Evaluating Systemic Immune-Inflammation Index and Mortality in Diabetic Retinopathy: A NHANES 2005-2018 Cohort Study

Diabetic retinopathy (DR) is a leading cause of preventable blindness and is linked to excess mortality. Systemic inflammation plays a central role in DR pathogenesis, and the systemic immune-inflammation index (SII) has emerged as a novel marker associated with adverse outcomes. However, its prognostic value in DR remains unclear.

Using nationally representative data from National Health and Nutrition Examination Survey 2005-2018, we investigated the association between the systemic immune-inflammation index (SII) and all-cause mortality among 209 US adults aged ≥ 50 years with DR. Mortality status was ascertained through linkage to the National Death Index through 2019.

Weighted Cox regression models showed that higher SII was modestly but significantly associated with increased mortality risk (HR = 1.01, 95% CI 1.00-1.002, p < 0.001), with restricted cubic splines indicating a non-linear relationship. SII exhibited moderate predictive ability for mortality, with AUCs declining from 0.762 at 24 months to 0.576 at 60 months. Subgroup analyses suggested that the association between SII and mortality persisted across most demographic and clinical strata.

These findings suggest that elevated systemic immune inflammation may independently predict long-term mortality risk in adults with DR, highlighting its potential value as a prognostic biomarker beyond traditional risk factors.