身体虚弱和遗传易感性与不可逆眼病风险的关联

IF 4.6 Q1 OPHTHALMOLOGY

Ophthalmology science Pub Date : 2025-09-25 DOI:10.1016/j.xops.2025.100910

Zhenyi Xu PhD , Ruilang Lin MMed , Xiaojun Wang PhD , Yahang Liu , Chen Huang PhD , Ce Wang PhD , Zhijun Bao PhD

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引用次数: 0

摘要

目的将虚弱与整体和特定的不可逆眼病联系起来的证据是有限的。此外，目前还不清楚，在不同的遗传风险谱中，虚弱是否与相似的风险增加有关。本研究的目的是研究虚弱与整体和特定的不可逆眼病之间的关系，并探讨青光眼、糖尿病视网膜病变和年龄相关性黄斑变性（AMD）的遗传风险在这些关联中的改变作用。前瞻性队列研究。参与者这项研究包括英国生物银行研究中的409579名白人参与者。方法将体质虚弱定义为体重减轻、疲劳、体力活动不足、步行速度慢和握力不足5个组成部分。参与者被分为非体弱、体弱或体弱。多基因风险评分分为低(1)、中(2)和高(3)。采用Cox回归来评估身体虚弱与不可逆眼病的关系。主要结局和测量方法：利用住院电子健康记录和死亡登记确定可逆性眼病。结果409579例患者（平均年龄56.5岁，男性46.5%）中位随访13.1年，其中非体弱组、体弱组和体弱组分别有10 927例、7 095例和919例被诊断为不可逆眼病。体弱和体弱个体出现整体不可逆眼病的风险增加，体弱个体的风险增加12%（危险比[HR]， 1.12； 95%可信区间[CI]， 1.09-1.16），体弱个体的风险增加47%（危险比，1.47；95%可信区间[CI]， 1.37-1.58）。特定不可逆眼病的风险也增加，包括青光眼（易患性的HR为1.11 [95% CI, 1.06-1.17]；易患性的HR为1.43 [95% CI, 1.28-1.61]）、糖尿病视网膜病变（易患性的HR为1.12 [95% CI, 1.03-1.21]；易患性的HR为1.53 [95% CI, 1.34-1.73]）和AMD（易患性的HR为1.13 [95% CI, 1.08-1.19]；易患性的HR为1.35 [95% CI, 1.20-1.52]）。此外，与遗传风险低、非遗传风险高的个体相比，体弱多病和遗传风险高的个体出现不可逆眼病的风险更高。结论：虚弱与不可逆眼病风险增加有关，特别是在遗传风险较高的个体中。这些发现表明，预防和管理虚弱的有针对性的策略可能有助于降低不可逆眼病的风险。作者在本文中讨论的任何材料中没有专有或商业利益。

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Association of Physical Frailty and Genetic Predisposition with Risk of Irreversible Eye Diseases

Objective

The evidence linking frailty to overall and specific irreversible eye diseases is limited. Moreover, it is unclear whether frailty is associated with similar increased risk across individuals with different genetic risk profiles. The aim of this study was to examine the association between frailty and overall and specific irreversible eye diseases and explore the modification effect of genetic risk of glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) in such associations.

Design

Prospective cohort study.

Participants

The study included a total of 409 579 White participants in the UK Biobank study.

Methods

Physical frailty was defined by 5 components: weight loss, exhaustion, low physical activity, slow walking speed, and low grip strength. Participants were classified as nonfrail, prefrail, or frail. Polygenic risk score was categorized as low (tertile 1), intermediate (tertile 2), or high (tertile 3). Cox regression was used to assess the association of physical frailty with irreversible eye diseases.

Main Outcomes and Measures

Irreversible eye diseases were identified using hospital admission electronic health records and death registries.

Results

Among 409 579 individuals (mean age, 56.5 years; 46.5% male) with a median follow-up of 13.1 years, 10 927, 7 095, and 919 were diagnosed with irreversible eye disease in the nonfrail, prefrail, and frail groups, respectively. Prefrail and frail individuals showed increased risks of overall irreversible eye diseases, with a 12% higher risk for prefrail individuals (hazard ratio [HR], 1.12; 95% confidence interval [CI], 1.09–1.16) and a 47% higher risk for frail individuals (HR, 1.47; 95% CI, 1.37–1.58). Increased risks were also observed for specific irreversible eye diseases, including glaucoma (HR, 1.11 [95% CI, 1.06–1.17] for prefrailty; HR, 1.43 [95% CI, 1.28–1.61] for frailty), diabetic retinopathy (HR, 1.12 [95% CI, 1.03–1.21] for prefrailty; HR, 1.53 [95% CI, 1.34–1.73] for frailty), and AMD (HR, 1.13 [95% CI, 1.08–1.19] for prefrailty; HR, 1.35 [95% CI, 1.20–1.52] for frailty). Furthermore, individuals with more severe frailty status and higher genetic risk exhibited higher risks of irreversible eye diseases than those with low genetic risk and nonfrailty.

Conclusions

Frailty was associated with an increased risk of irreversible eye diseases, particularly among individuals with higher genetic risk. These findings suggest that targeted strategies to prevent and manage frailty may contribute to reducing the risk of irreversible eye diseases.