Retinal integration with a subretinal honeycomb-shaped prosthesis

Abstract

Purpose : In patients with geographic atrophy, subretinal photovoltaic implants with 100µm pixels provided prosthetic acuity of 1.1-1.3 pixels (20/460 – 20/560). Rats with implants of 75 and 55µm pixels also demonstrated grating acuity matching the pixel pitch. However, stimulation threshold increases for smaller pixels in the current design and exceeds the charge injection limit with pixels below 40µm. To decrease the stimulation threshold and decouple it from the pixel width, we added honeycomb-shaped vertical walls surrounding each pixel. This approach relies on migration of the retinal cells into the honeycomb wells. Here, we investigate the structural integration of the inner retinal cells with the wells and its effect on retinal stimulation.

Methods : To evaluate the effect of honeycombs on retinal stimulation, 25µm tall walls were polymerized on flat photovoltaic arrays with 40µm and 20µm pixels. Visually evoked potentials (VEP) were recorded weekly for 9 weeks after implantation of the arrays beneath the degenerate rat retina. Retinal anatomy was examined by confocal imaging of immunolabelled whole mounts.

Results : With both, flat and honeycomb implants, VEP amplitude decreased after the day of implantation and then gradually increased back to the original level during 6-9 weeks post-op. However, stimulation thresholds with honeycombs and flat implants of both pixel sizes remained the same: 0.057±0.029 mW/mm². Majority of cells populating the wells were cone and rod bipolar cells, and much fewer horizontal cells. The macro- and micro-glial response to the honeycomb implants were comparable to that with flat implants and to the degenerate retina controls. The deep capillary plexus (DCP) and amacrine cells, as well as the inner plexiform layer remained entirely above the honeycomb walls.

Conclusions : Retinal migration into the honeycombs does not negatively affect its electrical excitability. Lack of cell death indicates that DCP above the wells provides oxygenation and nutrients to cells within the wells. Comparable glial response to flat implants suggests that migration and separation of the retinal cells by the walls does not cause additional stress. The 25µm deep wells accept majority of the INL, while leaving the tertiary neurons, such as amacrine and ganglion cells, outside. This is important for selective stimulation of the secondary neurons and preservation of the inner retinal signal processing in prosthetic vision.

This is a 2021 ARVO Annual Meeting abstract.