Triglyceride-Glucose–Related Indexes as Risk Factors for Vision-Threatening Ocular Diseases: A Prospective UK Biobank Study

Background: To evaluate the associations of the triglyceride-glucose (TyG) index and related obesity-combined indexes with the incidence of major vision-threatening ocular diseases. Methods: This prospective population-based cohort study included 400,237 participants from the UK Biobank. The TyG index and derived indexes (combined with waist circumference, waist-to-height ratio, and body mass index) were calculated using baseline laboratory and anthropometric data. The outcomes were incident cases of cataract, POAG, AMD, and diabetic retinopathy (DR), ascertained using self-reported data, hospital inpatient records, and primary care records. Cox proportional hazards models were used, with restricted cubic splines fitted to characterize dose-response relationships. Secondary analyses assessed the associations with retinal thicknesses and vascular features. Results: Over a median follow-up of 13.0 years, 46,151 cataract, 6317 POAG, 8276 AMD, and 5220 DR incident cases were identified. Distinct nonlinear associations were observed: the TyG index exhibited a reverse L-shaped relationship with cataract and DR, a J-shaped association with AMD, and a U-shaped relationship with POAG (all P total < 0.01, all P nonlinear < 0.05), suggesting an estimated optimal range from 8.6 to 9.1. Furthermore, elevated TyG-obesity indexes exhibited monotonic positive associations with the risk of cataract, AMD, and DR (all P total < 0.001), whereas moderate elevation was associated with a reduced risk of POAG (all P total < 0.01, all P nonlinear < 0.05). Elevated TyG-obesity indexes were also associated with retinal thinning and vascular abnormalities, providing supportive discrimination and risk-stratification information for incident DR. Conclusions: The TyG index and related obesity-combined indexes show disease-specific associations with major sight-threatening conditions, accompanied by retinal structural alterations. Maintaining these parameters within optimal ranges could help mitigate the risk of vision impairment.