title: Quantifying Variability in Longitudinal Peripapillary RNFL and Choroidal Layer Thickness Using Surface Based Registration of OCT Images.
abstract: OBJECTIVE
  To assess within-subject variability of retinal nerve fiber layer (RNFL) and choroidal layer thickness in longitudinal repeat optical coherence tomography (OCT) images with point-to-point measurement comparison made using nonrigid surface registration.
  
  
  METHODS
  Nine repeat peripapillary OCT images were acquired over 3 weeks from 12 eyes of 6 young, healthy subjects using a 1060-nm prototype swept-source device. The RNFL, choroid and the Bruch's membrane opening (BMO) were segmented, and point-wise layer thicknesses and BMO dimensions were measured. For each eye, the layer surfaces of eight follow-up images were registered to those of the baseline image, first by rigid alignment using blood vessel projections and axial height and tilt correction, followed by nonrigid registration of currents-based diffeomorphisms algorithms. This mapped all follow-up measurements point-wise to the common baseline coordinate system, allowing for point-wise statistical analysis. Measurement variability was evaluated point-wise for layer thicknesses and BMO dimensions by time-standard deviation (tSD).
  
  
  RESULTS
  The intraclass correlation coefficients (ICCs) of BMO area and eccentricity were 0.993 and 0.972, respectively. Time-mean and tSD were computed point-wise for RNFL and choroidal thickness and color-mapped on the baseline surfaces. tSD was less than two coherence lengths of the system 2ℓ = 12 μm at most vertices. High RNFL thickness variability corresponded to the locations of retinal vessels, and choroidal thickness varied more than RNFL thickness.
  
  
  CONCLUSIONS
  Our registration-based end-to-end pipeline produced point-wise correspondence among time-series retinal and choroidal surfaces with high measurement repeatability (low variability). Blood vessels were found to be the main sources contributing to the normal variability of the RNFL thickness measure. The computational pipeline with a measurement of normal variability can be used in future longitudinal studies to identify changes that are above the threshold of normal point-wise variability and track localized changes in retinal layers in high spatial resolution.
  
  
  CONCLUSIONS
  Using the registration-based approach presented in this study, longitudinal changes in retinal and choroidal layers can be detected with higher sensitivity and spatial precision.
authors.affiliation: School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Sieun
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Morgan
authors.initials: M
authors.lastname: Heisler
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Mackenzie
authors.affiliation: School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Marinko V
authors.initials: MV
authors.lastname: Sarunic
authors.affiliation: School of Engineering Science, Simon Fraser University, Burnaby, BC, Canada.
authors.forename: Mirza Faisal
authors.initials: MF
authors.lastname: Beg
keywords: OCT; RNFL; choroid; measurement variability; registration; retinal layer thickness measurement