THE ARGUS® II RETINAL PROSTHESIS SYSTEM: AN OVERVIEW
David D. Zhou, Ph.D., Jessy D. Dorn, Ph.D., Robert J. Greenberg, M.D., Ph.D., Argus II Study Group
Second Sight Medical Products, Inc. Sylmar, CA
ABSTRACT
The Argus II Retinal Prosthesis System is the only
commercially-approved treatment for severe to profound
Retinitis Pigmentosa in the world. Over 10 years of research
and development have gone into this device; it is now
commercially available in the European Economic Area,
Saudi Arabia, and in the United States. The Argus II System
consists of an implant (including an epiretinal electrode
array, an electronics case, and a receiver antenna), as well as
a body-worn computer and a pair of glasses with a miniature
video camera. It converts video images from the camera into
stimulation patterns that are transmitted to the implant in
real time, allowing users to perceive patterns of light. All
aspects of the System have been extensively bench tested
and found to provide long-term reliability. These findings
have been borne out in a clinical trial; in over 120 subject-
years of testing, there has been only one device failure.
Clinical trial results have established the safety and probable
benefit of the Argus II System.
Index Terms— Retinal prosthesis, epiretinal array,
Retinitis Pigmentosa
1. INTRODUCTION
Retinitis Pigmentosa (RP) is a genetic disease that slowly
robs fully-sighted people of their vision. Photoreceptors, the
light-sensing cells of the retina, degenerate, causing
irreparable vision loss. While the photoreceptors are lost in
RP, most other parts of the visual pathway remain largely
intact and functional, including bipolar cells and ganglion
cells (the output cells of the retina) as well as the optic nerve
and visual structures in the brain.
Retinal prostheses (also called retinal implants or bionic
eyes) work by electrically stimulating the remaining retinal
cells, bypassing the degenerated photoreceptors. The
electrical signals move up the visual pathway into the visual
cortex, where they are perceived as visual percepts. Many
different groups worldwide are investigating retinal
prostheses; some approaches involve inserting an electrode
or photodiode array subretinally, near the photoreceptors
[1], [2], some insert an array epiretinally, near the ganglion
cells [3], while others involve placing an array in the
suprachoroidal space [4], [5].
Until recently, all of these efforts were investigational.
After over 10 years of research and development, The Argus
II Retinal Prosthesis System is the first commercially-
available device approved for the treatment of RP. It is CE
Marked and has been available in the European Economic
Area since 2011. Recently, the FDA has approved it for sale
in the United States under a Humanitarian Device
Exemption.
This article provides an overview of the Argus II System,
including design, principle of operation, bench testing, and
clinical trial testing.
2. THE ARGUS II SYSTEM
The Argus II System consists of implanted and external
components.
2.1 Implant
The implant is an epiretinal prosthesis that includes a
receiver coil (antenna), electronics, and an electrode array.
These are implanted in and around the eye (Figure 1A). The
array has 60 platinum based electrodes arranged in a 6x10
grid. Each electrode is 200 µm in diameter; horizontal and
vertical pitch is 525 µm. The array covers about 20° of
visual field (diagonally). The flexible polymer thin-film
electrode array, which follows the curvature of the retina, is
attached to the retina over the macula with a retinal tack
(Figure 1B). The extra-ocular portion of the Argus II
Implant is secured to the eye by means of a scleral band.
Electronics case
Electrode array
Receiver coil
Figure 1A. Internal components of the Argus II System.

Figure 1B. A thin-film polymer 60 electrodee array in the eye
of a RP subject.
2.2 Externals
The external equipment consists of glasses, a video
processing unit (VPU), and a cable (Figuree 2). The glasses
include a miniature video camera and a trannsmitter coil. The
Argus II Clinician Fitting System softw ware is used to
configure the Argus II system stimulationn parameters and
video processing strategies for each subjeect. The software
provides modules for electrode control,, permitting the
clinicians to interactively construct test stim
muli with control
over amplitude, pulse-width, and freqquency of the
stimulation waveform of each electrode.
Camera
Transmitter coil
Video Processing Unit (VPU)
Figure 2. External components of the Arguss II System.
2.3 Principle of Operation
The Argus II System provides real-time viisual information
to blind patients. During use, the miniatuure video camera
housed in the patient’s glasses captures a scene. The video is
sent to the small patient-worn VPU where it is processed
and transformed into instructions that are sent back to the
glasses via a cable. These instructions are transmitted
wirelessly to the receiver coil in the implantt. The signals are
then sent to the electrode array, which emitts small pulses of
electricity. These pulses are intended to byppass the damaged
photoreceptors and stimulate the retina’s
r remaining cells,
which transmit the visual informatiion along the optic nerve
to the brain. This process is intended to create the
perception of patterns of light whiich patients can learn to
interpret as visual patterns (Figure 3).
3
Figure 3. The patient perceives pattterns of light created by
electrical stimulation.
TING
3. BENCH TEST
The Argus II Retinal Implant has been
b tested in-vitro at the
component, sub-assembly, and systtem levels for long-term
reliability. The hermetic electrronics case has been
demonstrated to prevent moisture accumulation inside the
device, extending the functional lifetime
l of the implant.
Finished implants have reached more m than 10 years of
lifetime in accelerated testing and so
s far reached more than
4 years in real time testing. Thin n-film polymer electrode
array insulation so far has reacheed 7 years in real-time
testing and an equivalent lifetim me of over 26 years in
accelerated testing.
3.1 Electrode Material
Electrode arrays withstood agg gressive constant pulse
stimulation and provided long-term m safe stimulation without
corrosion or material degradation. The electrode material
developed by Second Sight, Platinu um Gray, has been fully
verified with soak tests for over 10 years and has more than
sufficient chronic charge density capacity – up to 1.0
mC/cm2 for retinal stimulation. The high surface area
Platinum Gray is similar to the mo ore familiar soft platinum
black except it has significantly more
m mechanical stability
(Figure 4) [6].
Figure 4. SEM micrographs of Second Sighht Platinum
Gray electrode material (top) showing the m
material’s high
surface area and Platinum Gray coated thin--film electrodes
(bottom).
ms
3.2 Electrical Stimulation and Waveform
Electrical stimulation of Argus II Retinnal implant uses
biphasic cathodic first, charge balanced constant current
pulses. Electrode voltage excursion and electrode
impedance are monitored during active pullse stimulation to
assess device stability. The electrode vvoltage excursion
(Figure 5A) remains low during the long--term stimulation
and is far below the water window potenntial of platinum
electrode material. Electrode impedancee (Figure 5B) is
stable during the long-term stimulation.
RI) safety and
3.3 Magnetic Resonance Imaging (MR
compatibility
The System has also been tested for Maggnetic Resonance
Imaging (MRI) safety and compatibilitty. Test results
indicated that the exposure of the A Argus II Retinal
Prosthesis System to various conditions using 1.5-T/64-
MHz and 3.0-T/128-MHz systems will not damage the
device, alter its functionality, or have safeety consequences
for the patient [7].
Figure 5. The voltage excursion waaveforms (A. top) by
biphasic, cathodic first pulse stimulaation and electrode
impedance curves (B. bottom) recorrded during long-term
stimulation.
L TESTING
4. CLINICAL TRIAL
The Argus II System is being studieed in a clinical trial of 30
subjects in the U.S. and Europe, wh hich began in 2007 and is
still ongoing. These subjects will be followed for ten years.
As of December 2012, there were overo 120 subject-years in
the clinical trial. The average time implanted was 4.1 years
(SD 1.1 years), with a range of 1.2 – 5.6 years.
At the time of implant, all subjects’ residual vision had
n or worse (i.e., they were
deteriorated to bare light perception
only able to detect very bright liight, and had no useful
functional vision). Most (29) had retinitis pigmentosa.
4.1 Reliability
As of December 2012, there was on ne failure of an implanted
device, suspected to be due to damage sustained by the
device during implantation. Thee device has remained
implanted but is non-functional. Alll other devices continue
to function.
4.2 Safety 2.9 logMAR (or about 20/16000 on the Snellen acuity scale)
to 1.6 logMAR (~ 20/800).
Safety was monitored by recording and investigating
adverse events due to the device or surgery. There were no
unexpected device- or procedure-related adverse events (i.e.,
all events that occurred were part of a pre-defined list of the
events that could be expected from this type of ophthalmic
surgery). All adverse events that did occur were treated with
standard ophthalmic techniques.

4.2 Probable Benefit

All subjects perceived light with their Argus II Systems, and

all subjects used their Systems at home. Probable Benefit
was measured in the clinical trial with a battery of visual
function and functional vision assessments to determine Figure 6A. A subject performing the Square Localization
whether subjects showed better visual performance with the assessment.
System turned ON vs. turned OFF. Assessments were
administered at regular time points throughout the clinical
trial (e.g., baseline, 3 months, 6 months, 12 months, 2 years,
etc.).

4.2.1 Visual Function

The visual function assessments were computer-based tests

with high-contrast stimuli presented on a touch screen. The
most basic assessment was Square Localization [8]; it tested
subjects’ ability to locate and touch a white square at a
random location on a black touch screen monitor (Figure
6A). Each target square (40 trials total) remained on the Figure 6B. The Direction of Motion task.
screen until the subject touched the monitor where he or she
believed the square was located. The distance from the
center of the target square to the subject’s response was
calculated for each trial.
The second visual function test, Direction of Motion,
assessed subjects’ ability to determine the direction of a
white bar as it crossed the black touch screen at a random
angle (0-360°) [9]. After each bar moved across the screen
(80 trials total), the subject drew the direction he or she
perceived on the monitor (Figure 6B). The unsigned angle
difference between the target and response was calculated.
A successful performance on this test required spatial vision
ability: subjects must be able to perceive spatial information Figure 6C. The Grating Visual Acuity assessment.
from their electrode array (i.e., distinguish between
electrodes on different areas of the array) in order to
successfully determine the direction of motion. All visual function tests were performed with the subjects’
Grating Visual Acuity, the final visual function test used Systems turned ON and with it OFF (using only their
in the clinical trial, was designed to measure subjects’ visual residual vision) as a control.
acuity using principles similar to the standard Early As a group, subjects performed Square Localization and
Treatment Diabetic Retinopathy Study (ETDRS) letter Direction of Motion better with the System ON compared to
chart. In this test, subjects were required to determine the OFF at each time point (Figure 7). Grating Visual Acuity
orientation (horizontal, vertical, diagonal right, diagonal was the most difficult of the visual function tests. Only one
left) of black and white gratings of differing spatial subject was able to score on this test with the implanted eye
frequencies (Figure 6C). The test measured acuity in units of when the System was OFF, and that was achieved at only
log of the Minimum Angle of Resolution (logMAR), from one time point. With the System ON, between 31% and 50%
of subjects scored between 2.9 – 1.6 logMAR depending on
the time point (up to 24 months post-implant). The best
score to date was 1.8 logMAR (or 20/1262 on the Snellen
acuity scale).
The Functional Low-vision Observer Rated Assessment
(FLORA) involved interviews (self-report) and observation
of subjects performing real daily life and O&M tasks. It was
administered by trained independent blind and low-vision
rehabilitation therapists. The results were categorized
according to the effect the Argus II System had on the
subjects’ lives (both their functional vision and their well-
being). Results showed that the Argus II System had a
generally positive effect on a majority of subjects assessed
(20 of 26, or 76%) and a neutral effect on 23% of subjects.
No subjects had been negatively affected.
Two questionnaires, the Massof Activity Inventory and
the Visual Quality of Life (VisQoL), did not find clear
effects of the Argus II System on the daily life (Massof) or
quality of life (VisQoL), primarily because these
instruments have been designed and validated for patients
with significantly better vision.

Figure 7A. Square Localization results averaged across

subjects at yearly time points.

Figure 8. A blind subject walks along the line in an

Orientation & Mobility Task trial.

Figure 7B. Direction of Motion results (mean response error

± mean standard error) averaged across subjects at yearly
time points.

4.2.2 Functional Vision

The functional vision assessments were developed to test

subjects’ visual performance on more real-world tasks in
less controlled environments. They included Orientation and
Mobility tasks such as finding a door and following a line
(Figure 8), as well as questionnaires and observer-rated
assessments intended to measure subjects’ functional vision
in everyday life and their general well-being.
Figure 9A. Average success rate across subjects (± standard
On the Orientation and Mobility (O&M) tasks, the
error) on the “Find the Door” O&M task at yearly time
subjects as a group performed better with the System ON
points.
than OFF at each time point (Figure 9).

Figure 9B. Average success rate across subjects (± standard
error) on the “Follow the Line” O&M task at yearly time
points.
5. COMMERCIALIZATION
In 2011, the Argus II Retinal Prosthesis System was granted
CE Mark, thus becoming the first commercially-available
treatment for Retinitis Pigmentosa in the world. There are
currently six implanting centers in Europe and one in Saudi
Arabia. Over 20 patients have been implanted with the
commercial device. Several more countries and centers are
being added to the program in 2013.
In February 2013, the FDA granted approval to market
the Argus II System in the U.S. under the Humanitarian Use
Device exemption. It is expected to be available in the U.S.
to patients later in 2013. Roughly a dozen implanting
centers in the US are expected to be open by the end of
2013.
6. CONCLUSIONS
Recent years have seen major advances in retinal prostheses,
which are bringing hope to people with previously-
untreatable disorders such as Retinitis Pigmentosa. The
Argus II Retinal Prosthesis System, which has been shown
to be reliable, safe, and to provide probable benefit, is
currently available in the European Economic Area, Saudi
Arabia, and will soon be available for commercial sale in
the Unites States.
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