Some systemic drugs may be under-recognized causes of maculopathy

Early identification of systemic medications that may have unrecognized macular toxic effects might be important for vision preservation. Drug-induced maculopathy is a potentially preventable condition that, if undetected, can lead to visual impairment ranging from subtle changes to irreversible vision loss, depending on the severity of damage. Some drug-induced retinal toxic effects are well-documented, such as hydroxychloroquine retinopathy or pentosan polysulfate maculopathy. Whether other systemic drugs are associated with macular toxic effects has not been well studied.1 To identify systemic drugs potentially associated with maculopathy, investigators used pharmacovigilance data to identify drugs possibly associated with maculopathy and then examined the macular adverse effects of these drugs using data from a nationwide health claims database.1The study was conducted in two phases. The investigators first examined 15,748 maculopathy-related individual case safety reports from the US Food and Drug Administration Adverse Event Reporting System (FAERS) between July 2014 and December 2023 to identify signal drugs possibly associated with myopathy. They then conducted a population-based cohort study for association evaluation among users of the candidate signal drugs, using the South Korean Health Insurance Review and Assessment Service (HIRA) database, which covers approximately 50 million individuals.1 Key results:Five systemic drugs with underrecognized macular toxic effects were identified among the top 30 maculopathy signals in the US FAERS database—fingolimod, apixaban, paclitaxel, ibrutinib and sildenafil.In the Korean HIRA database, the incidence rate ratios for maculopathy following exposure (vs preexposure) were:fingolimod 1.92 (95%CI, 0.62–5.96)apixaban 3.08 (95%CI, 2.68–3.54) paclitaxel 2.85 (95%CI, 1.62–5.02) ibrutinib 3.71 (95%CI, 2.58–5.34) sildenafil 2.75 (95%CI, 2.17–3.48). The cumulative incidence rates of maculopathy ranged from 4.4% (fingolimod) to 15.7% (apixaban). Dose-response relationships were observed for paclitaxel (hazard ratio, 2.01; 95%CI, 1.77–2.29) and ibrutinib (hazard ratio, 4.82; 95%CI, 1.39–16.81).1The authors conclude that their integration of pharmacovigilance signal detection and nationwide health claims analysis identified associations of maculopathy with apixaban, paclitaxel, ibrutinib and sildenafil. They believe this two-step study design offers a cost-effective robust method for identifying systemic drugs with possible underrecognized macular adverse effects. If subsequent studies confirm these findings, regular ophthalmic monitoring of patients receiving these medications should become standard practice to enable early detection of macular changes and timely intervention.1An accompanying editorial points out that spontaneous adverse event reporting databases, such as FAERS, provide a valuable starting point for safety signal detection, especially for toxic effects (e.g., retinal toxic effects of systemic drugs) that arise after long-term use of a product, which may not have been observed during the clinical development phase prior to product approval. However, FAERS and other similar databases have inherent limitations due to their voluntary reporting nature and unknown accuracy of reports. These limitations can be mitigated by using complementary data sources, such as databases containing patient-specific electronic health records to identify systemic drugs associated with maculopathy, as was done in this study.2The commentary highlights that four systemic drugs were found to be associated with the greatest elevated risk of maculopathy: apixaban, paclitaxel, ibrutinib and sildenafil. These data call for attention from physicians of all specialties involved in prescribing these drugs, as well as ophthalmologists. Additional studies are warranted to identify patient characteristics predictive of developing maculopathy and to examine potential interventions that may prevent maculopathy after initiation of these drugs.2References1. Kim J, Ahn SJ, Park J, et al. Systemic drugs associated with maculopathy. JAMA Ophthalmol 2025; Published online October 23, 2025. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2840123 (accessed October 28, 2025).2. Kong X. Using big data for postmarket safety surveillance. JAMA Ophthalmol 2025; Published online October 23, 2025. https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2840132 (accessed October 28, 2025).

Some systemic drugs may be under-recognized causes of maculopathy

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