title: Retinal nerve fibre layer and visual function loss in glaucoma: the tipping point.
abstract: OBJECTIVE
  To determine the retinal nerve fibre layer (RNFL) thickness at which visual field (VF) damage becomes detectable and associated with structural loss.
  
  
  METHODS
  In a prospective cross-sectional study, 72 healthy and 40 glaucoma subjects (one eye per subject) recruited from an academic institution had VF examinations and spectral domain optical coherence tomography (SD-OCT) optic disc cube scans (Humphrey field analyser and Cirrus HD-OCT, respectively). Comparison of global mean and sectoral RNFL thicknesses with VF threshold values showed a plateau of threshold values at high RNFL thicknesses and a sharp decrease at lower RNFL thicknesses. A 'broken stick' statistical model was fitted to global and sectoral data to estimate the RNFL thickness 'tipping point' where the VF threshold values become associated with the structural measurements. The slope for the association between structure and function was computed for data above and below the tipping point.
  
  
  RESULTS
  The mean RNFL thickness threshold for VF loss was 75.3 μm (95% CI: 68.9 to 81.8), reflecting a 17.3% RNFL thickness loss from age-matched normative value. Above the tipping point, the slope for RNFL thickness and threshold value was 0.03 dB/μm (CI: -0.02 to 0.08) and below the tipping point, it was 0.28 dB/μm (CI: 0.18 to 0.38); the difference between the slopes was statistically significant (p<0.001). A similar pattern was observed for quadrant and clock-hour analysis.
  
  
  CONCLUSIONS
  Substantial structural loss (∼17%) appears to be necessary for functional loss to be detectable using the current testing methods.
authors.affiliation: Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh School of Medicine, 203 Lothrop Street, Eye and Ear Institute, Pittsburgh, PA 15213, USA.
authors.forename: Gadi
authors.initials: G
authors.lastname: Wollstein
authors.forename: Larry
authors.initials: L
authors.lastname: Kagemann
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bilonick
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishikawa
authors.forename: Lindsey S
authors.initials: LS
authors.lastname: Folio
authors.forename: Michelle L
authors.initials: ML
authors.lastname: Gabriele
authors.forename: Allison K
authors.initials: AK
authors.lastname: Ungar
authors.forename: Jay S
authors.initials: JS
authors.lastname: Duker
authors.forename: James G
authors.initials: JG
authors.lastname: Fujimoto
authors.forename: Joel S
authors.initials: JS
authors.lastname: Schuman
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005902:Glaucoma, Open-Angle / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009412:Nerve Fibers / Q000473:pathology / Q000502:physiology; D011446:Prospective Studies; D012160:Retina / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index; D041623:Tomography, Optical Coherence / Q000379:methods* / Q000706:statistics & numerical data; D014786:Vision Disorders / Q000473:pathology* / Q000503:physiopathology; D014794:Visual Fields / Q000502:physiology*