More Evidence Linking Common Bladder Medication to a Vision-threatening Eye Condition

A drug widely prescribed for a bladder condition for decades, now appears to be toxic to the retina, the light sensing tissue at the back of the eye that allows us to see. After an initial report last year that Elmiron (pentosan polysulfate sodium) may be associated with retinal damage, three ophthalmologists conducted a review of patients at Kaiser Permanente in Northern California. They found that about one-quarter of patients with significant exposure to Elmiron showed definite signs of eye damage, and that this medication toxicity could masquerade as other known retinal conditions, such as age-related macular degeneration or pattern dystrophy. The research will be presented today at AAO 2019, the 123nd?Annual Meeting of the American Academy of Ophthalmology.

Interstitial cystitis causes chronic pain in the bladder and pelvis area. More than 1 million people in the United States, mostly women, are estimated to have the condition. Elmiron is the only FDA-approved pill to treat it. As a mainstay of treatment for decades, hundreds of thousands of people have likely been exposed to the drug.

Last year, Nieraj Jain, M.D., of Emory Eye Center in Atlanta, Ga., reported that six patients who had been taking Elmiron for about 15 years had developed unusual changes in their macula, the central part of the retina responsible for delivering clear, crisp, central vison. Because nothing in the patients’ medical history or diagnostic tests explained the subtle, but striking pattern of abnormalities, Dr. Jain and his colleagues raised a warning flag that long-term use of Elmiron may damage the retina.

Robin A. Vora, M.D , Amar P. Patel, M.D., and Ronald Melles M.D., ophthalmologists at Kaiser Permanente, heeded that warning and looked at their population of patients. They initially found one woman on long-term treatment who was misdiagnosed as having a retinal dystrophy. This worrisome case prompted them to examine Kaiser’s entire database of 4.3 million patients.

They found 140 patients who had taken an average of 5,000 pills each over the course of 15 years. Of those 140 patients, 91 agreed to come in for an exam. Drs. Vora, Patel, and Melles took detailed images of the back of their eyes and then divided the images into three categories: normal, possible abnormality, definite abnormality. Twenty-two of the 91 patients showed clear signs of drug toxicity. The rate of toxicity rose with the amount of drug consumed, from 11 percent of those taking 500 to 1,000 grams to 42 percent of those taking 1,500 grams or more.

“It’s unfortunate,” said Dr. 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 it’s thought to have few side effects and few risks, and no one thinks about it again. And year after year, the number of pills they’re taking goes up and up.”

Because it’s unclear how much medication is too much, Dr. Vora recommends patients who show no signs of toxicity be screened for retina damage at least once a year. For those who do show some signs of damage, he recommends they speak with their urologist or ob/gyn about discontinuing the medication.

Good news is that if identified early, the damage may be mitigated by stopping the medication. In the late-stage, toxicity can mimic late-stage dry atrophic age-related macular degeneration and result in permanent vision loss.

Source: EurekAlert!


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How the Eyes Might Be Windows to the Risk of Alzheimer’s Disease

Scott LaFee wrote . . . . . . . . .

Alzheimer’s disease (AD) begins to alter and damage the brain years — even decades — before symptoms appear, making early identification of AD risk paramount to slowing its progression.

In a new study published online in the September 9, 2019 issue of the Neurobiology of Aging, scientists at University of California San Diego School of Medicine say that, with further developments, measuring how quickly a person’s pupil dilates while they are taking cognitive tests may be a low-cost, low-invasive method to aid in screening individuals at increased genetic risk for AD before cognitive decline begins.

In recent years, researchers investigating the pathology of AD have primarily directed their attention at two causative or contributory factors: the accumulation of protein plaques in the brain called amyloid-beta and tangles of a protein called tau. Both have been linked to damaging and killing neurons, resulting in progressive cognitive dysfunction.

The new study focuses on pupillary responses which are driven by the locus coeruleus (LC), a cluster of neurons in the brainstem involved in regulating arousal and also modulating cognitive function. Tau is the earliest occurring known biomarker for AD; it first appears in the LC; and it is more strongly associated with cognition than amyloid-beta. The study was led by first author William S. Kremen, PhD, and senior author Carol E. Franz, PhD, both professors of psychiatry and co-directors of the Center for Behavior Genetics of Aging at UC San Diego School of Medicine.

The LC drives pupillary response — the changing diameter of the eyes’ pupils — during cognitive tasks. (Pupils get bigger the more difficult the brain task.) In previously published work, the researchers had reported that adults with mild cognitive impairment, often a precursor to AD, displayed greater pupil dilation and cognitive effort than cognitively normal individuals, even if both groups produced equivalent results. Critically, in the latest paper, the scientists link pupillary dilation responses with identified AD risk genes.

“Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual’s inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer’s before symptom appear,” said Kremen.

Source: University of California San Diego


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Vehicle Exhaust Pollutants Linked to Near Doubling in Risk of Age Related Macular Degeneration

Long term exposure to pollutants from vehicle exhaust is linked to a heightened risk of the common eye condition age-related macular degeneration, or AMD for short, suggests research published online in the Journal of Investigative Medicine.

Exposure to the highest levels of air pollutants was associated with an almost doubling in risk among those aged 50 and older, the findings show.

AMD is a neurodegenerative condition that affects the middle part of the retina, known as the macula. It is one of the most common causes of poor vision in older people, and is most likely caused by an interplay between genetic and environmental risk factors.

Long term exposure to air pollution has been linked to a heightened risk of several conditions, including respiratory and cardiovascular diseases. But less is known about its potential effects on eye health.

To explore this further, the Taiwanese researchers analysed national health insurance and air quality data from 1998 to 2010 to see if there might be a link between long term exposure to the pollutants nitrogen dioxide (NO?) and carbon monoxide (CO) and a heightened risk of AMD.

As the condition is more common among older age groups, the researchers focused only on 39,819 people aged 50 and above, most of whom lived in either highly (30%) or moderately (32.5%) urbanised areas.

Because there are seasonal variations in air pollutant levels, the researchers calculated an average annual exposure, which was categorised into four different levels.

During the monitoring period, 1442 people developed AMD.

After taking account of potentially influential factors, such as age, sex, household income, and underlying illnesses, those with the highest level of exposure to NO? (more than 9825.5 ppb) were nearly twice (91%) as likely to develop AMD as those exposed to the lowest level (less than 6563.2 ppb).

And people who were exposed to the highest level of CO (more than 297.1 ppm) were 84% more likely to develop AMD than those exposed to the lowest level (less than 195.7 ppm).

The highest rate (5.8%) of newly diagnosed AMD was among people living in the area with the highest level of CO exposure.

This is an observational study, and as such, can’t establish cause. And the authors emphasise that the data didn’t include information on other risk factors, such as smoking, genetics, and inflammation.

This is the first study of its kind to “demonstrate a significant association between AMD and high levels of ambient NO? and CO,” they write.

Recent research has implicated NO? in cardiovascular and neurological ill health, and as the retina is part of the central nervous system, there is a plausible biological explanation for its vulnerability to this pollutant, they add.

Source: Science Daily


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New Study Finds Test of Protein Levels in the Eye a Potential Predictor of (Future) Alzheimer’s Disease

Low levels of amyloid-β and tau proteins, biomarkers of Alzheimer’s disease (AD), in eye fluid were significantly associated with low cognitive scores, according to a new study published in the Journal of Alzheimer’s Disease. Led by researchers at Boston Medical Center, the study is the first to connect these known AD protein biomarkers in the eye to mental status. These findings indicate that proteins in the eye may be a potential source for an accessible, cost-effective test to predict future Alzheimer’s disease.

Diagnosing and starting treatment for AD before symptoms begin is key to managing the disease, because by the time symptoms appear it is often too late for current treatments to have any meaningful effect. Abnormal amounts of amyloid- β and tau proteins are biomarkers of AD, and deposits of amyloid proteins in the brain begin many years prior to symptoms of the disease. Previous research has shown an association between low levels of amyloid-β and tau proteins found in the cerebrospinal fluid obtained by lumbar puncture tests and preclinical AD, when pathological changes of AD present in the brain, but before the onset of clinical symptoms. However, lumbar puncture tests are expensive and inconvenient for many patients to undergo.

In this study, researchers used samples of eye fluid from 80 patients who were previously scheduled for eye surgery. The fluid extracted during these surgeries is typically discarded. Researchers tested the eye fluid to determine the levels of amyloid-β and tau proteins, and correlated those levels to the results of a baseline cognitive test. Low levels of these biomarker proteins were significantly associated with lower cognitive scores among the patients.

“These findings could help us build an accessible, and minimally invasive test to determine Alzheimer’s disease risk, especially among patients with eye disease,” says Lauren Wright, MD, first author on the study and ophthalmology fellow at BMC. “We noted that some of the participants who had low levels of protein biomarkers in their eye fluid already had signs of mild to moderate dementia based on their cognitive scores.”

These results reaffirm previous studies suggesting that patients with eye disease are at-risk for the development of AD, and suggest that further investigation in patients with eye disease may yield results that could be generalizable to larger populations.

“This is a great step in discovering the eye’s potential role in diagnosing preclinical Alzheimer’s disease, and further study is needed comparing protein biomarkers in the eye with more in-depth neurological testing,” adds Manju Subramanian, MD, senior author, principal investigator, and ophthalmologist at BMC.

Source: Boston Medical Center


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Eating Colourful Fruits and Vegetables Lowering Risk of Age-related Cataracts

A $5.7 billion global medical bill to restore sight for the estimated 45 million people with cataracts could be slashed in half by a diet rich in colourful fruits and vegetables, according to an international study.

Researchers from China and the University of South Australia have published the first study of its kind to verify the link between foods high in antioxidants and a lower risk of age-related cataracts (ARC).

UniSA Senior Research Fellow Dr Ming Li and colleagues from Xi’an Jiaotong University analysed 20 studies from around the world looking at the impact of vitamins and carotenoids on cataract risk.

Despite some inconsistencies, the findings overwhelmingly support the benefits of eating citrus fruits, capsicum, carrots, tomatoes and dark green vegetables such as spinach, broccoli and kale to delay the onset of ARC.

Their paper has been published in the American Journal of Clinical Nutrition ahead of World Optometry Week (March 26-30).

“Age-related cataracts are the leading cause of visual impairment among the elderly throughout the world, with unoperated cataracts contributing to 35 per cent of all blindness,” Dr Li says. “Although cataract extraction surgery is an effective method to restore vision, it will have cost society more than $5.7 billion by 2020.”

With the population ageing dramatically and an increasing number of people needing surgery, urgent action is needed, the researchers say.

“If we could delay the onset of ARC by 10 years it could halve the number of people requiring surgery.”

Improvements would rely on global changes to most of the world’s diet, however, with current consumption of antioxidants well below the recommended level to prevent age-related cataracts.

Source: University of South Australia


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