Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank

Yu Peng¹, Yuzhou Zhang¹, Ka Wai Kam^{1

2}, Mary Ho^{1

2}, Simon Sezto¹, Sunny Au³, Charlene C Yim¹, Xiujuan Zhang^{1

4}, Mandy P H Ng¹, Patrick Ip⁵, Alvin Young^{1

2}, Chi Pui Pang^{1

6

7}, Clement C Tham^{1

2

6

7

8

9}, Li Jia Chen^{10

11

12

13

14}, Jason C Yam^{15

16

17

18

19

20}

Affiliations

¹ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
² Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Eye Hospital, Hong Kong SAR, China.
³ Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong SAR, China.
⁴ Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China.
⁵ Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁶ Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁷ Shantou University, The Chinese University of Hong Kong Joint Shantou International Eye Centre, Shantou, China.
⁸ Hong Kong Eye Hospital, Hong Kong SAR, China.
⁹ Department of Ophthalmology, Hong Kong Children's Hospital, Hong Kong SAR, China.
¹⁰ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹¹ Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Eye Hospital, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹² Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹³ Shantou University, The Chinese University of Hong Kong Joint Shantou International Eye Centre, Shantou, China. lijia_chen@cuhk.edu.hk.
¹⁴ Hong Kong Eye Hospital, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹⁵ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
¹⁶ Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Eye Hospital, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
¹⁷ Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
¹⁸ Shantou University, The Chinese University of Hong Kong Joint Shantou International Eye Centre, Shantou, China. yamcheuksing@cuhk.edu.hk.
¹⁹ Hong Kong Eye Hospital, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
²⁰ Department of Ophthalmology, Hong Kong Children's Hospital, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.

PMID: 41483391
DOI: 10.1007/s11357-025-02066-x

Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank

Yu Peng et al. Geroscience. 2026.

. 2026 Jan 2.

doi: 10.1007/s11357-025-02066-x. Online ahead of print.

Authors

Affiliations

¹ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
² Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Eye Hospital, Hong Kong SAR, China.
³ Department of Ophthalmology, Tung Wah Eastern Hospital, Hong Kong SAR, China.
⁴ Department of Ophthalmology, The University of Hong Kong, Hong Kong SAR, China.
⁵ Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
⁶ Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China.
⁷ Shantou University, The Chinese University of Hong Kong Joint Shantou International Eye Centre, Shantou, China.
⁸ Hong Kong Eye Hospital, Hong Kong SAR, China.
⁹ Department of Ophthalmology, Hong Kong Children's Hospital, Hong Kong SAR, China.
¹⁰ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹¹ Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Eye Hospital, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹² Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹³ Shantou University, The Chinese University of Hong Kong Joint Shantou International Eye Centre, Shantou, China. lijia_chen@cuhk.edu.hk.
¹⁴ Hong Kong Eye Hospital, Hong Kong SAR, China. lijia_chen@cuhk.edu.hk.
¹⁵ Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
¹⁶ Department of Ophthalmology and Visual Sciences, Prince of Wales Hospital, Hong Kong Eye Hospital, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
¹⁷ Hong Kong Hub of Paediatric Excellence, The Chinese University of Hong Kong, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
¹⁸ Shantou University, The Chinese University of Hong Kong Joint Shantou International Eye Centre, Shantou, China. yamcheuksing@cuhk.edu.hk.
¹⁹ Hong Kong Eye Hospital, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.
²⁰ Department of Ophthalmology, Hong Kong Children's Hospital, Hong Kong SAR, China. yamcheuksing@cuhk.edu.hk.

PMID: 41483391
DOI: 10.1007/s11357-025-02066-x

Abstract

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in the aging population. Although frailty has been recognized as a potential risk factor, previous studies relying on static assessments cannot capture its dynamic nature. This study aims to prospectively evaluate the association between dynamic frailty trajectories and incident AMD. The baseline cohort included 462,573 UK Biobank participants who were free of AMD and had frailty phenotype (FP) data at enrollment. Among them, 53,059 with at least one follow-up FP assessment comprised the trajectory cohort. Participants were categorized as nonfrail, prefrail, or frail based on their FP scores. Annualized frailty progression (ΔFP/year) was estimated via linear regression. Cox models assessed hazard ratios (HRs) and 95% confidence intervals (CIs) for AMD. During a median follow-up of 11.8 years in the baseline cohort, 13,428 incident AMD cases (2.9%) were documented. Prefrail (HR:1.14; 95% CI:1.10-1.18) and frail (HR:1.36; 95% CI: 1.26-1.47) individuals had significantly higher AMD risks compared to nonfrail participants. In the frailty trajectory analysis with a median follow-up duration of 3.3 years, 852 incident AMD cases (1.6%) were recorded. Each 1-point FP increase conferred 28% higher AMD risk (HR: 1.28; 95% CI: 1.18-1.38), while each 0.1-point/year ΔFP increase independently elevated risk by 15% (HR: 1.15; 95% CI: 1.10-1.21). Compared to stable nonfrail, prefrailty aggravation showed highest AMD risk (HR: 2.26; 95% CI: 1.51-3.37), followed by frailty alleviation (HR: 1.73; 95% CI: 0.98-3.04) and frailty maintenance (HR: 1.72; 95% CI: 0.86-3.41). Progressive frailty trajectories, independent of baseline status, is associated with increased incident AMD risk. Early interventions targeting frailty progression may mitigate AMD risk in aging populations.

Keywords: Age-related macular degeneration; Aging; Frailty; Trajectories; UK Biobank.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The UK Biobank study obtained approval from the North West Multi-Center Research Ethics Committee (21/NW/0157). Prior to enrollment, all participants provided informed consent. Competing interests: The authors declare no competing interests.

References

1. Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet. 2012;379(9827):1728–38. https://doi.org/10.1016/s0140-6736(12)60282-7 . - DOI - PubMed
1. Wong WL, Su X, Li X, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106–16. https://doi.org/10.1016/s2214-109x(13)70145-1 . - DOI - PubMed
1. Heesterbeek TJ, Lorés-Motta L, Hoyng CB, Lechanteur YTE, den Hollander AI. Risk factors for progression of age‐related macular degeneration. Ophthalmic Physiol Opt. 2020;40(2):140–70. https://doi.org/10.1111/opo.12675 . - DOI - PubMed - PMC
1. Peng Y, Zhang Y, Kam KW, et al. Associations of cardiovascular health and new-onset age-related macular diseases from UK Biobank. Invest Ophthalmol Vis Sci. 2025;66(4):63. https://doi.org/10.1167/iovs.66.4.63 . - DOI - PubMed - PMC
1. Keenan TDL, Cukras CA, Chew EY. Age-related macular degeneration: epidemiology and clinical aspects. Adv Exp Med Biol. 2021;1256:1–31. https://doi.org/10.1007/978-3-030-66014-7_1 . - DOI - PubMed

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Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank

Affiliations

Dynamic frailty trajectories and risk of age-related macular degeneration: a prospective cohort study in UK Biobank

Authors

Affiliations

Abstract

Conflict of interest statement

References

Grants and funding

LinkOut - more resources

Full Text Sources