A Better Test to Help Spot Glaucoma?

Glaucoma is a leading cause of vision loss in older people, and early detection can bring better treatment. Now, researchers in Australia say their experimental genetic test for glaucoma can identify 15 times more people at high risk for the disease compared to a current genetic test.

“Early diagnosis of glaucoma can lead to vision-saving treatment, and genetic information can potentially give us an edge in making early diagnoses and better treatment decisions,” said lead researcher Owen Siggs in a news release from Flinders University. Siggs is associate professor at the university, as well as the Garvan Institute of Medical Research in Darlinghurst, New South Wales.

The new test analyzes blood or saliva samples and may be able to identify people at high risk for glaucoma before they suffer irreversible vision loss, the authors explained in a study published online in JAMA Ophthalmology.

One U.S. eye expert said the new screening method shows promise.

“Chronic open-angle glaucoma is a painless sight-threatening disease that often goes undetected until extensive visual damage has occurred,” explained Dr. Mark Fromer, an ophthalmologist at Lenox Hill Hospital in New York City. However, when detected and “treated early, visual loss can be limited,” he added.

“Genetic testing is not currently used to detect glaucoma on a routine basis,” Fromer said, but it “may be a valuable screening adjunct for the identification of many, but not all, patients with glaucoma. This new test has the potential to change the way we identify patients with glaucoma.”

The new study involved more than 2,500 people in Australia with glaucoma, and more than 411,000 with or without glaucoma in the United Kingdom.

The findings show the potential of the new genetic test in glaucoma screening and management, according to study senior author Jamie Craig, a professor and consulting ophthalmologist who runs a glaucoma research program at Flinders University.

“We’re now in a strong position to start testing this in clinical trials,” Craig said in the news release.

Once glaucoma is diagnosed, there are several treatment options that can slow or halt the progression of vision loss, the study authors explained.

The research team members are forming a company to develop an accredited test for use in clinical trials, and recruitment is expected to begin in 2022.

Source: HealthDay

High Caffeine Consumption May be Associated with Increased Risk of Glaucoma

Consuming large amounts of daily caffeine may increase the risk of glaucoma more than three-fold for those with a genetic predisposition to higher eye pressure according to an international, multi-center study. The research led by the Icahn School of Medicine at Mount Sinai is the first to demonstrate a dietary – genetic interaction in glaucoma. The study results published in the journal Ophthalmology may suggest patients with a strong family history of glaucoma should cut down on caffeine intake.

The study is important because glaucoma is the leading cause of blindness in the United States. It looks at the impact of caffeine intake on glaucoma, and intraocular pressure (IOP) which is pressure inside the eye. Elevated IOP is an integral risk factor for glaucoma, although other factors do contribute to this condition. With glaucoma, patients typically experience few or no symptoms until the disease progresses and they have vision loss.

“We previously published work suggesting that high caffeine intake increased the risk of the high-tension open angle glaucoma among people with a family history of disease. In this study we show that an adverse relation between high caffeine intake and glaucoma was evident only among those with the highest genetic risk score for elevated eye pressure,” says lead/corresponding author Louis R. Pasquale, MD, FARVO, Deputy Chair for Ophthalmology Research for the Mount Sinai Health System.

A team of researchers used the UK Biobank, a large-scale population-based biomedical database supported by various health and governmental agencies. They analyzed records of more than 120,000 participants between 2006 and 2010. Participants were between 39 and 73 years old and provided their health records along with DNA samples, collected to generate data. They answered repeated dietary questionnaires focusing on how many caffeinated beverages they drink daily, how much caffeine-containing food they eat, the specific types, and portion size. They also answered questions about their vision, including specifics on if they have glaucoma or a family history of glaucoma. Three years into the study later they had their IOP checked and eye measurements.

Researchers first looked at the relationship looked between caffeine intake, IOP and self-reported glaucoma by running multivariable analyses. Then they assessed if accounting for genetic data modified these relationships. They assigned each subject an IOP genetic risk score and performed interaction analyses.

The investigators found high caffeine intake was not associated with increased risk for higher IOP or glaucoma overall; however, among participants with the strongest genetic predisposition to elevated IOP – in the top 25 percentile – greater caffeine consumption was associated with higher IOP and higher glaucoma prevalence. More specifically, those who consumed the highest amount of daily caffeine– more than 480 milligrams which is roughly four cups of coffee – had a 0.35 mmHg higher IOP. Additionally, those in the highest genetic risk score category who consumed more than 321 milligrams of daily caffeine – roughly three cups of coffee – had a 3.9-fold higher glaucoma prevalence when compared to those who drink no or minimal caffeine and in lowest genetic risk score group.

“Glaucoma patients often ask if they can help to protect their sight through lifestyle changes, however this has been a relatively understudied area until now. This study suggested that those with the highest genetic risk for glaucoma may benefit from moderating their caffeine intake. It should be noted that the link between caffeine and glaucoma risk was only seen with a large amount of caffeine and in those with the highest genetic risk,” says co-author Anthony Khawaja, MD, PhD, Associate Professor of Ophthalmology University College London (UCL) Institute of Ophthalmology and ophthalmic surgeon at Moorfields Eye Hospital. “The UK Biobank study is helping us to learn more than ever before about how our genes affect our glaucoma risk and the role that our behaviors and environment could play. We look forward to continuing to expand our knowledge in this area.”

Source: Icahn School of Medicine at Mount Sinai

Type of Glaucoma Linked to Increased Risk of Cognitive Impairment

A type of glaucoma called normal-tension glaucoma is associated with an increased risk of cognitive impairment and possibly dementia, finds research published online in the British Journal of Ophthalmology.

Glaucoma is a condition in which the optic nerve becomes damaged and this can eventually lead to blindness. In most types of glaucoma, the damage is caused by a build-up of pressure in the eye, but this is not the case with normal-tension glaucoma.

The disease pathway for normal-tension glaucoma – a subtype of primary open angle glaucoma (POAG) – is not fully understood, but the authors say their findings suggest that it may share similar neurodegenerative pathways with dementia.

Primary open-angle glaucoma and dementia have been linked in some previous studies, but not all studies have found this association.

Primary open angle glaucoma encompasses not only low-tension glaucoma or normal-tension glaucoma (NTG), where the pressure in the eye is not raised above normal levels, but also high-tension glaucoma (HTG), where pressure in the eye is high. Normal-tension glaucoma is more common in Asia, while high-tension glaucoma is more common in Europe.

Two of the studies which showed a link between primary open angle glaucoma and dementia included lots of people with Asian ethnicity. This led the authors to wonder whether it may be specifically normal-tension glaucoma that is linked to cognitive impairment and dementia.

To investigate, they used the Australian and New Zealand Registry of Advanced Glaucoma to randomly select 248 patients aged at least 65 years who had normal-tension glaucoma, and these were matched by age and sex with 349 patients with high-tension glaucoma.

All patients were invited to participate in a health questionnaire and cognitive assessment over the telephone. A total of 290 patients – 144 with normal-tension glaucoma and 146 with high-tension glaucoma – had the cognitive screen. There was no difference between the two groups in demographic and eye parameters at baseline.

Cognitive impairment was found to be more than twice as prevalent in patients with normal-tension glaucoma than it was in those with high-tension glaucoma.

This is an observational study, so can’t establish cause, and the authors cannot rule out the possibility that results were affected by unobserved differences in clinical features or cognition of patients who could not be contacted or did not participate.

And while cardiovascular disease risk factors strongly associated with dementia, such as stroke, smoking, high blood pressure and diabetes were accounted for in the analysis, other potentially influential factors, such as socioeconomic status were not.

Nevertheless, the authors conclude: “Our finding of an association between normal-tension glaucoma and cognitive impairment supports a growing body of evidence suggesting an association between normal-tension glaucoma and dementia.”

Source: BMJ

Want to Protect Your Eyes as You Age? Stay Away From Carbs

Glaucoma strikes many people as they age, but what if a simple dietary change could lower your risk?

New research suggests it can: Scientists found a low-carbohydrate diet might protect you against the vision-robbing disease.

The researchers analyzed data from 185,000 female nurses and male health professionals, aged 40 to 75, who took part in three large studies in the United States conducted between 1976 and 2017.

Over the course of the studies, the participants provided information about their diet and health.

Maintaining a long-term diet low in carbohydrates and high in fat and protein from vegetables was associated with a 20% lower risk of primary open angle glaucoma (POAG) with early paracentral visual loss, according to the study published online recently in the journal Eye.

Glaucoma is the leading cause of blindness in the United States and POAG is the most common type of glaucoma. Patients typically have few or no symptoms until the disease progresses and they lose their peripheral vision.

“A diet low in carbohydrates and higher in fats and proteins results in the generation of metabolites favorable for the mitochondrion-rich optic nerve head, which is the site of damage in POAG,” explained co-corresponding study author Dr. Louis Pasquale, deputy chair for ophthalmology research at Mount Sinai Health System, in New York City.

“It’s important to note that a low-carbohydrate diet won’t stop glaucoma progression if you already have it, but it may be a means to preventing glaucoma in high-risk groups,” he explained in a Mount Sinai news release. “If more patients in these high-risk categories — including those with a family history of glaucoma — adhered to this diet, there might be fewer cases of vision loss.”

Previous research has shown that a low-carbohydrate/high-fat (keto) diet may protect against neurologic disorders, the study authors noted.

“This was an observational study and not a clinical trial, so more work is needed, as this is the first study looking at this dietary pattern in relation to POAG,” Pasquale said. “The next step is to use artificial intelligence to objectively quantify paracentral visual loss in our glaucoma cases and repeat the analysis,” he explained.

“It’s also important to identify patients who have a genetic makeup of primary open angle glaucoma who may benefit from a low-carbohydrate diet,” he added. “This dietary pattern may be protective only in people with a certain genetic makeup.”

Source: HealthDay


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AI-supported Test for Very Early Signs of Glaucoma Progression

The technology, supported by an artificial intelligence (AI) algorithm, could help accelerate clinical trials, and eventually may be used in detection and diagnostics, according to the Wellcome-funded study published today in Expert Review of Molecular Diagnostics.

Lead researcher Professor Francesca Cordeiro (UCL Institute of Ophthalmology, Imperial College London, and Western Eye Hospital Imperial College Healthcare NHS Trust) said: “We have developed a quick, automated and highly sensitive way to identify which people with glaucoma are at risk of rapid progression to blindness.”

Glaucoma, the leading global cause of irreversible blindness, affects over 60 million people, which is predicted to double by 2040 as the global population ages. Loss of sight in glaucoma is caused by the death of cells in the retina, at the back of the eye.

The test, called DARC (Detection of Apoptosing Retinal Cells), involves injecting into the bloodstream (via the arm) a fluorescent dye that attaches to retinal cells, and illuminates those that are in the process of apoptosis, a form of programmed cell death. The damaged cells appear bright white when viewed in eye examinations – the more damaged cells detected, the higher the DARC count.

One challenge with evaluating eye diseases is that specialists often disagree when viewing the same scans, so the researchers have incorporated an AI algorithm into their method.

In the Phase II clinical trial of DARC, the AI was used to assess 60 of the study participants (20 with glaucoma and 40 healthy control subjects). The AI was initially trained by analysing the retinal scans (after injection of the dye) of the healthy control subjects. The AI was then tested on the glaucoma patients.

Those taking part in the AI study were followed up 18 months after the main trial period to see whether their eye health had deteriorated.

The researchers were able to accurately predict progressive glaucomatous damage 18 months before that seen with the current gold standard OCT retinal imaging technology, as every patient with a DARC count over a certain threshold was found to have progressive glaucoma at follow-up.

“These results are very promising as they show DARC could be used as a biomarker when combined with the AI-aided algorithm,” said Professor Cordeiro, adding that biomarkers – measurable biological indicators of disease state or severity – are urgently needed for glaucoma, to speed up clinical trials as the disease progresses slowly so it can take years for symptoms to change.

“What is really exciting, and actually unusual when looking at biological markers, is that there was a clear DARC count threshold above which all glaucoma eyes went on to progress,” she added.

First author Dr Eduardo Normando (Imperial College London and Western Eye Hospital Imperial College Healthcare NHS Trust) said: “Being able to diagnose glaucoma at an earlier stage, and predict its course of progression, could help people to maintain their sight, as treatment is most successful if provided at an early stage of the disease. After further research in longitudinal studies, we hope that our test could have widespread clinical applications for glaucoma and other conditions.”

The team is also applying the test to rapidly detect cell damage caused by numerous conditions other than glaucoma, such as other neurodegenerative conditions that involve the loss of nerve cells, including age-related macular degeneration, multiple sclerosis, and dementia.

The AI-supported technology has recently been approved by both the UK’s Medicines and Healthcare products Regulatory Agency and the USA’s Food and Drug Administration as an exploratory endpoint for testing a new glaucoma drug in a clinical trial.

The researchers are also assessing the DARC test in people with lung disease, and hope that by the end of this year, the test may help to assess people with breathing difficulties from Covid-19.

DARC is being commercialised by Novai, a newly formed company of which Professor Cordeiro is Chief Scientific Officer.

Source: University College London


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