Post-Marketing Ocular Adverse Events Associated with Tamoxifen and Raloxifene: A Population-Based Pharmacovigilance Study.

Abstract

Tamoxifen and raloxifene are selective estrogen receptor modulators used for breast cancer treatment, and osteoporosis prevention. While systemic adverse events (AEs) are well recognized, ocular AEs have been less comprehensively characterized. The purpose of this study was to evaluate postmarketing ocular AEs associated with tamoxifen and raloxifene using a pharmacovigilance database. The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) data from Q4 2003 to Q2 2025 were analyzed using OpenVigil 2.1. Disproportionality analyses were conducted to calculate reporting odds ratios (RORs) for drug-AE pairs compared with all other drugs. There were a total of 4,084 reports of AEs associated with tamoxifen (mean age 56.7 years), including 505 ocular AEs. The strongest signals were for corneal graft rejection (ROR 118.9), retrobulbar hemorrhage (104.6), ophthalmic vein thrombosis (82.7), retinal deposits (80.7), and macular hole (78.6). Additional events included maculopathy, retinopathy, and optic neuropathy. There were 5,600 reports of AEs associated with raloxifene (mean age 68.6 years), including 437 ocular AEs. The most prominent signals were vascular, including retinal vein thrombosis (ROR 340.0), retinal vascular thrombosis (133.8), retinal artery thrombosis (54.9), and retinal vein occlusion (42.9). Other events included reduced visual acuity, cataract, macular degeneration, and glaucoma. Tamoxifen and raloxifene had unique ocular AE profiles. Tamoxifen was primarily linked to retinal, optic nerve, and corneal disorders, whereas raloxifene was strongly associated with retinal vascular and thromboembolic events. These findings underscore the importance of clinician awareness and future prospective studies to further elucidate the risks.