Virtual reality validation of naturalistic modulation strategies to counteract fading in retinal stimulation.

Objective. Temporal resolution is a key challenge in artificial vision. Several prosthetic approaches are limited by the perceptual fading of evoked phosphenes upon repeated stimulation from the same electrode. Therefore, implanted patients are forced to perform active scanning, via head movements, to refresh the visual field viewed by the camera. However, active scanning is a draining task, and it is crucial to find compensatory strategies to reduce it.Approach. To address this question, we implemented perceptual fading in simulated prosthetic vision using virtual reality. Then, we quantified the effect of fading on two indicators: the time to complete a reading task and the head rotation during the task. We also tested if stimulation strategies previously proposed to increase the persistence of responses in retinal ganglion cells to electrical stimulation could improve these indicators.Main results. This study shows that stimulation strategies based on interrupted pulse trains and randomisation of the pulse duration allows significant reduction of both the time to complete the task and the head rotation during the task.Significance. The stimulation strategy used in retinal implants is crucial to counteract perceptual fading and to reduce active head scanning during prosthetic vision. In turn, less active scanning might improve the patient's comfort in artificial vision.

Naturalistic spatiotemporal modulation of epiretinal stimulation increases the response persistence of retinal ganglion cell.

Objective.Retinal stimulation in blind patients evokes the sensation of discrete points of light called phosphenes, which allows them to perform visually guided tasks, such as orientation, navigation, object recognition, object manipulation and reading. However, the clinical benefit of artificial vision in profoundly blind patients is still tenuous, as several engineering and biophysical obstacles keep it far away from natural perception. The relative preservation of the inner retinal neurons in hereditary degenerative retinal diseases, such as retinitis pigmentosa, supports artificial vision through the network-mediated stimulation of retinal ganglion cells (RGCs). However, the response of RGCs to repeated electrical stimulation rapidly declines, primarily because of the intrinsic desensitisation of their excitatory network. In patients, upon repetitive stimulation, phosphenes fade out in less than half of a second, which drastically limits the understanding of the percept.Approach.A more naturalistic stimulation strategy, based on spatiotemporal modulation of electric pulses, could overcome the desensitisation of RGCs. To investigate this hypothesis, we performed network-mediated epiretinal stimulations paired to electrophysiological recordings in retinas explanted from both male and female retinal degeneration 10 mice.Main results.The results showed that the spatial and temporal modulation of the network-mediated epiretinal stimulation prolonged the persistence of the RGC's response from 400 ms up to 4.2 s.Significance.A time-varied, non-stationary and interrupted stimulation of the retinal network, mimicking involuntary microsaccades, might reduce the fading of the visual percept and improve the clinical efficacy of retinal implants.

Capacitive-like photovoltaic epiretinal stimulation enhances and narrows the network-mediated activity of retinal ganglion cells by recruiting the lateral inhibitory network.

Photovoltaic retinal prostheses theoretically offer the possibility of stand-alone high-resolution electrical stimulation of the retina. However, achieving focused epiretinal stimulation is particularly challenging because of axonal activation and electrical cell coupling. Recent evidence shows that long electric pulses permit a more focal activation of retinal ganglion cells, and non-rectangular waveforms induce higher network-mediated indirect activity. OBJECTIVE: The role of the pulse shape in focusing the retinal ganglion cell activation and the underlying mechanisms are not yet fully understood. APPROACH: To address this question, we implemented a hybrid ex vivo and in silico approach. We recorded the evoked activity of retinas explanted from retinal degeneration ten mice upon photovoltaic and electrical stimulation with rectangular or non-rectangular capacitive-like voltage pulses. We used a biophysical model to investigate the role of the pulse shape and the pulse duration on the genesis and the extent of the network-mediated activity in retinal ganglion cells. MAIN RESULTS: Altogether, our results suggest that non-rectangular capacitive-like voltage pulses activate more strongly the inner excitatory and inhibitory layers of the retina, when compared to a rectangular stimulation with paired pulse amplitude and duration. This feature leads to an increase of the network-mediated activity and a decrease in the network-mediated electrical receptive field of the stimulated retinal ganglion cell. SIGNIFICANCE: These results demonstrate that recruiting the inner retinal cells with epiretinal stimulation enables us not only to bypass axonal stimulation, but also to obtain a more focal activation due to the natural lateral inhibition. The involvement of the inhibitory feedback from amacrine cells in the genesis of the network-mediated activity represents a novel biological tool with which to confine the response of the retinal ganglion cells. These results support future waveform engineering strategies and offer new perspectives on epiretinal devices to better shape prosthetic perception.

Design and validation of a foldable and photovoltaic wide-field epiretinal prosthesis.

Retinal prostheses have been developed to fight blindness in people affected by outer retinal layer dystrophies. To date, few hundred patients have received a retinal implant. Inspired by intraocular lenses, we have designed a foldable and photovoltaic wide-field epiretinal prosthesis (named POLYRETINA) capable of stimulating wireless retinal ganglion cells. Here we show that within a visual angle of 46.3 degrees, POLYRETINA embeds 2215 stimulating pixels, of which 967 are in the central area of 5 mm, it is foldable to allow implantation through a small scleral incision, and it has a hemispherical shape to match the curvature of the eye. We demonstrate that it is not cytotoxic and respects optical and thermal safety standards; accelerated ageing shows a lifetime of at least 2 years. POLYRETINA represents significant progress towards the improvement of both visual acuity and visual field with the same device, a current challenging issue in the field.