Researchers race to produce bionic
By Daithí Ó hAnluain
THE race to develop a bionic eye has caught the public imagination,
and fed the urgent hopes of millions of potential patients. While
researchers have made enormous progress over the last 15 years -
already 22 patients in the US and Europe are using prototype prostheses
involving three different technologies - fundamental problems remain.
There are more than 10 major groups studying four fundamental approaches
that could, in the long term, cure most forms of blindness. At present,
the most promising approaches apply to retinitis pigmentosa (RP),
'dry' age-related macular degeneration (AMD) and Usher's Syndrome,
conditions where the photoreceptors degenerate but the optical 'wiring'
is still in place.
The four approaches include subretinal implants, epiretinal implants,
optic nerve and cortical prosthetics. Within each approach there
are competing teams, and even within teams, variations and novel
solutions exist. Subretinal and epiretinal approaches are the furthest
advanced, with clinical trials already underway.
Two brothers, Drs. Alan Chow and Vincent Chow, one an electrical
engineer and the other a paediatric ophthalmic surgeon, have pioneered
the development of the sub-retinal chip. Their implant is just 2
mm across and contains 5,000 microphotodiodes, each with its own
stimulating electrode. They are powered by incident light, requiring
no added current.
These chips, produced by the Optobionics company (founded by the
Chow brothers), are designed to directly stimulate the remaining
overlying cells of the retina. The chip is surgically implanted
in the subretinal space and it is designed to produce visual signals
similar to those produced by the photoreceptor layer.
Optobionics currently leads the research pack, with 10 patients
having received the implants as part of a clinical trial begun three
years ago. Initial reports indicate that all patients have expressed
moderate to substantial improvement of visual function. Some patients
could read letters on an eye chart who could not do so before surgery.
Others have indicated improved ability to function in new environments,
to see facial features and to recognise people.
But the Chow brothers have come in for considerable criticism. Although
their results are good, critics argue that the chip has nowhere
near enough power to generate the effects recorded. Critics speculate
that the improvements are caused by neurotrophic factors, released
as a biological response to injury.
"In the long term the neurotrophic effect might be more important.
One could speculate that if you just put in a buzzer in there, and
give the retina and brain a little excitation, you could have the
same effect - at least temporarily. The Chow Brothers are well aware
of this neurotrophic effect, however, and they know that more work
needs to be done, with rigorous, regular testing," said Gerald
Chader MD, Chief Scientific Officer of the Foundation Fighting Blindness,
a US non-profit organisation that supports vision research
The Chow brothers are not alone in the pursuit of a subretinal prosthesis.
The German Southern Consortium, headquartered in the University
of Tuebingen, led by Professor Eberhart Zrenner, has taken a similar
approach, while the Japan Hybrid Retinal Implant team has added
a neat twist. That chip relies on living neural cells to transmit
the signals from the microphotodiodes.
With epiretinal technology, on the other hand, the implant is placed
atop the retina where an array of electrodes transmit light signals
through the retina. The most advanced project is led by Mark Humayun
MD, professor of ophthalmology at the University of Southern California:
"We have successfully completed enrolment and implantation
of three patients in the trial. And we have found that the devices
are indeed electrically conducting, and can be used by the patients
to detect light or even to distinguish between objects such as a
cup or plate in forced choice tests conducted with one patient so
far," Dr Humayun said.
The epiretinal device is a 4 x 5 mm sliver of silicone and platinum
with 16 electrodes in a
4 x 4 array. It receives signals from a video camera, held on a
pair of glasses. The epiretinal programme has received the imprimatur
of the US Department of Energy (DOE), which gave Dr Humayun's group
the largest grant it has awarded for implant research.
"The group we started with was Mark Humayun's group because
even before we got into it they put a device into one patient. There's
been a validation of the epiretinal device. This is not written
in stone, but we decided that the epiretinal device looked the most
promising. The 16-electrode device showed results in the first patient
that were even better than anticipated. We decided that we would
jump in on that and focus on a 1000-electrode device," said
Michael Viola MD, director of the medical science division of the
With an array of 32 x 32 (1024 electrodes) patients could expect
vision of 20/26, and even at 500+ electrodes (say a 25 x 25 array,
or 625 electrodes), a patient could read large print, one of the
internal goals set for the DOE's retinal project.
"The two key research questions that remain are what happens
at the electrode/tissue interface and how the brain perceives/adapts
to the signals that are presented to it (the psycho-physics of phosphene
vision). Humayun's group is the most advanced in terms of being
able to provide insights into the latter question," said Professor
Nigel Lovell of the Graduate School of Biomedical Engineering, University
of New South Wales and one of the leaders of the Australian Bionic
Other research teams working on epiretinal implants include a team
at Harvard University, headed by Professor John Rizzo, and the German
Northern Consortium, headquartered at the University of Bonn, led
by Professor Rolf Eckmiller.
Getting on patients' nerves
The optic nerve implant takes an entirely different approach. In
1998, a spiral cuff nerve electrode was implanted intracranially
and wrapped around the optic nerve of a RP volunteer. The cuff stimulates
the nerve fibres via four electrodes, though the team now hopes
to double that number. Very low current gives rise to the perception
of phosphenes. While there was no way of knowing in advance how
stimulation would affect the optical nerve fibres, trial-and-error
taught the team how to induce limited pattern recognition in the
"If you're going to do artificial vision, you don't have to
use the eyeball, do you? There is a problem, however. As someone
said, cynically, to underline just how difficult a task it could
be: 'The fibres are not colour coded.' You don't know what fibres
will provoke what images," notes microelectronics engineer
John Alderman of Ireland's National Microelectronics Research Centre.
Other problems dog the research, too, including large, external,
processing equipment and a transcutaneous power and data RF link,
as with the epiretinal device. But a new project by the team hopes
to improve the system. The team plans to implant three more patients
by 2005 and expects large-scale human trials to follow.
Yet another approach, the cortical implant, plugs directly into
the visual cortex bypassing the eye, the optic nerve and most of
the rest of the brain to stimulate the nervous system where the
majority of visual processing takes place.
"Depending on your point of view, the cortical implant is either
the Lowest Common Denominator or the Highest Common Multiple,"
commented Dr Chader.
"Cortical approaches offer the possibility of treatment for
a wider variety of vision problems but are considerably more difficult
due to the mapping of stimulation sites on the brain," adds
Several teams are following the cortical implant route, including
the US National Institutes of Health, and the University of Utah
headed by Professor Richard Normann.
The most successful, and most controversial of the cortical research
projects, is the Dobelle Group, based in Lisbon, Portugal, and headed
by William Dobelle. Dr Dobelle's research offers the first commercial
artificial vision system. One of his patients reportedly even drove
a car. But his secrecy and avoidance of standard US clinical trials
have prompted many to dismiss his work.
"Dobelle's group has virtually done an animal experiment on
a human. I was fortunate enough to attend a lecture by Dr. Dobelle
and its very interesting technology and hopefully it might work.
One thing that's very encouraging is that it looks like the safety
issues might have been solved by Dr. Dobelle, because one chip has
been in since the 1970s. That's a very long time," notes Dr.
Only time will tell which of the approaches now being studied will
produce functional artificial vision. Each of the four approaches
has advantages and disadvantages, and each faces its own technical
obstacles. Huge technical challenges remain in the areas of materials
sciences, microelectronics and computational modelling. There are
also unresolved issues with electrochemistry and neurochemistry.
Finally, there is the issue of the implantation surgery itself,
which has already shown to present a steep learning curve.
Nonetheless there is reason enough for optimism, since research
has already progressed further and faster than many would have thought
possible. The next few years should see even faster progress, fuelled
by the combined forces of scientific inquiry and commercial competition.
The Foundation Fighting Blindness
Mark Humayun MD
Keck School of Medicine
Ireland's National Microelectronics Research Centre,
Nigel Lovell PhD
Graduate School of Biomedical Engineering,
University of New South Wales
Michael Viola MD
US Department of Energy