Vessel damage may precede diabetic retinopathy, researchers find

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Posted on 1st May 2016 by Pacific ClearVision Institute in General |Retina

A University of Iowa-led study of diabetes-related vision impairment holds good news — and some bad news — for patients with signs of these disorders.

Scientists have long known that patients with diabetes mellitus — both Type 1 and Type 2 — are at high risk for developing diabetic retinopathy, the most common cause of irreversible blindness in adults. Vision loss occurs due to microvascular damage to the retina. People with diabetes are typically not aware that they are also at risk for developing retinal diabetic neuropathy, a loss of the nerve cells in the retina.

For many years, scientists believed patients developed retinopathy and, as a result of the damage to the blood vessels, later developed neuropathy. Doctors were focusing on early detection and treatment of retinopathy to prevent blindness, which they thought would then prevent the damage caused by neuropathy.

In this new study, however, researchers discovered that the sequence of events occurring in the retina due to diabetes is just the opposite of these long-held beliefs.

“What we’re finding here, unfortunately, is that the nerve damage actually does come first, before the vessel damage,” says Michael Abramoff, MD, PhD, UI professor in the Department of Ophthalmology and Visual Sciences and a member of the Stephen A. Wynn Institute for Vision Research, and senior author on the study. “Even people with diabetes who never get retinopathy can still develop this damage, and after many years, damage may be severe, similar to glaucoma.”

The study appears online the week of April 25, 20916 in the journal PNAS.

“Essentially, the order of damage in the retina from diabetes is different from what we originally thought, and preventing the effects of retinopathy by itself would not protect the nerves in the retina,” says Elliott Sohn, MD, UI associate professor in the Department of Ophthalmology and Visual Sciences and a member of the Stephen A. Wynn Institute for Vision Research, and first author on the study.

In the study, Sohn and Abramoff with their colleagues from the UI and the University of Amsterdam studied 45 people with diabetes and little to no diabetic retinopathy over a four-year span. They found “significant, progressive loss of the nerve fiber and ganglion cell layer,” proof of damage to the nerves before vascular changes typically found in the retina from diabetes.

At the same time, researchers found corresponding thinning of the nerve fiber layer in six donor eyes from patients with diabetes and little to no diabetic retinopathy, and the layer was considerably thinner than the layer in six donor eyes from patients who did not have diabetes. Similar results were found in diabetic mouse models in this study.

The good news, Abramoff says, is that better understanding of the sequence of damage may lead to new treatments that focus on preventing the nerve damage, and thereby hopefully also preventing retinopathy.

Gene therapy shows long-term benefit for treating rare blindness

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Posted on 1st May 2016 by Pacific ClearVision Institute in General |Retina

Pioneering gene therapy has restored some vision to patients with a rare form of genetic blindness for as long as four years, raising hopes it could be used to cure common causes of vision loss, new University of Oxford research published today shows.

A technique which involves injecting a virus into the eye to deliver billions of healthy genes to replace a key missing gene for choroideremia sufferers has provided sustained improvement in vision for up four years for some patients.

This provides the strongest evidence so far in humans that the effects of gene therapy are potentially permanent and could therefore provide a single treatment cure for many types of inherited blindness. These include retinitis pigmentosa, which affects young people, and age-related macular degeneration, which affects the older age group.

Reporting the results this week in the New England Journal of Medicine, doctors from the University of Oxford examined the vision of six patients up to four years after receiving gene therapy at Oxford’s John Radcliffe Hospital. These six were the first in the world to have the procedure for choroideremia in a trial funded by the Department of Health and the Wellcome Trust.

The gene therapy treatment was designed to slow or stop sight loss, however, two of the patients experienced a significant improvement in vision that was sustained for at least four years, despite a decline in their untreated eyes over this period. A further three maintained their vision in their treated eyes throughout this period. The sixth patient who had a lower dose had a slow decline in vision in both eyes.

It is hoped that gene therapy would ideally be applied to patients early in the disease process to prevent sight loss because the treatment is expected to be long lasting. Patients with choroideremia are missing a key gene in their retina and the technique involves injecting a virus to deliver billions of healthy genes to replace the missing gene.

Professor Robert MacLaren, the lead investigator of the study, said: “There have recently been questions about the long term efficacy of gene therapy, but now we have unequivocal proof that the effects following a single injection of viral vector are sustained. Even sharpening up the little bit of central vision that these patients have can give them considerable independence.

“Gene therapy is a new technique in medicine that has great potential. As we learn more about genetics we realise that correcting faulty genes even before a disease starts may be the most effective treatment. Gene therapy uses the infectious properties of a virus to insert DNA into a cell, but the virial DNA is removed and replaced with DNA that is reprogrammed in the lab to correct whichever gene is faulty in the patient.

“In this case, success in getting a treatment effect that lasts at least several years was achieved because the viral DNA had an optimal design and the viral vector was delivered into the correct place, using advanced surgical techniques. In brief, this is the breakthrough we have all been waiting for.”

Dr Stephen Caddick, Director of Innovation at the Wellcome Trust, added: “To permanently restore sight to people with inherited blindness would be a remarkable medical achievement.

“This is the first time we’ve seen what appears to be a permanent change in vision after just one round of treatment. It’s a real step forwards towards an era where gene therapy is part of routine care for these patients.”

Jonathan Wyatt, the first patient in the world to be treated with this gene therapy is still sight impaired, but he was able to double the level of vision in his treated left eye, which has been maintained for four years so far.

The retired barrister, 68, of Bristol, suffered vision problems since the age of 20. The right eye has continued to degenerate and the left eye is now dominant.

Mr Wyatt, married to Diana, for nearly 30 years, could read 23 letters in eye chart tests prior to the operation but by three-and-a-half years could read 44.

Mr Wyatt said: “I feel very lucky, privileged and honoured to be part of the fantastic John Radcliffe research group. I feel that even though I am the meat in a sandwich, my life will be making a contribution to help others.”

“The left eye is much improved to such an extent that I use it mostly to get about these days. It has substantially improved, it is fantastic.

“It has made me more independent, I think I would be more dependent. I think I would feel more cautious about train journeys on my own. Without it I think I would be tapping with a white stick, I think I would have remained cheerful but I would be at home more.”

Joe Pepper, a 24-year-old teacher from Croydon, who was the last patient to receive the gene therapy treatment (not in the original cohort of six), said: “I sat down and began the reading chart test on my treated right eye and I read the first two lines and for the first time in my memory I read on and on.

“I will remember that day for the rest of my life. I could see more than before the operation. I could read four lines beyond where I was earlier. I laughed and shed a tear. It was special.

“Six months on from the surgery the results have been more than I ever imagined. My vision now has a new found clarity and I am no longer putting stress on my vision when reading or looking into the distance. Instead of looking into the distance and seeing outlines of people or trees I am seeing their defined features. At night I now have a new found confidence in dimly lit areas that means I can feel independent and safe after dark.

“Without Professor MacLaren and his team, and their pioneering work I could have lost my sight and for the last 14 years I have feared I could. The work they do is special and I have nothing but thanks to them.”

Surprising central role of darks in brain visual maps

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Posted on 1st May 2016 by Pacific ClearVision Institute in General |Retina

Scientists have been studying how visual space is mapped in the cerebral cortex for many decades under the assumption that the map is equal for lights and darks. Surprisingly, recent work demonstrates that visual brain maps are dark-centric and that, just as stars rotate around black holes in the Universe, lights rotate around darks in the brain representation of visual space. The work was done by Jens Kremkow and collaborators in the laboratories of Jose Manuel Alonso at the State University of New York College of Optometry and will be published in the May 5, 2016 issue of Nature. A similar result will be reported in the same issue of Nature by Kuo-Sheng Lee et al. in the laboratories of David Fitzpatrick at the Max Planck Florida Institute for Neuroscience.

The primary visual cortex is the area of the cerebral cortex with the most detailed representation of visual space and the main recipient of eye inputs coming through the visual thalamus. In the first description of its functional architecture, Hubel and Wiesel demonstrated that the cortical map of visual space coexisted with other maps for eye input and stimulus orientation. Neurons responding to inputs from the left and right eyes segregated in visual cortex forming a map of alternating stripes that resembled a zebra pattern. Neurons responding to similar stimulus orientations also clustered forming a map with a pinwheel pattern that was discovered later by other scientists. More recent work also found additional maps for stimulus features related with motion and depth. However, while the maps for visual space and eye input were thought to originate from the segregation of thalamic afferents in visual cortex, the origin of the other maps remained unclear.

The work of Kremkow and colleagues indicates that the organization of all maps originates from the same principle: an arrangement of thalamic afferents that minimizes differences in spatial position, eye input and light/dark polarity among neighboring cortical neurons. Moreover, they show that the organization of visual space, for both monocular and binocular vision, is more precise for darks than lights. As a consequence of the greater spatial mapping of darks, a 0.5 x 0.5 mm cube of visual cortex can represent the same position of a dark spot but different positions of light spots that appear to rotate around a dark anchor in visual space. This surprising dark-centric organization could be a consequence of a size distortion for lights that originates at the photoreceptor (Kremkow et al., PNAS, 2014), the very first neuron in the visual pathway. Taken together, these findings explain why visual acuity is commonly measured with dark characters on light backgrounds and why visual resolution is lower for lights, as already noted by Leonardo da Vinci and Galileo Galilei when judging the size of light objects in paintings and the dark sky.

Can an iPad help you see?

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Posted on 1st May 2016 by Pacific ClearVision Institute in General |Retina

The proportion of older adults with age-related vision loss is estimated to be as high as one in three over the age of 50. In Canada, that’s roughly 3.6 million people. Many of these individuals turn to adaptive devices designed to magnify objects and text, but these devices can be prohibitively expensive, uni-functional and bulky.

Enter the iPad: a technological device that’s relatively cheap, serves many purposes, is smaller than most books, and — according to new research from Concordia University in Montreal — is just as effective a visual aid as traditional devices.

A study recently described in Good Times Magazine provides the first experimental evidence that the Apple iPad is as good as technology traditionally used in reading rehabilitation for individuals with visual impairment.

And that could help with stigmatization of the elderly and disabled.

For the study, the Concordia-based research team recruited 100 participants who ranged in age from 24 to 97. A little over half the participants had age-related macular degeneration, a disease characterized by the deterioration of the small central portion of the retina that is normally responsible for fine detailed vision tasks such as reading.

The researchers used questionnaires and tests to gauge participants’ visual ability, and then compared the Apple iPad versus two traditionally used magnification devices, to see if reading rates varied across devices.

“Unsurprisingly, we found that most participants found it hard to read small and medium text, while nearly a quarter of them reported that reading large text was much easier,” says Elliott Morrice, an MA student in Concordia’s Department of Psychology and the study’s first author.

“What was interesting to note was that it didn’t matter what technology was used to do the magnification: an iPad worked just as well as a traditional device like a closed circuit television system (CCTV),” he says.

“When we took previous experience into account, we found that participants who had used iPads before read on average 30 words per minute faster than those who were using the iPad for the first time. But there were no significant differences in the reading rates of participants who had previous experience using the CCTV, compared to the reading rates of first-time CCTV users.”

Another benefit is that many older adults feel stigmatized by using the traditional devices, because they identify them as having an impairment or disability.

“Tablet computers offer many of the same benefits while being socially acceptable,” says Aaron Johnson, the study’s senior author, and an associate professor in the psychology department, and a member of the Centre for Interdisciplinary Research in Rehabilitation of Greater Montreal (CRIR).

“What’s more, compared to the devices currently used by those with low vision, iPads are multi-functional, allowing the user to go online, check email, make video calls — and they cost less than the traditional devices,” he says. “This cost saving can be both to the individual, and if appropriate, to the insurance companies that may provide individuals with assistive devices.”