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Purpose: Extraocular electrical stimulation is known to provide neuroprotection for retinal cells in retinal and optic nerve diseases. Currently, the treatment approach requires patients to set up extraocular electrodes and stimulate potentially weekly due to the lack of an implantable stimulation device. Hence, a minimally-invasive implant was developed to provide chronic electrical stimulation to the retina, potentially improving patient compliance for long-term use. The aim of the present study was to determine the surgical and stimulation safety of this novel device designed for neuroprotective stimulation. Methods: Eight normally sighted adult feline subjects were monocularly implanted in the suprachoroidal space in the peripheral retina for 9--39 weeks. Charge balanced, biphasic, current pulses (100 μA, 500 µs pulse width and 50 pulses/s) were delivered continuously to platinum electrodes for 3--34 weeks. Electrode impedances were measured hourly. Retinal structure and function were assessed at 1-, 2-, 4-, 6- and 8-month using electroretinography, optical coherence tomography and fundus photography. Retina and fibrotic thickness were measured from histological sections. Randomized, blinded histopathological assessments of stimulated and non-stimulated retina were performed. Results: All subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. The device position was stable after a post-surgery settling period. Median electrode impedance remained within a consistent range (5-10 kΩ) over time. There was no change in retinal thickness or function relative to baseline and fellow eyes. Fibrotic capsule thickness was equivalent between stimulated and non-stimulated tissue and helps to hold the device in place. Therewas no scarring, insertion trauma, necrosis, retinal damage or fibroblastic response in any retinal samples from implanted eyes, whilst 19% had a minimal histiocytic response, 19% had minimal to mild acute inflammation and 28% had minimal to mild chronic inflammation. Conclusion: Chronic suprathreshold electrical stimulation of the retina using a minimally invasive device evoked a mild tissue response and no adverse clinical findings. Peripheral suprachoroidal electrical stimulation with an implanted device could potentially be an alternative approach to transcorneal electrical stimulation for delivering neuroprotective stimulation. [ABSTRACT FROM AUTHOR]

In this paper, we present a novel stimulation controller and monitoring system for evaluating the safety and efficacy of implantable neuroprosthetic devices in a preclinical setting. It features a programmable controller designed to be worn in a custom backpack by freely moving feline subjects. A custom controller powered two, modified, 22-channel clinical stimulators simultaneously. The controller and stimulators together weighed 140 g and measured 85 × 70 × 35 mm3. Power was supplied from a 3350 mAh lithium-ion battery. A Bluetooth-enabled laptop-PC base station managed up to six systems and allowed the remote adjustment of the stimulation amplitude and automated collection of stimulator telemetry data. The initial application was for the chronic safety testing of a 44-channel retinal prosthesis. Thirteen feline subjects were implanted with a suprachoroidal electrode array, which was then stimulated or monitored continuously for an average of 54.5 d. Batteries were changed twice weekly and electrode impedances were recorded hourly. This allowed broken electrodes and other issues to be quickly identified and addressed. The ability to remotely control the stimulation amplitude minimised the amount of subject handling that was required, likely reducing subject stress. Existing preclinical evaluation systems are either designed for short-term experiments and have many features but limited battery life, or for long-term static stimulation and are long-lived, but with restricted stimulation parameters and channel counts. Here, we have described a system designed to improve the chronic safety testing of electrode arrays. While it was used here with a suprachoroidal retinal implant, it could be readily adapted for other preclinical models requiring continuous, deterministic stimulation over a prolonged period. [ABSTRACT FROM AUTHOR]