PurposeTo assess the safety and efficacy of chronic electrical stimulation of the retina with a suprachoroidal visual prosthesis.MethodsSeven normally-sighted feline subjects were implanted for 96–143 days with a suprachoroidal electrode array and six were chronically stimulated for 70–105 days at levels that activated the visual cortex. Charge balanced, biphasic, current pulses were delivered to platinum electrodes in a monopolar stimulation mode. Retinal integrity/function and the mechanical stability of the implant were assessed monthly using electroretinography (ERG), optical coherence tomography (OCT) and fundus photography. Electrode impedances were measured weekly and electrically-evoked visual cortex potentials (eEVCPs) were measured monthly to verify that chronic stimuli were suprathreshold. At the end of the chronic stimulation period, thresholds were confirmed with multi-unit recordings from the visual cortex. Randomized, blinded histological assessments were performed by two pathologists to compare the stimulated and non-stimulated retina and adjacent tissue.ResultsAll subjects tolerated the surgical and stimulation procedure with no evidence of discomfort or unexpected adverse outcomes. After an initial post-operative settling period, electrode arrays were mechanically stable. Mean electrode impedances were stable between 11–15 kΩ during the implantation period. Visually-evoked ERGs & OCT were normal, and mean eEVCP thresholds did not substantially differ over time. In 81 of 84 electrode-adjacent tissue samples examined, there were no discernible histopathological differences between stimulated and unstimulated tissue. In the remaining three tissue samples there were minor focal fibroblastic and acute inflammatory responses.ConclusionsChronic suprathreshold electrical stimulation of the retina using a suprachoroidal electrode array evoked a minimal tissue response and no adverse clinical or histological findings. Moreover, thresholds and electrode impedance remained stable for stimulation durations of up to 15 weeks. This study has demonstrated the safety and efficacy of suprachoroidal stimulation with charge balanced stimulus currents.

Citation: Spencer TC, Fallon JB, Thien PC, Shivdasani MN. Spatial restriction of neural activation using focused multipolar stimulation with a retinal prosthesis. Invest Ophthalmol Vis Sci. 2016;57:3181-3191. DOI:10.1167/ iovs.16-19325 PURPOSE. The resolution provided by present state-of-the-art retinal prostheses is severely limiting for recipients, partly due to the broad spread of activation in the retina in response to monopolar (MP) electrical stimulation. Focused multipolar (FMP) stimulation has been shown to restrict neural activation in the cochlea compared to MP stimulation. We extended the FMP stimulation technique to a two-dimensional electrode array and compared its efficacy to MP and hexapolar (HP) stimulation in the retina.METHODS. Normally-sighted cats (n ¼ 6) were implanted with a suprachoroidal electrode array containing 42 electrodes. Multichannel multiunit spiking activity was recorded from the visual cortex in response to MP, HP, and FMP retinal stimulation.RESULTS. When inferring retinal spread using voltage recordings off the stimulating array, FMP stimulation showed significantly reduced voltages in regions surrounding the primary stimulating electrode. When measuring the retinal and cortical selectivity of neural responses, FMP and HP stimulation showed significantly higher selectivity compared to MP stimulation (separate 2-way ANOVAs, P < 0.05). However, the lowest cortical thresholds for each stimulating electrode were higher for FMP and HP compared to MP stimulation (1-way ANOVA, P < 0.001). No significant differences were observed between FMP and HP stimulation in any measures.CONCLUSIONS. Focused multipolar and HP stimulation using a two-dimensional array are promising techniques to reduce the spread of activation for a retinal prosthesis. Clinical application would be expected to result in smaller phosphenes; thus, reducing phosphene overlap between electrodes and increasing the resolution at the expense of higher thresholds for activation.

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 limitations (anatomic differences) with the feline model.

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 mm 3 . 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.