Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium

Purpose: To describe the clinical features of a unique pigmentary maculopathy noted in the setting of chronic exposure to pentosan polysulfate sodium (PPS), a therapy for interstitial cystitis (IC). Design: Retrospective case series. Participants: Six adult patients evaluated by a single clinician between May 1, 2015, and October 1, 2017. Methods: Patients were identified by query of the electronic medical record system. Local records were reviewed, including results of the clinical examination, retinal imaging, and visual function assessment with static perimetry and electroretinography. Molecular testing assessed for known macular dystrophy and mitochondrial cytopathy genotypes. Main Outcome Measures: Mean best-corrected visual acuity (BCVA; in logarithm of the minimum angle of resolution units), median cumulative PPS exposure, subjective nature of the associated visual disturbance, qualitative examination and imaging features, and molecular testing results. Results: The median age at presentation was 60 years (range, 37-62 years). All patients received PPS for a diagnosis of IC, with a median cumulative exposure of 2263 g (range, 1314-2774 g), over a median duration of exposure of 186 months (range, 144-240 months). Most patients (4 of 6) reported difficulty reading as the most bothersome symptom. Mean BCVA was 0.1 +/- 0.18 logarithm of the minimum angle of resolution. On fundus examination, nearly all eyes showed subtle paracentral hyperpigmentation at the level of the retinal pigment epithelium (RPE) with a surrounding array of vitelliform-like deposits. Four eyes of 2 patients showed paracentral RPE atrophy, and no eyes demonstrated choroidal neovascularization. Multimodal retinal imaging demonstrated abnormality of the RPE generally contained in a well-delineated area in the posterior pole. None of the 4 patients who underwent molecular testing of nuclear DNA returned a pathogenic mutation. Additionally, all 6 patients showed negative results for pathogenic variants in the mitochondrial gene MTTL1. Conclusions: We describe a novel and possibly avoidable maculopathy associated with chronic exposure to PPS. Patients reported symptoms of difficulty reading and prolonged dark adaptation despite generally intact visual acuity and subtle funduscopic findings. Multimodal imaging and functional studies are suggestive of a primary RPE injury. Additional investigation is warranted to explore causality further. (C) 2018 by the American Academy of Ophthalmology