At one time, it was believed that visual loss was permanent once the neural retina or optic nerve had been damaged. There were two events that modified this way of thinking. In 1968, a visual prosthesis was evaluated in a blind patient (1), and in 1974 an experiment was conducted in which a patient with no light perception vision could perceive light after an electrode was used to stimulate the visual cortex (2). At present there are a number of groups working on different approaches to developing a visual prosthesis for the blind.

Dobelle developed an approach that stimulated the visual cortex intracranially (2, 3, 4 and 5). In experiments conducted by Dobelle et al. and Norman et al., using either implanted surface electrodes or intracortical microelectrodes, cortical cells were activated thus stimulating the visual cortex (2, 3, 4 and 5). This type of electrical stimulation of the visual cortex requires intracranial surgery and as such, there is the potential for a high rate of complications such as CNS infection, epilepsy, and disturbance of the blood flow to the optic nerve.

On the other hand, Santos reported that 30% of the ganglion cells and approximately 80% of the inner nuclear layer cells remain histologically intact after death of photoreceptors in the eyes with severe visual loss due to retinitis pigmentosa (RP) (6). Other groups, therefore, have approached the development of a visual prosthesis stimulating those remaining inner retinal neurons. One such ophthalmological approach involves the use of subretinal electrodes and has been investigated by Chow et al. (7, 8 and 9) and Zrenner et al. (10,11) (Figs. 58-1 and 58-2). Using this method, lost photoreceptor function is replaced by a subretinal microphotodiode array (MPDA) that activates the remaining retinal network. Another approach used by certain groups such as Eckmiller et al. (12,13), Humayan et al. (14,15), Rizzo et al. (16,17) and Walter et al. (18) investigates the use of an epiretinal device to stimulate ganglion cells from an implanted microelectrode array from the vitreal side of the retina (Fig. 58-3). Another viable option is approaching the retinal prosthesis from within the suprachoroidal space. Sakaguchi and Tano et al. reported regarding the suprachoroidal transretinal stimulation system (STS) in which an electrode upon insertion into the suprachoroidal space elicits an electrical evoked potential (EEP) through transretinal stimulation (19), and Fujikado and Tano et al. also reported the effect of this system in clinical trial (20).

There are advantages and disadvantages to each method of electrical stimulation. Implanted cortical electrodes can treat blindness with complete atrophy of the retina or optic nerve, but requires intracranial procedures and may result in limited spatial perception. Retinal stimulation (Fig. 58-4), in contrast, utilizes the preexisting signal-processing network along the proximal visual pathways and is expected to have higher resolution. The visual field through an epiretinal electrode for instance, has a visual angle of 10 degrees (21). However, the area of visual field that will be reconstructed by a small (several millimeter square or in diameter) electrodes array is limited. Retinal stimulation involves predictable retinal damage due to the chronic direct attachment of an implant array. Moreover, the epiretinal or subretinal electrode necessitates that sufficient bipolar cells or ganglion cells remain in the small area around the electrode to elicit a response to electrical stimulation.

At present, there are five clinical trials underway to evaluate the efficacy of visual restoration through retinal prosthesis (22). Second Sight Medical Products, Inc has a 16-electrode epiretinal device that has been implanted in six subjects in the United States for over five years (23). A second-generation device has 60 electrodes and is currently in phase 2/3 of a clinical trial. In Germany, Intelligent Medical Implants GmBH has implanted four patients with a 49-electrode epiretinal array (24). The fourth clinical trial involves another epiretinal implant, the EPI RET3, which is a 25-electrode array that was implanted for four weeks in six blind patients (25). In the fifth clinical trial a 1550-MPDA and a 4 × 4 electrode array from Retina Implant AG, Reutlingen, Germany, was implanted in the subretinal space of eight patients (26).