Brain diseases manifest in the retina of the eye

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Posted on 5th December 2016 by Pacific ClearVision Institute in General |Retina

Diseases of the central nervous system (CNS) may manifest as pathological changes in the retina of the eye. Research from the University of Eastern Finland (UEF) shows that retinal changes may be detected earlier than brain changes. Findings from mouse models suggest that eye examination could be used as a noninvasive screening tool for human brain diseases.

Retina, the light sensing tissue on the bottom of the eye, can be considered an integral part of the central nervous system (CNS). During fetal development, it matures from part of the brain and its innervation closely resembles that of the brain. Retinal structure and function can be readily examined with noninvasive or minimally invasive methods, whereas direct brain research has numerous limitations. If the health status of the brain could be indirectly assessed through the eyes, diagnostic screening of brain diseases could become more efficient.

In his Ph.D. project, Dr. Henri Leinonen investigated functional abnormalities of the retina using mouse models of human central nervous system diseases. Electroretinography (ERG) and visual evoked potentials (VEP) were chosen as research techniques, since similar methodology can be applied in both laboratory animals and humans. ERG can precisely track the function of retina using corneal or skin electrodes, whereas VEP measures the function of visual cortex. These methods were used to test different attributes of vision in three distinct genetically engineered mouse models of human CNS diseases. Furthermore, basic life science methods were used to test the correlation between functional abnormalities and the anatomical status of the retina.

Day and color vision associated retinal dysfunction was found in a mouse model of Huntington´s disease (HD), while the mouse was presymptomatic. Retinal structure remained relatively normal, even in an advanced disease state, although aggregation of toxic mutated huntingtin-protein was widespread in the diseased mouse retina. Although the retinopathy in mice is exaggerated compared to human HD patients, the finding is partly in line with patient data showing impaired color vision but no clear-cut anatomical retinopathy.

In a mouse model of Alzheimer´s disease (AD), researchers observed abnormality in night vision associated retinal function. Specifically, rod-mediated inner retinal responses to dim light flashes were faster in diseased mice than in their wild-type controls. The observation may be explained by impaired cholinergic neurotransmission that is also partly causative for the deterioration of memory in AD.

In a mouse model of late infantile neuronal ceroid lipofuscinosis (NCL), a pediatric neurological disease, the researchers described retinal degenerative changes that mimic the characteristic pathology of age-related macular degeneration (AMD). These included impaired function of retinal pigment epithelium and subsequent blindness due to photoreceptor atrophy and death. It has been postulated that the retinal degeneration in human patients progresses similarly.

The results add to the growing body of evidence that show pathological changes in the retina in addition to the brain in CNS diseases. Functional changes of the retina were found in three mouse models of human CNS diseases whose phenotype, age of onset and pathological mechanism clearly differ from each other. Visual impairment was the fastest progressive symptom in two models tested. The findings support the idea of eye examinations as potential screening tools for CNS diseases. Development of efficient, safe and economic screening tools for CNS diseases is imperative, since the diagnosis of these diseases is often obtained only in the advanced disease state when as such satisfactory remedies are poorly effective. Since eye and vision research can be conducted noninvasively, advancement of trials from the preclinical to the clinical phase could be relatively fast.

The findings were originally published in PLoS One, Journal of Alzheimer’s Disease, and Human Molecular Genetics.

Alzheimer’s disease proteins could be at fault for leading cause of vision loss among older people

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Posted on 5th December 2016 by Pacific ClearVision Institute in General |Retina

Research from the University of Southampton gives new insight into possible causes of Age-related Macular Degeneration (AMD), a leading cause of vision loss among people aged 50 and older.

The study, published in the journal Experimental Eye Research, discovered that a group of proteins, which are linked to Alzheimer’s disease, are able to accumulate in the retina and damage it.

The researchers hope that the discovery could lead to better treatments for patients.

AMD is a progressive disease that causes the death of the retinal photoreceptors, the light-sensitive cells at the back of the eye. The most severe damage occurs in the macula, a small area of the retina that is needed for sharp, central vision necessary for reading, driving and other daily tasks.

There are two different types of AMD — ‘wet’ and ‘dry’. In wet AMD, the growth of leaky blood vessels which damage the retina can be stopped.. However, this does not work for everyone, and is a way to manage rather than cure wet AMD. By contrast, dry AMD has no approved treatment as yet.

Dr Arjuna Ratnayaka, a Lecturer in Vision Sciences at the University of Southampton, who led the study, said: “We know that AMD is caused by a combination of genetic, environmental and lifestyle risk factors, but this novel discovery could open up new possibilities to understand how the aging retina becomes damaged. Such advances are important if we are to develop better AMD treatments in the future.

“AMD currently affects more than 600,000 people in the UK and 50 million individuals worldwide. This figure is expected rise significantly as our society grows older. We urgently need new treatments to stop people spending their twilight years in blindness.”

The study, which used both cell cultures and mouse models, analysed how quickly Amyloid beta proteins, which are thought to be a likely cause of Alzheimer’s disease, entered the retina and how they damaged it.

The team found that the Amyloid beta proteins entered the cells of the retina within 24 hours of exposure and then began to break the cell’s scaffold structure.

Dr Ratnayaka added: “The speed in which these proteins entered the retinal cells was unexpected. These findings have given some insights into how a normal healthy retina can switch to a diseased AMD retina. We hope that this could lead to designing better treatments for patients in the future.”

The research team’s next step will be to evaluate how the Amyloid beta proteins get into retinal cells and study more closely how damage occurs, with a view of establishing preventative measures or treatment options.

Woman who lost vision to diabetes shares experience to raise awareness

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Posted on 5th December 2016 by Pacific ClearVision Institute in General |Retina

It was Labor Day 2015 when Rosetta Ivey-Foster, a 76-year-old retired bank clerk, learned first-hand how quickly diabetes can deteriorate vision. Swift action restored most of her eyesight.

Diagnosed with type 1 diabetes more than 25 years ago, Ivey-Foster had carefully managed her disease. That included getting regular comprehensive dilated eye exams to detect early signs of diabetic eye disease, a group of conditions that includes diabetic retinopathy, cataract, and glaucoma. The National Eye Institute recommends that people with diabetes get a dilated eye exam at least once a year to detect early signs of diabetic eye disease.

A few days before Labor Day, Ivey-Foster noticed the sudden appearance of a floater in her right eye. “It looked like a blob or a water bubble,” she said, noting that she’d had floaters before, but they’d always disappeared after a couple of days. This one persisted. As she sat on her balcony to watch a local Labor Day air show with a neighbor, she realized something was terribly wrong with her vision. “I couldn’t see the planes!” she said.

Diabetes, a growing threat to vision

More than 25 million Americans have diabetes, and that number may double or triple by 2050. All people with diabetes are at risk for diabetic eye disease. African Americans, American Indians/Alaska Natives, and Hispanics/Latinos are at higher risk for losing vision or going blind from diabetic eye disease. Diabetic retinopathy poses the greatest risk to vision. It is the most common cause of vision loss among people with diabetes and the most common cause of blindness among working-age Americans. Over time, high blood sugar levels from diabetes affect the tiny blood vessels in the tissue in the back of the eye called the retina.

Timely treatment saved her vision

Ivey-Foster saw her eye doctor at once. Suber Huang, M.D., founder of the Retina Center of Ohio in Cleveland, discovered that Ivey-Foster could read none of the letters on the eye chart with her right eye. She had developed proliferative diabetic retinopathy, an advanced stage of the disease. New, abnormal blood vessels were growing on the surface of her retina and leaking blood — the cause of her floaters.

Huang treated Ivey-Foster’s right eye with a laser to burn and shrink abnormal blood vessels in the retina. He also removed the bloody gel-like fluid in her eye and replaced it with a clear saline solution, a procedure called vitrectomy.

“I was so relieved when he took the bandages off of my eye and I could see again,” Ivey-Foster exclaimed. By Labor Day 2016, Ivey-Foster had regained enough vision to again see the planes in the air show.

Studies stress controlling diabetes

“Well-controlled glycemia, or blood sugar level, has a positive, measurable, and lasting effect on eye health,” said Emily Chew, M.D., deputy director of the NEI Division of Epidemiology and Clinical Applications. In a recent study, she and colleagues found less diabetic retinopathy progression among people with type 2 diabetes who intensively controlled their blood sugar levels. “This study sends a powerful message to people with type 2 diabetes,” she said. The message also applies to people with type 1 diabetes.

For people who have diabetes, the NEI’s National Eye Health Education Program recommends these important steps to keep their health on TRACK:

• Take your medications as prescribed by your doctor.
• Reach and maintain a healthy weight.
• Add physical activity to your daily routine.
• Control your ABC’s — A1C, blood pressure, and cholesterol levels.
• Kick the smoking habit.

Ivey-Foster emphasized, “I would say to anyone that has diabetes, make sure you get regular eye exams.” In addition to early detection, her experience highlights the importance of timely treatment.

Research reveals new treatment options

Today, people like Ivey-Foster have an alternative to laser therapy. In 2015, the NEI-funded Diabetic Retinopathy Clinical Research Network showed that eye injections of the anti-VEGF drug Lucentis (ranibizumab) are highly effective in treating proliferative diabetic retinopathy. VEGF is what stimulates abnormal blood vessel growth and leakage in the retina. The finding was the first major treatment advance for proliferative diabetic retinopathy in 40 years.

In 2016, the DRCR.net reported results of a clinical trial that compared three anti-VEGF drugs for diabetic macular edema, a complication of diabetic retinopathy that causes the build-up of fluid in a region of the retina called the macula. The study found that Lucentis, Avastin (bevacizumab), and Eylea (aflibercept) were similarly effective when patients’ vision loss was mild. Eylea outperformed Avastin and Lucentis among patients who started treatment with moderate (20/50) or worse vision.

Zika and glaucoma linked for first time in new study

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Posted on 5th December 2016 by Pacific ClearVision Institute in General |Retina

A team of researchers in Brazil and at the Yale School of Public Health has published the first report demonstrating that the Zika virus can cause glaucoma in infants who were exposed to the virus during gestation.

Exposure to the Zika virus during pregnancy causes birth defects of the central nervous system, including microcephaly. Brazilian and Yale School of Public Health researchers had reported early during the microcephaly epidemic that the virus also causes severe lesions in the retina, the posterior portion of the eye. However, until now, there has been no evidence that Zika causes glaucoma, a condition that can result in permanent damage to the optic nerve and blindness.

“We identified the first case where Zika virus appears to have affected the development of the anterior chamber or front portion of the eye during gestation and caused glaucoma after birth,” said Dr. Albert Icksang Ko, professor at the Yale School of Public Health and co-author of the study published in the journal Ophthalmology. Ko has longstanding research collaborations in Brazil and has worked with local scientists since Zika first appeared in the Americas to better understand the birth defects that are caused by the virus and the risk factors for Zika Congenital Syndrome.

While conducting their investigations of the microcephaly epidemic in Salvador in Northeast Brazil, the researchers identified a three-month-old boy who was exposed to Zika virus during gestation. While no signs of glaucoma were present at the time of birth, the infant developed swelling, pain, and tearing in the right eye. The research team diagnosed glaucoma as the cause of symptoms and together with local ophthalmologists, performed a trabeculectomy, an operation that successfully alleviated the pressure within the eye.

While this is the first known incidence of glaucoma in an infant with the Zika virus, clinicians treating patients with Zika should be aware that glaucoma is another serious symptom of the disease that should be monitored, said the investigators. Additional research is needed to determine if glaucoma in infants with Zika is caused by indirect or direct exposure to the virus, either during gestation or postpartum.

The Zika virus, which is primarily transmitted through infected mosquitoes, has reached epidemic levels in several areas worldwide, and is of particular concern in Brazil, where the Pan American Health Organization reports more than 200,000 suspected cases and 109,000 confirmed cases of the disease. Since the outbreak began in 2015, Zika has now reached the United States, with more than 4,000 travel-related cases reported, and 139 locally acquired mosquito-borne cases confirmed, according to the CDC. There is currently no vaccine for the Zika virus.

Brain training video games help low-vision kids see better

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Posted on 5th December 2016 by Pacific ClearVision Institute in General |Retina

A new study by vision scientists at the University of Rochester and Vanderbilt University found that children with poor vision see vast improvement in their peripheral vision after only eight hours of training via kid-friendly video games. Most surprising to the scientists was the range of visual gains the children made, and that the gains were quickly acquired and stable when tested a year later.

“Children who have profound visual deficits often expend a disproportionate amount of effort trying to see straight ahead, and as a consequence they neglect their peripheral vision,” said Duje Tadin, associate professor of brain and cognitive sciences at Rochester. “This is problematic because visual periphery — which plays a critical role in mobility and other key visual functions — is often less affected by visual impairments.”

“We know that action video games (AVG) can improve visual perception, so we isolated the AVG components that we thought would have the strongest effect on perception and devised a kid-friendly game that compels players to pay attention to the entire visual field, not just where their vision is most impaired,” said Tadin, who is also a professor in the Center for Visual Science. “As a result, we’ve seen up to 50 percent improvement in visual perception tasks.”

Successful AVG players distribute and switch their attention across a wide area, while at the same time they remain vigilant for unexpected moving targets to appear, all while ignoring irrelevant stimuli.

The researchers created a training game with these specific task characteristics while eliminating other components of AVGs, such as the demand for speeded hand-eye coordination, and any violent or other non-child-friendly material.

Game Training

Twenty-four low-vision youths from the Tennessee and Oklahoma Schools For The Blind participated in the training experiment that appears in Scientific Reports. Pre-training screening showed that while most children had central visual acuity worse than the 20/200 legal blindness limit, they also underutilized their peripheral vision.

According to the study’s lead author, Jeffrey Nyquist, founder and CEO of NeuroTrainer, the students’ issues with the periphery were in part attentional.

Nyquist and the team hypothesized that training the students to pay more attention to their peripheral visual field could have quick results.

“We didn’t improve the kids’ hardware — these children have profound physical problems with their optics, muscles, and retina, and we can’t fix that,” said Nyquist. “But we could improve their software by training their brain to reallocate attentional resources to make better use of their periphery vision.”

The students were divided into 3 groups: a control group that played a Tetris-like game; a group that played a kid-friendly commercially-available AVG, Ratchet & Clank; and a group that used the training game devised by the researchers. All games were played on a large projection screen to better involve visual periphery.

The game the researchers developed has a dual-task component. Students tracked multiple moving objects simultaneously while being on the lookout for another object that briefly appears and requires a response from the player.

“The goal is to pay attention to a number of objects over a large area, and to be prepared to react to unexpected events in the even further periphery,” explained Tadin. “It forces the low-vision students to expand their visual field — to shift their attention to the neglected areas of the visual field.”

After a total of eight hours of training, groups who trained with the commercially-available AVG and the custom dual-task game showed significant visual improvements.

Improvements were seen in a range of visual tasks. The students were able to better perceive moving objects (motion perception) in the far periphery, they were able to better attend to visual crowding, such as identifying a specific letter within a field of other letters, and they were much faster at finding objects in cluttered scenes (visual search), like finding a stapler on a messy desk.

“We were surprised by the range of improvements, and we were even more surprised when we tested a few of the students a year later and found that the gains they made were stable,” said Nyquist. “Within just a few hours of training, they were able to expand their usable visual field and visual search ability.”

Nyquist notes that when the researchers began their work with the students, it was to assess how they maneuver around their environments. “But we quickly went from assessing to thinking ‘maybe we have something that can train them and improve their real-life abilities,’” he said. “When we realized that the students achieved up to 50 percent improvement in visual tasks, we were blown away.”