FDA Approval for Argus II Retinal Prosthesis System

Staff
3/15/2013

After more than 20 years of research and development, Second Sight Medical Products announced that its Argus II Retinal Prosthesis System has received U.S. market approval from the Food and Drug Administration to treat individuals with late-stage retinitis pigmentosa. This announcement follows receipt of the European approval in 2011. (For a more extensive description of Argus II, see p. 60.)

“We are thrilled to be able to offer the only FDA-approved, long-term therapy for people suffering from advanced RP,” said Robert Greenberg, MD, PhD, president and CEO of Second Sight. “With this approval, we look forward to building a strong surgical network in the United States and recruiting new hospitals that will offer the Argus II retinal implant. This is a game-changer in sight-affecting diseases, that represents a huge step forward for the field and for these patients who were without any available treatment options until now.”

Argus II is intended to provide electrical stimulation of the retina to induce visual perception in blind individuals with retinitis pigmentosa and has the capacity to offer life-changing visual capabilities to those currently unable to see anything except, at best, extremely bright lights.

Although the resulting vision is not the same as when these patients had normal vision, investigators involved in the clinical trial of the Argus II are eager about the approval. “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. In the patients that have been implanted to date, the improvement in the quality of life has been invaluable,” said Mark Humayun, MD, PhD, Cornelius Pings Professor of Biomedical Engineering and Professor of Ophthalmology, Biomedical Engineering, Cell and Neurobiology, Keck School of Medicine of USC and USC Viterbi School of Engineering, University of Southern California.

“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, yet the promise to the patients is real and we expect it only to improve over time.”
With approval from the FDA, the Argus II is slated to be available later this year in clinical centers across the country. Second Sight will be actively adding sites to make the therapy more readily available and encourages interested facilities and patients to contact them.

The Argus II System works by converting video images captured by a miniature camera housed in the patient’s glasses into a series of small electrical pulses that are transmitted wirelessly to an array of electrodes on the surface of the retina. These pulses are intended to stimulate the retina’s remaining cells resulting in the corresponding perception of patterns of light in the brain. The patient then learns to interpret these visual patterns thereby regaining some visual function. Argus II is the only approved retinal prosthesis anywhere in the world. For more information, visit 2-sight.com.

CATT Analysis Sheds Light on AMD And Genetics
New findings from the Comparison of AMD Treatment Trials (CATT) show that although certain gene variants may predict whether a person is likely to develop age-related macular degeneration, these genes do not predict how patients will respond to Lucentis and Avastin, the two medications most widely used to treat wet AMD. This new data, published online in Ophthalmology, found no significant association between four gene variants and outcomes that measured the patients’ responses to treatment.

The CATT genetics research team wanted to learn whether the major AMD risk genes could be useful in tailoring treatment with Avastin and Lucentis to individual patients’ needs to boost treatment effectiveness and safety for patients. The main CATT study had confirmed that both medications significantly reduce or even reverse vision loss in many patients with wet AMD, but that study also found that treatment effectiveness varied among patients. The CATT genetics study, led by Stephanie Hagstrom, PhD, at the Cole Eye Institute at the Cleveland Clinic, clearly showed that the major AMD risk alleles do not predict patients’ response to treatment.

This genetics study cohort comprised 73 percent of the 1,149 CATT participants. Cohort patients were evaluated for four gene variants linked to AMD risk: CFH, ARMS2, HTRA1 and C3. The patients’ genotypes were then compared to their responses to treatment with Lucentis or Avastin. Both medications are anti-vascular epithelial growth factor therapies that work in similar ways to reduce or prevent abnormal blood vessel growth and leakage. The researchers found no significant associations among the four gene variants and the outcomes that measured the patients’ responses to treatment, which were improvement or loss of visual acuity, the status of the retinal anatomy, and the number of medication injections given.

“Our genetic research team remains hopeful that gene variants that predict patient response to AMD treatments will be identified soon,” said Dr. Hagstrom. “This would enable a significant leap forward in ophthalmologists’ ability to individualize treatment and care plans for their patients.”

The findings of the CATT genetic study lend further weight to the American Academy of Ophthalmology’s 2012 recommendation on the use of genetic testing. This study assessed the same four major gene variants that are most widely used in current AMD genetic tests and found that the treatment response in patients who carried the gene variants was no better or worse than in patients who did not. The AAO advises against routine genetic testing for AMD and other complex eye disorders until specific treatment or monitoring strategies have been shown in clinical trials to be of benefit to people with specific, risk-linked genotypes.

Altering Rods May Restore Vision
Altering the genetic program of the light-sensing cells of the eye may one day treat some forms of blindness, according to scientists at Washington University School of Medicine in St. Louis.

Working in mice with retinitis pigmentosa, the researchers reprogrammed rods, which enable night vision, making the cells more similar to cones, which sense light in the daytime and detect fine visual details. Doing so prevented degeneration of the retina. 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, Dr. 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.

In retinitis pigmentosa, the rods die first, leaving patients unable to see at night. Daytime vision often remains intact for some time until the cones also die.

Dr. Corbo and others have identified several genes that are active in rods or in cones but not in both types of photoreceptors. He wondered whether turning off a key gene that is activated only in rods could protect the cells from the loss of vision characteristic of retinitis pigmentosa.
‘”The question was, when retinitis pigmentosa is caused by a mutation in a protein only active in rods, can we reduce or stop vision loss by making the cells less rod-like?” he explains.

The new study focuses on a protein known as Nrl, which influences development of photoreceptors. Cells that make Nrl become rods, while cells that lack the protein become cones. Turning off the Nrl gene in developing mice leads to a retina packed with cone cells.
To see if this rod-to-cone change was possible in adult mice, Dr. Corbo created a mouse model of retinitis pigmentosa with an Nrl gene that could be switched on and off by scientists.

“In adult mice, switching off Nrl partially converts the rod cells into cone cells,” he says. “Several months later, when the mutant mice normally had very little vision left, we tested the function of their retina.” The test showed a healthier level of electrical activity in the retinas of mice that lacked Nrl, suggesting that the mice could still see.

Dr. Corbo now is looking for other critical development factors that can help scientists more fully transform adult rods into cones. He notes that if complete conversion of rods to cones were possible, this therapy could also be helpful for conditions where cone cells die first, such as macular degeneration.  REVIEW