title: Impact of age-related change of retinal nerve fiber layer and macular thicknesses on evaluation of glaucoma progression.
abstract: OBJECTIVE
  To investigate the impact of age-related change of macular and circumpapillary retinal nerve fiber layer (RNFL) measurements on evaluation of glaucoma progression.
  
  
  METHODS
  Prospective, longitudinal study.
  
  
  METHODS
  A total of 150 eyes of 90 patients with glaucoma and 72 eyes of 40 normal individuals.
  
  
  METHODS
  Both eyes were imaged by the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA; optic nerve head and macular scans were taken every 4 months for a mean of 45.8 months (range, 35.4-60.6 months). The mean age-related rates of change of macular (including the ganglion cell and inner plexiform layer [GCIPL], inner retina [IR], outer retina [OR], and total macular thicknesses) and circumpapillary RNFL measurements were estimated with linear mixed models in the normal group. Macular and RNFL progression were then evaluated in individual eyes in the glaucoma group, with trend analysis before and after accounting for age-related change using the lower 95% confidence intervals (CIs) of the mean age-related rates of change as cutoffs. The survival probability was evaluated with the Kaplan-Meier estimator, and the agreement of progression detection among the structural parameters was calculated with Kappa statistics.
  
  
  METHODS
  Detection of glaucoma progression and survival probability of macular and RNFL parameters.
  
  
  RESULTS
  Before accounting for age-related change, 50.0% (75 eyes) showed progression by the GCIPL thickness, 50.0% (75 eyes) showed progression by the IR thickness, 30.0% (45 eyes) showed progression by the total macular thickness, 27.3% (41 eyes) showed progression by the circumpapillary RNFL thickness, and 10.0% (15 eyes) showed progression by the OR thickness. The survival probability of GCIPL and IR thicknesses were significantly worse compared with circumpapillary RNFL thickness (P ≤ 0.001). After accounting for age-related change, the proportions decreased to 14.7%, 20.0%, 16.0%, 26.7%, and 1.3%, respectively, with the circumpapillary RNFL thickness demonstrating the worst survival probability. The agreement of progression detection between RNFL and macular measurements was poor with (kappa range, -0.055 to 0.185) or without (kappa range, -0.046 to 0.173) taking age-related change into consideration.
  
  
  CONCLUSIONS
  Age-related change of macular and circumpapillary RNFL measurements can be detected in normal eyes and can affect the analysis of glaucoma progression. The impact is more substantial in analyzing macular progression than circumpapillary RNFL progression.
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, PRC. Electronic address: tlims00@hotmail.com.
authors.forename: Christopher K S
authors.initials: CKS
authors.lastname: Leung
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, PRC.
authors.forename: Cong
authors.initials: C
authors.lastname: Ye
authors.affiliation: Hamilton Glaucoma Center and the Department of Ophthalmology, University of California, San Diego, California.
authors.forename: Robert N
authors.initials: RN
authors.lastname: Weinreb
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, PRC.
authors.forename: Marco
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, PRC.
authors.forename: Gilda
authors.initials: G
authors.lastname: Lai
authors.affiliation: Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, PRC.
authors.forename: Dennis S
authors.initials: DS
authors.lastname: Lam
mesh_terms: D000375:Aging / Q000502:physiology*; D018450:Disease Progression; D005260:Female; D005901:Glaucoma / Q000175:diagnosis* / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000502:physiology; D008137:Longitudinal Studies; D008266:Macula Lutea / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D009898:Optic Disk / Q000473:pathology*; D009901:Optic Nerve Diseases / Q000175:diagnosis* / Q000503:physiopathology; D011446:Prospective Studies; D012165:Retinal Ganglion Cells / Q000473:pathology*; D041623:Tomography, Optical Coherence; D014065:Tonometry, Ocular