Key Takeaways

  • Five medications were identified as having elevated wet AMD reporting signals in FAERS data
  • Integrative proteogenomic analyses implicated six candidate genes, with WARS1 showing evidence supporting colocalization with wet AMD risk
  • Immune and inflammatory pathways emerged as potential mechanistic links warranting further study

A large pharmacovigilance and proteogenomic analysis has identified several commonly used medications that may be associated with an increased reporting risk of wet age-related macular degeneration (AMD), while also highlighting potential molecular pathways that could help explain these signals.1

Investigators from China combined data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) with genetic, proteomic, and single-cell transcriptomic analyses to identify drug-associated risk signals and explore their biological underpinnings. The findings were published in Eye.

The researchers first analyzed FAERS reports for disproportionate reporting of wet AMD and identified five drugs associated with elevated reporting signals: apixaban, carbamazepine, latanoprost, rituximab, and semaglutide.

To move beyond signal detection and investigate potential mechanisms, the team mapped drug targets and integrated summary-based Mendelian randomization and colocalization analyses using cis-protein quantitative trait loci datasets. This approach identified six genes that may play a role in wet AMD susceptibility: IGFBP6, MAPKAPK2, NFKB1, RGMA, RNASE1, and WARS1. Among these candidates, WARS1 demonstrated evidence supporting colocalization, strengthening its candidacy as a potentially relevant molecular mediator.

Single-cell RNA sequencing analyses further showed that most candidate genes were predominantly expressed in vascular-remodeling endothelial cells, while WARS1 also exhibited strong expression specificity in monocytes. These findings suggest that vascular and immune cell populations may contribute to the biological processes linking drug exposure and disease development.

Additional pathway analyses pointed toward inflammatory and immune-related mechanisms, including involvement of Toll-like receptor, tumor necrosis factor (TNF), and NF-kappa B signaling pathways. The authors noted that these pathways have previously been implicated in retinal inflammation and angiogenesis, two central features of nAMD pathogenesis.

The investigators emphasized that the findings should be interpreted as hypothesis-generating rather than evidence of causality. Pharmacovigilance databases are subject to reporting biases and cannot establish definitive drug-related risk. Nevertheless, the integration of adverse event reporting with human genetic and proteomic data provides a framework for prioritizing signals for future laboratory and clinical investigation.

According to the authors, the results may help guide future research aimed at clarifying whether these observed associations reflect true biological effects and whether the identified genes could serve as therapeutic targets or biomarkers in wet AMD.

Reference

1. Source: Sun H, Bu F, Xin X, et al. “Uncovering drug-associated risk signals for neovascular age-related macular degeneration: an integrative pharmacovigilance and proteogenomic study,” Eye (2026).