Low-invasive large-field retinal modulation using an extraocular temporal interference stimulation electrode array

Retinal prostheses can restore rudimentary visual perception in retinal degenerated patients by electrically stimulating surviving retinal neurons. Conventional implantable systems require intraocular electrode array implantation, which involves complex surgical procedures and substantial invasiveness. Temporal interference stimulation (TIS) achieves noninvasive and focused deep brain stimulation by delivering kilohertz currents with slight frequency differences across stimulation channels (each consisting of a stimulating and a return electrode). Our research team was the first to propose a spatially selective extraocular retinal electrical stimulation and modulation approach using TIS. In this study, we designed a low-invasive extraocular electrode array based on TIS for large-scale, spatially selective retinal ganglion cell (RGC) modulation. The array consists of a stimulating electrode array positioned on the posterior sclera and a return electrode array on the cornea. Using simulation-based modeling, we optimized the number of stimulation channels and electrode configuration to improve spatial selectivity. The optimized electrode array produced convergent RGC activation across a 6 × 6 mm retinal region, with activated RGC receptive field centroids closely aligned with the corresponding stimulating electrodes. By adjusting stimulation intensity, consistent activation areas were achieved across different retinal locations. Furthermore, by leveraging virtual channel modulation, additional activation sites were created, thereby improving the theoretical spatial selectivity without increasing the number of physical electrodes. These results demonstrate the feasibility of low-invasive, large-field, spatially selective retinal neuromodulation using extraocular TIS and provide a theoretical foundation for future retinal prosthetic and therapeutic applications.

The online version contains supplementary material available at https://doi.org/10.1007/s11571-026-10573-6.