Spectrum of Colopathy and Severe Polyposis Associated With Pentosan Polysulfate Sodium Maculopathy: A Retrospective Case Series.

Abstract

To expand the spectrum of gastrointestinal (GI) manifestations associated with pentosan polysulfate sodium (PPS) maculopathy. Retrospective case series. Eight patients (16 eyes) diagnosed with PPS maculopathy who also underwent GI evaluation between 2019 and 2025. Electronic medical records were reviewed for demographics, PPS dosage and duration, ocular findings, GI history, diagnostic presentation, and histopathology. Multimodal imaging included fundus photography, fundus autofluorescence, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography. Colonoscopy was performed in all patients with histopathologic analysis in selected cases. PPS maculopathy was staged according to Wang et al.'s classification system. Genetic testing was obtained in selected cases to exclude any form of inherited maculopathy or familial adenomatous polyposis. Clinical and imaging features of PPS maculopathy and GI pathological diagnosis, including polyposis, dysplasia, and inflammatory bowel disease. The cohort included 6 women and 2 men (median age: 68.5 years). Median PPS exposure was 25.4 years with a median cumulative dose of 2899 grams. At presentation, 62.5% of eyes were stage 1, 31.3% stage 2, and 6.3% stage 3. At final follow-up, 25% of eyes were stage 1, 50% stage 2, and 25% stage 3. Overall, 37.5% of eyes showed progression of maculopathy stage, and cRORA was present in 75% of eyes at last follow-up. Additional findings included acquired vitelliform lesions, outer retinal tubulations, epiretinal membranes, and type 2 macular neovascularization. Colonoscopy revealed severe adenomatous polyposis in 6 of the 8 patients (75%), with 3 requiring partial or total colectomy and 2 undergoing endoscopic resection. One patient developed ulcerative colitis, and 2 additional patients were diagnosed with Crohn's disease or microscopic colitis. The median latency to GI diagnosis was 10 years after PPS initiation. This study expands the recognized systemic toxicity of PPS, demonstrating that PPS maculopathy patients are at risk of concomitant colonic disease, including severe polyposis and dysplasia. The frequent detection of asymptomatic polyposis underscores the importance of colonoscopy screening in exposed patients, even in the absence of GI symptoms. Heightened interdisciplinary awareness and long-term surveillance are warranted to mitigate the vision- and life-threatening consequences of PPS toxicity.