Lab team makes unique contributions to the first bionic eye

The Argus II will help people blinded by the rare hereditary disease retinitis pigmentosa or seniors suffering from severe macular degeneration.

As part of the multi-­institutional Artificial Retina Project, Los Alamos researchers helped develop the first bionic eye. Recently approved by the U.S. Food and Drug Administration, the Argus II will help people blinded by the rare hereditary disease retinitis pigmentosa or seniors suffering from severe macular degeneration—diseases that destroy the light-­sensing cell in the retina. Los Alamos scientists served as the Advanced Concepts team, focusing on fundamental issues and out-­of the box ideas.

Significance of the research

The Argus II operates by using a miniature camera mounted in eyeglasses that captures images and wirelessly sends the information to a microprocessor (worn on a belt) that converts the data to an electronic signal. Pulses from an electrode array against the patient’s retina in the back of the eye stimulate the optic nerve and, ultimately, the brain, which perceives patterns of light corresponding to the electrodes stimulated. Blind individuals can learn to interpret these visual patterns.

Los Alamos research achievements

The Los Alamos team examined how visual information is encoded in the pattern of electrical impulses traveling the optic nerve. The scientists developed better ways to visualize and interpret the resulting neural activity patterns when the retina is stimulated.

Using high-­performance video cameras and near-­infrared illumination, the Los Alamos team imaged tiny changes in the light scattering and birefringence properties of neural tissue that are associated with nerve electrical activity, the retina that were produced by stimulation. The team also advised the consortium on the use of compatible technologies to map the human brain function stimulated by the devices or by normal biological vision.

The Laboratory team developed  theory—supported with experimental data—of how electrical activity of nerve cells produces polarized light signals that were used to image retinal function. They created a computer model of the retina directly predicting the dynamics of retinal neurons firing as function of patterns of stimulation. They also created theoretical models of the response of nerve cells to electrical stimulation, which suggest new strategies to stimulate patterns of neural activity with higher resolution and a greater specificity, useful to a wider range of individuals with visual impairment.

The need to improve the retina and electronics interface was the largest technical recording and stimulating arrays, and developed new techniques for coating electrode arrays that might enable advanced neural interfaces in the future, with many more channels and greater tolerance for the challenging environment of electronics implanted in biological tissue.

About the Artificial Retina Project

The DOE Artificial Retina Project is a multi-­institutional collaborative effort to develop and implant a device containing an array of microelectrodes into the eyes of people blinded by retinal disease. The ultimate goal is to design a device to help restore limited vision that enables reading, unaided mobility and facial recognition.

The 10-­year project involved researchers from DOE national laboratories (Argonne, Lawrence Livermore, Los Alamos, Oak Ridge, and Sandia), universities (Doheny Eye Institute at the University of Southern California, California Institute of Technology, North Carolina State University, University of Utah, and the University of California—Santa Cruz), and private industry (Second Sight Medical Products, Inc.). Members of the Los Alamos artificial retina team include team leader John George and members Garrett Kenyon, Michael Ham, Xin-­cheng Yao, David Rector, Angela Yamauchi, Beth Perry, Benjamin Barrows, Bryan Travis, Andrew Dattelbaum, Jurgen Schmidt, James Maxwell and Karlene Maskaly.

The DOE Office of Science funded the Los Alamos portion of the Artificial Retina Project. Laboratory Directed Research and Development (LDRD), the National Institutes of Health and the National Science Foundation have sponsored different aspects of basic R&D on neuroimaging, computational modeling and analysis of neural function, and materials and fabrication techniques that enabled the Los Alamos role in this project. The work supports the Lab’s Global Security mission area and the Science of Signatures and Information, Science, and Technology science pillars.

What It’s Like to See Again with an Artificial Retina

Elias Konstantopoulos gets spotty glimpses of the world each day for about four hours, or for however long he leaves his Argus II retina prosthesis turned on. The 74-year-old Maryland resident lost his sight from a progressive retinal disease over 30 years ago, but is able to perceive some things when he turns on the bionic vision system.

“I can see if you are in front of me, and if you try to go away,” he says. “Or, if I look at a big tree with the system on I can maybe see some darkness and if it’s bright outside and I move my head to the left or right I can see different shadows that tell me there is something there. There’s no way to tell what it is,” says Konstantopoulos.

A spectacle-mounted camera captures image data for Konstantopoulos; that data is then processed by a mini-computer carried on a strap and sent to a 60-pixel neuron-stimulating chip that was implanted in one of his retinas in 2009.

Nearly 70 people around the world have undergone the three-hour surgery for the retinal implant, which was developed by California’s Second Sight and approved for use in Europe in 2011 and in the U.S. earlier this year (see “Bionic Eye Implant Approved for U.S. Patients”). It is the first vision-restoring implant sold to patients.

Currently, the system is only approved for patients with retinitis pigmentosa, a degenerative eye condition that strikes around one in 5,000 people worldwide, but it’s possible the Argus II and other artificial retinas in development could work for those with age-related macular degeneration, which affects one in 2,000 people in developed countries. In these conditions, the photoreceptor cells of the eye (commonly called rods and cones) are lost, but the rest of the neuronal pathway that communicates visual information to the brain is often still viable. Artificial retinas depend on this remaining circuitry, so cannot work for all forms of blindness.

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Bionic eye maker has vision of the future

Robert Greenberg got tired of hearing from senior engineers that it wasn’t possible to build his product idea: a bionic eye that gives sight to the blind.

"A lot of the folks straight out of school didn’t know any better, so I hired them instead," quipped Greenberg, chief executive of Second Sight Medical Products Inc., a Sylmar biotech company. "They didn’t know how hard it was going to be, that it was impossible. And so they tried."

Greenberg can laugh now that he once thought developing the device would take a year and $1 million. Some 20 years and $200 million later, the first bionic eye has helped more than 20 European patients regain some of their sight.

Called the Argus II Retinal Prosthesis System, the device recently was approved by the Food and Drug Administration. Second Sight, which has 100 employees, is allowed to sell the bionic eye system to patients in the U.S. with advanced retinitis pigmentosa, a degenerative eye disease that can cause blindness.

"We are a far cry from restoring 20/20 vision," said Brian V. Mech, Second Sight’s vice president of business development, who holds a doctorate in materials science and an MBA from the UCLA Anderson School of Management.

"We are taking blind people back up to low vision, and that is pretty significant."

Mech likes to show videos of once-sightless patients who, after receiving the retinal prosthesis, are able to follow a person walking down the street and discern a street curb without using their canes.

"Until our product, these patients had no other option to obtain the ability to see," Mech said of the $100,000 device, part of which rests on a pair of Oakley Inc. sunglass frames. The cost to European patients has been paid by insurance companies in most cases.

Palo Alto attorney Dean Lloyd, who lost his vision 17 years ago, got the bionic eye system as part of the U.S. testing process. It allows him to see “boundaries and borders, not images” but has had a profound effect on his life.

Lloyd cites an incident before he received the eye system that still rankles. In the middle of a courtroom trial, an opposing attorney said Lloyd didn’t stand a chance with his case because he couldn’t even keep his socks straight: Lloyd had mixed up his black, courtroom socks with his white athletic ones.

"What did I do after the surgical procedure that I hadn’t been able to do?" Lloyd said. "I went home and sorted all of my socks."

The story of how the bionic eye came to be made in Sylmar underscores the state’s long record of medical device advances and involves top university researchers who were brought to Southern California to work on the project.

Greenberg likened the degree of difficulty to “shrinking a television set to the size of a pea, then throwing it into the ocean and expecting it to work.”

For Greenberg, it began in the early 1990s when he was a doctoral candidate in the Department of Biomedical Engineering at Johns Hopkins University in Baltimore.

Some of the first work was being done there, testing patients who had lost their vision because of retinitis pigmentosa, to see if electrically stimulating their retinas would produce results. It did.

"Using one electrode, the patient saw one spot of light," Greenberg said. "Second electrode, and the patient was seeing two spots of light. During that experiment, I was hooked."

Greenberg said he thought: “This is just engineering. Put more spots and you could make more pixels, like lights on a scoreboard or pixels on your computer monitor. You could see images.”

There was a breakthrough of another sort a few years later, in Washington. There, Greenberg was working as a medical officer and a lead reviewer for the FDA’s Office of Device Evaluation when he met entrepreneur Alfred E. Mann.

Mann had already established himself as a medical device developer through Mannkind Corp. and several other Southern California companies. During the 1980s, the self-made billionaire founded Pacesetter Systems, which made cardiac pacemakers. From there, he moved on to insulin pumps and related equipment.

Another Mann-funded company, Advanced Bionics Corp., took on cochlear implants, which could restore hearing to the deaf. It was the electrode-based cochlear implant that formed the rough basis of Second Sight’s first bionic eye.

In 1998, Second Sight opened with the financial backing of Mann and Sam Williams, another successful entrepreneur whose company, Williams International, designed and built small, efficient turbofan jet engines.

"Sam Williams was blind from retinitis pigmentosa, the disease that we are treating," Mech said. "He had invested along with Al in Advanced Bionics, which restores hearing for deaf people, and they were already on the market in the ’90s. Sam said to Al, ‘Why can’t we do the same for blind people?’"

Retinal implant wins FDA approval

The U.S. Food and Drug Administration (FDA) approved the Argus II retinal prosthesis system for use in the United States.

Mark Humayun, who holds joint appointments at the Keck School of Medicine of USC and the USC Viterbi School of Engineering, was a key member of the team that developed the device, which will be available to qualified patients at the Keck Medical Center of USC.

The Argus II, which received a unanimous recommendation for approval by the FDA’s Ophthalmic Devices Advisory Panel in September, restores some visual capabilities for patients whose blindness is caused by Retinitis Pigmentosa (RP), an inherited retinal degenerative disease that affects about 100,000 people nationwide.

“It is incredibly exciting to have FDA approval to begin implanting the Argus II and provide some restoration of vision to patients blinded from RP,” said Humayun, Cornelius Pings Professor of Biomedical Sciences and professor of ophthalmology, biomedical engineering, cell and neurobiology at USC. “In the patients that have been implanted to date, the improvement in the quality of life has been invaluable.

“The fact that many patients can use the Argus implant in their activities of daily living, such as recognizing large letters, locating the position of objects and more, has been beyond our wildest dreams,” Humayun added, “yet the promise to the patients is real, and we expect it only to improve over time.”

The Argus II, which is manufactured by Sylmar, Calif.-based Second Sight, was approved for use in Europe in 2011 and has been implanted in 30 patients in a clinical trial that began in 2007. Humayun performed many of the surgeries to implant the device.

The FDA approval paves the way for Second Sight to build a surgical network in the United States to implant the device, as well as to recruit hospitals to offer it, according to Robert Greensburg, president and CEO of the company.

The Argus II system uses a camera mounted on special glasses that sends a signal to an electronic receiver with 60 electrodes implanted inside the eye.

The receiver sends signals to the retina that travel through the optic nerve to the brain, where they can be interpreted as a visual picture. The researchers hope that one day the device can be improved to also help individuals with age-related macular degeneration, a similar but far more common disease.

Public inquiries regarding the Argus II can be directed to the Second Sight public information line at (855) 756-3703.

As the Argus II retinal implant is refined, it will be housed in the USC Institute of Biomedical Therapeutics. The new $60 million endowed interdisciplinary institute will bring together scientists, engineers and clinicians from around the world to study neural networks to develop bioelectronic solutions for the millions of people impacted by traumatic brain injury, stroke and debilitating eye diseases.

Altering eye cells may one day restore vision

Doctors may one day treat some forms of blindness by altering the genetic program of the light-sensing cells of the eye, according to scientists at Washington University School of Medicine in St. Louis.

Working in mice with retinitis pigmentosa, a disease that causes gradual blindness, the researchers reprogrammed the cells in the eye that enable night vision. The change made the cells more similar to other cells that provide sight during daylight hours and prevented degeneration of the retina, the light-sensing structure in the back of the eye. The scientists now are conducting additional tests to confirm that the mice can still see.

“We think it may be significantly easier to preserve vision by modifying existing cells in the eye than it would be to introduce new stem cells,” says senior author Joseph Corbo, MD, PhD, assistant professor of pathology and immunology. “A diseased retina is not a hospitable environment for transplanting stem cells.”

The study is available in the early online edition of Proceedings of the National Academy of Sciences.

Mutations in more than 200 genes have been linked to various forms of blindness. Efforts are underway to develop gene therapies for some of these conditions.

Rather than seek treatments tailored to individual mutations, Corbo hopes to develop therapies that can alleviate many forms of visual impairment. To make that possible, he studies the genetic factors that allow cells in the developing eye to take on the specialized roles necessary for vision.

Totally blind mice get sight back

Totally blind mice have had their sight restored by injections of light-sensing cells into the eye, UK researchers report. The team in Oxford said their studies closely resemble the treatments that would be needed in people with degenerative eye disease. Similar results have already been achieved with night-blind mice.

Experts said the field was advancing rapidly, but there were still questions about the quality of vision restored. Patients with retinitis pigmentosa gradually lose light-sensing cells from the retina and can become blind. The research team, at the University of Oxford, used mice with a complete lack of light-sensing photoreceptor cells in their retinas. The mice were unable to tell the difference between light and dark.

Reconstruction

They injected “precursor” cells which will develop into the building blocks of a retina once inside the eye. Two weeks after the injections a retina had formed, according to the findings presented in the Proceedings of the National Academy of Sciences journal. Prof Robert MacLaren said: “We have recreated the whole structure, basically it’s the first proof that you can take a completely blind mouse, put the cells in and reconstruct the entire light-sensitive layer.”

Previous studies have achieved similar results with mice that had a partially degenerated retina. Prof MacLaren said this was like “restoring a whole computer screen rather than repairing individual pixels”. The mice were tested to see if they fled being in a bright area, if their pupils constricted in response to light and had their brain scanned to see if visual information was being processed by the mind.

Vision

Prof Pete Coffee, from the Institute of Ophthalmology at University College London, said the findings were important as they looked at the “most clinically relevant and severe case” of blindness. “This is probably what you would need to do to restore sight in a patient that has lost their vision,” he said.

However, he said this and similar studies needed to show how good the recovered vision was as brain scans and tests of light sensitivity were not enough. He said: “Can they tell the difference between a nasty animal and something to eat?”

Prof Robin Ali published research in the journal Nature showing that transplanting cells could restore vision in night-blind mice and then showed the same technique worked in a range of mice with degenerated retinas. He said: “These papers demonstrate that it is possible to transplant photoreceptor cells into a range of mice even with a severe level of degeneration. “I think it’s great that another group is showing the utility of photoreceptor transplantation.”

Researchers are already trialling human embryonic stem cells, at Moorfields Eye Hospital, in patients with Stargardt’s disease. Early results suggest the technique is safe but reliable results will take several years.

Retinal chips or bionic eyes are also being trailed in patients with retinitis pigmentosa.