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Evaluation of retinal nerve fibre layer thickness as a possible measure of diabetic retinal neurodegeneration in the EPIC-Norfolk Eye Study
  1. Sidra Zafar1,
  2. Kristen A Staggers2,
  3. Jie Gao3,
  4. Yao Liu4,
  5. Praveen J Patel5,
  6. Paul J Foster5,
  7. Benjamin J Frankfort3,
  8. Michael Abramoff6,
  9. Charles G Minard2,
  10. Alasdair Warwick7,
  11. Anthony P Khawaja7,
  12. Roomasa Channa4
  1. 1Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, Maryland, USA
  2. 2Institute for Clinical and Translational Research, Baylor College of Medicine, Houston, TX, USA
  3. 3Department of Ophthalmology, Baylor College of Medicine, Houston, Texas, USA
  4. 4Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI, USA
  5. 5NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust & UCL Institute of Ophthalmology, London, UK
  6. 6Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa city, Iowa, USA
  7. 7MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
  1. Correspondence to Roomasa Channa, Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA; rchanna{at}wisc.edu

Abstract

Background/aims Markers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness.

Methods Leveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also used to determine: (1) the relationship between: (A) glycated haemoglobin (HbA1c) irrespective of diabetes diagnosis and pRNFL thickness, (B) diabetes and pRNFL thickness and (2) which quadrants of pRNFL may be affected in participants with diabetes and in relation to HbA1c.

Results 7076 participants were included. After controlling for covariates, inferior pRNFL thickness was 0.94 µm lower (95% CI −1.28 µm to −0.60 µm), superior pRNFL thickness was 0.83 µm lower (95% CI −1.17 µm to −0.49 µm) and temporal pRNFL thickness was 1.33 µm higher (95% CI 0.99 µm to 1.67 µm) per unit increase in HbA1c. Nasal pRNFL thickness was not significantly associated with HbA1c (p=0.23). Similar trends were noted when diabetes was used as the predictor.

Conclusion Superior and inferior pRNFL was significantly thinner among those with higher HbA1c levels and/or diabetes, representing areas of the pRNFL that may be most affected by diabetes.

  • retina
  • imaging

Data availability statement

Data are available on reasonable request. Data may be obtained from a third party and are not publicly available. Data are available for approved research (see https://www.epic-norfolk.org.uk/).

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Data availability statement

Data are available on reasonable request. Data may be obtained from a third party and are not publicly available. Data are available for approved research (see https://www.epic-norfolk.org.uk/).

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Footnotes

  • APK and RC are joint senior authors.

  • Contributors SZ contributed to data interpretation, initial drafting, critical review and final revision of the manuscript; KAS contributed to data analysis and interpretation, critical review and final revision of the manuscript; JG, YL, PJF, BJF, MA, CGM and APK contributed to data interpretation, critical review and final revision of the manuscript; RC contributed to developing the study idea, designing the study, conducting the study, data analysis and interpretation, critical review, final revision of the manuscript and takes responsiblity as guarantor.

  • Funding The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC-UU_12015/1), Research into Aging (262) and Cancer Research UK (C864/A14136). We are grateful to all the participants who have been part of the project and to the many members of the study teams at the University of Cambridge who have enabled this research. RC is funded by the National Eye Institute (1K23EY030911-01). This work was supported in part by an Unrestricted Grant to the Department of Ophthalmology and Visual Sciences, University of Wisconsin, from Research to Prevent Blindness.

  • Competing interests APK has acted as a consultant to Abbvie, Aerie, Google Health, Novartis, Reichert, Santen and Thea.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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