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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.

 
Scientists Find the Brain Works to Minimize Loss of Vision PDF
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Ophthalmology and Optometry
Tuesday, 18 August 2015

Glaucoma is a neurodegenerative disease where patients lose seemingly random patches of vision in each eye. This random pattern of vision loss is in stark contrast to loss from a brain tumor or stroke, which causes both eyes to develop blind spots in the same location. Scientists have long thought that glaucoma’s progression is independent of – or uncontrolled by – the brain.

Last year, researchers found evidence that the progression of glaucoma is not random and that the brain may be involved after all. Specifically, they found patients with moderate to severe glaucoma maintained vision in one eye where it was lost in the other — like two puzzle pieces fitting together (a “Jigsaw Effect”). “This suggests some communication between the eyes must be going on and that can only happen in the brain,” explains the study’s lead author, William Eric Sponsel, MD, of the University of Texas at San Antonio, Department of Biomedical Engineering. 

In the latest Translational Vision Science & Technology (TVST) paper, Refined Frequency Doubling Perimetry Analysis Reaffirms Central Nervous System Control of Chronic Glaucomatous Neurodegeneration, Sponsel and his research team found that the Jigsaw Effect begins at the earliest stages of glaucoma and discovered clues as to which part of the brain is responsible for optimizing vision in the face of glaucoma’s slow destruction of sight.

However, these findings, which challenge longstanding assumptions about glaucoma, have been met with skepticism. Other glaucoma experts challenged the results in a letter to the TVST editor. “If the brain controls the distribution of vision loss in glaucoma, then a patient’s vision with their two eyes should be better than if you simply ‘mix and match’ the vision of right and left eyes from different patients,” explained letter co-author Paul Artes, PhD, of Plymouth University, Department of Eye and Visual Sciences. Along with co-author Jonathan Denniss, PhD, University of Nottingham, Visual Neuroscience Group, their letter analyzed a new cohort of glaucoma patients in which “that’s essentially what we did. And we did not find any visual advantage in a patient’s own eyes versus the combined vision in eyes from different patients; indeed we found the opposite effect.”

Sponsel and co-authors responded to the letter to the editor with their own. “Our analysis of the data [Artes and Denniss] introduced demonstrated conclusively that the ‘Jigsaw Effect’ was indisputably present in patients we had never even seen. Moreover, we were able to confirm that the alternative analytical method they proposed could not reliably detect very obvious computer-generated complementary visual field pairs,” like a left and right eye that could only see opposite halves of their normal field of vision, says Sponsel. “The problem with their approach was their assumption that a single brain could somehow combine information from the eyes of different human beings. We studied individual people with naturally paired eyeballs connected to a single brain.”

The key to finding where the brain coordinates vision loss was found in small-scale, arc-shaped patterns of vision displayed by patients. Co-author Ted Maddess, PhD, of the Australian National University, Center of Excellence in Vision Science, explains that these patterns mimic structures found at the very back of the brain, known as ocular dominance columns. While their function is not completely understood, what is known is that some ocular dominance columns are associated with the left eye and other columns with the right.

The new paper suggests that the narrow spaces between ocular dominance columns associated with the left and right eye are where the brain coordinates each eye’s working field of vision. Depending on what the brain needs, those narrow spaces can function with either eye “much like a bilingual person living near the border of two countries,” explains Sponsel. 

 
Japanese Researchers Develop Glasses That Block Facial Recognition PDF
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Ophthalmology and Optometry
Monday, 10 August 2015

Privacy VisorResearchers of The National Institute of Informatics in Japan have developed glasses that help users protect their privacy by blocking facial-recognition systems. The glasses, called Privacy Visor, created by the government-affiliated institute and an eyeglass maker in Japan’s Fukui prefecture, uses unique angles and patterns on its lens that reflect or absorb light. This prevents the recognition systems in digital cameras and smartphones from spotting a human face in a shot and focusing on it.

"The Privacy Visor is the world’s first product with this technology," the institute's Professor Isao Echizen told Japan Real Time. Mr. Echizen, who led the research, said his goal was to protect the privacy of individuals in a world where cameras and smartphones can automatically focus on people's faces without them knowing, and where such images are shared widely on social networks. "We are often told not to unveil our personal information to others, but our faces are also a type of an ID. There should be a way to protect that," he said.

Tests with cameras on smartphones showed that the eyeglasses were able to trick the facial-recognition system 90% of the time. The researchers have attached a novel material to the visors that confuses facial recognition systems by absorbing and reflecting light.

The glasses offer enough visibility for people to walk without trouble, but it may cause difficulty in driving or riding a bicycle. But Prof. Echizen said that the Privacy Visor is designed for use in crowded areas where others could be taking photos, and that drivers aren’t likely to require them while in their cars.

The glasses could also prevent security cameras from recording the face of a person, but Prof. Echizen said that its harm is limited since police investigations rely on other information as well to identify a person.

 
Less Is More When Treating Rare Eye Condition: Study PDF
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Ophthalmology and Optometry
Thursday, 06 August 2015

Dr Jaspreet RayatNew research from the University of Alberta's Faculty of Medicine & Dentistry in Canada is showing less is more when it comes to the treatment of optic disc pits, a rare eye condition.

Optic disc pits affect about one in every 10,000 people. Patients are born with a deformity in the back of the eye that looks similar to a pit, which allows fluid inside the eye to slip underneath the retina, decreasing vision.

In the study, published ahead of print in the journal Retina, the researchers reviewed the records of optic disc pit patients from centres in Edmonton, Calgary, Vancouver and London, Ontario, Canada, to compare the effectiveness of surgical techniques used to treat the condition. Currently, most surgeons perform a vitrectomy, in which the jelly inside the eye is removed and replaced with another fluid, allowing the passageway from the optic disc pit to close and begin healing. In addition, many surgeons also perform two other procedures concurrently—injecting gas into the eye, and using laser surgery around the pit.

Dr. Jaspreet Rayat, lead author of the study and an ophthalmology resident working at Edmonton’s Royal Alexandra Hospital says the study shows using multiple procedures simultaneously is not only unnecessary, but also potentially harmful. In the majority of cases, Rayat says, the vitrectomy alone will be enough for most patients, reducing both potentially harmful side-effects and recovery time.

 
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