Focal electrical stimulation of the retina

Abstract

Purpose : Epiretinal implants have restored partial vision to the blind by electrically stimulating surviving retinal neurons. Unintended stimulation of retinal ganglion cell (RGC) axons causes patients to see large, elongated visual phosphenes, making it difficult for them to perceive forms. This study tested whether alternative electrical stimulus waveforms could produce focal retinal activation.

Methods : The GCaMP5G calcium indicator was virally expressed in RGCs of wild-type (Long Evans) and retinal degenerate (S334ter-line-3) rats. Transduced retinas were isolated and mounted RGC-side-down on a multielectrode array. Calcium imaging was used to map the patterns of cells activated by different electrical stimulation protocols. Electrode diameter (30–200 µm) and pulse duration (0.06–100 ms/phase) were varied. Synaptic blockers were used in some experiments to pharmacologically isolate RGCs. The effect of pulse width on phosphene shape was tested in an epiretinal implant (Argus I) subject, blind with retinitis pigmentosa.

Results : In rats, pulse durations 16 ms/phase and shorter stimulated axons, activating a streak of RGCs that extended to the retina’s edge. Pulses 25 ms/phase and longer stimulated inner retinal neurons while avoiding RGC axons, producing focal responses. Threshold charge density became higher as pulse width increased (e.g., for 200-µm electrodes, stimulus thresholds were 1.8 and 22.4 µC/cm² for 0.1- and 25-ms/phase pulses, respectively). Response shapes in wild-type and degenerate retinas were similar, but stimulus thresholds of inner retinal cells were elevated by 3× in retinal degenerate rats. Multielectrode stimulation with 25-ms/phase pulses was used to pattern letters on the retina. The letter V, for example, was generated with seven 30-µm electrodes (see figure). The height of the V on the retina corresponds to 0.78° of human visual angle and is equivalent to viewing 5-mm-tall text from typical reading distance (40 cm). Psychophysical testing in an epiretinal implant patient demonstrated that short pulses (0.46 ms/phase) produce elongated phosphenes, while long pulses (25 ms/phase) evoke focal spots of light.

Conclusions : Our results demonstrate that stimulus pulse durations two orders of magnitude longer than those typically used in existing retinal implants avoid RGC axons and activate the retina focally. If validated through further human testing, these findings may lead to improved visual acuity for epiretinal implant users.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.