Biphasic pulse trains (> or =10 pulses) with a duration of 0.5-1.0 ms and a frequency of 20-50 Hz were efficient for evoking phosphenes by localized extraocular stimulation in normal subjects. With these parameters, STS is a feasible method to use with a retinal prosthesis even in advanced stages of RPs.

Our technique for STS with an intrascleral microelectrode array is safe in rabbit eyes, and EEPs were elicited by current densities that did not induce tissue damage. These results suggest that STS via intrascleral multichannel electrodes is a feasible method for stimulating the retina.

Transretinal electrical stimulation from the suprachoroidal space could elicit EEP, suggesting that this approach may be useful for a retinal prosthesis system.

The purpose of this study is to determine the threshold suprachoroidal-transretinal stimulation (STS) current that results in retinal damage in rabbits. Biphasic STS pulses (anodic first, frequency 20 Hz) were used to stimulate the retina of pigmented rabbits (n = 18) continuously for 1 h using a 100 microm diameter platinum wire electrode. The STS current that induced retinal damage after 1 h was determined by ophthalmoscopy or by fluorescein angiography (FA) independently. The effect of the pulse duration on the threshold current was investigated. Histological studies were performed after electrical stimulation experiments. The threshold for a safe current to the retina was 0.6 mA for a duration of 0.5 ms. The threshold for a safe charge increased approximately linearly with an increase of stimulus duration but the threshold for a safe current decreased logarithmically with an increase of duration. The threshold for a safe electrical energy remained almost constant for all durations. Histological examination showed severe retinal damage when the current exceeded the threshold, with more damage in the inner layers compared with the outer layers of the retina. The threshold for the safe current was higher than that reported for direct stimulation of neural tissues, suggesting that the STS method was safe and able to be used with a retinal prosthesis. Because the threshold for the safe charge was lower with shorter pulse durations, care should be taken using pulses of short durations.

This paper describes the technological developments underlying the realization of a reliable and reproducible microchip-based stimulator with a large number of stimulus electrodes. A microchip-based stimulator with over 500 electrodes for suprachoroidal transretinal stimulation (STS) is proposed in this paper, and an example is presented. To enhance reliability and reproducibility for such a large array, we introduce a flip-chip bonding technique and place microchips on the reverse side of a substrate. A square microchip of size 600 microm was fabricated using 0.35 microm standard CMOS process technology. Twelve microchips were flip-chip bonded on a polyimide substrate through Au bumps. To evaluate the feasibility of the proposed device, we successfully fabricated a stimulator with 12 microchips and 118 electrodes made of Pt/Au bumps, and demonstrated their operation in a saline solution for 2 weeks. Also, to evaluate the device operation in vivo, a stimulator with one active IrO(x) electrode was implanted into the scleral pocket of a rabbit and electrical evoked potential (EEP) signals with a threshold of 100 microA were obtained. We also fabricated a simulator with 64 microchips that has 576 electrodes (9 electrodes in a microchip times 64 microchips).