title: Onset and progression of peripapillary retinal nerve fiber layer (RNFL) retardance changes occur earlier than RNFL thickness changes in experimental glaucoma.
abstract: OBJECTIVE
  Longitudinal measurements of peripapillary RNFL thickness and retardance were compared in terms of time to reach onset of damage and time to reach a specific progression endpoint.
  
  
  METHODS
  A total of 41 rhesus macaques with unilateral experimental glaucoma (EG) each had three or more weekly baseline measurements in both eyes of peripapillary RNFL thickness (RNFLT) and retardance. Laser photocoagulation was then applied to the trabecular meshwork of one eye to induce chronic elevation of intraocular pressure and weekly imaging continued. Pairwise differences between baseline observations were sampled by bootstrapping to determine the 95% confidence limits of each measurement's repeatability. The first two sequential measurements below the lower confidence limit defined the endpoint for each parameter. Segmented linear and exponential decay functions were fit to each RNFL-versus-time series to determine the time to damage onset.
  
  
  RESULTS
  In all, 29 (71%) of the EG eyes reached endpoint by RNFL retardance and 25 (61%) reached endpoint by RNFLT. In total, 33 (80%) reached endpoint by at least one of the RNFL parameters and 21 (51%) reached endpoint by both RNFL parameters. Of the 33 EG eyes reaching any endpoint, a larger proportion reached endpoint first by retardance (n = 26, 79%) than did by RNFLT (n = 7, 21%; P = 0.002). Survival analysis indicated a shorter time to reach endpoint by retardance than by RNFLT (P < 0.001). Of the 21 EG eyes that reached endpoint by both measures, the median duration to endpoint was 120 days for retardance and 223 days for RNFLT (P = 0.003, Wilcoxon test). The time to onset was faster for retardance than that for RNFLT based on either segmented fits (by 31 days; P = 0.008, average R(2) = 0.89) or exponential fits (by 102 days; P = 0.01, average R(2) = 0.89).
  
  
  CONCLUSIONS
  The onset of progressive loss of RNFL retardance occurs earlier than the onset of RNFL thinning. Endpoints of progressive loss from baseline also occurred more frequently and earlier for RNFL retardance as compared with RNFLT.
authors.affiliation: Discoveries in Sight Research Laboratories, Devers Eye Institute, Portland, Oregon 97232, USA. bfortune@deverseye.org
authors.forename: Brad
authors.initials: B
authors.lastname: Fortune
authors.forename: Claude F
authors.initials: CF
authors.lastname: Burgoyne
authors.forename: Grant
authors.initials: G
authors.lastname: Cull
authors.forename: Juan
authors.initials: J
authors.lastname: Reynaud
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
mesh_terms: D017668:Age of Onset; D000818:Animals; D001718:Birefringence; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005901:Glaucoma / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D007429:Intraocular Pressure / Q000502:physiology; D053685:Laser Therapy / Q000379:methods; D008028:Light Coagulation / Q000379:methods*; D008253:Macaca mulatta; D008297:Male; D008954:Models, Biological; D009412:Nerve Fibers / Q000473:pathology; D012160:Retina / Q000473:pathology*; D012164:Retinal Diseases / Q000473:pathology / Q000503:physiopathology / Q000628:therapy; D012165:Retinal Ganglion Cells / Q000473:pathology; D057109:Scanning Laser Polarimetry; D041623:Tomography, Optical Coherence
keywords: birefringence; glaucoma; optical coherence tomography; retinal ganglion cell; retinal nerve fiber layer; scanning laser polarimetry