Grip Strength and Age-Related Ocular Diseases: Insights from Observational, Mendelian Randomization, and Mediation Analyses

Chao Chen; Dongling Guo; Jiaqi Meng, MD; Jiao Qi, MD; Keke Zhang, MD; Wenwen He, MD; Yih Chung Tham, PhD; Xiangjia Zhu, PhD

doi:10.1016/j.xops.2025.100831

Ophthalmology Science (Sep 2025)

Grip Strength and Age-Related Ocular Diseases: Insights from Observational, Mendelian Randomization, and Mediation Analyses

Chao Chen,
Dongling Guo,
Jiaqi Meng, MD,
Jiao Qi, MD,
Keke Zhang, MD,
Wenwen He, MD,
Yih Chung Tham, PhD,
Xiangjia Zhu, PhD

Affiliations

Chao Chen: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
Dongling Guo: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
Jiaqi Meng, MD: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
Jiao Qi, MD: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
Keke Zhang, MD: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China
Wenwen He, MD: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China; Wenwen He, MD, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, 200031, China.
Yih Chung Tham, PhD: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore; Centre for Innovation and Precision Eye Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Ophthalmology and Visual Science Academic Clinical Program, Duke-NUS Medical School, Singapore; Yih Chung Tham, PhD, Singapore Eye Research Institute, Singapore National Eye Centre, 168751, Singapore.
Xiangjia Zhu, PhD: Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Myopia and Related Eye Diseases; Key Laboratory of Myopia and Related Eye Diseases, Chinese Academy of Medical Sciences, Shanghai, China; Key Laboratory of Myopia, Chinese Academy of Medical Science, Shanghai, China; Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai, China; Correspondence: Xiangjia Zhu, MD, PhD, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai 200031, China.

DOI: https://doi.org/10.1016/j.xops.2025.100831
Journal volume & issue: Vol. 5, no. 5
p. 100831

Abstract

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Objective: We aimed to examine the cross sectional and causal associations of grip strength with cataract, glaucoma, diabetic retinopathy (DR), and age-related macular degeneration (AMD) and probe the underlying mechanisms by evaluating the mediating role of metabolomic alterations. Design: Cross sectional study. Subjects: A total of 307 796 UK Biobank participants with grip strength and covariates data available. Methods: Logistic regression models were used to evaluate the associations between grip strength and age-related ocular diseases. Two-sample Mendelian randomization analyses were conducted to assess the causality. Metabolic biomarkers from plasma samples were measured through nuclear magnetic resonance (n = 152 376), and principal component (PC) analysis was implemented to identify metabolic patterns (PC1–PC8). The mediation effects of both metabolic biomarkers and metabolic patterns were examined. Main Outcome Measures: The prevalence of age-related ocular diseases. Results: Compared with the highest tertile of grip strength, the lowest tertile had a higher prevalence of cataract (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.24–1.39), glaucoma (OR, 1.23; 95% CI, 1.13–1.33), and DR (OR, 2.80; 95% CI, 2.32–3.38). Genetic-associated elevated grip strength of at least 1 hand was associated with a lower risk of developing cataracts, DR, and AMD. Mediation analyses showed metabolic patterns, characterized by altered lipids and omega-3 polyunsaturated fatty acids (PUFAs) decrement (i.e., PC2 and PC8), significantly mediated the association of grip strength with cataract and DR. Conclusions: Weaker grip strength is associated with cataracts, glaucoma, and DR. Metabolomic alterations, especially disrupted lipid metabolism and omega-3 PUFA decrement, serve to be the critical mediators. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Published in Ophthalmology Science

ISSN: 2666-9145 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Ophthalmology
Website: https://www.journals.elsevier.com/ophthalmology-science/

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