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Sensors and Materials, Vol. 29, No. 12 (2017) 1667–1677
MYU Tokyo
S & M 1460

Sinusoidal Electrical Pulse
More Efficiently Evokes Retinal Excitation
than Rectangular Electrical Pulse in Retinal Prostheses
Yukari Nakano,1* Yasuo Terasawa,1,2 Hiroyuki Kanda,3 Hiroyuki Tashiro,4Koji Osawa,5 Tomomitsu Miyoshi,6 Hajime Sawai,7 and Takashi Fujikado3
1

Artificial Vision Institute, Research and Development Division, Nidek Co., Ltd.,
13-2 Hama-cho, Gamagori, Aichi 443-0036, Japan
2
Graduate School of Materials Science, Nara Institute of Science and Technology,
8916-5 Takayama-cho, Ikoma, Nara 630-0192, Japan3
Department of Applied Visual Science, Osaka University Graduate School of Medicine,
2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
4
Department of Health Sciences, Faculty of Medical Sciences, Kyushu University,
3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
5
Artificial Retina Development Office, Development Division, Nidek Co., Ltd.,
34-14 Maehama, Hiroishi-cho, Gamagori, Aichi 443-0038, Japan
6
Department of Integrative Physiology, Osaka University Graduate School of Medicine,
2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
7
Department of Health Sciences, School of Nursing, Osaka Prefecture University,
3-7-30 Habikino, Habikino, Osaka 583-8555, Japan(Received March 31, 2017; accepted June 23, 2017)

Keywords: retinal prosthesis, stimulation waveform, electrical stimulation parameter, retinitis
pigmentosa, threshold charge

Retinal prostheses for blindness due to retinal photoreceptor degeneration stimulate theretina electrically to evoke a pseudolight sensation (phosphenes). Although rectangular pulses
of electrical stimulation are commonly used in retinal prostheses, it remains unclear whether
nonrectangular pulses are effective in evoking this response. Here, we conducted in vivo
electrophysiological experiments to compare the effectiveness of sinusoidal and rectangular pulses.
Biphasic sinusoidal pulses (cathodic-first) applied suprachoroidally and transretinally to the rat eyeelicited larger field responses in the superior colliculus than did rectangular pulses. The thresholdcharge for the evoked response of the sinusoidal pulse was significantly lower than that of therectangular pulse, suggesting that a sinusoidal pulse is more effective than a rectangular pulse
in our retinal prosthesis. Because a sinusoidal pulse can evoke phosphenes with a small charge
magnitude even if the electrode area is reduced, the charge density does not increase; thus, thepulse can stimulate the retina without causing tissue injury. Because the sinusoidal pulse allows
us to reduce the electrode area, it is possible that phosphenes can be localized to a smaller areaby limiting the range of stimulated retinal ganglion cells. Therefore, high resolution of retinal
prostheses using the sinusoidal pulse can be expected.

*

Corresponding author: e-mail: yukari_nakano@nidek.co.jp
http://dx.doi.org/10.18494/SAM.2017.1611
ISSN 0914-4935 © MYU K.K.

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1.

Sensors and Materials, Vol. 29, No. 12 (2017)

Introduction

The recent development of brain–machine interfaces (BMIs) is promising for the treatment of
numerous disabilities. Such technology may extend patients’ abilities and overcome handicaps
in their daily living activities via devices that directly connect to the nervous system. BMIs areclassified into two major categories: output BMI and input BMI.(1) Output BMIs decode neural
outputs from the brain to control devices such as robotic arms.(2) Sensor devices receive externalsignals such as sound and light and transmit them to the sensory nervous system. Input BMIs areused for sensory disabilities such as blindness and deafness. The sensor devices receive externalsignals and provide the sensory nervous system with corresponding inputs. The most successful
example of an input BMI is the cochlear implant for neurosensory deafness. An electrodearray implanted into the degenerated cochlea electrically stimulates the cochlear nerve fibers toprovide auditory sensation. This device has been in practical use for more than 30 years and hasreconstructed the hearing of hundreds of thousands of people worldwide.(3) The visual equivalentof the cochlear implant is the retinal prosthesis. The target disease of the retinal prosthesis isretinitis pigmentosa (RP), a degenerative disease that is one cause of acquired blindness and affects
1 in 4000 people worldwide.(4) This incurable disease involves the progressive degeneration ofretinal photoreceptor cells. At present, no fundamental therapy for RP has been established.
Retinal prostheses have been studied as a means of restoring the visual function lost to RP. One of
the retinal prostheses has been approved recently in the United States and Europe.(5)The retinal prosthesis converts an image captured by a camera into electrical signals. Thesesignals stimulate the electrode array in the retinal implant to emit electrical signals to the retina.
This retinal stimulation evokes a pseudolight sensation called phosphenes, finally restoring vision
artificially. While RP results in severe damage to photoreceptor cells, other types of inner retinal
cells, such as retinal ganglion cells, remain even after blindness ensues.(6) This observationsuggests that vision could be reconstructed through electrical stimulation of the remaining retinal
cells. Retinal prostheses are based on this principle. Retinal prostheses are classified into fourtypes, depending on the position of the electrode array: (1) epiretinal (placed on the retina from thevitreous side),(5) (2) subretinal (placed between the choroid and the retina),(7) (3) placed between
the choroid and retinal pigment epithelium,(8) and (4) placed in the sclera.(9) We have beendeveloping a retinal prosthesis based on suprachoroidal transretinal stimulation (STS) in which
the electrode array is placed in a scleral pocket created by making a half-layer incision.(9) By thismethod, the fixation of the electrode array is more mechanically stable than that of other methods.
Further advantages are that the surgical invasion of the eye is small and a wide field of view canbe secured. However, since retinal cells are stimulated via the choroid, the stimulation charge
required to induce light sensation is greater than that of other approaches.(10) This problem might
be solved by investigating the stimulation parameters.
A biphasic rectangular current pulse is generally used for electrical stimulation in retinal
prostheses, regardless of the implantation position of the stimulating electrode array. For example,
biphasic rectangular current pulses are used in epiretinal,(5) suprachoroidal,(8) and STS prostheses.(9,11)
Charge-balanced biphasic pulses can carry out electrical stimulation safely without causing
damage to tissues.(12) The optimum pulse duration and frequency for retinal ganglion cell
activation (with respect to stimulation effectiveness) has been studied in vitro.(13–15) However,
the optimal stimulation waveform shape remains unknown. Accordingly, a rectangular pulse

Sensors and Materials, Vol. 29, No. 12 (2017)1669

may not be optimal as the stimulation waveform. Stimulation waveforms that reduce the required
threshold charge could allow for the realization of smaller electrodes with higher spatial resolution.
Therefore, determining the optimal waveform for high stimulation effectiveness is important forthe development of retinal prostheses. In a study of rat retina in vitro, Weitz et al. reported that asinusoidal pulse has a lower threshold charge than does a rectangular one.(13) However, this result
was obtained using epiretinal stimulation; therefore, the effect of a sinusoidal pulse in STS has
not been established. In addition, these in vitro results may not hold true in vivo. Therefore, we
conducted in vivo electrophysiological experiments to determine whether a sinusoidal pulse is also
effective in STS and in vivo.

2.

Materials and Methods

2.1

Animals

We used normal rats (Long–Evans; n = 13) aged 15–24 weeks and retinal-degenerated rats
[Royal College of Surgeons (RCS); n = 20] aged 30–37 weeks. All procedures were in accordancewith the Association for Research in Vision and Ophthalmology (ARVO) Statement for the Use of
Animals in Ophthalmic and Vision Research. This study was approved by the Institutional Animal
Care Committee of Nidek.
2.2

Surgical preparation

All animals were anesthetized for surgery and acute electrophysiological recordings byintraperitoneal injection of urethane (1.75 g/kg). The head of the rat was fixed with a stereotaxic
apparatus (SR-5R-HT, Narishige Science Institute Laboratory, Tokyo, Japan). The left eye of the
rat was exposed, and the partial sclera of the eye was resected surgically from approximately 1 mm
below the optic nerve to the vicinity of the equator. A platinum stimulating electrode (diameter, 0.5mm; height, 0.3 mm) was placed in the partial scleral resection using a micromanipulator (SF-1, S,
Tokyo, Japan). A return electrode (platinum–iridium wire; diameter, 0.2 mm) was placed into thevitreous body using a micromanipulator (Minimanisuke, S). After partial removal of the sclera,mineral oil was used around the eye to prevent drying. A craniotomy was performed to remove
the posterior two-thirds of the right parietal bone, and the underlying cortex was gently aspirated
to expose the dorsal surface of the right superior colliculus (SC). Mineral oil was applied to the
exposed SC area during the experiment to prevent drying. A stainless-steel screw acting as thereference electrode was inserted into the occipital bone.
2.3

Photic stimulation

To evaluate the survival of photoreceptors in the retina of RCS rats, we recorded visual evoked
potentials from the SC. The left eye of the rat was dilated with a mydriatic agent (Mydrin-P
ophthalmic solution, Santen Pharmaceutical, Osaka, Japan), and the cornea surface was covered
with a contact lens electrode combined with a light-emitting diode (LED) light source (R250
LEDT, Mayo, Aichi, Japan). After dark adaptation for 20 min, flashing light stimuli (luminance,
1000 cd/m2; duration, 1 ms; frequency, 1 Hz) were applied in a dark room using an LED (LS-100,Mayo).

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2.4

Sensors and Materials, Vol. 29, No. 12 (2017)

Electrical stimulation

Figure 1 shows the setup for electrical stimulation. A single biphasic current pulse was applied
between the stimulating electrode and the return electrode using a stimulus generator (STG 4002,
Multi Channel Systems, Reutlingen, Germany). The current pulse duration was 0.5 ms, and thestimulation frequency was 1 Hz. Electrical stimulation was performed using rectangular andsinusoidal pulses of the single biphasic current pulse (outward current/cathodic-first) (Fig. 2). The
current amplitudes ranged from 50 µA to 1 mA. The stimulation waveforms were confirmed using
an oscilloscope (TPS 2014, Tektronix, Oregon, USA).
2.5

Electrophysiological recordings

A tungsten microelectrode [resistance, 0.5 MΩ; diameter, approximately 5.0 µm (uninsulatedpart), Unique Medical, Tokyo, Japan] was inserted to the depth of 250 µm from the SC surface
using a micromanipulator (MMO-203, Narishige) to record local field potentials evoked by photic
and electrical stimulation. The recorded potentials were amplified using a differential amplifier(DP-301, Warner, Connecticut, USA) (amplification: photic stimulation, 100 times; electricalstimulation, 1000 times; band-pass filter, 10 Hz–3 kHz) and then digitally sampled and averaged
using PowerLab (2/26, ML 826, ADInstruments, Dunedin, New Zealand) with evoked potentials (EPs)collection software (LabChart, ADInstruments). The signal for photic stimulation was averaged 50
times for normal rats and 300 times for RCS rats. The signal averaging for electrical stimulation+-

Stimulator+-

Recording of collicular
evoked potentials

Fig. 1. (Color online) Setup for electrical stimulation and recording. Under anesthesia, a platinum stimulating
electrode (diameter, 0.5 mm; height, 0.3 mm) was set into a partial scleral resection of the rat eye. A return
electrode (platinum–iridium wire; diameter, 0.2 mm) was placed into the vitreous body. The single biphasic current
pulse (outward current/cathodic-first) was applied between the stimulating electrode and the return electrode. The
potential evoked by electrical stimulation was recorded with a needle electrode [tungsten; resistance, 0.5 MΩ;diameter, approximately 5.0 μm (uninsulated part)] in the superior colliculus.

(a)

(b)

Fig. 2. Waveforms of electrical stimulation: (a) rectangular pulse and (b) sinusoidal pulse. Both are biphasic
symmetric pulses (outward current first; i.e., cathode-first). The current pulses of the two types of waveforms had
a duration of 0.5 ms and current amplitude ranging from 50 μA to 1 mA.

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was 50 times for both normal and RCS rats. The position of the largest EP was determined bymoving the recording electrode along the rostral-caudal or medio-lateral axis of the SC at aninterval of 100–250 µm. The position with the maximum EP for electrical stimulation was set
as the point corresponding to the retinal location that was electrically stimulated. Subsequent
recordings were completed at this position.
2.6

Data analysis

The average waveform after 50 signal averages of the EP was evaluated. For the analysis, weused the difference (P1−N1) between the first positive wave (P1) and the subsequent first negative
wave (N1) at approximately 5 and 10 ms after stimulation. EP amplitudes (P1–N1) were plottedagainst the charge magnitude [Fig. 3(a)]. The regression line was calculated in the range between
E1 [Eq. (1)] and E2 [Eq. (2)] [Fig. 3(a)]. E1 and E2 are the ranges in which the averaged coefficientof determination of the regression line is maximal in all individuals. MAX was defined as thelargest EP [Fig. 3(a)]. The threshold charge was calculated as the intersection of the X-axis and theregression line [Fig. 3(b)].
E1 = MAX × 0.6(1)E2 = MAX × 0.05

(2)

A paired t-test was used to assess the differences in the threshold charge between stimulus
waveform shapes. The significance level was set at p < 0.05. Of the recorded data, we used
amplitudes for which the coefficient of determination of the regression lines was greater than 0.9
for statistical analysis. R version 3.3.2(16) was used for the statistical analysis.

2000

1000

MAX

1600

800

1200

E1 = MAX×0.6

800

BetweenE1 and E2
E2 = MAX×0.05

400
0

0

200

400

600

(nC)
Electric charge [nC]
(a)

600
400
200
0

Threshold charge
0

100

200

(nC)
Electric charge [nC](b)Fig. 3. Calculation of threshold charge. (a) EP amplitudes were plotted against the electric charge magnitude. (b)Magnified view of the region between E1 and E2. The regression line was calculated in the range between E1 andE2. The threshold charge was calculated as the intersection of the X-axis and the regression line. The ranges of E1
and E2 were set as those where linearity was obtained for all individuals. MAX was defined as the largest EP.

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Sensors and Materials, Vol. 29, No. 12 (2017)

Histological analysis

After completion of the experiment, rats were euthanized with an overdose of sodium
pentobarbital. The eyes were enucleated immediately after euthanasia in four rats. Two normal
rats and two RCS rats were randomly selected for histological analysis. The extracted eyes were
fixed for 24 h with a solution of 1.5% glutaraldehyde and 3% formaldehyde in phosphate buffer.
Next, the eyes were fixed with a neutral buffered formalin solution for 5–7 d. After embedding
in resin, the eyes were prepared into slices with thicknesses of 4–5 µm. The sliced tissues were
stained with hematoxylin and eosin (HE). The layered structure of the outer retina of normal and
RCS rats was histologically observed under a microscope.

3.

Results

3.1

Waveform of electrical stimulation

The actual waveform of the rectangular pulse confirmed with the oscilloscope is shown in Fig. 4.
In the case of a rectangular wave, overshoot or undershoot, a phenomenon in which the waveform
exceeds the base line and becomes a steady value, may occur at the rising and falling portions of
the waveform, respectively. Under the stimulation condition of this study, neither overshoot nor
undershoot was observed.
3.2

Response waveform

While EPs were clearly obtained in all normal rats 30 to 100 ms after photic stimulation[Fig. 5(a)], EPs after photic stimulation were not observed in any of the RCS rats [Fig. 5(b)]. This
result is likely due to the complete degeneration of photoreceptor cells typically seen in RCS rats.
As we previously reported(17) and also observed in this study, a rectangular pulse of electricalcurrent (>100 µA) applied to the eye globe elicited EPs composed of an initial positive wave (P1)
and a subsequent first negative wave (N1) in both normal and RCS rats (representative example,
Fig. 6). Peak latencies of P1 and N1 are approximately 5 and 10 ms after stimulation, respectively.

Fig. 4. Actual waveform of the rectangular pulse simulated. It is 16 times the average waveform when stimulatedwith 1 mA. Under the stimulation condition of this study, neither overshoot nor undershoot was observed.

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Evoked potential amplitude (µV)

Evoked potential amplitude (µV)

Sensors and Materials, Vol. 29, No. 12 (2017)

(a)

(b)

Fig. 5. Example of response waveforms observed by photic stimulation in (a) normal rats (Long–Evans) and(b) RCS rats. The artifacts of photic stimulation, indicated by arrows, show the application of the light flash. The
artifact appearing upon irradiation with the light flash was as small as 20 μV and could not be clearly confirmed.
Peaks of EP were observed about 30–100 ms after stimulation in all normal rats. In contrast, no response to photic
stimulation was observed in any of the RCS rats. This observation indicates that the photoreceptor cells in RCS
rats were degraded.

N1–400 µV
10 ms +N2

1 mA
500 µAN2

1 mA
500 µA P1

P1

300 µA

300 µA

100 µA

100 µATime (ms)Time (ms)0–400 µV
10 ms +

N1

20

40

60

80

100

0

20

40

(a)

–
400 µV
10 ms +

1 mA

N1

1 mA
500 µA P1

300 µA

300 µA

100 µA

100 µATime (ms)Time (ms)
40

60

(c)

100

–
400 µV
10 ms +

N2

500 µA P1

20

80

(b)

N1
N2

0

60

80

100

0

20

40

60

80

100

(d)

Fig. 6. Example of the response waveforms observed after electrical stimulation of 1 mA, 500 μA, 300 μA, and100 μA. (a) Normal rat, rectangular pulse, (b) normal rat, sinusoidal pulse, (c) RCS rat, rectangular pulse, and(d) RCS rat, sinusoidal pulse. The artifacts of electrical stimulation, indicated by arrows, show the application of
the current pulse. Regardless of the stimulation waveform shape at a current amplitude of 100 μA or more, theEPs were composed of the first positive wave and the subsequent negative wave at approximately 5.0 and 10 ms
after stimulation, respectively, in all normal rats. For 1 mA electrical stimulation, regardless of the stimulation
waveform shape, the second negative peak, N2, was observed at approximately 10 to 25 ms in all rats. N2
disappeared as the stimulation current amplitude decreased. Gentle peaks observed after 20 ms are indicated bytriangles. The gentle peaks disappeared as the stimulation current amplitude decreased.

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As shown in Figs. 6(b) and 6(d), the sinusoidal pulse was also able to generate P1–N1 responses
in normal as well as RCS rats. Accordingly, we assumed that the response waveform obtained inthis study was not an artifact or noise but rather a response to the electrical stimulation. For 1 mAelectrical stimulation, regardless of the stimulation waveform shape, the second negative peak (N2)
was observed at approximately 10–25 ms in all normal and RCS rats (Fig. 6). As the stimulation
current amplitude decreased, N2 disappeared in both the normal and RCS rats, regardless of thestimulation waveform. For all normal rats, a stimulation of 100 µA or more resulted in a gentle
peak at approximately 20–90 ms, regardless of the stimulation waveform shape [Figs. 6(a) and6(b)]. However, except for stimulation with 1 mA, peaks at 20 ms after stimulation were notobserved in any of the RCS rats [Figs. 6(c) and 6(d)].
3.3

Threshold charge

The EP amplitudes (P1−N1) are shown in Fig. 7. Of the 20 RCS rats tested, 7 had a coefficientof determination of a partial regression line less than 0.9 and were excluded from the data analysis.
In both normal and RCS rats, the threshold charge in the sinusoidal pulse was significantly
lower than that of the rectangular pulse (normal rats: rectangular, 39.6 ± 10.2 nC; sinusoidal,
32.9 ± 8.7 nC; p < 0.01; RCS rats: rectangular, 27.0 ± 16.7 nC; sinusoidal, 24.1 ± 13.8 nC; p < 0.05)[mean ± standard deviation (SD), paired t-test]. The mean threshold charge of the sinusoidal pulse
was 17% lower than that of the rectangular pulse in normal rats. In RCS rats, the threshold charge
was 11% lower with the sinusoidal pulse than with the rectangular pulse.
3.4

Histological analysis

An example of tissue specimens from normal rats and RCS rats is shown in Fig. 8. Analysisof tissue specimens of RCS rats revealed that the layered structures of the outer retina werecompletely deteriorated [Fig. 8(b)]. This observation suggested that the photoreceptor cells of RCS
rats were sufficiently degenerated. In the two RCS rats for which the tissues were observed, the

80

80

60

60

40

40

20

20

0

rectangular(a)sinusoidal

0

rectangularsinusoidal(b)Fig. 7. Threshold charges in (a) normal rats (Long–Evans) (n = 13) and (b) RCS rats (n = 13). The black
horizontal bars (―) indicate the mean threshold charge. The threshold values for each animal are indicatedby squares (□) for rectangular stimulation and circles (○) for sinusoidal stimulation. Lines connecting thesymbols indicate that the data are from the same individual. Paired t-test (*p < 0.05; **p < 0.01) was used todetect significant differences. The threshold charge was significantly lower for the sinusoidal pulse than for therectangular pulse (p < 0.05).

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Sensors and Materials, Vol. 29, No. 12 (2017)

(a)

(b)

Fig. 8 (Color online) Representative tissue specimens of (a) normal 23-week-old rats (Long–Evans) and (b)34-week-old RCS rats. The black bars represent 50 µm. The inner segment/outer segment (IS/OS), outer nuclear
layer (ONL), INL, inner plexiform layer (IPL), and GCL are indicated. Panel (b) confirms that the outer retina i
absent in RCS rats.

layered structures of the outer retina could not be detected. However, the layered structure in the
inner retina [from the inner nuclear layer (INL) to the ganglion cell layer (GCL)] was observed[Fig. 8(b)]. Both the inner and outer retinal layers were observed in the histological analysis of thetwo normal rats [Fig. 8(a)].

4.

Discussion

We evaluated the differences between the threshold charges of rectangular and sinusoidal
pulses. Under the stimulation conditions of this study, with rectangular pulse stimulation,
overshoot and undershoot were not observed. Therefore, it is considered that the rectangularwave used in this study was stimulated with a waveform close to the ideal shape (Fig. 4). The
EP amplitude used for calculating the threshold charge was defined as the difference between P1and N1, the peaks obtained upon stimulation with a current greater than 100 µA, regardless of thestimulation waveform shape. Therefore, we focused on P1 and N1.
In both normal and RCS rats, the mean threshold charge of the sinusoidal pulse wassignificantly lower than that of the rectangular pulse. Weitz et al. reported that the thresholdcharge at which retinal ganglion cells fired was 22.8 ± 35.5% greater for a rectangular pulse thanfor a sinusoidal pulse.(13) In their in vitro study, they applied direct stimulation to the ganglion cellside of the retina. Although this methodology differed from ours, the results are similar. From
this observation, we conclude that the sinusoidal pulse is more effective than the rectangular pulse,
regardless of the implantation site of the stimulating electrode. Because a sinusoidal pulse with asmall charge magnitude can evoke phosphenes, even if the electrode area is reduced, the charge
density does not increase and can stimulate the retina without causing tissue injury. Sekirnjak
et al. reported that reducing the electrode area can limit the range of stimulated retinal ganglion
cells to a spatially confined region.(14) The localization of stimulation indicates that the excitationof the retina and the primary visual cortex are both localized. Thus, the localization of phosphenes
is suggested to be achieved by optimizing the stimulation waveform.

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Efforts to improve the resolution of retinal prostheses using finer electrodes results in adecrease in the charge injection capability (CIC). The CIC is the maximum injectable charge that
does not cause an irreversible electrochemical reaction.(18) The use of smaller electrodes raises theconcern that the CIC will be lower than that of a large electrode. By lowering the threshold charge
through the use of a sinusoidal waveform, electrical stimulation can be safely applied, even if using
smaller electrodes. The CIC for rectangular pulse stimulation is reported by Terasawa et al.,(18)but that of sinusoidal pulse stimulation is unknown. Confirmation that sinusoidal pulses do notcause an irreversible electrochemical reaction on the electrode surface will be needed in the future.
Conveniently, a sinusoidal pulse can be easily produced using electronic circuits.
This study is the first to show the effectiveness of a sinusoidal pulse in vivo using STS. Results
are promising for future clinical applications of this method. Both functional evaluations basedon photic stimulation and on histological analyses of tissue samples indicate photoreceptor
degeneration in all RCS rats [Figs. 5(b) and 8(b)]. The effectiveness of the sinusoidal pulse in RCS
rats suggests that this method would be efficacious for patients suffering from RP. To facilitate
the clinical use of the sinusoidal pulse, we will conduct further assessments of safety, including theevaluation of electrochemical reactions on the electrode surface upon stimulation with thresholdcharge sinusoidal pulses, and investigate the effect of chronic stimulation with sinusoidal pulses
and their influence on neural tissue.

5.

Conclusions

The threshold charge of the sinusoidal pulse is smaller than that of the rectangular pulse.
Because a sinusoidal pulse can evoke phosphenes with a small charge magnitude even if theelectrode area is reduced, the charge density does not increase; thus, the pulse can stimulate
the retina without causing tissue injury. The sinusoidal pulse allows us to reduce the electrodearea, and it is possible that phosphenes can be localized to a smaller area by limiting the rangeof stimulated retinal ganglion cells. Therefore, high resolution of retinal prostheses using thesinusoidal pulse can be expected. Our results suggest that the sinusoidal pulse is effective for use
in retinal prosthetic devices.

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