Systemic inflammatory biomarkers as risk factors for age-related ocular diseases: a large-scale prospective cohort study

Aims To evaluate associations between systemic inflammation biomarkers and incident age-related ocular diseases while also investigating their correlations with retinal structures. Methods This population-based prospective cohort study analysed 415 599 UK Biobank participants. Systemic immune-inflammation index (SII) and low-grade inflammation score (INFLA-score) were calculated from baseline haematological parameters. Primary outcomes were incident diagnoses of cataract, primary open-angle glaucoma (POAG), age-related macular degeneration (AMD) and diabetic retinopathy (DR). Multivariable Cox proportional hazards models estimated HRs with 95% CIs. Secondary analyses assessed the associations with optical coherence tomography-derived retinal layer thicknesses and vascular features. Results Over a median 13.0-year follow-up, we identified 44 906 cataract, 5803 POAG, 7388 AMD and 3319 DR incident cases. Both SII and INFLA-score demonstrated significant, dose-dependent associations with all ocular outcomes (all p<0.05). Distinct exposure-response patterns emerged: J-shaped relationships for cataract and POAG (SII threshold >500; INFLA-score threshold >0), versus monotonically positive associations for AMD and DR. Elevated inflammatory markers also correlated with retinal thinning, especially in photoreceptor layers. Conclusions Systemic inflammation biomarkers could predict incident age-related ocular diseases with disease-specific patterns while concurrently associating with quantifiable retinal structural and vascular pathologies. These findings suggest that anti-inflammatory strategies might have potential to mitigate ocular ageing processes, although further evidence on causal mechanisms and interventions is warranted.