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Frailty-Driven Risk Stratification in Age-Related Ophthalmic Diseases: Thresholds, Precision Screening, and Mendelian
1Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Purpose:
To define frailty thresholds for accelerated progression of age-related ophthalmic diseases and inform precision intervention.
Methods:
Using NHANES 2005-2008 (n = 7081 adults ≥ 40 years), we constructed a 49-item frailty index (FI) via the deficit accumulation model. Missing data were addressed with complete-case analysis (n = 4120) and multiple imputation. Two analytic cohorts were defined: (1) objective diagnosis group and (2) composite diagnosis group. Multivariable logistic regression with restricted cubic splines (RCS) assessed associations between the FI and age-related macular degeneration (AMD), cataract, glaucoma, and diabetic retinopathy (DR). Bidirectional Mendelian randomization (MR) tested causality.
Results:
Findings were consistent across complete-case and imputed datasets. In continuous analyses, the FI was associated with AMD (composite odds ratio [OR] = 1.17; objective OR = 1.16), cataract (OR = 1.30), DR (OR = 1.33), and glaucoma (OR = 1.12). In categorical analyses, extreme frailty (FI > 0.45) conferred the highest risks: cataract (OR = 2.51), DR (OR = 2.04), AMD (OR = 1.77), and glaucoma (OR = 1.45). RCS analyses identified nonlinear thresholds at FI = 0.20 (AMD) and FI = 0.19 (cataract), whereas DR and glaucoma showed linear trends. MR supported a causal effect of frailty on four diseases, with no evidence for reverse causation.
Conclusions:
Frailty was shown to accelerate ophthalmic disease progression. Three clinical implications are proposed here: (1) prioritized screening for individuals with FI > 0.45, (2) recognizing FI thresholds around 0.19 to 0.20 as potential early warning signals for accelerated AMD and cataract, and (3) integrating geriatric and ophthalmic care.
Translational Relevance:
This study provides actionable FI thresholds to identify high-risk aging populations and reinforces frailty as a modifiable upstream driver of ocular aging.
