Two separate studies of patients who take pentosan polysulfate sodium have confirmed the drug’s association with retinal toxicity at high cumulative dosages and demonstrated that multimodal imaging techniques can identify even mild cases of the condition.1,2
Indeed, multimodal imaging is essential both to detect damage from the drug and to distinguish the condition from age-related macular degeneration (AMD) and other maculopathies, the studies concluded.
Systemic treatment, macular toxicity. Since 1996, pentosan polysulfate (Elmiron) has been the only FDA-approved oral drug for treating interstitial cystitis. However, evidence of macular toxicity in patients who take the drug emerged in 2018. That study found that, typically, these patients had taken 300 mg daily for a decade or more.3
In one of the current studies, multi-modal imaging of 105 suspected cases, which had been gathered by a Macula Society study group, confirmed pentosan polysulfate maculopathy in 74 patients. These patients had taken the drug for a median of 14 years (interquartile range [IQR], 10.2-18.9), and the median IQR dosage was 1,500 g (range, 900-2,400 g).2
A separate, prospective prevalence study examined 100 pentosan users with multimodal retinal imaging and detected drug-related maculopathy in 16% of cases.1 “This study is the first prospective analysis showing that this drug is associated with retinal toxicity, that the prevalence is significant, and that the toxicity is dose-related,” said coauthor David Sarraf, MD, at the University of California, Los Angeles. Dr. Sarraf added, “While there was a 16% prevalence of pentosan polysulfate maculopathy in general, if you look at the patients who had a cumulative dosage over 1,000 g, the prevalence rose to 40%, and for dosages over 1,500 g, it was 55%.”
Imaging recommendations. In both studies, the researchers found that many eyes with pentosan maculopathy initially were misdiagnosed as having AMD. They recommended the following to detect signs in the retina and choroid characteristic of drug-induced damage:
Fundus photography, to identify macular hyperpigmented spots, yellow-orange deposits, and/or patchy retinal pigment epithelium (RPE) atrophy.
Fundus autofluorescence imaging, to identify a speckled pattern of hypo- and hyperautofluorescence centered around the macula and, in some cases, the disc as well.
OCT, to identify focal thickening or elevation of the RPE.
Near-infrared reflectance, to identify hyperreflective lesions of the RPE corresponding to focal thickening or elevation of the RPE with OCT. (This method may be the best way to detect some early cases, the authors said.)
Need to screen patients. Because of the dose correlation and because a few affected patients in the studies were asymptomatic, ophthalmologists should screen patients taking pentosan polysulfate at baseline and then annually after the cumulative dosage reaches 500 g, Dr. Sarraf said.
Nieraj Jain, MD, coauthor of the Macula Society study, said his study group suggests that ophthalmologists may consider screening annually from the time patients start taking the drug.
“Unfortunately, the macular damage doesn’t appear to reverse once patients are off the drug, so early detection is important,” said Dr. Jain, at Emory University in Atlanta. “And in most cases, it will be prudent for the affected patients to come off the drug.”
Dr. Jain, who coauthored the original 2018 paper about this condition, said reports in journals appear to have informed many ophthalmologists about pentosan polysulfate maculopathy. Support also has come from advocacy groups that track new research about interstitial cystitis and discuss these issues online, he said. “The fascinating thing is that social media has helped us get the word out,” Dr. Jain said. “Patients on this drug have been taking our paper to their ophthalmologists and asking, ‘Do I have this?’”
1 Wang D et al. Am J Ophthalmol. 2021;227:125-138.
2 Jain N et al., for the Macula Society Pentosan Polysulfate Maculopathy Study Group. Ophthalmol Retina. Published online July 20, 2021.
3 Pearce WA et al. Ophthalmology. 2018;125(11):1793-1802.
Relevant financial disclosures—Dr. Jain: None; Dr. Sarraf: Janssen: C.
For full disclosures and the disclosure key, see below.
Full Financial Disclosures
Dr. Chen None.
Dr. Jain Foundation Fighting Blindness: S.
Dr. Lois None.
Dr. Sarraf Amgen: C; Bayer: C; Genentech: C,S; Heidelberg: S; Janssen: C; Novartis: L; Optovue: C,S; Regeneron: S; Topcon: S.
Dr. Shousha Heru: O; NEI: S; Resolve Ophthalmics: O,P.
||Consultant fee, paid advisory boards, or fees for attending a meeting.
||Employed by a commercial company.
||Lecture fees or honoraria, travel fees or reimbursements when speaking at the invitation of a commercial company.
||Equity ownership/stock options in publicly or privately traded firms, excluding mutual funds.
||Patents and/or royalties for intellectual property.
||Grant support or other financial support to the investigator from all sources, including research support from government agencies (e.g., NIH), foundations, device manufacturers, and/or pharmaceutical companies.
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