Our third and last article (for now) is on advances in vision care.
IN 1991 ROBERT GREENBERG was an M.D./Ph.D. student observing his first operation. On the table lay a blind man under local anesthesia. As Greenberg watched, an ophthalmic surgeon guided a tiny electrode into the man’s eye and brought it as close as possible to the surface of his retina.
“An assistant turned on the current, and the patient saw a spot of light,” Greenberg remembers. “Then he put in a second electrode, and the patient saw two spots of light.” The experiment was the first investigation into how a blind person’s retina would respond to electricity inside the eye and whether it might trigger something like sight.
What if you kept adding electrodes, Greenberg wondered. If he could find a way to deliver many precise bursts of electricity to targeted positions on the retina, it might produce a kind of synthetic vision. The idea combined two of his passions: medicine and electronics. That evening he told his girlfriend, “I think I know what I’m going to do with my career.”
Greenberg saw his task—bringing sight to the blind—as a relatively simple engineering problem. He would build a tiny implantable device with many electrodes, each producing a spot of light in the darkness, to restore the whole visual field. “I wanted to build it for my Ph.D. project,” says Greenberg.
Greenberg co-founded a company called Second Sight in 1998 to develop a retinal prosthetic, but it took until 2011 for the company’s Argus II device to be approved for market use in Europe; U.S. clinical approval came two years after that. And the device was not as effective in restoring vision as he had hoped. Activating its electrodes in careful patterns enables patients to see flickering arrangements of light and dark—just enough to make out a crosswalk or to tell whether someone’s face is turned their way.
Those limitations don’t obscure the extraordinary fact that this and other treatments for blindness are rapidly becoming a reality. And while the Argus II is the first artificial vision therapy to make it to the clinic, several other treatments are on their way, says Paul Sieving, director of the National Eye Institute.
“The retinal prosthesis is a tremendous advance that takes patients from nothing to something,” Sieving says. Other approaches to ending blindness use technology in similarly ingenious ways, he notes. In 2013, Sieving launched the NEI’s Audacious Goals Initiative to fund research on restoring vision by regenerating damaged cells in the retina. “We’ve made remarkable progress in understanding the biology of the eye,” Sieving says. “It seems time to harness this biology and do something big.”
Some therapies may eventually be adapted for treating people who are at the beginning stages of vision loss, making them more blindness prevention than cure. But Joan Miller, a retina specialist and chief of ophthalmology at Mass. Eye and Ear and Massachusetts General Hospital, says cures will probably always be needed. “People fall through cracks,” she says, “so the notion of having regenerative or hardware solutions is very appealing.”
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Many of the most promising approaches fall into four categories: the retinal prosthetic, gene therapy, stem cell treatments, and a technique that uses optogenetics, a way to engineer nerves to fire in response to bursts of light. Each approach has shown potential in restoring at least partial vision, says Stephen Rose, chief research officer of the Foundation Fighting Blindness. His group funds research on all of them.
No single therapy is likely to restore natural vision in the near future, Rose cautions. Progress is rapid but the problem is complex, and the treatments being developed may not work for everyone. But he wants patients to know that a cure is on the way. “Too many people still get a diagnosis from their doctor and are told there’s nothing that can be done; they’d better learn to use a cane or a guide dog,” Rose says. “Instead, patients should be told that great advances are being made. There is true hope.”
MILLIONS ARE WAITING IN the darkness for that hope. The World Health Organization estimates that 39 million people worldwide are blind from a host of causes, including infectious diseases and uncorrected cataracts. In well-off countries such as the United States, where 1.3 million people are legally blind, the most common causes involve the breakdown of cells in the retina.
The retina is a thin piece of tissue about the size of a postage stamp at the back of the eye; it’s so delicate that it’s often likened to wet, one-ply toilet paper. Light travels through the eyeball to reach the retina, then passes through several transparent layers of cells to strike the rod- and cone-shaped photoreceptor cells. The photoreceptors convert light into an electrical signal that travels along a complex network as a pattern of “firing” cells. It goes to a layer of bipolar cells for processing, and they convey the information to a layer of ganglion cells, which do more processing before sending the refined signal up the long sections (axons) of nerve cells that form the optic nerve, which brings the signal to the brain. There, the pattern of electrical pulses resolves into something recognizable—a landscape, printed words, a face.
Damage to any of these retinal cells can impair vision, and such damage is a major cause of blindness. It’s the root problem in macular degeneration, diabetic retinopathy, glaucoma and a handful of genetic diseases. Second Sight’s retinal prosthesis is currently approved only for patients with inherited retinal disorders (IRD), formerly known as retinitis pigmentosa, a group of genetic diseases characterized by a loss of photoreceptors.
A patient using the Argus II wears sunglasses with a tiny built-in video camera. A small processor that the person carries converts the camera’s stream of video data into simple patterns of light and dark on a grid of 60 pixels. The processor then sends that pattern wirelessly to a chip implanted above the retina, where 60 electrodes stimulate undamaged cells, creating signals that travel up the optic nerve. Two devices being developed by other companies, Retina Implant in Germany and Pixium Vision in France, operate on similar principles.
The Argus II’s 60 electrodes are trying to do the job of the eye’s roughly 125 million photoreceptor cells, so it’s not surprising that they produce extremely crude images. But Second Sight’s engineers are working on new software that will allow the video processors to increase resolution, an update that the more than 200 current users of Argus II will be able to download to their devices.
Second Sight’s other major initiative, dubbed Orion, has many similarities to the Argus II. It also uses sunglasses, a processor and an implant with electrodes to stimulate nerves. But the Orion implant is surgically installed on the brain’s surface, bypassing the retina and the optic nerve, sending data to electrodes pressed against the surface of the visual cortex. That connection may benefit those who have lost vision because of damage in the structures between the eye and the brain—the loss of an eye through trauma, for instance, or damage to the optic nerve. Greenberg expects clinical trials to begin this year.
