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Efforts to develop an independently functioning epiretinal device for patients with outer retina degeneration are also promising for restoring simple basic visual perception (67,72,75-78). It is a similar concept to the subretinal prosthesis. Epiretinal devices are constructed, however, to utilize the output capacity of spared ganglion cells to transmit the signals they generate to activate the visual system. They are designed to rest on the inner surface of the retina rather than being implanted in the subretinal space, where they can utilize the functional output potential of the ganglion cells and optic nerve to stimulate the visual cortex (Fig. 4).

The advantage of the epiretinal approach over subretinal implants is that the ganglion cells can be easily stimulated because of their accessibility in the inner surface of the retina. These implants have shown success in an

Figure 4 Patients with retinitis pigmentosa and macular degeneration become blind when the rods and cones degenerate and no longer convert incoming light into electrical impulses. While other parts of the retina remain healthy, the brain stops receiving impulses required to provide vision. The retinal prosthesis is designed to bypass the lost rods and cones and directly stimulate the surviving ganglion cells that are connected to the brain through the optic nerve. Specially designed glasses capture the visual scene and transmit this information into the eye through an invisible laser beam. The laser strikes a solar panel (photodiode array) located within the pupil to generate internal power. An ultra-thin electrode array carries the power to the retinal surface, where it stimulates the ganglion cells. (Courtesy of Dr. Joseph F. Rizzo, Harvard University, USA.)

Figure 4 Patients with retinitis pigmentosa and macular degeneration become blind when the rods and cones degenerate and no longer convert incoming light into electrical impulses. While other parts of the retina remain healthy, the brain stops receiving impulses required to provide vision. The retinal prosthesis is designed to bypass the lost rods and cones and directly stimulate the surviving ganglion cells that are connected to the brain through the optic nerve. Specially designed glasses capture the visual scene and transmit this information into the eye through an invisible laser beam. The laser strikes a solar panel (photodiode array) located within the pupil to generate internal power. An ultra-thin electrode array carries the power to the retinal surface, where it stimulates the ganglion cells. (Courtesy of Dr. Joseph F. Rizzo, Harvard University, USA.)

initial study that used flat platinum microelectrode arrays, embedded in a thin film of polyimide, as implants. The device was stabilized onto the inner retina surface of cat eyes using cyanoacrylate adhesive. Recordings of neuronal activities in the visual cortex indicated electrical responses to retinal stimulation experiments. Neither retinal detachment nor intraocular inflammatory responses were observed after prolonged periods of implantation (75). The retina microelectronic prosthetic field has expanded considerably in the last 5 years. Initial studies are exciting, and even though ambitious, the method is proving to be a feasible approach to restoring vision. Several types of retinal prosthesis have now been used to electrically stimulate the visual system to produce flashes of visual perception in blind individuals.

The technology is available for modification and microfabrication of less complex, sophisticated devices that promise hope for mechanically restoring vision. The challenges, however, that face the technology are numerous and formidable. Major obstacles facing the visual prosthesis technology include (65-68,71,77):

1. Establishing a functional connection between the implant, the neural retina and the brain

2. Detachment of the retina during microsurgical implantation

3. Inflammatory reactions of the retina against the implanted devices

4. Ocular infection following implantation procedures

5. Rejection of the electronic device

6. Wiring the retinal surface and maintaining mechanical stability of an epiretinal or subretinal implant

7. Epiretinal devices may stimulate formation of retinal surface membranes, which, in turn, could dislodge the implant and create an electrical resistance between the electrodes and the target output cell

8. Subretinal implants could stimulate the RPE cells to migrate into the retina, causing fibrosis, or impede the transport of nutrients and trophic factors from the choriocapillaris to the retina, resulting in further degeneration of the retina

9 Surviving photoreceptor cells could degenerate at the site of sub-retinal implants because the devices may block choroidal circulation to the outer retina.

It is possible that photoreceptor function could be replaced by retinal prosthesis? Could microelectronic devices establish a long-term functional connection between the inner retina and the brain? Could vision be restored to the blind? The preliminary studies have suggested that the use of retinal prosthesis to restore visual loss is possible if the mechanical and surgical limitations are reduced, precise electrical stimulation and integration with the brain are achieved, and long-term biocompatibility of the implants with the retina is attained. At the present time, however, the clinical usefulness of visual microelectronic prosthesis still remains at a conceptual level.

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