The U.S. Food and Drug Administration has granted approval to expand Second Sight® Medical Products’ Argus™ II Retinal Implant feasibility study. Up to 20 people in the United States who are blind or have severely impaired vision because of retinitis pigmentosa (RP), a genetic eye disease, will be able to participate. As of mid-July 2009, 30 RP patients worldwide have been implanted with the device, which incorporates advanced technologies from the U.S. Department of Energy’s (DOE) national laboratories.

In the largest visual prosthesis study to date, the Argus™ II continues to have a good safety profile. Implanted patients are using the artificial retina to successfully identify the position and approximate size of objects and detect movement of nearby objects and people. These implants also are providing subjects with sufficient vision to allow demonstrated improvement in orientation and mobility.

The Argus™ II is designed to transmit information directly to the retina of individuals about their physical surroundings, thereby bypassing photoreceptor cells that have been damaged because of RP. It consists of a 60-electrode grid that is surgically implanted and attached to the retina. The electrodes transmit information acquired from an external camera that is mounted on a pair of eyeglasses. This device has several advantages over the Argus™ I, a 16-electrode prosthesis that showed proof of concept with chronic stimulation demonstrated in 6 patients for more than 5 years. Argus™ II advantages include more stimulating electrodes and advanced image processing, and its smaller package requires less surgical time for the implant procedure. The Argus™ II underwent extensive in vivo and in vitro testing prior to clinical trials. While it is designed to last a lifetime, it can be safely removed if necessary. Further developments planned for the coming years are expected to enable reading and facial recognition.

Preliminary Results
All of the patients implanted so far with the Argus™ II system had bare light perception or worse vision before the surgery. Averaging 56.8 years, their ages range from 28 to 77 years. The median surgery time for the implant procedure in the United States is 3 hours.

Ongoing 3-year feasibility studies are testing the safety and efficacy of the device. For the 17 patients implanted with the device in the first 6 months, there have been no device failures and few serious adverse events, all of which were resolved with treatment. Such events included conjunctival erosion, hypotony, and endophthalmitis.

All 17 patients have seen phosphenes— patterns of light produced by electrical stimulation— and many are showing statistically significant improvements in orientation and mobility, spatial localization, and motion detection. They all are using the device outside the clinical setting.

Trials Enable Device Improvements
Feedback from the feasibility studies has led to several design improvements that are expected to increase the Argus™ II system’s clinical benefits. These data also have driven improvements to surgical techniques by advancing the development of an easier-to-handle device, which is making the implantation procedure more replicable.

Preclinical testing of a retinal prosthesis with more than 200 electrodes is under way and has the potential to significantly improve the visual acuity of people with RP and age-related macular degeneration. Additional research and development efforts by DOE laboratories are expected to produce artificial retinas with more than 1000 electrodes.

Hopeful First Steps Toward Meaningful Sight
The higher resolution that more advanced, 1000+ electrode prostheses potentially can provide is key to the goal of enabling reading of large print, unaided mobility, and facial recognition. To date, most of the patients with the artificial retina implants use them for orientation and large object detection. Higher-resolution implants are expected to enhance usage by allowing better vision not only for mobility, but also for object detection. With the 1000+ electrode device, patients are expected to be able to read and recognize faces.

Currently, “We’re replacing millions of photoreceptor cells with just 60 electrodes, so the corresponding vision that these patients are able to achieve is not as good as that of a normal-sighted person,” explains Elias Greenbaum, a physicist at Oak Ridge National Laboratory and a member of DOE’s artificial retina team (see box, Increasing Resolution). Consequently, continued clinical testing is crucial for further design improvements that would allow more implantees to realize the goal of near-normal sight.

“The clinical trial expansion for the Argus™ II retinal prosthesis is great news,” says Stephen Rose, chief research officer for the Foundation Fighting Blindness. “The technology holds real promise for giving some meaningful vision to people with the most advanced retinal degenerative diseases.”

And for people with severe, end-stage vision losses, the artificial retina may be the only option for restoring sight. Other potential treatments such as gene, pharmaceutical, and nutritional therapies are more appropriate for “rescuing” photoreceptor cells in the early stages of disease by halting their decline. Once those cells are lost, stem cell transplants one day might be used to replace them, but differentiating stem cells into photoreceptors poses a difficult challenge. So too does reconstructing the complex synapse and neural connections. In contrast, the retinal implant bypasses degenerated photoreceptor cells altogether and, to date, has progressed more quickly and demonstrated more success than stem cell transplants.