Risk factors for pentosan polysulfate maculopathy

To identify risk factors for pentosan polysulfate (PPS) maculopathy.

Cross-sectional study of PPS-exposed individuals seen at Emory Eye Center from January 2018 to March 2024. Data from standardized questionnaires and fundus imaging were evaluated. Multivariate analyses were used to evaluate toxicity risk factors, and subgroup analysis was used to compare characteristics in low-exposure (<800 g) and high-exposure (>1500 g) groups.

In total, 187 patients (mean age 59.5±13.8 years, 84.5% female) underwent screening. Risk of toxicity was dose-dependent, with those in the greatest exposure quartile (≥2000 g) showing the greatest risk (odds ratio [OR] 39.8, 95% confidence interval [CI] 10.6-205.1, P < .001). Other factors associated with risk included cumulative dose per body weight (OR 1.1, 95% CI 1.0-1.1, P < .001), female sex (OR 8.1, 95% CI 1.2-75.9, P = .04), older age (OR 1.03, 95% CI 1.02-1.1, P = .046), and inflammatory bowel disease or irritable bowel syndrome (OR 2.8, 95% CI 1.2-6.6, P = .02). In low-exposure cases (<800 g), those with maculopathy were older (67.1 vs 56.9 years, P = .01), had longer PPS exposure (11 vs 7.9 years, P = .03), a greater dose per body weight (9.7 vs 5.1 g/kg, P < .001), and lower body weight (63.9 vs 74.4 kg, P = .03). The prevalence of toxicity among PPS users at Emory is estimated as ranging between 3.8% and 24.5%.

This comprehensive screening study corroborates that the risk of PPS maculopathy is primarily driven by cumulative PPS exposure but also suggests a possible role for other factors including age, sex, and body weight. These findings have global public safety implications and may help inform dosing guidelines and screening protocols.