Sightseeing
The Microelectronic Retinal Implant Providing a Semblance of sight to Two Pioneering Patients is the first Generation of a Device that may One Day Give sight to Blind People
Do you see anything, Mr. B.?" James Weiland, Ph.D., assistant p
rofessor of ophthalmology at the
Keck School of Medicine of USC, was fiddling with the buttons on a computer
keyboard.
"No sir," James Bueller* replied.
"How about now?" Weiland asked.
"No sir."
"Now?"
"No sir."
It was a quiet morning in late February 2002. The exam room in
the Doheny Eye Institute's fourth-floor clinic space was jammed
with an improbable number of people-physicians, technicians and
a video crew. And James Bueller, with a patched left eye and
swollen right eye, was the center of all the attention. His retina
had been implanted with a tiny microelectronic device that-it
was hoped-would restore sight to the eye for the first time in
more than 50 years.
The people in the room, many of who had been working on this
device or its earlier incarnations since the mid-1980s, were
completely silent as they concentrated on the event happening
just a few feet away.
"OK, Mr. B.," Weiland said after a few more button-taps.
"How about now?"
"No sir. Hold on. Yes! Yes! Yes sir!"
And, just like that, a blind man saw.
Testing
Bueller became the first-ever person to receive a permanent microelectronic
retinal implant on Feb. 19, 2002. He had been chosen out of a
field of numerous eager volunteers after undergoing a battery
of tests to determine, among other things, whether or not his
eye was capable of responding to the sort of electrical stimulation
given off by the implant.
After that, the ophthalmologists working on the implant had to
decide which eye to put the implant in, explains Mark Humayun,
M.D., Ph.D., professor of ophthalmology at the Keck School, associate
director of research at the Doheny Retina Institute and the principal
investigator on this FDA-approved trial. The idea, he says, was
to see if one eye had degenerated more than the other, and to
choose the "worse" eye for the implant, so as not to
compromise any remaining vision.
Once the tests were completed, Bueller was given a neuromuscular
block to paralyze his right eye's muscles for the surgery. Because
the drug-induced paralysis takes time to set in, the surgery
was scheduled for two weeks later.
That surgery took place at the USC University Hospital Outpatient
Surgery Center. Humayun performed the procedure; representatives
from the Valencia, Calif.-based Second Sight, LLC, and Weiland
tested the device throughout the surgery to ensure that it was
functioning properly.
Other participants in the surgery from the Keck School included
Eugene de Juan Jr., M.D., professor of ophthalmology and chief
executive officer of the Doheny Retina Institute; USC oculoplastic
surgeon Michael Burnstine, M.D.; Gretchen Van Boemel, Ph.D.,
assistant professor of ophthalmology; otolaryngologist Dennis
Maceri, M.D., and Robert Greenberg, M.D., Ph.D., president and
chief executive officer of Second Sight.
Implanting
Implanting an intraocular retinal prosthesis is a multi-step
procedure. First, an implantable chronic stimulator case, which
holds all the electronics for the prosthesis, is placed behind
the ear; wires are then run under the skin to the eye.
At that point, the delicate electrode array is inserted into
the eye itself and attached to the retina. "Although there
are many incisions," says Humayun, "they are all in
the hairline or hidden under the white of the eye. To most people,
the procedure should be cosmetically acceptable."
It is only once the receiver is in place that the sliver of silicone
and platinum-what many incorrectly refer to as a 'chip'-is implanted,
using a novel surgical approach and custom-built instrumentation
developed by de Juan and colleagues at Second Sight.
Although the retinal prosthesis had been tested in the past,
it was always done on a temporary basis, with the prosthesis
being removed less than an hour after being implanted. In this
trial, the prosthesis is intended to be a permanent implant;
unless complications occur, the working electronics will remain
in place indefinitely.
Bueller stayed at USC University Hospital overnight after the
surgery, then was released. A few weeks later-on Feb. 27, 2002-he
returned to the Doheny Eye Institute to have the implant turned
on for the first time.
After Bueller detected that first flash of light-from the stimulation
of just one of the 16 electrodes-the team went on to test the
rest of the electrodes. With each positive response from Bueller,
the mood in the room became "unbelievable, exhilarating,"
Humayun recalls.
For Bueller, it was a moment he had barely dared believe possible.
"It's as bright as the noon-day sun," he said of one
particular flash of light. "I haven't seen anything that
bright in 50 years."
Since then, both Bueller and a second patient enrolled in the
trial-Susan Locher*-have been able to discern shapes and patterns
displayed to them. Most importantly, they have been able to pick
out lit doorways and windows in a darkened room. This, notes
Humayun, is the beginning of what is known as ambulatory vision-the
ability to navigate through a space using only visual information.
Still, Humayun cautions, all of this remarkable progress is only
the first step in a long journey. Testing the retinal pro-sthesis
will take time, he notes, because "it's a Class III device-the
highest-
risk device, according to the FDA. That's because it's an implant
that will be left in for the rest of the person's life."
To date, the prosthesis has been implanted in just Bueller and
Locher. It will be tested in at least one more patient-and possibly
several more-before this first phase of the trial will be considered
complete. After that, several more small trials will be conducted;
if those results are favorable, larger-scale tests will be initiated.
In all, says Humayun, it will likely take another three to five
years for an upscale, later-generation version of the prosthesis
to be available to patients worldwide.
Seeing
The intraocular retinal prosthesis floating just on top of the
retinas of Bueller and Locher originally sprang from the minds
of Humayun and de Juan-and from a long-standing collaboration
between these two prominent scientist-physicians.
Intended to stand in for the damaged retinal cells in patients
suffering from such degenerative eye diseases as retinitis pigmentosa
and macular degeneration, the retinal prosthesis works, in essence,
by taking over the job of cells damaged by these diseases. The
implant has 16 electrodes studded in a 4-by-4 grid. The electrodes
are stimulated by an incoming image and they, in turn, stimulate
the remaining retinal cells. The information is then relayed
via the optic nerve to the vision centers of the brain to create
a representation of that image.
In the first few months after Bueller's surgery, those images
were transmitted to him via computer. A few testing sessions
later, Humayun and his colleagues tried out a small video camera
to capture the image. Today, Bueller does most of his 'looking'
though a tiny camera mounted on a pair of shaded glasses. The
signal received by the camera is digitized and transmitted to
the radio receiver behind Bueller's ear and from there to the
device itself, where it "lights up" electrodes and
stimulates the remaining retinal neurons.
The advantage of having so much of the device outside of the
body is immense, even if not immediately obvious, says Humayun.
"It means that we can replace or update a lot of it easily
and without surgery."
The next generation of devices, says Weiland, will have a greater
number of electrodes and thus a greater level of resolution.
He believes such a device should be available within the next
few years. "We're benefiting from the drive to miniaturization,"
he notes.
"The key," adds Humayun, "is getting to understand
the stimulation of the retina better. Right now, the amount of
electrical energy it takes to activate the retina forces us to
make a device that may not give fine perception.
"What we need to figure out now is how to stimulate the
retina even more efficiently; then, we may be able to reduce
the size and increase the number of electrodes on each implant."
Humayun has been quite pleased with the results of these first tests of the
d
evice, although not
entirely surprised by them. After all, he notes, the cochlear implant, on
which this device is loosely based, uses just six electrodes to replace the
30,000 nerve fibers in the auditory nerve, and allows most of its users to
hear a telephone conversation. In this case, however, just 16 electrodes are
used to stimulate the 1.2 million fibers that make up the optic nerve. While
that may not seem like a good ratio, Humayun notes, "The brain has an
incredible ability to recognize patterns, to fill in the blanks where necessary.
Based on simulated testing in sighted volunteers, we figure it could take
just a thousand or so electrodes to get enough resolution to read large print."
Several such thousand-electrode models are under development
at Second Sight, Greenberg says, but are a decade away from being
available to patients worldwide.
Despite the work ahead and the years of testing they face, Humayun
and his team say they are energized by the results of the first
patients-and, in particular, by the day that Bueller saw that
simple but profound flash of light.
"This is like the Wright Brothers," says Humayun. "This
is the first time we've been able to fly. It took a lot of work
to get to this point, but this time, when we took off, we flew."
n
The National Institutes of Health/National Eye Institute and
Second Sight, LLC, provided funding to support the research and
development of the retinal prosthesis implanted in this trial.
The National Science Foundation, the Department of Energy, the
Office of Naval Research, the Whitaker Foundation, The Foundation
Fighting Blindness, the Defense Advanced Research Projects Agency
and Second Sight, LLC, have provided other funding toward the
development of a retinal prosthesis.
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