Ageing changes in retinal outer nuclear layer thickness and cone photoreceptor density using adaptive optics-free imaging

Juliane Matlach, Padraig Mulholland, Marketa Cilkova, Reena Chopra, Nilpa Shah, Tony Redmond, Steven C Dakin, David F. Garway-Heath, RS Anderson

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Purpose: To investigate age-related changes of the outer nuclear layer (ONL) thickness and cone density, and their associations in healthy participants using a modified, narrow scan-angle Heidelberg Retina Angiograph (HRA2). Methods: Retinal cones were imaged outside the fovea at 8.8° eccentricity and cone density was compared to ONL thickness measurements obtained by Spectral-Domain Optical Coherence Tomography (SD-OCT) at the same locations. Fifty-six eyes of 56 healthy participants with a median age (interquartile range, IQR) of 37 years (29–55) were included. Results: Median (IQR) cone count was 7,472 (7,188, 7,746) cones/mm 2 and median (IQR) ONL thickness was 56 (52, 60) µm for healthy participants. Both cone density and ONL thickness were negatively associated with age: cone density, R 2 = 0.16 (F(1,54) = 10.41, P = 0.002); ONL thickness, R 2 = 0.12 (F(1,54) = 7.41, P = 0.009). No significant association was seen between cone density and ONL thickness (R 2 = 0.03; F(1,54) = 1.66, P = 0.20). Conclusion: Cone density was lower, and ONL thinner, in older compared to younger participants, therefore, image-based structural measures should be compared to age-related data. However, cone density and ONL thickness were not strongly associated, indicating that determinants of ONL thickness measurements other than cone density measurements, and including measurement error, have a major influence.

Original languageEnglish
Pages (from-to)1434-1442
Number of pages9
JournalEuropean Journal of Ophthalmology
Issue number3
Early online date2 Jan 2023
Publication statusPublished online - 2 Jan 2023

Bibliographical note

Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was supported by Dr Hans and Mrs Gertrude Hirsch award from Fight for Sight UK to Tony Redmond and Roger S Anderson. Juliane Matlach received funding from Dr. Werner Jackstädt-Stiftung. Pádraig J Mulholland receives support from the College of Optometrists (UK), in the form of a Clinical Research Fellowship. David Garway-Heath is funded in part by the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital and UCL Institute of Ophthalmology. David Garway-Heath's chair at UCL is supported by funding from the International Glaucoma Association. The sponsors or funding organizations named above had no role in the design or conduct of this research. The views expressed are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research, or the Department of Health.

Publisher Copyright:
© The Author(s) 2023.


  • cone imaging
  • outer nuclear
  • OCT
  • imaging
  • Cone imaging
  • outer nuclear layer


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