title: Progressive Loss of Retinal Ganglion Cells and Axons in Nonoptic Neuritis Eyes in Multiple Sclerosis: A Longitudinal Optical Coherence Tomography Study.
abstract: OBJECTIVE
  To examine the rate of retinal ganglion cell (RGC) layer and retinal nerve fiber layer (RNFL) changes in nonoptic neuritis (NON) eyes of relapsing remitting multiple sclerosis (RRMS) patients, and to find a specific imaging parameter useful for identifying disease progression.
  
  
  METHODS
  Forty-five consecutive RRMS patients and 20 age- and sex-matched healthy subjects were enrolled. All patients were followed up for 3 years with annual optical coherence tomography (OCT) scans, which included a peripapillary ring scan protocol for RNFL analysis and a macular radial star-like scan to obtain RGC/inner plexiform layer (IPL) thickness measures. Healthy controls were scanned twice, 3 years apart.
  
  
  RESULTS
  Retinal ganglion cell/inner plexiform layer and temporal RNFL (tRNFL) demonstrated highly significant thinning (P < 0.01), but all nasal segments and global RNFL (gRNFL) were not significantly different from normal controls. While receiver operating characteristics (ROC) analysis showed no advantage of RGC/IPL over tRNFL in cross-sectional detection of thinning, cut-off point based of fifth percentile in healthy controls demonstrated higher rate of abnormality for RGC/IPL. There was a significant progressive loss of RGC/IPL and tRNFL during the follow-up period. The largest thickness reduction was observed in tRNFL. ROC analysis demonstrated that tRNFL provided better sensitivity/specificity for detecting change over time than RGC/IPL (area under the curve [AUC] 0.78 vs. 0.52), which was confirmed by higher detection rate when 95th percentile of progression in healthy controls was used as a cut-off.
  
  
  CONCLUSIONS
  This study confirmed significant thinning of RGC/IPL and tRNFL in NON eyes of RRMS patients. Progressive losses were more apparent on tRNFL, while RGC/IPL showed less change over the follow-up period.
authors.affiliation: Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Graham
authors.affiliation: Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia 2Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Yuyi
authors.initials: Y
authors.lastname: You
authors.affiliation: Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: Con
authors.initials: C
authors.lastname: Yiannikas
authors.affiliation: St Vincent Hospital, Sydney, New South Wales, Australia.
authors.forename: Raymond
authors.initials: R
authors.lastname: Garrick
authors.affiliation: Royal North Shore Hospital, Sydney, New South Wales, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Parratt
authors.affiliation: Brain and Mind Research Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Barnett
authors.affiliation: Save Sight Institute, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia 2Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South Wales, Australia 5Brain and Mind Research Institute, Sydney Medical Sch.
authors.forename: Alexander
authors.initials: A
authors.lastname: Klistorner
mesh_terms: D000328:Adult; D001369:Axons / Q000473:pathology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000150:complications / Q000473:pathology*; D009443:Neuritis / Q000209:etiology* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence