Implantation and testing of subretinal film electrodes in domestic pigs.

By definition, an electronic subretinal visual prosthesis requires the implantation of stimulation electrodes in the subretinal space of the eye. Polyimide film electrodes with flat contacts were implanted subretinally and used for electrical stimulation in acute experiments in anaesthetised domestic pigs. In two pigs, the film electrode was inserted through a sclerostomy into the vitreous cavity and, subsequently, via a retinotomy into the subretinal space around the posterior pole (ab interno approach). In three other pigs the sclera and pigment epithelium were opened for combined ab interno and transscleral positioning of the subretinal electrode. In all cases, perfluorocarbon liquid (PFCL) was used to establish a close contact between the film electrode and the outer retina. After cranial preparations of three pigs for epidural recording of visual cortex responses, retinal stimulation was performed in one pig with a film electrode implanted ab interno and in two pigs with film electrodes implanted by the ab interno and transscleral procedure. The five subretinal implantations were carried out successfully and each polyimide film electrode tip was positioned beneath the outer retina of the posterior pole. The retina was attached to the stimulation electrode in all cases. Epidural cortical responses to light and electrical stimulation were recorded in three experiments. Initial cortical responses to Ganzfeld light and to electrical stimuli occurred about 40 and 20 ms, respectively, after stimulation onset. The stimulation threshold was approximately 100 microA and, like the cortical response amplitudes, depended both on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. Our results in a domestic pig model demonstrate that polyimide film electrodes can be implanted subretinally and tested by recording cortical responses to electrical stimulation. These findings suggest that the domestic pig could be an appropriate animal model for basic testing of subretinal implants.

Transscleral implantation and neurophysiological testing of subretinal polyimide film electrodes in the domestic pig in visual prosthesis development.

Loss of photoreceptor function is responsible for a variety of blinding diseases, including retinitis pigmentosa. Advances in microtechnology have led to the development of electronic visual prostheses which are currently under investigation for the treatment of human blindness. The design of a subretinal prosthesis requires that the stimulation device should be implantable in the subretinal space of the eye. Current limitations in eye surgery have to be overcome to demonstrate the feasibility of this approach and to determine basic stimulation parameters. Therefore, polyimide film-bound electrodes were implanted in the subretinal space in anaesthetized domestic pigs as a prelude to electrical stimulation in acute experiments. Eight eyes underwent surgery to demonstrate the transscleral implantability of the device. Four of the eight eyes were stimulated electrically. In these four animals the cranium was prepared for epidural recording of evoked visual cortex responses, and stimulation was performed with sequences of current impulses. All eight subretinal implantation procedures were carried out successfully with polyimide film electrodes and each electrode was implanted beneath the outer retina of the posterior pole of the operated eyes. Four eyes were used for neurophysiological testing, involving recordings of epidural cortical responses to light and electrical stimulation. A light stimulus response, which occurred 40 ms after stimulation, proved the integrity of the operated eye. The electrical stimuli occurred about 20 ms after the onset of stimulation. The stimulation threshold was approximately 100 microA. Both the threshold and the cortical responses depended on the correspondence between retinal stimulation and cortical recording sites and on the number of stimulation electrodes used simultaneously. The subretinal implantation of complex stimulation devices using the transscleral procedure with consecutive subretinal stimulation is feasible in acute experiments in an animal model approximating to the situation in humans. The domestic pig is an appropriate animal model for basic testing of subretinal implants. Animal experiments with chronically implanted devices and long-term stimulation are advisable to prepare the field for successful human experiments.

Subretinal implantation and testing of polyimide film electrodes in cats.

BACKGROUND: Progress in the field of microelectronics has led to the development of visual prostheses for the treatment of blinding diseases. One concept under investigation is an electronic subretinal prosthesis to replace the function of lost photoreceptors in degenerative diseases, such as retinitis pigmentosa. METHODS: In the subretinal prosthesis design concept, an array of stimulation electrodes is placed in the subretinal space. To test the feasibility of the concept and to determine basic stimulation parameters, wire-bound stimulation devices were used in acute trials for up to 12 h in three eyes in anaesthetised cats. These wire-bound stimulation elements were based on strips of polyimide film. The film strips were introduced through a sclerostomy into the vitreous cavity and via a retinotomy into the subretinal space during a modification of the standard three-port vitrectomy procedure. On entry through the retinotomy, the film was advanced mechanically to the desired position in the area centralis. Perfluorocarbon liquid (PFCL) was used to establish close contact between the electrode array and the outer retina. Stimulation was performed with computer-generated sequences of current waveforms in acute trials immediately after surgical implantation of the stimulation film. Cortical recordings in the primary visual cortex were performed with electrodes placed in locations corresponding to the retinal stimulus site. RESULTS: All three implantations were carried out successfully with the stimulation array implanted beneath the outer retina of the area centralis of the operated eye. The retina was attached over the stimulation array in all cases. No cortical responses were recorded in one of the stimulation sessions. The results from another session revealed clear intracortical responses to subretinal stimulation with polyimide films. Following single-site retina stimulation, the estimates of spatial cortical resolution and temporal resolution were approximately 1 mm and 20-50 ms, respectively. DISCUSSION: Our results indicate that focal subretinal stimulation evokes localised spatio-temporal distribution of cortical responses. These findings offer hope that coarse restoration of vision may be feasible by subretinal electrical stimulation.