Drug-induced macular edema: a global pharmacovigilance study using the WHO VigiBase database

Macular edema (ME) is a vision-threatening condition characterized by the accumulation of extracellular fluid in the macula due to disruption of the blood-retinal barrier. Although ME is commonly associated with underlying diseases such as diabetic retinopathy and age-related macular degeneration, pharmacologic agents may independently contribute to its development. The purpose of this study was to identify drugs associated with ME using a large global pharmacovigilance database and to evaluate differences in risk among drug classes. Data were obtained from VigiBase, the World Health Organization’s global database of individual case safety reports. All reports registered up to October 2, 2023 were screened, and cases in which ME was reported as an adverse event were extracted. Disproportionality analyses were performed to evaluate drug-event associations using the information component (IC), proportional reporting ratio (PRR), and odds ratio (OR). A positive lower bound of the 95% credibility interval for IC (IC 025 >0) was considered statistically significant. Among 35,715,461 adverse drug reaction reports in VigiBase, 429,883 were classified as ocular adverse events, of which 5,083 involved ME. The number of reports increased steadily over time and was most frequent in individuals aged 45–64 years. Disproportionality analysis identified 3,864 drug-event pairs significantly associated with ME. The most frequently implicated drug classes included sphingosine-1-phosphate receptor modulators, anti-vascular endothelial growth factor agents, diabetes-related medications, prostaglandin analogue eye drops, anticancer agents, and corticosteroids. Fingolimod showed the strongest association after adjustment for potential confounding, followed by Siponimod, Latanoprost, and Fluocinolone acetonide. Additional analyses revealed substantial variability in ME risk among drugs within the same therapeutic class. This large-scale pharmacovigilance study identified multiple drugs and therapeutic classes significantly associated with ME. Several commonly prescribed medications, including systemic and ophthalmic agents, may contribute to the development of ME independently of underlying disease. These findings may improve clinical awareness of drug-induced ME and support safer treatment selection in patients at risk.