Light-controlled retinal stimulation on rabbit using CMOS-based flexible multi-chip stimulator.

We implemented a light-sensing function on CMOS-based multi-chip stimulator for retinal prosthesis. Using the light-sensing circuitry attached to each stimulation electrode, the flexible multi-chip stimulator is capable of image-based patterned stimulation. We verified the function of the light-controlled decision based on the light intensity measured just beside the stimulation site. We also experimentally demonstrated in vivo retinal stimulation on rabbit's retina with light-controlled decision. The result of the present work is a simplified demonstration for the concept of retinal prosthesis with on-site imaging.

Multi-finger structure and pulsed-powering operation scheme for CMOS LSI-based flexible stimulator for retinal prosthesis.

Multi-finger structure was proposed to improve flexibility of the CMOS LSI-based multi-chip retinal stimulator. A dual-finger retinal stimulator was fabricated and its functionality was demonstrated in retinal stimulation experiments on rabbit's retina, We also proposed an idea of pulsed-powering operation scheme for the multi-chip flexible retinal stimulator. We compared the pulsed-powering scheme with conventional one in a simulation, and show that the pulsed-powering can be an alternative operation scheme for the neural stimulator that provides an improved safety to the biological tissue.

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.

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).

Utility of Etest in choosing appropriate agents to treat fungal keratitis.

PURPOSE: To evaluate the utility of Etest in choosing the appropriate treatment of fungal keratitis. METHODS: Etest was used to determine the drug sensitivities of isolates from the eyes of three patients with fungal keratitis, and the clinical outcomes of treatment with selected drugs were evaluated. RESULTS: In all cases, drug sensitivity demonstrated by Etest accorded with clinical efficacy of the drugs. CONCLUSION: The results in these cases suggest that evaluating drug sensitivities with Etest is an efficient means of selecting optimal pharmacotherapy for fungal keratitis.

Expression of Na+/myo-inositol cotransporter mRNA in normal and hypertonic stress rat eyes.

We studied the localization of Na+/myo-inositol cotransporter (SMIT) mRNA in normal and hypertonic stress rat eyes by in situ hybridization histochemistry using cRNA probes. SMIT mRNA signals were observed in the iris-ciliary body, the lens epithelial cells, and the ganglion cell layer and the inner nuclear layer of the retina. There was a rapid increase on SMIT mRNA in the retina of hypertonic stress rats compared with control rats. These findings suggest that Na+/myo-inositol cotransporter gene expression is osmotically regulated in vivo to protect retinal neuronal function against hypertonic stress.

[Clinical evaluation of fluconazole in patients with mycotic infection].

Fluconazole, a triazole antifungal agent newly developed by Pfizer Inc.. was given orally to 4 patients with deep mycosis. Fluconazole was markedly effective against septicemia due to Candida and oral candidiasis accompanied with lingual ulcer in spite of seriousness of these underlying disease. In 2 patients with aspergilloma, eradication or contraction of fungus ball was observed and the drug was judged to be effective. In vitro MICs of fluconazole against clinically isolated Aspergillus spp. were much higher than its serum levels leaving a large discrepancy between in vitro activity and clinical efficacy. Although the dosage was 100-300 mg daily for 8 days to 6 months, neither adverse reactions nor laboratory parameter abnormalities were observed. The above results suggest that fluconazole is a useful agent in the treatment of fungal infections.