Pentosan polysulfate sodium and retinal safety: reconciling conflicting evidence and defining a pragmatic clinical pharmacology framework

INTRODUCTION: Pentosan polysulfate sodium (PPS) remains an oral treatment option for selected patients with bladder pain syndrome, but recognition of PPS-associated pigmentary maculopathy has created uncertainty about long-term prescribing. The central clinical problem is that reported retinal-risk estimates vary markedly between studies. AREAS COVERED: A narrative review of PubMed/MEDLINE, Embase, Scopus and Google Scholar was updated through 31 July 2026, with emphasis on clinical pharmacology, efficacy trials, case reports, ophthalmic screening cohorts, claims and population studies, pharmacovigilance, cumulative exposure, causality, regulatory guidance and screening recommendations. Study findings were compared according to population selection, exposure measurement, retinal ascertainment, follow-up and comparator design. EXPERT OPINION: PPS-associated maculopathy is a credible exposure-related safety signal, although its absolute risk and individual susceptibility remain uncertain. Divergent estimates largely reflect differences in population selection, cumulative exposure range and retinal ascertainment rather than contradictory evidence. Cumulative exposure should inform review but not act as a mandatory stopping rule. We propose shared PPS stewardship, combining patient education and longitudinal shared decision-making with prescriber ownership of cumulative-exposure tracking and ophthalmic surveillance. Formal monitoring pathways are needed to support safe, equitable access to PPS while preserving individualized continuation or cessation decisions.