Retinal implants usher in a new era for eye surgery and offer new hope for previously incurable blindness, reports E&T.
Hopes have been raised for millions of people suffering from macular degeneration and the less common pigmentosa by early trials of retinal implants that have demonstrated restoration of partial vision.
Last April, Moorfields Eye Hospital in London implanted devices, as part of an international phase I clinical trial, onto the retinas of two sufferers from pigmentosa who had almost totally lost their vision. Phase I trials are designed primarily to establish the safety of a procedure and in this case are being carried out on around 20 patients at various hospitals in Europe, the US and Mexico. The trial involves a retinal implant called Argus II, manufactured by the US company Second Sight (see 'The Technology' below).
While none of the hospitals have commented on this round of trials, there is reason for optimism: the first-generation Argus I device restored limited sight for six patients who received these implants during 2002 and 2004. Patients were able to detect light and motion, make out large letters and distinguish between objects such as cups, knives and plates. There are hopes that Argus II will facilitate finer resolution by generating about four times as many signals, although it is still a long way short of restoring full sight.
"This is very exciting; this type of technology will provide a solution in the future," says David Head, chief executive of the British Retinitis Pigmentosa Society, the registered charity dedicated to finding a cure for retinitis pigmentosa. As Head notes, one major advantage of these implants is that they are equally applicable to all sufferers from pigmentosa, irrespective of the genetic defect that caused it. "As RP is caused by many different gene flaws, some of which have not yet been identified, this is very valuable," says Head.
Argus II commercial availability
"The big question mark though is over the timescales," he continues. "The companies concerned would claim that it will be available within two years. Personally I would be more inclined to look at a four to five-year timescale."
In fact, manufacturer Second Sight is now equally cautious over timescales. "The Argus II could be commercially available in 2010, but that may be optimistic," admits Brian Mech, Second Sight's senior director of business development. Mech also agrees that cost could be an inhibitor, particularly in situations or countries where the operation is not covered by health insurance. "Pricing has not been determined, but active implants of similar complexity cost tens of thousands of dollars. We are hopeful that the devices will be covered by insurance," says Mech.
The other major point is that the efficacy and safety remain to be fully proven, with implants still representing work in progress. Second Sight is working on a third generation of the Argus technology, which Head believes will come closer to the ultimate goal of restoring full vision.
"I'm not in a position to answer this directly, but strong advocates of the technology believe it will ultimately enable patients to read, which would be fantastic," he says. "How many versions of Argus or others it takes to get there I don't know." However, the immediate goal is to enable people with visual impairment to regain independence, comments Head. "Being able to locate people, doors and other basics is the starting point." That could in principle be achieved with the Argus II technology, depending on results of the current phase I trials.
One interesting aspect of the implant is that it does not completely simulate normal vision, and does require time and training for patients to become attuned to it. Trial patients report that initially objects appear in a pixillated form as rows and columns of light dots. This reflects the actual mechanism involving the implanted chip's electrodes, creating signals resembling dots on a screen. However, with time, the brain seems to adjust and recreate more coherent images, so that a plate is then seen as a saucer of light rather than dots, according to Professor Humayun, who conducted some of the first implantations with Argus I.
As Second Sight's Mech points out, it is not clear whether this adaptation is just a standard learning process, or whether it involves reconfiguration of circuits within the visual centre. "It is difficult to isolate whether this is a training effect or a neural plasticity effect, or both," agreed Mech. "We suspect that neural plasticity is important."
There is good evidence for this view from the fact that the implant has failed to work in people who are blind from birth and whose visual cortex therefore never developed any circuitry for vision that could then adapt to the signals generated by the implant.
One aim of the trials is to understand the mechanisms of adaptation to the implant. Head also stresses that even if the implant fails on its own to restore full vision, there is still the possibility of combining it with alternative technologies. "The implant technology does not have to be considered in isolation," he says. "Advances in biometrics could be coupled with this technology. If a retinal implant enabled a blind individual to locate a person, and the camera and computer were also able to use face recognition software to identify that person, wouldn't that be a great combination?"
There is also hope that the technology can be adapted in future to treat people with other forms of blindness by stimulating cells further downstream in the human's visual processing cycle, in the optic nerve and even the brain, according to Mech.
More immediately, there is scope for tuning the system more closely to the varying requirements of individuals which is a line being pursued by another maker of implants, the German company Intelligent Medical Implants. While it is too early to say whether any of these approaches will restore full vision, there is already hope that many people with previously incurable conditions may have the option of partial vision.
At least three firms make eye implants that stimulate the retinal ganglion cells, with subtle differences between them. In all cases, the aim is to substitute the signals, normally generated in response to light by the retinal ganglion cells, which are neurons near the inner surface of the retina. Projections from the retinal ganglia called axons make up the optic nerve hooking up with the brain's visual centre.
The second version of the Argus system from US firm Second Sight is the best known and farthest ahead in clinical testing, having three components. First in line of sight is a pair of glasses with an embedded camera that transmits images to the second component - a radio receiver implanted against the eye. This, in turn, transmits signals via a tiny cable to a 4mm square chip , implanted on the retina and made of silicon and platinum, an inert metal chosen to minimise risk of immunological rejection by the patient. The chip incorporates electrodes that stimulate the retina ganglion cells, which then transmit visual information via the optical nerve into the brain for reconstruction of the original image. With current systems, the images are monochrome, although future versions may produce colour. The first version of the Argus chip had 16 electrodes, but the second-generation device under trial at Moorfields Eye Hospital (see main article), has 60 electrodes which should generate higher-resolution images.
The German company Intelligent Medical Implants makes a device called the Learning Retinal Implant System. This is outwardly quite like Argus, with three similar components, but incorporates learning software that allows the system to be tuned in response to the patient during the learning phase, although there is little firm evidence yet from trials that this results in better vision. The third contender, from US company Optobionics, is rather different in structure, with no external device and a smaller solar-powered microchip implanted, in this case, behind the retina, through a small surgical incision. Unlike the other two, this chip is wireless and needs no external power source or signal but requires a more complicated surgical procedure to install and has had teething problems with the chip structure, although the company believes these have now been resolved.
Who could benefit?
Current implant technology can only be used to treat blindness caused by loss of ability of the retinal ganglion photoreceptor cells - popularly known as rods and cones - to respond to light. The technology relies on normal working both of the optic nerve and the brain's visual centre and cannot be used to treat blindness caused by failure of those. It is therefore no use for blindness caused by glaucoma, for the latter damages the optic nerve, or by a stroke in the visual cortex, since the brain then loses its ability to process optical signals. The two conditions that can be treated by these implants with partial success are macular degeneration, the commonest cause of blindness affecting up to 15 per cent of over 75-year-olds and the rarer pigmentosa, which affects around one in 3,500 people. Even for these conditions, the implant does not appear to work for people who were blind from birth, probably because their visual cortex has not developed the ability to process optical signals into images, having been recruited for processing of other sensory stimuli, such as sound and touch.