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Retinal age gap as a predictive biomarker for future risk of clinically significant diabetic retinopathy

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Abstract

Aims

Retinal age derived from fundus images has been verified as a novel ageing biomarker. We aim to explore the association between retinal age gap (retinal age minus chronological age) and incident diabetic retinopathy (DR).

Methods

Retinal age prediction was performed by a deep learning model, trained and validated based on 19,200 fundus images of 11,052 disease-free participants. Retinal age gaps were determined for 2311 patients with diabetes who had no history of diabetic retinopathy at baseline. DR events were ascertained by data linkage to hospital admissions. Cox proportional hazards regression models were performed to evaluate the association between retinal age gaps and incident DR.

Results

During the median follow-up period of 11.0 (interquartile range: 10.8–11.1) years, 183 of 2311 participants with diabetes developed incident DR. Each additional year of the retinal age gap was associated with a 7% increase in the risk of incident DR (hazard ratio [HR] = 1.07, 95% confidence interval [CI] 1.02–1.12, P = 0.004), after adjusting for confounding factors. Participants with retinal age gaps in the fourth quartile had a significantly higher DR risk compared to participants with retinal age gaps in the lowest quartile (HR = 2.88, 95% CI 1.61–5.15, P < 0.001).

Conclusions

We found that higher retinal age gap was associated with an increased risk of incident DR. As an easy and non-invasive biomarker, the retinal age gap may serve as an informative tool to facilitate the individualized risk assessment and personalized screening protocol for DR.

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Acknowledgements

This present work was supported by the NHMRC Investigator Grant (APP1175405), high-level Talent Flexible Introduction Fund of Guangdong Provincial People’s Hospital (No. KJ012019530), Fundamental Research Funds of the State Key Laboratory of Ophthalmology, National Natural Science Foundation of China (82000901), Project of Investigation on Health Status of Employees in Financial Industry in Guangzhou, China (Z012014075), Science and Technology Programme of Guangzhou, China (202002020049). Professor Mingguang He receives support from the University of Melbourne through its Research Accelerator Programme and the CERA Foundation. The Centre for Eye Research Australia (CERA) receives Operational Infrastructure Support from the Victorian State Government.

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Author notes

  1. Ruiye Chen and Yanping Chen Contributed equally.

Authors and Affiliations

  1. Centre for Eye Research Australia; Ophthalmology, University of Melbourne, Melbourne, Australia

    Ruiye Chen, Junyao Zhang, Wenyi Hu, Mingguang He & Zhuoting Zhu

  2. Department of Ophthalmology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

    Ruiye Chen, Wenyi Hu, Mingguang He & Zhuoting Zhu

  3. Ophthalmology, Department of Surgery, University of Melbourne, Melbourne, Australia

    Ruiye Chen, Wenyi Hu, Mingguang He & Zhuoting Zhu

  4. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Sun Yat-Sen University, Guangzhou, China

    Yanping Chen, Wei Wang & Mingguang He

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  1. Ruiye Chen
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Contributions

Study concept and design were performed by ZZ. Acquisition, analysis or interpretation was provided by all authors. Drafting of the manuscript was done by CR, ZJ and CY. Critical revision of the manuscript for important intellectual content was analyzed by WW, ZZ and HM. Statistical analysis was conducted by ZZ and HW. Obtained funding was carried out by HM, ZZ and WW. Administrative, technical or material support was given by ZZ, WW and HM. Study supervision was revised by ZZ and HM.

Corresponding authors

Correspondence to Mingguang He or Zhuoting Zhu.

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Conflict of interest

We declare no competing interests.

Human and Animal Rights Disclosure Statement

This study was reviewed and approved by the National Information Governance Board for Health and Social Care and the NHS North West Multicenter Research Ethics Committee (11/NW/0382) and the Biobank consortium (application No. 94372). The study was conducted according to the Declaration of Helsinki. No animal experiments were carried out in this study.

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Informed consent was obtained from all participants.

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This article belongs to the Topical Collection “Diabetic Eye Disease”, managed By Giuseppe Querques.

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Chen, R., Chen, Y., Zhang, J. et al. Retinal age gap as a predictive biomarker for future risk of clinically significant diabetic retinopathy. Acta Diabetol 61, 373–380 (2024). https://doi.org/10.1007/s00592-023-02199-5

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  • DOI: https://doi.org/10.1007/s00592-023-02199-5

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