No Link Found Between Genetic Risk Factors and Two Top Wet AMD Treatments

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Posted on 22nd February 2013 by Pacific ClearVision Institute in General |Retina

New findings from a landmark clinical trial show that although certain gene variants may predict whether a person is likely to develop age-related macular degeneration (AMD), a potentially blinding eye disease that afflicts more than nine million Americans, these genes do not predict how patients will respond to Lucentis™ and Avastin™, the two medications most widely used to treat the “wet” form of AMD. This new data from the Comparison of AMD Treatment Trials (CATT), published online in Ophthalmology, the journal of the American Academy of Ophthalmology, found no significant association between four gene variants and outcomes that measured the patients’ responses to treatment.

The CATT genetics research team wanted to learn whether the major AMD risk genes could be useful in tailoring treatment with Avastin and Lucentis to individual patients’ needs to boost treatment effectiveness and safety for patients. The main CATT study had confirmed that both medications significantly reduce or even reverse vision loss in many patients with wet AMD, but that study also found that treatment effectiveness varied among patients. The CATT genetics study, led by Stephanie Hagstrom, Ph.D., at the Cole Eye Institute at the Cleveland Clinic, clearly showed that the major AMD risk alleles do not predict patients’ response to treatment.

This genetics study cohort comprised 73 percent of the 1,149 CATT participants. Cohort patients were evaluated for four gene variants linked to AMD risk: CFH, ARMS2, HTRA1, and C3. The patients’ genotypes were then compared to their responses to treatment with Lucentis or Avastin. Both medications are anti-vascular epithelial growth factor (anti-VEGF) therapies that work in similar ways to reduce or prevent abnormal blood vessel growth and leakage. The researchers found no significant associations among the four gene variants and the outcomes that measured the patients’ responses to treatment, which were improvement or loss of visual acuity, the status of the retinal anatomy, and the number of medication injections given.

“Our genetic research team remains hopeful that gene variants that predict patient response to AMD treatments will be identified soon,” said Dr. Hagstrom. “This would enable a significant leap forward in ophthalmologists’ ability to individualize treatment and care plans for their patients.”

The main CATT study was a multi-center clinical trial that was funded by the National Institutes of Health and led by Daniel F. Martin, M.D., Chairman of the Cole Eye Institute at the Cleveland Clinic. The study compared Lucentis and Avastin for effectiveness and safety in treating the wet form of AMD.

The findings of the CATT genetic study lend further weight to the American Academy of Ophthalmology’s 2012 recommendation on the use of genetic testing . This study assessed the same four major gene variants that are most widely used in current AMD genetic tests and found that the treatment response in patients who carried the gene variants was no better or worse than in patients who did not. The Academy advises against routine genetic testing for AMD and other complex eye disorders until specific treatment or monitoring strategies have been shown in clinical trials to be of benefit to people with specific, risk-linked genotypes.

Wet AMD, also called neovascular AMD, can severely damage vision if not treated in time. About 10 percent of patients suffer from the wet form, in which abnormal blood vessels grow underneath the retina, the tissue at the back of the eye that is crucial to good vision. These vessels leak fluid or blood, which blurs or distorts the central vision that enables people to read, recognize faces, drive, and perform other daily activities. Scientists now think that about half of all cases of AMD are related to specific genes.

New Genes for Short-Sightedness: 24 New Genes That Cause Refractive Errors and Myopia Identified

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Posted on 22nd February 2013 by Pacific ClearVision Institute in General |Retina

An international team of scientists led by King’s College London has discovered 24 new genes that cause refractive errors and myopia (short-sightedness).

Myopia is a major cause of blindness and visual impairment worldwide, and currently there is no cure. These findings, published February 10 in the journal Nature Genetics, reveal genetic causes of the trait, which could lead to finding better treatments or ways of preventing the condition in the future.

Thirty per cent of Western populations and up to 80 per cent of Asian people suffer from myopia. During visual development in childhood and adolescence the eye grows in length, but in myopes it grows too long, and light entering the eye is then focused in front of the retina rather than on it. This results in a blurred image. This refractive error can be corrected with glasses, contact lenses or surgery. However, the eye remains longer, the retina is thinner, and this may lead to retinal detachment, glaucoma or macular degeneration, especially with higher degrees of myopia. Myopia is highly heritable, although up to now, little was known about the genetic background.

To find the genes responsible, researchers from Europe, Asia, Australia and the United States collaborated as the Consortium for Refraction and Myopia (CREAM). They analysed genetic and refractive error data of over 45,000 people from 32 different studies, and found 24 new genes for this trait, and confirmed two previously reported genes. Interestingly, the genes did not show significant differences between the European and Asian groups, despite the higher prevelance among Asian people. The new genes include those which function in brain and eye tissue signalling, the structure of the eye, and eye development. The genes lead to a high risk of myopia and carriers of the high-risk genes had a tenfold increased risk.

It was already known that environmental factors, such as reading, lack of outdoor exposure, and a higher level of education can increase the risk of myopia. The condition is more common in people living in urban areas. An unfavourable combination of genetic predisposition and environmental factors appears to be particularly risky for development of myopia. How these environmental factors affect the newly identified genes and cause myopia remains intriguing, and will be further investigated by the consortium.

Professor Chris Hammond from the Department of Twin Research and Genetic Epidemiology at King’s College London, and lead author of the paper, said: ‘We already knew that myopia — or short-sightedness — tends to run in families, but until now we knew little about the genetic causes. This study reveals for the first time a group of new genes that are associated with myopia and that carriers of some of these genes have a 10-fold increased risk of developing the condition.

‘Currently myopia is corrected with glasses or contact lenses, but now we understand more about the genetic triggers for the condition we can begin to explore other ways to correct it or prevent progression. It is an extremely exciting step forward which could potentially lead to better treatments or prevention in the future for millions around the world.’

Currently, possibilities to reduce progression of myopia are very limited. While one drug, called atropine, may reduce progression, it dilates the pupil and causes problems with light sensitivity and difficulty with reading. New options are necessary. Chances are good that the insights gained from this study will provide openings for development of new strategies.

FDA Approves First Retinal Implant for Adults With Rare Genetic Eye Disease

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Posted on 22nd February 2013 by Pacific ClearVision Institute in General

The U.S. Food and Drug Administration today approved the Argus II Retinal Prosthesis System, the first implanted device to treat adult patients with advanced retinitis pigmentosa (RP). The device, which includes a small video camera, transmitter mounted on a pair of eyeglasses, video processing unit (VPU) and an implanted retinal prosthesis (artificial retina), replaces the function of degenerated cells in the retina (a membrane inside the eye) and may improve a patient’s ability to perceive images and movement. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the retinal prosthesis.

RP is a rare genetic eye condition that damages the light-sensitive cells that line the retina. In a healthy eye, these cells change light rays into electrical impulses and send them through the optic nerve to the area of the brain that assembles the impulses into an image. In people with RP, the light-sensitive cells slowly degenerate resulting in gradual loss of side vision and night vision, and later of central vision. The condition can lead to blindness.

“This new surgically implanted assistive device provides an option for patients who have lost their sight to RP — for whom there have been no FDA-approved treatments,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health. “The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities.”

The Argus II system is intended for use in adults, age 25 years or older, with severe to profound RP who have bare light perception (can perceive light, but not the direction from which it is coming) or no light perception in both eyes, evidence of intact inner layer retina function, and a previous history of the ability to see forms. Patients must also be willing and able to receive the recommended post-implant clinical follow-up, device fitting, and visual rehabilitation.

In addition to a small video camera and transmitter mounted on the glasses, the Argus II Retinal Prosthesis System has a portable video processing unit (VPU) and an array of electrodes that are implanted onto the patient’s retina. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the electrodes. The electrodes transform the data into electrical impulses that stimulate the retina to produce images. While the Argus II Retinal Prosthesis System will not restore vision to patients, it may allow them to detect light and dark in the environment, aiding them in identifying the location or movement of objects or people.

The FDA approved the Argus II Retinal Prosthesis System as a humanitarian use device, an approval pathway limited to those devices that treat or diagnose fewer than 4,000 people in the United States each year. To obtain approval for humanitarian use, a company must demonstrate a reasonable assurance that the device is safe and that its probable benefit outweighs the risk of illness or injury. The company also must show that there is no comparable device available to treat or diagnose the disease or condition.

The FDA reviewed data that included a clinical study of 30 study participants with RP who received the Argus II Retinal Prosthesis System. Investigators monitored participants for adverse events related to the device or to the implant surgery and regularly assessed their vision for at least two years after receiving the implant.

Results from the clinical study show that most participants were able to perform basic activities better with the Argus II Retinal Prosthesis System than without it. Some of the activities tested included locating and touching a square on a white field; detecting the direction of a motion; recognizing large letters, words, or sentences; detecting street curbs; walking on a sidewalk without stepping off; and matching black, grey and white socks.

Following the implant surgery, 19 of the 30 study patients experienced no adverse events related to the device or the surgery. Eleven study subjects experienced a total of 23 serious adverse events, which included erosion of the conjunctiva (the clear covering of the eyeball), dehiscence (splitting open of a wound along the surgical suture), retinal detachment, inflammation, and hypotony (low intraocular pressure).

Three government organizations provided support for the development of the Argus II. The Department of Energy, National Eye Institute at the National Institutes of Health and the National Science Foundation collaborated to provide grant funding totaling more than $100 million, support for material design and other basic research for the project.

Study Aims to Use Stem Cells to Help Save Sight of Diabetes Sufferers

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Posted on 22nd February 2013 by Pacific ClearVision Institute in General

Scientists at Queen’s University Belfast are hoping to develop a novel approach that could save the sight of millions of diabetes sufferers using adult stem cells.

Currently millions of diabetics worldwide are at risk of sight loss due to a condition called Diabetic Retinopathy. This is when high blood sugar causes the blood vessels in the eye to become blocked or to leak. Failed blood flow harms the retina and leads to vision impairment and if left untreated can lead to blindness.

The novel REDDSTAR study (Repair of Diabetic Damage by Stromal Cell Administration) involving researchers from Queen’s Centre for Vision and Vascular Science in the School of Medicine, Dentistry and Biomedical Sciences, will see them isolating stem cells from donors, expanding them in a laboratory setting and re-delivering them to a patient where they help to repair the blood vessels in the eye. This is especially relevant to patients with diabetes were the vessels of the retina become damaged.

At present there are very few treatments available to control the progression of diabetic complications. There are no treatments which will improve glucose levels and simultaneously treat the diabetic complication.

The €6 million EU funded research is being carried out with NUI Galway and brings together experts from Northern Ireland, Ireland, Germany, the Netherlands, Denmark, Portugal and the US.

Professor Alan Stitt, Director of the Centre for Vision and Vascular Science in Queen’s and lead scientist for the project said: “The Queen’s component of the REDDSTAR study involves investigating the potential of a unique stem cell population to promote repair of damaged blood vessels in the retina during diabetes. The impact could be profound for patients, because regeneration of damaged retina could prevent progression of diabetic retinopathy and reduce the risk of vision loss.

“Currently available treatments for diabetic retinopathy are not always satisfactory. They focus on end-stages of the disease, carry many side effects and fail to address the root causes of the condition. A novel, alternative therapeutic approach is to harness adult stem cells to promote regeneration of the damaged retinal blood vessels and thereby prevent and/or reverse retinopathy.”

“This new research project is one of several regenerative medicine approaches ongoing in the centre. The approach is quite simple: we plan to isolate a very defined population of stem cells and then deliver them to sites in the body that have been damaged by diabetes. In the case of some patients with diabetes, they may gain enormous benefit from stem cell-mediated repair of damaged blood vessels in their retina. This is the first step towards an exciting new therapy in an area where it is desperately needed.”

The research focuses on specific adult stem-cells derived from bone-marrow. Which are being provided by Orbsen Therapeutics, a spin-out from the Science Foundation Ireland-funded Regenerative Medicine Institute (REMEDI) at NUI Galway.

The project will develop ways to grow the bone-marrow-derived stem cells. They will be tested in several preclinical models of diabetic complications at centres in Belfast, Galway, Munich, Berlin and Porto before human trials take place in Denmark.

Queen’s Centre for Vision and Vascular Science is a key focus of the University’s ambitious £140m ‘together we can go Beyond’ fundraising campaign. It is due to expand its Vision Sciences programme further when the University’s new £32m Wellcome-Wolfson Centre for Experimental Medicine opens in 2015. Along with vision, two new programmes in Diabetes and Genomics will also be established in the new Centre which is set to stimulate additional investment, lead to further global collaborations and create more opportunities for new health and biotech companies in Northern Ireland.

Zebrafish May Hold the Answer to Repairing Damaged Retinas and Returning Eyesight to People

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Posted on 22nd February 2013 by Pacific ClearVision Institute in General |Retina

Zebrafish, the staple of genetic research, may hold the answer to repairing damaged retinas and returning eye-sight to people.

University of Alberta researchers discovered that a zebrafish’s stem cells can selectively regenerate damaged photoreceptor cells.

Lead U of A researcher Ted Allison says that for some time geneticists have known that unlike humans, stem cells in zebrafish can replace damaged cells involved in many components of eyesight. Rods and cones are the most important photoreceptors. In humans, rods provide us with night vision while cones give us a full colour look at the world during the day-time.

What was not known says Allison was whether stem cells could be instructed to only replace the cones in its retina. This could have important implications for human eyesight.

“This is the first time in an animal research model that stem cells have only repaired damaged cones,” said Allison. “For people with damaged eyesight repairing the cones is most important because it would restore day-time colour vision.

The researchers say that to date almost all success in regenerating photoreceptor cells has been limited to rods not cones. Most of these previous experiments were conducted on nocturnal rodents, animals that require good night vision so they have far more rods than cones.

“This shows us that when cones die in a cone-rich retina, it is primarily cones that regenerate,” said Allison. “This suggests the tissue environment provides cues to instruct stem cell how to react.”

The researchers say this shows some hope for stem cell therapy that could regenerate damaged cones in people, especially in the cone-rich regions of the retina that provide daytime/colour vision.

Allison says the next step for his team is to identify the particular gene in zebrafish gene that activates repair of damaged cones.

Color Vision: Explaining Primates’ Red-Green Vision

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Posted on 22nd February 2013 by Pacific ClearVision Institute in General

Our eyes are complicated organs, with the retina in the back of the eyeball comprising hundreds of millions of neurons that allow us to see, and to do so in color. Scientists have long known that some retinal ganglion cells — neurons connecting the retina to the rest of the brain — are tuned to specific wave-lengths of light (colors). In humans and other primates they are excited by red and inhibited by green, for example. An important question is: how are these “color-opponent” cells wired to discriminate wavelengths so that we perceive colors?

Scientists in the lab of Thomas Euler, professor at the Werner Reichardt Centre for Integrative Neu-roscience and the Institute for Ophthalmology at the University of Tübingen, have been working on the problem of retinal color processing for several years. Their article in the journal Neuron shows that whether or not ganglion cells become color-opponent depends on the chromatic preference of the light-sensitive photoreceptor cells in the vicinity. The research looked at mice, which have a striking distribution of photoreceptors across their retina, with a green-sensitive upper half and blue-sensitive lower half. This differs from most mammals, yet they are an excellent model system for studying important aspects of mammalian color processing.

Researchers found that when stimulated with light, ganglion cells that have never before been implicated in color vision become color-opponent if they are located close to the border between the green- and the blue-dominated retina halves, but nowhere else. Their findings show that color vision can arise from neural circuits in the retina that are not specifically “wired” for color processing.

Although these findings were made in mice, they represent an important contribution to our understanding of color processing in humans and other primates, which are considered the color specialists among the mammals. Such random wiring has long been proposed for primate red-green color vision, which resulted from a gene duplication event that occurred quite recently on an evolutionary time scale — possibly leaving not enough time for a specific neural circuit to evolve. The new findings support this idea and suggest more similarities in the general principles of color discrimination in mice and primates than previously thought.