Development and implantation of a minimally invasive wireless subretinal neurostimulator

Abstract

A wirelessly operated, minimally invasive retinal prosthesis was developed for preclinical chronic implantation studies in Yucatan minipig models. The implant conforms to the outer wall of the eye and drives a microfabricated polyimide stimulating electrode array with sputtered iridium oxide electrodes. This array is implanted in the subretinal space using a specially designed ab externo surgical technique that fixes the bulk of the prosthesis to the outer surface of the sclera. The implanted device is fabricated on a host polyimide flexible circuit. It consists of a 15-channel stimulator chip, secondary power and data receiving coils, and discrete power supply components. The completed device is encapsulated in poly(dimethylsiloxane) except for the reference/counter electrode and the thin electrode array. In vitro testing was performed to verify the performance of the system in biological saline using a custom RF transmitter circuit and primary coils. Stimulation patterns as well as pulse strength, duration, and frequency were programmed wirelessly using custom software and a graphical user interface. Wireless operation of the retinal implant has been verified both in vitro and in vivo in three pigs for more than seven months, the latter by measuring stimulus artifacts on the eye surface using contact lens electrodes.

Fig. 1.

(Left) and (center) Graphical images of the ab externo approach for insertion of the electrode array. Inset: the array enters the subretinal space through a scleral flap, after a retinal bleb (center) has been raised to keep the delicate retina out of harm’s way. (Right) Photograph showing a polyimide guide strip entering the eye of a Yucatan minipig prior to insertion of the 16-μm-thick stimulating electrode array.

Fig. 2.

Engineering design of the subretinal microstimulator system. (a) Implanted components are built on a flexible, polyimide substrate. After assembly, the entire unit is coated in poly(dimethylsiloxane) except for the stimulating array and the current return electrode. The overall dimensions of the device are 12 mm × 31 mm. (b) Schematic diagram showing wireless operation of the visual prosthesis system. A camera (or external computer) and transmitter collect and then rebroadcast an image signal to the implanted stimulator chip, which is commanded to retransmit biphasic current pulses, in patterns corresponding to the desired image, to the stimulating electrode array located in the subretinal space.

Fig. 3.

(a) Primary power and data transmitter circuits. (b) Primary transmitting coils encapsulated in poly(dimethylsiloxane). (c) Schematic diagram of the power and data inductive link-based transmission systems for the visual prosthesis. The implanted components are contained within the outer envelope, the rectifier and reset delay circuit are near the top, and the ASIC architecture is shown in the bottom half.

Fig. 4.

Micrograph of the custom stimulator chip used in these trials [50]. There are 15 output current drivers. Reconstruction of the input waveform is performed using a delay-locked loop.

Fig. 5.

(a) Schematic cross section diagram showing the electrode array fabrication process. (b) Light micrograph of an IrO_x stimulating site immediately postfabrication, and at right, an SEM of an identical 400-μm-diameter site after one year of continuous, biphasic current pulsing (0.76 mC/cm², 0.95 μC/phase). (c) A 100-mm-diameter Si host wafer with IrO_x electrode arrays for both acute and chronic stimulation studies. (d) Close-up micrograph showing numerous arrays, each having 15 IrO_x electrode sites (small dark circles).

Fig. 6.

Comparison of the CVs of a representative SIROF stimulating electrode, initially and after 228 days pulsing (0.76 mC/cm², 0.95 μC/phase) at 16 pulses/s. The increase in charge storage capacity is attributed to rehydration and structural modification of the SIROF during pulsing.

Fig. 7.

(a) Implantation of a microstimulator. (b) Prosthesis is sutured over the location of the sclera flap. In this surgery, a polyimide guide was used to prepare the way for the electrode array (seen here prior to insertion). (c) Array has been inserted, the guide removed, and the sclera flap sutured back in place. (d) Conjunctiva has been sutured back over the implant.

Fig. 8.

(a) Fundus photograph of an electrode array in the subretinal space taken one week postsurgery. Note retinal blood vessels over the implant site. (b) Histological slide showing minimal adverse tissue responses to the presence of a polyimide strip (center of photograph) in the subretinal space of a Yucatan minipig. There is only slight gliosis and limited proliferation of dark colored retinal pigment epithelial (RPE) cells near the array (after [16]).

Fig. 9.

Typical electrode voltage waveforms (a) when the stimulator drove a dummy load consisting of a series resistor of 4 kΩ (representing the access resistance and the series resistance of the lead), and a parallel combination of a 20 kΩ resistor and a 0.047 μF capacitor representing the electrode–tissue interface (the top trace shows the binary bitstream used to command the device and the bottom trace shows the voltage output.) (b) Representative electrode voltage waveform when the stimulator was wirelessly powered in saline solution, measured using a “test tail” extension of the IrO_x electrode array that reached back out of the bath. The noise is due to RF interference from the transmitter.

Fig. 10.

(a) Testing the wireless microstimulator in a saline bath. (b) In vitro test setup. (c) Measured potential difference (in millivolts) between two needle electrodes placed in close proximity to the prosthesis in a saline bath, while biphasic test current pulses of 25 μA were stimulated. Time scale: 1 ms/division.

Fig. 11.

In vivo testing. (a) Representative ERG traces showing no significant changes in waveform between preoperative and postoperative measurements. (b) Photograph showing the wireless transmission system and PXI computer driver in operation. The cart also contains dc power supplies and the power and data transmitters. (c) System in operation during surgery. (d) and (e) Contact lens electrode is applied to the eye to measure stimulus artifacts, and the primary coils are positioned to drive the prosthesis.

Fig. 12.

Representative waveforms of stimulus artifacts from wirelessly driven retinal microstimulators in Yucatan minipigs at 0, 2, 6, and 12 weeks postoperation. The “control” waveform was collected when transmitted power to the implant was reduced below the threshold that was required for stimulation to begin. The potential scale (in millivolts) is only relative, as the readings were highly sensitive to changes in the position of the contact lens electrode. Time scale: 1 ms/division.

Fig. 13.

Photographs demonstrating partial exposure of different implanted microstimulators through the minipig conjunctiva. (a) 3 weeks after surgery. (b) 18 weeks after surgery.