Medical Bionics - Research Publications

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    Techniques for Processing Eyes Implanted with a Retinal Prosthesis for Localized Histopathological Analysis: Part 2 Epiretinal Implants with Retinal Tacks
    Nayagam, DAX ; Durmo, I ; McGowan, C ; Williams, RA ; Shepherd, RK (JOURNAL OF VISUALIZED EXPERIMENTS, 2015-02)
    Retinal prostheses for the treatment of certain forms of blindness are gaining traction in clinical trials around the world with commercial devices currently entering the market. In order to evaluate the safety of these devices, in preclinical studies, reliable techniques are needed. However, the hard metal components utilised in some retinal implants are not compatible with traditional histological processes, particularly in consideration for the delicate nature of the surrounding tissue. Here we describe techniques for assessing the health of the eye directly adjacent to a retinal implant secured epiretinally with a metal tack. Retinal prostheses feature electrode arrays in contact with eye tissue. The most commonly used location for implantation is the epiretinal location (posterior chamber of the eye), where the implant is secured to the retina with a metal tack that penetrates all the layers of the eye. Previous methods have not been able to assess the proximal ocular tissue with the tack in situ, due to the inability of traditional histological techniques to cut metal objects. Consequently, it has been difficult to assess localized damage, if present, caused by tack insertion. Therefore, we developed a technique for visualizing the tissue around a retinal tack and implant. We have modified an established technique, used for processing and visualizing hard bony tissue around a cochlear implant, for the soft delicate tissues of the eye. We orientated and embedded the fixed eye tissue, including the implant and retinal tack, in epoxy resin, to stabilise and protect the structure of the sample. Embedded samples were then ground, polished, stained, and imaged under various magnifications at incremental depths through the sample. This technique allowed the reliable assessment of eye tissue integrity and cytoarchitecture adjacent to the metal tack.
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    Development of a surgical procedure for implantation of a prototype suprachoroidal retinal prosthesis
    Saunders, AL ; Williams, CE ; Heriot, W ; Briggs, R ; Yeoh, J ; Nayagam, DAX ; McCombe, M ; Villalobos, J ; Burns, O ; Luu, CD ; Ayton, LN ; McPhedran, M ; Opie, NL ; McGowan, C ; Shepherd, RK ; Guymer, R ; Allen, PJ (WILEY, 2014)
    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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    First-in-Human Trial of a Novel Suprachoroidal Retinal Prosthesis
    Ayton, LN ; Blamey, PJ ; Guymer, RH ; Luu, CD ; Nayagam, DAX ; Sinclair, NC ; Shivdasani, MN ; Yeoh, J ; McCombe, MF ; Briggs, RJ ; Opie, NL ; Villalobos, J ; Dimitrov, PN ; Varsamidis, M ; Petoe, MA ; McCarthy, CD ; Walker, JG ; Barnes, N ; Burkitt, AN ; Williams, CE ; Shepherd, RK ; Allen, PJ ; Mori, K (PUBLIC LIBRARY SCIENCE, 2014-12-18)
    UNLABELLED: Retinal visual prostheses ("bionic eyes") have the potential to restore vision to blind or profoundly vision-impaired patients. The medical bionic technology used to design, manufacture and implant such prostheses is still in its relative infancy, with various technologies and surgical approaches being evaluated. We hypothesised that a suprachoroidal implant location (between the sclera and choroid of the eye) would provide significant surgical and safety benefits for patients, allowing them to maintain preoperative residual vision as well as gaining prosthetic vision input from the device. This report details the first-in-human Phase 1 trial to investigate the use of retinal implants in the suprachoroidal space in three human subjects with end-stage retinitis pigmentosa. The success of the suprachoroidal surgical approach and its associated safety benefits, coupled with twelve-month post-operative efficacy data, holds promise for the field of vision restoration. TRIAL REGISTRATION: Clinicaltrials.gov NCT01603576.
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    Effects of deafness and cochlear implant use on temporal response characteristics in cat primary auditory cortex
    Fallon, JB ; Shepherd, RK ; Nayagam, DAX ; Wise, AK ; Heifer, LF ; Landry, TG ; Irvine, DRF (ELSEVIER SCIENCE BV, 2014-09)
    We have previously shown that neonatal deafness of 7-13 months duration leads to loss of cochleotopy in the primary auditory cortex (AI) that can be reversed by cochlear implant use. Here we describe the effects of a similar duration of deafness and cochlear implant use on temporal processing. Specifically, we compared the temporal resolution of neurons in AI of young adult normal-hearing cats that were acutely deafened and implanted immediately prior to recording with that in three groups of neonatally deafened cats. One group of neonatally deafened cats received no chronic stimulation. The other two groups received up to 8 months of either low- or high-rate (50 or 500 pulses per second per electrode, respectively) stimulation from a clinical cochlear implant, initiated at 10 weeks of age. Deafness of 7-13 months duration had no effect on the duration of post-onset response suppression, latency, latency jitter, or the stimulus repetition rate at which units responded maximally (best repetition rate), but resulted in a statistically significant reduction in the ability of units to respond to every stimulus in a train (maximum following rate). None of the temporal response characteristics of the low-rate group differed from those in acutely deafened controls. In contrast, high-rate stimulation had diverse effects: it resulted in decreased suppression duration, longer latency and greater jitter relative to all other groups, and an increase in best repetition rate and cut-off rate relative to acutely deafened controls. The minimal effects of moderate-duration deafness on temporal processing in the present study are in contrast to its previously-reported pronounced effects on cochleotopy. Much longer periods of deafness have been reported to result in significant changes in temporal processing, in accord with the fact that duration of deafness is a major factor influencing outcome in human cochlear implantees.
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    A Wide-Field Suprachoroidal Retinal Prosthesis Is Stable and Well Tolerated Following Chronic Implantation
    Villalobos, J ; Nayagam, DAX ; Allen, PJ ; McKelvie, P ; Luu, CD ; Ayton, LN ; Freemantle, AL ; McPhedran, M ; Basa, M ; McGowan, CC ; Shepherd, RK ; Williams, CE (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2013-05)
    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.
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    Visual prostheses for the blind
    Shepherd, RK ; Shivdasani, MN ; Nayagam, DAX ; Williams, CE ; Blamey, PJ (ELSEVIER SCIENCE LONDON, 2013-10)
    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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    Cortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis
    Villalobos, J ; Fallon, JB ; Nayagam, DAX ; Shivdasani, MN ; Luu, CD ; Allen, PJ ; Shepherd, RK ; Williams, CE (IOP PUBLISHING LTD, 2014-08)
    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.