Devastating new research has emerged from the eye research team at Emory University (Atlanta GA), who were the first to identify retinal disease (pigmentary maculopathy) in patients using Elmiron/pentosan polysulfate.(1) They sought to determine if eye and retinal health improved or worsened over time AFTER stopping the medication.(2)  Dr. Neiraj Jain, co-author of the study, said “We have a learned a lot from this four-year prospective study, and are indebted to the participants for their involvement.  Unfortunately, the results aren’t what we had all hoped for. This study suggests that individuals with pentosan polysulfate maculopathy do not improve after stopping the medication. In many cases, the disease continues to worsen.”  This is critical information for patients who are considering starting this medication and for those who might be in litigation and considering settlement offers.

What is Elmiron®/Pentosan Polysulfate?

Pentosan polysulfate (brand name: Elmiron®) is an oral medication suggested for the treatment of IC/BPS. First approved in the USA in 1996, it acts as a protective coating for the bladder wall. Available in both oral form and bladder instillations, it has been used by tens of thousands of patients in our country.  In 2017, it was approved by the European Union as their only treatment for IC/BPS where it is available both under the brand name and also as a generic medication. It has also been available in Canada, Australia and Asia. Given its widespread use, thousands of patients may be living with this maculopathy with many more at risk.(3)

What Are the Symptoms of PPS Pigmentary Maculopathy?

Patients with PPS toxicity may have difficult reading, or difficulty adapting to darkness. As the disease progresses, atrophy can occur resulting in more severe visual symptoms and, for some, legal blindness.

Current Study Methods & Results

Twelve patients (23 eyes) with a diagnosis of pigmentary maculopathy (average age of 58) were studied over four years.  The average length of time they had previously used pentosan was 14 years (8 to 17.6 years). None of the participants had prior exposure to known retinal toxic agents though one had used hydroxychloroquine for a year. Participant ten was the only participant with a history of smoking.

The researchers tracked visual function and retinal health using a variety of retinal testing, including: BCVA, LLVA, MNREAD, contrast sensitivity, microperimetry  and dark adaptometry. Results showed that both functional and structural outcomes continued to deteriorate over time, describing PPS toxicity as an alarming and “relentlessly progressive degenerative maculopathy.”

Previous Research & Case Studies Also Found Progression

Several studies have previously suggested that retinal disease/toxicity could progress after stopping the medication.In August of 2020, Emory researchers found that eleven patients (17 eyes) showed worsening changes in the retina in the first six month after stopping the medication.(4) They also noted that no eyes showed any improvement after stopping the medication.

In 2023, the Stein Eye Institute (UCLA) released a study of 26 eyes that were followed for 12 to 30 months. All eyes “exhibited remarkable progression” and significant expansion of disease in all eyes studied, with new areas of atrophy developing in four eyes after the medication was stopped. (5)

Dr. Rachel Huckfeldt was the first to share a case of a woman who presented with severe retinal disease in one eye for which she could find no obvious cause, concluding that the patient was experiencing a toxic maculopathy from exposure to an unknown chemical. Six years later, the patient returned with the same condition in the other eye. When the PPS pigmentary maculopathy research emerged, Dr. Huckfeldt found that her patient had been on PPS for an extended period of time. (6) What makes this notable is the fact that the second eye developed retinal damage years after the medication had been stopped.

In January 2024, a case report was published of a woman with 13 years of retinal imaging available. This is the longest follow-up imaging available showing progressive damage over time. (7)

In November 2024, a remarkable case report was published of a woman who had been using fairly low levels of PPS over ten years but had also taken hydroxychloroquine for five years, possibly due to a previous diagnosis of lupus. It, too, has a well known record of retinal damage. The combination of using both of these medications resulted in severe maculopathy and cystoid macular edema (CME).(8)

One encouraging case study from Duke University reported on a 66 year old woman with progressive pigmentary maculopathy from long-term PPS use but her condition appeared to improve after stopping the medication. (9)

Conclusion

While we still do not understand how and why the damage occurs, this study refutes those who suggest that PPS toxicity is minor. In fact, it suggests that the damage could be progressive over time and increases the likelihood that severe damage could occur in both eyes, including legal blindness.

Dr. Jain encouraged more communication and discussion between patients and providers about the risks vs. benefits of pentosan. He said “Moving forward, we have to strive to prevent this from happening in the first place, and that starts with judicious use of this medication.”

I encourage patients to bring this article to your local urologists to inform them of this new research. The AUA Guidelines for IC/BPS charge doctors with educating patients about the risks vs. benefits of using this medication. Given this new data, that discussion becomes all the more important.

This is particularly important in patients who live in the European Union for which pentosan was approved in 2017 as the only treatment for IC/BPS(10). Remarkably and inexplicably, their on-line information on Elmiron® does not mention any risk for retinal disease despite many studies. We can only wonder “why?”  Patients should be encouraged to have retinal examinations and, most importantly, to cease using the medication if eye symptoms begin to occur. The goal, of course, is to protect their eyesight. Similarly, we also hope that drug information sheets, particularly for the generic pentosan, will be updated to show the alarming risk of progressive macular disease after stopping the medication.

The ICN is proud of the role that we have played in educating patients about this alarming adverse event. If you find reporting like this to be helpful or if you have received a settlement, please consider making a donation. We still have about $15,000 of legal fees that we had to incur while responding to the federal subpoena for our research. Attorneys are very expensive!!! Your donation would be very much appreciated.

References:

  1. Pearce WA, et al. Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium. Ophthalmology. 2018 Nov;125(11):1793-1802.
  2. Hall BP, et al. Pentosan Polysulfate Maculopathy: Final Outcomes from a 4-Year Prospective Study of Disease Progression after Drug Cessation. Am J Ophthalmol. 2024 Dec 10:S0002-9394(24)00562-2.
  3. Kim J, et al. Nationwide Usage of Pentosan Polysulfate and Practice Patterns of Pentosan Polysulfate Maculopathy Screening in South Korea. Ophthalmol Retina. 2024 Mar;8(3):246-253
  4. Shah R, et al. Disease Course in Patients With Pentosan Polysulfate Sodium-Associated Maculopathy After Drug Cessation. JAMA Ophthalmol. 2020 Aug 1;138(8):894-900.
  5. Somisetty S, et al. Progression of Pentosan Polysulfate Sodium Maculopathy in a Prospective Cohort. Am J Ophthalmol. 2023 Nov;255:57-67. doi: 10.1016/j.ajo.2023.05.021. Epub 2023 Jun 15. PMID: 37327961.
  6. Huckfeldt RM, et al. Progressive Maculopathy After Discontinuation of Pentosan Polysulfate Sodium. Ophthalmic Surg Lasers Imaging Retina. 2019 Oct 1;50(10):656-659. doi: 10.3928/23258160-20191009-10. PMID: 31671200.
  7. Pinto AM, et al. Pentosan Polysulfate Maculopathy With 13 Years of Follow-up Imaging. J Vitreoretin Dis. 2024 Jan 31;8(3):325-333
  8. Flester E, et al. Advanced pentosan polysulfate sodium maculopathy with low cumulative exposure and hydroxychloroquine use. Am J Ophthalmol Case Rep. 2024 Nov 22;36:102224. doi: 10.1016/j.ajoc.2024.102224. PMID: 39691632; PMCID: PMC11650262.
  9. Gupta PR, Grewal DS. VISUAL AND ANATOMICAL CHANGES AFTER DRUG CESSATION IN PENTOSAN POLYSULFATE SODIUM-ASSOCIATED MACULOPATHY. Retin Cases Brief Rep. 2023 Sep 1;17(5):507-510. doi: 10.1097/ICB.0000000000001242. PMID: 37643033.
  10. European Medicines Agency – Science Medicines Health – Elmiron