@meduniwien.ac.at
authors.forename: Berthold
authors.initials: B
authors.lastname: Pemp
authors.forename: Randy H
authors.initials: RH
authors.lastname: Kardon
authors.forename: Karl
authors.initials: K
authors.lastname: Kircher
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pernicka
authors.forename: Ursula
authors.initials: U
authors.lastname: Schmidt-Erfurth
authors.forename: Andreas
authors.initials: A
authors.lastname: Reitner
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D009412:Nerve Fibers; D015588:Observer Variation; D009898:Optic Disk / Q000033:anatomy & histology*; D012016:Reference Values; D015203:Reproducibility of Results; D012165:Retinal Ganglion Cells / Q000166:cytology*; D041623:Tomography, Optical Coherence / Q000706:statistics & numerical data*; D014792:Visual Acuity