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Factors affecting the diagnostic performance of circumpapillary retinal nerve fibre layer measurement in glaucoma
  1. Damon Wong1,2,3,
  2. Jacqueline Chua3,4,
  3. Mani Baskaran3,
  4. Bingyao Tan1,2,3,
  5. Xinwen Yao1,2,3,
  6. Samuel Chan5,
  7. Yih Chung Tham3,4,
  8. Rachel Chong3,
  9. Tin Aung3,4,5,
  10. Ecosse Luc Lamoureux3,4,
  11. Eranga N Vithana3,4,
  12. Ching Yu Cheng3,4,
  13. Leopold Schmetterer1,3,6,7,8
  1. 1 SERI-NTU Advanced Ocular Engineering (STANCE) Program, Singapore
  2. 2 NTU Institute for Health Technologies, Nanyang Technological University, Singapore
  3. 3 Singapore Eye Research Institute, Singapore National Eye Centre, Singapore
  4. 4 Academic Clinical Program, Duke-NUS Medical School, Singapore
  5. 5 Yong Loo Lin School of Medicine, National University of Singapore, Singapore
  6. 6 School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore
  7. 7 Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria
  8. 8 Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria
  1. Correspondence to Professor Leopold Schmetterer, Ocular Imaging, Singapore Eye Research Institute, Singapore 169856, Singapore; leopold.schmetterer{at}


Background/aims To identify factors that influence the diagnostic performance of circumpapillary retinal nerve fibre layer (RNFL) thickness measurements in the detection of primary open-angle glaucoma (POAG).

Methods 1592 eyes from 1076 healthy controls and 758 eyes from 502 patients with POAG underwent optical coherence tomography (OCT) imaging to assess RNFL parameters. Visual field (VF) mean deviation (MD) from standard automated perimetry was used to indicate severity in subjects with glaucoma.

Results RNFL thickness significantly decreased with age (ρ=−0.10 to −0.16, p<0.001) and increased with spherical equivalent (SE) refractive error (ρ=0.23–0.29, p<0.001) in healthy and glaucoma groups but showed a significant reduction with SE (ρ=−0.20, p<0.001) in the temporal RNFL of healthy subjects. RNFL measurements significantly decreased with VF MD (ρ=0.08–0.53, p<0.05) in subjects with POAG. When healthy subjects and subjects with glaucoma were matched to subgroups within a factor, significant differences in area under the curve (AUC) between subgroups were only found with SE AUCs increased significantly with disease severity, particularly in the global, inferior and superior measurements (p<0.001). Overall, the diagnostic performance of the inferior and global RNFL measurements were found to be more resilient to different factors.

Conclusion Diagnostic accuracy in glaucoma was influenced by SE but could be mitigated by using controls with similar refractive characteristics. Increasing disease severity led to significantly better diagnostic accuracy. These factors should be considered when using OCT for glaucoma diagnosis in practice.

  • imaging
  • glaucoma
  • diagnostic tests/Investigation

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  • Contributors All the authors met the criteria of contributorship. Study design: LS, ENV and CYC. Collection of data: MB, SC and YCT. Data preparation and analysis: DW, JC, BT, YX and LS. Drafting of the manuscript: DW and LS. Critical revision of the manuscript and administrative, technical or material support: all authors.

  • Funding The study is funded by National Medical Research Council (grant CG/C010A/2017), Singapore.

  • Competing interests None declared.

  • Patient consent for publication Written informed consent was obtained from all participants.

  • Ethics approval All studies obtained approval from the institutional review board of the Singapore Eye Research Institute and were performed in accordance with the tenets of the Declaration of Helsinki.

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

  • Data availability statement Data are available upon reasonable request. Deidentified participant data were used and may be available upon request (Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower, Level 6, Singapore 169856).

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