Improved visual acuity using a retinal implant and an optimized stimulation strategy

Abstract

Objective. Retinal prosthetic devices hold great promise for the treatment of retinal degenerative diseases such as retinitis pigmentosa and age-related macular degeneration. Through electrical stimulation of the surviving retinal neurons, these devices evoke visual signals that are then relayed to the brain. Currently, the visual prostheses used in clinical trials have few electrodes, thus limiting visual acuity. Electrode arrays with high electrode densities have been developed using novel technologies, including diamond growth and laser machining, and these may provide a more promising route to achieve high visual acuity in blind patients. Approach. Here, we studied the potential spatial resolution of electrical stimulation using diamond electrodes. We did this by labeling retinal ganglion cells in whole mount retina with a calcium indicator in wild-type rats and those with retinal degeneration. We imaged the ganglion cell responses to a range of stimulation parameters, including pulse duration and return electrode configuration. Main results. With sub-retinal stimulation, in which electrodes were in contact with the intact or degenerated photoreceptor layer, we found that biphasic pulses of 0.1 ms phase duration and a local return configuration was the most effective in confining the retinal ganglion cell activation patterns, while also remaining within the safety limits of the materials and providing the best power efficiency. Significance. These results provide an optimized stimulation strategy for retinal implants, which if implemented in a retinal prosthetic is expected to improve the achievable visual acuity.

Stimulation Strategies for Improving the Resolution of Retinal Prostheses

“…Both simulation and experimental results also indicate that more charge or current will be required for neural stimulation when using local returns, due to the decrease of electric field intensity (Tong et al, 2019a). The elevated thresholds will lead to larger power consumption and a greater charge requirement for the electrodes.…”

“…Multicell bolus loading (Borghuis et al, 2011) using membrane permeable indicators was reported but uniform staining was difficult. Other methods that successfully stained RGCs in mammalian retinas include electroporation (Baden et al, 2016), dye incubation after dissolving the ILMs (Cameron et al, 2016), direct dye injection into the optic nerve (Tong et al, 2019a), and transduction with genetically encoded calcium indicators through adenoassociated viral vectors (Weitz et al, 2015). To reveal the activities of degenerated photoreceptors to electrical stimulation, incubation of retina with cell permeable dyes has been reported (Haq et al, 2018).…”

“…To confine electric fields generated by stimulating electrodes, attempts have been made to shape the electric fields with current focusing, e.g., replacing the remote return electrodes with local returns (Abramian et al, 2011(Abramian et al, , 2014Flores et al, 2016Flores et al, , 2018Matteucci et al, 2016;Fan et al, 2019;Tong et al, 2019a). Different local return configurations have been reported and compared, including connecting several stimulating electrodes as the return (Abramian et al, 2011(Abramian et al, , 2014Matteucci et al, 2016), and specially designing a ring-shaped electrode surrounding the stimulating electrode as the local return (Flores et al, 2016(Flores et al, , 2018Fan et al, 2019;Tong et al, 2019a). A more detailed discussion about different local return configurations can be found in section Simultaneous Stimulation.…”

“…Furthermore, axon bundle activation was also neglected in this study, which is another main origin of RGC spread for epiretinal stimulation. In another investigation, Tong et al (2019a) compared the effect of return configurations for sub-retinal stimulation and showed different results depending on pulse durations and retinal degeneration. In the healthy retina, local returns were more effective in confining RGC activation when 0.1 and 0.2 ms pulses were used in comparison with 0.5 ms pulses.…”

“…For sub-retinal stimulation, Tong et al (2019a,b) also reported the spread of RGC activation when using 25 ms long pulses that mainly stimulated inner retinal neurons. One possible hypothesis (Tong et al, 2019a) is that network stimulation could lead to the activation of RGC dendritic fields, which could be as large as 500 µm in certain RGC types. The discrepancy could be due to the different techniques used for recording.…”