A large-scale study published in JAMA Ophthalmology is drawing renewed attention to the macular risks of certain systemic medications — some well-known, others unexpectedly implicated. Using an innovative combination of pharmacovigilance data and real-world insurance claims, researchers have identified five systemic drugs associated with maculopathy, four of which appear to pose significant, quantifiable risks.
Led by researchers at Hanyang University in Seoul, the study sought to bridge a critical gap in drug safety monitoring. The team first screened nearly 16,000 maculopathy-related adverse event reports in the FDA’s Adverse Event Reporting System (FAERS) between 2014 and 2023. Using disproportionality analysis, they pinpointed five systemic drugs with unexpectedly strong reporting odds ratios: fingolimod, apixaban, paclitaxel, ibrutinib, and sildenafil.
They then tested these findings against the South Korean Health Insurance Review and Assessment Service (HIRA) database, which covers nearly the entire national population (around 50 million individuals). By comparing the incidence of maculopathy before and after drug exposure, the team quantified real-world risk and explored dose–response effects.
The results were striking. Apixaban, paclitaxel, ibrutinib, and sildenafil all showed statistically significant increases in maculopathy incidence post-exposure. Incidence rate ratios ranged from 2.75 for sildenafil to 3.71 for ibrutinib, while apixaban — the most frequently used — had the highest cumulative incidence, reaching 15.7% during the study period.
Patterns of maculopathy varied. Fingolimod and paclitaxel were mainly associated with macular edema, consistent with their vascular permeability effects. Apixaban, ibrutinib, and sildenafil, meanwhile, were more often linked to macular degeneration-like changes, suggesting ischemic or degenerative pathways. Notably, both paclitaxel and ibrutinib showed clear dose–response relationships, with hazard ratios climbing as cumulative exposure increased.
For ophthalmologists, the findings highlight the need for routine macular screening in patients receiving these agents — particularly those on long-term anticoagulation, chemotherapy, or kinase inhibitor therapy. A baseline retinal examination, followed by periodic OCT monitoring, may allow earlier intervention before irreversible changes occur.
While causality has yet to be confirmed, the study’s design — integrating pharmacovigilance with nationwide claims — sets a precedent for cost-effective, large-scale ocular safety research. As the study authors conclude, clinicians should remain cautious when prescribing these four drugs in higher cumulative doses to patients, and make sure to integrate regular ophthalmic screenings for these patients.
Led by researchers at Hanyang University in Seoul, the study sought to bridge a critical gap in drug safety monitoring. The team first screened nearly 16,000 maculopathy-related adverse event reports in the FDA’s Adverse Event Reporting System (FAERS) between 2014 and 2023. Using disproportionality analysis, they pinpointed five systemic drugs with unexpectedly strong reporting odds ratios: fingolimod, apixaban, paclitaxel, ibrutinib, and sildenafil.
They then tested these findings against the South Korean Health Insurance Review and Assessment Service (HIRA) database, which covers nearly the entire national population (around 50 million individuals). By comparing the incidence of maculopathy before and after drug exposure, the team quantified real-world risk and explored dose–response effects.
The results were striking. Apixaban, paclitaxel, ibrutinib, and sildenafil all showed statistically significant increases in maculopathy incidence post-exposure. Incidence rate ratios ranged from 2.75 for sildenafil to 3.71 for ibrutinib, while apixaban — the most frequently used — had the highest cumulative incidence, reaching 15.7% during the study period.
Patterns of maculopathy varied. Fingolimod and paclitaxel were mainly associated with macular edema, consistent with their vascular permeability effects. Apixaban, ibrutinib, and sildenafil, meanwhile, were more often linked to macular degeneration-like changes, suggesting ischemic or degenerative pathways. Notably, both paclitaxel and ibrutinib showed clear dose–response relationships, with hazard ratios climbing as cumulative exposure increased.
For ophthalmologists, the findings highlight the need for routine macular screening in patients receiving these agents — particularly those on long-term anticoagulation, chemotherapy, or kinase inhibitor therapy. A baseline retinal examination, followed by periodic OCT monitoring, may allow earlier intervention before irreversible changes occur.
While causality has yet to be confirmed, the study’s design — integrating pharmacovigilance with nationwide claims — sets a precedent for cost-effective, large-scale ocular safety research. As the study authors conclude, clinicians should remain cautious when prescribing these four drugs in higher cumulative doses to patients, and make sure to integrate regular ophthalmic screenings for these patients.
