01 October 2009

Retinal prosthetics: light at the end of the tunnel

Retinas-implants gave the blind a second sightmembrana
Electronic retinas cease to be props from science fiction films.

Several scientific groups and companies are working on similar prostheses at once. As experiments are carried out in test tubes, on animals and even on humans, the developers of such devices can also be said to gain vision. The structures are constantly being polished. And this gives hope to the blind.

One of the largest initiatives in this field and, perhaps, the oldest is the Boston Retinal Implant Project (BRIP). It was launched back in the 1980s, when the design and features of the artificial vision system were seen by scientists only in the most general terms. Now BRIP has unveiled its most recent version of the prosthesis. Within three years, the creators intend to test it on humans.

In short, everything looks simple: a miniature camera on glasses wirelessly transmits a signal to a tiny chip mounted on the eyeball. The chip translates this information into a set of weak electrical signals sent to a grid of electrodes that are embedded in the thickness of the retina. They stimulate nerve cells, and a person gains vision.

The search for the best option for such a scheme has been going on for more than one year, and not only in BRIP. We chose it among other schemes, considering it the optimal technical way to restore vision, the most suitable for rapid implementation.

In an early BRIP project, the receiving coil was located on the side of the eyeball,
the chip processing the signal is on top, and the grid of electrodes is in the back of the retina.
(it is not visible in the upper figure, but is shown in the diagram below).
On the upper inset is a picture of such a chip. On the bottom is a mock–up of a system with a camera on glasses.
Later, the device for receiving signals from the camera changed its location.
(illustrations by the Boston Retinal Implant Project).

There are several options for delivering images from the camera to the destination. The most tempting in terms of effect is the connection of electrical contacts directly to the cerebral cortex. But he is also the most risky for health. Another move is to connect a set of electrodes to the optic nerve, on its way from the eye to the brain. But it requires a masterly surgical operation.

At the same time, according to scientists from the BRIP project, the most common diseases that lead to vision loss are age–related macular degeneration and pigmentosis. With them, photosensitive cells in the retina fail. But its bipolar and ganglion "cells", transmitting a signal from photoreceptors to a network of nerve fibers inside the eye itself, and through them to the optic nerve, remain functional. Why not try to send signals to these intermediate cells?

One of the important issues is the place of implantation of the electrodes. In the eyeball, the rods and cones are located farther from the vitreous body and from the lens than the nerve cells. Accordingly, if we want to get to them from the outside of the eye, and from its back wall, we need to overcome more layers, and this can lead to severe damage to the retina.

This is how they tried to act in previous projects. The authors of the new implant say: for its normal operation, it is enough to place the electrodes (made of iridium oxide, by the way) on the outside of the eye. More precisely, in the layer lying directly under the retina. This reduces the risk of damage and reduces surgical intervention when installing the device.

The sequence of the key shells of the eye
and two ways of placing a stimulating chip with electrodes –
in the depth of the eyeball, above the retina (1)
or closer to its outer surface, actually under the retina (2).
Pay attention to the fact that the light comes from above
(illustration by Boston Retinal Implant Project).

The second improvement of the team from Boston is a chip that processes the signal. It should be attached to the surface of the eyeball, but at the same time inside the eye socket, so that it will not be visible from the outside. In the new BRIP project, this chip is hidden in a sealed titanium case.

This should reduce the negative impact of the implant on the body. It is equally important that the destructive impact of the body environment on the implant itself will be reduced. Scientists expect that the device "in a new design" will be able to work flawlessly inside a person for at least a dozen years.

The method of transmitting a useful signal and power supply to the prosthesis was also adjusted. In the new device, a metal ring embedded in the sclera around the iris is responsible for this. In fact, it consists of two concentric rings-antennas. One of them is responsible for the wireless reception of power pulses of the circuit, and the second is responsible for receiving the picture. Accordingly, special glasses with transmitting antennas in the frame should supply the implant with both power and information flows.

The model of the new implant (photo by Shawn Kelly)
and a grid of electrodes from BRIP (shown at high magnification),
embedded in a pig's eye (photo by Boston Retinal Implant Project).
Note that the chip is placed under the vascular membrane of the eyeball –
you can see how the capillaries pass over the chip.

The experimental BRIP device has only 15 channels – it can broadcast 15 pixels to the retina. This is no longer a record. But for now, it is important for the project participants to check the operability of the scheme. In addition, according to them, after tests on volunteers, it will be possible to improve the signal processing algorithm.

When it becomes clear what exactly and in what form the blind perceive when applying current pulses to the grid, image optimization will help convey "more meaning" at the same points. Further, the number of contacts can be increased by an order of magnitude, or even by two.

BRIP reported on his project in detail in an article in IEEE Transactions on Biomedical Engineering. So far, the new implant has been tested for 10 months on pigs. The purpose of the test was not to test the possibility of restoring vision, but to test the scheme for biological compatibility: whether it causes inflammation and so on. Checking the novelty on people is the next in the plan.

And the Americans are sure that in some form vision can be restored with the help of such electrodes. About a decade ago, the same BRIP team conducted experiments on blind volunteers without any chips.

A set of electrodes was temporarily connected to the photosensitive shell of the eye and a weak voltage was applied to them. The subjects reported the appearance of a chain of visual spots, the number of which coincided with the number of contacts activated at a given time.

Other scientists have managed to move even further along this path BRIP. The American company Second Sight, which closely cooperates with a number of scientific institutions in California, uses a similar approach in its developments. They build such a chain: a camera on glasses – a video processor worn on a belt – a transmitter in glasses – wireless signal transmission to a chip receiver inside a person, and then - through thin wires into a grid of electrodes mounted on the retina.

Now, clinical trials of the Argus II device, which includes an implant with 60 stimulating electrodes, are in full swing. This is also far from the coveted several thousand pixels, at which patients could already distinguish people's faces near and read. But it's better than nothing: even the ability to identify the boundaries of light and shadow (doorways, stairs) or bright objects is worth a lot.

Artificial retina from Second Sight has already been introduced to 18 volunteers, one of whom – 68-year–old Dean Lloyd (Dean Lloyd) - has been living with her for about two years. Experiments show that he can accurately point his finger at a bright dot appearing in an arbitrary place on a dark screen, walk along a white line drawn on a dark floor, and distinguish the general contours of objects.

At the same time, he even has a different color perception (basic colors pop up). It is not entirely clear how they are consistent with the color of the objects presented, but for a person who has lived in absolute darkness for 20 years, these red, blue and green flashes are a miracle.

Blind patient Lloyd tests the work of the second "Argus".
In the background is one of the researchers, neuroscientist Matthew McMahon.
A tiny camera transmitting a picture for Lloyd,
almost imperceptibly mounted in the frame of glasses (on the bridge of the nose).
The video processor unit is visible in the hands of the subject,
in which he himself can adjust the parameters of the broadcast signal
(photo by Paul Chinn/The Chronicle).

The Argus tests, as well as the upcoming test on volunteers of a minimally invasive implant from BRIP, should show that the "external video camera – artificial retina" bundle can claim to be a mass method of ridding people of a terrible disease. But ideally, scientists and doctors want to get rid of the external components of the system altogether. And projects of this kind also exist.

For example, an implant from the American company Optobionics was tested not only on cats, but also on humans. The prototype of the electronic retina from the University of Pennsylvania is similar to it in many ways.

Both implants are united by one principle: artificial photoreceptors are located in the implant itself and perceive light that has passed naturally – through the lens and vitreous. Stimulating electrodes are located behind the photodetectors.

Back in 2004, Optobionics reported in an article in Archives of Ophthalmology about the first successes of its microchip. The company managed to place 5,000 photodetectors and electrodes on a two-millimeter silicon plate and implanted this device in six patients with retinal pigmentosis. The volunteers wore the chip for 18 months.

The founders of Optobionics are Vincent and Alan Chow (Vincent, Alan Chow).
A microchip (black circle) on the surface of the coin and it is also embedded in the human retina.
Because of the main material, silicon, this experimental device is called Artificial Silicon Retina, or ASR.
The place where ASR is being implemented is shown below. The thickness of the chip, by the way, is 25 micrometers
(photos by Optobionics, illustration by Mike Zang).

The subjects showed some improvement in vision. And long-standing tests have proved that the microchip does not cause rejection and inflammation. But all the details of the interaction of such an extensive set of contacts and the nerve cells that accidentally fell under them had yet to be sorted out.

Alas, later the company stopped its work for a long time for reasons unrelated to science. And only relatively recently, Optobionics resumed its activities, promising to continue experiments with its microscopic implant.

As you can see, this whole "bioengineering arms race" is taking place rather slowly. It takes years to improve the solutions found, and no less to test their effectiveness "in real combat". But millions of blind people do not care who exactly will come to the finish line first and will receive "prize money" in the form of mass sales of this equipment. For the disabled, the most valuable prize is returned vision. Even with a resolution of several tens of pixels.

Are you able to admire the full Moon in the night sky if it appears to you as a set of just a few light points, without the slightest hint of details? One of the patients checking the Argus II retina now knows the true price of such beauty. She hadn't seen the moon in 15 years.

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