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Abstract #128293 Published in IGR 25-3
Grip Strength and Age-Related Ocular Diseases: Insights from Observational, Mendelian Randomization, and Mediation Analyses
Chen C; Guo D; Meng J; Qi J; Zhang K; He W; Tham YC; Zhu XOphthalmology science 2025; 5: 100831
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 DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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