RETINA Article Feature: Pentosan Polysulfate and Vision – Findings from an International Survey of Exposed Individuals

Pentosan Polysulfate and Vision: Findings from an International Survey of Exposed Individuals” by Uner et al. July 2021

Elizabeth Rossin M.D., Ph.D.
Instructor in Ophthalmology, Mass Eye and Ear
Boston, MA

Avni Finn, M.D., M.B.A.
Northern California Retina Vitreous Associates
Mountain View, CA

Pentosan polysulfate (PPS), an oral therapy for a chronic pain syndrome of the bladder called interstitial cystitis (IC), has been associated with the development of a characteristic bilateral degenerative maculopathy. Since the original report of PPS associated maculopathy by Pearce et al. in 2018, there have been several case reports and series describing similar findings of pigmented spots in the macula, subretinal deposits, and more pronounced atrophy in advanced disease. In the July 2021 issue of RETINA, Uner et al. published an international retrospective survey study out of Emory looking at the dose-dependent association of PPS use with patient-reported visual symptoms, retinal referrals and diagnoses. This study attempted to access a much broader population of patients with a wider range of exposure than prior reports.

Between November 28th 2018 and December 30th 2018, a 27-question survey was distributed via email to members of the international IC Network. PPS exposure was assessed by subjective reporting and the primary outcome measures were subjective visual function and self-reported referral to a retina doctor and diagnosis of macular disease. 912 members completed the survey (a 15.9% response rate). The standard daily dose of PPS is 300mg for treatment of IC, but patient doses in this study ranged from 100mg to 500mg daily. Respondents were broken up into no PPS exposure or one of 3 tertiles of lifetime exposure.

After adjusting for age, sex, race and smoking status, respondents in the highest exposure tertile were more likely to have had a referral to a retina specialist compared to the unexposed group (38.7% compared to 22.1%) with an adjusted OR of 1.99 (p=0.003) and were more likely to carry a macular diagnosis (such as AMD, drusen, pattern dystrophy, macular dystrophy; 32.3% compared to 15.2%) with an adjusted OR of 2.41 (p<0.001). Interestingly, among the 10 respondents with a daily dose of 500mg (the highest dose), 60% reported a diagnosis of AMD or pigmentary retinopathy. This is in contrast to only 16.7% of those on a daily dose of 100mg over at least 15 years reporting a maculopathy (an overall higher lifetime dose than the 500mg QD group), highlighting the possibility that the risk of high daily dose may be even greater than the risk of lifetime cumulative dose.

Though very few reported poor vision, respondents in the highest exposure group were more likely to report difficulty with small print (such as a newspaper) after adjusting for age, race, sex, smoking status and splenic disease (13.2% compared to 6.4%) with an OR of 2.29 (p=0.02).

This study represents the largest number of patients thus far in comparison to previous reports of PPS maculopathy. The findings are in line with prior studies which showed that cumulative PPS dose is a risk factor for maculopathy, and here they find that a lifetime dose of ≥ 1,031g is associated with retina referral, a self-reported diagnosis of maculopathy and difficulty reading small print in a statistically significant manner. Because this is a self-reported survey study subject to certain biases and confounders, follow-up studies with objective measures will be needed.

Representative multimodal imaging of pentosan polysulfate maculopathy demonstrating macular pigment clumping on photos photography, hyperautofluorescent spots on FAF and RPE pigment migration on OCT. (Courtesy: Avni Finn MD)