Browsing by Author "Williams, Chris"

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    An automated system for rapid evaluation of high-density electrode arrays in neural prostheses
    (Institute of Physics, 2011-06) John, Sam; Shivdasani, Mohit; Leuenberger, James; Fallon, James; Shepherd, Robert; Millard, Rodney; Rathbone, Graeme; Williams, Chris
    The success of high density electrode arrays for use in neural prostheses depends on efficient impedance monitoring and fault detection. Conventional methods of impedance testing and fault detection are time consuming and are not always suited for in-vivo assessment of high density electrode arrays. Additionally the ability to evaluate impedances and faults such as open and short circuits both, in-vitro and in-vivo are important to ensure safe and effective stimulation. In the present work we describe an automated system for the rapid evaluation of high density electrode arrays. The system uses a current pulse similar to that used to stimulate neural tissue and measures the voltage across the electrode in order to calculate the impedance. The switching of the system was validated by emulating a high density electrode array using light emitting diodes and a resistor- capacitor network. The system was tested in-vitro and in-vivo using a range of commercially available and in-house developed electrode arrays. The system accurately identified faults on an 84 electrode array in less than 20 seconds and reliably measured impedances up to 110 kn using a 200µA, 250 µs per phase current pulse. This system has direct application for screening high density electrode arrays in both a clinical and experimental setting.
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    Biocompatibility of Immobilized Aligned Carbon Nanotubes
    (Wiley, 2011) Nayagam, David; Williams, Richard; Chen, Jun; Magee, Kylie; Irwin, Jennifer; Tan, Justin; Innis, Peter; Leung, Ronald; Finch, Sue; Williams, Chris; Clark, Graeme; Wallace, Gordon
    In vivo host responses to an electrode-like array of aligned carbon nanotubes (ACNTs) embedded within a biopolymer sheet are reported. This biocompatibility study assesses the suitability of immobilized carbon nanotubes for bionic devices. Inflammatory responses and foreign-body histiocytic reactions are not substantially elevated when compared to negative controls following 12 weeks implantation. A fibrous capsule isolates the implanted ACNTs from the surrounding muscle tissue. Filamentous nanotube fragments are engulfed by macrophages, and globular debris is incorporated into the fibrous capsule with no further reaction. Scattered leukocytes are observed, adherent to the ACNT surface. These data indicate that there is a minimal local foreign-body response to immobilized ACNTs, that detached fragments are phagocytosed into an inert material, and that ACNTs do not attract high levels of surface fouling. Collectively, these results suggest that immobilized nanotube structures should be considered for further investigation as bionic components.
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    Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis
    (IOP Publishing, 2014-06) Villalobos, Joel; Fallon, James; Nayagam, David; Shivdasani, Mohit; Luu, Chi; Allen, Penelope; Shepherd, Robert; Williams, Chris
    OBJECTIVE: The research goal is to develop a wide-field retinal stimulating array for prosthetic vision. This study aimed at evaluating the efficacy of a suprachoroidal electrode array in evoking visual cortex activity after long term implantation. APPROACH: A planar silicone based electrode array (8 mm × 19 mm) was implanted into the suprachoroidal space in cats (ntotal = 10). It consisted of 20 platinum stimulating electrodes (600 μm diameter) and a trans-scleral cable terminated in a subcutaneous connector. Three months after implantation (nchronic = 6), or immediately after implantation (nacute = 4), an electrophysiological study was performed. Electrode total impedance was measured from voltage transients using 500 μs, 1 mA pulses. Electrically evoked potentials (EEPs) and multi-unit activity were recorded from the visual cortex in response to monopolar retinal stimulation. Dynamic range and cortical activation spread were calculated from the multi-unit recordings. MAIN RESULTS: The mean electrode total impedance in vivo following 3 months was 12.5 ± 0.3 kΩ. EEPs were recorded for 98% of the electrodes. The median evoked potential threshold was 150 nC (charge density 53 μC cm(-2)). The lowest stimulation thresholds were found proximal to the area centralis. Mean thresholds from multiunit activity were lower for chronic (181 ± 14 nC) compared to acute (322 ± 20 nC) electrodes (P < 0.001), but there was no difference in dynamic range or cortical activation spread. SIGNIFICANCE: Suprachoroidal stimulation threshold was lower in chronic than acute implantation and was within safe charge limits for platinum. Electrode-tissue impedance following chronic implantation was higher, indicating the need for sufficient compliance voltage (e.g. 12.8 V for mean impedance, threshold and dynamic range). The wide-field suprachoroidal array reliably activated the retina after chronic implantation.
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    Development of a surgical procedure for implantation of a prototype suprachoroidal retinal prosthesis
    (John Wiley & Sons Inc, 2014-09) Saunders, Alexia; Williams, Chris; Heriot, Wilson; Briggs, Robert; Yeoh, Jonathan; Nayagam, David; McCombe, Mark; Villalobos, Joel; Burns, Owen; Luu, Chi; Ayton, Lauren; McPhedran, Michelle; Opie, Nicholas; McGowan, Ceara; Shepherd, Robert; Guymer, Robyn; Allen, Penelope
    BACKGROUND: Current surgical techniques for retinal prosthetic implantation require long and complicated surgery, which can increase the risk of complications and adverse outcomes. METHOD: The suprachoroidal position is known to be an easier location to access surgically, and so this study aimed to develop a surgical procedure for implanting a prototype suprachoroidal retinal prosthesis. The array implantation procedure was developed in 14 enucleated eyes. A full-thickness scleral incision was made parallel to the intermuscular septum and superotemporal to the lateral rectus muscle. A pocket was created in the suprachoroidal space, and the moulded electrode array was inserted. The scleral incision was closed and scleral anchor point sutured. In 9 of the 14 eyes examined, the device insertion was obstructed by the posterior ciliary neurovascular bundle. Subsequently, the position of this neurovascular bundle in 10 eyes was characterized. Implantation and lead routing procedure was then developed in six human cadavers. The array was tunnelled forward from behind the pinna to the orbit. Next, a lateral canthotomy was made. Lead fixation was established by creating an orbitotomy drilled in the frontal process of the zygomatic bone. The lateral rectus muscle was detached, and implantation was carried out. Finally, pinna to lateral canthus measurements were taken on 61 patients in order to determine optimal lead length. RESULTS: These results identified potential anatomical obstructions and informed the anatomical fitting of the suprachoroidal retinal prosthesis. CONCLUSION: As a result of this work, a straightforward surgical approach for accurate anatomical suprachoroidal array and lead placement was developed for clinical application.
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    Evaluation of stimulus parameters and electrode geometry for an effective suprachoroidal retinal prosthesis
    (IOP Publishing Ltd, 2010) Shivdasani, Mohit; Luu, Chi; Cicione, Rosemary; Fallon, James; Allen, Penny; Leuenberger, James; Suaning, Gregg; Lovell, Nigel; Shepherd, Robert; Williams, Chris
    Several approaches have been proposed for placement of retinal prostheses; epiretinal, sub-retinal, and suprachoroidal. We aimed to systematically evaluate the effectiveness of varying a range of stimulus parameters and electrode geometry for a suprachoroidal electrode array, using cortical evoked responses to monopolar electrical stimulation in cats. Our results indicate that charge thresholds were not dependent on electrode size, pulse widths or position of the return electrode tested, but were dependent on the number of sites stimulated in parallel. Further, we found that the combination of monopolar stimulation with large diameter electrodes, wide pulse widths and parallel stimulation minimized the voltage requirements for stimulation. These results provide useful insights for the design specifications of a low voltage suprachoroidal stimulator.
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    In Vivo Feasibility of Epiretinal Stimulation Using Ultrananocrystalline Diamond 1 Electrodes
    (IOP Publishing, 2020-07) Shivdasani, Mohit; Evans, Mihailo; Burns, Owen; Yeoh, Jonathon; Allen, Penelope; Nayagam, David; Villalobos, Joel; Abbott, Carla; Luu, Chi; Opie, Nicholas; Sabu, Anu; Saunders, Alexia; McPhedran, Michelle; Cardamone, Lisa; McGowan, Ceara; Maxim, Vanessa; Williams, Richard; Fox, Kate; Cicione, Rosemary; Garrett, David; Ahnood, Arman; Ganesan, Kumaravelu; Meffin, Hamish; Burkitt, Anthony; Prawer, Steven; Williams, Chris; Shepherd, Robert
    PURPOSE: Due to their increased proximity to retinal ganglion cells (RGCs), epiretinal visual prostheses present the opportunity for eliciting phosphenes with low thresholds through direct RGC activation. This study characterised the in vivo performance of a novel prototype monolithic epiretinal prosthesis, containing Nitrogen incorporated ultrananocrystalline (N-UNCD) diamond electrodes. METHODS: A prototype implant containing up to twenty-five 120×120 µm N-UNCD electrodes was implanted into 16 anaesthetised cats and attached to the retina either using a single tack or via magnetic coupling with a suprachoroidally placed magnet. Multiunit responses to retinal stimulation using charge-balanced biphasic current pulses were recorded acutely in the visual cortex using a multichannel planar array. Several stimulus parameters were varied including; the stimulating electrode, stimulus polarity, phase duration, return configuration and the number of electrodes stimulated simultaneously. RESULTS: The rigid nature of the device and its form factor necessitated complex surgical procedures. Surgeries were considered successful in 10/16 animals and cortical responses to single electrode stimulation obtained in 8 animals. Clinical imaging and histological outcomes showed severe retinal trauma caused by the device in-situ in many instances. Cortical measures were found to significantly depend on the surgical outcomes of individual experiments, phase duration, return configuration and the number of electrodes stimulated simultaneously, but not stimulus polarity. Cortical thresholds were also found to increase over time within an experiment. CONCLUSIONS: The study successfully demonstrated that an epiretinal prosthesis containing diamond electrodes could produce cortical activity with high precision, albeit only in a small number of cases. Both surgical approaches were highly challenging in terms of reliable and consistent attachment to and stabilisation against the retina, and often resulted in severe retinal trauma. There are key challenges (device form factor and attachment technique) to be resolved for such a device to progress towards clinical application, as current surgical techniques are unable to address these issues.
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    Oculomotor Responses to Dynamic Stimuli in a 44-Channel Suprachoroidal Retinal Prosthesis
    (tvst, 2020-12) Titchener, Samuel; Kvansakul, Jessica; Shivdasani, Mohit; Nayagam, David; Epp, Stephanie; Williams, Chris; Barnes, Nick; Kentler, William; Kolic, Maria; Balin, Elizabeth; Ayton, Lauren; Abbott, Carla; Luu, Chi; Allen, Penelope; Petoe, Matthew
    PURPOSE: To investigate oculomotor behavior in response to dynamic stimuli in retinal implant recipients. METHODS: Three suprachoroidal retinal implant recipients performed a four-alternative forced-choice motion discrimination task over six sessions longitudinally. Stimuli were a single white bar ("moving bar") or a series of white bars ("moving grating") sweeping left, right, up, or down across a 42″ monitor. Performance was compared with normal video processing and scrambled video processing (randomized image-to-electrode mapping to disrupt spatiotemporal structure). Eye and head movement was monitored throughout the task. RESULTS: Two subjects had diminished performance with scrambling, suggesting retinotopic discrimination was used in the normal condition and made smooth pursuit eye movements congruent to the moving bar stimulus direction. These two subjects also made stimulus-related eye movements resembling optokinetic reflex (OKR) for moving grating stimuli, but the movement was incongruent with stimulus direction. The third subject was less adept at the task, appeared primarily reliant on head position cues (head movements were congruent to stimulus direction), and did not exhibit retinotopic discrimination and associated eye movements. CONCLUSIONS: Our observation of smooth pursuit indicates residual functionality of cortical direction-selective circuits and implies a more naturalistic perception of motion than expected. A distorted OKR implies improper functionality of retinal direction-selective circuits, possibly due to retinal remodeling or the non-selective nature of the electrical stimulation. TRANSLATIONAL RELEVANCE: Retinal implant users can make naturalistic eye movements in response to moving stimuli, highlighting the potential for eye tracker feedback to improve perceptual localization and image stabilization in camera-based visual prostheses.
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    Ring and peg electrodes for minimally-Invasive and long-term sub-scalp EEG recordings
    (Elsevier, Ltd., 2017-06) Benovitski, Yuri; Lai, Alan; McGowan, Ceara; Burns, Owen; Maxim, Vanessa; Nayagam, David; Millard, Rodney; Rathbone, Graeme; le Chevoir, M.A.; Williams, R.A.; Grayden, David; May, C.N.; Murphy, M.; D'Souza, Wendyl; Cook, Mark; Williams, Chris
    OBJECTIVE: Minimally-invasive approaches are needed for long-term reliable Electroencephalography (EEG) recordings to assist with epilepsy diagnosis, investigation and more naturalistic monitoring. This study compared three methods for long-term implantation of sub-scalp EEG electrodes. METHODS: Three types of electrodes (disk, ring, and peg) were fabricated from biocompatible materials and implanted under the scalp in five ambulatory ewes for 3months. Disk electrodes were inserted into sub-pericranial pockets. Ring electrodes were tunneled under the scalp. Peg electrodes were inserted into the skull, close to the dura. EEG was continuously monitored wirelessly. High resolution CT imaging, histopathology, and impedance measurements were used to assess the status of the electrodes at the end of the study. RESULTS: EEG amplitude was larger in the peg compared with the disk and ring electrodes (p<0.05). Similarly, chewing artifacts were lower in the peg electrodes (p<0.05). Electrode impedance increased after long-term implantation particularly for those within the bone (p<0.01). Micro-CT scans indicated that all electrodes stayed within the sub-scalp layers. All pegs remained within the burr holes as implanted with no evidence of extrusion. Eight of 10 disks partially eroded into the bone by 1.0mm from the surface of the skull. The ring arrays remained within the sub-scalp layers close to implantation site. Histology revealed that the electrodes were encapsulated in a thin fibrous tissue adjacent to the pericranium. Overlying this was a loose connective layer and scalp. Erosion into the bone occurred under the rim of the sub-pericranial disk electrodes. CONCLUSIONS: The results indicate that the peg electrodes provided high quality EEG, mechanical stability, and lower chewing artifact. Whereas, ring electrode arrays tunneled under the scalp enable minimal surgical techniques to be used for implantation and removal.
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    Safety and efficacy of explanting or replacing suprachoroidal electrode arrays in a feline model
    (John Wiley and Sons, 2015-04) Leung, Ronald; Nayagam, David; Williams, Richard; Allen, Penelope; Salinas-La Rosa, Cesar; Shivdasani, Mohit; Ayton, Lauren; Basa, Meri; Yeoh, Jonathan; Saunders, Alexia; Shepherd, Robert; Williams, Chris
    BACKGROUND: A key requirement for retinal prostheses is the ability for safe removal or replacement. We examined whether suprachoroidal electrode arrays can be removed or replaced after implantation. METHODS: Suprachoroidal electrode arrays were unilaterally implanted into 13 adult felines. After 1 month, arrays were surgically explanted (n = 6), replaced (n = 5) or undisturbed (n = 2). The retina was assessed periodically using fundus photography and optical coherence tomography. Three months after the initial implantation, the function of replaced or undisturbed arrays was assessed by measuring the responses of the visual cortex to retinal electrical stimulation. The histopathology of tissues surrounding the implant was examined. RESULTS: Array explantation or replacement was successful in all cases. Fundus photography showed localized disruption to the tapetum lucidum near the implant's tip in seven subjects following implantation. Although optical coherence tomography showed localized retinal changes, there were no widespread statistically significant differences in the thickness of the retinal layers or choroid. The distance between the electrodes and retina increased after device replacement but returned to control values within eight weeks (P < 0.03). Staphylomas developed near the scleral wound in five animals after device explantation. Device replacement did not alter the cortical evoked potential threshold. Histopathology showed localized outer nuclear layer thinning, tapetal disruption and pseudo-rosette formation, but the overall retinal morphology was preserved. CONCLUSIONS: It is feasible to remove or replace conformable medical grade silicone electrode arrays implanted suprachoroidally. The scleral wound requires careful closure to minimize the risk of staphylomas.
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    Safety Studies for a 44-Channel Suprachoroidal Retinal Prosthesis: A Chronic Passive Study
    (IOVS, 2018-03) Abbott, Carla; Nayagam, David; Luu, Chi; Epp, Stephanie; Williams, Richard; Salinas-LaRosa, Cesar; Villalobos, Joel; McGowan, Ceara; Shivdasani, Mohit; Burns, Owen; Leavens, Jason; Yeoh, Jonathon; Brandli, Alice; Thien, Patrick; Zhou, Jenny; Feng, Helen; Williams, Chris; Shepherd, Robert; Allen, Penelope
    Abstract Purpose: Following successful clinical outcomes of the prototype suprachoroidal retinal prosthesis, Bionic Vision Australia has developed an upgraded 44-channel suprachoroidal retinal prosthesis to provide a wider field of view and more phosphenes. The aim was to evaluate the preclinical passive safety characteristics of the upgraded electrode array. Methods: Ten normal-sighted felines were unilaterally implanted with an array containing platinum electrodes (44 stimulating and 2 returns) on a silicone carrier near the area centralis. Clinical assessments (color fundus photos, optical coherence tomography, full-field electroretinography, intraocular pressure) were performed under anesthesia prior to surgery, and longitudinally for up to 20 weeks. Histopathology grading of fibrosis and inflammation was performed in two animals at 13 to 15 weeks. Results: Eight animals showed safe electrode array insertion (good retinal health) and good conformability of the array to the retinal curvature. Eight animals demonstrated good mechanical stability of the array with only minor (<2 disc diameters) lateral movement. Four cases of surgical or stability complications occurred due to (1) bulged choroid during surgery, (2) hemorrhage from a systemic bleeding disorder, (3) infection, and (4) partial erosion of thin posterior sclera. There was no change in retinal structure or function (other than that seen at surgery) at endpoint. Histopathology showed a mild foreign body response. Electrodes were intact on electrode array removal. Conclusions: The 44-channel suprachoroidal electrode array has an acceptable passive safety profile to proceed to clinical trial. The safety profile is expected to improve in human studies, as the complications seen are specific to imitations (anatomic differences) with the feline model.
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    Spatiotemporal interactions in the visual cortex following paired electrical stimulation of the retina
    (The Association for Research in Vision and Ophthalmology Inc., 2014-11) Cicione, Rosemary; Fallon, James; Rathbone, Graeme; Williams, Chris; Shivdasani, Mohit
    PURPOSE: Retinal prostheses use spatiotemporal patterns of electrical stimulation across multiple electrodes to provide visual percepts to blind patients. It is generally assumed that percepts produced by individual electrodes are independent of one another, which may not be the case. In this study, we aimed to quantify interactions between pairs of electrical stimuli delivered to the retina. METHODS: Normally sighted cats were implanted with a suprachoroidal electrode array. The retina was stimulated with a paired-pulse paradigm that consisted of a conditioning stimulus followed by a test stimulus, while recording multiunit activity in the visual cortex. Conditioning current, and spatial and temporal separation between the conditioning and test stimuli were varied. Cortical interactions were quantified by changes in multiunit activity elicited by stimulation with the paired-pulse paradigm, compared to stimulation of the test stimulus alone (control). RESULTS: Interactions varied as a function of conditioning current and temporal separation between the two stimulating pulses. Cortical activity increased compared to the control condition at an interstimulus delay of 1.025 ms and was significantly suppressed for delays between 20 and 90 ms, returning to near control levels for longer delays. The level of interactions increased when the conditioning current was increased. Interactions were found to be similar for electrode separations up to 3 mm. CONCLUSIONS: Interactions between sequential stimulation of pairs of electrodes in a suprachoroidal retinal prosthesis occur for delays up to 100 ms and electrode separations of several millimeters. Knowledge of these spatiotemporal interactions is essential for developing effective patterns of stimulation for retinal prostheses.
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    Suprachoroidal electrical stimulation: Effects of stimulus pulse parameters on visual cortical responses
    (IOPscience, 2013-10) John, Sam; Shivdasani, Mohit; Williams, Chris; Morley, John; Shepherd, Robert; Rathbone, Graeme; Fallon, James
    Objective. Neural responses to biphasic constant current pulses depend on stimulus pulse parameters such as polarity, duration, amplitude and interphase gap. The objective of this study was to systematically evaluate and optimize stimulus pulse parameters for a suprachoroidal retinal prosthesis. Approach. Normally sighted cats were acutely implanted with platinum electrode arrays in the suprachoroidal space. Monopolar stimulation comprised of monophasic and biphasic constant current pulses with varying polarity, pulse duration and interphase gap. Multiunit responses to electrical stimulation were recorded in the visual cortex. Main results. Anodal stimulation elicited cortical responses with shorter latencies and required lower charge per phase than cathodal stimulation. Clinically relevant retinal stimulation required relatively larger charge per phase compared with other neural prostheses. Increasing the interphase gap of biphasic pulses reduced the threshold of activation; however, the benefits of using an interphase gap need to be considered in light of the pulse duration and polarity used and other stimulation constraints. Based on our results, anodal first biphasic pulses between 300–1200 µs are recommended for suprachoroidal retinal stimulation. Significance. These results provide insights into the efficacy of different pulse parameters for suprachoroidal retinal stimulation and have implications for the design of safe and clinically relevant stimulators for retinal prostheses.
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    Techniques for Processing Eyes Implanted With a Retinal Prosthesis for Localized Histopathological Analysis.
    (JoVE Corp, 2013-02) Nayagam, David; McGowan, Ceara; Villalobos, Joel; Williams, Richard; Salinas-La Rosa, Cesar; McKelvie, Penelope; Lo, Irene; Basa, Meri; Tan, Justin; Williams, Chris
    With the recent development of retinal prostheses, it is important to develop reliable techniques for assessing the safety of these devices in preclinical studies. However, the standard fixation, preparation, and automated histology procedures are not ideal. Here we describe new procedures for evaluating the health of the retina directly adjacent to an implant. Retinal prostheses feature electrode arrays in contact with eye tissue. Previous methods have not been able to spatially localize the ocular tissue adjacent to individual electrodes within the array. In addition, standard histological processing often results in gross artifactual detachment of the retinal layers when assessing implanted eyes. Consequently, it has been difficult to assess localized damage, if present, caused by implantation and stimulation of an implanted electrode array. Therefore, we developed a method for identifying and localizing the ocular tissue adjacent to implanted electrodes using a (color-coded) dye marking scheme, and we modified an eye fixation technique to minimize artifactual retinal detachment. This method also rendered the sclera translucent, enabling localization of individual electrodes and specific parts of an implant. Finally, we used a matched control to increase the power of the histopathological assessments. In summary, this method enables reliable and efficient discrimination and assessment of the retinal cytoarchitecture in an implanted eye.
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    Virtual electrodes by current steering in retinal prostheses
    (ARVO, 2014) Dumm, Gerald; Fallon, James; Williams, Chris; Shivdasani, Mohit
    PURPOSE:Retinal prostheses are an approved treatment for vision restoration in retinal degenerative diseases; however, present implants have limited resolution and simply increasing the number of electrodes is limited by design issues. In cochlear implants, virtual electrodes can be created by simultaneous stimulation of adjacent physical electrodes (current steering). The present study assessed whether this type of current steering can be adapted for retinal implants. METHODS:Suprachoroidal electrode arrays were implanted in four normally sighted cat eyes. Electrode pairs were driven simultaneously at different current levels and current ratios. Multiunit spiking activity in the visual cortex was recorded. Spike distribution across channels enabled generation of cortical activation maps and calculation of centroid positions. For each current configuration, centroid shifts between two virtual electrodes were compared to shifts obtained from physical electrode stimulation. RESULTS:Using current steering, virtual electrodes with different cortical activation maps could be created. Cortical centroids were found to shift as a function of the current ratio used for virtual electrodes and were similar to the centroid shifts seen when using physical electrodes. In addition, the cortical response to stimulation of a physical electrode could be reproduced by applying current steering to electrodes on either side of the physical electrode. CONCLUSIONS:These results suggest that current steering can alter activation patterns in the visual cortex and could enhance visual perception in retinal implants by eliciting phosphene percepts intermediate between those elicited by physical electrodes. These results inform development of new electrode arrays that can take advantage of current steering.
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    Visual Cortex Responses to Single-and Simultaneous Multiple-Electrode Stimulation of the Retina: Implications for Retinal Prostheses
    (The Association for Research in Vision and Ophthalmology, 2012) Shivdasani, Mohit; Fallon, James; Luu, Chi; Cicione, Rosemary; Allen, Penny; Morley, John; Williams, Chris
    Purpose: The aim of this study was to compare simultaneous stimulation of multiple electrodes to single electrode stimulation in a retinal prosthesis. Methods: A platinum electrode array was implanted into the suprachoroidal space in six normally-sighted anesthetized cats. Multi-unit activity from the primary visual cortex in response to retinal stimulation was recorded. Cortical thresholds, yield of responses, dynamic ranges, and the spread of retinal activation were measured for three modes of stimulation; single electrode, half-row (6-electrode horizontal line) and column (7-electrode vertical line). Results: Stimulation of the best half-rows and columns was found to elicit activity with higher yield and lower charge thresholds per electrode compared to the best single electrodes. Dynamic ranges between the three modes were similar. As expected, peak voltages measured for columns and half-rows were lower than those measured for single electrodes. Spread of retinal activation, determined by the increase in threshold with distance in the retina from the best site was found to be similar between single and multiple electrode stimulation but dependent on orientation. Conclusions: The lower thresholds, higher yield, equivalent dynamic ranges and equivalent spread of retinal activation observed from simultaneous stimulation of multiple electrodes may be due to current and/or neural summation within the retina. Such stimulation techniques could be useful for the presentation of lines and edges of objects using a suprachoroidal retinal stimulator with low voltage compliance. Furthermore, the results suggest more complex visual processing strategies in addition to sequential stimulation of individual electrodes should be considered for retinal prostheses.
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    Visual cortex responses to suprachoroidal electrical stimulation of the retina: effects of electrode return configuration
    (IOP Publishing Ltd, 2012) Cicione, Rosemary; Shivdasani, Mohit; Fallon, James; Luu, Chi; Allen, Penny; Rathbone, Graeme; Shepherd, Robert; Williams, Chris
    A clinically effective retinal prosthesis must evoke localized phosphenes in a retinotopic manner in response to stimulation of each of the retinal electrodes, evoke brightness cues over a wide dynamic range and function within safe stimulus limits. The effects of varying return configuration for retinal stimulation are currently unknown. To investigate this, we implanted a flexible, 7x12 electrode array into the suprachoroidal space of normally-sighted, anesthetized cats. Multi-unit activity in the primary visual cortex was recorded in response to electrical stimulation using various return configurations: monopolar vitreous (MPV), common ground (CG), hexagonal (HX), monopolar remote (MPR) and bipolar (BP_N). MPV stimulation was found to be the most charge efficient and was most likely to induce cortical activity within safe charge limits. HX and CG stimulation were found to exhibit greater retinal selectivity compared to the MPV return at the expense of lower cortical yield and higher P50 charge levels, while cortical selectivity was unaffected by choice of return. Responses using MPR and widely spaced BP_N configurations were similar to those using the MPV return. These results suggest that choice of return configuration for a retinal prosthesis will be balanced between resolution and stimulation within safe charge limits.
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    Visual prostheses for the blind.
    (Elsevier, 2013-01) Shepherd, Robert; Shivdasani, Mohit; Nayagam, David; Williams, Chris; Blamey, Peter
    After more than 40 years of research visual prostheses are moving from the laboratory into the clinic. These devices are designed to provide prosthetic vision to the blind by stimulating localized neural populations in one of the retinotopically organized structures of the visual pathway - typically the retina or visual cortex. The long gestation of this research reflects the many significant technical challenges encountered including surgical access, mechanical stability, hardware miniaturization, hermetic encapsulation, high density electrode arrays and signal processing. This review provides an introduction to the pathophysiology of blindness; an overview of existing visual prostheses, their advantages and drawbacks; the perceptual effects evoked by electrical stimulation, as well as the role played by plasticity and training in clinical outcomes.
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    A wide-field suprachoroidal retinal prosthesis is stable and well tolerated following chronic implantation
    (Association For Research In Vision And Ophthalmology (ARVO), 2013-04) Villalobos, Joel; Nayagam, David; Allen, Penelope; McKelvie, Penelope; Luu, Chi; Ayton, Lauren; Freemantle, Alexia; McPhedran, Michelle; Basa, Meri; McGowan, Ceara; Shepherd, Robert; Williams, Chris
    Purpose. The safety of chronic implantation of a retinal prosthesis in the suprachoroidal space has not been established. This study aimed to determine the safety of a wide-field suprachoroidal electrode array following chronic implantation using histopathologic techniques and electroretinography. Methods. A platinum electrode array in a wide silicone substrate was implanted unilaterally in the suprachoroidal space in adult cats (n = 7). The lead and connector were tunneled out of the orbit and positioned subcutaneously. Postsurgical recovery was assessed using fundus photography and electroretinography (ERG). Following 3 months of passive implantation, the animals were terminated and the eyes assessed for the pathologic response to implantation. Results. The implant was mechanically stable in the suprachoroidal space during the course of the study. The implanted eye showed a transient increase in ERG response amplitude at 2 weeks, which returned to normal by 3 months. Pigmentary changes were observed at the distal end of the implant, near the optic disc. Histopathologic assessment revealed a largely intact retina and a thin fibrous capsule around the suprachoroidal implant cavity. The foreign body response was minimal, with sporadic presence of macrophages and no active inflammation. All implanted eyes were negative for bacterial or fungal infections. A midgrade granuloma and thick fibrous buildup surrounded the extraocular cable. Scleral closure was maintained in six of seven eyes. There were no staphylomas or choroidal incarceration. Conclusions. A wide-field retinal prosthesis was stable and well tolerated during long-term suprachoroidal implantation in a cat model. The surgical approach was reproducible and overall safe