Patients who are blind from retinitis pigmentosa continue to benefit from a safe retinal implant after 3 years, Ophthalmology reported. Dr Allen Ho and coworkers in the Argus II study group present the complete 1- and 3-year data from the largest, longest-running clinical trial of a retinal prosthesis to date.

The Argus II Retinal Prosthesis System is made up of a device implanted on and in the eye-a receiving antenna, electronics case and intraocular array-and external equipment worn by the user that comprises a glasses-mounted video camera and a small processing unit worn on a shoulder strap or belt.

The device received a CE mark in Europe in 2011 and gained approval from the FDA in 2013.

Trial participants

Profound loss of vision from retinitis pigmentosa, itself a rare disease, is extremely rare, so the trial included only 30 patients. Subjects were recruited at ten centres in the UK, France, Switzerland and the US to have the device implanted in one eye, typically the eye with poorer vision. The system could be turned on or off during assessments, allowing patients to act as their own controls.

Eligible patients, while having bare or no light perception in both eyes, had functional ganglion cells or optic nerve so that the proximal visual system is stimulated when visual data are transmitted from the camera to the array, creating the perception of patterns of light that patients can learn to interpret. They had a previous history of useful form vision.

Next: Visual function

Visual function

To evaluate patients’ visual skills, three new computer-based tests were developed during the trial: the Square Localization test, in which subjects had to locate and touch a white square on a black touchscreen; the Direction of Motion test, which required patients to draw the direction in which they perceived a white bar to be moving across the same black screen; and the Grating Visual Acuity test, in which patients gave the perceived orientation of a black and white grating, the spacing of which was varied to assess resolution.

Most patients showed significantly better visual function (system on versus system off) in Square Localization and Direction of Motion at both 1 and 3 years. Some performance decline over time was noted but was considered to probably be a statistical feature of the late introduction of some of the tests and the better array used in patients who enrolled later in the trial: 1-year data were not available for all tests from the patients who enrolled early, which skewed some of the 3-year data.

One-third to one-half of patients scored on the Grating Visual Acuity test with the system turned on (no patients scored with it turned off).

The study’s secondary end-points were related to real-world performance and day-to-day life. Patients were better at finding a simulated (black) door in a (light) room and following a 6-inch-wide white line on a black floor with the system turned on.

The Functional Low-vision Observer Rated Assessment (FLORA), which incorporates extensive interview and observation to evaluate the device’s impact on patients’ everyday lives, was developed in partnership with the FDA for the purposes of this trial. The Argus II System was related as overwhelmingly positive using FLORA, with no negative ratings from any patient at any time point.

Next: Safety and reliability

Safety and reliability

The longest duration of implant at the time of report was 7.2 years. After 3 years, 29 of the 30 patients retained a functioning device: 1 device was removed at 1.2 years to treat recurrent conjunctival erosion. No devices had failed.

No eyes were lost and there were no safety concerns. It is worth bearing in mind that the usual concern with ophthalmic adverse events is deterioration of vision, so the risks in patients with such profound blindness are inherently low.

Rates of adverse events were broadly similar to those seen with glaucoma drainage devices and retinal tacks. Eleven subjects experienced a total of 23 serious adverse events-those requiring treatment-that were related to device or surgery; they included hypotony, conjunctival dehiscence and conjunctival erosion, and there were three cases of presumed endophthalmitis (culture negative) early in the trial. Nineteen of the 30 patients experienced no serious adverse events at all. All serious adverse events were managed with standard ophthalmologic approaches.

Most adverse events occurred within the early post-operative period, with those few that occurred later tending to be part of a cascade of events that had begun before rather than a new problem.

Seven early subjects underwent elective revision surgeries to improve the position of the array. Two required surgery 1 week after implantation to reattach the array to the retina.

New trial

A new trial is recruiting legally blind patients with severe dry age-related macular degeneration to receive the implant system.