Breakthrough in Sight for Cataract Treatment

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Posted on 18th March 2013 by Pacific ClearVision Institute in Cataracts |General

Research carried out by Professor Barbara Pierscionek and a team of fellow vision experts suggests that the way proteins are distributed in the lens of the eye may cause its gradient to be stepped rather than smooth as previously thought. The finding could give a new insight into the way the eye grows and lead to major improvements in synthetic lenses used in surgery to treat patients who have developed cataracts.

Artificial replacements did not currently match the quality of real ones, Professor Pierscionek said. “However this research could help give patients better vision if manufacturers use it to develop an improved lens able to change focus,” she explained.

Professor Pierscionek, the Associate Dean of Research and Enterprise at Kingston’s Faculty of Science, Engineering and Computing, has devoted two decades to researching the eye’s lens. Her work has explored its biochemical, optical and mechanical properties. Since the lens is one of the few organs in the body that does not replenish itself, it is a model for ageing. “The lens is the key to a lot of things – we just haven’t unlocked its full potential yet. It has the capacity to tell us what has happened to a person throughout their life and their disease state,” Professor Pierscionek said.

Cataracts can occur at any age, but often develop as people get older. In the United Kingdom, an estimated one in three people over the age of 65 is affected. Smoking and UV radiation are thought to be causes and they can also occur in people with diseases such as diabetes. The condition may gradually make vision more blurred and make it difficult to see in poor light. Treatment usually involves replacing the affected lens with an artificial one.

Professor Pierscionek’s discovery could give a new insight into the way the eye grows.Professor Pierscionek carried out much of her most recent research at Japan’s Spring-8 synchrotron facility – home of the world’s largest third generation synchrotron. It accelerates electrons close to the speed of light to generate X-rays and other beams. The electrons are injected into a storage ring 1.4km in diameter, with the resultant X-rays fed into experimental stations dotted around the site. “These X-rays can penetrate parts of the body and soft tissue better than other forms of radiation,” Professor Pierscionek said. “This allows engineers and scientists to look deeply into anything from metal to bacteria.” When taking measurements it was important to keep the sample as close as possible to its natural state, Professor Pierscionek said. “The synchrotron is so sophisticated that it allows us to measure the lenses while they are still in the eyeball.”

Some of the research has been conducted in collaboration with scientists from the Spring-8 facility and Cardiff University. It is being funded by eye research charity Fight for Sight as well as grants from Spring-8, which has provided use of the synchrotron.

Further analysis is now being carried out in laboratories at Kingston University. Professor Pierscionek and her team are working with Dr Mehdi Bahrami, a researcher funded by Fight for Sight, using ray tracing and mathematical modelling. The work involves projecting lasers of different colours through different parts of the lens to trace their paths. The information will then be used to help develop lenses with improved optical quality.

‘OK’ Contact Lenses Work by Flattening Front of Cornea, Not the Entire Cornea

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Posted on 18th March 2013 by Pacific ClearVision Institute in General |LASIK

A contact lens technique called overnight orthokeratology (OK) brings rapid improvement in vision for nearsighted patients. Now a new study shows that OK treatment works mainly by flattening the front of the cornea, reports a recent study, “Posterior Corneal Shape Changes in Myopic Overnight Orthokeratology,” appearing in the March issue of Optometry and Vision Science.

“This study appears to show that it is only, or primarily, the very front surface layers of the cornea that are altered by OK contact lens treatment,” comments Anthony Adams, OD, PhD, Editor-in-Chief of Optometry and Vision Science. The study was performed by Jeong Ho Yoon, PhD, of University of Choonhae Health Science, Ulsan, Republic of Korea, and Helen A. Swarbick, PhD, FAAO, of University of New South Wales, Sydney, Australia.

Overnight Orthokeratology Works — But How?

Orthokeratology is a clinical technique to reduce nearsightedness (myopia) using specially designed rigid contact lenses to manipulate the shape of the cornea — the transparent front part that lets light into the eye. Dr Adams likens OK therapy to orthodontic treatment using braces to change the alignment of the teeth.

He explains “Wearing these lenses overnight for about six hours is currently the treatment approach for most clinicians who use OK for the temporary correction of low to moderate myopia.” But it has been unclear exactly how OK works to reduce myopia: Do the contact lenses reshape just the front surface of the cornea, or do they bend and flatten the entire cornea?

To find out, Drs Yoon and Swarbick had 18 young adults with “low” (relatively mild) myopia wear OK lenses overnight for 14 days. Using sophisticated techniques, the researchers made detailed measurements of corneal shape and thickness before, during, and after treatment.

As in previous studies, wearing OK contact lenses led to reduced myopia, thus improving vision. The changes were significant after the first night wearing OK lenses, By 14 days, myopia was almost completely eliminated and the participants had near-normal uncorrected (without glasses) visual acuity.

Results ‘Achieved Primarily through Remodeling of Anterior Cornea’

These changes were linked to significant flattening of the anterior (front) portion of the cornea. Like the vision changes, the change in corneal shape was significant after the first night wearing OK lenses. Although corneal flattening continued throughout the 14-day treatment period, about 80 percent of the change occurred in the first four days.

In contrast, OK lenses caused only a small and temporary change in the shape of the posterior (rear) cornea, and only slight thinning of the central cornea. “Overall, our results support the current hypothesis that the OK refractive effect is achieved primarily through remodeling of the anterior corneal layers, without overall corneal bending,” according to Drs Yoon and Swarbick.

Overnight OK contact lenses provide an effective treatment for relatively mild myopia. It requires custom-made rigid contact lenses designed to accommodate the shape and desired change of the patient’s eye. While OK lenses provide an alternative to LASIK surgery for correction of myopia, the patient must continue nightly contact lens wear to maintain the improvement.

The authors hope their results “will provide a more complete picture of overall corneal changes during myopic OK.” In particular, the study demonstrates that overnight OK lenses don’t change the curvature of the posterior cornea — “at least in the first two weeks of lens wear.”

Seven Genetic Risk Factors Found to Be Associated With Common Eye Disorder

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Posted on 18th March 2013 by Pacific ClearVision Institute in General |Retina

An international group of researchers has discovered seven new regions of the human genome — called loci-that are associated with increased risk of age-related macular degeneration (AMD), a leading cause of blindness. The AMD Gene Consortium, a network of international investigators representing 18 research groups, also confirmed 12 loci identified in previous studies. The findings are reported online today in the journal Nature Genetics. Supported by the National Eye Institute (NEI), a part of the National Institutes of Health, the study represents the most comprehensive genome-wide analysis of genetic variations associated with AMD.

“This compelling analysis by the AMD Gene Consortium demonstrates the enormous value of effective collaboration,” said NEI Director Paul A. Sieving, M.D., Ph.D. “Combining data from multiple studies, this international effort provides insight into the molecular basis of AMD, which will help researchers search for causes of the disease and will inform future development of new diagnostic and treatment strategies.”

AMD affects the macula, a region of the retina responsible for central vision. The retina is the layer of light-sensitive tissue in the back of the eye that houses rod and cone photoreceptor cells. Compared with the rest of the retina, the macula is especially dense with cone photoreceptors and is what humans rely on for tasks that require sharp vision, such as reading, driving, and recognizing faces. As AMD progresses, such tasks become more difficult and eventually impossible. Some kinds of AMD are treatable if detected early, but no cure exists. An estimated 2 million Americans have AMD.

Scientists have shown that age, diet, and smoking influence a person’s risk of developing AMD. Genetics also plays a strong role. AMD often runs in families and is more common among certain ethnicities, such as people of Asian or European descent.

Since the 2005 discovery that certain variations in the gene for complement factor H — a component of the immune system — are associated with major risk for AMD, research groups around the world have conducted genome-wide association studies to identify other loci that affect AMD risk. These studies were made possible by tools developed through the Human Genome Project, which mapped human genes, and related projects, such the International HapMap Project, which identified common patterns of genetic variation within the human genome.

The AMD Gene Consortium combined data from 18 research groups to increase the power of prior analyses. The current analysis identified seven new loci near genes. As with the previously discovered 12 loci, these seven loci are scattered throughout the genome on many different chromosomes.

“A large number of samples was needed to detect additional genetic variants that have small but significant influences on a person’s disease risk,” said Hemin Chin, Ph.D., NEI associate director for ophthalmic genetics, who assembled the consortium and helped coordinate the study. “By cataloging genetic variations associated with AMD, scientists are better equipped to target corresponding biological pathways and study how they might interact and change with age or other factors, such as smoking.”

The consortium’s analysis included data from more than 17,100 people with the most advanced and severe forms of AMD, which were compared to data from more than 60,000 people without AMD. The 19 loci that were found to be associated with AMD implicate a variety of biological functions, including regulation of the immune system, maintenance of cellular structure, growth and permeability of blood vessels, lipid metabolism, and atherosclerosis.

“Like a map that identifies neighborhoods where the electricity has been knocked out by a storm, the AMD Gene Consortium’s study effectively tagged regions within the genome where researchers are most likely to find short circuits in DNA that cause AMD,” said Anand Swaroop, Ph.D., chief of the NEI Laboratory of Neurobiology and Neurodegeneration and Repair, and one of the group leaders of this consortium effort. “Once you are in the right neighborhood, going block to block or house to house to look for downed power lines goes much faster. Likewise, by limiting their search to the 19 genomic regions identified by the AMD Gene Consortium, scientists can more efficiently search for specific genes and causative changes that play a role in AMD.”

As with other common diseases, such as type 2 diabetes, an individual person’s risk for getting AMD is likely determined not by one but many genes. Further comprehensive DNA analysis of the areas around the 19 loci identified by the AMD Gene Consortium could turn up undiscovered rare genetic variants with a disproportionately large effect on AMD risk. Discovery of such genes could greatly advance scientists’ understanding of AMD pathogenesis and their quest for more effective treatments.

Turf Battle in Retina Helps Internal Clocks See the Light

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Posted on 18th March 2013 by Pacific ClearVision Institute in General |Retina

With every sunrise and sunset, our eyes make note of the light as it waxes and wanes, a process that is critical to aligning our circadian rhythms to match the solar day so we are alert during the day and restful at night. Watching the sun come and go sounds like a peaceful process, but Johns Hopkins scientists have discovered that behind the scenes, millions of specialized cells in our eyes are fighting for their lives to help the retina set the stage to keep our internal clocks ticking.

In a study that appeared in a recent issue of Neuron, a team led by biologist Samer Hattar has found that there is a kind of turf war going on behind our eyeballs, where intrinsically photosensitive retinal ganglion cells (ipRGCs) are jockeying for the best position to receive information from rod and cone cells about light levels. By studying these specialized cells in mice, Hattar and his team found that the cells actually kill each other to seize more space and find the best position to do their job.

Understanding this fight could one day lead to victories against several conditions, including autism and some psychiatric disorders, where neural circuits influence our behavior. The results could help scientists have a better idea about how the circuits behind our eyes assemble to influence our physiological functions, said Hattar, an associate professor of biology in the Krieger School of Arts and Sciences.

“In a nutshell, death in our retina plays a vital role in assembling the retinal circuits that influence crucial physiological functions such as circadian rhythms and sleep-wake cycles,” Hattar said. “Once we have a greater understanding of the circuit formation underlying all of our neuronal abilities, this could be applied to any neurological function.”

Hattar and his team determined that the killing among rival ipRGCs is justifiable homicide: Without this cell death, circadian blindness overcame the mice, who could no longer distinguish day from night. Hattar’s team studied mice that were genetically modified to prevent cell death by removing the Bax protein, an essential factor for cell death to occur. They discovered that if cell death is prevented, ipRGCs distribution is highly affected, leading the surplus cells to bunch up and form ineffectual, ugly clumps incapable of receiving light information from rods and cones for the alignment of circadian rhythms. To detect this, the researchers used wheel running activity measurements in mice that lacked the Bax protein as well as the melanopsin protein which allows ipRGCs to respond only through rods and cones and compared it to animals where only the Bax gene was deleted.

What the authors uncovered was exciting: When death is prevented, the ability of rods and cones to signal light to our internal clocks is highly impaired. This shows that cell death plays an essential role in setting the circuitry that allows the retinal rods and cones to influence our circadian rhythms and sleep.

Hattar’s study was funded by the National Institute of General Medical Sciences and the National Institute of Neurological Disorders and Stroke and was carried out in close collaboration with Rejji Kuruvilla, an associate professor who is another member of the mouse tri-lab community in the Department of Biology at Johns Hopkins.

Researchers Test Holographic Technique for Restoring Vision

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Posted on 18th March 2013 by Pacific ClearVision Institute in General |Retina

Researchers led by biomedical engineering Professor Shy Shoham of the Technion-Israel Institute of Technology are testing the power of holography to artificially stimulate cells in the eye, with hopes of developing a new strategy for bionic vision restoration.

Computer-generated holography, they say, could be used in conjunction with a technique called optogenetics, which uses gene therapy to deliver light-sensitive proteins to damaged retinal nerve cells. In conditions such as Retinitis Pigmentosa (RP) — a condition affecting about one in 4000 people in the United States — these light-sensing cells degenerate and lead to blindness.

“The basic idea of optogenetics is to take a light-sensitive protein from another organism, typically from algae or bacteria, and insert it into a target cell, and that photosensitizes the cell,” Shoham explained.

Intense pulses of light can activate nerve cells newly sensitized by this gene therapy approach. But Shoham said researchers around the world are still searching for the best way to deliver the light patterns so that the retina “sees” or responds in a nearly normal way.

The plan is to someday develop a prosthetic headset or eyepiece that a person could wear to translate visual scenes into patterns of light that stimulate the genetically altered cells.

In their paper in the Feb. 26 issue of Nature Communications, the Technion researchers show how light from computer-generated holography could be used to stimulate these repaired cells in mouse retinas. The key, they say, is to use a light stimulus that is intense, precise, and can trigger activity across a variety of cells all at once.

“Holography, what we’re using, has the advantage of being relatively precise and intense,” Shoham said. “And you need those two things to see.”

The researchers turned to holography after exploring other options, including laser deflectors and digital displays used in many portable projectors to stimulate these cells. Both methods had their drawbacks, Shoham said.

Digital light displays can stimulate many nerve cells at once, “but they have low light intensity and very low light efficiency,” Shoham said. The genetically repaired cells are less sensitive to light than normal healthy retinal cells, so they preferably need a bright light source like a laser to be activated.

“Lasers give intensity, but they can’t give the parallel projection” that would simultaneously stimulate all of the cells needed to see a complete picture, Shoham noted. “Holography is a way of getting the best of both worlds.”

The researchers have tested the potential of holographic stimulation in retinal cells in the lab, and have done some preliminary work with the technology in living mice with damaged retinal cells. The experiments show that holography can provide reliable and simultaneous stimulation of multiple cells at millisecond speeds.

But implementing a holographic prosthesis in humans is far in the future, Shoham cautioned.

His team is exploring other ways, aside from optogenetics, to activate damaged nerve cells. For instance, they are also experimenting with ultrasound for activating retinal and brain tissue.

And Shoham said holography itself “also provides a very interesting path toward three-dimensional stimulation, which we don’t use so much in the retina, but is very interesting in other projects where it allow us to stimulate 3-D brain tissue.”

In mid-February, the U.S. Food and Drug Administration approved the first artificial retina and retinal prosthesis, which works in a different fashion than the Technion project. The FDA-approved device, the Argus II, uses an artificial “retina” consisting of electrodes, and a glasses-like prosthesis to transmit light signals to the electrodes.

“I think Shy’s lab is very smart to pursue many methods of restoring vision,” said Eyal Margalit, a retinal disease specialist at the University of Nebraska Medical Center. He said researchers around the world are also looking for ways to use stem cells to replace damaged retinal cells, to transplant entire layers of healthy retinal cells, and in some cases “bypass the eye entirely, and stimulate the cortex of the brain directly” to restore lost vision.

Shoham’s co-authors on the paper included Dr. Inna Reutsky-Gefen, Lior Golan, Dr. Nairouz Farah, Adi Schejter, Limor Tsur, and Dr. Inbar Brosh.