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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].