Using data from the FDA Adverse Event Reporting System, researchers investigated the prevalence of pentosan polysulfate sodium–associated retinal disorders.
Results of a disproportionality analysis published in JAMA Ophthalmology show users of pentosan polysulfate sodium (PPS) were more likely to report adverse events associated with retinal disorder compared with those who used different drugs for interstitial cystitis (IC) and bladder pain.
According to the authors, these findings “add to the growing evidence that PPS use is associated with an increased risk of maculopathy.”
PPS is the only FDA-approved pharmacological treatment for IC, the researchers explained. Although the drug has been available since 1996, concerns regarding its association with maculopathy have only recently been raised, while previous epidemiological studies on PPS and macular disease have yielded mixed results.
To better elucidate this relationship, the investigators assessed data from the US FDA Adverse Event Reporting System (FAERS), a voluntary reporting tool used for postmarketing surveillance of medications and biologics. In the current analysis, data were gleaned from January 2013 to June 2020. For comparison, information on adverse events associated with drugs other than PPS taken for IC, cystitis, bladder disorder, or bladder pain, was also assessed.
A total of 9608 reports were included; 2775 made up the PPS group (70.9% women) and 6833 made up the other drugs group (59.1% women). IC predominately affects women but has no known causative mechanism.
Overall, “the proportion of adverse events for any macular event relative to all other events was elevated for the users of PPS compared with those using other IC and bladder pain drugs (proportionate reporting ratio [PRR], 1.21; 95% CI, 1.01-1.44),” the researchers wrote.
Specific retinal conditions were also proportionally more common among those who took PPS compared with other drugs, respectively:
However, decreased associations were also found between PPS use and photophobia, blurred vision, reduced visual acuity, visual impairment, and vitreous floaters.
“Because of the lack of events in the comparison group, PRRs were not estimable for conditions such as retinal drusen, retinal dystrophy, retinal injury, retinal toxicity, [and] retinal pigmentation, although the differences were truly or borderline significant,” the authors noted.
They added the heterogeneity of adverse events reported in this analysis is associated with the self-reported nature of FAERS. As such, they were unable to validate reports and cautioned a causal relationship between PPS and adverse events cannot be inferred. Small numbers of reported specific retinal events also mark a limitation to the study.
“Although individual observational studies are unable to establish cause-and-effect associations, the growing body of epidemiologic, clinical, and pathophysiologic research strengthens the interpretation that PPS use may lead to maculopathy,” the authors concluded.
“Additional research including prospective observational studies of individuals with normal fundi are needed to further elucidate this association,” they said.
McGwin G, MacLennan P, and Owsley C. Association between pentosan polysulfate sodium and retinal disorders. JAMA Ophthalmol. Published online November 18, 2021. doi:10.1001/jamaophthalmol.2021.4778