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Age-related macular degeneration with neovascularization of torn and rolled-up retinal pigmented ... [+] epithelium. (Photo By BSIP/UIG Via Getty Images)

Evidence continues to mount that a drug commonly prescribed for decades to treat a painful bladder condition known as interstitial cystitis (IC) is linked to retinal damage and toxicity. The retina is the light-sensing tissue at the back of the eye that allows us to see our world.

A 2018 study by Nieraj Jain, M.D, Assistant Professor of Ophthalmology, Emory University School of Medicine, Emory Eye Center, reported reading difficulty and visual changesespecially under dark conditionsamong six patients who had been taking the drug, Elmiron (pentosan polysulfate sodium, PPS) for an average of 15 years (range of 12-20 years).

Jain found that this group of six patients (median age 60; age range 37-62) all had atypical changes in their macula, the central part of the retina that allows us to have clear central vision. The patients described difficulty reading in dim light and diminished central visual acuity. The patients underwent genetic testing to determine if there was any basis for hereditary retinal loss, with none demonstrating any such evidence of a link. Other than Elmiron, there was no clear etiology based on other findings in their medical history that explained the concerning retinal changes found in all six patients. This led the researchers to issue a warning in 2018 that long-term use of Elmiron could potentially lead to retinal damage.

An additional 10 patientsage range of 38-68 years of agewith similar retinal changes were also reported by the same researchers in May of 2019, and presented at the 2019 annual meeting of the American Urological Association. The authors concluded that structural changes in the retina were certainly present, stating that it was unclear if stopping the medication would reverse the noted changes.

This ongoing concern led researchers from Kaiser Permanente in Northern California to study this phenomenon further in their own patients taking this medication.

They found that about 25% of their patients with significant exposure to Elmiron showed clear evidence of retinal damage. The concern is that toxicity from this medication could also appear to mimic other well-known retinal conditions, such as age-related macular degeneration (AMD) or an uncommon retinal condition known as pattern dystrophy.

The research was presented last week at AAO 2019, the 123nd Annual Meeting of the American Academy of Ophthalmology.

Interstitial cystitis (IC) is a cause of unrelenting pain in the bladder and pelvic regions of the lower abdomen. Its estimated that at least 1 million people, mostly women, in the U.S. have thispainful condition. While other pharmacologic (NSAIDS, antihistamines, bladder installation therapy) and behavioral approaches are available, Elmiron is the only FDA-approved medication to treat this painful and disabling condition. It effectively works by forming a protective coating on the inner lining of the bladder that reduces irritation by substances present in the urine. Since its a first-line drug used for many decades, its believed that at least several hundred of thousand people have likely been exposed to the drug.

Robin A. Vora, M.D., Consultant in Medical Retina, Chair of Ophthalmology, Kaiser Permanente, Northern California and colleagues (Amar Patel, M.D., and Ronald Melles, M.D.) described a woman on long-term Elmiron who was misdiagnosed as having a retinal dystrophy, a genetic cause of progressive vision loss that may lead to permanent blindness. As a result of their concern that more patients that could be affected, they decided to evaluate all 4.3 million Kaiser patients.

Searching the database, they identified 140 patients who had each taken an average of 5,000 pills over a period of 15 years. Ninety-one patients of the 140 were evaluated. The investigators captured retinal images and rated them as normal, possible abnormality, or definite abnormality. The toxicity involved specialized cells known as retinal pigmented epithelium (RPE) that help nourish precious vision-producing cells in the retina known as the macula. Twenty-two of the 91 patients showed clear signs of drug toxicity. The rate of toxicity increased with the amount of drug taken, from 11% of those taking 500 to 1,000 grams to 42% of those taking 1,500 grams or more.

Its unfortunate, said Vora. You have a patient with a chronic condition like interstitial cystitis, for which there is no cure and no effective treatment. They get put on these medications because its thought to have few side effects and few risks, and no one thinks about it again year after year, the number of pills theyre taking goes up and up.

Since there is no comprehensive data yet available to guide treatment, Vora recommends patients who are asymptomatic and show no retinal signs of toxicity be screened for retinal damage at least annually. Patients who are showing signs of toxicity need to have a conversation with their health care provider whether to stop taking the medication.

Urologists and gynecologists are the primary medical providers for patients with IC. Elizabeth Kavaler, M.D., a urologist with Lenox Hill Hospital in New York City, suggested active retinal surveillance of patients would be prudent in managing patients with IC.

The impact of IC on the life of people who suffer with it cannot be minimized, she said. For women who have had good success with Elmiron, and are able to live their lives without chronic, unremitting pain, perhaps yearly or biyearly retinal exams should be done.

The mechanism behind the toxicity is unclear, but may involve the production of a toxic metabolite of Elmiron. Jains team has suggested that a component of Elmiron, a glycosaminoglycan (GAG) with a highly negative charge, may also play a potential role in disrupting the interphotoreceptor matrix in the macula. Other research by Singh and colleagues from Cleveland Clinic has suggested that Elmiron acts as an antagonist of signaling pathways related to fibroblast growth factor (FGF), a protein integral to retinal maintenance and function. There is no research that has yet elucidated the exact mechanism.

Jain has been in contact with the FDA, which is aware of his and other research linking Elmiron to retinal damage. To date, the FDA has not taken any action or issued any alerts regarding the toxicity of the medication.

The researchers are expressing growing concern that the presentation of these patients is unique and does not resemble any other identified acquired or hereditary maculopathy. At this time, an association or link with PPS exposure and maculopathy exists, but no definitive cause and effect relationship. The broader question is whether visual problems may be an unrecognized effect of IC; there have been no studies to link these two conditions as of yet.

If the changes are picked up early, its unclear whether retinal damage is reversible by discontinuing the medication. Long term monitoring will be required to make this clinical determination. For those with no clear evidence of damage who are currently taking the medication, close monitoring is critical, according to Vora and Jain. However, in later stages, toxicity can resemble late-stage dry atrophic age-related macular degeneration (AMD) and result in permanent vision loss.

Here is the original post:
New Study Adds Concern That Medication To Treat Painful Bladder Condition Linked To Vision-Threatening Eye Condition - Forbes

This entry was posted on October 18, 2019 at 6:45 pm and is filed under Opthalmology. You can follow any responses to this entry through the RSS 2.0 feed. Both comments and pings are currently closed. |