Drugs Recognized as Potential Maculopathy Risk Factors

The FDA Adverse Event Reporting System was used to find five drug candidates with the highest underrecognized maculopathy risk—fingolimod, apixaban, paclitaxel, ibrutinib and sildenafil. However, cumulative incidence rates were high among four of these candidates—apixaban, paclitaxel, ibrutinib and sildenafil—meaning they should be evaluated further for maculopathy both in practice and in clinical trials to ensure their safety in patients. Photo: Care Formulation Labs. Click image to enlarge. Clinicians are well aware of the many potential drug toxicities that may arise from systemic medication use. However, given the proliferation of treatments available, some prescriptions go unrecognized as being harmful. Researchers from North Carolina and South Korea analyzed reports from United States and Korean databases to evaluate pharmacological effects leading to maculopathy.1Using the FDA’s Adverse Event Report System (FAERS) and the South Korean Health Insurance Review and Assessment Service (HIRA), researchers determined which drugs were associated with toxic events and the risk of developing maculopathy. Only therapies with undiscovered connections to maculopathy were considered for this study; therefore, hydroxychloroquine and pentosan polysulphate, which have been studied before as potential causes of retinopathy and maculopathy, were not analyzed. Maculopathy-related individual case reports were collected from the FAERS database to determine systemic drugs, and a separate evaluation of incidence rates was conducted using the HIRA database. Results were published in JAMA Ophthalmology.After assessing 15,748 reports from the FAERS database, many medications were newly discovered in relation to a maculopathy-related adverse event. The top five reported drugs that have gone unexplored were fingolimod (788 reports), apixaban (262 reports), paclitaxel (248 reports), ibrutinib (175 reports) and sildenafil (92 reports).Now that five drugs with relation to maculopathy-related cases have been established, risk ratios were calculated using data from the HIRA database. Incidence rate ratios were used to determine risk after exposure to the drug, and cumulative incidence rates were used to determine risk over time—six months, one year and end of study. Fingolimod (brand name Gilenya), a drug for multiple sclerosis, had an incidence rate ratio of 1.92, apixaban (a blood thinner) had a ratio of 3.08, paclitaxel (a cancer drug) had a ratio of 2.85, ibrutinib (another cancer drug) had a ratio of 3.71 and sildenafil (Viagra) had a ratio of 2.75.The highest cumulative incidence ratios were recorded at the end of study period. Apixaban had the highest, with 15.7%, followed by ibrutinib at 9.9%, paclitaxel at 6.6%, sildenafil at 6% and fingolimod at 4.4%.“The cumulative incidence rates, approaching or exceeding 10%, suggest that clinicians should remain vigilant in monitoring macular changes in patients prescribed these medications, especially if subsequent studies confirm these findings,” said the authors in their paper. “These findings suggest that regular, long-term ocular monitoring should be integrated into clinical practice for candidate drug users to enable timely detection and intervention to manage associated maculopathy.”A commentary, also published in JAMA Ophthalmology, commended the researchers for their study’s methodology and their contribution to eye care.2 They noted that the study’s methods and sensitivity analyses support the robustness of the findings regarding medications that have been overlooked for maculopathy risk.  In the commentary, the author finds the recent investigation an acceptable update in the field with safety information about systemic drugs such as apixaban, which had a high reported incidence rate. This drug is not uncommon in practice, and the commentator noted this, saying that physicians who prescribe this medication should be aware of this study, and additional studies are warranted to further understand its maculopathy risk.Additionally, the commentary author believes this study promotes the importance of larger databases reporting on adverse events, such as FAERS. As physicians continue to prescribe treatments, spontaneous adverse event reporting databases can be useful, as the author suggests that they can be readily applied to examine safety events for many medically approved products and conditions.“The fact that drugs such as hydroxychloroquine, with a known risk of maculopathy, can be identified by the analytical pathway suggests the utility of FAERS and electronic health record data in postmarket surveillance and indicates that the proposed analytical methodology is sound,” wrote the commentators in their paper. “Future applications of the methodology should also consider and document these design aspects.” Click here for the journal source and here for the commentary. 1. Kim J, Ahn SJ, Park J, et al. Systemic drugs associated with maculopathy. JAMA Ophthalmol. October 23, 2025. [Epub ahead of print].2. Kong X. Using big data for postmarket safety surveillance. JAMA Ophthalmol. October 23, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.