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Retinal nerve fibre layer and visual function loss in glaucoma: the tipping point
  1. Gadi Wollstein1,
  2. Larry Kagemann1,2,
  3. Richard A Bilonick1,
  4. Hiroshi Ishikawa1,2,
  5. Lindsey S Folio1,
  6. Michelle L Gabriele1,2,
  7. Allison K Ungar1,
  8. Jay S Duker3,
  9. James G Fujimoto4,
  10. Joel S Schuman1,2,5
  1. 1Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  2. 2Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  3. 3New England Eye Center, Tufts Medical Center, Tufts University School of Medicine, Boston, Massachusetts, USA
  4. 4Department of Electrical Engineering and Computer Science and Research Laboratory of Electronics, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
  5. 5The McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Joel S Schuman, Department of Ophthalmology, UPMC Eye Center, University of Pittsburgh School of Medicine, 203 Lothrop Street, Eye and Ear Institute, Suite 816, Pittsburgh, PA 15213, USA; schumanjs{at}upmc.edu

Abstract

Aims 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.

  • Glaucoma
  • retinal nerve fibre layer
  • visual field
  • structure function relationship
  • imaging

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Footnotes

  • Gadi Wollstein and Larry Kagemann shared equal part in preparation of the manuscript.

  • Presented in part at the Association of Research in Vision and Ophthalmology (ARVO) annual meeting, Ft. Lauderdale, Florida, May 2009, American Glaucoma Society annual meeting, Naples, Florida, Mar 2010, and the American Ophthalmological Society annual meeting, White Sulphur Springs, West Virginia, May 2010.

  • Funding NIH R01-EY013178, R01-EY011289, 1T32EY017271, P30-EY08098 Other Funders: Air Force Office of Scientific Research; Research to Prevent Blindness. Supported in part by National Institute of Health contracts R01-EY013178, R01-EY011289, 1T32EY017271, P30-EY08098 (Bethesda, MD); Air Force Office of Scientific Research FA9550-070-1-0101; The Eye and Ear Foundation (Pittsburgh, PA); and unrestricted grants from Research to Prevent Blindness (New York, NY). Financial Disclosures: Drs Wollstein and Duker received research funding from Carl Zeiss Meditec and Optovue. Drs Wollstein, Ishikawa and Schuman have intellectual property licenced by the University of Pittsburgh to Bioptigen. Dr Duker received research funding from Topcon Medical Systems, and is a consultant to Alcon, Genetech and Ophthotech and is a member of the advisory board of Paloma Pharmaceuticals. Dr Fujimoto is a scientific advisor and has stock options in Optovue. Drs Fujimoto and Schuman receive royalties for intellectual property licensed by Massachusetts Institute of Technology to Carl Zeiss Meditec.

  • Competing interests Drs Wollstein and Duker received research funding from Carl Zeiss Meditec and Optovue. Drs Wollstein, Ishikawa and Schuman have intellectual property licenced by the University of Pittsburgh to Bioptigen. Dr Duker received research funding from Topcon Medical Systems, is a consultant to Alcon, Genetech and Ophthotech and is a member of the advisory board of Paloma Pharmaceuticals. Dr Fujimoto is a scientific advisor and has stock options in Optovue. Drs Fujimoto and Schuman receive royalties for intellectual property licensed by Massachusetts Institute of Technology to Carl Zeiss Meditec.

  • Ethics approval This study was conducted with the approval of the University of Pittsburgh.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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