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Microchips in the Eye.
Electronic retinal implants are gaining popularity as research into the
technology continues to show improvements for patients.
About 30 research groups worldwide are currently working on an electronic
retinal implant. Retina Implant AG, a company in Reutlingen, Germany, has
conducted a successful clinical pilot study demonstrating that the
technique of
subretinal stimulation permits visual recognition of patterns and letters
of the
alphabet. This study confirms electronic retinal implants can give very
useful
visual perceptions to the blind (See three videos regarding Retina AG
study
results and demonstrations
http://www.mddionline.com/video-vault-retina-implant-ag-electronic-microchip )
.
Hereditary retinal degeneration (retinitis pigmentosa) results in a
progressive
loss of photoreceptors and in most cases leads gradually to a complete
loss of
vision. More than 100,000 people in the United States and an estimated
three
million people worldwide suffer from various forms of this disease.
Although
drugs are currently under development, there is as yet no therapy for this
ailment. However, many of those affected may soon be able to recover a
certain
degree of vision by means of an implanted camera chip.
In the normal eye, incident light passes through the transparent tissue of
the
retina and falls on some 120 million rods and six million cones at the
fundus of
the eye. The light is converted in a multiple-stage process into
electrical
signals. These signals undergo preliminary processing in the underlying
layers
of bipolar, horizontal, and amacrine cells and are then passed on to the
ganglion cells. For their part, the axons of the ganglion cells
communicate with
the optic nerve, which forwards the information gained thus far to the
visual
cortex (i.e., visual center) of the brain.
Subretinal Implants.
Diseases like retinitis pigmentosa (RP) are distinguished by the fact that
a
large part of the retina remains functional even after loss of sight.
Although
the rods and cones that normally convert light into nerve signals are
destroyed
by this disease, most of the retinal nerve tissue, which has the task of
pre-processing information on its way to the brain, remains intact. In
other
words, the visual apparatus is functional; it just lacks input. Based on
this
concept, Eberhart Zrenner at the University Eye Clinic of Tübingen has
developed
a subretinal implant in cooperation with that university’s Institute of
Natural
Science and Medicine (NMI).
For the university’s implant, natural optical stimulus is simply replaced
by
pulsed, light-dependent electrical stimuli, resulting in the perception of
phosphenes (artificially triggered light phenomena). Because the
electrical
excitation invariably involves a number of cells, the patients cannot
visualize
objects sharply, but are nevertheless able to locate light sources and
localize
physical objects.
The implant is located subretinally, i.e. behind the retina. From an
anatomical
point of view, it exactly replaces the photoreceptors that have been lost
(see
Figure 1). From the viewpoint of signal processing, this is an
all-important
advantage; the implant’s subretinal excitation exploits the full range of
neuronal circuitry in the retina along the way to the optic nerve. The
electrical signal is triggered at the point of brightness, and the
stimulation
strength corresponds to the intensity of the incident light. The optical
image
is thus exactly replaced by an electrical pattern of excitation.
The retinal implant consists of a silicon chip about 3 × 3 mm in size and
70-µm
thick, with 1500 individual pixels. Each of these pixel cells contains a
light-sensitive photodiode, a logarithmic differential amplifier, and a 50
×
50-µm iridium electrode into which the electrical stimuli at the retina
are
guided. The circuitry was developed in collaboration with the IMS in
Stuttgart
and is made by applying 0.8-µm CMOS technology.2 The result is a pure
analog
chip, with the advantage that its power consumption is very low (maximum
10 mW),
and the heat passed on to the retina by electrical power from the chip
remains
below 0.5 K. The microchip is positioned on a thin, highly flexible
circuit
board of polyimide with gold circuits that transmit power and control
signals
(See Figure 2). The very fine polyimide strip is connected in turn to a
thin,
coiled cable through which the electricity of the chip is supplied. This
elastic
cable passes through the orbital cavity to the bone of the temple and from
there
to a point behind the ear, where it is connected to an inductive power
supply
unit in a ceramic housing. The electrical energy is received inductively
from
the outside through a second coil that is located on the skin. Permanent
magnets
in the two coils ensure close contact.
All of the components must of course be biocompatible—that is, well
tolerated by
the body—and must possess long-term stability. This is an enormous
technological
challenge that requires, among other things, the use and combination of
new
materials. The components must be provided with a hermetically sealed
protective
layer at the point of contact with the surrounding tissue. They must
undergo
numerous tests to demonstrate the device’s ability to withstand the
corrosive
environment within the body. An especially critical point is that the
presence
of electrical voltage can greatly accelerate the corrosion process. The
selection of materials and the manner in which they are processed is
critical.
Above all, the electrodes and their contact points on the chip are of
decisive
importance. The useable electrode surface must be as small as possible but
also
offer as large a surface as possible to ensure good contact with the
retina. For
this reason, the electrodes are manufactured of fractal iridium, whereby
the
materials permit a higher transmission of charges.
Optimal visual perception is present when pulse durations are around 1
microsecond and the charge amounts to 2–5 nC per pixel. This corresponds
to a
voltage of up to 2 V. The repetition rate of excitation is normally 5–7
Hz,
because higher rates would result in overstimulation of the retina. The
patient’s visual perception therefore flickers somewhat.
Clinical Studies and Results.
During a clinical pilot study at the University Eye Clinic in Tübingen,
the
retinal implant was first tested over a period of up to four months in 11
patients. The development of a new type of surgical procedure was given
high
priority in collaboration with the University Eye Clinic in Regensburg,
Germany.
It involves creating a small access opening through the external sclera of
the
eye. After removal of the vitreous, the retina is lifted up from its
underlying
support layer so that the flexible film with the chip can be advanced
under the
retina to the vicinity of the macula. This is the point at which density
of the
nerve cells is greatest and can be expected to result in the most
effective
stimulation. Following exact positioning, the small window through the
sclera is
again closed, thus attaching the film securely in the globe of the eye so
that
the chip can assume a stable position and is not subjected to tension due
to
movements of the eye.
It was already possible to conduct initial tests with the patients only
one week
after implantation. The majority of patients recognized not only
horizontal and
vertical lines but also the direction in which electrodes were activated
one
after another and simple geometric patterns. However, the threshold value
for
triggering a stimulus varied widely in the different patients. In some
cases, it
was possible to trigger a phosphene with individual electrodes and a
charge
transfer of only a few nanocoulombs. However, many of the patients
experienced
visual perception only when several.
adjacent electrodes were stimulated simultaneously.3 The causes of these
patient-specific threshold values may be both the position of the
electrodes
relative to the macula and the distance between the electrodes and the
bipolar
cells in the retina.
Most of the patients reported blurred visual perception. Many were able to
distinguish light sources or bright objects against a dark background. As
the
ability to recognize objects grew in each patient, it became possible to
continuously optimize the stimulation parameters and the position of the
chip in
the eye so that three of the 11 patients were reliably able to recognize
simple
patterns when the chip was turned on and even bright objects against a
dark
background. In fact, the last test subject correctly recognized letters of
the
alphabet that measured ca. 8 cm high, was able to localize people in a
room, and
identified their size. A standard visual examination of this patient with
Landolt C Rings resulted in a visual acuity of 1/50, which is slightly
above the
threshold of legally defined blindness (according to WHO). This was
conclusive
proof that the basic concept of the subretinal implants functions
successfully
and can lead to usable visual perception.4
The learning effects that the authors observed were noteworthy: the
patients
needed only a few hours to learn how to process visual perceptions that
were new
to them. One patient who had been completely blind for the last 15 years
was
able to see the letters of the alphabet, and told the investigator that
the
letters looked “exactly as I learned them at school.” When his name was
presented to him, he immediately recognized a spelling error in it. In
addition,
hand-eye coordination was also relearned within a few hours. The patients
were
able to localize physical objects precisely and point to them immediately.
Geometric patterns and physical objects from daily life were recognized,
especially when they had very characteristic forms (such as a banana).
They were
also able to distinguish items of tableware (spoons, knives, forks) from
one
another.
Now that the pilot study is complete, the implant has become the subject
of a
multicentered main study with a larger patient set. The aim of the
investigation
is to gain regulatory approval for use as a medical product in 1-2 years.
After
it has been successfully used in retinitis pigmentosa patients, the plan
is to
test and apply the visual chip in patients with age-related macula
degeneration
(AMD) as well.
Acknowledgements.
This research was supported by the German Federal Ministry of Education
and
Research, the Kerstan Foundation, and ProRetina Germany.
References.
1. E Zrenner, “Will Retinal Implants Restore Vision?” Science 295, no.
5597
(February 2002): 1022–1025.
2. HG Graf et al., “High Dynamic Range CMOS Imager Technologies for
Biomedical Applications,” IEEE Journal of Solid-State Circuits 44, no. 1
(January 2009): 281–289.
3. E Zrenner, “Restoring Neuroretinal Function: New Potentials,
Documenta
Ophthalmologica (2007): 56–59.
4. E Zrenner et al., “Subretinal Electronic Chips Allow Blind Patients
to
Read Letters and Combine Them to Words,” Proceddings of the Royal Society,
Biological Sciences, online (November 3, 2010):
doi:10.1098/rspb.2010.1747.
5. L Rothermel et al., “A CMOS Chip With Active Pixel Array and
Specific
Test Features for Subretinal Implantation” IEEE Journal of Solid-State
Circuits
44, no. 1 (January 2009): 290–300.
Walter-G. Wrobel, PhD, is president and CEO of Retina Implant AG. Alex
Harscher,
PhD, is vice president of operations at the company.
Source URL:
http://www.mddionline.com/article/microchips-eye
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