Relationships between Frailty and the Risk of Glaucoma in Middle-aged and Older Adults.

PURPOSE: Increased frailty in older individuals increases health risks, but its relationship with glaucoma, the leading cause of irreversible blindness in middle-aged and older adults, is unclear. We investigated the association between frailty and glaucoma in a large-scale representative sample and explored possible causal relationships.

DESIGN

Combined cross-sectional and Mendelian randomization (MR) study.

PARTICIPANTS

In the cross-sectional analysis, we included 5744 participants of the US National Health and Nutrition Examination Surveys 2005 to 2008 ≥ 40 years of age. For the MR analysis, frailty genome-wide association study (GWAS) data were sourced from a UK Biobank and TwinGen meta-analysis, and GWAS data on glaucoma subtypes were derived from FinnGen.

METHODS

According to the 49-item frailty index, we classified participants into nonfrail (≤ 0.10), prefrail (0.10-0.21), and frail (> 0.21) groups. Using survey-weighted logistic regression models adjusted for multiple covariates, we explored the association between frailty and glaucoma. We further assessed causation using MR.

MAIN OUTCOME MEASURES: The associations between different levels of frailty (nonfrail, prefrail, and frail) and glaucoma, as well as causal relationships between genetically predicted frailty and various subtypes of glaucoma (primary open-angle glaucoma [POAG], primary angle-closure glaucoma [PACG], normotensive glaucoma [NTG], exfoliation glaucoma, and suspected glaucoma).

RESULTS

After adjusting for covariates, higher frailty levels were significantly associated with glaucoma in frail individuals (odds ratio [OR] = 1.83, 95% confidence interval [CI] = 1.05-3.19, P = 0.036) but not prefrail (OR = 1.90, 95% CI = 0.99-3.64, P = 0.052). The association was significantly stronger among male participants (P interaction = 0.042). The variation in the association between frailty and glaucoma did not reach statistical significance across age groups (P interaction = 0.575) or race groups (P interaction = 0.092). Mendelian randomization revealed that genetically predicted frailty was linked to greater risks for POAG (OR = 1.67, 95% CI = 1.24-2.25, P = 0.001), PACG (OR = 2.78, 95% CI = 1.48-5.20, P = 0.001), exfoliation glaucoma (OR = 1.70, 95% CI = 1.18-2.43, P = 0.004), and suspected glaucoma (OR = 1.74, 95% CI = 1.30-2.34, P < 0.001) but not for NTG (OR = 1.01, 95% CI = 0.61-1.68, P = 0.956).

CONCLUSIONS

Our study revealed an association between frailty and increased glaucoma risk and emphasized the significance of glaucoma screening in frail individuals. Targeted health-care strategies can help prevent or delay irreversible blindness among middle-aged and older adults.

FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.