**Background:** Blinding eye diseases—glaucoma, cataract, and macular degeneration—are major causes of visual impairment worldwide. Inflammation is implicated in their pathogenesis, but whether circulating inflammatory cytokines are causal or consequential remains unclear. This study used bidirectional Mendelian randomization (MR) to assess causal relationships between 41 circulating inflammatory cytokines and these three eye diseases.
**Methods:** Summary-level GWAS data were obtained from publicly available sources. For cytokines, data came from a meta-analysis of 8,293 participants (YFS, FINRISK 1997, FINRISK 2002). For eye diseases: glaucoma (361,194 individuals; 1,715 cases), cataract (337,199; 2,651 cases), and macular degeneration (150,642; 3,553 cases). Single-nucleotide polymorphisms (SNPs) associated with exposures at p < 5×10⁻⁶ were selected as instrumental variables, with clumping (r² < 0.001, window 10,000 kb) and F-statistic > 10. The inverse variance weighted (IVW) method was primary; sensitivity analyses included MR-Egger, weighted median, weighted mode, Cochran's Q test, MR-PRESSO, and leave-one-out. Bonferroni correction set significance at p < 0.0004 (0.05/123).
**Key Results:** Forward MR identified six potential causal associations (all p < 0.05 but not Bonferroni-significant): MIG with increased glaucoma risk (OR: 1.0009, 95% CI: 1.0002–1.0015, p = 0.0085); IL-1ra (OR: 1.0015, 95% CI: 1.0001–1.0030, p = 0.0339), IL-6 (OR: 1.0029, 95% CI: 1.0007–1.0050, p = 0.0083), and IL-10 (OR: 1.0012, 95% CI: 1.0000–1.0024, p = 0.0477) with increased cataract risk; PDGFbb with decreased cataract risk (OR: 0.9990, 95% CI: 0.9980–1.0000, p = 0.0430); MIG with increased macular degeneration risk (OR: 1.0076, 95% CI: 1.0031–1.0122, p = 0.0009); and HGF with decreased macular degeneration risk (OR: 0.9912, 95% CI: 0.9844–0.9979, p = 0.0106). Reverse MR showed cataract associated with lower VEGF levels (OR: 3.326×10⁻⁴, 95% CI: 5.198×10⁻⁷–2.129×10⁻¹, p = 0.0151). Sensitivity analyses confirmed no significant heterogeneity or horizontal pleiotropy.
**Clinical Implications:** These findings suggest that specific inflammatory cytokines (MIG, IL-1ra, IL-6, IL-10, PDGFbb, HGF) may be upstream mediators in the development of glaucoma, cataract, and macular degeneration, while VEGF may be a downstream effector in cataract. The results highlight potential biomarkers for early risk stratification and novel therapeutic targets. However, the lack of Bonferroni significance and limited statistical power necessitate validation in larger, diverse populations and further mechanistic studies.