Three Australians with retinitis pigmentosa will be implanted with a bionic eye this year when the second clinical trial of an Australian developed and manufactured bionic eye commences. This trial will be supported by Bionic Vision Technologies (BVT), a commercial spinoff from the successful Bionic Vision Australia (BVA) research consortium (2010–2016). Commercialisation may still be five to seven years away but according to Dr. Lauren Ayton, Bionic Eye Clinical Research Team Leader and Senior Research Fellow at the Centre for Eye Research Australia (CERA), it will be worth the wait.
In a healthy eye, the photoreceptors (rods and cones) in the retina convert light into tiny electrochemical impulses that are sent through the optic nerve and into the brain, where they are decoded into images. If the photoreceptors no longer function correctly – due to conditions such as retinitis pigmentosa (RP) – the first step in this process is disrupted, and the visual system cannot transform light into images.
Around the world research groups are working to develop bionic eye implants to overcome this loss of functionality, thereby restoring some useable sight for people who currently see nothing or very little at all. Bionic Vision Australia is one of those research groups.
Having successfully implanted its first prototype bionic eye in three Australian patients in 2012, Bionic Vision Australia has moved into the next exciting phase of its development. The group, originally comprising a consortium of researchers from organisations including the University of Melbourne, the University of NSW, the Centre for Eye Research Australia, the Bionics Institute and NICTA (Australia’s Information Communications Technology Research Centre of Excellence) has licensed its technology exclusively to Bionic Vision Technologies (BVT) Pty Ltd, in a move which is set to accelerate the scientific effort.
…given the superior safety of BVT’s bionic eye, it will disrupt the market share Second Sight has gained…
The company is headed by Executive Chairman Robert Klupacs, a registered Australian patent attorney with extensive experience in “translating and commercialising early stage intellectual property into viable, investable corporate entities”. Mr. Klupacs was the Managing Director of the Australian Stock Exchange listed company Circadian Technologies, a biologic drug developer which has developed OPT-302, for the treatment of wet age-related macular degeneration.
While BVT’s second trial will initially involve three patients, up to 20 patients are expected to be recruited for a larger clinical trial, which will provide evidence on safety and efficacy for a regulatory approval application.
How BVT’s Bionic Eye Works
The first trial conducted by Bionic Vision Australia commenced in 2012 and involved the implant of a 24-electrode array into three patients in the suprachoroidal space behind the retina. The recipients of this original prototype bionic eye all had severe vision loss (with only light perception vision remaining) from retinitis pigmentosa.
The prototype electrode array was approximately 8mm x 16mm, and made of a silicon sheet with platinum electrodes embedded within. This implanted electrode was then connected to an external neurostimulator, which transformed video images captured by a camera on a pair of glasses into electrical signals to stimulate the electrodes. These electrical impulses then stimulated remaining cells in the inner retina (such as the bipolar cells and retinal ganglion cells). The impulses passed along the optic nerve to the vision processing centres of the brain, where they were interpreted as an image.
Designed to be completed within 18-months, the study period was extended to two years because of its initial success, and at its conclusion, patients had the external wires connected to the implant removed.
A second trial, involving three new patients with profound vision loss from retinitis pigmentosa, will commence in 2016. The second-generation device will have 44 electrodes – almost double the number of electrodes contained in the first implant – and will be fully implantable. Dr. Ayton said the latter feature of this next generation technology is what makes it so exciting.
“People get very focused on the number of electrodes contained in an implant, because we are used to thinking about pixels in an image. Our first implant had 24 electrodes and the US device Argus II has 60. In Germany, Retina Implant Group’s implant has 1,600 photodiodes. But in reality, all of these groups are achieving relatively similar levels of visual navigation and object detection for their patients. We think it is actually more important to have advanced vision processing, and to maximise the amount of training and rehabilitation we can provide to the patients. This next clinical trial will have these features.”
Dr. Ayton said that the most exciting aspect of this next generation device for her is the fact that patients will be able to use it long-term and in their natural environment.
“The first proof-of-concept study looked at whether an implant placed in the suprachoroidal space could generate visual percepts for people with profound vision loss. It could only be used by patients one day a week at the hospital or research institute. With this next-generation implant, people will learn to use it in their home environment, where they know where things are, and so they can be better trained. We will be optimising their learning and rehabilitation, and hence we expect improved outcomes,” said Dr. Ayton.
Although it was once believed that the longer a person had a degenerative eye disease, the less likely it was that their sight could be recovered, Dr. Ayton said this was not necessarily the case. “We now know that because of neuroplasticity it is possible to remap brain functionality that has been lost. So although in the event of vision loss, over time other senses may compensate – maybe your tactile senses become stronger for instance – it seems possible to remap the neural pathways by reintroducing vision cues. There is a lot of work to be done in this area, and researchers are currently using MRI to see how this remapping occurs.”
Too Little, Too Late?
All going well, Dr. Ayton believes BVT’s bionic eye could be ready for FDA approval and commercialisation within the next five to seven years.
With that timeline in mind, you could be forgiven for asking whether this will be too little, too late. After all, the Argus II system, developed by Second Sight, is already approved for use in the United States and the European Economic Area and, having been implanted in over 150 eyes with retinitis pigmentosa as well as three patients with macular degeneration, is rapidly becoming a household name. However Dr. Ayton is confident that, given the superior safety of BVT’s bionic eye, it will disrupt the market share Second Sight has gained.
The novel surgical procedure uses a natural pocket called the suprachoroidal space whereas currently used surgical methods involve tacking the implant to the eye, thus increasing the chance of retinal damage. Indeed, small scale studies of BVT’s bionic eye have demonstrated no unexpected serious adverse effects.
With world leading vision processing technology that will allow BVT to constantly upgrade the patients’ experience without the need for further surgery, BVT Executive Chairman Robert Klupacs said the device will also be more effective than those developed by competitors. “We believe our approach is a safer, simpler and faster surgical procedure than that employed by our international competitors. Combined with our proprietary vision processing capabilities, BVT offers the potential for much improved acuity – or sight – than competing products.”
In Germany, Retina Implant AG Research began implanting human patients in 2005 and started a second, larger clinical trial in 2010. In July 2013, the company’s wireless subretinal implant technology, Alpha IMS, received CE mark.
The company presented results from 29 previously-blind RP patients who were implanted with the Alpha IMS subretinal microchip last November at the 2015 American Academy of Ophthalmology (AAO) annual meeting.
Dr. Helmut Sachs, Retina Implant’s senior consultant and head of the Department of Ophthalmology, Clinic Dresden-Friedrichstadt, Germany said, “For decades, researchers have searched for solutions to re-establish useful vision for late-stage RP patients living in darkness. We are making significant progress with technologies like the Alpha IMS but, of course, there is still much more we hope to achieve.”
Key findings from the presentation include:
- 72 per cent of patients reached the primary efficacy endpoints of the study, showing a significant improvement in daily living tasks, recognition and mobility.
- Light detection drastically improved, with more than 86 per cent of patients able to detect light, including the identification of specific light sources.
- Transchoroidal implantation surgery was found to be a safe strategy for inserting subretinal implants, and patients did not experience any adverse events.
Direct to Brain
Back in Australia, a collaboration between Monash University, Alfred Health, MiniFAB and Grey Innovation known as the Monash Vision Group has developed a direct to brain bionic eye for people with vision impairment caused by other conditions, including glaucoma and traumatic injury. This intracortical device will be able to help people who have damage to the optic nerve or anterior visual pathway, who would not be suitable for a retinal prosthesis. Jeanette Pritchard, Chief Operating Officer of Monash Vision, said the device is undergoing extensive tests for safety and an ethics submission is being prepared for Alfred Hospital, approval of which was required prior to patient recruitment.
“Our goal is to have the submission completed in the first half of 2016, and all being well, to start recruiting our first patients over the latter part of 2016,” said Dr. Pritchard.
While the final device design had been “locked down” for some time, Dr. Pritchard said work was underway in conjunction with Monash Art, Design and Architecture to refine the headgear, which will need to be worn for long periods of time by those who receive the implants.
She said Monash Vision was also working closely with the Bionics Institute and the Centre for Eye Research Australia to plan the program for clinical testing. “It will be a similar process to that undertaken by Bionic Vision Australia,” said Dr. Pritchard. “Once implanted we will switch on and calibrate the device to understand exactly how it’s working, then spend time working with participants in a controlled laboratory environment. The device has been designed to be mobile, so that over a two-year period participants can begin using it outside and in other still controlled, but more flexible, environments. Ultimately, we hope the participants can take the device home and use it in their everyday environment.”
The advent of the bionic eye is disrupting traditional processes for measuring changes in vision. Letter acuity, for instance, is often not sensitive enough when it comes to reviewing people who have received an implant.
At CERA, Dr. Ayton is leading an international task force with Professor Joseph Rizzo at Harvard University, with the aim of generating gold standards and protocols on the ways to measure and report in vision restoration trials.
“The HOVER (Harmonisation of Outcomes and Vision Endpoints in Vision Restoration Trials) task force is looking at a comprehensive range of issues; psychophysics, letter recognition, grating acuity, navigation via mobility tests and activities of daily living. Additionally, groups within the task force are examining patient quality of life using questionnaires and the psychological impact of a bionic implant.”
She said the work being done by the HOVER task force is evidence of the way in which researchers from around the world are collaborating for better outcomes.
“These projects are publically funded and so of course there is a need to protect intellectual property, however there is a lot of collaboration, especially on the clinical aspects,” said Dr. Ayton.
Recruitment is underway for patients who have profound vision loss from retinitis pigmentosa and who may be interested in participating in future clinical trials of BVT’s bionic eye device. To find out more, or express interest on behalf of a patient, email Lauren Ayton: [email protected]