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AMD Cure Steps Closer with New Stem Cell Trial PDF
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Ophthalmology and Optometry
Friday, 02 October 2015

AMDSurgeons in the UK have successfully transplanted eye cells derived from stem cells behind the retina of a patient with wet age-related macular degeneration in the London Project to Cure Blindness. The London Project to Cure Blindness, which was established 10 years ago with the aim of curing vision loss in patients with wet AMD, and is the result of a partnership between the Moorfields Eye Hospital, the UCL Institute of Ophthalmology, and the National Institute for Health Research (NIHR). In 2009, Pfizer Inc. joined the partnership with the goal of helping to turn the original idea into a potential therapy.

The trial is investigating the safety and efficacy of transplanting eye cells (retinal pigment epithelium) derived from stem cells to treat people with sudden severe visual loss from wet AMD. These cells are used to replace those at the back of the eye that are diseased in AMD. This is done using a specially engineered patch inserted behind the retina in an operation lasting one to two hours.

The first surgery was successfully performed on a patient last month and there have been no complications to date. The patient wishes to remain anonymous, but the team hope to determine her outcome in terms of initial visual recovery by early December 2015.

“There is real potential that people with wet age-related macular degeneration will benefit in the future from transplantation of these cells,” says retinal surgeon Professor Lyndon Da Cruz from Moorfields Eye Hospital, who is performing the operations and is co-leading the London Project.

The trial will recruit 10 patients in total over a period of 18 months. Each patient will be followed for a year to assess the safety and stability of the cells and whether there is an effect in restoring vision.

Professor Pete Coffey of the UCL Institute of Ophthalmology, who is also co-leading the London Project, said: “We are tremendously pleased to have reached this stage in the research for a new therapeutic approach. Although we recognise this clinical trial focuses on a small group of AMD patients who have experienced sudden severe visual loss, we hope that many patients may benefit in the future.”

Professor Sir Peng Tee Khaw, Director of the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital and the UCL Institute of Ophthalmology, added: “We are delighted to be the site for this very exciting new clinical trial in stem cell therapy, which has the potential to give hope and make such a difference to the lives of people with blinding retinal conditions,”.

Professor Philip J Luthert, Director of the UCL Institute of Ophthalmology, said: “The trial has shown the power of collaboration between the University, Moorfields Eye Hospital NHS Foundation Trust and Pfizer in establishing a new treatment paradigm for AMD. The London Project has been funded by large philanthropic donations, government funding agencies, charities, the NIHR and many private donors over the past few years, and Pfizer’s commitment has been vital in moving this project forward.”

Dr Berkeley Phillips, UK Medical Director, Pfizer Ltd concluded: “At Pfizer we believe that great science comes through collaboration; no one person has all the answers and together, we can achieve more and move faster. Stem cell-derived therapy was only a theory until recent years, and to be part of a project that is applying the latest scientific breakthroughs to help restore patients’ eyesight is truly rewarding”

Retinal Changes Offer Clues about Brain Pathology of Schizophrenia PDF
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Ophthalmology and Optometry
Monday, 14 September 2015

SchizophreniaTracking changes in the eye’s retina may help doctors provide more effective treatment for people with schizophrenia, according to researchers at Rutgers University and Mount Sinai’s New York Eye and Ear Infirmary.

A link between vision problems and schizophrenia is well established, with as many as 62 percent of adult patients with schizophrenia experiencing visual distortions involving form, motion or color. Researchers reported on and summarized multiple, replicated indicators of eye abnormalities in schizophrenia in a literature review published online in the journal Schizophrenia Research: Cognition.

They described a widening of small blood vessels in the eyes of schizophrenia patients, and in young people at high risk for the disorder, perhaps caused by chronic low oxygen supply to the brain – which they said could explain vision changes and signal disease risk and progression. They also found a thinning of the retinal nerve fiber layer, known to be related to the onset of hallucinations and visual acuity problems in patients with Parkinson’s disease.

“Our analysis of many studies suggests that measuring retinal changes may help doctors in the future to adjust schizophrenia treatment for each patient,” said study co-author Richard B. Rosen, director of ophthalmology research, New York Eye and Ear Infirmary of Mount Sinai, and an ophthalmology professor at the Icahn School of Medicine at Mount Sinai. “More studies are needed to drive the understanding of the contribution of retinal and other ocular pathology to disturbances seen in these patients, and our results will help guide future research.”

Abnormalities in the way the brain processes visual information contribute to the difficulties people with schizophrenia have with social interactions and in recognizing what is real. That makes it harder for them to track moving objects, perceive depth, draw contrast between light and dark or different colors, organize visual elements into shapes and recognize facial expressions, according to previous research. One past study also found that poorer visual acuity at age 4 predicted a diagnosis of schizophrenia in adulthood, and another that children who later develop schizophrenia have elevated rates of strabismus, or misalignment of the eyes, compared to the general population.

Rosen and co-author Steven M. Silverstein, director of the division of schizophrenia research at Rutgers University Behavioral Health Care and Robert Wood Johnson Medical School Department of Psychiatry, examined the results of approximately 170 existing studies. They grouped the findings into multiple categories, including changes in the retina compared with those in other parts of the eye, and changes related to dopamine compared with those related to other neurotransmitters, key brain chemicals associated with the disease.

Interestingly, the analysis uncovered no reports of people with schizophrenia who were born blind, suggesting that congenital blindness may completely or partially protect against the development of schizophrenia. Because congenitally blind people tend to have cognitive abilities in certain domains (such as attention) that are superior to those of sighted individuals, understanding brain re-organization after blindness may have implications for designing cognitive remediation interventions for people with schizophrenia.

“The retina develops from the same tissue as the brain,” Rosen said. “Thus retinal changes may parallel or mirror the integrity of brain structure and function. When present in children, these changes may suggest an increased risk for schizophrenia in later life. Additional research is needed to clarify these relationships, with the goals of better predicting emergence of schizophrenia, and of predicting relapse and treatment response and people diagnosed with the condition.”

In addition, the research found abnormal electrical responses by retinal cells exposed to light (as measured by electroretinography), suggesting possible cellular-level differences in the eyes of schizophrenia patients. 

Certain Gene Leads to Nearsightedness When Children Read PDF
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Ophthalmology and Optometry
Wednesday, 09 September 2015

Children playing outsideVision researchers at Columbia University Medical Center in U.S. have discovered a gene that causes myopia, but only in people who spend a lot of time in childhood reading or doing other “nearwork.” Using a database of approximately 14,000 people, the researchers found that those with a certain variant of the gene – called APLP2 – were five times more likely to develop myopia in their teens if they had read an hour or more each day in their childhood. Those who carried the APLP2 risk variant but spent less time reading had no additional risk of developing myopia.

“We have known for decades that myopia is caused by genes and their interactions with environmental factors like reading and nearwork, but we have not had hard proof. This is the first known evidence of gene-environment interaction in myopia,” says the study’s lead investigator, Andrei Tkatchenko, MD, PhD, of CUMC. The research was published August 27 in PLOS Genetics.

Though a drug or gene therapy to prevent myopia may be years away, Dr. Tkatchenko says spending time outdoors is the best way to reduce kids’ risk of developing myopia. “We pretty much know all the environmental risk factors: time spent reading increases the risk, while time spent outdoors reduces it,” Dr. Tkatchenko says.

Peripheral Lesions in Retina Point to Risks of Progression PDF
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Ophthalmology and Optometry
Tuesday, 01 September 2015

For decades, clinicians have detected and monitored diabetic eye disease with standard retinal photographs that cover about a third of the retina. In recent years, an emerging class of ultrawide field (UWF) cameras has given a substantially larger view of the retina, providing new insight on the presentation and natural history of retinal disease. Investigators at the Joslin Diabetes Center in the U.S. now have shown that eyes with diabetic retinal lesions predominantly in peripheral areas of the retina that are seen in UWF images but not in traditional retinal photographs show surprisingly higher risks of progressing to advanced stages of vision-threatening diabetic retinopathy.

If these results are confirmed in a larger trial, they will help to change how diabetic eye disease is evaluated and treated, says Paolo Silva, M.D., staff ophthalmologist and assistant chief of telemedicine at Joslin's Beetham Eye Institute.

The Joslin study began with 100 people with diabetes who had participated in an earlier trial to validate the agreement between UWF images and ETDRS photography in determining the presence and severity of diabetic retinopathy. Observations in this initial study showed that peripheral diabetic retinal lesions are present in over a third of patients and increased the severity of retinopathy in 10 percent of eyes. Based on these initial observations, a follow-up prospective study was conducted in which the initial validation study participants were asked to return for retinal imaging after four years.

This follow-up study demonstrated that eyes with predominantly peripheral diabetic retinopathy lesions during the initial study had more than a three-fold increased risk of retinopathy progression. These eyes also had almost a five-fold increased risk of progression to proliferative diabetic retinopathy, the most advanced form of the disease. The findings held true even after the researchers adjusted for a patient's diabetes type, diabetes duration, average blood glucose levels and other measures.

The Joslin team was not surprised that lesions in the retinal periphery might affect the likelihood of disease progression. "What was a big surprise is how much of a risk this added and how much of the disease was found outside of the area we've traditionally evaluated," says Lloyd Paul Aiello, M.D., Ph.D., Director of the Beetham Institute, Professor of Ophthalmology at Harvard Medical School and senior author on the paper.

A related trial run by the Diabetic Retinopathy Clinical Research Network, which will follow more than 350 diabetes patients across the United States with UWF imaging for at least four years, is now underway.

If the results of the Joslin study are confirmed by this larger study, they will bring major changes for clinical care and research--likely changing the system for rating disease progression in diabetic retinopathy, which is a leading cause of blindness in working-age people.

While UWF devices are in use for regular patient exams in many eye centers and eye clinics, their adoption has been slowed by relatively large size and high cost, with prices in the ballpark of $100,000. Aiello notes, however, that a tabletop UWF system is now available, and he hopes that equipment pricing will drop over time.

Wider adoption of UWF imaging also might have major implications for the telemedicine programs run by Joslin and many other institutions around the world, which aid treatment for underserved populations with diabetes. Many of these efforts already use UWF systems to generate images that are then interpreted by doctors at a remote center. The systems can acquire high-resolution images very rapidly. These high-quality images are more readily evaluated and analyzed more efficiently by experts than conventional ETDRS photos, Silva says.

In addition to studying peripheral retinal lesions in the clinic, Joslin scientists are looking for the causes of the lesions, with one likely suspect being a failure of blood flow in the affected regions. Better understanding of the underlying mechanisms could help improve the ability to judge each patient's risks and eventually lead to interventions "that help prevent vision loss in a more effective or more easily delivered manner than we have today," Aiello says.

Gut Microbes Linked to Major Autoimmune Eye Disease PDF
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Ophthalmology and Optometry
Friday, 28 August 2015

One major cause of human blindness is autoimmune uveitis, which is triggered by the activation of T cells, but exactly how and where the T cells become activated in the first place has been a long-standing mystery. A study published August 18 in the journal Immunity reveals that gut microbes produce a molecule that mimics a retinal protein, which most likely activates the T cells responsible for the disease. By shedding light on the cause of autoimmune uveitis in mice, the study could contribute to a better understanding of a broad range of autoimmune disorders and pave the way for novel prevention strategies in the future.

"Given the huge variety of commensal bacteria, if they can mimic a retinal protein, it is conceivable that they could also mimic other self-proteins that are targets of inappropriate immune responses elsewhere in the body," says senior study author Rachel Caspi of the National Institutes of Health. "We believe that activation of immune cells by commensal bacteria may be a more common trigger of autoimmune diseases than is currently appreciated."

Autoimmune uveitis, which accounts for up to 15% of severe visual handicap in the Western world, affects the working-age population and significantly affects public health. Patients often have detectable immune responses to unique retinal proteins involved in visual function, and these proteins can elicit the disease in animal models. However, these observations present a paradox: because of the blood-retinal barrier, retinal proteins remain sequestered within the healthy eye and cannot reach T cells in the rest of the body, and T cells cannot enter the eye unless they have already been activated by the retinal proteins or similar antigens. Therefore, it has remained a mystery how and where the T cells become activated and cause the disease.

One potential clue came from studies showing that gut microbes are important for the development and activation of T cells that have been linked to autoimmune uveitis. Moreover, gut microbes contribute to a range of autoimmune diseases, and in particular there have been anecdotal reports that uveitis is reactivated after bacterial infections. Based on these findings, Caspi and her team reasoned that gut microbes could be the culprits behind uveitis.

To test this idea, the researchers examined natural triggers of the disease by using a mouse model that spontaneously develops uveitis. Before the clinical onset of uveitis, the intestines of these mice showed high numbers of activated T cells. Treatment with antibiotics reduced numbers of these T cells in the gut and delayed and attenuated the development of the disease in the mice. Moreover, bacteria-rich protein extracts from the gut contents of these mice activated retina-specific T cells, making them capable of breaching the blood-retinal barrier to enter the eye and cause uveitis. Taken together, the findings provide compelling evidence that gut microbes activate the T cells that cause uveitis, and they offer a novel mechanism explaining how a tissue-specific autoimmune disease can arise from responses to gut microbes at a distal site in the body.

Caspi and her team are now trying to identify specific bacteria that could produce the protein mimicking the retinal antigen in their animal model of uveitis. They will also look for additional signals that could contribute to the activation of disease-causing immune cells. "Bioinformatic analyses combined with biological tests will help us to reach this goal, but there is still much work to be done," Caspi says. If researchers are able to identify the bacteria and signals that activate the retina-specific T cells, she says. "we may be able in the future to use this knowledge to selectively eliminate the responses that lead to the development of this disease."

Researchers Develop Insect Eye for Drones PDF
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Ophthalmology and Optometry
Friday, 21 August 2015

Insect EyesInspired by the compound eyes of fruit flies, a team of researchers from EPFL (Ecole polytechnique fédérale de Lausanne) in Switzerland has developed an artificial eye that allows robots to detect and avoid obstacles. From E-textiles to cars, the potentials applications are numerous.

Small insects seem to possess a sixth sense that allows them to dodge any threats. Yet there is no magic trick, but only a compound eye that is an organ of vision made of thousands of ommatidia. These visual receptors allow insects to perceive precisely their environment, including the direction and speed of movements. Inspired by this natural model, the EPFL team, headed by Dario Floreano, has developed an artificial compound eye, described in a recent publication of Interface, a journal of the Royal Society.

The compound eyes of flies have many interesting properties. Each ommatidium is slightly offset from its neighbors, allowing the brain to collect and compare the information produced by the set of visual sensors. Insects can thus accurately perceive their environment and detect movement, even in dark places. All without spending a lot of energy.

These advantages have led several research teams to develop an artificial compound eye. Specifically, the sensor consists of three hexagonal photodetectors arranged in a triangular shape, covered with a single lens. The artificial eye is capable of operating the focus and to adapt to the ambient light. These three detectors, slightly offset, then send information to the microprocessor. Based on this flow, it will establish a summary map of the surrounding environment. "One must not imagine that this is a high quality image, explain Ramón Pericet Cámara, the project coordinator, it is only a three pixels picture." This figure may seem far too low, but it is sufficient for the artificial eye to detect surrounding objects and their motion vector. Better yet, the device also notices stationary objects through their relative velocity.

Despite measuring only 1925 * 475 * 860 microns (1 micron = 0.001 mm) and weighing only 2 mg, the electronic eye is capable of recording 300 frames per second, three times more than that of the fly. Moreover, it does not just capture the optical flow: it processes it directly and converts it from analog into digital.

Such an eye has ideal attributes for equipping an unmanned aerial vehicle. "One of the project goals was to develop a sensor for very small drones”, says Ramón Pericet Cámara. “To be relatively autonomous, these flying robots must be able to detect and avoid their surroundings. The biggest challenge was to miniaturize all the components", he added. Like its animal counterpart, the electronic eye is very energy efficient. It may also be attached on all sorts of structures, whether rigid, soft, planar or curved.

All these advantages open the way to multiple applications. Beyond its integration into drones built for rescue or surveillance tasks, the artificial eye could be used in many other sectors. For instance, EPFL teams are currently developing a connected cap to help the blind: visual sensors detect obstacles and guide the wearer via a system of vibrations. It is also possible to imagine automotive applications, either to optimize the operation of unmanned cars or prevent collisions.

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