Study Confirms Links Between Use of Pentosan Polysulfate Sodium and Retinal Damage
Key findings
- This systematic review identified 14 articles reporting on retinopathy related to interstitial cystitis and the use of pentosan polysulfate sodium (PPS): four case reports, four case series and six cross-sectional studies
- Most studies suggested an association between long-term PPS exposure and development of maculopathy
- The prevalence of maculopathy in PPS users varied widely but seemed to be related to the cumulative dose: most affected patients had cumulative exposure over 1,000 g
- The most common symptoms were difficulty seeing in dim or night light, difficulty with reading and metamorphopsia (distorted vision in which a set of straight lines appears wavy)
- Urologists and other clinicians should carefully weigh the risks and benefits of prescribing PPS, especially because its therapeutic benefit has been brought into question and maculopathy can worsen even after PPS is discontinued
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Since 1996, pentosan polysulfate sodium (PPS) has been the only oral medication approved by the Food and Drug Administration for treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). In a 2018 study, researchers reported on six patients who developed a unique pigmentary maculopathy after long-term PPS exposure (median 186 months). (Published in Ophthalmology) the patients experienced problems with reading and dark adaptation.
Since then, several other groups have investigated this potential risk. One large study had contrary results, but as of June 2020, a warning about retinal pigmentary changes appears in the PPS package insert.
Urologist Elise J.B. De, MD, of the Department of Urology at Massachusetts General Hospital, and a colleague recently conducted a systematic review of the data on this issue. In Urology, they conclude that chronic PPS use does increase the risk of retinopathy and patients should be warned of this possibility.
Study Methods
On June 6, 2020, the researchers independently searched PubMed, Ovid, MEDLINE, EBSCO and Google Scholar (the latter to find non-standard publications because of the recency of the diagnosis). They included any paper reporting on retinopathy related to PPS use or IC itself, without language exclusions.
Case Reports
Four case reports described patients with chronic PPS exposure (average time, 201 months; average cumulative dose, 1,461 g) who had retinal pigment epithelium (RPE) abnormalities. Three of them complained of blurry vision and trouble adapting to low-light conditions; the fourth was asymptomatic. One patient continued to develop retinal changes seven years after discontinuing PPS.
Case Series
Including the aforementioned Ophthalmology study, four case series reported on 68 PPS users who developed maculopathy. All had used PPS for at least three years (average time, 177 months; average cumulative dose, 1,818 g). Except in one series, difficulty with dark adaptation was the most common symptom (59% of patients), followed by reading difficulty (55%) and metamorphopsia (10%, distorted vision in which a set of straight lines appears wavy). Nearly all patients had bilateral pigmentary changes at the level of the RPE.
Cross-Sectional Studies
Macular disease was also identified in six cross-sectional studies, of which two made use of large U.S. medical claim databases:
- The first involved 223,325 patients with IC who were retrospectively followed in the database for five years. 23% of those subjects filled a PPS prescription, with an average exposure time of 41 months. The percentage who were diagnosed with maculopathy (2.37%) was statistically similar to the percentage among patients who did not fill a prescription (2.77%). (Published in Ophthalmology)
- The other matched a PPS-exposed group to an unexposed group by age, sex, race and insurance start date. At the seven-year follow-up, 5.4% of 1,604 exposed subjects had atypical maculopathy, drusen or age-related macular degeneration compared with 4% of 8,017 unexposed subjects (OR, 1.41, 95% CI, 1.09–1.83, P = 0.009). (Published in the British Journal of Ophthalmology)
The other four cross-sectional studies also supported an association between long-term PPS use and the development of maculopathy.
Recommendations
Case reports and retrospective studies are prone to confounders. Still, urologists and other clinicians should carefully weigh the risks and benefits of prescribing PPS, especially because:
- Its therapeutic benefit has been brought into question—One double-blind study found no significantly greater efficacy of PPS versus placebo for treating IC (Published in The Journal of Urology)
- Maculopathy can worsen even after PPS is discontinued, as noted above and in a case series after this systematic review was conducted (Published in JAMA Ophthalmology)
Clinicians should consult the PPS package insert about the need for a detailed ophthalmological history before starting PPS and the timing of referrals for ophthalmic examinations. Patients should be informed of the risk of vision damage as part of shared decision-making about PPS.
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