title: The effect of test variability on the structure-function relationship in early glaucoma.
abstract: OBJECTIVE
  To determine whether the weakness of the structure-function relationship could be produced by test variability alone, without implying underlying dissociation between the true rates of structural and functional change.
  
  
  METHODS
  Perimetric mean deviation (MD), and rim area (RA) and cup volume (CV) from confocal scanning laser ophthalmoscopy, over six visits, were taken from 166 eyes of 92 participants with high-risk ocular hypertension or suspected/early glaucoma in the Portland Progression Project. Models were created of each measure's variability. A further model predicted the rate of functional change from the rate of structural change. These were used to generate realistic simulated sequences of both functional and structural data with different standard deviations σ between the underlying rates of change. 'Observed' structure-function relationships were calculated. An empirical p-value was derived, equaling the proportion of simulated series for which the 'observed' structure-function dissociation was greater than that seen in patient data.
  
  
  RESULTS
  The correlation between the rates of structural (RA) and functional (MD) change was 0.171, consistent with σ < 0.02 dB/yr. Using CV, the correlation was -0.091, consistent with σ < 0.01 dB/yr. By comparison, the models predicted that the standard deviation of the rate of functional change for a healthy eye due to test variability would be 0.18 dB/yr.
  
  
  CONCLUSIONS
  Test variability is sufficiently large that realistic patient data can be simulated without requiring a large variability between the underlying rates of structural and functional change. This absence of implied dissociation is a necessary condition for it to be valid to combine structural and functional measures to improve estimates of functional change and/or to reduce perimetric variability.
authors.affiliation: Discoveries In Sight Laboratories, Devers Eye Institute, Legacy Health System, 1225 NE 2nd Ave, Portland, OR 97232, USA. sgardiner@deverseye.org
authors.forename: Stuart K
authors.initials: SK
authors.lastname: Gardiner
authors.forename: Chris A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Shaban
authors.initials: S
authors.lastname: Demirel
mesh_terms: D005902:Glaucoma, Open-Angle / Q000175:diagnosis*; D006801:Humans; D007429:Intraocular Pressure; D008875:Middle Aged; D008954:Models, Biological; D009412:Nerve Fibers / Q000473:pathology*; D009798:Ocular Hypertension / Q000175:diagnosis; D009887:Ophthalmoscopy; D012165:Retinal Ganglion Cells / Q000473:pathology*; D014786:Vision Disorders / Q000175:diagnosis*; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology*