Download ARVO 2015 Annual Meeting Abstracts 144 Retinal prosthesis and

ARVO 2015 Annual Meeting Abstracts
144 Retinal prosthesis and electrophysiology
Sunday, May 03, 2015 1:30 PM–3:15 PM
Exhibit Hall Poster Session
Program #/Board # Range: 747–780/D0141–D0174
Organizing Section: Retina
Contributing Section(s): Physiology/Pharmacology, Retinal Cell
Biology, Visual Neuroscience
(C); Jorge E. Moreno Cuevas, NeuroSyntek Modeling and
Manufacturing (C); Sergey N. Cherenkevich, NeuroSyntek
Modeling and Manufacturing (C); Andrei A. Denisov, NeuroSyntek
Modeling and Manufacturing (F); Pavel M. Bulai, NeuroSyntek
Modeling and Manufacturing (F); Victor V. Boksha, NeuroSyntek
Modeling and Manufacturing (E); Christine Lopez-Yang, None;
Raquel Cuevas Diaz, None
Program Number: 747 Poster Board Number: D0141
Presentation Time: 1:30 PM–3:15 PM
On-chip stem cell preparation system for retinal disease
treatment
Charles A. Garcia1, Pavel G. Molchanov2, Martín M. Hernández
Torre3, Jorge E. Moreno Cuevas4, Sergey N. Cherenkevich2, Andrei A.
Denisov2, Pavel M. Bulai2, Victor V. Boksha6, Christine Lopez-Yang5,
Raquel Cuevas Diaz4. 1Ophthal-Herman Eye Ctr, Univ of Texas
Houston Med Sch, Houston, TX; 2Biophysics department, Belarusian
State University, Minsk, Belarus; 3TEC SALUD, Monterrey Institute
of Technology, Monterrey, Mexico; 4School of Medicine, Monterrey
Institute of Technology, Monterrey, Mexico; 5The Retinal Vascular
Center, Houston, TX; 6NeuroSyntek Modeling and Manufacturing,
Los Altos, CA.
Purpose: Stem cell therapy is an emerging field in ophthalmology. To
improve outcomes, our goal is to increase the specificity and quantity
of stem cells through sorting. Current FACS and MACS cell sorting
methodologies are costly and have limited specificity (91-95% purity
of the desired cell type) as well as a low yield. We have developed
a new cell sorting technique, which increases the specificity of cell
lineages and total number of cells.
Methods: The technique is system-on-chip designed for long-term
monitoring of cell cultures. It is a layer of electro-optical sensors,
designed for long-term measurements of electrical and optical
characteristics of cultured cells, as well as for cell elimination by
electroporation. The system does not require human intervention in
its operations. The array structure of the system allows individual
monitoring and stimulation of any cell. With the use of selective
dye labels, the system allows sorting of cells against specific cell
markers on the basis of fluorescent signals. The important result
of the electrical cell stimulation arises when the stimulating field
strength reaches a sufficiently high intensity. This evokes the
electroporation of the cellular membrane located on a microelectrode.
Electroporation of individual cells can be achieved by choosing
specific values of duration and frequency of stimulation of each
microelectrode. Thus, it becomes possible to electroporate selective
individual cells even in a heterogeneous culture.
Results: We have tested our system on different cell lines and stem
cell types. It has shown effective cell selection (more than 95%) by
applying dye labels and close to 100% selective elimination through
electroporation. Up to 60 million cells can be obtained from bone
marrow aspirate after 3-4 days of sorting with high homogeneity
(more than 95%) of cell lineages. We have shown accelerated cell
proliferation (up to 45%) under chronic electrical stimulation. Onchip cell sorting shows many advantages in comparison to FACS
and MACS: higher viability (less cell damage via reduction of shear
stress), single use disposables, and no contamination issues in an easy
to use, compact device.
Conclusions: We have developed an economical, efficient, higher
yielding apparatus for cell separation for planned clinical trials, such
as hESC or autologous CD34+ cells for diabetic retinopathy.
Commercial Relationships: Charles A. Garcia, NeuroSyntek
Modeling and Manufacturing (C); Pavel G. Molchanov,
NeuroSyntek Modeling and Manufacturing (F); Martín M.
Hernández Torre, NeuroSyntek Modeling and Manufacturing
Program Number: 748 Poster Board Number: D0142
Presentation Time: 1:30 PM–3:15 PM
Post-surgical findings in 10 rabbits implanted with the VLARS
(Very Large Array Retina Stimulator) device in two shapes over a
period of 12 weeks
Tibor K. Lohmann1, Anne C. Rieck1, Florian Waschkowski2, Wilfried
Mokwa2, Thomas Laube3, Claudia Brockmann3, Norbert Bornfeld3,
Claudia Etzkorn1, Gernot Roessler1, Peter Walter1. 1Department
of Ophtalmology, University Hospital Aachen, RWTH Aachen
University, Aachen, Germany; 2Institute for Materials in Electrical
Engineering I, RWTH Aachen University, Aachen, Germany;
3
Department of Ophtalmology, University Hospital Essen, Essen,
Germany.
Purpose: Over the last years noteworthy improvements in visual
prosthetics have been achieved but restoring a substantial visual field
is yet a task to be accomplished. Our research group created a large
stimulation array with a 12mm diameter covering 37.6° visual angle
and mounting 250 individual electrodes to address this problem. In
an animal trial study two different shapes of these arrays have been
implanted into 10 rabbits in order to observe the surgical outcome
and biocompatibility.
Methods: 10, 4 to 6 months old rabbits (4 albino, 6 pigmented)
were implanted with the VLARS-device through vitreous surgery.
Post-surgery examinations were performed 1 day, 1 respectively 2,
4, 6, 8 and 12 weeks after surgery and included clinical examination,
funduscopy, OCT (optical coherence tomography) and ultrasound
imaging. Finalization took place after the 12th post-surgical week.
The implanted eyes were enucleated and underwent histological
examination in order to observe damage or cellular immigration.
Results: During surgery 3 eyes experiences retinal detachment which
lead to the termination of the implantation in one animal. At least
2 eyes experienced noteworthy intra-vitreal bleeding which was
being staunched during surgery. Due to the corneal incision, damage
occurred and corneal blur rendered optical examination impossible
in most animals during the first weeks after surgery. After application
of steroids, imaging could be performed showing an overall
positive outcome in terms of long-term compatibility. No cellular
immigration, additional retinal detachments or other adverse events
were observed, the arrays stayed fixated at implantation site. A gap
between the stimulator array and the retinal surface enlarging towards
the periphery has been unmasked. Histologic examination showed
expected mild gliosis in the area of retinal fixation.
Conclusions: The long-term implantations showed no adverse effects
on behalf of the used materials. The surgical process, and especially
the trans-corneal Insertion caused damage on the cornea. This was
improved by using different techniques of corneal insertion in order
to minimize the incision’s size. The vitreous surgery itself and the
fixation of the array regularly healed off. To establish a closer contact
between the array and the retina additional ways of fixation have to
be introduced in the study.
Commercial Relationships: Tibor K. Lohmann, None; Anne
C. Rieck, None; Florian Waschkowski, None; Wilfried Mokwa,
None; Thomas Laube, None; Claudia Brockmann, None; Norbert
Bornfeld, None; Claudia Etzkorn, None; Gernot Roessler, None;
Peter Walter, None
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Support: Jackstädt Foundation “VLARS” grant
Program Number: 749 Poster Board Number: D0143
Presentation Time: 1:30 PM–3:15 PM
Fluctuations in projected percept locations in subjects with
retinal prostheses that use external cameras
Michael P. Barry1, Gislin Dagnelie2. 1Biomedical Engineering, Johns
Hopkins University, Baltimore, MD; 2Ophthalmology, Johns Hopkins
University, Baltimore, MD.
Purpose: To characterize the nature of how the projected locations of
percepts (PLPs) in subjects with retinal prostheses change over time.
Methods: Three end-stage RP patients implanted with the Argus®
II epiretinal prosthesis participated in this study. These prostheses
stimulate the retina based on a set 17° x 10° area selected within the
camera’s 66° x 49° field of view. The center of this processed area is
referred to as the camera position (CP). Participants touched a white
square on a black background on a touchscreen monitor. Camerascreen distance was set before every trial run. Typical targets had
sides spanning 5° of visual field. Locations of each square target
and subject response, together with approximate camera locations,
were used to calculate localization errors in degrees of visual field.
Average errors were calculated for each trial run. CPs were adjusted
to reduce errors when necessary. Trial runs with average errors of
less than 1 degree were used to identify CPs that accurately reflected
PLPs, relative to the camera. PLP estimates were confirmed by asking
subjects to localize physical objects. Estimated PLPs were tracked
over periods ranging 154-853 days. Significance of horizontal and
vertical differences in PLPs for individual subjects across test session
dates was evaluated using a bootstrap variation of ANOVA.
Results: Test session date, and therefore time, had a significant effect
on both horizontal and vertical components of PLPs for all three
subjects (p < 10-4). PLP component spread ranged from 6.2°-24°,
mean = 16°, standard deviation (SD) = 5.9°. Between-session rates of
change for PLP components ranged 0°-1.6°/day, mean = 0.21°/day,
SD = 0.36°/day. No measured PLPs displayed long-term stability.
Conclusions: PLPs displayed a lack of long-term stability in all
three subjects. Periods of short-term stability were broken by shifts
as dramatic as up to 1.6°/day. As prosthesis subjects with constant
corrective feedback display much slower rates of adaptation to
inaccurate CPs, and no adaptation without corrective feedback
(ARVO 2014, #1817), regular recalibrations of prosthesis CPs are
required to maintain subject hand-camera coordination.
Commercial Relationships: Michael P. Barry, Second Sight
Medical Products (F); Gislin Dagnelie, Second Sight Medical
Products (F)
Support: R01 EY021220, T32 EY07143
Clinical Trial: NCT00407602
Program Number: 750 Poster Board Number: D0144
Presentation Time: 1:30 PM–3:15 PM
A prototype suprachoroidal retinal prosthesis: device reliability
and patient safety report of a 2 year clinical study
Penelope J. Allen1, 2, Lauren N. Ayton1, 2, Jonathan Yeoh1, 2,
Robert Briggs2, David Nayagam3, 2, Richard Williams4, 5, Cynthia
Whitchurch6, Chi D. Luu1, 2, Robert Shepherd3, 2, Robyn H. Guymer1, 2.
1
Macular Research Unit, CERA, Melbourne, VIC, Australia; 2Bionic
Vision Australia, Melbourne, VIC, Australia; 3Bionics Insitute,
Melbourne, VIC, Australia; 4Department of Anatomical Pathology,
St.Vincent’s Hospital, Melbourne, VIC, Australia; 5Department of
Pathology, University of Melbourne, Melbourne, VIC, Australia; 6The
ithree Insitute, University of Technology, Sydney, NSW, Australia.
Purpose: To determine whether implantation and electrical
stimulation of a retinal prosthesis in the suprachoroidal space is
surgically safe and efficacious. This study reports on the two-year
stability and safety data of this novel device.
Methods: A retinal prosthesis was implanted in the suprachoroidal
space in three patients with bare light perception due to retinitis
pigmentosa (clinical trials.gov NCTO1603576). Stimulation was
made via a percutaneous connector for a period of two years. Clinical
assessments, retinal imaging and CT scans were performed regularly
to assess the ocular health and the stability of the implant. At the end
of the study, the external components were explanted in two patients,
and the entire device removed in the third. Specimens were collected
for microbiology and histopathology.
Results: The surgical implantation was uncomplicated in all three
patients. All three developed limited suprachoroidal haemorrhage
and in one case, vitreous haemorrhage, postoperatively, but this
cleared spontaneously in all cases. Stimulation enabled reliable
phosphenes to be generated for all three patients within safe charge
limits throughout the study. The devices remained stable over the
two years with no wire breakages or loss of electrode function. A
fibrous capsule developed around all three devices, but stimulation
remained within safe limits. During the trial no serious ocular adverse
events occurred. The only device-related serious adverse events
were infections around the percutaneous connector. Analysis of the
explanted devices revealed no significant presence of organisms.
Histology of scleral sections adjacent to the insertion wound revealed
homogeneous fibrous encapsulation, but no evidence of active
inflammatory response or micro-organisms in the eye tissue.
Conclusions: Implantation of a retinal prosthesis in the
suprachoroidal space was surgically safe, and the device remained
stable over a two-year period. Electrical stimulation resulted in
reliable phosphenes within safe charge limits.No serious ocular
complications developed in the three patients. Although some
fibrous encapsulation of the intraocular arrays occurred, effective
stimulation was able to continue until the conclusion of the study.
Post-explant analysis of the arrays, and surrounding tissue, confirmed
the encapsulation was fibrotic tissue and that there were no infective
organisms present.
Commercial Relationships: Penelope J. Allen, Bionic Vision
Australia (P); Lauren N. Ayton, None; Jonathan Yeoh, None;
Robert Briggs, None; David Nayagam, Bionic Vision Australia (P);
Richard Williams, None; Cynthia Whitchurch, None; Chi D. Luu,
None; Robert Shepherd, None; Robyn H. Guymer, None
Support: Bionic Vision Australia (ARC SRI on Bionic Vision
Science and Technology), CERA ( Victorian Government,NHMRC),
NICTA (DBCDE, Australian Govt and ARC), BI (Vic Govt
infrastructure funding)
Clinical Trial: NCTO1603576
Program Number: 751 Poster Board Number: D0145
Presentation Time: 1:30 PM–3:15 PM
Oculomotor behavior of blind patients seeing with subretinal
visual implant Alpha IMS
Eberhart Zrenner1, 2, Katarina Stingl2, Ziad M. Hafed1. 1Werner
Reichardt Centre for Integrative Neuroscience (CIN), Tuebingen,
Germany; 2Centre for Ophthalmic Research, University of Tuebingen,
Tuebingen, Germany.
Purpose: The CE-approved Retina Implant Alpha IMS senses light
through the eye’s optics and subsequently stimulates retinal bipolar
cells via ~1500 independent pixels. Because it is directly implanted
beneath the fovea, it can harness the benefit of eye movements in
vision. However, so far, oculomotor strategies of patients with light
sensitive subretinal implants have not been characterized.
Methods: Eye movements were tracked in two patients after
presentation of white geometric shapes (eg. squares, circles) on a
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
dark background non-invasively using a high-speed, high-resolution
video-based system. Patients reported seeing them by pressing a
button.
Results: 1. Once patients visually localized shapes, they fixated
well and exhibited classic oculomotor fixational strategies,
including generating microsaccades and drifts (Fig. 1). 2. Saccade/
microsaccade frequency varied during periods of visibility of a
stimulus such that these eye movements tended to be fewer right
before losing a percept compared to when first acquiring one 3. Gaze
location corresponded to the location of the stimulus, and stimulus
shape/size were reflected in saccade direction and size.
Conclusions: There is a clear relation between perception and ability
to fixate a target via a subretinal implant. The impact of saccades/
microsaccades on “refreshing” images can be strong at retinal level.
Our results pave the way for eye tracking in subretinal implant
patients, not only to understand their oculomotor behavior, but also to
design oculomotor training strategies that can improve their quality
of life.
Sample trial (A) Horizontal bars indicate periods in which the
patient reported seeing/not seeing the stimulus. Eye movements
were large (arrows) when the patient could not see the stimulus but
fixation became stable during a percept. (B) Magnified representation
of stable fixation during a percept. Classic fixational drifts and
microsaccades (example-arrows) occurred. (C) Eye position with
two visibility intervals separated by several seconds without. During
intervals, eye position showed repeatable behavior. (D) Eye position
trajectories for the two percept intervals in (C). In both intervals,
percept onset/offset occurred at specific eye positions, which
presumably brought the implant onto/away from the stimulus. Dashed
circle shows stimulus shape/size, and provides a reference for the
amount of drift needed before the stimulus was lost.
Commercial Relationships: Eberhart Zrenner, Retina Implant AG
(C), Retina Implant AG (F), Retina Implant AG (I), Retina Implant
AG (P), Retina Implant AG (S); Katarina Stingl, Retina Implant AG
(F); Ziad M. Hafed, None
Support: Retina Implant AG, DFG EXC 307 (CIN), Bernstein
Centre Tübingen TP A3
Clinical Trial: NCT01024803, NCT01497379
Program Number: 752 Poster Board Number: D0146
Presentation Time: 1:30 PM–3:15 PM
Long-term evaluations of a Liquid Crystal Polymer (LCP)-based
Retinal Prosthesis in vitro and in vivo
Joonsoo Jeong1, So Hyun Bae2, Kyou S. Min1, Jeong Hoan Park1,
Jong-Mo Seo1, 3, Hum Chung3, Sung J. Kim1. 1Electrical & Computer
Engineering, Seoul National University, Seoul, Korea (the Republic
of); 2Department of Ophthalmology, Kangnam Sacred Heart Hospital,
Seoul, Korea (the Republic of); 3Department of Ophthalmology,
Seoul National University College of Medicine, Seoul, Korea (the
Republic of).
Purpose: A miniaturized, light-weight and eye-conformable retinal
prosthesis was developed using monolithic fabrication of liquid
crystal polymer (LCP), and its in vitro and in vivo functionality were
verified (J.Jeong; TBME 2015, ARVO 2014). The 16-channel, allLCP device has an eye-conformable package of 14 mm in diameter
and 1.3 mm in the maximum thickness with 0.38g of total weight. In
this study, we present long-term testing results of the new LCP-based
retinal implant to evaluate its long-term reliability and safety in vitro
and in vivo.
Methods: The long-term reliability tests were conducted using
the electrode part of the implant to assess the durability of LCPmetal interface which is the weakest point against water ingression
compared to other leakage pathways. LCP-based retinal electrodes
were soaked in PBS solution at elevated temperature of 87. Voltage
transient was monitored under continuous stimulation (50 μA,
500μs, 30Hz) to detect water leakage. Chemical stability of Iridium
oxide was examined through voltage waveforms, impedance and
CSC measurements after long-term pulsing in saline at the room
temperature. The long-term in vivo safety was evaluated using OCT
imaging, visual and fundus observation after implantation of dummy
devices into rabbit eyes for 2 years.
Results: In the accelerated aging test, the LCP-based retinal
electrodes have reached 80 days in 87 saline as of this writing
with no significant changes in voltage waveforms under 24-hour
stimulation. The impedance spectrum and CSC values of IrOx have
remained unchanged from their initial values (1.7 kΩ at 1 kHz,
45.5mC/cm2) for 30 days of 30 Hz pulsing in saline. In the in vivo
examination after 2-years of implantation, the system package has
been well placed under the conjunctiva without causing inflammation
and protrusion. The electrode array in the supra-choroidal space did
not migrate and retinal structure was well preserved as confirmed by
fundus observation and OCT, respectively.
Conclusions: In the in vitro and in vivo long-term testing, the newly
developed LCP-based retinal implant showed promising results with
electrodes lasting 80+ days in 87 and implantation stability proven
for 2 years. The long-term tests using fully functional device in vitro
as well as in vivo are ongoing at this moment.
Commercial Relationships: Joonsoo Jeong, None; So Hyun Bae,
None; Kyou S. Min, None; Jeong Hoan Park, None; Jong-Mo Seo,
None; Hum Chung, None; Sung J. Kim, None
Support: NRF & MSIP of Korea: Public Welfare & Safety
research(2011-0020987), Pioneer Research Center (2009-0082961),
Global Ph.D Fellowship (2011-0007411)
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Program Number: 753 Poster Board Number: D0147
Presentation Time: 1:30 PM–3:15 PM
Post-Illumination Pupil Response in Argus II Prosthesis Users
Naheed W. Khan, Husam Alghanem, Thiran Jayasundera.
Ophthalmology, Univ of Michigan-Kellogg Eye Ctr, Ann Arbor, MI.
Purpose: To use chromatic pupillometry to assess function of
intrinsic photosensitive (melanopsin) retinal ganglion cells (ipRGCs)
in patients using the ArgusII retinal prosthesis and to associate the
sustained post-illumination pupil response (PIPR) with measures of
visual outcome.
Methods: Subjects were 3 Argus patients (56 y/o male, 65 y/o
female, 75 y/o female) fitted 3 to 6 months prior with the Argus II 60
electrode epiretinal implant (Second Sight Medical Products, Sylmar,
CA) in their left eye. Control subjects were advanced RP patients
that also met criteria for implantation, and 9 healthy normal subjects.
Monocular PIPR was measured after 10 minutes of dark adaptation
on both eyes using a Ganzfled system which was equipped with an
eye tracking camera/software and emitted 1 second flashes at 2.6 log
cd-s/m2 and 625 nm (red) or 470 nm (blue) wavelengths ( Roland
Consult, Germany). Constriction as a percent of baseline at 6 seconds
for red stimulus was subtracted from blue stimulus PIPR to yield an
estimate of melanopsin response (Park et al., 2011). Visual function
was quantified by having the subject localize a high contrast square
shaped target on a touch screen.
Results: Argus patients and RP subjects had bare light perception
acuity. Rod- and cone-mediated pupil response was significantly
diminished in the Argus patients and in the RP control subjects. The
ipRGC PIPR for the Argus patients was of comparable amplitude
to the normal control and RP subjects: AR1: 70% OS and 72% OD;
AR2: 77.1% OD and 69.9% OS; AR3: 60.1% OD, 52.5% OS. Mean
percent PIPR was 71.5% ± 6.7% SD for RP subjects, and 70.4%
± 7.96% SD for normal controls. Difference in PIPR amplitude
between the implanted and non-implanted eye was minimal for the
Argus patients. For the square localization visual function test, 40
trials were presented in two subsequent sessions, once with the device
on and once with the device off. Number of correct responses were AR1: 15%, AR2: 30%, and AR3: 20% with the device on, and AR1:
12.5%, AR2: 17.5%, with the device off. AR3 did not take the test in
the device off condition.
Conclusions: The ipRGC pupillary response in Argus patients and
RP control subjects is comparable to normal mean indicating normal
ipRGC function. There was no association between PIPR amplitude
and visual function tests at least at 6 months after implantation.
Park et al., Invest Ophthalmol Vis Sci. 2011, 52: 6624-6635.
Commercial Relationships: Naheed W. Khan, None; Husam
Alghanem, None; Thiran Jayasundera, None
Program Number: 754 Poster Board Number: D0148
Presentation Time: 1:30 PM–3:15 PM
Five-year data from the Argus II Retinal Prosthesis System
Clinical Tria
Robert J. Greenberg1, Mark S. Humayun2, Lyndon da Cruz3, 4,
Gislin Dagnelie5, Paulo E. Stanga6, 7, Allen C. Ho8, David G. Birch9,
Jacque L. Duncan10, José Sahel11. 1Second Sight Medical Products,
Inc, Sylmar, CA; 2University of Southern California, Los Angeles,
CA; 3Moorfields Eye Hospital, London, United Kingdom; 4NIHR
Biomedical Research Centre for Ophthalmology, London, United
Kingdom; 5Lions Vision Research and Rehab Center, Johns Hopkins
University, Baltimore, MD; 6Manchester Royal Eye Hospital,
Manchester, United Kingdom; 7Manchester Vision Regeneration Lab
at NIHR/Wellcome Trust Manchester, Manchester, United Kingdom;
8
Wills Eye Hospital, Philadelphia, CA; 9Retina Foundation of the
Southwest, Dallas, TX; 10University of California San Francisco, San
Francisco, CA; 11Centre Hospitalier National d’Ophtalmologie des
Quinze-Vingts, Paris, France.
Purpose: To present five-year results from the Argus II Retinal
Prosthesis Study (clinicaltrials.gov NCT00407602) and update on the
commercial implant program.
Methods: All subjects implanted with a Second Sight Argus II
implant were blind from retinitis pigmentosa or similar disorders.
In the clinical trial, visual function was evaluated by visual function
tests such as Square Localization, Direction of Motion, and Grating
Visual Acuity. Assessments of functional vision included controlled
Orientation and Mobility (O&M) tasks, and the Functional LowVision Observer Rated Assessment (FLORA).
Results: As of October 15, 2014, 30 subjects have been implanted
at 10 centers in the clinical trial. Subjects (excluding three who have
been explanted) have been implanted an average of 6.2 ± 0.9 years
(range of 5.2 – 7.4). The Argus II remains implanted and functioning
in 24 subjects. The safety profile remains acceptable. Performance
has remained better with the System ON than OFF on all visual tests,
with these results sustained out beyond 5 years of chronic use.
As of October 15, 2014, there have been 54 additional implants of the
Argus II commercially in Europe, the U.S., Canada, and the Middle
East.
Conclusions: With 176 cumulative subject-years of clinical trial
follow-up on 30 clinical trial subjects, this is the largest study of a
visual prosthesis to date. The results confirm previous reports on
the ability of the Argus II prosthesis to provide visual function and
functional vision over several years of chronic device use. Current
research efforts are directed toward a feasibility study for age-related
macular degeneration, and the development of a prosthesis for the
primary visual cortex.
Commercial Relationships: Robert J. Greenberg, Second Sight
Medical Products, Inc. (E), Second Sight Medical Products, Inc.
(I), Second Sight Medical Products, Inc. (P); Mark S. Humayun,
Second Sight Medical Products, Inc. (C), Second Sight Medical
Products, Inc. (I); Lyndon da Cruz, None; Gislin Dagnelie, None;
Paulo E. Stanga, None; Allen C. Ho, None; David G. Birch, None;
Jacque L. Duncan, None; José Sahel, Pixium Vision (I)
Clinical Trial: NCT00407602
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Program Number: 755 Poster Board Number: D0149
Presentation Time: 1:30 PM–3:15 PM
Enhancing object contrast using augmented depth improves
mobility in patients implanted with a retinal prosthesis
Nick M. Barnes1, 2, Adele F. Scott1, Ashley Stacey1, Chris McCarthy1,
2
, David Feng1, 2, Matthew A. Petoe5, Lauren N. Ayton4, Rebecca
Dengate1, Robyn H. Guymer4, Janine Walker1, 3. 1Canberra Vision
Research Group, NICTA, Canberra, ACT, Australia; 2College of
Engineering and Computer Science, Australian National University,
Canberra, ACT, Australia; 3National Institute for Mental Health
Research, Australian National University, Canberra, ACT, Australia;
4
Centre for Eye Research Australia, Melbourne, VIC, Australia; 5The
Bionics Institute of Australia, Melbourne, VIC, Australia.
Purpose: Prosthetic vision shows promise for improving
performance in orientation and mobility tasks. To date, prosthetic
vision research has occurred mainly in high-contrast (e.g., black/
white) environments with limited investigation of performance in
environments with low contrast. In retinal implants, vision processing
is critical for scene understanding including detecting objects of low
contrast with their environment, and ensuring their visibility. The
ability to detect objects that are poorly contrasted is impaired with
the state-of-the-art vision processing, i.e., Intensity-based visual
representations. We evaluated the effectiveness of an Augmented
Depth-based vision processing algorithm (ADVP) compared to
Intensity-based vision processing (IVP) and System Off (SO) for
avoiding low-contrast trip hazards in retinal prosthetic vision.
Methods: Two participants with profound vision loss (bare light
perception) due to retinitis pigmentosa who were implanted with
a 24-channel retinal prosthesis (400 or 600 μm diameter) into the
suprachoroidal space.
Participants traversed a straight corridor (2.2 x 7.5 meters; dark floor,
white walls) with dark ground-based obstacles that varied in number,
size and placement. The presentation order was randomized for
Visual Representation and the obstacle characteristics. Participants
1 and 2 completed 60 and 25 traversals,respectively, over a two-day
period. The primary outcome measure was the number of contacts
with the objects and walls per traversal.
Results: ADVP (P1 n=21, mean=.714±.784; P2 n=12,
mean=1.33±1.44) was associated with significantly fewer
contacts than IVP (P1 n=22, mean=1.18±.907, p=.025; P2 n=7,
mean=3.14±1.77, p=.025) and SO (P1 n=17, mean=1.76±1.20,
p=.002; P2 n=6, mean=6.17±3.55, p=.001) for both participants. No
significant difference was evident between IVP and SO in the number
of collisions for either P1 (p=.237) or P2 (p=.067).
Conclusions: Vision processing techniques that provide scene
understanding through enhanced depth perception can improve the
performance of a retinal prosthesis for detecting and avoiding lowcontrast trip hazards compared to the standard Intensity-based visual
representation and System Off. These findings highlight the need
for robust vision processing methods in retinal prostheses especially
given the display limitations of current devices.
Commercial Relationships: Nick M. Barnes, NICTA (P); Adele
F. Scott, None; Ashley Stacey, None; Chris McCarthy, None;
David Feng, None; Matthew A. Petoe, None; Lauren N. Ayton,
None; Rebecca Dengate, None; Robyn H. Guymer, None; Janine
Walker, None
Support: Bionic Vision Australia (Australian Research
Council Special Research Initiative on Bionic Vision Science
and Technology), CERA (Victorian Government, National
Health & Medical Research Council), NICTA (Department of
Communications, Australian Government, and Australian Research
Council), BI (Victorian Government).
Clinical Trial: NCT01603576
Program Number: 756 Poster Board Number: D0150
Presentation Time: 1:30 PM–3:15 PM
Interaction between normal and prosthetic vision in a model of
local retinal degeneration
Henri Lorach1, 4, Yossi Mandel2, Georges A. Goetz3, phililp huie4,
Roopa Dalal4, Keith Mathieson5, Xin Lei3, Theodore Kamins3,
James Harris3, Daniel V. Palanker4, 1. 1Hensen Experimental Physics
Lab, Stanford University, Stanford, CA; 2The Mina & Everard
Goodman Faculty of Life Sciences, Bar Ilan University, Bar Ilan,
Israel; 3Electrical Engineering, Stanford University, Stanford, CA;
4
Ophtalmology, Stanford University, Stanford, CA; 5Institute of
Photonics, University of Strathclyde, Glasgow, United Kingdom.
Purpose: To create a non-genetic model of local retinal degeneration
in rats and assess the interactions of normal and prosthetic vision in
such model.
Methods: Local retinal degeneration in Long Evans rats was induced
by chronic separation of the retina from the pigment epithelium
(RPE) using sub-retinal implant of 1mm in width and 30mm in
thickness. Plastic disks were used for histological analysis, and
photovoltaic arrays of the same size have been utilized to assess
the interactions between normal and prosthetic vision. Each pixel
of 70mm or 140mm in these arrays is composed of two or three
photodiodes in series, which convert the near infrared (NIR) light into
electrical pulses to stimulate the nearby retinal neurons. Prosthetic
and visually evoked cortical activity was measured via transcranial
screw electrodes above the visual cortex. Interaction of prosthetic
and normal vision was assessed using a multifocal protocol with
simultaneous activation of the implant using NIR radiation (915nm)
and normal retina with visible light (532nm).
Results: Photoreceptors above the subretinal implant degenerated
over time, with 80% of the outer nuclear layer disappearing within
a month, and the rest by 3 months. Cells in the inner nuclear layer
and ganglion cell layer were preserved during the 1 year follow-up,
although there were signs of rewiring and decrease in the size of the
bipolar cell terminals, labeled with PKC, in the implanted area.
Both prosthetic and normal visual stimulation produced cortical
responses, which interact in a quasi-linear fashion. Retinal adaptation
to bright ambient had no significant effect on prosthetic responses as
opposed to the effect on visible light responses.
Conclusions: A subretinal implant induces highly reproducible local
degeneration of the photoreceptors above it, with preservation of the
inner retinal neurons but signs of synaptic plasticity. This non-genetic
model of local loss of photoreceptors might be convenient for basic
studies of the retinal degeneration and for development of therapeutic
strategies in a wide variety of species with vascular retina. It allows
investigating the interactions between the artificial sight (prosthetic,
optogenetic or optopharmacological) and normal vision, which are
important for patients preserving significant areas of normal retina,
such as in Age Related Macular Degeneration.
Commercial Relationships: Henri Lorach, Pixium Vision (F);
Yossi Mandel, None; Georges A. Goetz, None; phililp huie, None;
Roopa Dalal, None; Keith Mathieson, None; Xin Lei, None;
Theodore Kamins, Pixium Vision (C); James Harris, None; Daniel
V. Palanker, Pixium Vision (C), Pixium Vision (P)
Support: NIH: grant R01-NEI-018608, Air Force: grant FA9550-04,
NIH: award UL1 RR025744, Pixium Vision and Fondation Voir et
Entendre
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Program Number: 757 Poster Board Number: D0151
Presentation Time: 1:30 PM–3:15 PM
Comparison of the electrical stimulation performance of PEDOTCNT and iridium oxide electrodes
Guenther Zeck1, Ramona Samba2, Thoralf Herrmann1. 1Neurochip
Research, NMI at the University of Tubingen, Reutlingen, Germany;
2
BioMEMS, NMI at the University Tübingen, Reutlingen, Germany.
Purpose: Stimulating microelectrodes must be able to stimulate
retinal neurons using low voltage to avoid electrochemical surface
reactions and using low charge to avoid tissue damage. Here
we address these two challenges by comparing two different
microelectrode materials – the conductive polymer composite
comprising poly-3,4-ethylenedioxythiophene and carbon nanotubes
(PEDOT-CNT) and iridium oxide (IrOx) – at activating spikes in
retinal ganglion cells through stimulation of retinal interneurons.
Stimulation efficacy of the microelectrodes was analyzed by
comparing voltage, current and transferred charge at stimulation
threshold.
Methods: Ex vivo retinas from adult, female Sprague-Dawley
rats were interfaced ganglion-cell side down on microelectrode
arrays comprising either iridium oxide or PEDOT-CNT coated gold
electrodes. Cathodal constant-voltage pulses (duration: 0.1 – 1ms)
were applied to a ring-like stimulation electrode configuration. The
stimulus-induced ganglion cell spiking was recorded by an additional
electrode located in the center. Threshold voltage was determined as
the pulse amplitude required to evoke network-mediated ganglion
cell spiking in a defined post stimulus time window (10 – 20
milliseconds) in 50% of identical stimulus repetitions. For each of the
two electrode materials nine experiments were compared with respect
to threshold voltage, transferred charge at threshold, maximum
current and the residual current at the end of the pulse.
Results: The two materials exhibit a similar charge injection capacity
of 11 mC/cm2 as inferred from cyclic voltammetry. However, the
threshold voltages for stimulus durations of 0.5 ms and 1 ms were
significantly lower using PEDOT-CNT coated electrodes compared
to IrOx electrodes (p<0.05, n= 9 experiments for each condition).
Threshold voltages for shorter stimulus durations (0.1 ms and 0.2 ms
respectively) did not different significantly for the two materials. A
preliminary evaluation (n=5) of the maximal charge injected during
the pulse (0.5 ms and 1 ms) suggests a smaller value for PEDOTCNT electrodes as compared to IrOx.
Conclusions: In retinal implants, PEDOT-CNT coated electrodes
may allow for smaller electrodes, stimulation in a safe voltage regime
and lower energy consumption. The presented framework can be
easily extended to estimate stimulation efficacy of different electrode
materials.
Commercial Relationships: Guenther Zeck, None; Ramona
Samba, None; Thoralf Herrmann, None
Support: BMBF Grant FKZ 1312038
Program Number: 758 Poster Board Number: D0152
Presentation Time: 1:30 PM–3:15 PM
Long Term Recording of Charge Injection Capacities of
Suprachoroidally implanted Porous Platinum Electrodes
Yasuo Terasawa1, 2, Hiroyuki Tashiro3, Yukari Nakano1, Koji Osawa1,
Motoki Ozawa1, Toshihiko Noda2, Takashi Tokuda2, Jun Ohta2,
Takashi Fujikado4. 1Vision Institute, NIDEK Co Ltd, Gamagori,
Japan; 2Graduate School of Materials Science, Nara Institute
of Science & Technology, Ikoma, Japan; 3Division of Medical
Technology, Department of Health Sciences, Faculty of Medical
Sciences, Kyushu University, Fukuoka, Japan; 4Applied Visual
Science, Osaka University Graduate School of Medicine, Suita,
Japan.
Purpose: We have been developing a retinal prosthesis based on
Suprachoroidal-Transretinal Stimulation (STS). We previously
reported the stability of charge injection capacities (CICs) of
electrodes developed for STS in vivo during one month electrical
stimulation [Terasawa et al., ARVO E-abstracts 1803, 2014], but little
is known about long-term behavior of in vivo CICs. The purpose of
this study is to investigate the long-term trend of CICs of electrodes
implanted suprachoroidally.
Methods: An electrode array with two stimulating electrodes was
developed for this study. The diameter and height of an electrode
were 0.5mm and 0.3mm respectively. The in vivo experimental
details were described elsewhere [Terasawa, et al, proceedings of
IEEE EMBC, pp. 3567-3570, 2013]. In brief, the electrode array
was inserted into a scleral pocket of a rabbit eye and sutured onto
the sclera. Charge-balanced biphasic pulses were applied to one of
two electrodes on the array for eight hour per day for six months.
The CICs were recorded every four weeks during six-month
chronic stimulation period. All in vivo experiments were conducted
in accordance with the Association for Research in Vision and
Ophthalmology statement for the use of animals in ophthalmic and
vision research, and institutional guidelines for the care and use of
laboratory animals.
Results: In vivo CICs of active (pulses were applied) and inactive
(pulses were NOT applied) electrodes averaged during stimulation
period were 108μC/cm2 and 89μC/cm2 respectively. No apparent
trend of increase or decrease in CICs was found in six-month chronic
stimulation period. The CICs of active electrodes tended to be
greater than those of inactive ones. This difference was statistically
significant at second month (p=0.02) and fifth month (p=0.003) of
chronic stimulation.
Conclusions: CICs of porous platinum electrodes implanted in
suprachoroidal space were generally stable for six months. Chronic
electrical stimulation did not affect the stability of CICs. The
difference of CICs between active and inactive electrodes suggested
that electrochemical environment of electrodes was slightly modified
by chronic electrical stimulation.
Commercial Relationships: Yasuo Terasawa, NIDEK Co.,Ltd. (E);
Hiroyuki Tashiro, NIDEK Co.,Ltd. (F); Yukari Nakano, NIDEK
Co.,Ltd. (E); Koji Osawa, NIDEK Co.,Ltd. (E); Motoki Ozawa,
NIDEK Co.,Ltd. (E); Toshihiko Noda, None; Takashi Tokuda,
None; Jun Ohta, None; Takashi Fujikado, None
Program Number: 759 Poster Board Number: D0153
Presentation Time: 1:30 PM–3:15 PM
Pharmacological effects on excitability and threshold sensitivity
of mouse retinal ganglion cells
Feng Pan, Stewart A. Bloomfield. SUNY College of Optometry, New
York, NY.
Purpose: Dark adapted mouse retinal ganglion cells (RGCs) can be
distinguished based on their extensive range of thresholds covering
3 log units. We previously showed that blockade of GABA circuits
shifted the thresholds of RGCs suggesting that inhibition controls
their sensitivity. Here we compared the effects of GABAergic,
glycinergic, and dopaminergic drugs on the threshold sensitivity and
excitability of RGCs.
Methods: We recorded the spike activity of mouse RGCs with a
MEA. The intensity-response (I-R) functions were computed under
control and drug conditions. The threshold sensitivity of single cells
was computed as 5% of the maximum response spike frequency.
Overall excitability was calculated from the average spike frequency
to threshold, half-maximal, and maximal responses to light.
Results: Application of the GABA receptor blocker PTX (100
μM) produced an increased threshold sensitivity of most RGCs of
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
between 1-3 log units (n=33). Measurements of excitability showed
an average 2.7 ± 0.1 fold increase in spiking. However, while
high sensitivity (HS) cells also showed a 2.7 ± 0.2 fold increase in
spike frequency following PTX application, they did not show an
increase in threshold sensitivity (0.03 ± 0.03 log unit change, n=10).
Application of the glycine blocker strychnine produced a very
small increase in RGC threshold sensitivity (0.07 ± 0.07 log units,
n=42). However, these cells showed a large increase in excitability
evidenced by a 3.6 ± 1.0 fold increase in light-evoked spiking with
strychnine. Application of the D1 receptor blocker SCH-23390
(10 μM) produced a 0.66 ± 0.37 log unit (n=51) reduction in the
threshold sensitivity, whereas application of the D2 receptor blocker
eticlopride (25 μM) decreased the threshold sensitivity of RGCs by
0.30 ± 0.33 (n=97) log units. However, neither DI nor D2 receptor
blockade produced a change in cell excitability (1.0 ± 0.1 fold
change).
Conclusions: Our results indicate that GABAergic inhibition has
the most profound effects on threshold sensitivities of mouse RGCs.
Dopaminergic pathways also control RGC threshold sensitivity,
but to a smaller degree. Glycinergic circuits clearly affected overall
RGC excitability, but had little effect on threshold sensitivity. The
disassociation of the changes in threshold sensitivity and excitability
of single RGCs suggests that these properties arise from and are
controlled by different mechanisms.
Commercial Relationships: Feng Pan, None; Stewart A.
Bloomfield, None
Support: NIH Grant EY007360
Program Number: 760 Poster Board Number: D0154
Presentation Time: 1:30 PM–3:15 PM
Simultaneous dynamic retinal vessel analysis and pulsed anodal
transcranial electrical stimulation at the eye
Stefanie Freitag, Alexander Hunold, Matthias Klemm, Jens Haueisen.
Institute for Biomedical Engineering and Informatics, Technische
Universität Ilmenau, Ilmenau, Germany.
Purpose: Variations in neuronal activity cause changes in blood
flow, an effect that is part of the neurovascular coupling (NVC).
In neurosciences transcranial electrical stimulation (TES) methods
are used to provoke excitation or inhibition of neuronal activity in
the human cortex. We propose to adapt these techniques to analyze
the mechanisms of NVC in the retina using dynamic retinal vessel
analysis. This study tested the hypothesis that pulsed anodal TES
at the eye evokes changes in the dynamic retinal vessel response to
flicker.
Methods: Retinal vessel reactions were observed in 13 healthy
volunteers (23.8±1.6 years) using the Dynamic Vessel Analyzer
(DVA) in two cases: (a) flicker light stimulation; (b) flicker light
stimulation and simultaneous TES. To apply TES we developed a
ring-shaped rubber electrode (ca. 37cm2) placed around one eye as
the anode and a square rubber electrode (100cm2) at the occiput as
the cathode. We applied anodal rectangular current pulses (frequency:
10Hz; current intensity: 800mA). The DVA measurements consisted
of 60s baseline and two periods of 60s stimulation (application of
flicker light or simultaneous flicker light and TES) followed by
120s observation. The retinal vessel responses were calculated by
the DVA as the mean of the two measurement cycles and expressed
in the stimulation induced dilation of the vessels compared to their
baseline diameters. The maximum dilation of one arterial and venous
vessel segment was measured in each subject under both stimulation
conditions. Wilcoxon rank-sum test was used to compare the mean
values of retinal vessel dilation for flicker light stimulation and
simultaneous flicker light stimulation and TES.
Results: At flicker light stimulation retinal vessels provided
physiological reactions with a maximum arterial dilation of 3.9±1.6%
and a maximum venous dilation of 6.0±2.1%. For simultaneous
flicker light stimulation and TES maximum arterial dilation was
significantly increased (5.5±1.7%; p=0.018), maximum venous
dilation showed no significant change (6.6±2.1%; p=0.329).
Conclusions: The results confirm our hypothesis that pulsed anodal
TES affects retinal vessel reactions to flicker light, especially shown
in arterial reactions. Thus, the NVC in the retina can be modulated
by electrical stimulation and observed using dynamic retinal vessel
analysis.
Commercial Relationships: Stefanie Freitag, None; Alexander
Hunold, None; Matthias Klemm, None; Jens Haueisen, None
Support: German Federal Ministry of Education and Research
(Grant 03IPT605A)
Program Number: 761 Poster Board Number: D0155
Presentation Time: 1:30 PM–3:15 PM
The Animal Model Pattern-Reversal EEP Study of A ContactLens-Shaped, Flexible Retinal Prosthesis
Long-Sheng Fan1, Chang-Hao Yang2, Ta-Ching Chen2, Frank Yang1,
Eunice Liu1, Ya-TIng Cheng1, CC Teng1, Chung-May Yang2. 1NEMS,
National Tsing Hua University, Hsinchu, Taiwan; 2Ophthalmology,
National Taiwan University, Taipei, Taiwan.
Purpose: We previously reported a high-density flexible retinal
prosthesis chip using a 180 nm mixed-signal CMOS Image Sensor
technology with pixel array sensing image and generating bi-phasic
electrical stimulations to enable the possibility of high visual acuity
and cover a large field of view. The image-sensing retinal prosthesis
is made into a contact lens shape conforming to the surface of a 25
mm eyeball for a better stimulation resolution and a lower stimulation
threshold. The current study evaluates the efficacy of such contactlens-shaped retinal prosthesis through in vivo experiments of patternreversal electrical evoked potential (pEEP) in the visual cortex using
a rabbit animal model.
Methods: Pattern-reversal EEP experiments w. animal model are
used to assess the potential visual acuity of the implanted highdensity retinal prosthesis in the subretinal space. We surgically
implanted stainless steel electrodes (1 mm OD) contacting the dura
of the visual cortex of a rabbit model 2~3 weeks before the retinal
prosthesis is implant in the subretinal space of the model and measure
the electrically evoked potential. The electrical stimulation through
the implanted microelectrode array (arranged in hexagonal array
30um in pitch) is grouped as stripe patterns in the perpendicular
direction to the rabbit high-acuity horizontal stripe. The stripes are
formed by selectively activating 2,500 electrodes with a pulse rate of
20 Hz to achieve the flicker fusion and the stripe pattern is reversed
at 2Hz. The animal model is placed in a dark room and the patternreversal EEP measurements are repeated 100 times and recorded for
each stripe width ranging from 750um to 30um.
Results: Recorded EEP data show that flicker fusion is formed with a
pulse rate of 20 Hz, and the N1, P1, N2 peak signals can be measured
for the stripe width between 750um to 30um with a signal-to-noise
ratio up to 14.5dB. With a stripe width of 60um, the averaged EEP
signal measured has an SNR of 8.7dB, and the average EEP signal
amplitude falls within the background signal at a stripe width of
30um.
Conclusions: Pattern-reversal EEP experiments w. a rabbit animal
model are used to assess the potential visual acuity of the implanted
high-density retinal prosthesis in the subretinal space and the initial in
vivo experiments show encouraging results toward achieving a visual
acuity between 30um to 60um in the animal model.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Commercial Relationships: Long-Sheng Fan, HMTC (I), IMTC
(I), NTHU (P); Chang-Hao Yang, IMTC (I); Ta-Ching Chen, None;
Frank Yang, None; Eunice Liu, None; Ya-TIng Cheng, None; CC
Teng, None; Chung-May Yang, None
Support: NTHU102A0367JA
Program Number: 762 Poster Board Number: D0156
Presentation Time: 1:30 PM–3:15 PM
RELATIONSHIP BETWEEN GENOTYPE
AND ELECTROPHISIOLOGY ASSESSED BY
ELECTRORETINOGRAM AND VISUAL EVOKED
POTENTIALS IN 44 YOUNG PEOPLE AFFECTED BY
JOUBERT SYNDROME
Giulio Ruberto1, Sabrina Signorini2, Enza M. Valente3, 4, Mauro
Antonini2, Federica Ferro2, Carmine Tinelli5, Paolo E. Bianchi1,
Umberto Balottin2, Chiara Bertone1. 1Ophthalmic Clinic, IRCCS
Policlinico San Matteo, Pavia, Italy; 2Department of Child Neurology
and Psychiatry, IRCCS C. Mondino, Pavia, Italy; 3genetic, Salerno
University, Salerno, Italy; 4genetic, Css-Mendel, Roma, Italy;
5
Biometric service, IRCCS San Matteo Hospital, Pavia, Italy.
Purpose: Joubert syndrome (JS) is a rare autosomal recessive
congenital malformation of the brainstem and cerebellar vermis.
It can be associated with visual system anomalies and oculomotor
system defects. Congenital anomalies, implying also retinal
dystrophy in a percentage, related with this diseases, are increasingly
found in the last years. The aim of the present study is to correlate the
genetic findings of the JS with the electrophysiology results.
Methods: We show the results of a pluri-annual follow-up in
a large cohort of children affected by JS. 44 infants, mean age
8,52±5,06 years, were assessed for genetic mutations. All the
children underwent a complete ophthalmologic and neuropsychiatric
assessment. In 37 subjects electrophysiologic tests were performed
via electroretinogram( ERG) and visual evoked potentials (VEP)
done at five spatial frequencies ( from 300 to 15 minutes of arc)
registered in awake conditions. Eight infants had electroretinogram
achieved under anaesthesia. The results of latencies and amplitudes in
ERG and VEP as well were matched with the genetic outcomes.
Results: Mutations were found in 29 on 44 subjects.
Mutation in CEP290 was found in 9 children, mutations in
INPP5,TMEM216,RPGRIP1L, AHI1, C5orf42, KIF7, TCTN1,
NPHP1(EX2), in 4,4,3, 2,2,1,1,1,1,1 children respectively. Fundus
signs of retinal dystrophy were established in 19 subjects. ERG
amplitudes were lower in both “a” and “b” wave amplitudes in JS
with mutation respect the JS without . In the VEP, a significant “p”
( 0.002) was seen in the 120’ spatial frequency amplitude. The 15’
spatial frequency was not perceived in the affected subjects with
mutations. The ERG done under anaesthesia showed significant “p”
values in all the amplitudes matched with a normal children sample.
Conclusions: Genetic and electrophysiologic follow-up in JS may
aid to separate children affected or not by retinal dystrophy. The
electrophysiology alone can identify, in the early stages of the
disease, if a photoreceptors alteration is present. This is an obvious
chance about diagnosis and prognosis in these patients.
Commercial Relationships: Giulio Ruberto, None; Sabrina
Signorini, None; Enza M. Valente, None; Mauro Antonini, None;
Federica Ferro, None; Carmine Tinelli, None; Paolo E. Bianchi,
None; Umberto Balottin, None; Chiara Bertone, None
Program Number: 763 Poster Board Number: D0157
Presentation Time: 1:30 PM–3:15 PM
Electrical stimulation alters light responses in mouse retinal
ganglion cells.
Archana Jalligampala1, 2, Daniel L. Rathbun1, Eberhart Zrenner1.
1
Institute for Ophthalmic Research & Center for Integrative
Neuroscience, University of Tuebingen, Tuebingen, Germany;
2
Graduate Training Center of Neuroscience, University of Tuebingen,
Tuebingen, Germany.
Purpose: A goal of visual prosthetics is selective activation of the
parallel information channels that are established in the retina. Here,
we demonstrate that visual responses of retinal ganglion cells (RGCs)
can be altered by electrical stimulation, suggesting stimulationinduced changes affect visual encoding of retinal prosthetic devices.
Methods: RGC spiking responses were recorded in vitro from adult
(P28-P35) wt (C57BL/6) and degenerating (rd10) mouse retinas, with
a multi-electrode array. Visual stimuli were interleaved within an
electrical stimulation experiment spanning ~70 minutes of recording
time. Each of the 6 visual stimulation blocks consisted of a full-field
white flash stimulus (2 s on, 2 s off) cycled 20 times without pause.
Epiretinal electrical stimuli consisted of a series of 114 different
square wave monophasic voltage pulses of varying voltage and
duration (+ 2.5 V to -2.5 V, 0.06 to 5 ms, 5 repetitions each, interpulse
interval ≥5 s). We defined ‘nearby responsive cells’ as cells with a
significant response to at least one pulse and recorded on electrodes
at a distance of 200 or 283 mm from the stimulating electrode.
‘Distant non-responsive cells’ did not have significant responses
and were recorded on electrodes > 300 mm away. Visual response
characterization was similar to Carcieri et al. (J Neurophysiol. 2003;
90:1704–13).
Results: For wt ‘nearby responsive cells’ (n=108) both on and off
visual response amplitudes increased, off latencies decreased slightly,
and on response duration increased following electrical stimulation.
For rd10 retina (n=122), only off latencies decreased. As a withinexperiment control we examined ‘distant-non responsive cells’ (n=
1267 wt, 931 rd10) to see whether responsiveness changes over time
in vitro, independent of electrical stimulation. In these cells we found
similar response changes, but the magnitude of wt ‘nearby responsive
cell’ amplitude changes remained significantly greater than control.
We found no significant changes in the on/off index under any
conditions – despite large changes for individual cells.
Conclusions: Visual response properties can be altered by electrical
stimulation. As electrical stimulation influences cellular and/
or network responsiveness, it is advisable to incorporate such
dynamic network effects into response models for prosthetic retinal
stimulation.
Commercial Relationships: Archana Jalligampala, None; Daniel
L. Rathbun, None; Eberhart Zrenner, Retina Implant AG (F),
Retina Implant AG (I), Retina Implant AG (P), Retina Implant AG
(R), Retina Implant AG (S)
Support: BMBF SysRetPro FKZ: 031A308 BMBF FKZ: 01GQ1002
DFG EXC307 Kerstan Foundation, ProRetina
Program Number: 764 Poster Board Number: D0158
Presentation Time: 1:30 PM–3:15 PM
ERG Findings after One Year Intravitreal Ranibizumab and
Single or Multiple Spot Panphotocoagulation Treatment for
Proliferative Diabetic Retinopathy
Katharina Messias, Rafael de Montier Barroso, Fabiano Sakamoto,
Vinicius M. Castro, Amanda Marega, Rodrigo Jorge, Andre Messias.
Ophthalmology, Ribeirão Preto School of Medicine, Ribeirao Preto,
Brazil.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Purpose: To compare the effects of intravitreal Ranibizumab (IVR)
associated or not with panphotocoagulation (PRP) using single
(EDTRS) or multiple (pattern scan laser – PASCAL) spot targeting
laser on retinal function in proliferative diabetic retinopathy.
Methods: A total of 44 patients have been enrolled in this
randomized, prospective clinical trial, and assigned to treatment
with only IVR, IVR-PASCAL or IVR-EDTRS. Comprehensive
ophthalmological evaluations were performed at baseline and every
4 weeks after treatment including full-field electroretinography
(ERG) using a recording protocol in accordance with the ISCEV
standard, to measure a- and b-wave amplitude and implicit time for
dark-adapted 0.01 cd.s/m2 (Rod) and 3.0 cd.s/m2 (CR); and lightadapted 3.0 cd.s/m2 (Cone) single flash and 30 Hz flicker, and LED
full-field stimulator, first using red (635 to 638 nm), then blue (465 to
470 nm), and then white (6500 K) stimulus, with 5 minutes intersession interval at baseline and at 12, 24 and 48 weeks after treatment
(Espion E2 – Diagnosys LLC, Lowell, MA). PRP was performed
exclusively at baseline in 2 sessions. In eyes with macular edema,
macular short-pulse grid laser was associated to IVR at baseline.
IVR was repeated monthly if central subfield macular thickness
measured with SDOCT was higher than 300 mm, or quarterly if
neovascularization was detected by angiography.
Results: IVR=13, PASCAL=14, and ETDRS=13 eyes finished
the 48 weeks follow-up. No significant difference was observed
between groups for any ERG parameters at baseline. A significant
amplitude reduction was observed dark and light adapted ERG
stimuli, for EDTRS and PASCAL groups, but not for IVR, up to 48
weeks. No difference was observed between EDTRS and PASCAL
groups regarding ERG amplitude reduction. There was no significant
correlation between ERG amplitude or amplitude reduction and OCT
macular thickness or visual acuity.
Conclusions: These data indicate that single spot or PASCAL laser
PRP associated to IVR cause similar ERG amplitude reductions,
which is not observed with IVR alone, up to one year follow-up.
Commercial Relationships: Katharina Messias, None; Rafael
de Montier Barroso, None; Fabiano Sakamoto, None; Vinicius
M. Castro, None; Amanda Marega, None; Rodrigo Jorge, None;
Andre Messias, None
Support: FAESP 2012/16265-0
Clinical Trial: NCT02005432
Program Number: 765 Poster Board Number: D0159
Presentation Time: 1:30 PM–3:15 PM
Clinical and electroretinography features observed in patients
taking ezogabine
Thomas B. Connor. Vitreoretinal Service, Eye Institute Med Coll WI,
Milwaukee, WI.
Purpose: To present clinical and electrophysiologic features
of patients taking the anti-seizure medication ezogabine. FDA
warnings from 4/26/13 anounced that ezogabine can cause blue skin
disoloration and eye abnormalities characterized by pigment changes
in the retina, though detailed information has been limited.
Methods: Retrospective chart review of patients taking ezogabine
referred by the neurology service for ophthalmic examination.
Charts were reviewed for features of ophthalmic examination and
additional testing of ganzfeld electroretinography (ERG), perimetry,
and imaging using auto-fluorescence, wide-field fundus imaging, and
retinal optical coherence tomography (OCT).
Results: Six patients were identified:4 men and 2 women aged 18-63
yrs (mean 46.8). All had long histories of seizure disorders that had
been diificult to control, often requiring multiple trials of medications
and surgery. One patient had used ezogabine for 11 months, stopping
because of muscle irrritation. The other 5 had used ezogabine for
1.5 - 2yrs ( mean 1.8 yrs). All patients denied any visual symptoms.
No abnormal coloration of skin, nail beds, lips, or sclera was noted.
Visual acuity, Ishihara color vision testing, and perimetry were
unaffected. Ocular examination was unremarkable save for two
patients with mild pigment mottling of the inferior post-equatorial
RPE. Autofluorescence and macular OCT were unremarkable.
Ganzfeld ERG results were unremarkable in 3 patients. 2 patients
demonstarted a reduction in photopic/cone response (with essentially
unaffected scotopic/rod response) and 1 patient had extinguished rod
and cone responses, demonstrated on two separate testings 2 months
apart.
Conclusions: Ophthalmic findings including ganzfeld ERG features
are described in 6 patients who had used ezogabine for 1-2 years.
ERG findings ranged from normal in 3 patients to reduced response
in 2 patients and extinguished in 1 patient. All patients noticed
no visual symptoms and had unremarkable exams save for two
patients with mild RPE pigment mottling. Detailed examination with
extended follow-up of a larger population of patients on ezogabine
may help our understanding of the significance of these findings.
Commercial Relationships: Thomas B. Connor, None
Support: unrestricted grant from Research to Prevent Blindness
Program Number: 766 Poster Board Number: D0160
Presentation Time: 1:30 PM–3:15 PM
Responses of retinal ganglion cells to electrical stimulation with a
subretinal photovoltaic prosthesis
Yueh-Chun Tsai6, 1, Po-Han Kuo2, 3, Po-Kang Lin4, 5, Chung-Yu
Wu2, 3, Chuan-Chin Chiao6, 1. 1Institute of Systems Neuroscience,
National Tsing Hua University, Hsinchu, Taiwan; 2Department of
Electronics Engineering, National Chiao Tung University, Hsinchu,
Taiwan; 3Biomedical Electronics Translational Research Center,
National Chiao Tung University, Hsinchu, Taiwan; 4Ophthalmology
Department, Taipei Veterans General Hospital, Taipei, Taiwan;
5
National Yang Ming University, Taipei, Taiwan; 6Department of Life
Science,National Tsing Hua University, Hsinchu, Taiwan.
Purpose: In photovoltaic subretinal prosthesis, the electrical current
for reliably stimulating retinal ganglion cells (RGCs) is demanding.
This study was aimed to evaluate the efficacy of enhanced current
output with a divisional power supply scheme (DPSS) circuit, which
provides power alternately to a subset of electrodes at a time with all
the electricity.
Methods: The photovoltaic prosthesis was fabricated by the Taiwan
Semiconductor Cooperation (TSMC). The prosthetic chip is equipped
with a centrally located 8x8 CMOS sensors array, fabricated with 65
nm line width technology of TSMC. An independent output electrode
is accompanied by individual sensor and corresponding return
electrode. The chip is powered by on-chip integrated solar cells in the
periphery. The chip was investigated systematically in vitro to verify
the electrophysiological response of RGCs from isolated rabbit and
mouse retinas using a multi-electrode array (MEA).
Results: With this chip, RGCs were successfully activated by
electrical stimulation of the retinal neural network. In both rabbit
and mouse retinas, the evoked spiking responses of RGCs were
successfully recorded by MEA. The spike latency of these electrically
evoked responses was consistent with previous studies. Furthermore,
the effects of stimulation strength and frequency on RGC responses
were also characterized.
Conclusions: Reliable activation of RGCs by electrical stimulation
in vitro using a subretinal photovoltaic prosthesis with DPSS design
demonstrates the potential and could be developed into a power-free
device able to restore vision in the future.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Commercial Relationships: Yueh-Chun Tsai, None; Po-Han Kuo,
None; Po-Kang Lin, None; Chung-Yu Wu, None; Chuan-Chin
Chiao, None
Support: The National Science Council of Taiwan, NSC-1022220-E-010-001
Program Number: 767 Poster Board Number: D0161
Presentation Time: 1:30 PM–3:15 PM
Experimentally determination of optimal electrical stimulation
pulse parameters for designing high resolution epiretinal implant
system
Irfan Karagoz1, Mahmut E. Celik1, Mustafa Ozden2, Gungor Sobaci3.
1
Electrical and Electronics Engineering, Gazi University, Ankara,
Turkey; 2Electrical&Electronics Engineering, Kirikkale University,
Kirikkale, Turkey; 3Opthalmology, Hacettepe University, Ankara,
Turkey.
Purpose: It is aimed that parameters related to optimal electrical
stimulation pulse to be used for high resolution epiretinal prosthesis
are experimentally determined by examining neural activity recorded
from rabbit retina.
Methods: Preparation phase of the retina includes anesthesia,
enucleation, removing of eyeball and retinal dissection in accordance
with institutional guidelines for the care and use of animals. Isolated
retina tissue 8-10 mm in diameter is placed to microelectrode
array which faces ganglion cell layer. A microelectrode array
(60HexaMEA-Ti, Multi Channel Systems MCS GmbH), which can
both inject current pulses to stimulate the retina and record action
potentials and has 60 recording electrodes with interelectrode spacing
of 30, 60, 90 mm and diameter of 10, 20, 30 mm, is used. Biphasic
pulses with zero net charge are used to avoid electrode corrosion
and tissue damage and applied in dark. Two methods, threshold and
slope mode, are used to detect and extract spike activity. Then, spike
activity is analyzed using MC_Rack and MATLAB.
Results: It is seen in neural activity that 89 ± 9 spikes on average
form as a result of applied biphasic stimulation. The highest spike
activity range is observed when stimulation pulse, which have
width of 400 ms and amplitude of 80 and 120 mA, is used with
electrode template 20 mm in diameter and interelectrode spacing
of 60 mm. Based upon this electrode template and results, when a
square electrode matrix of 3mm x 3mm targeted to macula region
is designed, maximum electrode resolution is found as 37 x 37.
Additionally, instant power requirement is determined as 0.6845 ±
0.1369 Watt for this structure.
Conclusions: Considering animal experiments, it is concluded that
biphasic pulses with bigger pulse widths are more effective for
spike formation and threshold method yields better results for less
fluctuating signals with respect to slope method.
Commercial Relationships: Irfan Karagoz, None; Mahmut E.
Celik, None; Mustafa Ozden, None; Gungor Sobaci, None
Support: This work was supported by a grant from
TUBITAK(113E181)
Program Number: 768 Poster Board Number: D0162
Presentation Time: 1:30 PM–3:15 PM
30Hz Photopic ERG Implicit Time and Combined Score are
Associated with Referable Diabetic Retinopathy
Taras V. Litvin1, 2, George H. Bresnick2, Glen Y. Ozawa2, Kuniyoshi
Kanai2, Jorge Cuadros2, 1. 1Vision Science, UC Berkeley, Berkeley,
CA; 2Optometry, UC Berkeley, Berkeley, CA.
Purpose: To investigate the association between the level of
retinopathy and implicit time (IT), amplitude (Amp), and a combined
score (Score) of the 30Hz flicker ERG, measured using a novel hand-
held ERG device, in a cohort of adult patients with type 1 and type 2
diabetes mellitus.
Methods: Subjects were recruited from a pool of patients refered by
their primary care provider to Eastmont Wellness Center, Oakland,
CA for an eye examination. All subjects underwent a comprehensive
ocular examination. Photopic 30Hz flicker ERG measurements were
obtained from each eye using the RETeval hand-held ERG device
(LKC Technologies, Inc.). Fundus photographs were obtained and
evaluated using the Canon CR-DGI fundus camera, following the
EyePACS protocol and grading system, a modified ETDRS protocol.
Results were analyzed based on the subject’s eye with the worse
level of retinopathy. If both eyes of the subject had the same level of
retinopathy, the right eye was selected.
Results: 58 ethnically diverse patients were enrolled. Mean age was
53±11 years. 67% were females. Mean duration of diabetes was
9.2±6.6 years and mean hemoglobin A1c was 8.1±2.1. The analysis
herein is based on the 50 patients who had not had PRP and had
both RETeval device results and gradable photos. 25 (50%) patients
showed no retinopathy, 7 (14%) had mild non-proliferative diabetic
retinopathy (NPDR), 14 (28%) had moderate NPDR, 4 (8%) had
severe NPDR, and 0% had proliferative retinopathy (PDR). 1 (2%)
patient had clinically significant macular edema (CSME). Patients
were assigned to referable (severe NPDR and/or CSME) and nonreferable groups. Retinopathy had significant effect on Score, IT,
and Amp (p=0.03, one-way MANOVA). Only IT, was significantly
associated with referable retinopathy in our logistic regression
analysis (p =0.02). A delay in one millisecond of IT was associated
with the odds ratio of referable retinopathy diagnosis equal to 1.96,
95% CI: 1.18 – 4.17. In this preliminary analysis the RETeval device
score had a sensitivity of 100% (4/4) and a specificity of 69.5%
(32/46) to referable retinopathy.
Conclusions: A delay in photopic 30Hz flicker IT, measured using a
hand-held ERG device was associated with significant increase in the
odds of being diagnosed with severe NPDR or CSME. The RETeval
device score had perfect sensitivity, albeit more cases are required for
a conclusive analysis.
Commercial Relationships: Taras V. Litvin, None; George H.
Bresnick, EyePACS, LLC (I); Glen Y. Ozawa, LKC Technologies,
Inc. (F); Kuniyoshi Kanai, None; Jorge Cuadros, EyePACS (I)
Support: NIH K12
Program Number: 769 Poster Board Number: D0163
Presentation Time: 1:30 PM–3:15 PM
Multifocal electroretinogram and en-face OCT in patients who
underwent retinal detachment surgery
Fanny Ricouard, Guillaume Bigan, Perle TUMAHAI, Mathieu
Flores, Marie Castelbou, Bernard Y. Delbosc, Maher Saleh.
Department of Ophtalmology, University Hospital of Besançon,
Besançon, France.
Purpose: To study the anatomical and functional recovery after
retinal detachment (RD) surgery by studying the reflectivity of the
outer retina on en-face optical coherence tomography (OCT) and with
multifocal electroretinogram (Mf-ERG).
Methods: Prospective study of a consecutive series of patients
successfully operated for RD and examined at baseline, at
month 3 (M3) and month 6 (M6) postoperatively. At each visit,
a comprehensive ophthalmologic examination was performed. A
spectral-domain OCT imaging (Spectralis, Heidelberg Engineering,
Heidelberg, Germany) was also obtained. The operated eyes were
separated according to their macular status at baseline. At the M6
visit, en-face OCT and Mf-ERG (Metrovision, Perenchies, France)
were also performed. The ISe band reflectivity was measured
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
on C-scan in the two central degrees and correlated with the
corresponding Mf-ERG results.
Results: The group with initial macular involvement displayed
decreased RMS amplitude compared to the macula on group (<2°,
p<0.0001; 2°-5°, p=0.007). A reduction of the P1 wave amplitude
was also found (<2 °, p = 0.03). In the central two degrees, the RMS,
P1, N1 and N2 amplitudes but not implicit times were significantly
correlated with the visual acuity (p <0.001). The ISe band reflectivity
was lower in the macula-off group (Mann-Whitney test, p<0.05) and
was correlated with the visual acuity measured at M3 and M6 visits
(p<0.001). The decrease in reflectivity, suggesting a cone loss, was
also correlated with the duration of the macula detachment (p=0.01).
There was no relationship between the decrease of ISe reflectivity in
the one hand and with the impairment of the Mf-ERG signal on the
other hand.
Conclusions: The central P1 and RMS amplitudes were the most
affected Mf-ERG parameters after retinal detachment surgery. At the
same time, there was a decrease in ISe band reflectivity in eyes with
an initial macular involvement. The absence of relationship between
these two findings suggests that the outer retina plays a limited role
in the impairment of the Mf-ERG signal after retinal detachment. The
implication of the inner retinal layers is currently investigated.
Commercial Relationships: Fanny Ricouard, None; Guillaume
Bigan, None; Perle TUMAHAI, None; Mathieu Flores, None;
Marie Castelbou, None; Bernard Y. Delbosc, None; Maher Saleh,
None
Program Number: 770 Poster Board Number: D0164
Presentation Time: 1:30 PM–3:15 PM
Electrical Impedance of wild-type and rd1 Mouse Retina
Boshuo Wang1, James D. Weiland1, 2. 1Biomedical Engineering,
University of Southern California, Los Angeles, CA;
2
Ophthalmology, University of Southern California, Los Angeles,
CA.
Purpose: Electrical impedance of the retina is a critical factor in
retinal prostheses, determining the intraretinal current flow and
potential distribution of electrical stimulation. This experimental
study measured the resistivity profiles of wild type and rd1 mice,
providing basis for computational simulations and predictive
modeling studies.
Methods: Female wild type and rd1 mice (Jackson Lab) were
euthanized at ca. 12-14 wks postnatal. After enucleation of the eye,
the retina was dissected in Ames solution and placed on top of agar in
a custom-made recording chamber with the ganglion cell side up. A
bipolar microelectrode with a pencil-tip profile (FHC, Inc.) was used
for impedance measurement. The inner pole of Pt/Ir is 25 microns
in diameter and height. A microcontroller lowered the electrode into
the saline, approaching the retina and penetrating through the tissue.
Impedance spectra were recorded at regular intervals depth and more
frequently when impedance began to increase when the tip neared
and entered the retina. The Peak Resistance Frequency (PRF) method
was used to extract the resistance of the tissue and/or electrolyte, and
the converted to resistivity using the cell constant of the electrode.
Measurement was terminated when the impedance decreased to
baseline as the electrode reached the agar beneath the retina.
Results: The wild type retina profile showed an increase in resistivity
starting from the retina ganglion cell side inward, from 1.4±0.4
Ω•m to a peak resistivity of 4.8±0.4 Ω•m, and then decreasing down
to initial values on the photoreceptor side. The peak is located at
about 75% thickness, which is consistent with literature data on rat
and embryonic chick retina. Compared to the wild type retina, the
rd1 resistivity profile is thinner by about 80 μm, as expected due to
degeneration. The peak resistivity is lower (3.4±0.6 Ω•m), but still in
the nominal range of neural tissue, while its location is at about 60%
thickness.
Conclusions: Peak retinal resistivity decreased as retina thinned
due to degeneration. The apparent resistivity determined with the
above-described method is on a “mesoscopic” scale comparable
to the electrode size. Therefore it was mostly influenced by
geometric factors, while tissue structure at the cellular level, e.g.
retinal remodeling and glial hypertrophy, could not be detected.
Measurements with higher spatial resolution will be needed to assess
the impact of these phenomena.
Commercial Relationships: Boshuo Wang, None; James D.
Weiland, Second Sight Medical Products, Inc. (P)
Support: National Institutes of Health, Grant No. U01 GM104604;
Unrestricted Departmental Grant from Research to Prevent
Blindness, New York, NY 10022
Program Number: 771 Poster Board Number: D0165
Presentation Time: 1:30 PM–3:15 PM
Modeled direct and indirect activation of retinal ganglion cells
during subretinal stimulation
Paul Werginz1, Jörg Encke1, Archana Jalligampala2, Daniel L.
Rathbun2, Frank Rattay1. 1Institute for Analysis and Scientific
Computing, Vienna University of Technology, Vienna, Austria;
2
Institute for Ophthalmic Research, University of Tübingen,
Tübingen, Germany.
Purpose: Although several experimental studies have been
performed, it is still unclear how an applied electric potential
activates retinal ganglion cells (GC) in detail. This modeling study
tries to reveal how direct and indirect (synaptic) activation of GCs
can be achieved during subretinal stimulation.
Methods: We combined models of a bipolar cell (BC), a GC and a
connecting ribbon synapse. Cell geometry data was either extracted
from 2D depictions from the literature and converted into 3D cell
models or taken from a database (www.neuromorpho.org) and further
modified. Hodgkin-Huxley-like membrane kinetics were incorporated
into the multi-compartment models. Calculations of the membrane
potential, synaptic activity, ionic currents etc. were performed in
MatLab. External potentials evoked by a monopolar disc electrode
were modeled using finite element software COMSOL Multiphysics.
Results: Responses of the model neurons to 1ms and 5ms pulses
were computed for 3 different electrode locations (directly under the
somas (Fig); 100μm and 300μm shifted in x-direction). Both pulse
durations were able to trigger direct and indirect spikes. Because
of the kinetic characteristics of the ribbon synapse longer pulses
preferably activate the BC. For electrode positions closer to the
soma, indirect stimulation thresholds are lower than direct activation
thresholds. Depending on electrode location either cathodic or anodic
pulses result in lower thresholds.
Conclusions: Modeled activation thresholds are comparable
to actual applied stimuli in current retinal implants (0.2-1.5V).
Furthermore, the site of spike initiation is heavily depending on the
GC morphology. Up to now, no general assumptions can be made
how each activation mechanism can be triggered by specific stimulus
protocols. Further investigations and more detailed cell models will
help to gain deeper insight into activation characteristics.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
diameter, prospectively. Visual acuity examined at the day of mfERG
recording (VA@rec) and at the last visit (VA@LV) were compared.
Results: The P50 was absent only in 3 eyes (P50-positive: n = 12,
-negative: n = 3). The difference in age was not significant (P > 0.4)
between 2 groups. The mean VA@rec and VA@LV in P50-postive
eyes were significantly higher than those in P50-negative eyes (VA@
rec: P50-positive: 0.42 logMAR, -negative: 0.94 logMAR, p < 0.01;
VA@LV: P50-positive: 0.18 logMAR, -negative: 0.80 logMAR, p <
0.01). In the P50-negative group, no eye obtained visual acuity better
than 0.2 of VA@rec (0.05-0.2) or 0.4 of VA@LV (0.05-0.4). In the
P50-positive group, VA@rec (0.15-0.9) and VA@LV (0.15-1.0) were
widely varied.
Conclusions: Presence of P50 implies the preservation of the specific
function in the fovea. P50-positive eyes with BRVO had significantly
better visual acuity than P50-negative eyes had. However, P50negative eyes with BRVO were in a minority and visual acuity in
P50-positive eyes were varied. It is notable P50 positive eyes did not
always have a good visual prognosis.
Commercial Relationships: Yoshiaki Shimada, None; Atsuhiro
Tanikawa, None; Masayuki Horiguchi, None
(A) Distribution of electric potentials across the simulated volume. A
BC and one GC are connected via a ribbon synapse. (B) Direct and
indirect spikes in the GC during anodic stimulation. The direct spike
is initiated within the sodium channel band whereas indirect spikes
are triggered by synaptic activity. SOCB = Sodium channel band, IS
= Initial segment.
Commercial Relationships: Paul Werginz, None; Jörg Encke,
None; Archana Jalligampala, None; Daniel L. Rathbun, None;
Frank Rattay, None
Support: Austrian Science Fund, Grant No. P 27335-B23
Program Number: 772 Poster Board Number: D0166
Presentation Time: 1:30 PM–3:15 PM
The foveal wavelet (P50) and visual prognosis of branch retinal
vein occlusion
Yoshiaki Shimada1, Atsuhiro Tanikawa2, Masayuki Horiguchi2.
1
Ophthalmology, Fujita Health Univ Banbuntane Hosp, Nagoya,
Japan; 2Ophthalmology, Fujita Health Univ, Toyoake, Japan.
Purpose: We reported that healthy subjects commonly have the
foveal wavelet, a slow positive component with a long peak time
approximately 50 ms (P50) in the first slice of the second order kernel
(K2.1) of multifocal electroretinogram (mfERG) only in the fovea
(ARVO2011). The prognostic value of the P50 in eyes with branch
retinal vein occlusion (BRVO) was evaluated.
Methods: mfERGs (75 Hz base rate, 37 stimulus hexagons) recorded
from 15 eyes of 15 patients with BRVO were retrospectively
examined. Eyes were classified into two groups, P50-positive and
P50-negative, by the presence or absence of the P50 at the centermost
element corresponding to the fovea, approximately 4.4 degrees in
Program Number: 773 Poster Board Number: D0167
Presentation Time: 1:30 PM–3:15 PM
Finding stage-specific degenerative patterns of retinal ganglion
cell (RGC) firing in rd10 mice
Dae-jin Park1, 2, Jeong yeol Ahn1, 2, Yongsook Goo1, 2. 1Department
of Physiology, School of Medicine, Chungbuk National University,
Cheong-ju, Korea (the Republic of); 2Nano Artificial Vision Research
Center, Seoul National University Hospital, Seoul, Korea (the
Republic of).
Purpose: Mammalian retinal degenerations show different
physiological features in each progression stage. In this study, retinal
degenerative changes and response characteristics to electrical stimuli
are investigated according to each stage. The stage-specific response
may provide us the guideline for optimal time window for the
implement of retinal prosthesis.
Methods: After isolating retina from rd10 mice, good animal model
for RP, retinal patch was placed retinal ganglion cell (RGC) layer
down onto 8x8 multi-electrode arrays (MEA). Spontaneous and
electrically-evoked RGC spikes were recorded at postnatal week
(PNW) 2 to 34. Cathodic phase-first biphasic current pulses (sine
or square pulse) were applied (duration: 500 ms, amplitude: 5 ~ 60
mA, frequency: 1~20 Hz). Mean frequency of RGC spikes, 2nd peak
latency of inter-spike interval histogram, power spectral density,
correlation index, evoked RGC spike number and valid response ratio
(VRR) were compared among each age group. We defined VRR as
RGC spike numbers in post-stimulus 100 ms / those in post-stimulus
1000 ms since among multiple peaks in PSTH, the dominant peak is
observed around 100 ms, like in wild-type mice.
Results: Mean frequency of RGC spike is the highest at PNW4.5
(p<0.001). Inter-burst intervals linearly increase after PNW4.5 and
reach the maxima (200 ms) at PNW26 (p<0.001). During electrical
stimulation, mean frequency of RGC spike and oscillatory local field
potentials are fixed to 15~20 and 10~13 Hz, respectively. Evoked
spike numbers in post-stimulus 100 ms linearly increase and stabilize
after PNW6.5. VRR is the lowest at PNW3~4.5 and stabilized after
PNW6.5 (p<0.001).
Conclusions: Our results might be a reflection of the rapid rod
photoreceptor degeneration during PNW3~4.5 and synaptic changes
after PNW6.5. In PNW3~4.5, RGC spontaneous firing is the highest
and VRR is the lowest, which suggest the therapeutic potential with
retinal prosthesis during this period may be not so good because 1st
peak at 100 ms in PSTH is less dominant. 5 Hz oscillatory rhythm
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
observed after PNW6.5, well known property in rd mice retina, is
a major cause of poor signal-to-noise ratio for visual perception.
However, since VRRs are relatively high between PNW6.5~20, we
suggest that this period would be a good time window for prosthesis
implement.
Figure 1. VRR is compared among different postnatal age groups (:
statistical difference among all ages).
Commercial Relationships: Dae-jin Park, None; Jeong yeol Ahn,
None; Yongsook Goo, None
Support: Supported by grants of the MEST (NRF-2010-0020852,
NRF-2013R1A1A3009574) of Korea to Y. Goo
Program Number: 774 Poster Board Number: D0168
Presentation Time: 1:30 PM–3:15 PM
Electrical stimulation of rat retina elicits retinotopic cortical
electrophysiology activity with a dose response characteristic
Kiran Nimmagadda1, 2, James Weiland3, 4. 1Neuroscience Graduate
Program, University of Southern California, Los Angeles, CA; 2MD/
PhD Program, USC-Caltech, Los Angeles, CA; 3Ophthalmology,
University of Southern California, Los Angeles, CA; 4Biomedical
Engineering, University of Southern California, Los Angeles, CA.
Purpose: The purpose of this study is to characterize
electrophysiological response in the visual cortex elicited by
electrical stimulation of rat retina.
Methods: Three Long Evans female rats under anesthesia were
used for this study. A 75 m diameter cylindrical Pt-Ir electrode
was inserted into the left eye.The tip of the electrode was placed
50-100 m from the ventral temporal area of the retina. Charge
balanced biphasic stimulus current pulses from 30 to 100 A and 0.5
ms duration were delivered to the retina at 1 Hz. A craniotomy was
performed to expose the right visual cortex. A tungsten recording
electrode was advanced into the visual cortex to capture elicited
electrophysiological signals. The electrically evoked response (EER)
was amplified (gain 2000) and low-pass filtered (cutoff frequency 8
kHz), and sampled at 20 kHz. EERs were recorded at multiple sites
in the visual cortex of each rat. For each stimulus condition, the EER
was averaged over 25 stimulus pulses. Digital filtering was applied
to remove high frequency and 60 Hz noise before analysis. The root
mean square (rms) value of the EER after stimulus pulse over 40 ms
(signal) was compared with the rms value before stimulus (noise) to
calculate signal to noise ratios (SNR) for each stimulus condition.
Results: We measured detectable EERs (defined as > 10 dB SNR
with 100 uA stimulus) 3.25 – 4 mm lateral and 0.75 mm anterior –
0.5 mm posterior to lambda. Previous studies have shown that light
stimulus of ventral temporal retina evokes cortical activity in the
region 3 – 5 mm lateral and 2 mm anterior – 0.5 mm posterior to
lambda. No detectable EERs were measured 0.25 mm away from
this cortical region. The measured EER SNR (n=17 locations in 3
rats) showed a dose response relationship with respect to stimulus
current with some locations showing monotonic behavior (n = 6) and
some locations showing peak SNR at intermediate current (n = 8). At
100 A stimulus current, the mean SNR was 17.3 dB with a standard
deviation of 3.3 dB (n=15) in the cortical regions that showed
detectable EERs.
Conclusions: Our results show that focal electrical stimulation
of rat retina elicits visual cortex activity in the same region where
light stimulus generates activity. This study will form a baseline to
evaluate long-term stimulation of rat retina.
Commercial Relationships: Kiran Nimmagadda, None; James
Weiland, None
Support: NSF-CBET-1353018, NSF-CBET-1343193, Research to
Prevent Blindness
Program Number: 775 Poster Board Number: D0169
Presentation Time: 1:30 PM–3:15 PM
Characterization of indirect ganglion cell responses to electrical
stimulation in the mouse retina
Daniel L. Rathbun1, Archana Jalligampala1, 2, Eberhart Zrenner1.
1
Institute for Ophthalmic Research & Center for Integrative
Neuroscience, University of Tuebingen, Tuebingen, Germany;
2
Graduate Training Center of Neuroscience, University of Tuebingen,
Tuebingen, Germany.
Purpose: The most successful approach for vision restoration
following retinal degeneration-induced blindness so far has been
electrical stimulation of the retina via neuroprosthetic devices. Such
stimulation restores visual perception by creating a pattern of action
potentials (spikes) in the optic nerve that approximates that found
during healthy vision. While some prostheses seek to control the
spike pattern through direct stimulation of retinal ganglion cells
(RGCs), we target the underlying retinal network. This indirect
stimulation of RGCs via electrical stimulation of second order
neurons (e.g. bipolar cells), however, results in complex spike
patterns that remain poorly understood. Here we present our efforts to
demystify these spike patterns.
Methods: Spiking responses of adult mouse RGCs were recorded
in vitro with a planar multielectrode array. Monophasic voltage
pulses with 114 unique voltage-duration combinations (+ 2.5 V to
-2.5 V, 0.06 to 5 ms, 5 repetitions each, interpulse interval ≥5 s)
were delivered from the ganglion cell side of the retina (epiretinal
configuration). A full-field white flash stimulus (2 s ON, 2 s
OFF) was cycled 20x without pause in each of 6 stimulus blocks,
interleaved with the electrical stimulation. To quantify the preference
of RGCs for either positive or negative voltage pulses, a voltage
polarity index was created. To quantify how much RGC responses
decreased above the voltage that produced a maximal response, a
suppression index was created.
Results: The polarity index revealed that although all cells
responded to negative voltages, only a subset of cells also responded
to positive voltages. The suppression index revealed that the
majority of RGCs did not have significant response suppression
above the voltage required for a peak response. Simple visual
response characteristics (amplitude, latency, and duration of ON and
OFF responses) had only weak correspondence to the polarity index
and suppression index.
Conclusions: Electrical response patterns resulting from indirect
RGC stimulation are diverse. Although we were unable to
demonstrate strong correlations between the electrical and visual
response properties examined here, we continue to search for
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
appropriate methods to distinguish the ~20 distinct RGC types that
have been identified using morphological analysis.
Commercial Relationships: Daniel L. Rathbun, None; Archana
Jalligampala, None; Eberhart Zrenner, Retina Implant AG (F),
Retina Implant AG (I), Retina Implant AG (P), Retina Implant AG
(R), Retina Implant AG (S)
Support: BMBF SysRetPro FKZ: 031A308; BMBF FKZ:
01GQ1002; DFG EXC307; Kerstan Foundation, Pro-Retina
Program Number: 776 Poster Board Number: D0170
Presentation Time: 1:30 PM–3:15 PM
Antagonistic Cortical Activation Evoked by Transcorneal
Electrical Stimulation: Study by Intrinsic Optical Imaging and
Electrophysiological Recording
Yao Chen, Zengguang Ma, Pengjia Cao, Pengcheng Sun, Xinyu Chai.
Biomedical Engineering, Shanghai Jiao Tong University, Shanghai,
China.
Purpose: Revealing the hemodynamic changes in visual cortex
occurred after electrical stimulation can contribute to comprehension
of neurophysiological underpinnings underlying prosthetic vision.
Our previous work found transcorneal electrical stimulation (TcES)
through an ERG-jet corneal electrode could consistently elicit
response areas in cats’ visual cortex, using optical imaging of
intrinsic signals (OIS) (IOVS, 2014). These OIS activation regions
were mainly located in cortical areas representing peripheral visual
field. Both the extent of activation areas and the strength of intrinsic
signals were increased with higher current intensities and longer
pulse widths. Furthermore, we found an antagonistic spatial pattern
of positive and negative OIS response (POR and NOR) evoked by
TcES. This phenomenon was similar to the pervasive negative blood
oxygenation level-dependent (BOLD) response reported in functional
magnetic resonance imaging (fMRI) study. The purpose of this study
was to investigate the spatialtemporal patterns of cortical antagonistic
OIS response and its relationship to local neuronal activity.
Methods: Multiwavelength OIS response was recorded from area
17/18 in cats to investigate the cortical responses to TcES through an
ERG-jet contact lens electrode. Multiunit activity (MUA) and local
field potentials (LFPs) were recorded from the 96-channels Utah
microelectrode array placed in positive and negative OIS response
regions. Linear microelectrode array was also used to measure the
laminar neuronal activity throughout the depth of the cortex.
Results: The regions of POR were mainly located in cortical areas
representing peripheral visual field while the NOR regions were
corresponding to visual centre. Similar to the positive OIS response,
the amplitude and activated areas of negative OIS response were
also related to electrical stimulation. Furthermore, the POR regions
exhibited stronger LFP and MUA responses. Spectral power analysis
showed that the power of electrophysiological signal in ranges
30–130 Hz (LFP) and 300–2500 Hz (MUA) from the POR regions
were significantly higher than those from the NOR regions (Mann–
Whitney test, P < 0.005, n = 7 cats).
Conclusions: This work provides evidence that the negative
hemodynamic response may not due to the decreased neuronal
activity in that region.
Commercial Relationships: Yao Chen, None; Zengguang Ma,
None; Pengjia Cao, None; Pengcheng Sun, None; Xinyu Chai,
None
Support: The National Basic Research Program of China (973
Program, 2011CB707502/3), the National Natural Science
Foundation of China (31070981, 61171174, 91120304).
Program Number: 777 Poster Board Number: D0171
Presentation Time: 1:30 PM–3:15 PM
Perceptions elicited by electrical stimulation of human visual cortex
Eduardo Fernandez1, 2, Arantxa Alfaro2, 3, Rafael Toledano4, Julio
Albisua5, Alejandro García1. 1Instituto de Bioingenieria, Univ of
Miguel Hernandez, Elche, Spain; 2Neural Engineering, CIBER BBN,
Madrid, Spain; 3Hospital Vega Baja, Orihuela, Spain; 4Hospital Ruber
International, Madrid, Spain; 5Fundacion Jimenez Díaz, Madrid,
Spain.
Purpose: Appropriate delivery of electrical stimulation to visual
structures can evoke patterned sensations of light, called technically
phosphenes. This pivotal finding settled the physiological basis for
present efforts to develop a visual prosthesis for the blind. Here we
aim to study the visual perceptions elicited by electrical stimulation
of human visual cortex.
Methods: Electrical stimulation of occipital cortex was performed in
patients with a diagnosis of intractable epilepsy that had to undergo
a surgical resection. Electrical stimulation was applied through
implanted subdural electrodes or using penetrating micro-electrodes.
Electrical stimulation was applied using a biphasic neurostimulator.
For mapping the visual perceptions we used a wireless system
including an autofocus infrared (IR) camera and one IR projector.
After each electrical stimulation, subjects were asked to make
drawings of the perceptions with particular emphasis on the size,
main features and localization within the visual field. A customized
program allowed easy registration and analysis of collected data.
Results: All study subjects perceived phosphenes and tolerated
the procedure without complications. The probability of detecting
phosphenes or scotoma varied with the position of the electrodes.
Most of the phosphenes were circular or dotted and appeared in
the visual field contralateral to the cerebral hemisphere stimulated.
Stimulation of early visual areas induced visual perceptions but
stimulation of extrastriate occipital cortex was also able to induce
phosphenes with retinotopic representation. Furthermore our
procedure allowed an easy calculation of the position and area of the
subjective perceptions from the coordinates of the drawings.
Conclusions: Electrical stimulation of visual areas in humans
provides a unique opportunity to study the qualitative properties of
induced perceptions, which can offer insights about the functional
organization of human visual cortex and help to the development
new rehabilitative strategies for profoundly blind based on multiple
cortical microelectrodes.
Commercial Relationships: Eduardo Fernandez, None; Arantxa
Alfaro, None; Rafael Toledano, None; Julio Albisua, None;
Alejandro García, None
Support: Grant MAT2012-39290-C02-1 from the Spanish
Government, Research Chair “Bidons Egara” and National
Organization of the Spanish Blind (ONCE).
Program Number: 778 Poster Board Number: D0172
Presentation Time: 1:30 PM–3:15 PM
Safety assessment of chronic electrical stimulation to rabbit
retina for six months by Femtosecond Laser-induced Porous
electrode of visual prosthesis
Yukari Nakano1, Yasuo Terasawa1, 2, Hiroyuki Tashiro3, Koji Osawa1,
Motoki Ozawa4, Takashi Fujikado5. 1Research and Development
Division, NIDEK CO., LTD., Gamagori, Japan; 2Graduate School of
Materials Science, Nara Institute of Science & Technology, Ikoma,
Japan; 3Department of Health Sciences, Faculty of Medical Sciences,
Kyushu University, Fukuoka, Japan; 4NIDEK CO., LTD., Gamagori,
Japan; 5Applied Visual Science, Osaka University Graduate School of
Medicine, Osaka, Japan.
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
Purpose: We have been developing a visual prosthesis based on
Suprachoroidal-Transretinal Stimulation (STS). In this study, we
applied electrical stimulation to the retinae of seven rabbits with
our system for six months in order to clarify the effect of long-term
electrical stimulation to their eyes.
Methods: Platinum stimulation electrodes (diameter: 0.5 mm, height:
0.3 mm) with Femtosecond Laser-induced Porous surface [Terasawa
et al., ARVO E-abstracts 5538, 2012] were used for electrical
stimulation. The electrode array was implanted into a scleral pocket
on the eye of a rabbit. Current pulses were applied between the
stimulation electrode and the return electrode (Cathodic-First, 1.5mA,
0.5ms, 50Hz, 8h/day). We performed ophthalmological examination
with fundus photography and optical coherence tomography
(OCT) before electrical stimulation and every four weeks during
electrical stimulation. The presence of retinal damage was assessed
histologically in the tissue samples of the enucleated eyes. All
procedures conformed to the ARVO Statement for the Use of Animals
in Ophthalmic and Vision Research.
Results: Chronic electrical stimulation for six months did not cause
any damages of retinae in six of seven cases. However, decrease of
cell density in the outer layer of the retina was observed in one case.
In this one case, the thickness of the sclera between the choroid and
the electrode tip was 78 μm, which was about 30% of the average
thickness of the other six cases (259 μm). It is inferred that proximity
of the electrode to the retina was one of the factors that caused the
cell decrease in the outer layer of the retina. Given the different of
the thickness of sclera between rabbit and human, this proximity is
unlikely occur in human case. There was no significant difference in
the thickness of the sclera on the electrode between before and after
the electrical stimulation in all the seven cases.
Conclusions: In six of seven cases, electrical stimulation did not
cause damage to the retinae and surrounding tissues, therefore
electrical stimulation of retinae was shown to be safe. However, the
cell decrease in the outer layer of the retina was observed in one case.
We are going to investigate the relationship between the thickness
of the sclera on the electrode and occurrence of cell decrease in the
future.
Commercial Relationships: Yukari Nakano, NIDEK CO., LTD.
(E); Yasuo Terasawa, NIDEK CO., LTD. (E); Hiroyuki Tashiro,
Kyushu University (F); Koji Osawa, NIDEK CO., LTD. (E); Motoki
Ozawa, NIDEK CO., LTD. (E); Takashi Fujikado, None
Program Number: 779 Poster Board Number: D0173
Presentation Time: 1:30 PM–3:15 PM
Effects of different three-dimensional electrodes on epiretinal
electrical stimulation by modeling analysis
Chuanqing Zhou, Xinyu Chai, Yao Chen, Xun Cao, Qing Lyu.
School of Biomedical Engineering, Shanghai Jiao Tong University,
Shanghai, China.
Purpose: The objective of this study was to investigate the effects
of different three-dimensional electrodes placed at epiretinal space
on the excitation of retinal ganglion cells (RGCs) by computational
modeling analysis.
Methods: The 3-D finite element models of retinal electrical
stimulation were established, consisting of the platinum
microelectrode, vitreous body, multi-layered retina, and retinitis
epithelium (RPE). Different three-dimensional models of disk
and non-planar electrodes were used in the epiretinal electrical
stimulation. Multi RGCs including somas and axons were modelled
using NEURON software to study the responses of RGCs under
electrical stimulation by different-type electrodes. Threshold current,
threshold charge density and RGCs activated area were the three
key factors to evaluate the performance of stimulating electrodes.
Threshold current or threshold charge density was defined as the
minimum stimulating current or charge density which can activate
only one RGC in our model. RGCs activated area represented the
region of activated RGCs under a certain stimulating current.
Results: With the increment of distance between disk electrode and
retina, both threshold currents and threshold charge density showed
approximately linear relationship with the distance increasing. With
the increment of diameter of the disk electrode, threshold current
increased while threshold charge density decreased. Non-planar
electrodes could provoke different activation responses of RGCs
compared with disk electrodes. Concave electrodes performed
superior stimulation localization and electrode safety, while convex
electrodes acted relatively poor.
Conclusions: The combination of finite element analysis and
NEURON software provides an efficient way to evaluate the
influences of various 3-D electrodes on epiretinal electrical
stimulation. Non-planar electrodes had larger threshold currents
than the disk one. Among the five types of electrodes, concave
spherical electrode might be the ideal candidate considering the good
stimulation localization and electrode safety.
Commercial Relationships: Chuanqing Zhou, None; Xinyu Chai,
None; Yao Chen, None; Xun Cao, None; Qing Lyu, None
Support: The National Basic Research Program of China (973
Program, 2011CB7075003); The National Natural Science
Foundation of China (61472247, 61273368, 91120304,81171377).
Program Number: 780 Poster Board Number: D0174
Presentation Time: 1:30 PM–3:15 PM
Axon activation with focal epiretinal stimulation in primate
retina
Lauren E. Grosberg1, 5, Pawel Hottowy2, Lauren H. Jepson3,
Shinya Ito4, Frederick Kellison-Linn5, Alexander Sher4, Wladyslaw
Dabrowski2, Alan Litke4, EJ Chichilnisky1, 5. 1Neurosurgery, Stanford
University, Stanford, CA; 2Faculty of Physics and Applied Computer
Science, AGH University of Science and Technology, Krakow,
Poland; 3Systems Neurobiology Laboratories, Salk Institute for
Biological Studies, La Jolla, CA; 4Santa Cruz Institute for Particle
Physics, University of California, Santa Cruz, Santa Cruz, CA;
5
Hansen Experimental Physics Laboratory, Stanford University,
Stanford, CA.
Purpose: Epiretinal prostheses aim to mimic natural vision by direct
stimulation of retinal ganglion cells (RGCs). Selective activation of
individual RGCs of different types is necessary to accurately recreate
the activity that occurs during normal vision. Our experiments
indicate that in some cases, activation at single-cell single-spike
resolution is possible, suggesting high potential for future prostheses.
However, these data also reveal unwanted activation of RGC axons,
from distant areas of the visual field, consistent with the phosphenes
produced in recent clinical studies. The purpose of the present work
is to develop approaches to selectively activate of RGCs without
simultaneously activating axons.
Methods: A custom 512-electrode stimulation and recording system
was used to measure electrical activation in hundreds of RGCs from
isolated macaque retina. Stimulation current was provided through
one or more electrodes while RGC spikes were simultaneously
recorded on all electrodes. Electrodes had diameters of 8-15 μm and
were separated by 60 μm. Cell types and axon locations of RGCs
were identified using their recorded responses to white noise visual
stimuli.
Results: At stimulation current levels similar to those that produced
somatic RGC activation, bidirectional signal propagation, apparently
attributable to axon bundle activation, was observed originating
from the vicinity of the stimulating electrode. To investigate if
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].
ARVO 2015 Annual Meeting Abstracts
spatially patterned electrical stimulation can reduce unwanted axon
activation, responses of RGCs stimulated with various individual
electrodes and pairs of electrodes near their somas and along their
axons were recorded. Preliminary results show that in many cases,
testing multiple spatial stimulation patterns for a given target RGC
revealed a particular pattern that activated the cell at its soma without
activating the axon bundle. However, significant variability was
observed in the efficacy of this approach between retinal preparations.
Ongoing studies aim to determine the conditions in which spatial
patterns, with two or more electrodes, may provide an improvement
in specific somatic activation.
Conclusions: The use of spatial patterns of electrical stimulation
can, in some cases, increase the odds of evoking somatic activation
without axon activation. However, variability in the results points
to the need for a more systematic approach to spatially patterned
stimulation and axon avoidance.
Commercial Relationships: Lauren E. Grosberg, None;
Pawel Hottowy, None; Lauren H. Jepson, None; Shinya Ito,
None; Frederick Kellison-Linn, None; Alexander Sher, None;
Wladyslaw Dabrowski, None; Alan Litke, None; EJ Chichilnisky,
None
Support: This work was supported by NIH Grant 1F32EY025120
(LEG), NIH Grant R01EY021271 (EJC), Polish National Science
Centre grant 2013/10/M/NZ4/00268 (PH), BWF CASI (AS), NSF
Grant PHY-0750525 (AML), NIH Grant 5R21EB004410 (AML), and
the Polish Ministry of Science and Higher Education and its grants
for Scientific Research (WD).
©2015, Copyright by the Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Go to iovs.org to access the version of record. For permission
to reproduce any abstract, contact the ARVO Office at [email protected].