The Argus II Retinal Prosthesis System
Five-year safety and performance results from the Argus II Retinal Prosthesis System Clinical Trial showed that the device offered navigational vision to many patients who are blind from retinitis pigmentosa and was safe over an extended period of time.
By Todd Farley
In late 2016, Second Sight Medical Products (Sylmar, CA) released 5 years’ worth of results of their clinical study of the effects of the Argus II retinal prosthesis system for patients who are blind from retinitis pigmentosa (RP), a group of hereditary diseases that can cause retinal degeneration. The results of the clinical study, which was initiated in 2006, were published in Ophthalmology, the journal of the American Academy of Ophthalmology, and indicate that the Argus II is a safe and beneficial way to return functional vision to patients who are blind from RP.
In the past 10 years, clinical trials have been undertaken for various new retinal treatment paradigms (including gene therapy, stem cell transplantation, and electronic neural prostheses in different eye locations), each of which has shown promise. Still, only retinal prostheses are currently on the market as a means to restore some visual function for those patients blind from RP, which affects approximately 1 in 4000 in the developed world. The Argus II is the only retinal implant to have been approved for sale in the European Economic Area, the US, and Canada.
“Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial” described the prospective, multicenter, single-arm clinical trial that enrolled 30 patients (considered an acceptable amount of participants given the relative lack of prevalence of RP) at ten sites across the US and Europe for this long-term, 10-year study.1
“This is the largest and longest-running clinical trial of a retinal prosthesis device anywhere in the world, and the study will continue through 10 years post-implant. As of March 30, 2017, there were almost 240 subject-years of data altogether,” said Jessy Dorn, PhD, senior director of clinical and scientific research at Second Sight, on behalf of co-author Dr. Mark Humayun, MD, PhD, University of Southern California. “Patients with end-stage RP, who have experienced the degeneration of normal vision to total blindness, have no treatment options other than retinal prosthesis. The purpose of this clinical trial was to evaluate the long-term safety and efficacy of the Argus II Retinal Prosthesis System in patients with bare or no light perception due to end-stage retinitis pigmentosa.”
How It Works
The Argus II Retinal Prosthesis System is a visual prosthesis that has both external components and implanted ones. It is implanted into the worse-seeing eye of blind patients, who then wear glasses mounted with a tiny camera and video processor (connected via a cable worn on the belt or over the shoulder) that converts images into simulation patterns sent back to the electrode array on the retina. Elements of the system implanted include a hermetically sealed enclosure for the electronics (and a receiving antenna) secured to the eye with sutures and a scleral band, including 60 electrodes attached to the eye and tacked over the macula.
When turned on, the visual information collected by the camera is converted by the video processing unit into a brightness map in real time, while data and power are sent between an external antenna on the glasses and an internal antenna implanted into the eye. Video brightness values are converted into stimulation current amplitudes on each of the 60 implanted electrodes, with activated retinal neurons ultimately travelling through the visual system and being perceived as light patterns by the patients implanted with the Argus II.
While not a sham-controlled double-blind study (due to the rarity of the disease and the limited number of subjects enrolled), comparisons could be made of both implanted and non-implanted eyes as well as performance of the system both ON and OFF; and in terms of both safety and visual function, initial results of the study indicate that the Argus II works.
“Outcomes were excellent overall,” Dr. Dorn said. “At 5 years post-implant, 24 out of 30 patients remained implanted with functioning Argus II Systems; adverse events were noted but were treated with standard ophthalmic techniques, and there were no lost eyes; and performance was better with the System ON than OFF on all visual function and functional vision assessments.”
J. Fernando Arevalo, MD, chairman of ophthalmology at Johns Hopkins Bayview Medical Center, agreed that the outcomes of the trial showed that the Argus II performed well for patients who are blind from RP. “This is more than 200 patient-years of data, and the longest implant duration to date is 8.4 years. The devices continue to function, reliably enhancing basic visual function for these patients who otherwise can see almost nothing. They definitely help in their daily visual activities as demonstrated by the quality of life measurements.”
Computerized and real-life tests were used to compare the patients’ functional vision with the Argus II turned both ON and OFF, and in each instance vision was improved when the system was engaged. For example, in a computerized test of square localization (the ability to find a white square on a black background), patients were 81% more successful with the Argus II turned ON rather than OFF. With the aid of the Argus II, they were also 50% more likely to be able to identify the direction a high-contrast bar was moving on a screen, and even 38% more successful on a test of visual acuity that requires the patient to identify different spatial frequencies on a computer monitor. Similarly, in terms of real-life assessments, patients were more likely to succeed at the “door task” (finding a large piece of felt on a wall meant to simulate a door) and the “line task” (following a white line painted on to black tiles) when the Argus II was ON vs OFF.
While serious adverse events were reported in some cases, the trial showed that the Argus II retinal prosthesis system is safe overall. In fact, 5 years after implantation, 60% of patients (18 of 30)) had experienced no serious adverse events from the Argus II, either device- or surgery-related. Of the 12 patients who did experience adverse events, 23 incidents occurred within 3 years of implantation, with only one other adverse event (a successfully treated retinal detachment) occurring between the third and fifth years after implantation. No eyes were lost (enucleated) in the study, while all serious adverse events were treated with standard ophthalmic procedures.
“Some serious adverse events that were reported were conjunctival erosion, retinal detachment, endophthalmitis, and hypotony, and were treated with standard ophthalmic techniques,” Dr. Dorn explained. “There were no unanticipated adverse events reported, and many of these events are known risks of any vitrectomy or ophthalmic implant.”
Implications and Further Studies
“I think we need to study younger patients, who may have better results than older patients, as the inner retina will be better preserved at the time of implantation,” Dr. Arevalo said. “Plus, new indications need to be investigated, including other retinal degeneration and dry age-related macular degeneration, like the study going on in the UK.”
“This study will continue through 10 years post-implant for each enrolled patient,” Dr. Dorn said. “As the device is now commercially viable in many markets, research has turned to investigating the Argus II in other populations, such as patients with age-related macular degeneration, as well as developing a visual prosthesis to be implanted in the visual cortex of the brain.”
Costs for the Argus II treatment system (including the device and hospitalization) are estimated to be approximately $150,000 and are already covered by some Medicare contractors and various commercial insurance plans, with coverage hopefully continuing to grow as technological advances are more broadly adopted. Of course, given the relative rarity of RP, and the even greater rarity of RP patients whose vision has deteriorated to bare light perception, the current market for the Argus II is quite small. Nonetheless, the population who can use the Argus II currently has no other hope for vision recovery, while in the future the product may be used to help RP patients with better vision or patients who are blind from other causes.
The consensus is that the Argus II retinal prosthesis system works.
“The main strength of the trial is that the device is safe over a period of longer follow-up and that the rate of complications is acceptable for such a complex procedure,” said Rajiv Anand, MD, MS, FRCS, of Texas Retina Associates. “For patients who are completely blind to begin with, improvement to navigational vision with the Argus II is nothing short of a miracle.”
Disclosures: Dr. Dorn is senior director of clinical and scientific research at Second Sight., and Dr. Arevalo is a consultant for Second Sight.
1. da Cruz L, Dorn JD, Humayun MS, et al; the Argus II Study Group. Five-Year Safety and Performance Results from the Argus II Retinal Prosthesis System Clinical Trial. Ophthalmology. 2016 Oct;123(10):2248–54.