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Genetic Test Identifies Eye Cancer Tumors Likely To Spread PDF Print E-mail
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Ophthalmology and Optometry
Friday, 18 May 2012

Eye CancerResearchers at Washington University School of Medicine in St. Louis (US) have developed a genetic test that can accurately predict whether the most common form of eye cancer will spread to other parts of the body, particularly the liver.

In 459 patients with ocular melanoma at 12 centers in the United States and Canada, the researchers found the test could successfully classify tumors more than 97 percent of the time. Principal investigator J. William Harbour believes the test should allow ocular oncologists to quickly evaluate the risks associated with particular tumors and to begin treatment the moment they can detect any spread of the cancer.

Melanoma of the eye is relatively rare, diagnosed in about 2,000 people in the United States each year. Advances in treatment have allowed surgeons to preserve patients’ vision, but when cancer spreads beyond the eye, it often is deadly.

About a decade ago, Harbour began using gene expression profiling to monitor the activity of thousands of genes in and around ocular melanoma tumors. Initially, Harbour’s group identified differences in approximately 1,000 genes between class 1 and class 2 tumors, but they whittled down that number, hoping to develop a simple test that could be used easily by ophthalmologists. Eventually, they settled on about a dozen genes that could be evaluated in tumor samples collected with a needle biopsy. Testing tumor tissue from his own ocular melanoma patients at the Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University in St. Louis, Harbour found that the gene expression profile test was very good at identifying the two classes of tumors. Then he started recruiting other centers to test the method, too.

Doctors at the other centers collected tumor samples and shipped them to Harbour’s lab. Not knowing anything about which tumor samples came from which patients, the lab then analyzed the samples and made predictions about which tumors were likely to spread. Although it can take up to five years before there is any evidence that cancer has spread beyond the eye, this study went back less than two years later and tested predictions against what actually had happened. Almost 62 percent of those tested (276 patients) had class 1 tumors, which were unlikely to spread. About a year and a half after the samples were tested, only three of those tumors had metastasized. Meanwhile, 38 percent of those tested (170 patients) had class 2 tumors, indicating that spread of the cancer was more likely. In that group, 44 (26 percent) developed metastatic disease during the study period. Had patients been followed longer, more likely would have experienced spread of their cancer. Statistical predictions estimate that among class 2 patients, about 60 percent would have metastatic disease within three years, and approximately 80 percent in five years.

In the past, some centers relied on a chromosome test to identify eye tumors that were likely to spread. That test looked at chromosome 3 because many ocular melanoma tumors have only one copy of that chromosome. But the 15-gene expression profile test is more accurate. It takes a more complete “snapshot” of the entire tumor. Harbour says the results of the chromosome test can change, depending on which part of a tumor gets sampled.

Another strength of the test is that it can identify which patients will need the closest monitoring. On the other hand, the current study found that more than 60 percent of patients with ocular melanoma have class 1 tumors. Those patients don’t need to be followed with the same frequency.

The study will appear in an upcoming issue of the journal Ophthalmology, but is now online.

 
New Way To Protect Eyes From Strong Light Damage PDF Print E-mail
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Ophthalmology and Optometry
Monday, 14 May 2012

IR LightTreating eyes with gentle infra-red light can help prevent the damage caused by subsequent exposure to bright light, new scientific research has found. A  breakthrough by researchers at The Vision Centre offers new hope to people who suffer vision loss due to constant exposure to bright sunlight or artificial lights – such as construction workers, sportspeople, fishermen, farmers, welders, actors, entertainers and others.

Dr Krisztina Valter and PhD researcher Rizalyn Albarracin at The Vision Centre and Australian National University have shown that pre-treatment with near infra-red light prevents a build-up of scar tissue in the retina causing subsequent harm to sight.

“There’s a group of cells that look after our vision and work behind the scenes,” says Ms Albarracin, “called Müller cells. They act to protect the retina by clearing toxins and inducing healing whenever there is injury to the vision cells. However, their protection is a double-edge sword for the eyes. When the retina comes under extreme stress, as when it is exposed to intensely bright light and loses a large number of vision cells, the Müller cells can over-react by multiplying and forming scar tissue behind the retina. When this occurs, two things happen: first, the vision cells close to where the scar tissue forms will stop working. Secondly, the scar tissue blocks the blood supply to the outer retina, so that other vision cells are starved of oxygen, glucose and other nutrients vital to their survival. As a result more vision cells die, which in turn provokes Müller cells to work even harder, forming more scar tissues and setting up a vicious cycle,” Ms Albarracin explains.

“We found that the treatment with mild NIR successfully inhibits the Müller cells from multiplying and forming scar tissue,” says team leader Dr Krisztina Valter. “Technically, our results showed that 670 nm light pretreatment ameliorates light-induced changes in the expression of Müller-cell specific markers for structure, stress, metabolism and inflammation. This suggests that 670 nm light pre-treatment may promote neuroprotective effects in the retina from light-induced damage. Our findings indicate that it may be possible to pre-treat someone who knows that they will be exposed to bright lights and so reduce the potential damage it can cause. This would be very helpful for people working in bright sunlight, under powerful artificial lamps or in occupations such as welding, as it would reduce the amount of cumulative damage they can suffer to their vision of years of exposure to bright light,” Dr Valter says.

The researchers used an array of small LEDs (light emitting diodes) that have been tuned to produce near infra-red light at a particular wavelength – 670 nanometres. These units are low-cost, making a future preventative treatment for vision loss highly affordable – especially when compared with cost of lost sight, Dr Valter says. “Near infra-red therapy is very benign, easy to use and involves no discomfort to the patient,” she adds. “It is already approved by the US Food and Drug Administration for use in sports medicine, for hair loss and so on – so developing a novel therapeutic application for the eyes is likely to be less complex and protracted than, say, developing a new drug,” she adds. The study “670nm Red Light Preconditioning Supports Müller Cell Function: Evidence from the White Light-induced Damage Model in the Rat Retina” by Rizalyn Albarracin and Krisztina Valter is published in the journal Photochemistry and Photobiology.

 
Myopia Linked to Increased Schooling PDF Print E-mail
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Ophthalmology and Optometry
Tuesday, 08 May 2012

MyopiaProfessor Ian Morgan, from the Australian Research Council Centre of Excellence in Vision Science, and the Australian National University in Canberra, and team report in the second paper in The Lancet Series on Ophthalmology that this extremely high prevalence of myopia is linked to increased schooling, according to recent data, which indicates that the lack of daylight exposure could have a major impact on this gigantic problem.

It was previously believed that myopia was mainly based on genetics. However, more recent evidence shows that environmental factors are involved as well. For instance, the three key ethnic groups in Singapore, i.e. Chinese, Indians and Malays have all experienced steep increases since 1996, indicating a similar sensitivity to the risk factors they were all exposed to.

Myopia has emerged as a major health issue in east Asia, because of its increasingly high prevalence in the past few decades (now 80 to 90% in school-leavers), and because of the sight-threatening pathologies associated with high myopia, which now affects 10 to 20% of those completing secondary schooling in this part of the world. Similar, but less marked, changes are occurring in other parts of the world. The higher prevalence of myopia in east Asian cities seems to be associated with increasing educational pressures, combined with life-style changes, which have reduced the time children spend outside. There are no reported major genes for school myopia, although there are several genes associated with high myopia. Any genetic contribution to ethnic differences may be small. However, to what extent many genes of small effect and gene-environment interactions contribute to variations in school myopia within populations remains to be established. There are promising optical and pharmacological interventions for preventing the development of myopia or slowing its progression, which require further validation, and promising vision-sparing treatments for pathological myopia.

 
Major Breakthrough In Macular Degeneration Research PDF Print E-mail
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Ophthalmology and Optometry
Friday, 04 May 2012

University of Kentucky researchers, led by Dr. Jayakrishna Ambati, have made a major breakthrough in the “dry” form of age-related macular degeneration known as geographic atrophy (GA). GA is an untreatable condition that causes blindness in millions of individuals due to death of retinal pigmented epithelial cells. The paper, "DICER1 loss and Alu RNA Induce Age-Related Macular Degeneration via the NLRP3 Inflammasome and MyD88," was published in the April 26 online edition of the premier journal Cell.

Ambati, professor of physiology, and professor and vice chair of ophthalmology and visual sciences at University of Kentucky, is a leader in the field of macular degeneration research. Previous research from the Ambati laboratory published in the journal Nature showed that in human eyes with geographic atrophy there is a deficiency of the enzyme DICER1, leading to accumulation of toxic Alu RNA molecules in the retinal pigmented epithelium. The Cell paper shows that when these RNAs build up in the eye they trigger activation of an immune complex known as the NLRP3 inflammasome. In turn, this leads to the production of a molecule known as IL-18, which causes death of retinal pigmented epithelial cells and vision loss by activating a critical protein known as MyD88.

Importantly, Ambati and colleagues found evidence that activity of the inflammasome, IL-18, and MyD88 were all increased in human eyes with GA. They then showed that blocking any of these components could prevent retinal degeneration in multiple disease models. The researchers are excited that blocking these pathways could herald a new potential therapy for GA, for which there is no approved treatment.

 
Caffeine May Offer Relief To Dry Eye Sufferers By Boosting Tear Production PDF Print E-mail
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Ophthalmology and Optometry
Monday, 23 April 2012

Researchers at the University of Tokyo's School of Medicine have shown for the first time that caffeine intake can significantly increase the eye's ability to produce tears, a finding that could improve treatment of dry eye syndrome. This common eye condition affects about four million people age 50 and older in the United States. For many, dry eye syndrome is simply uncomfortable and annoying, but for others it escalates into a vision-threatening disease. All of the 78 participants in the new study produced significantly more tears after consuming caffeine than after taking a placebo. The study is available online in Ophthalmology, the journal of the American Academy of Ophthalmology.

Dry eye syndrome involves malfunction of the rate of tear production, the quality of tears, and/or the rate of evaporate from the surface of the eye. Anyone can experience dry eye, though it is more common among women. Symptoms can include gritty, scratchy or burning sensations, excessive tearing, and/or production of stringy mucus.

The research team, by Reiko Arita, MD, PhD, was motivated by an earlier study that had shown a reduced risk for dry eye in caffeine users: 13 percent of users had the syndrome compared with nearly 17 percent of non-users. The team knew that caffeine was likely to stimulate tear glands, since it is known to increase other secretions, such as saliva and digestive juices. They also knew that people respond differently to caffeine, so they analyzed study participants' DNA samples for two genetic variations that play important roles in caffeine metabolism. Tear production proved to be higher in study subjects who had the two genetic variations.

"If confirmed by other studies, our findings on caffeine should be useful in treating dry eye syndrome," said Dr. Arita. "At this point, though, we would advise using it selectively for patients who are most sensitive to caffeine's stimulating effects." The study subjects were divided into two groups: one received caffeine tablets in the first session and a placebo in the second session, while the order was reversed for the other group. Tear volume was measured within 45 minutes of consuming the tablets. All sessions took place between 10 a.m. and noon, a time of day when tear production is usually stable. No subjects knew whether they received caffeine or the placebo. All abstained from caffeine use for six days prior to each session and used no drugs during the sessions. To be eligible for the study subjects had to be free of high blood pressure, dry eye syndrome, allergies that affect the eye, glaucoma, and other eye diseases and conditions that can interfere with tear production. The study also found that tear drainage rates were not affected by caffeine.

 
Corneal Thickness Linked to Early Stage Fuchs Endothelial Corneal Dystrophy PDF Print E-mail
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Ophthalmology and Optometry
Wednesday, 18 April 2012

Corneal Thickness MeasurementA US national consortium of researchers has published new findings that could change the standard of practice for those treating Fuchs’ Endothelial Corneal Dystrophy (FECD), a disease characterized by cornea swelling that can eventually lead to the need for corneal transplantation. The Fuchs’ Endothelial Corneal Dystrophy Genetics Multi-Center Study Group, led by co-principal investigators Jonathan Lass, MD, Charles I Thomas Professor and chair, Case Western Reserve University Department of Ophthalmology and Visual Sciences and director, University Hospitals Eye Institute, and Sudha Iyengar, PhD, professor, Departments of Epidemiology and Biostatistics, Genetics, and Ophthalmology, Case Western Reserve University School of Medicine, found that changes in the corneal thickness occur in patients at early stages of FECD even before swelling is observed in the clinical setting. Their study is published in the journal Archives of Ophthalmology.

This new evidence suggests that FECD patients should have the thickness of their corneas measured annually to monitor progression of the disease. The disease affects the eye’s endothelial cells or the back cell layer of the cornea, which maintains the cornea’s normal thickness. However, as the disease advances, it was believed at its earlier stages the cornea remained clear and its thickness did not change. This study shows that the cornea in fact experiences a gradual swelling and becomes progressively thicker. Patients typically see an ophthalmologist only when the swelling becomes critical and the surface becomes swollen and the vision blurs. This study suggests ophthalmologists use ultrasonic technology to measure the potential progressive thickening of the cornea to assist in counseling patients on early surgical intervention before scarring develops and interferes with visual recovery.

“It’s important if you have the disease, to be checked regularly and have your thickness measured. In the short term, if your vision is decreasing, an ophthalmologist can determine whether it is coming from your cornea or a concurrent cataract and that would assist a surgeon in intervening earlier with either cataract surgery, corneal transplantation, or continuing monitoring of the disease’s progression,” says Dr. Lass. “In the long term, it might be a way of determining drug intervention based on an individual’s gene set, which may be causing the disease.”

FECD is the most common reason for corneal transplantation in the United States. The disease usually becomes apparent on examination at its earlier stages in the 40s and 50s with visual impairment developing in the 60s and 70s. In addition, while the disease is more common in women than men and does have some familial heredity, it does occur sporadically. The study group is working to identify the genes that cause the disease.

 
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