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Ophthalmology and Optometry
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Study Reveals How Brain Processes Color and Motion PDF
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Ophthalmology and Optometry
Tuesday, 23 September 2014

Despite the barrage of visual information the brain receives, it retains a remarkable ability to focus on important and relevant items. How the brain accomplishes this, however, has been poorly understood. Now, University of Chicago scientists have identified a brain region that appears central to perceiving the combination of color and motion. They discovered a unique population of neurons that shift in sensitivity toward different colors and directions, depending on what is being paid attention to. The study, published Sept. 4 in the journal Neuron, sheds light on a fundamental neurological process that is a key step in the biology of attention.

"Most of the objects in any given visual scene are not that important, so how does the brain select or attend to important ones?" said study senior author David Freedman, PhD, associate professor of neurobiology at the University of Chicago. "We've zeroed in on an area of the brain that appears central to this process. It does this in a very flexible way, changing moment by moment depending on what is being looked for."

The visual cortex of the brain possesses multiple, interconnected regions that are responsible for processing different aspects of the raw visual signal gathered by the eyes. Basic information on motion and color are known to route through two such regions, but how the brain combines these streams into something usable for decision-making or other higher-order processes remained unclear.

To investigate this mechanism, Freedman and postdoctoral fellow Guilhem Ibos, PhD, studied the response of individual neurons to a simple task. Monkeys were shown a rapid series of visual images. An initial image showed either a group of red dots moving upwards or yellow dots moving downwards, which served as an instruction for which specific colors and directions were relevant during that trial. The subjects were rewarded when they released a lever when this image later reappeared. Subsequent images were composed of different colors of dots moving in different directions, among which was the initial image.

 
Scientists Develop Eye Drops to Treat Molecular Basis of Glaucoma PDF
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Ophthalmology and Optometry
Monday, 15 September 2014

Northwestern University scientists in the U.S. have discovered a novel cause of glaucoma in an animal model, and related to their findings, are now developing an eye drop aimed at curing the disease. They believe their findings will be important to human glaucoma.

A cure for glaucoma, a leading cause of blindness, has been elusive because the basis of the disease is poorly understood. In glaucoma, pressure builds from poor drainage of fluid from the anterior chamber of the eye, destroying retinal ganglion cells and eventually the optic nerve. The eye becomes like a bathtub that can’t drain because the pipe is clogged. The clogged or defective vessel, known as Schlemm’s canal, is part of the lymphatic system that is essential for drainage in the eye.

The new study for the first time identifies the molecular building blocks needed to make the 'drainage' vessels, providing the necessary chemical tools to repair the eye's plumbing and restore normal drainage. Up until now, the molecular basis of the disease caused by an absent or defective canal was unknown.

The study was published Sept. 9 in The Journal of Clinical Investigation.

 
New Target Identified For Treatment of Abnormal Blood Vessels and Leakage in Eyes PDF
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Ophthalmology and Optometry
Tuesday, 09 September 2014

Working with mice, a multicenter team of researchers has found a new way to reduce the abnormal blood vessel growth and leakage in the eye that accompany some eye diseases. The finding could lead to the development of new drugs for wet macular degeneration and diabetic macular edema.

The current standard of clinical care for wet macular degeneration and diabetic macular edema is repeated injections into the eye of antibodies against a protein called VEGF. Each injection costs thousands of dollars. This study revealed a way to indirectly mitigate the bad effects of VEGF by activating a biochemical chain of events, or pathway, that suppresses the protein.

This indirect way of reducing VEGF's effects is not as dangerous as directly blocking the protein. Antibodies that block VEGF must be injected into the eye to minimize side effects to the rest of the body, such as stroke. But a drug with the indirect action identified in this study could potentially be injected under the skin with relative safety, the researchers say. Patients could thus give themselves the drug, potentially reducing the need for frequent clinic visits and injections in the eye. The study also indicates that people with particularly severe disease may have a much better outcome if the current eye injections are combined with type of skin injections reported on in this study, the researchers say.

"We've known for several years that activating the Tie2 pathway that indirectly suppresses the effects of VEGF had great potential, and the new approach we tested in this study provides a great way to take advantage of that," says Peter Campochiaro, M.D., the George S. and Dolores D. Eccles Professor of Ophthalmology at the Johns Hopkins University School of Medicine and a faculty member at the Wilmer Eye Institute at Johns Hopkins. "This new agent not only makes blood vessels in the eye less responsive to VEGF, but it also reduces leakage caused by other proteins that are active in eye diseases."

Working with mice genetically engineered to have vascular eye diseases, the team treated some with injections into the eye of an antibody that blocks an enzyme called VE-PTP. VE-PTP normally suppresses the pathway that reduces blood vessel growth and leakage, so the net effect was to activate the pathway.

The second method involved the use of a small molecule, AKB-9778, developed by Aerpio Therapeutics, which also blocks VE-PTP. Because of its size, AKB-9778 can easily enter the eye from the bloodstream, and the indirect action appears not to carry the same risks to the body as directly blocking VEGF, Campochiaro says. "If further studies show that the small molecule is safe and effective for people, patients could give themselves an injection under the skin every day," he says. "Our studies in animals so far suggest it doesn't have major side effects." If confirmed in clinical studies, this could reduce the need for patients to come in frequently to get injections in the eye. He says AKB-9778 may have the additional benefits of stabilizing blood vessels in other parts of the body and lowering blood pressure.

An estimated 2 million people in the United States suffer from age-related macular degeneration, with the incidence expected to rise to 3.5 million by 2030 and to 5.5 million by 2050. Roughly 20 percent of patients with age-related macular degeneration suffer from abnormal blood vessel growth and vascular leakage, says Campochiaro, and so may be helped by this new therapy, if it proves to work in clinical trials. An equally large number of patients have diabetic macular edema and could also potentially benefit from the treatment. The incidence of these diseases is increasing very quickly, because our population is aging and the number of patients with diabetes is increasing so rapidly, he says.

The finding could also have implications for other diseases, Campochiaro notes, because VE-PTP is a phosphatase, a type of enzyme that had never before been blocked with therapeutic effect. Targeting other members of this common family of enzymes might also prove beneficial, he says.

The findings have been reported in the Sept. 2 issue of The Journal of Clinical Investigation.

 
Newly Developed Eye Implant Could Lead To Better Glaucoma Treatments PDF
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Ophthalmology and Optometry
Wednesday, 03 September 2014

GlaucomaFor people battling glaucoma, the main course of action for staving off blindness involves weekly visits to eye specialists who monitor and control increasing pressure within the eye. Now, a tiny eye implant developed at Stanford University could enable patients to take more frequent readings from the comfort of home. Daily or hourly measurements of eye pressure could help doctors tailor more effective treatment plans.

Internal optic pressure (IOP) is the main risk factor associated with glaucoma, which is characterized by a continuous loss of specific retina cells and degradation of the optic nerve fiber. The mechanism linking IOP and the damage is not clear, but in most patients IOP levels correlate with the rate of damage. Reducing IOP to normal or below-normal levels is currently the only treatment available for glaucoma. This requires repeated measurements of the patient's IOP until the levels stabilize. The trick with this, though, is that the readings do not always tell the truth. Like blood pressure, IOP can vary day-to-day and hour-to-hour; it can be affected by other medications, body posture or even a neck-tie that is knotted too tightly. If patients are tested on a low IOP day, the test can give a false impression of the severity of the disease and affect their treatment in a way that can ultimately lead to worse vision.

The new implant was developed as part of a collaboration between Stephen Quake, a professor of bioengineering and of applied physics at Stanford, and ophthalmologist Yossi Mandel of Bar-Ilan University in Israel. It consists of a small tube; one end is open to the fluids that fill the eye; the other end is capped with a small bulb filled with gas. As the IOP increases, intraocular fluid is pushed into the tube; the gas pushes back against this flow.

As IOP fluctuates, the meniscus, the barrier between the fluid and the gas, moves back and forth in the tube. Patients could use a custom smartphone app or a wearable technology, such as Google Glass, to snap a photo of the instrument at any time, providing a critical wealth of data that could steer treatment. For instance, in one previous study, researchers found that 24-hour IOP monitoring resulted in a change in treatment in up to 80 percent of patients. The implant is currently designed to fit inside a standard intraocular lens prosthetic, which many glaucoma patients often get when they have cataract surgery, but the scientists are investigating ways to implant it on its own.

The findings have been published in Nature Medicine.

 
DNA Testing Can Diagnose Rare Diseases Marked by Childhood Blindness PDF
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Ophthalmology and Optometry
Monday, 25 August 2014

Researchers in the United Kingdom have demonstrated that advanced DNA testing for congenital cataracts can quickly and accurately diagnose a number of rare diseases marked by childhood blindness, according to a study published in Ophthalmology, the journal of the American Academy of Ophthalmology. Using a single test, doctors were able to tailor care specifically to a child's condition based on their mutations, reducing the time and money spent on diagnosis and enabling earlier treatment and genetic counseling.

Each year, between 20,000 and 40,000 children worldwide are born with congenital cataracts, a disease that clouds the lens of the eye and often requires surgery and treatment to prevent blindness. The disease can arise following a maternal infection or be inherited as an isolated abnormality. Congenital cataracts can also appear as a symptom of more than 100 rare diseases, making mutations in the 115 genes associated with congenital cataracts useful as diagnostic markers for the illnesses.

Diagnosing these rare diseases previously proved a lengthy, costly and inconclusive process involving numerous clinical assessments and taking a detailed family history. DNA testing, one gene at a time, would have taken years to complete. Employing new DNA sequencing technology, called targeted next-generation sequencing, researchers at the University of Manchester sped up diagnosis to a matter of weeks by testing for mutations in all 115 known congenital cataracts genes at one time.

In 75 percent of the 36 cases tested, the DNA test determined the exact genetic cause of congenital cataracts. In one case, the DNA test helped diagnose a patient with Warburg Micro syndrome, an extremely rare disease that is marked by an abnormally small head and the development of severe epilepsy, among other medical issues. Having a clear diagnosis allowed for genetic counseling and appropriate care to be delivered quicker than previously possible without the test.

 
EYLEA Injection Receives FDA Approval for DME Treatment PDF
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Ophthalmology and Optometry
Wednesday, 20 August 2014

Regeneron Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has approved EYLEA® (aflibercept) Injection for the treatment of Diabetic Macular Edema (DME). The recommended dosage of EYLEA in patients with DME is 2 milligrams (mg) every two months (8 weeks) after five initial monthly injections. Although EYLEA may be dosed as frequently as 2 mg every 4 weeks, additional efficacy was not demonstrated when EYLEA was dosed every 4 weeks compared to every 8 weeks.

The approval of EYLEA in DME was based on the one-year data from the Phase 3 VISTA-DME and VIVID-DME studies of 862 patients, which compared EYLEA 2 mg given monthly, EYLEA 2 mg given every two months (after five initial monthly injections), or macular laser photocoagulation (at baseline and then as needed). In the DME studies, after one year, the mean changes in Best Corrected Visual Acuity (BCVA), as measured by the Early Treatment Diabetic Retinopathy Study (ETDRS) chart for the monthly and every two month EYLEA groups, were statistically significantly improved compared to the control group and were similar to each other. Across both trials, patients in both EYLEA dosing groups gained, on average, the ability to read approximately two additional lines on an eye chart compared with almost no change in the control group.

 
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