Scientists have been working for decades to create an optical prosthesis that restores at least partial vision to those suffering from retinitis pigmentosa, macular degeneration and other retina-damaging diseases. Some retinal implants have begun to deliver on that promise, but the challenge remains for researchers to develop a technology that, in addition to providing clear images, can be worn comfortably over the long term.

Germany's Retina Implant, AG, thinks it has made great strides in both areas, an assertion that will be put to the test later this year when the company launches its second clinical trial, placing subretinal (under retina) implants in about 50 patients over the next few years. Meanwhile, Sylmar, Calif.–based Second Sight Medical Products plans to make its epiretinal (over retina) implants commercially available in Europe later this year. Researchers at the Massachusetts Institute of Technology and other institutions and medical technology companies are likewise developing retinal implants—the retina lines the eye's inner surface and records images in patterns of light and color—but are not as far along as Retina Implant or Second Sight.

Retinal reawakening
Retina Implant's initial human clinical trial, started in 2005, improved the eyesight of 11 patients to the point where they were able to recognize objects as well as see shapes so clearly they could combine individual letters to form words or, essentially, read at a basic level at normal reading distance and in regular light conditions, says Eberhart Zrenner, the company's co-founder and director and chairman of the University of Tübingen's Institute for Ophthalmic Research in Germany. Zrenner presented the trial's results in May at the 2010 Association for Research in Vision and Ophthalmology's annual meeting in Fort Lauderdale, Fla.

Retina Implant's second clinical trial seeks to implant the latest version of the company's technology in a larger pool of patients. The new implant no longer has external parts—its power supply is positioned under the skin behind the ear, connected with a thin cable that leads to the eyeball so that the chip does not move once implanted. (This could damage the chip.)

Retinitis pigmentosa kills the retina's photoreceptors, which are the rod and cone cells that convert light into electrical signals for the brain, leading to vision loss. This disease, one of the most common forms of inherited retinal degeneration, affects about one in 4,000 people in the U.S. Age-related macular degeneration (AMD), a leading cause of vision loss in the U.S. among people 60 years and older, gradually destroys sharp, central vision. The macula (the light-sensitive retinal tissue at the back of the eye) degenerates in two ways: In "dry" AMD the macula's light-sensitive cells slowly break down; in the "wet" form abnormal blood vessels behind the retina start to grow under the macula, thereby displacing it.

Retina Implant's device is a three- by three-millimeter microelectronic chip (0.1 millimeter thick), containing about 1,500 light-sensitive photodiodes, amplifiers and electrodes that is implanted directly under the retina to generate artificial vision by stimulating inner retina nerve cells. The chip, which is placed in the retina's macular region, absorbs light entering the eye and converts it into electricity that stimulates any still-functioning retinal nerves. This stimulation is relayed to the brain through the optical nerve.

It takes the brain one or two days to adapt to chip-assisted vision, according to Zrenner. "Lines are typically all that can be expected to be seen initially by people with retinal implants," he says. "However, scientists are finding that the human brain can quickly retrain itself to interpret the lines and shapes of different gray levels into meaningful images." With the aid of a chip one Retina Implant patient reported seeing images and words slightly flickering as though they were viewed through small waves at the bottom of a pool, Zrenner adds.

Power (im)plant
"The major advance of the subretinal approach is that the implant itself is light sensitive," says Robert MacLaren, a consultant vitreoretinal surgeon and professor of ophthalmology at University of Oxford's Merton College. MacLaren, who specializes in treating patients with AMD, retinitis pigmentosa, choroideremia and Stargardt disease, is the lead surgeon for Retina Implant's second clinical trial in the U.K. The trials will also be conducted in Germany, Hungary and Italy.

MacLaren likes the idea of placing the implant beneath the retina, where it can stimulate the retina's bipolar cells, which transmit signals from photoreceptors to ganglion cells. "Another advantage is that the implant is placed in the preferred location for stimulating the eye's photoreceptors," he says. "The fact that it's light sensitive simplifies the arrangement, although the actual surgery is still very complicated."

One of the difficulties designing a subretinal implant has been powering the device. Some researchers were hoping to tap light coming into the retina but they found the amount of energy inadequate, according to MacLaren. "This idea of a subretinal implant has been around since the 1970s," he adds. "But it hasn't been proved functional in a trial until Retina Implant did it."

Light, camera, action
Whereas the subretinal approach places the implant under the surface of the retina to stimulate bipolar cells, an epiretinal implant directly stimulates ganglia using signals sent from a camera and power sent from an external transmitter, both mounted on a pair of glasses. In the case of Second Sight technology, a receiver is implanted under the eyeball's clear mucus membrane, called the conjunctiva. A small camera on a pair of sunglasses captures an image and sends the information to a video processor, worn on the belt along with a wireless microprocessor and battery pack.* After the video processor converts the images to an electronic signal, a transmitter on the glasses sends that information wirelessly to the receiver, which in turn conveys the signals through a tiny cable to an electrode array, stimulating it to emit electrical pulses. The pulses induce responses in the retina that travel via the optic nerve to the brain, which perceives patterns of light and dark spots corresponding to the electrodes stimulated. Patients learn to interpret the visual patterns produced into meaningful images.

With the epiretinal approach, "you could potentially stimulate more of the retina than with a subretinal implant, and it would be easier to adjust for contrast and light," MacLaren says. A drawback to epiretinal implants is that they require a camera mounted on a pair of glasses, which is cumbersome and requires the patient to move his entire head (rather than simply the eyeball) to take in his surroundings, he adds.

Epiretinal implants have met with some success: For example, last year a 73-year-old man receiving a Second Sight Argus II implant at Moorfields Eye Hospital in London was able to see again for the first time in 30 years. All together, 30 people are testing Argus II implants and some of these devices have been in place for more than three years, according to the company, which anticipates a commercial launch of the Argus II in Europe later this year.

*Correction (6/16/10): This article originally stated that the video processor was mounted on the glasses.