Abstract
PURPOSE: To describe an advanced case of pentosan polysulfate sodium (PPS)-associated retinopathy with extensive macular and peripheral retinal involvement following prolonged high-dose exposure. OBSERVATIONS: An 86-year-old male presented with bilateral hand motion visual acuity and a 26-year history of PPS use (400mg daily, ∼3769g cumulative dose) for treatment of interstitial cystitis. Fundus examination revealed widespread retinal degeneration characterized by confluent nummular patches of retinal atrophy in a radial distribution from the optic nerves. Ocular coherence tomography (OCT) demonstrated severe outer retinal disorganization, and fundus autofluorescence (FAF) showed extensive RPE loss and absence of the Robson Holder ring. Genetic testing excluded choroideremia and late-onset retinal dystrophy, identifying only variants of uncertain significance in candidate genes DNAJC17 and SPP2. The patient had a history of excessive coffee consumption, which may have exacerbated his interstitial cystitis and potentially contributed to retinal vascular compromise. CONCLUSIONS AND IMPORTANCE: This case supports the dose-dependent nature of PPS toxicity and demonstrates that high cumulative doses can lead to widespread retinal degeneration beyond the typical macular involvement. The potential severity of irreversible vision loss highlights the importance of periodic retinal evaluation using multimodal imaging to facilitate early recognition of PPS toxicity in patients on long-term PPS therapy and supports ongoing efforts to establish widely accepted, comprehensive screening guidelines and cumulative dose thresholds for patients on long-term PPS therapy, similar to protocols for other potentially toxic drug-related retinopathies.