What is Pentosan Polysulfate Maculopathy?
Pentosan polysulfate (PPS) is a medicine with blood-thinning properties, originally used in the 1950s for breaking down clots in the blood vessels. Its primary usage now is for treating interstitial cystitis (IC), a condition causing bladder pain, and it’s the only medicine approved for this by the U.S. Food and Drug Administration.
IC causes bladder pain that gets worse when the bladder fills and improves when it’s emptied. It also results in small bleeding spots in the bladder and makes the bladder less flexible. This condition is widespread, with over 1 million Americans affected, mainly women. PPS works in the bladder by binding to the bladder lining and replacing damaged substances, offering protection to the bladder. Sometimes, doctors may also use PPS to treat irritable bowel syndrome, pelvic pain syndrome, and cracks in the inner bladder wall. The usual dosage of PPS is 100 mg, taken three times a day.
However, it’s important to note that twenty-two years after PPS was approved for treating IC, studies found that prolonged use of this drug could lead to a condition called maculopathy, which causes changes in the central part of the retina and can affect vision. This association has been confirmed and extensively studied by researchers.
What Causes Pentosan Polysulfate Maculopathy?
Studies have suggested that the length of time someone uses PPS (a type of drug) and the total amount taken over that period are key factors in the development of PPSM, a side effect of the drug. Even though there was a case of PPSM in a patient with a relatively small exposure to PPS (325g over 2.25 years), most people develop the condition many years later. A review in 2022 summarized several studies and found, on average, people had been exposed to PPS for around 15 years and had taken in total about 1824g of the drug. This data matches a later review’s findings. It was revealed that 16% of all patients developed this toxicity, but the percentage went up when the dosage increased – 40% of patients with cumulative dosages greater than 1000g and 55% of patients with dosages more significant than 1500g developed PPSM.
It’s crucial to note that these statistics are from the time when patients were diagnosed with PPSM. They might have started developing the disease earlier. The severity of the disorder was associated with how long people used PPS and how much in total they took. Still, it was not related to the daily dosage. This was proven by another large study of insurance records that showed people using PPS for more than three years were more likely to develop PPSM than those who used it less (approx. 9.5 times vs. 2.2 times higher).
Although daily dosage and dosage by body weight are often discussed as possible factors affecting toxicity, these studies showed mixed results. One study found patients affected by PPSM, on average, were taking larger daily doses (445g vs. 302g). In another study, patients taking 100mg of PPS for 15 years were less likely to report maculopathy (damage to the central part of the retina) compared to patients on 500mg for around 5 years. Lastly, the body mass index (BMI) of affected patients was usually within the normal range, albeit slightly on the higher end.
In simple terms, this means that those who use PPS for longer periods and in higher total quantities are more likely to develop PPSM; however, more research is needed to understand the full impact of diet, body weight, and dosage on this toxicity.
Risk Factors and Frequency for Pentosan Polysulfate Maculopathy
People who suffer from PPSM (Pentosan Polysulfate Sodium Maculopathy) are mostly white (93%) and female (90%), with an average age of around 62.2 years. It’s challenging to determine the exact number of PPSM cases among people who use PPS because the studies vary in design, duration of drug use, total drug dose, and sometimes patients are mistakenly identified as having other eye diseases. Also, some early signs and symptoms of the disease can be overlooked if proper screening methods aren’t in place.
Even with these challenges, studies have roughly estimated that between 0.7% and 2.4% of people who use PPS may develop PPSM. These estimates come from large-scale studies analyzing insurance claim databases. However, these studies might not give a completely accurate picture because people would need to have been diagnosed with another eye disease, and the follow-up time in these databases sometimes limits the ability to find a connection between PPS and an eye disorder.
In more specific studies that regularly check for PPSM in known PPS users, the estimated prevalence levels between 16.5% and 23.1%. These numbers, however, may be a bit high due to possible selection bias in the studies.
Signs and Symptoms of Pentosan Polysulfate Maculopathy
People who take pentosan polysulfate sodium (PPS) for an extended period may develop a condition known as PPSM. Usually, symptoms of PPSM are not immediately visible, but over time, the patient may experience problems with their vision. They might notice their sight becoming increasingly blurred, difficulty seeing in low light, changes in their perception of shapes, blind spots in their central vision, and difficulties adapting to darkness. While these symptoms often progress slowly, they can develop quickly. There’s even been a case of advanced PPSM occurring within two years.
In terms of vision clarity, most patients face only mild impairment, with vision usually remaining close to the standard level (20/25). However, this doesn’t capture the full extent of the visual disability caused by PPSM. According to patient reports on the National Eye Institute Visual Functioning Questionnaire, people with moderate to advanced PPSM often struggle more with visual-based tasks than those dealing with age-related macular degeneration.
The challenges they face usually concern driving, handling dim or extreme lighting conditions. Although darkness might take longer to adjust to for many patients, tests using rod intercept times – which measures how quickly eyes adapt to the dark – have shown varied results, making them an ineffective method for detecting PPSM. Issues with contrast sensitivity, or our ability to distinguish between light and dark, do not typically become problematic until the later stages of the condition.
Testing for Pentosan Polysulfate Maculopathy
An eye check-up typically includes tests on the front part of your eye (anterior segment) and the back of your eye (poster segment). For people of a certain age, the front part of the eye is often found to be normal. However, when looking at the back of the eye, doctors can sometimes spot subtle signs of problems.
They might spot small, packed areas of color change in both eyes, with surrounding yellow spots and thinned areas. These spots are usually found in the back of the eyes (posterior pole), but in about a third of cases, they can also be found in the outer parts of the retina.
Special techniques, like autofluorescence, can highlight these changes more clearly. This technique can show tiny spots of light and dark, usually in a specific area. This test is also able to show dark spots around the optic nerve (the nerve that transmits visual information to the brain) in all eyes examined.
A scan called optical coherence tomography (OCT) can provide an even more detailed picture, matching up areas of color change and light spots with changes in the eye’s pigment cells. Over time, these cells change and become bumpy and merge together, casting shadows onto the layer beneath them. This test also helps ensure that these changes aren’t caused by a common age-related condition known as ‘drusen’.
Other tests like near-infrared reflectance (NIR), which is often done at the same time as an OCT, can be really good for picking up these changes, especially in the mild cases of eye disease. Sometimes, these tests are even better than autofluorescence in showing these changes due to the longer wavelength of light used in NIR.
There’s another scan called OCT Angiography (OCT-A) that can show doctors different clues to help figure out what is causing the disease. This test can identify abnormal shapes of blood vessels, decreased blood flow, and areas of eye tissue damage.
Tests on your eyes’ electrical activity, such as electroretinography (ERG), can show a range of results from normal to slightly diminished responses. Another similar test called the electro-oculogram mainly shows normal responses, though it often takes longer for the eyes to adjust to the darkness.
Genetic testing can help rule out other eye conditions. However, at present, there have been no clear links found between this disease and specific genetic markings. However, there is a thought that some people might have a genetic predisposition to more severe eye disease based on some of these tests.
Based on these tests, doctors have proposed a set of criteria to define and understand the severity of this disease. The criteria involve looking for changes in the eye’s pigmentation, areas of light and dark under autofluorescence, changes in the thickness of the pigment cells, a dark halo around the optic nerve, and maximum spot size under autofluorescence.
The severity of the disease is generally classified into mild, moderate, and severe based on autofluorescence patterns, the extent of eye tissue changes and thinning, and whether the disease has reached the center of your vision.
A correlation has also been found between disease severity and the dosage of medication taken, although this cannot be confirmed due to the small sample size of the study.
Treatment Options for Pentosan Polysulfate Maculopathy
There isn’t a specific treatment available for PPSM, a condition related to the eye. As a result, it’s crucial to prevent it in the first place by avoiding certain medications or using them in the smallest effective doses when necessary. Some negative effects of PPSM on the eyesight can, however, be managed with common drugs that are already used for similar conditions.
For instance, cystoid macular edema, a condition that causes swelling in the eye, has been successfully treated with two types of drugs: carbonic anhydrase inhibitors and anti-vascular endothelial growth factor (anti-VEGF) drugs. Carbonic anhydrase inhibitors are used to decrease fluid production in the eye, while anti-VEGF drugs block a protein that promotes the growth of new blood vessels in the eye.
Moreover, a condition where abnormal blood vessels grow in the eyes has been managed with injections of anti-VEGF medications directly into the eyes. These drugs help reduce the growth of these blood vessels, helping to manage this condition.
What else can Pentosan Polysulfate Maculopathy be?
When diagnosing a condition known as PPSM, doctors need to differentiate it from other similar conditions. The main conditions that are compared and differentiated from PPSM are AMD (Age-related Macular Degeneration), Pattern Dystrophy, and Mitochondrial Dystrophy.
1. AMD:
- Both PPSM & AMD affect similar patient demographics and can lead to macular changes. They are differentiated by imaging techniques and identifying PPSM’s typical pattern. Key features of PPSM include dark spots with yellow-orange deposits at the level of Retinal Pigment Epithelium (RPE) and not below, coupled with varying degrees of fluorescence (brightness) spots, especially around the optic nerve (peripapillary autofluorescent halo). On the other hand, AMD is indicated by drusen (deposits under the RPE). In one study, no drusen were found in PPS-diagnosed eyes, but more RPE pigmentary lumps were found in AMD-diagnosed eyes of patients with previous PPS exposure.
2. Pattern Dystrophy:
- When distinguishing PPSM from Pattern Dystrophy, doctors pay special attention to three features in patients with borderline imaging. First, the peripapillary hypoautofluorescent halo is highly helpful, although less so if the disease hasn’t spread to the optic nerve. Second, the number of abnormalities in PPSM is significantly higher than in inherited macular diseases. Third, PPSM could involve the central spot of the eye (the central fovea) early on, but this isn’t always the case. Further understanding can be provided by inquiring about the family history or conducting genetic testing.
3. Mitochondrial Dystrophy:
- PPSM and mitochondrial retinopathies share some physical overlaps, like a mesh-like appearance of the back of the eye (reticulated-appearing fundus), peripapillary atrophy, and trouble seeing at night (nyctalopia). The distinction can lie in the fact that while PPSM may affect the central spot of the eye early on, mitochondrial diseases usually do not. Additionally, mitochondrial diseases often come with systemic manifestations that aren’t seen in PPSM, such as muscle weakness (for example, cardiomyopathy).
What to expect with Pentosan Polysulfate Maculopathy
PPSM is a condition that progressively damages a part of the eye called the macula. This can lead to areas of damage in another part of the eye called the RPE, which can reduce how sharp your vision is, potentially leading to legal blindness. Other effects can include difficulty seeing at night (nyctalopia), distorted vision (metamorphopsia), a blind spot in the center of your vision (a paracentral scotoma), and delayed adjustment to darkness.
Despite these severe effects, discontinuing certain behaviors may help slow down or reverse the progression of the disease.
Possible Complications When Diagnosed with Pentosan Polysulfate Maculopathy
Besides the reduced vision resulting from RPE atrophy, severe vision complications of PPSM may also include CME, deposits under the central part of the retina, and macular blood vessel growths.
Noteworthy Complications:
- Lessened visual acuity from RPE atrophy
- CME (a disease that destroys vision by causing swelling in a small area of the retina responsible for sharp, straight-ahead vision)
- Deposits under the central part of the retina (subfoveal vitelliform deposits)
- New blood vessels that form in the macula (a part of your retina) and disrupt your central vision (macular neovascular membranes).
Preventing Pentosan Polysulfate Maculopathy
There is a collective agreement among urologists (urinary tract specialists) and urogynecologists (women’s pelvic floor disorder experts) about the need to educate patients on PPSM, a health concern that both these specialists often treat. There are several suggested guidelines for screening this condition. The usual recommendation is to carry out an initial test when the treatment with PPS, a specific medication, begins. After that, additional testing is suggested every year. The doctors and patients should collectively decide on whether to discontinue the drugs when the total amount taken surpasses 1500 g.
At each check-up with the eye doctor (ophthalmologist), different imaging techniques, such as NIR (an eye imaging test), FAF (an eye health check), and OCT-A (an eye tissue scan), should be employed whenever feasible. This routine has already been efficiently incorporated into an electronic health record system in one healthcare institution. This can help immensely in keeping track of the patient’s condition and any changes that might have occurred over time.
