Leroy Benedict Adisapuro
5/27/22
The Use of The Argus® II in the Treatment and Support of
Patients Diagnosed with Retinitis Pigmentosa
Introduction
Found in almost 1 in every 4000 people (Bruninx & Lepièce, 2020), Retinitis Pigmentosa (RP) is
amongst the most prominent genetic eye diseases among humans. RP can cause varying intensities of
vision loss, from blurry vision to little to no light reception. RP is defined as the progressive loss of
photoreceptor and pigment epithelial function in the retina (Bruninx & Lepièce, 2020). Currently there
are no treatments for RP. As of now, the most common solution people turn to is either: (1) using visual
aids such as the Argus® II or (2) rehabilitation programs. The Argus® II obtained the CE mark in 2011
and FDA approval as a humanitarian device in 2013 (Ahuja & Behrend, 2013). The device has since
been used as a commercial retinal prosthesis to treat patients with intense vision loss from RP and in
rarer cases, choroideremia, and even for those who suffer from extensive geographic atrophy from age
related macular degeneration (AMD) (Luo & Da Cruz, 2015). The Argus® II is a retinal prosthesis
implanted in the eye, which allows patients with RP to see their surroundings with greater detail when
compared to without the use of a retinal prosthesis. The Argus® II works by stimulating electrodes in
the eye with the use of electrical signals, allowing the patient to better perceive their surroundings to a
certain extent. This literature review will examine how The Argus® II is used to treat patients affected
by RP. I will discuss the methods of implantation, functionality, as well as future developments that may
be needed for The Argus® II.
Methods
This literature review was based on the data collected across multiple peer-reviewed papers found on
the PubMed database. The search strings used included: (“argus ii”) AND (“clinical trial”) AND (“vision
restoration”); (“argus ii”) AND (“clinical trial”); (“argus ii”); (“argus ii”) AND (“retinal prosthesis”). Papers
published before the year 2013 were excluded. The initial search only included clinical trials, but the
final literature review included randomized controlled trials (RCTs), qualitative studies and clinical trials.
Research with subjects of all genders was included. The outcomes measuring the effectiveness of The
Argus® II included being able to see a flashing beacon; being able to perceive items in front of them;
being able to grab an artificial doorknob under different conditions; recognizing letters; reading reduced
letter sizes; and word reading.
Results
My final search yielded 14 articles. I refer to all 14 of the papers in this literature review.
The patients from all the studies varied in ages between 24 - 75 years old. Most patients were
self-reportedly blind while others were medically diagnosed. With all patients having the Argus® II
implanted on the oculus dextrus(OD), which is their right eye. The patients included came from multiple
clinical sites worldwide. These clinical sites were: Puerta de Hierro Centro Médico (Guadalajara,
Mexico); The Doheny Eye Institute at the University of Southern California (Los Angeles, CA); Wilmer
Eye Institute at the Johns Hopkins School of Medicine (Baltimore, MD); University of California at San
Francisco (San Francisco, CA); The Greenville Surgical Center (Dallas, TX); Hôpitaux Universitaires de
Genève (Geneva, Switzerland); Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts (Paris,
France); Moorfields Eye Hospital (London, UK); The Edward S. Harkness Eye Institute at Columbia
University (New York, NY); and Wills Eye Institute at the University of Pennsylvania (Philadelphia, PA).
Two studies were clinical trials that measured the effects of the Argus® II on patients with RP and how
effective the device was under different visual conditions. One clinical trial asked participants to
observe a flashing beacon, perceive items in front of them, and grab an artificial doorknob under
different conditions (Luo et al., 2014). This study included five patients which were considered blind
with bare light perception (BLP) from RP, or worse vision impairment in both eyes (Luo et al., 2014).
Another trial focused on recognizing letters, recognizing letters with a reduction in letter sizes and
recognizing and reading words (Ahuja & Behrend, 2013). Two studies focused on the implementation of
the Argus® II on patients with RP (Luo & Da Cruz, 2015; Delyfer et al., 2018). The second clinical trial
consisted of 24 different patients with BLP from RP prior to the procedure (Ahuja & Behrend, 2013).
One paper presented a software called Acuboost™, this software is used for image-procesing and is
much better than the more conventional software used for the Argus® II. Acuboost™ allows patients to
read letters with 4 magnification allowed the patient to read large-print (2.3 cm) letters from a notebook
at 30 cm (Sahel et al, 2013).
There were 11 papers which described and discussed the means of implantation of the Argus® II.
These papes also discussed about the components of teh Argus® II and how it functioned as well as
talking about what makes patients eligible.
Discussion
Implantation
The Argus® II is usually implanted in patients with severe to intense retinal degeneration. The
prerequisites needed for this device are: (1) the patient must be at least 25 years old, (2) have little to
no light perception in both eyes and, (3) have a history of useful form vision (Schaffrath et al., 2019).
The Argus® II is implanted in patients’ eyes through a surgical procedure. The surgical procedure
implants a device on either one of the patient’s eyes. This surgical implantation of the Argus® II retinal
prosthesis involves the standard vitreoretinal surgery techniques of pars plana vitrectomy, the removal
of the vitreous through the pars plana, (Machemer et al., 1971; Machemer et al., 1972) and scleral
buckling procedures, (Friedman, 1958; Schepens, 1957). The surgical procedure required for the
implantation for the Argus® II takes about 3 hours 34 minutes (Delyfer et al., 2018). Different surgeons
performed the procedure and out of 5 different surgeons, none of them had any complications with the
surgical procedure (Delyfer et al., 2018)
There are different parts to the internal component of the Argus® II which are implanted in the patient’s
eye. These parts include: (1) The internal coil, (2) The inbuilt Application Specific Integrated Circuit
(ASIC), (3) and the 60-channel microelectrode epiretinal array.
The surgical procedures for implantation were similar across different studies and clinical trials. For one
of the studies , the procedures starts with a standard 3-port pars plana vitrectomy, with removal of the
posterior hyaloid face to prevent future development of an epiretinal membrane (when a sheet of cells
develop above the retina) (Luo & Da Cruz, 2015). A 360 degree conjunctival peritomy is then
performed to allow isolation of the recti muscles. The internal coil and ASIC are sealed in protective
cases which have a concave surface allowing them to conform to the curvature of the eyeball. These
components are then placed on the scelra surface and sutured into the scelera. A pars plana
sclerotomy in the supero-temporal quadrant allows the microelectrode array to be placed in the vitreous
cavity. Once the array is positioned properly, a spring-tensioned titanium retinal tack is inserted at the
heel of the array. The sclerotomy is then sutured close around the traversing cable connecting the array
to the ASIC. An encircling band is used to tighten the ASIC cases on the sclera. Last but not least, an
autologous fascia-lata patch is sutured over the hermetic cases. Though this procedure can be done
relatively quickly and safely, there might still be room for improvement regarding the safety and
efficiency of this procedure. This complex procedure helps tell us how the Argus® II can be implanted
but how does it really work? Let’s explore how these different components on the Argus® II actually
work.
All procedures produced similar results. The procedures were equally invasive with the eye being
opened up and the internal component being fitted around the eye. Both methods took, on average, an
equal amount of time to be carried out. With an average time of 3 hours 34 minutes. (Delyfer et al.,
2018)
Software // Hardware Technology
The Argus® II consists of both internal and external components. The external component is used to
capture the surroundings and convert the images into an electrical signal before sending that signal to
the internal component where the signal is sent to the brain for processing.
The Argus® II consists of 3 external components: (1) a video camera mounted on a pair of glasses, (2)
the visual processing unit (VPU), and (3) an external coil. The video camera is used to capture images
of the patient’s surroundings in real time. The VPU is worn on the body and converts the captured
images into electrical stimulating parameters which encode and ‘represent’ the surroundings. Lastly,
the external coil is used for wireless transmission of the electrical stimulating parameters from the VPU
and provides electrical power to the internal components through radio frequency telemetry (Luo & Da
Cruz, 2015).
The Argus® II also consists of 3 internal components: (1) an inbuilt Application Specific Integrated
Circuit (ASIC), (2) the 60-channel microelectrode epiretinal array, and (3) the internal coil. The ASIC is
used to generate electrical signals in the form of pulses in accordance to the electrical stimulating
parameters provided by the VPU. The 60-channel microelectrode epiretinal array consists of 60
platinum electrodes which can be independently activated. The array connects the ASIC to the retinal
surface allowing stimulation of the underlying retinal tissues and send electrical pulses to the brain
allowing the patient to form an image of their surroundings. Lastly, the internal coil is used as a wireless
receiver for the radio frequency telemetry converting the radio waves into signals allowing for the
internal component to receive both data and electrical power (Luo & Da Cruz, 2015).
These components allow the Argus® II to function efficiently as the internal component is powered by
electromagnetic waves which are transmitted from the external component allowing the internal
component to work without needing to be charged. The components being seperate also allow for a
more versatile use of the Argus® II as it means that the external component does not need to be worn
at all times allowing the patient to have more comfort. However, these components do not come
without their limitations. Patients with RP who use the Argus® II can see better than without it, but they
are still unable to see their surroundings completely or even clearly. Patients are able to see the
difference between a flashing object and one that is not flashing (Luo et al, 2014). However, a clinical
study showed that only about 71.3±27.1 % of patients are able to grasp the specific location of an
object placed in 1 of 4 different possible locations (Luo et al, 2014). Though the Argus® II significantly
helps patients who are suffering from RP, the device needs development for better patient experience.
Surgeons may also have trouble fitting the internal component in patients as each patient has a
different shape and size of the eye.
The simplest solution to overcome the limitations of the Argus® II is to upgrade or even change the
existing internal and eternal components to ones that work better or have better features. This is not a
simple task; however, it is the most feasible method that can be used to improve upon the already
existing features of the Argus® II.
Future Development
Although the Argus® II is a working retinal prosthesis, the device is still not capable enough to return
the visual ability of the patients to one that is on par to when they did not suffer from RP. The ability of
the retinal prosthesis to return one’s visual ability is what defines how well it works. In this case, it is the
ability for the Argus® II to act as a replacement of the damaged photoreceptor cells in the retina that
defines how successful the Argus® II is in serving its function - returning the vision loss to patients with
RP. This goal is achieved by efficiently capturing the patient’s surroundings in the form of images, the
conversion of these images into electrical stimulating parameters and lastly the activation of the inner
retina. The current version of the Argus® II works well enough to allow patients to see their
surroundings. However, it does not allow patients to have a clear vision of their surroundings.
In terms of software, increasing edge contrast by enhancing the outlines of objects have increased the
performance of shape and object recognition for patients who use the Argus® II. As presented by
Sahel et al. (2013), an image processing software called Acuboost™ uses a combination of techniques
such as zooming in and out as well as image enhancement to allow patients to see an image resolution
which does not rely on the number of electrodes used. This software is proven to be useful as it
allowed one Argus® II patient to read large-print letters relatively quickly in multiple instances, whereas
previous softwares did not show this level of feasibility. Some other features of the Argus® II which are
being developed is facial recognition which allow patients to more efficiently locate and detect who they
are talking to or who is around them by presenting the image of the face in an isolated view (Stanga et
al., 2013). Another more experimental feature that is being developed is of spatiotemporal interaction
between adjacent electrodes. Described by Hosager et al. (2010; and 2011), pseudo-electrodes can be
created through the phase difference interference of the electromagnetic waves subsequently allowing
the patient who is using the Argus® II to have a better resolution of their surroundings allowing them to
see more clearly.
In terms of hardware, the most immediate needs as stated by Luo & Da Cruz (2015) is an increase in
the number of electrodes as well as an increase in the area of retina stimulated. This is because it will
subsequently result in an increase of the patient’s visual feed which allows them to see more, which
lets them be more aware of their surroundings. Intraocular cameras can be used to mitigate the
misalignment between the position of the external camera mounted on the glasses and a patient's eye
position. This is important as misalignment may cause the patient’s perception of the surroundings to
be skewed. The intraocular camera would be placed within the patient’s lens allowing for visual
information to be transmitted to an external VPU before being transmitted again into the implanted
internal component of the Argus® II allowing users to have a more accurate perception of their
surroundings (Luo & Da Cruz, 2015).
These proposals can help improve the performance of the Argus® II. However, with new
improvements, there could be an increase in the cost of the Argus® II. The Argus®II already costs
around $150,000. This is already costly for many people and improving on the Argus® II could mean even
more costs that are added and thus making it less accessible to people.
Conclusion
Retinitis pigmentosa is extremely common and hinders the visual ability of those affected by degrading
a person’s photoreceptors. The Argus® II plays an important role in acting as a retinal prosthesis for
patients with retinitis pigmentosa. It allows patients to see by using a camera to capture the
surroundings, followed by a VPU to process those images, and finally transmitting the processed
images into the internal component via radio frequency in the form of electrical signals. Previous
studies show how to implement the Argus® II, how the Argus® II functions and possible developments
for the future. Some flaws that may need to be addressed in the clinical trials is the relatively small
number of patients used in some studies, (Luo et al, 2014). There are some areas where more
research is needed such as improving upon the existing software and hardware while also researching
on how the Argus® II can be more accessible to those who need it as it is not available worldwide and
is an extremely expensive prosthetic.
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