A Review of Artificial Vision by Jason Dowling

1. Review
10.1586/17434440.2.1.xxx © 2005 Future Drugs Ltd. ISSN 1743-4440 1
CONTENTS
Blindness & mobility defined
AHV technology
& requirements
Cortical stimulation
Retinal stimulation
Optic nerve devices
AHV simulation studies
Expert opinion
Five-year view
Information resources
Key issues
References
Affiliation
www.future-drugs.com
Artificial human vision
Jason Dowling
Queensland University of
Technology, School of Electrical and
Electronic Systems Engineering,
Faculty of Built Environment and
Engineering,, Brisbane, Australia
Tel: +617 3864 1608
Fax: +617 3864 1516
j.dowling@qut.edu.au
KEYWORDS:
artificial human vision, bionic
eye, blind mobility, cortical
stimulation, epiretinal
stimulation, subretinal
stimulation, visual prosthesis
Can vision be restored to the blind? As early as 1929 it was discovered that stimulating the
visual cortex of an individual led to the perception of spots of light, known as phosphenes
[1]. The aim of artificial human vision systems is to attempt to utilize the perception of
phosphenes to provide a useful substitute for normal vision. Currently, four locations for
electrical stimulation are being investigated; behind the retina (subretinal), in front of the
retina (epiretinal), the optic nerve and the visual cortex (using intra- and surface
electrodes). This review discusses artificial human vision technology and requirements and
reviews the current development projects.
Expert Rev. Med. Devices 2(1), xxx–xxx (2005)
Blindness & mobility defined
Blindness
In 1997 the World Health Organization esti-
mated that there were close to 150 million indi-
viduals with significant visual disability (or
legally blind) worldwide, with 38 million of
those totally blind (without light perception) [2].
In economically developed societies, the lead-
ing cause of blindness and visual disability in
adults is diabetic retinopathy. The most com-
mon nonpreventable cause of blindness in the
developed world is age- related macular degen-
eration, which occurs in 25% of individuals
80 years of age and over [3]. Retinitis pigmen-
tosa (RP) is a condition characterized by a grad-
ual loss of the visual field, leading to the loss of
peripheral vision and eventually to blindness.
Approximately 90% of blind people live in the
developing world. In general, more than two-
thirds of today’s blindness could be prevented or
treated by applying existing knowledge and tech-
nology [4]. Nearly half of all blindness is due to
cataract and a quarter of the world’s blindness is
due to trachoma. Other major causes of blind-
ness are glaucoma (a group of eye diseases char-
acterized by an increase in intraocular pressure),
trachoma and onchocerciasis (both parasitic dis-
eases) and xerophthalmia (caused by vitamin A
deficiency) [5].
It has been estimated that if all avoidable
blindness in the USA in individuals under
the age of 20 and working-age adults were
prevented, the federal budget would save
US$1 billion per year [6].
Blind mobility
Blind mobility is affected by physical and
mental health factors, such as multiple disa-
bilities. Age is a mobility issue as many of the
blind are elderly, which can restrict their abil-
ity to use some mobility aids (such as a guide
dog). Many congenitally blind children have
hypotonia or abnormally low muscle tone
(due to delayed sensorimotor development)
which can affect mobility [7]. An additional
problem, experienced by most blind patients
without light perception, is falling out of
phase with the 24 h day which often leads to
severe sleep disorders.
In 1996, The US National Research Council
published the following summary of blind
pedestrian needs in 1996 [8]:
• Detection of obstacles in the travel path
from ground level to head height for the full
body width
• Travel surface information
• Detection of objects bordering the travel path
• Distant object and cardinal direction
information
• Landmark location and identification
information
• Information enabling self-familiarization
and mental mapping of an environment

2. Dowling
2 Expert Rev. Med. Devices 2(1), (2005)
Most existing mobility aids for the blind provide information
in either tactile or auditory form. The two most widely used
devices are the long cane and the guide dog, however, these
devices have limitations; the long cane is only effective over a
short range and a guide dog requires expensive training and
maintenance. A number of electronic travel aids (ETAs) have
also been developed, generally using ultrasound or lasers.
These devices have usually failed commercially due to their
expense, lack of benefit in improved mobility and cosmetic
unattractiveness [9]. The objective assessment of technical aids
for the blind (e.g., using Percentage of Preferred Walking
Speed [10]) could provide useful information during device
development and for consumers.
AHV technology & requirements
The development of an artificial human vision (AHV) system is
a multidisciplinary field, involving inputs from neuroscience,
engineering, computer science and ophthalmology, in addition
to orientation and mobility specialists.
With the exception of subretinal prostheses, most AHV sys-
tems have similar system requirements. The main components,
which will need to function in real time, are:
• A Camera – required to capture and digitize image informa-
tion from the environment. Charged Coupled Device
(CCD)-based digital cameras are inexpensive, small and can
be easily interfaced to other system components. An adaptive
mechanism (such as an automatic gain in current video cam-
eras) will also be required to allow the device to function at
different levels of illumination [11]. CCD camera sensors have
a linear response to light intensity. A logarithmic camera has
a similar response to the human visual system and can reduce
saturation in high contrast visual scenes. The use of a loga-
rithmic camera in an AHV is being investigated in at least
one current research project [12].
• Image processing – there will be more data retrieved from the
camera than can be used in an AHV device. The image data
will usually be preprocessed to reduce noise. After this, an
information reduction (such as edge detection or segmenta-
tion) or a scene understanding approach, attempting to
extract information, can be used. Cortical prosthesis research
by the Dobelle Institute (Portugal) has found that edge detec-
tion and image reversal enhance the ability of subjects to rec-
ognize important scene components (such as doorways) [13].
An alternate, and alternative, approach to traditional image
processing is the use of neuromorphic vision systems,
designed to mimic the design of the human visual system [14].
• Transmitter/receiver – a link is required from the cam-
era/image processing components to the stimulator and elec-
trode array, which are usually located inside the body. Percuta-
neous connections have been used for most research due to
their simplicity and reliability [15], however, the risk of chronic
infection is higher with this type of connection. The Dobelle
Institute system uses a percutateous connecting pedestal for
connection to the image processing unit (a notebook PC). A
transcutaneous connection, as used in cochlear implants, uses
radiofrequency telemetry to send data and power to the
embedded stimulator, reducing the risk of infection. Most
AHV research projects plan to eventually use transcutaneous
connections. Reverse telemetry can also be used to provide
details of stimulation voltage waveforms, impedance measure-
ments and reconstruction of stimulation voltage waveforms
[16]. A good description of a high efficiency transcutaneous
data link for implanted electronic devices is provided by
Troyke and Schwan [17].
• Stimulator/electrodes – an electrode is a thin wire, which
allows a small amount of precisely controlled electrical cur-
rent to pass through it. Electrodes can be used for either
stimulation or recording the electrical activity of the brain.
The purpose of the stimulator is to send current through
multiple electrodes. There are two main types of electrodes
discussed in the AHV literature; surface electrodes, which lie
flat against the stimulation/recording target and penetrating
electrodes, which are inserted inside the stimulation/record-
ing target. The biocompatability, long-term effectiveness
and safe threshold levels for implanted electrodes need to be
carefully considered.
Cortical stimulation
In the functioning human vision system, two types of photore-
ceptors in the retina (rods and cones) are activated by light,
which has been focused by the lens and cornea in the eye. Elec-
trical signals from these photoreceptors are then processed
through a layer of bipolar and ganglion cells within the retina,
before passing to the optic nerve [18]. The amount of informa-
tion entering the eye is reduced considerably - there are over 120
million photoreceptors and only about 1 million ganglion cells
[19]. Most of the signals from the optic nerve pass through the
lateral geniculate body to the visual cortex, although, approxi-
mately 20–30% of fibers connect to the superior colliculus,
which appears to be responsible for eye movements [20].
Cortical-based AHV systems use either surface or intracorti-
cal stimulation, using penetrating electrodes. Cortical stimula-
tion is the only treatment available for blindness caused by
glaucoma, optic atrophy or diseases of the central visual path-
ways, such as brain injuries or stroke. The main negative feature
of a cortical implant is the lack of preliminary processing by the
brain, particularly in the retina where much of the information
reduction takes place.
Most research regarding AHV has focused on sending a cap-
tured image to the brain as a bitmap representation. The bitmap
approach to cortical devices has been questioned [21]. Research
performed by Hubel and Weisel in macaque monkeys has found
that, in addition to spatial location of a stimulus in the visual
field, neurons in the visual cortex are selective for spatial, tempo-
ral, chromatic and binocular cues [22]. A greater knowledge of
cortical physiology may be required before a cortical prosthesis
provides useful vision. Evidence
has also been found to suggest that there may be specialized
cortical areas for the analysis of biologically important images
(such as faces) [23].

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Cortical surface stimulation
The early developments in cortical prostheses involved surface
electrode arrays. The first person to expose the human occipital
pole to electrical stimulation was the German researcher For-
ester in 1929, who noticed that stimulation caused the subject
to see a spot of light in a position that depended on the site of
stimulation [1].
Brindley & Lewin
Brindley and Lewin published the results of a groundbreak-
ing study on cortical stimulation in 1968. In their study, a
52-year-old legally blind subject was implanted with an array
of 80 platinum electrodes, a design which had previously
been tested in baboons. These electrodes were stimulated by
pulsed radio signals from an oscillator. Stimulation of these
electrodes produced discernible phosphenes [24]. Brindley
and Lewin suggested that there was probably no flicker
fusion frequency for this implant. They also found that phos-
phenes moved with eye movements and that phosphene per-
ception usually (but not always) stopped when stimulation
ceased. Stimulation of one electrode was found to produce
multiple phosphenes and when multiple electrodes in close
vicinity were activated, a larger, straight light phosphene was
produced. Unfortunately, the monophasic stimulus pulses
used long-term in these earlier studies were also likely to
cause irreversible damage at the electrode-tissue interface [25].
Dobelle & Mladejovsky
Brindley and Lewin’s research inspired pioneering work
involving 37 human subjects by Dobelle and Mladejovsky in
1974, where electrical stimulation was applied to patients
hospitalized for cranial surgery [26]. Supporting Brindley and
Lewin’s work, they found eye movements caused phosphenes
to move and multiple phosphenes could be produced from a
single electrode. However, Dobelle and Mladejovsky found
that constant stimulation caused phosphenes to fade, sug-
gesting that phosphenes need to be refreshed. In a later paper,
it was reported that subjects were able to read electrode-
induced Braille characters more efficiently than using their
tactile sense [27].
In 2000, Dobelle published a paper describing a subject who
had been using a cortical visual prosthesis system for over
20 years [13]. The system used a 64-channel electrode array,
which had been implanted on the mesial surface of the subject’s
right occipital lobe in 1978. When stimulated, each electrode
produced one to four closely spaced phosphenes. The stimula-
tion parameters and phosphene locations had been stable for
the past 20 years, however, the electrode thresholds required a
15-min recalibration every morning. This system utilized a
black and white camera connected to a notebook computer.
Cables from the notebook were connected to a percutaneous
connecting pedestal, which interfaced to the microcontroller,
stimulus generator and electrode array. Dobelle reported that
frame rates of around 4 fps have been found to be optimal. The
subject has a visual acuity of approximately 20/200.
Bionic eye research project
Although research in the early 1990s moved towards intrac-
ortical stimulation, a recently commenced project at the
University of New South Wales ([NSW], Australia) is investi-
gating the use of technology adapted from cochlear implants
(which generally use surface electrodes). An in vivo model
has been reported, in which the transcallosal evoked
response to cortical stimulation on the opposite hemisphere.
Future psychophysical experiments in a human subject are
planned [28,29].
Intracortical stimulation
National Institute of Health
The Neuroprosthesis Program at the US National Institute of
Health (NIH) was the first to publish research concerning the
use of intracortical stimulation to produce phosphenes. In this
study by Bak and colleagues, three normally sighted patients,
undergoing occipital craniotomies for other conditions, were
tested for an hour each [30]. Surface stimulation produced the
same phosphenes described by Dobelle and Brindley. Following
this, a dual microelectrode was inserted to level 4B in the pri-
mary visual cortex and stimulation applied. Unlike surface elec-
trodes, the intracortical electrode phosphenes did not flicker.
An important finding from this research was the discovery that
intracortical stimulation required 10–100 times less electrical
current to produce phosphenes than surface electrodes. In addi-
tion, intracortical electrodes located as closely as 500 µm could
evoke distinct phosphenes.
A more detailed experiment by the NIH team was described
in 1996 by Schmidt and colleagues [31]. 38 microelectrodes
were inserted into the right visual cortex of a 42-year-old
woman for 4 months. The patient, who had been blind for
22 years, was consistently able to perceive phosphenes at stable
positions in visual space. Phosphenes were produced with 34 of
the microelectrodes, at thresholds usually at 25 µA. It was
found that these phosphenes did not flicker and changing the
stimulus amplitude, frequency and pulse duration could change
phosphene brightness. A perception of depth from the stimula-
tion was also reported and as the stimulation level was
increased, the phosphenes generally changed color (white, yel-
lowish and grayish). Supporting earlier research, phosphenes
moved with eye movements. Schmidt and colleagues suggested
that electrodes could be placed five times closer than surface
stimulation. An important result of this study concerned after-
discharge; one phosphene was observed for up to 25 min after
cessation of stimulation, which suggests that even small electri-
cal currents from repeated, patterned stimulation may be epi-
leptogenic. At least six of the electrode leads broke during the
study, due to accidental movement of the patient during sleep,
which limited testing on pattern recognition. The percutaneous
leads and electrodes were removed after 4 months.
The NIH Neuroprosthesis Program was discontinued by
2001 [32]. However, there is continuing collaboration with the
intracortical visual prosthesis team at the Illinois Institute of
Technology (IL, USA).

4. Dowling
4 Expert Rev. Med. Devices 2(1), (2005)
University of Utah
The University of Utah (UT, USA) currently has an active
intracortical research group led by Richard Normann. This
team has focused mainly on electrode array design for stimula-
tion and recording, behavioral experiments and psychophysical
experiments.
The University of Utah has developed an array of 100 pene-
trating cortical electrodes, each 1.5 mm in length and separated
by 400 µ. This length has been selected to reach level 4Cb of
the visual cortex, where neurons have the smallest and simplest
receptive fields and where lower thresholds can be used for gen-
erating phosphenes [33]. Manual insertion of the array was
found to cause cortical deformation, therefore, a pneumatic
insertion device has also been developed and tested [34]. The
biocompatibility of this array has been extensively evaluated
and arrays have been inserted for up to 14 months in cats [35].
The Utah electrode array (UEA) has been investigated as a
recording structure for potential brain-computer interfaces [36]
and recently for investigating representations of simple visual
stimuli in the cat visual cortex [37]. A modification of the UEA
is available which has graded electrodes, allowing stimulation
and recording to be conducted in both horizontal and vertical
directions [38].
Cortical implant for the blind
The Cortical Implant for the Blind (CORTIVIS) project, com-
menced in 2001, is lead by Edwardo Fernandez of the Univer-
sity of Miguel Hernandez (Spain), and involves researchers
from Spain, Germany, Austria, France and Portugal.
The group has investigated the use of the UEA in animal
experiments (cats, rabbits and rats) over a period of 12 h to
6 months. The electrodes were found to be well-tolerated by
the cortex, despite some inflammatory responses in the vicinity
of the electrode tracks [39].
In order to develop a methodology to identify feasibility of a
cortical prosthesis for a patient and the preferred location for
the prosthesis, Fernandez and colleagues have used transcranial
magnetic stimulation (TMS) to evoke phosphenes in 13 legally
blind and 19 normally sighted patients [40]. The advantage of
TMS is that it is painless and noninvasive. In total, 28-posi-
tions arranged in a 2 × 2 cm grid over the occipital area were
stimulated and phosphenes were perceived by 94% of the nor-
mally sighted participants. However, only 54% of the legally
blind patients perceived phosphenes (even after adjusting the
stimulation parameters). Evoked phosphenes were topographi-
cally organized and the mapping results could generally be
reproduced between participants.
The CORTIVIS project is also developing a retina-like proc-
essor, designed to simulate the functioning of the human retina
to produce optimal electrode stimulation at the cortical level
[41]. The output of this system is a series of spike patterns,
which could be used to stimulate neurons in the visual cortex.
In a study of brain plasticity by the CORTIVIS group, fMRI
was used to study the differences in reading Braille in normally
sighted and congenitally blind people [42]. Unlike normally
sighted participants, activation of the occipital cortex was
recorded in blind participants. The authors note that where
cross modal plasticity has been activated in this way, the
processing of tactile information is associated with significantly
improved tactile reading skill.
Intracortical visual prosthesis
The intracortical visual prosthesis (Illinois Institute of Technol-
ogy) project is led by Philip R Troyk, Director of the Laboratory
of Neuroprosthetic Research, and involves collaboration with
other institutions and former staff from the NIH Neuroprosthe-
sis Program. Their approach is to use small implanted arrays
(consisting of eight electrodes) in groups of intracortical elec-
trodes which tile the visual cortex. In a recent paper, Troyke and
colleagues describe an interesting animal experiment, using a
male macaque, designed to investigate visual prosthesis function-
ing with this tiled design [21]. Prior to implantation, the animal
was presented with a flash of light, and then trained to continue
staring at the flash location (so only the memory of the flash
remains); 192 tiled electrodes were then implanted into area V1
of the animal. Only 114 electrodes were functioning post
implantation. The receptive field coordinates for each implanted
electrode were estimated and a phosphene was generated in that
location. The macaque received a reward if its eye position
moved within 2° of the known receptive field for that electrode.
Retinal stimulation
The most common nonpreventable reason for blindness in the
developed world is age-related macular degeneration. This con-
dition affects the retina at the back of the eye, while leaving the
remaining components of the visual system intact. Retinal pros-
thesis research aims to use the remaining visual pathway com-
ponents to provide partial restoration of sight. An Australian
researcher, in 1956, was the first to describe placing a light sen-
sitive selenuium plate behind the retina of a blind individual
and restoring some intermittent light sensation [43].
There are significant advantages to the retinal approach to
AHV. Implantation of a cortical prosthesis requires intercranial
neurosurgery, which may expose a patient to higher risk. At a
fine scale, the mapping of a stimulus to the appropriate place on
the cortex may be variable between subjects [44]. An alternate
approach is to stimulate the eye rather than the brain. A retinal
prosthesis could assist people who still have a functioning optic
nerve. In post-mortem examinations of people without light
perception, 80% of the optic nerve and approximately 30% of
the ganglion cell layer was found to be functioning [45]. How-
ever, there may also be continual remodeling by the retina which
could lead to spatial corruption and cryptic synapse formation
after a retinal implant has been attached [46].
The two types of retinal prosthesis, discussed in the following
sections, are subretinal and epiretinal.
Subretinal stimulation
There are approximately 130 million receptors in the retina,
which are reduced down to 1 million fibers in of the optic

5. Artificial human vision
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nerve. This information reduction takes place in the inner
nuclear layer (consisting of amacrine, bipolar and horizontal
cell nuclei) of the retina. Targeting this layer, a subretinal
implant is located behind the photoreceptor layer of the retina
and in front of the pigmented layer called the retinal pigment
epithelium. Therefore, the subretinal approach, unlike the
epiretinal, may be capable of utilizing the information reduc-
tion functions in the retina, provided the electric field produced
does not interfere with other retina components (such as the
ganglion cell layer).
Optobionics Corp.
Since the 1980s Alan and Vincent Chow have been investigat-
ing subretinal microphotodiodes for subretinal stimulation [47]
and their company, Optobionics Corp. (USA), was awarded the
original patent for an artificial subretinal device in 1991 [48].
In an early animal experiment, an implanted strip electrode
was inserted behind the photoreceptor layer in a rabbit’s eye.
The evoked electrical response of stimulation to the operated
eye was compared with the normal eye by presenting a flash of
light and then measuring the response from the scalp over the
visual cortex. It was found that a brief electrical spike was gen-
erated during stimulation [49]. This experiment demonstrated
the feasibility of converting light into electrical energy using
subretinal stimulation to produce a cortical electrical evoked
response [50].
A further animal experiment focused on the long-term bio-
compatibility of subretinal stimulation [51]. Cats were selected
for this study as they have both retinal and choroidal circula-
tion (unlike rabbits). The implants, approximately 50 µm in
thickness, with a diameter of 2–2.5 mm, consisted of a doped
and ion implanted silicon substrate, surrounded by a gold elec-
trode layer. Following implantation in the cat’s right eye, the
arrays were evaluated over 10 to 27 months. During this time, a
gradually decreased response to light was found, due to the dis-
solution of the gold electrode layer. In addition, the silicon sub-
strate blocked choroidal nourishment to the retina, which led
to a degeneration of the photoreceptors, which are highly
dependent on blood supply for oxygenation. The loss of pho-
toreceptors may not be important as they may be damaged any-
way. However, design work commenced on a fenestrated design
in order to improve the flow of nutrients from the choroid to
the retina [51]. The positive findings from this study were that
the implant maintained a stable position over time and there
was no rejection, inflammation or degeneration of the retina
outside the location of the implant [52].
By June 2000, Optobionics received approval from the US
Food and Drug Administration (FDA) to commence safety and
feasibility trials in six patients [53]. The artifical silicon retina
(ASR), consisting of 5000 microelectrode-tipped microphoto-
diodes in a 2-mm diameter device, was implanted into the right
eyes of six legally blind patients with RP. During a follow-up
period of 6–18 months, all ASRs were found to function elec-
trically and there were no signs of rejection, inflammation, ero-
sion, retinal detachment or migration of the device. During this
study it was found that all patients experienced improvements
in visual function (such as improved color perception) and
there were also unexpected improvements in retinal areas dis-
tant from the implant. These improvements may have been due
to neurotropic effects, rather than the device and further stud-
ies are intended to explore this improvement. Additional
planned research will examine the implant and age-related mac-
ular degeneration, and whether the neurotropic effect can be
effective in earlier stages of RP [53].
An issue with the Optobionics research has been the lack of an
experimental control (by implanting an inactive device or con-
ducting sham surgery) to evaluate against the ASR. Pardue and
colleagues have recently conducted research addressing this issue
[54]. Their experiment involved 15 RCS rats, which have a
genetic mutation resulting in photoreceptor degeneration over
approximately 77 days. The rats received either the ASR device,
an inactive device, sham surgery or no surgery. The outer retinal
function was assessed with weekly electroretinogram (ERG)
recordings. After 4–6 weeks there was a 30–70% higher b-wave
amplitude response with the ASR compared with the inactive
device, indicating that the ASR device appears to produce some
temporary improvement in retinal function. However, after
8 weeks, there was no significant difference in b-wave amplitude
response between the inactive and active devices. At 8 weeks,
there was a significantly greater number of photoreceptors
remaining for rats who had received either the ASR or inactive
device compared with those rats that had undergone sham sur-
gery or no surgery. Pardue and colleagues suggest that enhanced
protective effects from the ASR may be possible by altering the
design to increase current levels or by increasing environmental
light levels to produce higher stimulation levels [54].
MPDA project
After collaborating with the Optobionics group between 1994
and 1995 [55], a Southern German team led by the University
Eye Hospital in Tübingen, was formed in 1995 to develop a sub-
retinal prosthesis. In 1996, the Institute of Micro-Electronics in
Stuttgart developed a prototype microphotodiode array
(MPDA) containing 7600 microelectrodes on a 3-mm disc, 50
µm in diameter [56]. In vitro techniques have been predominantly
reported by the German subretinal project.
The first generation of MPDAs were tested using a sandwich
technique, which involved the retinae from newly hatched
chickens being adhered to a recording multielectrode array (the
ganglion cell side was adhered). The photoreceptor outer seg-
ments were then damaged and an MPDA placed onto the ret-
ina. This technique allowed the recording of stimuli from the
MPDA [56]. A later study examined degenerated rat retinae [57].
The retinae were removed and cut into 5 × 5 mm
segments, then attached to a 60-electrode microelectrode
array. Beams of white light were flashed onto the MPDA and it
was found that intrinsic ganglion cell activity could be recorded
even with a highly degenerated retinal network. Further experi-
ments have demonstrated that it should be possible to transform
the basic features of images, such as points, bars and edges into

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6 Expert Rev. Med. Devices 2(1), (2005)
activity of the existing retinal network; which suggests that shape
perception and object location may be possible with a subretinal
device [58]. However, recent epiretinal results from Rizzo and col-
leagues have not confirmed the pattern perception of phosphenes
from patterned electrical stimulation of the retina [59].
Further tests have been conducted in order to test the bio-
compatibility stability of the MPDA. Various materials were
placed in Petri dishes with the retinae of pigmented rats. For
comparison, a control dish containing only the retinae and
solution was used. None of the MPDA materials demonstrated
a toxic effect. Retinal cell cultures from rats were also used by
Guenther and colleagues to screen for technical implant mate-
rial [60]. Although most materials (including iridium and silica)
showed good biocompatibility, a reduced biocompatibility was
found for titanium materials. Interestingly, a later paper by
Hammerle and colleagues found that titanium nitrate had
excellent biostability, both in vivo and in vitro [61].
Similarly to the Optobionics research, electroretinography
was performed in rabbits and rats in order to measure the effec-
tiveness of the MPDA. As the MPDA are sensitive to infrared
light, it is possible to stimulate the retina and measure the cur-
rent discharged from the MPDA. This method should be useful
for the localizing electrical responses from an MPDA.
As with the early Optobionics MPDA [49], Zrenner and col-
leagues found in their early work that metabolic processes in
the photoreceptor layer can be disrupted by the MPDA and
they placed very thin holes in their device to allow nutrients to
be passed [56].
As natural photoreceptors are far more efficient than photo-
diodes, visible light is not powerful enough to stimulate the
MPDA. Therefore, infrared enhancement of the photodiode
arrays (by inserting an additional layer in the array) has been
suggested to enhance the stimulation current [43].
The German team commenced in vivo experiments in 2000,
when evoked cortical potentials were measured from Yucantan
micropigs and rabbits. The micropigs have eyes which are com-
parable in size and function with human eyes [62]. At 14 months
post implantation, the implant and retina surrounding it were
examined and there were no noticeable changes to anatomical
integrity [63]. However, because the existing MPDA does not
function in ambient light conditions, an electrode foil prototype
with similar properties was implanted. The micropigs required a
higher threshold level than the rabbits [64], however, 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 [64].
The latest reports from this group concern the results of
in vivo experiments in cats. Volker and colleagues described the
use of optical coherence tomography to examine the morpho-
logic and circulatory conditions of the cat neuroretina and it’s
interface with an implanted MPDA [65].
Other subretinal methods
A team of Japanese researchers, led by Tohru Yagi of Nagoya
University has been investigating the attachment of cultured
neurons onto electrodes and then guiding the axons towards
the CNS. As this hybrid retinal implant will not require retinal
ganglion cells or an optic nerve, it could be useful for patients
with diseases in these components of the visual pathway.
Results of an experiment with neural cells obtained from the
spinal cords of a 3–4- week-old rat are described by Ito and col-
leagues [66]. Another study by this team investigated electrical
stimulation requirements by stimulating the lateral geniculate
nucleus in a cat. Recordings of the evoked potentials from the
cat’s cortex found that pulse amplitude was a more important
factor than pulse duration and that a biphasic pulse pattern was
the most effective stimulation pattern [67]. Further studies have
suggested using a computer model for the 3D configuration of
electrode arrays [68].
Peterman and colleagues are also investigating the use of
directed cell growth and localized neurotransmitter release for a
retinal interface. They have been successful in directing the
growth of neurons in a defined direction, using micropatterned
substrates [69] and have demonstrated that the localized chemi-
cal stimulation of excitable cells is feasible. The authors suggest
that chemical stimulation can have a similar spatial resolution
as an electrical stimulation but with the ability to mimic the
major functions of synaptic transmission [70].
An interesting design for a MPDA has been recently reported
by Ziegler and colleagues, who propose a device where each pixel
acts as an independent oscillator whose frequency is controlled
by light intensity [71].
Kanda has suggested an alternative stimulation method for a
retinal device: suprachoroidal-transretinal stimulation (STS),
which does not involve the attachment of electrodes to the ret-
ina [72]. This should result in less complicated surgery for blind
patients. The anodic-stimulating electrode is located on the
choroidal membrane and the cathode is located in the vitreous
body. This technique has been used in animal experiments
where evoked potentials were recorded from the superior collic-
ulus in rats. The authors are planning long-term, in vivo bio-
compatability studies [72]. However, it has been demonstrated
that neural cells should not be separated from electrodes by
more than a few µm, due to overheating, crosstalk between
neighboring pixels and electrochemical erosion [73]. The thick-
ness of the choroid is approximately 400 µm, therefore, supra-
choroidal placement precludes close proximity between elec-
trodes and cells, which will limit the potential visual acuity of
the STS approach.
Epiretinal stimulation
An epiretinal device involves a neurostimulator chip being
implanted against the ganglion cells in the retina. This approach
attempts to stimulate the remaining retinal neurons of patients
who are blind from end-stage photoreceptor diseases.
Retinal implant
Formerly from the Wilmer Ophthalmological Institute, John
Hopkins Hospital, Mark Humayun and Eugene De Juan Jr are
currently based at the Doheny Retina Institute at the University

7. Artificial human vision
www.future-drugs.com 7
of Southern California (CA, USA). Humayun’s PhD thesis
demonstrated that a visually impaired person could perceive
phosphenes during stimulation of the retina [74]. The engineer-
ing aspects of developing electronic stimulators and supporting
electronics have been mainly conducted by Wentai Liu and his
team at North Carolina State University [75].
In the first experiment to demonstrate successful phosphene
perception from local electrical stimulation of the retina,
14 patients (12 with RP, and two with age-related macular
degeneration) had their inner retinal surface electrically stimu-
lated under local anaesthesia [76]. The responses were retinotop-
ically correct in 13 of the patients, with the remaining patient,
blind from birth, unable to distinguish anything apart from
flashing light. The phosphenes were perceived exactly with the
timing of the electrical stimulation [76]. Flicker fusion was
tested in two subjects and found to occur at approximately
50 Hz; the phosphenes also appeared brighter at higher fre-
quency [77]. An earlier paper also reported on five of these
patients [78].
In 1999, a further experiment was reported on nine subjects,
involving nine or 25 electrode array electrodes [45]. The elec-
trodes were placed against the retinal surface and handheld in
place using a silicon-coated cable with the guidance of a surgi-
cal microscope. The flicker fusion frequency was found to be
50 Hz in two subjects and 40 Hz in another two subjects (the
remaining subjects were not tested). By scanning with the head-
mounted camera, subjects were able to perceive simple shapes
in response to stimulation (e.g., horizontal and vertical lines
and ‘U’ and ‘H’ shapes).
A report on the long-term biocompatibility of an implanted,
inactive epiretinal device was also published in 1999 [79], in
which 25 platinum disc-shaped electrodes in a silicon matrix
were implanted into the retinal surface of four normally sighted
dogs. The arrays were held in place using metal alloy tacks.
Over a 6-month period the implants were biologically tolerated
well, mechanically stable and could be securely attached to the
retinal surface [79].
A design for a functioning retinal prosthesis system has been
described in joint papers by Liu and colleagues at North Caro-
lina State University and the John Hopkins team in 1999 [80,81].
The proposed device, termed the multiple unit artificial retina
chipset (MARC), consists of the extraocular unit containing the
video camera and video processing board, connected by a tele-
metric inductive link to the intraocular unit. The power and
signal transceiver, stimulation driver and electrode array are
contained in the intraocular unit.
In 2003, after obtaining FDA approval, the Doheny Eye
Institute team and Second Sight (CA, USA), a company
formed by former North Carolina State University team
member, Robert Greenberg and Alfred Mann, developed the
first human epiretinal implant. A subject with advanced RP
received an implanted 4 × 4-electrode array, connected by a
subcutaneous cable to an extraocular unit which was surgi-
cally attached to the temporal area of the skull. A wireless
link transferred data and power from a belt-worn visual-
processing unit to the extraocular unit. All 16 electrodes
produced phosphenes and the subject was able to detect
ambient light, motion and correctly recognize the location
of phosphenes (e.g., left vs. right or upsidedown). Future
plans are to develop more complex stimulation control and
provide a higher number of electrodes [82]. The use of micro-
wire glass is also being investigated as a method to assist
with the mapping of flat microelectric stimulator chips and
curved neuronal tissue [83].
Retinal prosthesis project
Following earlier collaborative work with Humayan and
deJuan, Wentai Liu and his team have continued with the
development of an epiretinal prosthesis. A 60-electrode stimu-
lating chip, which integrates power transfer and back telemetry,
has been developed [84]. One of the advantages of this system
would be removing the requirement for the cable connecting
the intraocular and extraocular units described in the Doheny
Eye Institute team implant [82].
Second Sight
Second Sight is a company formed by Robert Greenberg (from
the Retinal Prosthesis Project led by Wentai Lui) and Alfred
Mann (also the founder of the Cochlear Implant company
Advanced Bionics). Second Sight developed the epiretinal device
implanted into a blind patient by the Doheny Eye Institute team,
as described previously [82].
Boston retinal implant project
This project is a collaboration between Joseph Rizzo (Massa-
chusetts Eye and Ear Infirmary, Harvard Medical School,
MA, USA) and John Wyatt (Massachusetts Institute of Tech-
nology, MA, USA) to develop an epiretinal prosthesis. The
main difference between their approach and Humayun and
colleagues, is the use of a miniature laser, located in a pair of
glasses, to transfer power and data to a stimulator chip.
Although the laser is required to be accurately directed to the
implant and needs to cope with blinking, it will not be
effected by electronic noise interference (unlike radiofre-
quency transmission) [85]. Electrically invoked cortical poten-
tials have been successfully recorded from stimulation of a
rabbit retina [86].
Recently, the microelectrode arrays have been tested with
six patients, five of them legally blind from RP. The sixth
patient was normally sighted, however their eye required
removal due to orbital cancer. All patients were able to per-
ceive phosphenes in response to stimulation, however, the
results were mixed. Threshold charge densities were found
to be significantly higher and above safe levels, in blind
patients compared with the normally sighted patient [59]. In
this study, it was often found that multiple phosphenes
would be presented when a single electrode was stimulated,
for example, 60% of tests in one subject. In addition, multi-
ple-electrode stimulation did not reliably produce matching
phosphenes [87].

8. Dowling
8 Expert Rev. Med. Devices 2(1), (2005)
EPI-RET
Rolf Eckmillar from the University of Bonn (Germany), leads
the German EPI-RET project, which involves 14 research
groups. The aim of their first epiretinal device is to allow blind
people to identify the location and shape of large objects [88].
Their approach involves replicating a healthy retina with a reti-
nal encoder device, which consists of a photosensor array of
10,000–100,000 pixel inputs and simulated output of
100–1000 ganglion cells. Eventually, this project aims to embed
this encoder into a contact lens. The output from the encoder is
then sent to an implanted retinal stimulator. Eckmilliar and col-
leagues suggest that a future epiretinal prosthesis will be tuned
(to optimize phosphene perception) during a dialog between a
subject and their retinal encoder [89–92]. More recently, a learn-
ing active vision encoder (LAVIE) has been proposed to com-
pensate for spontaneous eye (drift or nystagmus) and head
movements in the absence of vision. A smooth pursuit function
is also being investigated [93].
Flat platinum microelectrodes have been developed for the
EPI-RET project and evoked cortical potentials have been
recorded after stimulation in rabbits [94]. In 2000, Hesse and
colleagues reported problems with the fixation of the electrode
film and the retina in a cat experiment, partly due to the very
thin posterior sclera [95]. Research into alternate electrode shape
and fixation techniques is planned.
The company Intelligent Implants was formed in 1998 to
commercialize research by the EPI-RET group [93].
University of NSW and University of Newcastle Vision
Prosthesis Project
Australian research on an epiretinal prosthetic vision system is
occurring at the Vision Prosthesis Project at the Universities of
NSW and Newcastle, led by Gregg Suaning and Nigel Lovell.
This project aims to extend concepts from the development of
cochlear prostheses.
A 100-channel neurostimulator circuit for the retina has been
developed, which uses bidirectional radiofrequency telemetry
for transferring data and power [16,44]. A data format protocol
has been introduced. The 100-channel neurostimulator was
found to function and successfully produce evoked potentials
in sheep [96–98]. An inexpensive technique for manufacturing
platinum spherical electrodes has also been proposed [99].
Recently, an hexagonal mosaic of intraocular electrodes has
been suggested by Hallum and colleagues to optimize the place-
ment of electrodes and therefore improve visual acuity in pros-
thesis patients [100]. A prototype for an epiretinal system, capa-
ble of 840 stimulating events per second, using this electrode
placement combined with a filtering approach to image
processing, has also been described [101].
Optic nerve devices
The optic nerve is a collection of 1 million individual fibers
running from the retina to the lateral geniculate body. This
nerve can be reached surgically and could provide a suitable
location for implanting a stimulation electrode array.
Microsystems-Based Visual Prosthesis & OPTIVIP projects
(ESPRIT programme of the European Union)
The Microsystems-Based Visual Prosthesis (MiVip) team, led
by Claude Veraat of the Neural Rehabilitation Engineering
Laboratory, Université Catholique de Louvain in Belgium,
has developed a prosthesis system which includes a spiral cuff
silicon electrode to stimulate the optic nerve.
In February 1998, a 59-year-old blind patient was implanted
with the optic nerve visual prosthesis. Localized phosphenes
were successfully produced throughout the visual field and
changing pulse duration or amplitude could alter their bright-
ness. After training it was reported that the patient could per-
ceive different shapes, line orientations and even letters [102].
However, this system only displays one phosphene at a time and
pattern recognition was achieved by the subject scanning with a
head-mounted camera over a time period of up to 3 min. An
interesting feature of this study has been the different phos-
phene shapes that have been generated; if these could be reliably
replicated they might add a useful dimension to prosthetic
vision. The cuff electrode consists of four platinum contacts and
is able to adapt continuously to the diameter of the optic nerve.
Initially a subcutaneous connector conducted stimulation of the
electrode, however, in August 2000, a neurostimulator and
antenna were implanted and connected to the electrode. An
external controller with telemetry was then used for stimulating
the cuff electrode. Recently, an adaptive neural network tech-
nique has been proposed to classify the phosphenes generated by
this device [103,104].
AHV simulation studies
Due to the difficulty in obtaining experimental participants
with an AHV device implanted, a number of simulation studies
have been conducted with normally sighted subjects. However
the simulation approach assumes that normally sighted people
are receiving the same experience as a blind recipient of an
AHV system. Weiland and Humayun have stated that human
implant studies are the only method of verifying the effective-
ness of a visual prosthesis and have questioned the validity of
simulation studies [105].
A frequently cited prosthetic vision simulation was con-
ducted in 1992 at the University of Utah by Cha and col-
leagues, in order to calculate the minimum number of phos-
phenes required for adequate mobility [106]. The pixelized
vision simulator device consisted of a video camera connected
to a monitor in front of the subject’s eyes. A perforated mask
was placed on the monitor to reproduce the effect of individual
phosphenes. The artificial environment consisted of an indoor
maze, which contained paper column obstacles. Walking speed
and frequency of contact were used as dependant variables.
This research found that a 25 × 25 array of phosphenes, with a
field of view of 30° would be required for a successful device.
The simulation display employed by Cha and colleagues
used a simple television-like display. Hayes and colleagues have
described a more sophisticated approach [107], in which two
different image-processing applications were used to display

9. Artificial human vision
www.future-drugs.com 9
simulated phosphenes to a seated subject, who wore a head-
mounted display. The first image processing application used a
simple square phosphene array, where each phosphene con-
sisted of a solid grey scale value equal to the mean luminance
of the contributing image pixels. The second image processing
application used a Gaussian filter. Array size, contrast level,
dropout percentage, simulated phosphene size and back-
ground noise were adjustable features of the simulation.
Object recognition (including plate, cup and spoon), reading,
candy pouring and cutting accuracy tasks were conducted
under different simulation conditions. The main result was to
conclude that the phosphene array size would be the most
important factor in a useable prosthesis.
Another image processing approach investigated the require-
ments for AHV facial recognition in [108]. A low vision
enhancement system connected to a PC and driven by a visual
basic program was used to display the images. Subjects were
required to select which simulation image best matched a set of
four normal images of human faces (the images of the same
person were varied by head angle and whether the person was
smiling or serious). All images displayed occupied a visual field
of 13° horizontally and 17° vertically. The simulation display
was presented in a circular dot mask, rather than the contigu-
ous square blocks. Electrode properties (such as dropouts; size
and gaps), contrast and grey levels could be varied experimen-
tally. The grid sizes used in this study varied from 10 × 10 to 32
× 32 phosphenes. The authors found high accuracy for all high
contrast tests (except those with significant dropout and two
gray levels) and suggest that reliable face recognition using a
crude pixelized grid is feasible.
Research at the Queensland University of Technology (Aus-
tralia), has examined the use of various image-processing
techniques (such as enhancing edges, using different grey
scales and extracting the most important image features) to
identify a recognition threshold for low-quality stationary
images [109]. These images are used to represent the limited
number of phosphenes available to the subject (typically a 25
× 25 array). This research has found that at these low infor-
mation levels the use of image- processing techniques is not
helpful in the identification of static scenes, although an auto-
matic zoom feature did aid image understanding. Additional
research at Queensland University of Technology is investigat-
ing methods for the assessment and enhancement of mobility
for AHV system users [110].
Expert opinion
With our current understanding of neuronal mechanisms in
the visual system, AHV systems do not appear likely to
replace the functioning of normal human vision. It is not
likely that a regularly organized array of phosphenes will
occur as a result of current technology microelectrodes [21].
While the development of AHV systems continues, research
into retinal transplantation, growth factors and gene therapy
has commenced which may also provide alternative treatment
options for blindness.
AHV systems are likely to offer benefits in the areas of mobility
and reading. An important question is whether the benefits from
these systems are worth the cost. Despite the overloading of
another sensory input channel, traditional mobility aids and ETA
devices (such as the vOICe system from Peter Meijer [201]), are
probably cheaper, less invasive and may require a similar amount
of training to AHV systems. Additionally, most people who are
classified as blind are elderly and still have some remaining
vision, and therefore are probably not suited to an AHV system.
The need for standard psychophysical assessment methods
have been noted by a number of AHV researchers [101,111]. To
inform consumers on the benefits of an AHV system compared
with other technical aids for the blind, future research compar-
ing the effectiveness of these devices would be useful. The lack
of a method to compare mobility has also been raised by
Dobelle [13]. However, there are a number of mobility assess-
ment methods presented in the Orientation and Mobility Liter-
ature which could be useful for comparison of AHV systems
and other devices [112–114].
AHV research offers important insight regarding the function-
ing of the human visual system and in brain-computer interface
technology. The subretinal device from Optobionics has shown
impressive results, however, these results may be due to neuro-
trophic effects rather than the microphotodiode implant used.
Current research in other AHV systems is promising, however,
there appears to be significant development required before they
can provide useful mobility and reading. Excellent additional
review papers on AHV include [38,50,115,116].
Five-year view
The subretinal implants demonstrate the greatest promise in
restoring some vision, however, there are doubts over whether
the improvements in vision are due to neurotrophic effects or
the device itself. Further tests to determine the reason for the
improvements are planned. If the device is responsible, it is
conceivable to see these implants available in the next 5 years.
The cortical implant system from the Dobelle institute is
commercially available; however it has not been approved by
the FDA. A 5-year view on this system is not possible, as infor-
mation regarding the system and patient outcomes are not
made public. A recent article in the Wall Street Journal [117]
reported a 33-year-old female recipient who paid US$100,000
for the Dobelle system and was only able to use it for 15 min
per day (as it was tiring and caused head pain).
The remaining cortical and optic nerve systems are still in
varying stages of preliminary human or animal testing. Prelimi-
nary research has also commenced on microstimulation of the
lateral geniculate nucleus [118]. Although progress will be made,
it does not appear likely that a commercial system using these
methods will be available in the next 5 years.
Acknowledgements
This research was supported by Cochlear Ltd and the Aus-
tralian Research Council through ARC Linkage Grant project
0234229.

10. Dowling
10 Expert Rev. Med. Devices 2(1), (2005)
Information resources
Main contacts and project websites:
• Bionic Eye Research Project (Cortical Neuroprosthesis, Uni-
versity of New South Wales, Australia)
Vivek Chowdhury and John Morley
http://ophthalmology.med.unsw.edu.au/bioniceye.htm
• Cortical Implant for the Blind (CORTIVIS, Europe)
Edwardo Fernandez
http://cortivis.umh.es/
• EPI-RET (Retina implant research in Cologne, Germany)
Rolf Eckmiller
www.medizin.uni-koeln.de/kliniken/augenklinik/epi-
ret3e.htm
• Intracortical visual prosthesis (Illinois Institute of Technol-
ogy)
Phillip Troyk
http://neural.iit.edu/intro.html
• Microsystems-Based Visual Prosthesis (MiVip, ESPRIT pro-
gram of the European Union, now OPTIVIP)
Claude Veraart
www.md.ucl.ac.be/gren/Projets/mivip.html
• OPTIVIP projects (ESPRIT program of the EU)
Claude Veraart
www.dice.ucl.ac.be/optivip/
• Optobionics Corporation (USA)
Alan Chow and Vincent Chow
www.optobionics.com
• Retinal Implant (Doheny Retina Institute, University of
Southern California, USA)
Mark Humayun and Eujene De Juan Jr
www.usc.edu/hsc/doheny/
• Retinal Implant & Biohybrid Implant (Japan)
Tohru Yagi
www.bmc.riken.jp/~ yagi/retina/
• Retinal Implant-AG (was SUB-RET project, Germany)
Eberhart Zrenner
www.retina-implant.de/tour/
• Retinal Prosthesis Project (North Carolina State University)
Wentai Liu
www.icat.ncsu.edu/projects/retina/
• Retinomorphic chip (University of Pennsylvania, USA)
www.neuroengineering.upenn.edu/boahen/pub/fs_pub.htm
• Second Sight (CA, USA)
Alfred E Mann and Robert Greenberg
www.2-sight.com/
• The Boston Retinal Implant Project (USA)
John Wyatt and Joseph Rizzo
www.bostonretinalimplant.org/
• The Dobelle Institute (Lisbon, Portugal)
William Dobelle
www.dobelle.com/
• University of Utah (Intracortical prosthesis, USA)
Richard A Normann
www.bioen.utah.edu/cni/projects/blindness.htm
• Vision Prosthesis Project (Retinal prosthesis, Universities of
NSW and Newcastle, Australia)
Gregg Suaning
http://bionic.gsbme.unsw.edu.au/
Key issues
• Artificial human vision (AHV) involves the electrical
stimulation of a component of the human visual system,
which may invoke the perception of a phosphene or point
of light.
• Four locations for AHV implants are currently utilized;
subretinal, epiretinal, optic nerve and the visual cortex
(using intra- and surface electrodes).
• The only commercially available system is the cortical
surface stimulation device from the Dobelle Institute.
• The most impressive gains in vision have been reported
from the subretinal device developed by the Optobionics
Corp., however, these results may not be related to the
microphotodiode device used.
• Psychophysical and mobility assessment standards would
help in comparing AHV systems with other technical aids
for the blind.
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(Accessed December, 2004)
Affiliation
• Jason Dowling
Queensland University of Technology, School of
Electrical and Electronic Systems Engineering,
Faculty of Built Environment and Engineering,,
Brisbane, Australia
Tel.: +617 3864 1608
Fax: +617 3864 1516
j.dowling@qut.edu.au