As a health publishing company dedicated to interstitial cystitis, it is our duty to share news which can impact you, the IC patient. Unfortunately, we must share some distressing news. If you have or are currently taking pentosan polysulfate PPS (brand name: Elmiron®) and are experiencing eye issues, researchers at the Emory Eye Center (Emory School of Medicine, Atlanta, GA) have now documented cases of retinal maculopathy (aka retinal injury) in SOME IC patients who have used pentosan for long periods of time. They urge patients who have used or are using pentosan to be screened by ophthalmologists if they are experiencing any unusual eye symptoms (difficulty reading, vision loss, difficulty seeing in lower lights) and to cease pentosan therapy if eye disease is present.
2018 – First Case Series & Report
In Spring 2018, Dr. Neiraj Jain and collages wrote a letter to the editor of the Journal of Urology that stated “We wish to alert readers to a concerning new observation of vision threatening retinal changes associated with long-term exposure to PPS. We recently reported our findings of retinal pigmentary changes in six patients undergoing long-term therapy with PPS….Each patient had received a standard dosage of PPS, ranging from 200 to 400 mgs daily, for a median duration of 15.5 years (range 12 to 20) … Examination findings of patients with this condition are suggestive of injury to the retina and the underlying retinal pigment epithelium. After extensive investigations, which included molecular testing for hereditary retinal disease, we found these cases to resemble no other retinal disease.”(1)
IC experts Robert Moldwin and Curtis Nickel responded with concern, stating “It is quite unlikely that urologists treating patients with IC/BPS ever would have made this association…. yet the implications are either frightening if our treatment is causing this condition or instructive if this condition is a previously unknown manifestation of IC/BPS.”(2) They noted that the Emory Eye Center had identified additional cases in their clinic as well as in the clinics of colleagues.
“Pigmentary Maculopathy Associated With Chronic Exposure to Pentosan Polysulfate Sodium” was published in the Journal of Ophthalmology in May 2018. A case series, it focused on six women with interstitial cystitis who presented to their clinic between May 2015 and October 2017 with pigmentary maculopathy.(3) A maculopathy is condition which affects the center of the retina, an area associated highly sensitive and accurate vision, such as Age-Related Macular Degeneration.(4) Most of these patients had difficulty reading and difficulty in darkness. Two patients experienced a generalized dimming of their vision as the first symptom. Two others had difficulty with near vision. One had paracentral scotomas (vision loss) in part of their eye while the other had metamorphopsia (distorted vision where straight lines become wavy).
All six patients underwent rigorous diagnostic imaging and DNA testing to determine if they had any genes associated with hereditary retinal loss. None had a family history of retinal disease nor the discovery of any pathogenic process. What they did have in common was the use of pentosan (aka Elmiron®) for long periods of time (a median of 186 months.) Five had been treated at a dose of 400mg daily (two of whom reduced their dosage to 200mg daily after 17 years). One patient was treated with a 300mg daily dose. No other medications were used by more than 2 patients in the study.
Examinations of their eyes showed clear changes “Nearly all eyes (10 eyes of 5 patients) showed subtle parafoveal pigmented deposits at the level of the retinal pigment epithelium (RPE).” All eyes “showed subtle viteliform deposits that increased in number and extended beyond the major arcade of vessels in cases judged to be more severe. Four eyes of 2 patients showed RPE atrophy that was noted to increase in area and encroach on the central fovea over time. “ Findings were “fairly symmetrical” between the eyes of each patient. Retinal imaging also found clear diseased regions and/or atrophy though the size varied among patients.
It’s important to note that youngest patient in the study was just 37 years old. Patient #4 diagnosed at the age of 23. She was taking 400mgs of Pentosan a day. She began showing visual symptoms (difficulty with near vision and difficulty reading) at the age of 30, just six years after she was diagnosed. She took Elmiron® for a total of 168 months. She had the most severe damage in the study with deep scotomas of both eyes.
The authors suggest that the retinal cells may be accumulating PPS or a toxic metabolite over time. They express concern that “the region of affected tissue may expand over time…” Remarkably, they point to the results of a very early Elmiron study of 2499 patients who received the drug for up to four years in which vision related adverse events were reported including: optic neuritis, amblyopia and retinal hemorrhage.
While they say that it is to soon to conclude a definite relationship between PPS and maculopathy, they note that it is a unique presentation that does not resemble any other hereditary or acquired maculopathy. Could vision problems be a previously unrecognized effect of IC? There is no research which has demonstrated any long term connection between IC and eye health. The authors, experts in the study of rare eye diseases, said that they cannot hypothesize a pathophysiological mechanism between the IC, the bladder and/or eye health. They also state that its unusual to speculate on a drugs toxicity 21 years after FDA approval and wonder if “perhaps chronic exposure is a requirement for development of maculopathy and we are now beginning to see patients who have met the exposure threshold to manifest a toxic maculopathy.”
They concluded with a plea for education and an urgent need for additional research. “Clinicians should be aware of this condition because it can be mistaken for other well-known macular disorders, such as pattern dystrophy and age related macular degeneration.” In their original letter to the editor they also say “We encourage drug cessation in affected patients. Furthermore, we currently recommend that any patient with suggestive visual symptoms undergo a comprehensive ophthalmic examination”
May 2019 – Expanded Study From Emory
At the American Urology Association Annual Meeting (Chicago, IL) in May 2019, the Emory team submitted a new study of ten interstitial cystitis patients who had taken pentosan and experienced macular disease.(5) Ranging in age from 38 to 68, the most commonly reported symptoms were difficulty reading (7/10) and difficulty adapting to dim lighting (7/10). Patients had a medium cumulative exposure to pentosan of 2062 grams over time (range 325 to 2883.5) with a median duration of 186 months (range 27 to 240 months). Eye examinations showed symmetric pigmentary changes in the retina. Retinal imaging with FAF and OCT technology demonstrated that the abnormalities were primary in the retinal pigment epithelium. They note that their clinic has seen 156 patients with IC/BPS who did not have any pentosan exposure and these patients showed no pigmentary maculopathy.
They conclude that structural changes of the retina are occurring and they are unclear if stopping the medication will alter the course of this retinal disease. They encourage affected patients to discontinue the use of medications and to undergo comprehensive ophthalmic examinations with OCT and FAF imaging.
October 2019 – First Clinical Population Based Study
Researchers at Kaiser Permanente (Oakland, CA) found 140 of their patients who had taken Elmiron for a minimum of 5 years, 91 of whom agreed to an eye examination. Twenty two (24%) of these patients showed eye damage and that the damage increased with the quantity of Elmiron taken.(6) The study only assessed patients who were currently using Elmiron. The principle investigator, Dr. Vora, shared by phone that they will also gather information from patients who had stopped the medication and will be expanding their studies.
November 2019 – First National Multicenter Study Released
Researchers at the Emory Eye Center (Atlanta, GA) share data from a national study of patients. Using data from a large US medical claims database from 2002 to 2016, a total of 3012 and 1604 PPS users were compared with 15,060 and 8,017 matched controls at 5 and 7 years, respectively. The primary outcome measures included (1) any new diagnosis of a hereditary or secondary pigmentary maculopathy (atypical maculopathy outcome), and (2) any new diagnosis of dry age-related macular degeneration (AMD). At 5 years, multivariate analysis showed no significant association (p>0.13) but at 7 years, pentosan users had significantly increased odds of having the atypical maculopathy+AMD outcome (OR=1.41, 95% CI 1.09 to 1.83, p=0.009).(7)
November 2019 – First Case Study Suggesting Progression of Eye Disease After Pentosan Is Halted
Dr. Rachel Huckfeldt MD PhD, of the Harvest Medical School Dept. Ophthalmology, published a case study of an IC patient who had used a low dosage of Elmiron (200mg per day) for 18 years who first presented to their clinic at the age of 62 with blurry vision in her left eye and difficulty seeing at night. This had been occurring for a year. Eye studies noted pigmentary changes in the retina that, at that time, left the physicians wondering if the patient had been exposed to a retinotoxic agent. Six years later, the patient returned with worsening vision in both eyes. Examination found significantly more retinal atrophy and damage. The patient returned another two years later at the age of 69 with yet more extensive eye damage noted. Diagnostic testing was negative for any disease causing genes and no other causes could be determined.
After the initial report of eye disease in pentosan was released in 2018, this patients case was found to be consistent with pentosan associated maculopathy. The patient confirmed that she had stopped using Elmiron at the age of 63, prior to her second and third visits to the Harvard clinic. The authors raise a serious concern of progression over time – “The present case adds a new layer of concern by demonstrating progressive maculopathy continuing for up to 6 years after the cessation of PPS.” They compare their findings with another medication, hydroxychloroquine (Plaquenil), which has been determined to cause serious eye damage that can progress after that medication is stopped. “This case emphasizes the need for a screening regiment that balances the demands of patients and physicians with the importance of prompt identification of early toxicity.” (8)
- Re: FDA BRUDAC 2018 Criteria for Interstitial Cystitis/Bladder Pain Syndrome Clinical Trials: Future Direction for Research: J. C. Nickel and R. Moldwin J Urol 2018; 200: 39–42. William A. Pearce, Adam M. Hanif, Nieraj Jain The Journal of Urology. Published online: August 3, 2018 (Just two pages)
- Reply by Authors. The Journal of Urology. Published online: August 3, 2018 (Just two pages)
- Pigmentary Maculopathy Associated with Chronic Exposure to Pentosan Polysulfate Sodium. Pearce WA, Chen R, Jain N. Ophthalmology. 2018 May 22.
- Maculopathy – Wikipedia – Accessed September 1, 2018
- Foote, et al. Chronic Exposure to Pentosan Polysulfate Sodium is Associated with Retinal Pigmentary Changes and Vision Loss. AUA 2019 Abstract MP47-03.
- More Evidence Linking Common Bladder Medication to a Vision-threatening Eye Condition. American Academy of Ophthalmology Press Release. October 11, 2019. Accessed 10/16/19 – https://www.mdlinx.com/urology/top-medical-news/article/2019/10/14/7582080/ZZ4409FC7974EA48ACAABAE02B898A5B4
- Jain N, et al. Association of macular disease with long-term use of pentosan polysulfate sodium: findings from a US cohort. Br J Ophthalmol. 2019 Nov 6.
- Huckfeldt R, et al. Progressive Maculopathy After Discontinuation of Pentosan Polysulfate Sodium. Opthalmic Surgery, Lasers & Imaging Retina. 2019;50(10):656-659
What does this mean for you
- Don’t Panic! Remember that information is power! Ask your doctor for copies of the articles above or visit a local medical library to find them. I’ve summarized them as best as I can but that’s no substitute for actually reading the articles. (They are copyright protected thus I’m not allowed to copy them.)
- Seek An Eye Examination – If you have taken Elmiron® and have also developed some eye issues, out of an abundance of caution I believe that you should seek a full eye examination.
- Educate your Urologist & Consult With Them – I encourage you to print this article out and/or reference the articles above as you talk with your urologist. Ask them to review the two very brief articles in the Journal of Urology as well as the larger article in Ophthalmology. We must spread the word!
- Alternatives To Elmiron – The Emory Eye Center researchers encourage the cessation of pentosan if eye disease is noted. Other bladder coating therapies are available, such as Heparin/Lidocaine instillations as well as OTC supplements CystoProtek, Cysto Renew and/or Desert Harvest Aloe. Please discuss the pros and cons with your urologist.
An Urgent Plea – Help Us Develop More Data
I’ve created a survey to help assess if the other patients might also be struggling with eye issues and/or the role that pentosan may or may not be playing in those patients.
If you have interstitial cystitis, PLEASE TAKE THIS SURVEY NOW – even if you have never used Elmiron or don’t have eye issues. This is important foundational data that could help justify a more intensive study.