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More than 1 million Americans are legally blind and another 10% cannot detect light.1 With increased mean lifespan, the frequency of age-related eye disease will double in the next 30 years.2 A significant percentage of the non-treatable blindness stems from loss of photoreceptors (the rods and cones).3,4 Once photoreceptors are lost, restoring useful vision to blind patients has been impossible.5
However, after nearly a century of research into the use of electrical stimulation to restore sight, the Argus II system (Second Sight Medical Products, Inc. Sylmar, CA) was just approved by the FDA as the first medical implant to restore sight to patients who are blind from near total loss of their photoreceptors.
NON-RETINAL VISUAL PROSTHESES
The concept of artificial vision was first tested in 1929 when electrical stimulation of the visual cortex resulted in a blind patient seeing a spot of light (phosphene).6 More than 30 years later, Giles Brindley’s implantation of an 80-electrode device onto the visual cortex of a blind patient renewed the possibilities of artificial vision restoration.7-14 But, this goal of developing a visual cortical implant to restore vision remains elusive.12,13, 15-27
RETINAL PROSTHESES
Analogous to the cochlear implants for some forms of deafness, retinal prostheses propose to restore useful vision by converting visual information into patterns of electrical stimulation that would excite the remaining inner retinal neurons after photoreceptor loss in diseases such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). However, knowing that the retina has more than 100 million photoreceptors while the cochlea has only 15,000 hair cells, the retinal implant is obviously a much more complicated challenge. First, there must be enough viable retinal cells remaining to initiate a neural signal. Post mortem studies on patients’ eyes with end-stage RP and AMD have revealed that that plentiful numbers of non-photoreceptor neurons in the retina do survive the disease process. Although neurons in the retina survive despite photoreceptor loss, there is significant reorganization of the remaining neural network.44
In spite of these well-documented changes in the inner retina after photoreceptor loss, when hand-held electrodes were inserted in the eye of blind test subjects in an operating room, the test subject detected small spots of light when the electrodes were activated and the apparent location of the spot of light in general corresponded with the retinal area stimulated. These critical experimental findings led directly to the development of chronic retinal implant systems.
Two approaches have been evaluated thus far—subretinal implants (microphotodiode arrays inserted between the bipolar cell layer and retinal pigment epithelium) and epiretinal prostheses, in which visual information from devices like cameras provide the patterns of stimulation to the residual retinal neuronal networks. The implantation of a subretinal prosthesis, as well as maintaining its electronic functionality over long-term, is much more difficult than the Argus II epiretinal prosthesis. As of now, no subretinal implants have been successful to be approved as medical implants.47-52
ARGUS II- EPIRETINAL PROSTHESIS
Epiretinal implants vary in terms of how much of the required electronic circuitry is contained in the intraocular device and how they are connected to the extraocular elements (induction coils, penetrating wires, or lasers).
The ARGUS™ II System (figure 1-2) is a two system implant in which the wearable and implantable units communicate wirelessly. The wearable components include a miniature camera in the glasses from which information goes to a belt-worn pocket size video processing unit (VPU) with rechargeable battery. The VPU encodes the information and both power and data are then sent back to the glasses and then wirelessly (via a near field inductive link) sent to the implanted components. The implanted components consist of a receiver coil which then send the information to an implanted electronic chip inside a hermetic metal can. The implanted chip then decodes and routes controlled pulses via an integrated flexible cable with electrodes to excite retinal neurons. The electrode array is 6mmx5.5mmx0.5mm and when implanted in the center of the retina (i.e., macula) its diagonal dimension spans the central 20 degrees of visual field. All components of the Argus II fit inside the eye socket (orbit) and only the integrated cable with electrodes are placed inside the eye with the rest of the device sutured to the eye wall (sclera) and covered by the conjunctiva.
Figure 1:
Argus II Wearable components: (A) Glasses with camera and inductive (radio frequency) coil and associated electronics. (B) Video processing unit (VPU) with rechargeable battery. The VPU connects to the glasses via a cable and encodes the camera input and sends it back to the coil to be transmitted wirelessly to the implanted components. (C) Example of how the system can be worn with VPU using a shoulder sling. Alternatively VPU can be worn on a waist belt or put into a pocket.
Figure 2:
Argus II implantable components. (A) shows the device expanded and shows the various components. (B) Shows the device as it would be when wrapped around the eye; note the electrode array would be inserted through the eye wall (sclera). The entire implant is under the conjunctiva so it is not visible or exposed reducing the chances of infection. (C) Picture of the retina showing the electrode array places in the central retina (macula) in a subject with RP.
(Credit: Mark Humayun and Second Sight Medical Products)
The Argus II safety and efficacy data from an international study of 30 patients with a cumulative follow up of approximately 100 years was submitted to the European and US regulatory bodies, leading to approval in Europe in 2011 and FDA approval in the US in 2013. All subjects were able to perceive light during electrical stimulation and 27 out of 28 subjects (96%) performed better in localizing the object with System ON versus OFF. Seven subjects have been able to reliably score on the visual acuity scale with the System ON. The best result to date is 1.8 logMAR (equivalent to Snellen 20/1262).70 When letter reading was tested in 30 subjects, six could identify any letter of the alphabet at a 63.5% success rate (vs. 9.5% with the system off). Some subjects were able to put the letters together into words and read sentences.62
Conjunctival erosion remained the most common adverse event and was seen in 3 patients but in the other patients the defect was small and either self-repaired or was easily repaired with a few sutures. Details of all the adverse events as well as the benefits from the Argus II are provided in the reference listed.71
CONCLUSIONS
Currently, the Argus II is the only approved visual prosthesis. It is approved in Europe and in the US. It is intended for patients with severe visual loss from photoreceptor loss. It does require a major operation and there are associated risks with the procedure, but the benefits were deemed to outweigh the risks by the US and European regulatory bodies, leading to its approval as a medical implant. The approval of the Argus II is a major milestone in the field of artificial vision and provides a treatment option for patients for whom there was no near-term foreseeable treatment.
The development of retinal prostheses to generate artificial vision for the blind is indeed a complex, long-term, expensive, and interdisciplinary undertaking, but it does now provide the much awaited “good news” for many blind patients.
DISCLOSURES
Mark Humayun, M.D., Ph.D. has equity in, is a patent holder for, receives royalties from, and is a consultant to Second Sight Medical Products, Inc.
