Visual Prostheses Market Moves in New Directions
by Jennifer French, senior editor
September 2017 issue
The market for visual prostheses is attracting new players and new methodologies from existing vendors. In recent months, commercial and research teams have shown progress on a number of fronts.
One of the pioneers in the field is the Artificial Retina team. Within that group are names like Mark Humayun and Jim Weiland at the Doheny Eye Institute at the University of Southern California, Robert Greenberg from Second Sight and Wentai Liu of the University of California Santa Cruz. Other research teams developing an epiretinal device include the RWTH Aachen University and the University of Ulm in Germany as well as KN Toosi University of Technology in Iran.
The Boston Retinal Implant team out of MIT is developing a subretinal visual prosthesis. Also pursuing this concept are teams at Tubingen University in Germany and Loyola University in the U.S. An alternative approach is to directly stimulate the optic nerve. Three teams are exploring this option, in Australia at the University of Melbourne & Australian National University, in Belgium at Catholique Universite de Louvain, and in China the out of China’s Shanghai Jiao-Tong University.
The other main approach to restoring vision is by stimulating the visual cortex within the human brain. In this method information is transcutaneously transferred from an external image capture system, processed, and cortically stimulated within the brain. Teams leading this effort are based at the Dobelle Institute in Portugal, the Polytechnique Montreal University in Canada, and in the U.S. at the University of Utah and the Illinois Institute of Technology
Second Sight Medical Products in Valencia, CA, pioneered the commercial space with its Argus device. The Argus II implant has a 60-electrode array. It has gained regulatory approval in countries around the world including the U.K, Australia, and most recently Russia, South Korea, and Taiwan. It is also currently reimbursed by NHS for RP in the U.K. CMS in the U.S. also reimburses for the device with an outpatient payment rate of $150,000.50 in 2017, which includes payment for the surgical procedure as well as two Category III CPT codes for initial programming and subsequent programming of the system.
Now led by CEO Will McGuire, Second Sight’s next generation is the 256-electrode array, a wireless cortical stimulation system for the treatment of blindness. Late in 2016, Second Sight announced the first successful implantation and activation of the Orion I in a human subject. In the UCLA study supported by Second Sight, a 30-year old patient was implanted with a wireless multichannel neurostimulation system on the visual cortex and was able to perceive and localize individual phosphenes with no significant adverse side effects. Second Sight submitted an application to the FDA in 2017 and gained approval to conduct the a feasibility study with two sites and implanting a total of five people. Assuming positive initial results in patients and discussions with regulators, an expanded pivotal clinical trial for global market approvals is planned.
Another vendor of retinal prostheses is Retina Implant AG, based in Reutlingen, Germany. Founded in 2003 by Eberhart Zrenner of the Centre for Ophthalmology at the University of Tuebingen. Zrenner and his colleagues were part of a subretinal photodiode research consortium that also included the Institut for Mikroelektronik in Stuttgart, the University Eye Hospital in Regensberg and the Institute of Microelectronics at the University of Ulm. The German government provided €6 million in funding to initiate the consortium.
One advantage of subretinal implants over other approaches is the topological fidelity with the point of stimulation. Epiretinal implants must use image processing algorithms to adjust the image coming from an external camera before stimulating the retina. Subretinal implants are positioned at the level of the photoreceptor layer and can thus make full, correct use of the retinotopy of bipolar cells linked to it. With the subretinal approach, light receivers are located beneath the retina, and assistance is provided by natural microsaccades which constantly refresh the image. In addition, the eye’s direction of gaze can be used to find the object viewed without need of resorting to movement of the head.
The microchip, called the Alpha AMS, consists of 1,500 elements each of which contains a silicon photodiode, a differential amplifier and an electrode. Incident light is collected point for point by the photodiodes and converted into electrical signals. An amplifier passes a strong electrical charge to bipolar cells in the retina. The implant also includes a subdermal power supply behind the ear with a connecting cable. The chip is connected to its power supply via 20-um thick sheet of polyimide film and a thin silicon cable with gold wire. The energy transferred to this power supply takes place via electromagnetic inductions through a subdermal secondary coil and an epidermal primary coil which is held magnetically in place, much like a cochlear implant.
Yet another European retinal prosthesis company is Pixium Vision of Paris, France. Developers of this retinal implant closed a €15 million series A extension financing in 2013. Led by Sofinnova Partners, support also came from Bpifrance, Omnes Capital, and Abingworth LLP. Pixium was co-founded by Bernard Gilly and Jose-Alain Sahel in November 2011 and built upon a close relationship with the Vision Institute at the National Eye Hospital in Paris. The funds raised were used to advance the development of Pixium’s IRIS retinal implant system.
IRIS consists of an intraocular implant that is surgically placed into the eye and attached to the surface of the retina. The user wears a pair of glasses containing an integrated mini-camera and wireless transmitter. The spectacles are connected to a pocket computer, which processes the image captured by the camera into a signal that is transferred back through the spectacles and projected onto the retinal implant to stimulated the optic nerve and generates an image. The brain of the user learns to interpret the signals received from the implant. Pixium’s first implant system, IRIS 1, containing 49 microelectrodes, entered a clinical trial in April 2013.
The next generation, IRIS II, containing 150 microelectrodes, is registered and undergoing clinical trials at multiple centers across France, Germany, and Austria. Pixium is also developing a subretinal implant, dubbed PRIMA, which is in preclinical trials. Earlier this month, Pixium announced the first successful implantation and activation of its IRIS II device in the U.K. The implant was performed by Mahi Muqit at Moorfields Eye Hospital.
Among the vendors there is some carnage; Bionic Vision Australia ceased operations 2016. However, the technology and commercialization initiatives were picked up by the Canadian company, iBIONICS. Based out of Ottawa-Gatineau, Canada, the company has clinical operations in Montreal and the R&D subsidiaries in Melbourne, Australia. The company is further developing the Diamond Eye, an implanted technology to stimulate the retina. The system uses a high density silicon microchip, with 256 electrodes and scalable to 1024 electrodes. The company is still in early stages but receiving accolades in Canada as an innovative start-up.
There are other approaches in the research stage. A team of researchers from Massachusetts General Hospital, Harvard Medical School, the University of Florida, and Xerox PARC is developing a new visual prosthetic platform for restoring high levels of visual acuity.
Earlier this year, Applied Genetic Technologies Corp., a public biotechnology firm conducting human clinical trials of adeno-associated virus-based gene therapies, announced that it entered into a strategic research and development collaboration with Bionic Sight, an optogenetics startup developing visual neuroprosthetics based on the company’s retinal coding technology.