Tag: glaucoma

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The Search for an Effective Treatment for Glaucoma

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Photo by Ksenia Chernaya

Pete Williams at Karolinska Institutet is one of the few researchers in Sweden concentrating on glaucoma. The goal is an effective treatment, something that stops the degenerative process in the nerve cells of the eye. He is the senior author of a new paper in Nature Communications on how deficiency of the enzyme NMNAT2 renders the nerve cells of the eye vulnerable to neurodegeneration and could be a key in the search for a treatment. 

Glaucoma is very common. Eighty million people worldwide have the eye disease. There is no cure, but there are treatments that lower the pressure in the eye and that can slow down the progression of the disease, which otherwise leads to irreversible blindness.

Not always treatable

“Most people who have heard of glaucoma believe that it can be treated with eye drops and surgery. Unfortunately, this is not entirely true. For many of the patients, the treatment lower the eye pressure but doesn’t prevent further vision loss,” says Pete Williams.

Knowledge about glaucoma has taken time to develop because the disease progresses slowly. This means that in the past, it took many years before researchers could see if a particular treatment had any effect. However, in the last decade or so, the availability of instruments that measure changes in the eye much earlier than the patient experiences them has given new impetus to research into the eye disease.

The importance of NAD

In the 1980s, research into neurodegenerative diseases discovered a link with NAD, a co-enzyme, ie a molecule that binds to an enzyme and makes it active.  Pete Williams’ group was the first to show that NAD levels were low in animal models of glaucoma.

“NAD has many important functions in the body. A lack of it is important for neuronal health and survival in many diseases, but we don’t yet know how to use this information to create a better treatment ” says Pete Williams.

When the body makes NAD, it uses an enzyme NMNAT1. However, in neurons, it needs another enzyme: NMNAT2 (which is only found in neurons). 

“In our recent paper in Nature Communications, we show that NMNAT2 is needed to protect neurons in the eye and that gene therapy can be used to increase levels,” says Pete Willams. “

The research team is now moving on to try to develop new substances that target NMNAT2 in nerve cells. 

Source: Karolinksa Institutet

Categories : OphthalmologyTags :

Many Old People may be Unaware that They Have Glaucoma

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Photo by Mari Lezhava on Unsplash

Research on 70-year-olds carried out at the University of Gothenburg, found that nearly 5% had glaucoma – with half of whom were unaware that they had the disease. The study also confirmed hereditary factors were involved in the disease and that intraocular pressure was normal in two-thirds of those newly diagnosed.

Glaucoma is a common eye disease that damages the optic nerve and thereby the field of vision and can lead to blindness. One of the most common risk factors for it is raised intraocular pressure, exceeding the normal range of 11–21mmHg.

The research, published in Acta Ophthalmologica, was carried out by Lena Havstam Johansson, a PhD student at the University of Gothenburg and a specialist nurse at Sahlgrenska University Hospital. The study shows that 4.8% of the 560 study participants examined by eye specialists had glaucoma.

“Of those who were diagnosed with glaucoma via the study, 15 people – or 2.7% of all participants – were unaware that they had the disease before being examined,” says Lena Havstam Johansson. “So half of those who turned out to have glaucoma were diagnosed because they took part in the study.”

For those who were newly diagnosed, the discovery of the disease meant they could start treatment with daily eye drops to reduce intraocular pressure, slowing the progression of optic nerve damage.

Glaucoma impacts some areas of life – but not others

People with glaucoma had similar levels of physical activity to those without the disease and did not smoke more, or drink more alcohol. They rated their overall quality of life as being just as good as others, they were not more tired or more depressed.

“This was a positive surprise, and was a finding that I hope can bring comfort to many people who have been diagnosed with glaucoma. It’s hard to live with a disease that gradually impairs vision, but life can still be good in many ways.”

By contrast, people with glaucoma reported that their vision-related quality of life was poorer.

“It’s harder to climb stairs, see curbs in the evening, and notice things in your peripheral vision. This means that people with glaucoma may avoid visiting others, or going to restaurants or parties, and instead stay at home. They lose their independence, and may feel frustrated about it.”

Ongoing study of 70-year-olds

The research was carried out as part of the H70 study, examining the health of older people, which has been conducted at the University of Gothenburg for fifty years. The H70 study continuously invites all 70-year-olds born in a certain year in Gothenburg to attend several comprehensive physical and cognitive examinations. The 1203 70-year-olds included in the glaucoma study were born in 1944. For these studies, 1182 participants answered written questions about their eye health and the presence of glaucoma in their family. Eye specialists at Sahlgrenska University Hospital also examined 560 of the participants.

The findings confirm that there are hereditary factors behind the disease, as those diagnosed with glaucoma were more likely to have a close relative with the same diagnosis. The results also confirm that glaucoma involves higher intraocular pressure, although they also show that the majority of those who were newly diagnosed (67%) still had normal eye pressure.

During the early stages of the disease, the healthy eye can compensate for the loss of vision, meaning that many people believe their vision is as good as before. These studies confirm that glaucoma often does not initially involve a loss of visual acuity, which may make it harder to detect the disease.

Source: University of Gothenburg

Categories : Metabolic DisordersTags :

Early Diabetes, Hypertension Accelerates Development of Glaucoma

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Credit: National Eye Institute

Developing Type 2 diabetes or hypertension earlier in life is linked to the earlier development of the most common form of glaucoma, according to a study published in Clinical Ophthalmology. These findings could lead to better screening protocols for primary open-angle glaucoma (POAG), the leading cause of irreversible blindness worldwide, which makes up nearly 90% of all cases of glaucoma.

“Currently, we lack the tools to cure glaucoma, but with enough advanced notice, we can preserve patients’ vision. Early detection of glaucoma is the key to better control of intraocular pressure and preventing blindness,” said study leader Karanjit Kooner, MD, PhD, MBA, Associate Professor of Ophthalmology at UTSW.

Tens of millions of people have POAG around the globe. Because this disease has few symptoms in its earliest stages, Dr. Kooner explained, patients are frequently diagnosed in its later stages when vision has already been permanently damaged. Although researchers have identified several risk factors for POAG – including Type 2 diabetes, hypertension, migraines, and obstructive sleep apnoea — how they might influence the onset of POAG is not well understood.

To answer this question, Dr Kooner and his colleagues collected data from the medical records of 389 of his patients with POAG. The researchers found no link between migraines and/or obstructive sleep apnoea and the age of POAG onset. However, the researchers found that the age of Type 2 diabetes and/or hypertension diagnosis was significantly linked with the onset of POAG – the earlier patients presented with either or both of these conditions, the earlier they tended to develop POAG.

Dr Kooner noted that both Type 2 diabetes and hypertension are diseases that affect blood vessels of both the optic nerve and retina, thus potentially causing changes that predispose patients to POAG, another condition with a vascular root. If these connections hold up in future research, he said, Type 2 diabetes and hypertension could be added to the list of factors that can trigger POAG screening — including a family history of POAG, elevated intraocular pressure, and Black race — and lead to earlier diagnosis of POAG, preserving patients’ vision and quality of life.

Source: UT Southwestern Medical Center

Categories : Neurodegenerative DiseasesTags :

Little to No Link Between Glaucoma and Cognitive Function

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Older woman smiling
Photo by Ravi Patel on Unsplasj

Previous studies looking for an association between the neurodegenerative disorder glaucoma and cognitive function have produced mixed results. Now, findings from a large study recently published in the Journal of the American Geriatrics Society suggest that any association, if it exists, will only be small.

Glaucoma, the leading cause of irreversible blindness, is a progressive optic neuropathy with incompletely understood pathogenesis that results in progressive vision loss, often beginning with peripheral visual field defects. As a neurodegenerative process, glaucoma is associated with trans-synaptic degeneration in the brain, specifically in the lateral geniculate nucleus and visual cortex. Some prior studies have suggested that the pathogenesis of primary open angle glaucoma (POAG) and normal tension glaucoma (NTG), specifically, may be part of a broad neurodegenerative mechanism with ocular and non-ocular manifestations. Evidence also suggests that impaired vision is associated with a significant increase in the risk of accelerated cognitive decline and incident dementia. Therefore, there is interest in measuring an association between glaucoma and dementia.

The study included 7073 US adults aged 51 years and older who were interviewed by phone every two years. Those who developed glaucoma tended to have higher cognitive function scores but steeper rates of cognitive score decline over a maximum follow-up time of 18 years. The observed associations between glaucoma and cognitive function were small and unlikely to be clinically meaningful. 

“In this large longitudinal study, a diagnosis of glaucoma was not associated with steeper rates of cognitive decline; however, this study did not have access to clinical data to determine whether glaucoma-related vision loss is a risk factor for cognitive decline and dementia,” said senior author Joshua R. Ehrlich MD, MP, of the University of Michigan Medical School. “This is an important question for future studies to consider.” 

Source: Wiley

Categories : Diseases, Syndromes and Conditions UncategorizedTags :

Diabetes Drug Could Halve Glaucoma Risk

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Source: Pixabay CC0

GLP-1R agonists, a popular class of diabetes drugs, may also have a protective effect against glaucoma in diabetic patients, according to a new study published in the British Journal of Ophthalmology.

The researchers examined retrospective data of 1961 diabetic patients who were new users of this class of drugs and matched them to 4371 unexposed control subjects. After 150 days on average, 10 patients in the medicated group were newly diagnosed with glaucoma (0.5%) compared to 58 patients (1.3%) in the control group. These results indicate that GLP-1 receptor agonists could halve a diabetic patient’s risk of developing glaucoma.

The findings are supported by a Penn Medicine study from 2020, which found that GLP-1R agonists reduced neuroinflammation and prevented retinal ganglion cell death in mice. This class of drugs has also shown similarly protective effects against Alzheimer’s and Parkinson’s diseases in animal models, and clinical trials are underway to test the medications against neurodegenerative diseases in humans.

Glaucoma is the second leading cause of blindness worldwide, and people with diabetes are twice as likely to develop the condition.

“It was very encouraging to see that a popular diabetes medication could significantly reduce the risk of developing glaucoma, and our study suggests that these medications warrant further study in this patient population,” said Qi N. Cui, MD, PhD, with Brian VanderBeek, MD, MPH, both assistant professors of Ophthalmology at Penn.

Source: EurekAlert!

Categories : NeurologyTags :

Eye Pressure in Glaucoma not the Whole Story

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The findings of a new study in rats show that a chemical known to protect nerve cells also slows glaucoma, the leading cause of irreversible blindness.

According to the National Glaucoma Foundation, in the US, over 3 million have glaucoma, with only half being aware of the fact and more than 120 000 are blind from the disease. The World Health Organization estimates that, worldwide, over 60 million individuals suffer from glaucoma.  

Led by researchers at NYU Grossman School of Medicine, the study centred on the watery fluid inside the eye on which its function depends. In patients with glaucoma, a buildup of fluid pressure wears down cells in the eyes and the nerves connecting them to the brain.

Previous research that despite eye pressure having been controlled, the condition progressively worsened. The relationship between pressure buildup and impaired vision remains poorly understood

The new study showed that when rats ingested the compound citicoline, optic nerve signals between the brain and eye were almost fully restored. Citicoline is a major source of choline, a building block in the membranes that line nerve cells and enhance nerve cell communication. It is produced in the brain but also commercially produced.

The study confirmed that increased eye pressure levels contributes to nerve damage in glaucoma, but  it also showed that citicoline reduced vision loss in rats without reducing pressure levels.

“Our study suggests that citicoline protects against glaucoma through a mechanism different from that of standard treatments that reduce fluid pressure,” said senior author Kevin Chan, PhD, an assistant professor in the Department of Ophthalmology at NYU Langone Health. “Since glaucoma interrupts the connection between the brain and eye, we hope to strengthen it with new types of therapies.”

The findings are helping scientists better understand how glaucoma works and add to past evidence that citicoline may counter the disease, said Chan, also the director of the Neuroimaging and Visual Science Laboratory at NYU Langone. It is known that humans and rodents with glaucoma have lower than normal levels of choline in the brain, but until now, Prof Chan says, there’s been little concrete evidence of the effectiveness of choline supplements as a therapy for glaucoma or why choline occurs in lower levels in glaucoma patients.

Prof Chan and his team tested whether increasing levels of that chemical would slow or even stop the degradation of the optic nerve and other regions of the brain involved in vision. Using a comprehensive study of the eye-brain connection in glaucoma, his team found that giving rats oral doses of citicoline over a three-week period protected nerve tissues and reduced vision loss sustainably even after the treatment stopped for another three weeks.

To simulate glaucoma, the researchers used a clear gel in rats to build up eye pressure mildly without otherwise blocking their vision. Then, the team used MRI imagery to measure the structural integrity and the amount of functional and physiological activity along the visual pathway. To test the clarity of vision of each eye, the researchers tracked the rodents’ visual behaviour .

It was found that for rats with mildly elevated eye pressure, the tissues that connect the eye and brain, including the optic nerve, degraded for up to five weeks after the injury. Nerve structure breakdown in the citicoline-treated rodents slowed by up to 74%, which the researchers said indicates that the chemical had protective effects on nerve cells.

However, more research is necessary before citicoline supplements to treat glaucoma in humans, as commercial drugs have yet to be proven fully effective in clinical trials. The researchers are planning next to look into how choline protects the eye and why it is depleted in glaucoma patients.

Source: Medical Xpress

Journal information: Yolandi van der Merwe et al, Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control, Neurotherapeutics (2021). DOI: 10.1007/s13311-021-01033-6