A Study of the Causal Association Between Autoimmune Diseases and Blinding Eye Diseases

Introduction: Autoimmune diseases (ADs) are known to affect multiple organs, including the eyes. This study aims to evaluate the causal associations of rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and ankylosing spondylitis (AS) with cataracts, age-related macular degeneration (AMD), and glaucoma using Mendelian randomization (MR). Methods: Genome-wide association study (GWAS) data were utilized to identify single- nucleotide polymorphisms (SNPs) strongly associated with AS, SLE, RA, cataracts, AMD, and glaucoma, which served as instrumental variables (IVs). The basic analysis was performed via inverse variance weighting (IVW), complemented by weighted median (WM), MR-Egger regression, weighted mode, simple mode, and MR-Robust Adjusted contour scoring technique (RAPS). The Cochran Q test, MR-Egger intercept test, MR-Steiger test, leave-one-out analysis, funnel plot, and MR-PRESSO model were used to assess the robustness of doing sensitivity analysis. Result: IVW estimated that primary angle-closure glaucoma (PACG) (OR=1.265), AMD (OR=1.063), DRY-AMD (OR=1.088), and cataracts were significantly related to RA. SLE is associated with drug-induced cataract (OR=1.113) and senile cataract (OR=1.012). AS is being linked with glaucoma (OR=1.265), PACG (OR=2.436), and primary open-angle glaucoma (POAG) (OR=1.400). Discussion: RA, SLE, and AS can directly contribute to the development of cataracts, AMD, and glaucoma. These results endorse the interdisciplinary interventions approach that can incorporate rheumatology and ophthalmology. All investigations were restricted to individuals of European descent. These findings should be verified and expanded by performing multi-ethnic studies. Conclusion: The study is generally reliable in establishing the causal relationship between AS, SLE, RA, and selective blinding eye illnesses, with the rationale of applying clinical screening techniques and specific intervention strategies.