by Dan Roberts
Updated April 27, 2013
Research is currently being conducted by several groups in the area of retinal microchip implantation. This is a report on the work being done by the Optobionics Company in Chicago, the Harvard-M.I.T. Retinal Implant Project, the Intraocular Retinal Prosthesis Group at the University of Southern California, a cooperative effort between the Stanford University School of Medicine and the Kresge Eye Institute and work being done at Retina Implant AG. The device developed by the Intraocular Retinal Prosthesis Group is the first to gain FDA approval (see below).
Optobionics
Optobionics is located in Wheaton, Illinois, and owned by pediatric ophthalmologist and inventor Dr. Alan Chow and his brother, Vincent, an electrical engineer.
Microchips just three millimeters across holding 4,000 to 5,000 microscopic solar cells can be implanted into the back of the eye. When light strikes those solar cells, it is converted into electrical signals that travel through the optic nerve to the brain and are interpreted as an image. This piece of silicon can then act as a replacement for a malfunctioning retina. The replacement retina has a diameter of two millimeters, and is about half the thickness of a sheet of paper. The two-hour operation is done through an incision in the white part of the eye (the sclera), and the chip is inserted into a pocket beneath the retina.
The Chows originally tested their chip in blind animals and successfully produced visual sensations. Their device displays only black and white images and works best in well-lit rooms, but they hope that the addition of more solar cells on the chip will eventually improve the results. Much of this technology hinges upon the ability of the human eye to accept silicon chip implants, and six retinitis pigmentosa patients have undergone the procedure during the past year. Dr. Chow reports that, as yet, there has been no sign of rejection, infection, inflammation, or detachment, and that the patients (all affected by retinitis pigmentosa) are reporting improved vision.
A press release from Optobionics (May 2002) reported these positive results, and also that the chips seem to be stimulating remaining healthy cells. Initial expectations were to gain some light perception at the site of the implant, but improvement outside the implant areas is also being seen: something Dr. Chow calls a "rescue effect." His report was also presented at the 2002 meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Ft. Lauderdale, Florida.
In the 2004 article, "The Artificial Silicon Retina Microchip for the Treatment of Vision Loss From Retinitis Pigmentosa" (Alan Y. Chow, MD [et al], Arch Ophthalmol. 2004;122:460-469), Optobionics researchers reported on the progress of the six subjects since implantation of the chips. They wrote:
"During follow-up that ranged from 6 to 18 months, all ASRs functioned electrically. No patient showed signs of implant rejection, infection, inflammation, erosion, neovascularization, retinal detachment, or migration. Visual function improvements occurred in all patients and included unexpected improvements in retinal areas distant from the implant. Subjective improvements included improved perception of brightness, contrast, color, movement, shape, resolution, and visual field size."
They explain the improvement of cell function far from the implant site as "a possible generalized neurotrophic-type rescue effect on the damaged retina caused by the presence of the ASR [artificial silicone retina]," and emphasize that "a larger clinical trial is indicated to further evaluate the safety and efficacy of a subretinally implanted ASR."
Three centers are involved in the Optobionics trial. Wilmer Eye Institute at Johns Hopkins, Baltimore, Maryland, reports that five patients received an ASR chip implant in early December 2004, and another three were implanted in mid-February 2005. Emory University in Atlanta, Georgia has also reported progress with this study, reporting seven implant surgeries as of March 2005. Rush University in Chicago, Illinois has accomplished five in the same period, for a total of twenty implants so far from the three sites.
Harvard-M.I.T. Retinal Implant Project
A retinal prosthesis is being developed by a group led by Dr. Joseph Rizzo, professor of ophthalmology at Harvard and co-director of the Harvard-M.I.T. Retinal Implant Project. Rather than being positioned near the photoreceptors, his research group's chip will be positioned near the ganglion cells, which send nerve impulses to the brain. The prototype uses a camera mounted on a pair of eyeglasses to capture and transmit a light image to the chip. The light and images are converted into electrical impulses, which are transmitted to the brain along the optic nerve. The camera could be replaced with a digital signal processor, which is currently being developed by Germany's Retina Implant Association.
Dr. Florian Gekeler of the University Eye Hospital in T=FCbingen, Germany, is part of a consortium working on subretinal implants. His work shows that light entering the eye would not be strong enough to power photocells to stimulate retinal neurons, so his device uses an infrared diode mounted in a lens frame to deliver the necessary amount of light.
The first implant was developed in 2007-2008. In March of 2008, it was implanted in a Yucatan minipig and demonstrated that it was functional following the surgery. In May of 2008, the surgery was successfully repeated twice more.
A more refined second generation prosthesis, better suited to humans, was developed, with expectations of human trials beginning in 2011. (ref: www.rle.mit.edu/rleonline/ProgressReports/3677_29_PR152.pdf)
Intraocular Retinal Prosthesis Group, University of Southern California
Dr. Mark S. Humayun agrees with Dr. Gekeler about the intensity of light required to stimulate the retina. To solve this problem, his group is using a small external camera to transmit an image to the implanted chip, which is positioned near the ganglion cell layer.
Dr. Humayun teamed with Eugene de Juan to form the Intraocular Retinal Prosthesis Group at Doheny Retina Institute at the University of Southern California. Humayun and de Juan conceived the original retinal prosthesis and then turned over further development to the Oak Ridge, Sandia, Argonne, and Los Alamos national laboratories, with each lab working on a different aspect of the electrode array/retina interface. This $9m collaborative effort also involves the University of Southern California (where the devices are implanted to test their effectiveness), Second Sight in Santa Clarita, California (who will commercially produce the finished system), and North Carolina State University in Raleigh, North Carolina (where development of the in-situ medical electronics is taking place).
On September 5, 2002, researchers at Sandia Labs announced that they had developed the Multiple-unit Artificial Retinal Chipset (MARC). According to the company's press release, the chip involved "multiple components mounted both inside and outside the eye. A spectacle-mounted camera takes video that is then processed and transmitted into the eye by radio. There, a chip made from micro-machined silicon and protective coatings receives the signal and extracts data with which to stimulate the retinal nerves. Like a crystal radio set, it also extracts the power it needs to run from the radio signal, removing the need for any external wires or internal power pack." The camera is currently mounted on a pair of goggles, with plans for eventually placing it on the cornea of the eye. The receiver will be placed directly on the retina.
On January 9, 2007, Second Sight announced that the FDA approved an Investigational Device Exemption (IDE) to conduct a clinical study of the Argus II Retinal Prosthesis System. This more advanced system replaced the ArgusT 16, which was implanted in six RP subjects between 2002 and 2004 and has enabled them to detect when lights are on or off, describe an object's motion, count discrete items, as well as locate and differentiate basic objects in an environment.
On February 14, 2013, the FDA unanimously approved the Argus II system for retinitis pigmentosa patients age 25 and up who have severe to profound disease with little or no light perception in both eyes. The FDA specified that eligible patients also have to have inner layer retina function and a history being able to see forms, and will be required to have clinical follow-up and visual rehabilitation. More information about the Argus II implant.
Stanford University School of Medicine and Kresge Eye Institute
Two researchers are working on a nerve interface system which will drip neurotransmitters onto the cells, rather than jolting them with impulses from electrical implants. Harvey Fishman, MD, PhD, director of the Ophthalmic Tissue Engineering Laboratory at Stanford University School of Medicine, and Raymond Iezzi, MD, assistant professor of ophthalmology at the Kresge Eye Institute, Wayne State University, Detroit, are hoping that this approach will lead to higher resolution artificial vision. By comparison, implanted electrode arrays use relatively large electrodes, which stimulate hundreds or thousands of cells at once to create images (electrophosphenes). As a result, the images are not well-defined, and the best acuity achieved so far is only 20/1800.
The device being developed by Drs. Fishman and Iezzi is expected to be more precise. It is a microchip with 50-nm-wide holes which drip chemicals to attract nerve endings (axons) from the bipolar cells. This restores the connection which is lost when the cone cells in the macula degenerate. Once the connection is restored, light signals can once again travel from the photoreceptors to the optic nerve.
Dr. Fishman is working on the nerve interface system, and Dr. Iezzi is developing the delivery system for the neurotransmitters. His approach is to cage neurotransmitters (such as glutamate) in molecules, inject them into the retina, and then expose the molecules to ultraviolet light. The light exposure would cause the molecule to break open and free the glutamate to make connection with the bipolar cells. The patient would carry his own supply of neurotransmitters, perhaps in a reservoir worn behind the ear.
Tests on animals for this system were planned to begin by the year 2004.
Retina Implant AG
In March 2006, Reutlingen-based medtech company (Germany), Retina Implant AG, announced that it had developed an electronic chip that is now in the clinical trial stage. At the end of 2005, operations were successfully performed for the first time on two patients, who up to then had been completely blind. The surgical team was headed by Professor Karl Ulrich Bartz-Schmidt from TFCbingen and Regensburg-based Professor Veit-Peter Gabel.
The scientists at Retina Implant AG are primarily developing the retinal implants for patients with retinitis pigmentosa. A silicon chip, with miniature photosensors that control an electronic circuit, stimulates the nerve cells in the retina to varying degrees of intensity, depending upon the brightness of the light. The nerve cells send signals to the brain in normal fashion, and the brain uses the signals to generate an image pattern.
Direct stimulation is enabled by a 4x4-array of identical electrodes located at the tip of the implant plate. The chip and direct stimulation field, which are attached to a narrow subretinal polyimide ribbon, were implanted in two blind patients by a team of doctors at the Oxford Eye Hospital. Electrical current is supplied via the sclera by a thin cable under the skin that lead to a radio-controlled, battery-operated receiver. As of May 2012, the two formerly-blind patients can only perceive light and some basic shapes, but each patient's brain is expected to eventually better interpret the signals coming from the implant.