Joel Salzmann

Long-Term Results from an Epiretinal Prosthesis to Restore Sight to the Blind

PURPOSE Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. DESIGN The study is a multicenter, single-arm, prospective clinical trial. PARTICIPANTS There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). METHODS The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. MAIN OUTCOME MEASURES The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. RESULTS A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. CONCLUSIONS The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Preliminary 6 month results from the argus tm ii epiretinal prosthesis feasibility study

The Argus™ II 60 channel epiretinal prosthesis has been developed in order to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. To date the device has been implanted in 21 subjects as part of a feasibility study. In 6 month post-implantation door finding and line tracking orientation and mobility testing, subjects have shown improvements of 86% and 73%, respectively, for system on vs. system off. In high-contrast Square Localization tests using a touch screen monitor 87% of tested subjects performed significantly better with the system on compared with off. These preliminary results show that the Argus II system provides some functional vision to blind subjects.

Subretinal electrode implantation in the P23H rat for chronic stimulations

Background: In age related macular degeneration and inherited dystrophies, preservation of retinal ganglion cells has been demonstrated. This finding has led to the development of various models of subretinal or epiretinal implant in order to restore vision. This study addresses the development of a polyimide subretinal electrode platform in the dystrophic P23H rat in vivo. Methods: A technique was developed for implanting a subretinal electrode into the subretinal space and stabilising the distal extremity of the cabling on the rat cranium in order to allow future electrical stimulations of the retina. Results: In vivo imaging of the retina with the scanning laser ophthalmoscope demonstrated reabsorption of the surgically induced retinal detachment and the absence of major tissue reactions. These in vivo observations were confirmed by retinal histology. The extraocular fixation system on the rat cranium was effective in stabilising the distal connector for in vivo stimulation. Conclusion: This study demonstrates that a retinal implant can be introduced into the subretinal space of a dystrophic rat with a stable external connection for repeatable electrical measurements and stimulation. This in vivo model should therefore allow us to evaluate the safety and efficacy of electrical stimulations on dystrophic retina.

Intravitreal ranibizumab and bevacizumab for bilateral subretinal neovascularization secondary to idiopathic juxtafoveal telangiectasia type 2A.

Editor, I diopathic juxtafoveal telangiectasia (IJT) type 2A is characterized by the presence of bilateral acquired ectatic capillaries that involve the temporal half of the fovea (Yannuzzi et al. 2006). Neovascularization and foveal atrophy may occur with progression of the disease and cause severe visual loss (Yannuzzi et al. 2006). We report the successful use of intravitreal ranibizumab and bevacizumab in a case of IJT, complicated by bilateral and simultaneous subretinal neovascularization (SRN). A 62-year-old woman presented at our department with a 2-month history of bilateral visual loss and metamorphopsia. A diagnosis of IJT 2A had been made 7 years earlier. Visual acuity (VA) had remained stable at 20 ⁄25 in both eyes during the subsequent period. At the time of presentation, best corrected Snellen VA (BCVA) was 20 ⁄ 80 in the right eye (RE) and 20 ⁄ 50 in the left eye (LE). Anterior segment biomicroscopy was unremarkable in both eyes. Fundus examination showed dilated rightangled retinal vessels (mainly venules) dipping deep into the retina, whitish elevated subretinal tissue in both eyes and a retinal haemorrhage in the RE (Fig. 1A, B). Fluorescein angiography (FA) revealed telangiectatic perifoveal capillaries associated with SRN with leakage in both eyes (Fig. 1C–F). Macular optical coherence tomography (OCT) (Stratus OCT; Carl Zeiss Meditec, Dublin, CA, USA) showed deep intraretinal and subretinal neovascular tissue associated with increased macular thickness and subretinal fluid (Fig. 2A, B). Central retinal

Long-term in vivo impedance changes of subretinal microelectrodes implanted in dystrophic P23H rats.

Retinal prostheses are being developed to restore vision in blind patients with photoreceptor degeneration. Electrodes arrays were subretinally implanted in transgenic P23H rats with their photoreceptors degenerated. Electrical stability of the implants was evaluated by long-term monitoring of their impedance changes. Electrode impedances were found to increase by two log units over a three weeks period whereas no impedance increase was noted when the implants were located in the vitreous. In case of hemorrhage or major fibrous reactions, the impedance continued to increase steadily. After explantation, it recovered its initial value indicating no deterioration of the implant. Although the glial cell layer at the surface of the subretinal space was slightly larger, no major glial reaction was seen in direct contact to the implant. These results indicate that no functional testing should be considered before at least three weeks post implantation.

Retinal prosthesis : Testing prototypes on a dystrophic rat retina

The retina contains a mosaic of photoreceptors coupled to a intelligent neural network extracting important information on object edges, movements. This visual information is then transferred to the brain through the optic nerve. In pathologies like age macular degeneration or retinitis pigmentosa, photoreceptor degeneration leaves the retinal neuronal network unstimulated. Retinal prostheses propose to stimulate electrically this neuronal network to restore a useful vision for locomotion and reading. We are testing prototypes of subretinal prostheses on the retina of dystrophic rats with photoreceptor degeneration. Our experiments have enabled us to introduce reproducibly these prototypes into the subretinal space, to observe regularly the implant in vivo and measure longitudinally the electrode impedance. These in vivo measurements can then be correlated with the histological examination of the retinal tissue. In parallel, techniques were implemented to record retinal ganglion cell activity on the isolated retina to test different stimulation protocols. Classic retinal ganglion cell responses can be recorded with these techniques and allow to measure ganglion cell response to electrical stimulation. These studies should therefore contribute to improving the selectivity in the electrode retinal stimulation by retinal prostheses.

In vivo evaluations of retinal prostheses

In this article, the in vivo evaluation of retinal prostheses were achieved either in animals with normal vision or in blind persons. To assess the stimulating electrodes in vivo on an animal with photoreceptor degeneration, we have implanted a P23H rhodopsin rats. The present study describes the implant design and our surgical strategy. The experiments indicate clearly that the implant electrodes can be tested on a leaving rat with photoreceptor degeneration. Future studies can assess the electrode characteristics and the stimulating protocol to trigger cellular and/or animal behavior responses.