CLINICAL TRIAL SPOTLIGHT

Rods, Cones, and Prosthesis

With the Argus Retinal Prosthesis System, a company is testing an implant for retinitis pigmentosa.

ANDREW E. MATHIS, PhD, MEDICAL EDITOR

Argus Panoptes was the giant from Greek mythology who had 100 eyes and was thus able to see everything. Conversely, for people with retinitis pigmentosa, one of the more common forms of inherited macular degenerative disease, vision becomes compromised over time, sometimes leading to total vision loss.

Second Sight Medical Products, Inc., of Sylmar, CA, has developed an ocular implant that shares a name with the mythical Greek giant. And while the Argus II Retinal Prosthesis System may not offer 100 eyes with which to see, it may offer hope to patients with retinitis pigmentosa for whom other therapies have not worked. Rajat Agrawal, MD, assistant professor of research at the Doheny Eye Institute at the University of Southern California and an investigator in Second Sight's phase 2 trial of the device, spoke with Retinal Physician and explained how the implant works and what promise it may hold for patients with inherited retinal disease.

"The Argus II Retinal Prosthesis System consists of an external portion and an active implantable medical device," Dr. Agrawal said. "The external portion of the system consists of a tiny camera and transmitter mounted in glasses, while the implanted portion consists of a receiver and an electrode-studded array that is secured to the epiretinal surface of the retina by a microtack. A video processor and battery pack worn on the belt power the entire device."

The glasses work within the system by capturing images and sending them to the video processor, which converts them to electronic signals and sends them to the transmitter, Dr. Agrawal explained. "The implanted receiver wirelessly receives these data and sends the signals through a tiny cable to the electrode array, causing it to emit electrical stimulation pulses. The pulses are intended to induce responses in the retina that travel through the optic nerve to the brain, which perceives patterns of light and dark spots corresponding to the electrodes stimulated."

A portion of the implant (the electronics and coil) sits on the sclera and is covered by the conjunctiva. It is attached to a cable with electrodes, which enter the eye through the pars plana (following 3-port pars plana vitrectomy). The electrodes are attached to the macula with a microtack. The whole procedure takes about 3 hours.

At this juncture, only 10 patients have been enrolled in this clinical trial at 4 centers in the United States. Nevertheless, Second Sight was able to present some interim data at ASRS in October 2008, including data from patients enrolled in other countries.

"The safety profile was acceptable," Dr. Agrawal said, with the most common adverse events being conjunctival congestion (occurring in about 60% of subjects), and hypotony (~30%). "The most serious adverse event occurring at the 1-month postop time frame was a culture-negative endophthalmitis (1 subject), which resolved with treatment. Efficacy data related to orientation and mobility were also presented for the first 10 subjects to participate in the trial at the 3- and 6-month follow-up points. These showed a statistically significant improvement in their ability to follow a line for 20 feet, and locate a door 20 feet away while using the device," Dr. Agrawal explained.

Because of certain restrictions placed by the FDA on the testing of medical devices, the Argus II system is only being investigated in US trials for retinitis pigmentosa, while it is being studied for use in outer retinal degeneration in foreign trials. Retinitis pigmentosa patients develop photoreceptor degeneration, Dr. Agrawal explained, leading to significant visual impairment. "It is believed that such a population, where end-stage disease can result in essentially complete loss of vision, including central vision (where the prosthesis array is currently located), had the best risk/benefit ratio for an early-stage device." Other forms of outer retinal degeneration (dry AMD, for example) typically progress in the opposite fashion, Dr. Agrawal said, "with early loss of central vision and late loss of peripheral vision, if at all. There is no reason, however, to believe that a prosthesis such as this cannot function for all forms of outer retinal degeneration." RP