Biological considerations
The
ability to give sight to a blind person via a bionic eye depends on the
circumstances surrounding the loss of sight. For retinal prostheses,
which are the most prevalent visual prosthetic under development (due to
ease of access to the retina among other considerations), patients with
vision loss due to degeneration of photoreceptors (retinitis pigmentosa, choroideremia,
geographic atrophy macular degeneration) are the best candidate for
treatment. Candidates for visual prosthetic implants find the procedure
most successful if the optic nerve was developed prior to the onset of
blindness. Persons born with blindness may lack a fully developed optical nerve, which typically develops prior to birth, though neuroplasticity makes it possible for the nerve, and sight, to develop after implantation.
Technological considerations
Visual prosthetics are being developed as a potentially valuable aid for individuals with visual degradation. Argus II, co-developed at the University of Southern California (USC) Eye Institute and manufactured by Second Sight Medical Products
Inc., is now the only such device to have received marketing approval
(CE Mark in Europe in 2011). Most other efforts remain investigational;
the Retina Implant AG's Alpha IMS won a CE Mark July 2013 and is a
significant improvement in resolution. It is not, however, FDA-approved
in the US.
Ongoing projects
Argus retinal prosthesis
Mark Humayun, who joined the faculty of the Keck School of Medicine of USC Department of Ophthalmology in 2001; Eugene Dejuan, now at the University of California San Francisco; engineer Howard D. Phillips; bio-electronics engineer Wentai Liu, now at University of California Los Angeles; and Robert Greenberg, now of Second Sight, were the original inventors of the active epi-retinal prosthesis and demonstrated proof of principle in acute patient investigations at Johns Hopkins University in the early 1990s. In the late 1990s the company Second Sight was formed by Greenberg along with medical device entrepreneur, Alfred E. Mann, Their first-generation implant had 16 electrodes and was implanted in six subjects by Humayun at University of Southern California between 2002 and 2004.
In 2007, the company began a trial of its second-generation,
60-electrode implant, dubbed the Argus II, in the US and in Europe.
In total 30 subjects participated in the studies spanning 10 sites in
four countries. In the spring of 2011, based on the results of the
clinical study which were published in 2012,
Argus II was approved for commercial use in Europe, and Second Sight
launched the product later that same year. The Argus II was approved by
the United States FDA on 14 February 2013. Three US government funding
agencies (National Eye Institute, Department of Energy, and National
Science Foundation) have supported the work at Second Sight, USC, UCSC,
Caltech, and other research labs.
Microsystem-based visual prosthesis (MIVP)
Designed by Claude Veraart at the University of Louvain,
this is a spiral cuff electrode around the optic nerve at the back of
the eye. It is connected to a stimulator implanted in a small depression
in the skull. The stimulator receives signals from an externally worn
camera, which are translated into electrical signals that stimulate the
optic nerve directly.
Implantable miniature telescope
Although
not truly an active prosthesis, an Implantable Miniature Telescope is
one type of visual implant that has met with some success in the
treatment of end-stage age-related macular degeneration. This type of device is implanted in the eye's posterior chamber
and works by increasing (by about three times) the size of the image
projected onto the retina in order to overcome a centrally located scotoma or blind spot.
Created by VisionCare Ophthalmic Technologies in conjunction with
the CentraSight Treatment Program, the telescope is about the size of a
pea and is implanted behind the iris of one eye. Images are projected onto healthy areas of the central retina, outside the degenerated macula,
and is enlarged to reduce the effect the blind spot has on central
vision. 2.2x or 2.7x magnification strengths make it possible to see or
discern the central vision object of interest while the other eye is
used for peripheral vision because the eye that has the implant will
have limited peripheral vision as a side effect. Unlike a telescope
which would be hand-held, the implant moves with the eye which is the
main advantage. Patients using the device may however still need glasses
for optimal vision and for close work. Before surgery, patients should
first try out a hand-held telescope to see if they would benefit from
image enlargement. One of the main drawbacks is that it cannot be used
for patients who have had cataract surgery as the intraocular lens would obstruct insertion of the telescope. It also requires a large incision in the cornea to insert.
A Cochrane systematic review
seeking to evaluate the effectiveness and safety of the implantable
miniature telescope for patients with late or advanced age-related
macular degeneration found only one ongoing study evaluating the OriLens
intraocular telescope, with results expected in 2020.
Tübingen MPDA Project Alpha IMS
A
Southern German team led by the University Eye Hospital in Tübingen,
was formed in 1995 by Eberhart Zrenner to develop a subretinal
prosthesis.
The chip is located behind the retina
and utilizes microphotodiode arrays (MPDA) which collect incident light
and transform it into electrical current stimulating the retinal ganglion cells.
As natural photoreceptors are far more efficient than photodiodes,
visible light is not powerful enough to stimulate the MPDA. Therefore,
an external power supply is used to enhance the stimulation current. The
German team commenced in vivo experiments in 2000, when evoked cortical
potentials were measured from Yucatán micropigs and rabbits. At 14
months post implantation, the implant and retina surrounding it were
examined and there were no noticeable changes to anatomical integrity.
The implants were successful in producing evoked cortical potentials in
half of the animals tested. The thresholds identified in this study were
similar to those required in epiretinal stimulation.
Later reports from this group concern the results of a clinical pilot
study on 11 participants suffering from RP. Some blind patients were able to read letters, recognize unknown objects, localize a plate, a cup and cutlery. Two of the patients were found to make microsaccades
similar to those of healthy control participants, and the properties of
the eye movements depended on the stimuli that the patients were
viewing—suggesting that eye movements might be useful measures for
evaluating vision restored by implants.
In 2010 a new multicenter Study has been started using a fully
implantable device with 1500 Electrodes Alpha IMS (produced by Retina
Implant AG, Reutlingen, Germany), 10 patients included so far; first
results have been presented at ARVO 2011. The first UK implantations took place in March 2012 and were led by Robert MacLaren at the University of Oxford and Tim Jackson at King's College Hospital in London. David Wong also implanted the Tübingen device in a patient in Hong Kong. In all cases previously blind patients had some degree of sight restored.
Harvard/MIT Retinal Implant
Joseph
Rizzo and John Wyatt at the Massachusetts Eye and Ear Infirmary and MIT
began researching the feasibility of a retinal prosthesis in 1989, and
performed a number of proof-of-concept epiretinal stimulation trials on
blind volunteers between 1998 and 2000. They have since developed a
subretinal stimulator, an array of electrodes, that is placed beneath
the retina in the subretinal space and receives image signals beamed
from a camera mounted on a pair of glasses. The stimulator chip decodes
the picture information beamed from the camera and stimulates retinal
ganglion cells accordingly. Their second generation prosthesis collects
data and sends it to the implant through RF fields from transmitter
coils that are mounted on the glasses. A secondary receiver coil is
sutured around the iris.
Artificial silicon retina (ASR)
The
brothers Alan Chow and Vincent Chow have developed a microchip
containing 3500 photodiodes, which detect light and convert it into
electrical impulses, which stimulate healthy retinal ganglion cells. The ASR requires no externally worn devices.
The original Optobionics Corp. stopped operations, but Chow
acquired the Optobionics name, the ASR implants and plans to reorganize a
new company under the same name.
The ASR microchip is a 2mm in diameter silicon chip (same concept as
computer chips) containing ~5,000 microscopic solar cells called
"microphotodiodes" that each have their own stimulating electrode.
Photovoltaic retinal prosthesis (PRIMA)
Daniel Palanker and his group at Stanford University have developed a photovoltaic retinal prosthesis
that includes a subretinal photodiode array and an infrared image
projection system mounted on video goggles. Images captured by video
camera are processed in a pocket PC and displayed on video goggles using
pulsed near-infrared (IR, 880–915 nm) light. These images are projected
onto the retina via natural eye optics, and photodiodes in the
subretinal implant convert light into pulsed bi-phasic electric current
in each pixel.
Electric current flowing through the tissue between the active and
return electrode in each pixel stimulates the nearby inner retinal
neurons, primarily the bipolar cells, which transmit excitatory
responses to the retinal ganglion cells.
This technology is being commercialized by Pixium Vision (PRIMA), and is being evaluated in a clinical trial (2018).
Following this proof of concept, Palanker group
is focusing now on developing pixels smaller than 50μm using 3-D
electrodes and utilizing the effect of retinal migration into voids in
the subretinal implant.
Bionic Vision Australia
An Australian team led by Professor Anthony Burkitt is developing two
retinal prostheses. The Wide-View device combines novel technologies
with materials that have been successfully used in other clinical
implants. This approach incorporates a microchip with 98 stimulating
electrodes and aims to provide increased mobility for patients to help
them move safely in their environment. This implant will be placed in
the suprachoroidal space. Researchers expect the first patient tests to
begin with this device in 2013.
The Bionic Vision Australia consortium is concurrently developing
the High-Acuity device, which incorporates a number of new technologies
to bring together a microchip and an implant with 1024 electrodes. The
device aims to provide functional central vision to assist with tasks
such as face recognition and reading large print. This high-acuity
implant will be inserted epiretinally. Patient tests are planned for
this device in 2014 once preclinical testing has been completed.
Patients with retinitis pigmentosa
will be the first to participate in the studies, followed by
age-related macular degeneration. Each prototype consists of a camera,
attached to a pair of glasses which sends the signal to the implanted
microchip, where it is converted into electrical impulses to stimulate
the remaining healthy neurons in the retina. This information is then
passed on to the optic nerve and the vision processing centres of the
brain.
The Australian Research Council
awarded Bionic Vision Australia a $42 million grant in December 2009
and the consortium was officially launched in March 2010. Bionic Vision
Australia brings together a multidisciplinary team, many of whom have
extensive experience developing medical devices such as the cochlear implant (or 'bionic ear').
Dobelle Eye
Similar in function to the Harvard/MIT device, except the stimulator chip sits in the primary visual cortex,
rather than on the retina. Many subjects have been implanted with a
high success rate and limited negative effects. Still in the
developmental phase, upon the death of Dobelle, selling the eye for
profit was ruled against in favor of donating it to a publicly funded research team.
Intracortical visual prosthesis
The Laboratory of Neural Prosthetics at Illinois Institute Of
Technology (IIT), Chicago, is developing a visual prosthetic using
intracortical electrode arrays. While similar in principle to the
Dobelle system, the use of intracortical electrodes allow for greatly
increased spatial resolution in the stimulation signals (more electrodes
per unit area). In addition, a wireless telemetry system is being
developed
to eliminate the need for transcranial wires. Arrays of activated
iridium oxide film (AIROF)-coated electrodes will be implanted in the
visual cortex, located on the occipital lobe of the brain. External
hardware will capture images, process them, and generate instructions
which will then be transmitted to implanted circuitry via a telemetry
link. The circuitry will decode the instructions and stimulate the
electrodes, in turn stimulating the visual cortex. The group is
developing a wearable external image capture and processing system to
accompany the implanted circuitry. Studies on animals and psyphophysical
studies on humans are being conducted to test the feasibility of a human volunteer implant.
