Figure 1A. The Argus II Implant attaches to the retinal surface with a tack. The cable that both powers the chip and conducts the image signal from the episcleral housing is seen temporally (on the right side of the photographs).   Figure 1B. An early frame of a fluorescein angiogram in a patient with the Argus II Implant demonstrates some persistent macular perfusion. (Argus images: Elaine Leibenbaum, Julia Haller, MD, and Carl Regillo, MD.)

Degenerative retinal diseases such as atrophic macular degeneration and retinitis pigmentosa can cause severe vision loss. While vision loss is devastating at any age, RP often affects working-age adults. The current treatment options are limited. Vitamins help slow disease progression. Visual cycle modulators are in clinical trials; initial experience suggests they slow disease progression and may improve vision in patients with mild to moderate disease. For blind patients with light perception, or even no light perception vision, retinal chip implants offer hope.

RP is an outer retinal degeneration that affects the retinal pigment epithelium and the photoreceptors. Eyes with RP respond to electrical stimulation because in many patients, the inner retina and ganglion cell layer still have some function. The retinal chip implants stimulate these cells. 

More than a dozen groups of investigators and companies around the world are working on retinal implants (Table 1). In order to restore visual function, chip implants have to detect light, convert the light energy to electrical energy, and then stimulate the retina. Different groups approach this in different ways.^1,2 This article focuses on two implants that are furthest along the path to clinical availability: the Argus II Implant by Second Sight and the Active Subretinal Implant by Retinal Implant AG. The Argus Implant directly stimulates the ganglion cells. The Active Subretinal Implant recreates some of the signals that normally would have been made by the photoreceptors. 

Developed by Mark Humayun, MD, and colleagues at the Doheny Eye Institute, University of Southern California, the Argus II Implant has received a CE Mark in Europe and, this month, was granted approval by the U.S. Food and Drug Administration (See Review News, p. 3). The Argus II epiretinal implant is a 60-channel electrode array that directly stimulates the ganglion cells.³

The Argus II Implant consists of four parts. The power comes from a battery pack worn on the hip. An external video camera wirelessly delivers images to the electrical housing that is affixed to the episclera (similar in some sense to the plate of a glaucoma filtering tube). The image and data processing are done here. A cable from the electrical housing enters the eye through an incision in the pars plana and the electrical impulses then are sent through the cable to the chip. The chip itself is attached to the retina with a tack (See Figure 1A). 

All 30 patients who received the implant during the trial were able to perceive light during stimulation. More than half of the patients were able to see the motion of a white bar moving across a black background. Many of the implanted patients were able to identify some 3 to 4.5 cm letters on a high-contrast background. The best vision to date was 20/1,262. These initial results are encouraging and will allow further refinement of the device.

A number of groups around the world are working on visual prostheses of all types, including some on the tongue, optic nerve and brain. (This table is not intended to be an all-inclusive listing.)  (Please click here for a larger version of this table.)

There were a few adverse events. Approximately 10 percent of patients had conjunctival erosion over the implant. This was able to be repaired in all patients but one. Three cases of endophthalmitis and three cases of hypotony occurred, and all were successfully treated. One patient had to have the implant removed. One patient was found to have an intraoperative tear, and two patients developed post-procedure retinal detachments. These were all successfully repaired. 

One of the advantages of this implant is that it attaches directly to the ganglion cells, which are ultimately the cells that need to be stimulated to generate a visual signal that is then sent to the brain. As the electrode array becomes larger and/or is able to contain more electrodes, the cable might be able to be exchanged while keeping the electronic housing intact. From the patient’s perspective, the main disadvantage is the use of an external camera. To scan an area, the patient has to move the camera (basically his head) around. The current implant has a limited number of electrodes so the images only have rudimentary shapes, but this will be improved in future iterations.

Developed by Eberhard Zrenner, MD, and colleagues at the University of Tubingen in Germany, the Active Subretinal Implant is currently in clinical trials in several European centers and in Asia. The device is under review by the FDA as an investigational device and once FDA approval is obtained, Wills Eye Institute will be the lead clinical trial site in the United States. This implant contains a 1,500-electrode array that directly stimulates the inner retina. In contrast to the Argus II implant, which bypasses the inner retina, the Active Subretinal Implant aims to replace the dysfunctional photoreceptors.

The Active Subretinal Implant contains photodiodes on the subretinal chip, so there is no camera. The light stimulation occurs similar to the way we see—the light coming from an object goes through the pupil and activates the implant, which then converts the light directly into electrical stimulation. In contrast to the epiretinal implant, the subretinal implant does the image processing within the chip itself. However, using this technology requires more energy than light can provide. This is provided via a handheld battery pack that also has controls for brightness and contrast. The necessary energy is transmitted transdermally via a receiver induction coil and a magnet that is implanted under the skin behind the ear. A subdermal cable tacked to the lateral canthus connects the receiver to the subretinal implant for energy.

Figure 2. Left: The Active Subretinal Implant is powered by a handheld battery pack that transmits electrical energy to an inductive coil with magnet that is surgically implanted behind the ear; the connecting cable to the implant is tunneled under the skin toward the eye. Right: The implant has a 1,500-electrode array that both detects light and processes the image. (Images courtesy Retina Implant AG.)

There are published reports on a total of 21 patients who have received the subretinal 1,500-photodiode implant.^4,5 Patients receiving the subretinal implant have achieved VA of up to 20/1,000 within an 11 degree by 11 degree visual field. Functional outcomes included localization of objects of daily life such as plates and drinking glasses; increased mobility; motion detection; orientation in outside environments; recognition of facial details; even reading and detecting spelling errors in words written in letters 6-8 cm in size. Reports show that the implant can be safely removed and a new implant reinserted as the technology evolves. There have been no cases of endophthalmitis, two cases of conjunctival erosion, one case of retinal hemorrhage that cleared spontaneously, and one case of retinal detachment that was surgically repaired.

Figure 3. The Active Subretinal Implant is placed under the retina without the use of fixation devices such as a tack.

One of the main advantages of this subretinal implant is that, other tahn the battery pack, no hardware has to be worn by the patient. There is no external camera, so images are seen by moving the eye, and not the head. With 1,500 electrodes on the chip, it has the potential to give patients a higher-resolution image. While these results are encouraging, a larger cohort, with longer follow-up is needed.

Although both the Argus II Implant and the Active Subretinal Implant surgeries are somewhat complicated, both use techniques familiar to vitreoretinal surgeons. 

The ability to integrate retinal implant technology into the human neural system to restore limited vision has not only been a major scientific advance, but also a positive life-changing experience for many of the selected patients in these limited clinical trials. The results of these trials, current and future engineering and technical advances, and the evolving adaptive ability of patients learning to resume normal activities of daily living offer hope for our blind patients.  REVIEW