Expanded Clinical Spectrum of Pentosan Polysulfate Maculopathy: A Macula Society Collaborative Study

Purpose: Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings. Design: Multi-institutional retrospective study. Participants: Patients exhibiting findings suggestive of PPS maculopathy identified from April 30, 2019, to December 4, 2020. Methods: Members of the Macula Society submitted cases of presumed PPS maculopathy for consideration in this series. Diagnosis was confirmed by masked review of fundus imaging. Clinical characteristics of confirmed cases were summarized with descriptive statistics. Main Outcome Measures: Pentosan polysulfate exposure characteristics and fundus imaging features. Results: There were 74 patients with PPS maculopathy included in the current study. Median (interquartile range) age at diagnosis was 62.0 years (56.0–65.8). The median duration of exposure to PPS was 14.0 years (10.2–18.9), with a median cumulative exposure of 1.5 kg (0.9–2.4). The most common presenting symptom was decreased or blurry vision (66.2%), followed by prolonged dark adaption or nyctalopia (32.4%). The most common referral diagnosis was age-related macular degeneration (54.1%); 16.2% of patients were referred for suspected PPS maculopathy. Novel imaging findings emerged, including highly asymmetric disease in 2 patients and a prominent vitelliform maculopathy in 2 patients. Conclusions: Most patients with PPS maculopathy exhibit characteristic findings on multimodal fundus imaging in the setting of high cumulative exposure to the oral drug. Some patients in the current study manifested novel imaging findings, expanding our understanding of the phenotypic spectrum of this condition. We recommend considering standardized ophthalmic screening of patients treated with PPS.