Kazuaki Nakauchi

Transretinal Electrical Stimulation with a Suprachoroidal Multichannel Electrode in Rabbit Eyes

PurposeSeveral approaches for placing an electrode device for visual prosthesis have been previously proposed. In this study, we investigated if transretinal stimulation from the suprachoroidal space can elicit an electrical evoked potential (EEP) in albino rabbits.MethodsA flat electrode array (polyimide plate, platinum electrode) was developed and used for this study. After performing a scleral incision at 2–2.5 mm from the limbus and placing an anchoring suture, the array was inserted into the suprachoroidal space in the posterior portion of the eye by direct observation under a microscope. A platinum wire was implanted into the vitreous space as a reference electrode. For electrical stimulation, a biphasic pulse was used. When the electrode was stimulated, the EEP was recorded.ResultsWhen the electrical stimulation from the suprachoroidal space was applied, the EEP could be recorded with an epidural electrode, and the threshold was 66.0 ± 32.1μA (42.0μC/cm2). Histological examination indicated the absence of major damage to the retina and choroid from the insertion and placement of the array and the electrical stimulation.ConclusionsTransretinal electrical stimulation from the suprachoroidal space could elicit EEP, suggesting that this approach may be useful for a retinal prosthesis system.

Threshold suprachoroidal–transretinal stimulation current resulting in retinal damage in rabbits

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.

Laboratory investigation of microelectronics-based stimulators for large-scale suprachoroidal transretinal stimulation (STS)

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).

Electrical stimulation with a needle-type electrode inserted into the optic nerve in rabbit eyes.

PurposeTo investigate whether electrical stimulation of the optic nerve can elicit an electrical evoked potential (EEP) in rabbits and to determine whether such stimulation is a useful approach for the placement of a visual prosthesis.MethodsTwo needle-type electrodes were inserted into the optic nerve using a transvitreal approach. For electrical stimulation, monophasic and biphasic pulses were used. By stimulating the optic nerve, the EEP was elicited. After evaluation of the EEP, a histological study was carried out.ResultsWhen electrical stimulation was applied, the EEP could be recorded. The threshold with monophasic and biphasic stimulation was 10 ± 0 µA and 20 ± 8.2 µA, respectively. Histological examination revealed no major complications, such as bleeding or degeneration, which might have resulted from the insertion of electrodes or the electrical stimulation.ConclusionsElectrical stimulation of the optic nerve can elicit an EEP, suggesting that this approach may be useful for a visual prosthesis system. Jpn J Ophthalmol 2004;48:552–557

In vivo Stimulation on Rabbit Retina using CMOS LSI-based Multi-Chip Flexible Stimulator for Retinal Prosthesis

We have performed in vivo electric stimulation experiments on rabbit retina to demonstrate feasibility of CMOS LSI-based multi-chip flexible neural stimulator for retinal prosthesis. We have developed new packaging structure with an improved flexibility and device control system which totally controls the LSI-based multi-chip stimulator, counter electrode, and stimulation generator. We have implanted the fabricated multi-chip stimulator into sclera pocket for STS (Suprachoroidal Transretinal Stimulation) configuration. We successfully obtained EEP (Electrically Evoked Potential) on visual cortex evoked by the multi-chip stimulator.

Retinal Stimulation on Rabbit Using Complementary Metal Oxide Semiconductor Based Multichip Flexible Stimulator toward Retinal Prosthesis

The Functionality of a complementary metal oxide semiconductor (CMOS) LSI-based, multichip flexible retinal stimulator was demonstrated in retinal stimulation experiments on rabbits. A 1×4-configured multichip stimulator was fabricated for application to experiments on animals. An experimental procedure including surgical operations was developed, and retinal stimulation was performed with the fabricated multichip stimulator. Neural responses on the visual cortex were successfully evoked by the fabricated stimulator. The stimulator is confirmed to be applicable to acute animal experiments.

A Tissue Change After Suprachoroidal-Transretinal Stimulation with High Electrical Current in Rabbits

Purpose: To investigate the safety range of current by suprachoroidal-transretinal stimulation (STS) using a high-current continuous stimulation. Method: Sclerotomy was performed at the area just beneath the visual streak of rabbits and the platinum (Pt) electrode (diameter: 100μm or 200μm) embedded in silicone plate was attached on the fenestrated sclera. Return electrode was placed in the vitreous cavity. Retina was stimulated by biphasic pulses (anodic first, duration: 0.5,msec, frequency: 20,Hz) with a current ranged from 1 to 3,mA continuously for an hour. The rabbit eyes were enucleated immediately after microscopic fundus observation, fixated with glutar-aldehide, embedded in paraffin and stained with hematoxylin-eosin.

A Case of Reversed Ophthalmic Artery Flow without Occlusion of the Internal Carotid Artery.

Background: We report a case of reversed ophthalmic artery (OA) flow showing neither occlusion of the internal carotid artery (ICA) nor ophthalmic symptoms.Case: An 82-year-old man had transient blindness in both eyes. After left carotid endarterectomy, ophthalmic symptoms improved in the right and left eyes. Afterwards, he had a relapse in the left eye.Results: There was no unusual impression in the ophthalmic examinations, but color Doppler imaging showed reduced flow in the left OA, reversal of flow direction in the right OA. The central retinal artery (CRA) and short posterior ciliary arteries (SPCA) were not detected in the left eye but were detected in the right eye. Digital subtraction angiography demonstrated that the right OA was not contrasted with the right ICA, despite there being no stenosis or occlusion of the right ICA.Conclusions: We suggest that carotid surgery may affect the ocular circulation of the opposite side, and reversed OA flow as a collateral pathway from the external carotid artery may occur in the absence of carotid artery stenosis. Good circulation of the CRA and SPCA may preclude manifestation of ophthalmic symptoms even if the OA flow is reversed.

Si-LSI Based Stimulators for Retinal Prosthesis

In this presentation, we demonstrate a pulse-frequency-modulation (PFM)-based retinal stimulator for sub-retinal implantation using standard CMOS technology with low voltage operation of 1.2 V. A PFM-based photosensor converts input light intensity to electrical pulse trains whose frequency is proportional to the input light intensity. To employ simple image processing function, 1-bit pulse domain operation is introduced and demonstrated. A packaging technology for ocular implantation is also discussed. We have proposed and demonstrated a multi-chip architecture with expandability of the number of stimulus electrodes and flexibility of bending along the eye-ball. A fabricated stimulator based on this architecture is implanted in a rabbit eye and achieved to obtain EEP (electrical evoked potential) signals.

A multi-microchip retinal stimulator for in vitro / in vivo experiments

This paper describes the fabrication and in vitro/in vivo operation of a retinal stimulator based on CMOS multi-microchips. To enhance reliability and reproducibility for in vitro/in vivo with large array size, we introduce a flip-chip bonding technique and place microchips on the reverse side of a substrate. A microchip with a size of 600 mum square was fabricated using 0.35-mum standard CMOS process technology. Twelve microchips were flip-chip bonded on a polyimide substrate through Au bumps. We successfully fabricated a stimulator with 12 microchips and 118 electrodes made of Pt/Au bumps. For in vitro, we demonstrated their operation in a saline solution over two weeks. Also, for in vivo, a stimulator with one active IrOx electrode was implanted into the scleral pocket of a rabbit and EEP signals with a threshold of 100 muA were obtained.