Phenotypic Spectrum of Pentosan Polysulfate Sodium-Associated Maculopathy: A Multicenter Study

Hanif AM, Armenti ST, Taylor SC, Shah RA, Igelman AD, Jayasundera KT, et al. · JAMA Ophthalmology

Defined the phenotype: a distinctive retinal-pigment-epithelium maculopathy, bilateral and centred on the fovea in every affected eye, with blurred vision and subjectively prolonged dark adaptation the commonest symptoms at 17 patients each and metamorphopsia in 4. Visual acuity was largely preserved — 60 of 70 eyes (86%) at 20/40 or better, 2 eyes (3%) at 20/200 or worse — with the worst acuity in the 6 eyes whose atrophy involved the foveal centre. Within this series cumulative exposure did not track severity: mean cumulative dose was 1.81, 1.74 and 1.74 kg across the three severity grades (P=.85), and dose per unit body mass explained neither grade (r2=0.016) nor acuity (r2=0.014).

Population

35 patients (70 eyes) with the characteristic maculopathy after long-term oral PPS

Intervention

Chronic oral PPS (Elmiron): median 15 years of use, median cumulative exposure 1.61 kilograms (range 0.44–4.31 kg)

Comparator

None

Limitations

Case series without controls; establishes the phenotype and the exposure range of affected patients, not incidence or causation. The 35 cases were drawn from 404 patients reporting active PPS use at the four centres, but many of the rest had no evaluation adequate to assess the macula, so no rate follows. The authors name three further limits: a case definition built from their own earlier series of 6 patients, a retrospective design and sample too small to settle the phenotypic spectrum or a dose-response, and cases identified mostly at tertiary referral centres. Exposure is not uniformly long: one patient had 3 years of it and became symptomatic several years after stopping. Funded by the VitreoRetinal Surgery Foundation, the Foundation Fighting Blindness, Research to Prevent Blindness and NIH core grants, with no manufacturer support; several authors declare industry consulting.