Frailty and the incidence of major ocular diseases: a prospective cohort study integrating proteomic mediation analysis – BMC Ophthalmology

The long-term association between frailty phenotype and major vision-threatening ocular diseases (age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, and cataract), as well as the potential molecular correlates of this association, remain unclear.

Using data from the UK Biobank, Cox proportional hazards models were used to assess the association between frailty status (classified as non-frail, prefrail, or frail) and the incidence of four ocular diseases. Olink proteomics identified plasma protein signatures associated with frailty status and ocular diseases. Mediation analysis assessed overall and stage-specific (prefrail vs. frail) proteins as potential statistical mediators.

During a median follow-up of 15.7 years, prefrailty and frailty were associated with significantly elevated risks of AMD (Prefrail: HR = 1.17; Frail: HR = 1.49), DR (Prefrail: HR = 1.96; Frail: HR = 3.91), glaucoma (Prefrail: HR = 1.13; Frail: HR = 1.61), and cataract (Prefrail: HR = 1.16; Frail: HR = 1.49) (all P < 0.001). Proteomic profiling revealed 1,068 and 1,387 proteins associated with prefrailty and frailty, respectively, enriched in immune-inflammatory pathways (e.g., leukocyte migration). Similarly, proteins associated with all four ocular diseases were enriched in inflammatory and cell adhesion pathways. Mediation analysis further showed that a spectrum of plasma proteins statistically accounted for part of these associations, with a stage-related increase in the proportion of proteins showing positive (same-direction) indirect effects in DR. Prefrailty and frailty were associated with higher incidence of AMD, DR, glaucoma, and cataract in the UK Biobank. Circulating proteins related to inflammation and extracellular matrix statistically accounted for part of these associations, with a stage-related pattern most evident for DR. These findings suggest that frailty may mark shared systemic and ocular aging processes, but they do not establish causality.…Read more by Fujian Medical University Cancer Hospital, Wang, Urumqi, China, The First Affiliated Hospital of Xi’an Jiaotong University, Jiayu, Xi’an, Ning, Pei, Xinjiang Medical University, peich71@163.com, Department of Gyn-Surgical Oncology, 38518412@qq.com, Tao, Fuzhou, Deng, Cheng, School of Public Health, Xiao, Xuan, Ziyu, xiaoxuan1111@whu.edu.cn, Zhimin, Fujian Cancer Hospital, Renmin Hospital of Wuhan University, Wuhan, Department of Ophthalmology