A research project underway in Melbourne could see diamonds – the hardest and most chemically inert material in nature – restore vision to people made blind due to age-related macular degeneration and retinitis pigmentosa.
One day, in the not so distant future, people blinded from age-related macular degeneration (AMD) or retinitis pigmentosa may be able to recognise the faces of their loved ones and read large letters. Over time, the diamond bionic eye devices embedded on their retinas to facilitate this sight may be upgradeable as technology advances – using routine software upgrades – delivering more complex visual capacity to open up new worlds of independence and vastly improve quality of life.
We’ve already seen navigational vision given back to a tiny number of patients in Melbourne via a prototype 24 channel platinum bionic eye device developed by the Bionic Vision Australia consortium. A further clinical trial of the next generation, 44-channel suprachoroidal device will commence in early 2017. The 44 Channel device using platinum electrodes is expected to offer patients a wider field of vision, which will assist with navigation.
Now another offshoot of the BVA consortium is getting closer to trialling a diamond bionic eye device that it believes holds the potential to deliver even higher resolution sight – with 256 to 1024 channels.
…the diamond bionic eye devices embedded on their retinas to facilitate this sight may be upgradeable
The project is a partnership between Professor Michael Ibbotson, Director of the National Vision Research Institute (NVRI), a division of the Australian College of Optometry – and Professor Steven Prawer, University of Melbourne (UoM) and Chief Technology Officer of a Canadian-Australian start-up company, iBionics. All going well, they anticipate moving into clinical trials in approximately five years.
Prof. Ibbotson explained how it came about.
“Back in 2008, we were a group of independent scientists working in different locations around Australia discussing the possibility of a collaboration, mainly trying to work out how to fund it. Then came a fortuitous event: the then Prime Minister, the Hon. Kevin Rudd, MP, convened the Vision 2020 meeting.
More than 1000 Australians responded to an invitation from the Prime Minister, to attend Parliament House in Canberra for the 2020 Summit. The purpose was to discuss “the agenda for the nation”, with the challenge being “to help shape a long-term strategy for the nation’s future, to tackle the long-term challenges confronting Australia by thinking in new ways”.
“At the meeting, it was put to the Prime Minister that 2020 Vision by 2020 would be a powerful slogan – and that to this end, he should support research into bionic vision. Kevin Rudd loved the idea, and ultimately committed $50 million to bionic vision research over five years.”
That funding brought together a team of researchers from the University of Melbourne, University of New South Wales and several other institutions. Known as Bionic Vision Australia, the team pursued several devices.
“We did our work together and we took it to a really high level. The funding took us through until the end of 2014, and since then we’ve developed several offshoots, all aimed at developing improved bionics technology.”
Prof. Ibbotson said that right from the start, the consortium of researchers agreed to develop several bionic eye devices – some platinum-based and one diamond, knowing that the diamond device would be significantly more technically challenging and would take longer to develop. It was decided that platinum-based devices might offer the best chance at a wide-view system optimal for improving mobility, while the diamond device would be best suited for providing high-resolution vision.
Platinum-based devices were implanted in humans during the term of the grant, and significant developments were made in furthering the diamond device.
“BVA had to prove its worth – to prove our devices could be implanted into humans safely and that it would work. So within that first funding period, from 2009 – 2014, we put in an enormous effort and we achieved our goal.”
Indeed, they did with the successful implant of a 24-electrode array into three patients in the suprachoroidal space behind the retina.
Prof. Ibbotson explains that working on multiple devices at the same time is an accepted scientific principle. “Many people believe all funding should go into a single effort, however if you get to a point where that effort isn’t working, you’ve got nothing. This way there is a much better chance that something will work and be suitable for further development. As it happened, all of the developed devices proved themselves in their own way, leading to significant cross-fertilization of ideas.”
How the Device Works
The device works in the following way:
- A tiny camera sits in the middle of a pair of glasses, worn by the patient
- Images are transmitted wirelessly to the electronic device implanted at the back of the eye
- The electronic device consists of a 4mm x 4mm microchip, with 256 diamond electrodes, hermetically encased in a diamond box, which sits next to the retina (epiretinal placement), and stimulates the retinal ganglion cells. The desired pattern of stimulation is provided to the microchip via an external vision processing unit which processes the image from the camera and sends the appropriate instructions to the chip
- These electrical pulses activate remaining nerve cells in the retina, which automatically do their job by sending signals to the brain, where the signals are processed and converted into perception.
Following the successful first implant, and the conclusion of the Labor Government’s five-year research grant, Bionic Vision Australia’s project was terminated.Research into a platinum device was taken up by Bionic Vision Technologies to further the aim of developing a wide-view system. Profs. Ibbotson and Prawer, along with Drs. Hamish Meffin (NVRI) and David Garrett (UoM) combined to pursue the diamond technology.
“We knew the platinum device was far closer to an end product, however, we wanted to progress the diamond technology – it had been our baby right from the start and its potential for flexible high-resolution vision is enormous. As the devices had different end goals, they were likely to reach different markets.”
Last year, the diamond research team was approached by Canadian entrepreneurs who could see the potential to commercialise and productise the bionic implant. As a consequence, the Australian Canadian start-up iBionics was formed with Prof. Steven Prawer appointed as co-founder and Chief Technology Officer.
While iBionics plans to raise the significant funding required to put the diamond device through FDA approval prior to human clinical trials, Prof. Ibbotson said there are several milestones to meet before this can occur. Winning a AU$1 million Development Grant from the National Health and Medical Research Council (NHMRC) has helped them get there.
“The problem with most devices like this, which have an external camera, is effecting transmission of images from the camera to the electrode device and on to what is called an electrode array, which stimulates the retina” he said.
In the case of BVT’s bionic eye, this has been managed by connecting fine wires (otherwise known as tracks) from the microchip controller to the stimulating array.
According to Prof. Ibbotson, one way of obtaining higher resolution images is to increase the number of electrodes on the array. “In the case of the platinum device, as you increase the number of electrodes the number of connecting tracks also has to increase. This becomes a logistical problem – after all there is only a tiny amount of space available in which to work.”
In contrast, Prof. Ibbotson explained, the diamond device has no tracks – every diamond electrode is directly bonded to the microchip. Because there are no wires, the device is scalable.
“For practical reasons, right now we are using 256 electrodes on a 4mm x 4mm microchip, but our near-term goal is to get to 1,024 electrodes which should give substantially improved resolution – perhaps even enough to see faces and read large text. A high electrode count is necessary but not sufficient. We need to know what patterns of stimulation provide the best perceptual outcomes. As the number of electrodes increases, the number of possible patterns, both in time and space increase exponentially. The challenge is how to converge on the best stimulation strategy in a reasonable time scale.”
“It is imperative to prove that adding more electrodes to the device stimulates a corresponding increase in retinal cell activity, which in turn delivers higher resolution images for the patient.”
To do this, Prof. Ibbotson’s team have implemented optical recording techniques that flood the rodent retina with a fluorescent dye. “The technique is activity dependent so only those cells that come to life with stimulation light up under fluorescence.”
The result is transformational when it comes to watching the responses of many retinal cells to electrical stimulation. “In the past we could only observe the response of a single cell through an electrode, now we can observe hundreds of cells simultaneously as they are stimulated. So with our 256 electrode device, for example, we can see whether or not 256 independent groups of cells are switching on in response to the stimulus.”
Prof. Ibbotson said it was also important to develop a more efficient way to stimulate cells simultaneously via electrode arrays.
“To do this we’ve developed algorithms that enable us to stimulate more electrodes with a greater degree of specificity.
“It’s been a long, time-consuming process, and because the developments have been mostly software driven, there has been little to show in terms of something people can see or hold in their hand. However, after three years of solid work, we’ve completed the basic research and this means that going forward, we know we have a scalable device which can deliver high resolution vision, which we are able to accurately observe in pre-clinical trials.”
“Now, as we move into rodent trials ahead of seeking FDA approval for patient studies, we can focus more on finessing the device itself to further improve the resolution achievable.”
Prof. Ibbotson said the team is also working on achieving wireless power delivery, which would obfuscate the need for power to be delivered through wires connected to the device via a junction in the eye. Additionally, a surgeon in Canada is developing “tricky technology” which will enable the diamond device to be implanted more securely against the retina with a surgery that is much quicker and simpler than existing techniques.
He said while the team’s achievements to date have exceeded their early expectations, they have together, shifted the goalposts and there is more to be done.
“We are a team of four and really, when we’re in a room together, innovation is our middle name – we’re really trying to push the boundaries to see what we can achieve. Already we’ve done more scientifically in the last few years than Steven and I could have ever imagined as junior academics all those years ago. Now we want to go to the next level, we want to interact with industry and push something out into the community that helps people now, not just in 30 years’ time.
“While our main focus was to develop a device that would give people navigational mobility, now our aim is much higher. We want to give people enough resolution to be able to genuinely and repeatedly recognise objects and text, with the wholly grail being face perception.”
The Advance of Diamond Technology
Diamond technologies are increasingly used in medicine. Being bioinert, diamonds are not perceived to be foreign to the body, which means they are not likely to be rejected. Commonly used to coat body parts like heart valves and hip joints due to its durability and low rejection rate; stem cells and other cells such as blood cells can be successfully cultured on diamond surfaces.
Diamond implants will also last longer than traditional implants, because of their inert qualities. In contrast to conventional implants, there is little chance of inflammation or a build-up of scar tissue, which can otherwise build up to a point that electrical signals can no longer be passed between the implant and the nerve cells, necessitating implant replacement.2
It was Prof. Steven Prawer who discovered that diamonds can be used to stimulate nerves, making them useful in the development of implants.
”We have discovered a form of diamond that we can make which is bio-compatible and very good as a stimulating electrode, which means we can put an electrical signal onto it that then causes the neurons to fire and get a response,” he told The Age.1
Man-made diamonds can be made with methane and hydrogen and “cooked” in five days using the microwave-like diamond reactor. When nitrogen is added, this otherwise insulating material can become conductive, making it ideal for transmitting electrical currents required to stimulate nerves.
The man-made diamonds being used in the iBionics device are black, however the team is currently looking into making them transparent. “Working with transparent diamonds means that in the future we may be able to upgrade the microchips by beaming information directly to the implanted bionic device, much as software is upgraded on a computer,” said Prof. Ibbotson. We’re looking at a whole new world.
Monash Vision Group
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 aims to help people who have damage to the optic nerve or anterior visual pathway, who would not be suitable for a retinal prosthesis. In January 2016, MVA stated that it hoped to begin recruiting patients for an initial trial in the latter part of that year. However in December 2016, Jeanette Pritchard, Chief Operating Officer of Monash Vision, more recently advised mivision that the device was undergoing “an extended testing period”. No indication was given as to when a clinical trial would commence.
Orion 1 Visual Cortical Prosthesis
In October 2016, US company Second Sight reported the first successful implantation and activation of its Orion I Visual Cortical Prosthesis in a human subject. A 30 year old patient was implanted with the wireless multichannel neurostimulation system on the visual cortex and was able to perceive and localise individual phosphenes or spots of light with no significant adverse side effects. The implant, performed as part of a proof of concept clinical trial, was not fitted with a camera.
Dr. Robert Greenberg, Chairman of the Board of Second Sight, said, “this initial success in a patient is an exciting and important milestone even though it does not yet include a camera. By bypassing the optic nerve and directly stimulating the visual cortex, the Orion I has the potential to restore useful vision to patients completely blinded due to virtually any reason, including glaucoma, cancer, diabetic retinopathy, or trauma. Today these individuals have no available therapy and the Orion I offers hope, increasing independence and improving their quality of life.”
Dr. Nader Pouratian, the neurosurgeon from University of California Los Angeles who performed the surgery said, “based on these results, stimulation of the visual cortex has the potential to restore useful vision to the blind, which is important for independence and improving quality of life.”
Second Sight plans to submit an application to the FDA early this year (2017) to gain approval for conducting an initial clinical trial of the complete Orion I system, including the camera and glasses. Assuming positive initial results in patients and discussions with regulators, Second Sight has stated it will undergo an expanded pivotal clinical trial for global market approvals.
Second Sight’s much talked about Argus II System has now been implanted in over 200 people with severe to profound outer retinal degeneration such as retinitis pigmentosa (RP). The first artificial retina to receive widespread approval, the Argus II is available to be implanted at approved centers in Austria, Canada, France, Germany, Italy, Netherlands, Saudi Arabia, Spain, Switzerland, Turkey, United Kingdom and the United States.
The device provides electrical stimulation that bypasses the defunct retinal cells and stimulates remaining viable cells, inducing visual perception in individuals with severe to profound outer retinal degeneration. The Argus II works by converting images captured by a miniature video camera mounted on the patient’s glasses into a series of small electrical pulses, which are transmitted wirelessly to an array of electrodes implanted on the surface of the retina. These pulses are intended to stimulate the retina’s remaining cells, resulting in the perception of patterns of light in the brain. The patient then learns to interpret these visual patterns, thereby regaining some useful vision. The system is controlled by software and is upgradeable, which, the company states, may provide improved performance as new algorithms are developed and tested.
Enrollment has now been completed in a feasibility trial to test the safety and utility of the Argus II in individuals with dry age-related macular degeneration.