Evaluation of phosphenes elicited by extraocular stimulation in normals and by suprachoroidal-transretinal stimulation in patients with retinitis pigmentosa.
ABSTRACT To determine the efficient parameters to evoke electrical phosphenes is essential for the development of a retinal prosthesis. We studied the efficient parameters in normal subjects and investigated if suprachoroidal-transretinal stimulation (STS) is effective in patients with advanced retinitis pigmentosa (RP) using these efficient parameters.
The amplitude of pupillary reflex (PR) evoked by transcorneal electrical stimulation (TcES) was determined at different frequencies in eight normal subjects. The relationship between localized phosphenes elicited by transscleral electrical stimulation (TsES) and the pulse parameters was also examined in six normal subjects. The phosphenes evoked by STS were examined in two patients with RP with bare light perception. Biphasic pulses (cathodic first, duration: 0.5 or 1.0 ms, frequency: 20 Hz) were applied through selected channel(s). The size and shape of the phosphenes perceived by the patients were recorded.
The maximum PR was evoked by TcES with a frequency of 20 Hz. The brightest phosphene was elicited by TsES with a pulse train of more than 10 pulses, duration of 0.5-1.0 ms and a frequency of 20 to 50 Hz. In RP patients, localized phosphenes were elicited with a current of 0.3-0.5 mA (0.5 ms) in patient 1 and 0.4 mA (1.0 ms) in patient 2. Two isolated or dumbbell-shaped phosphenes were perceived when the stimulus was delivered through two adjacent channels.
Biphasic pulse trains (> or =10 pulses) with a duration of 0.5-1.0 ms and a frequency of 20-50 Hz were efficient for evoking phosphenes by localized extraocular stimulation in normal subjects. With these parameters, STS is a feasible method to use with a retinal prosthesis even in advanced stages of RPs.
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ABSTRACT: Short-term pattern electrical stimulation of the retina via multielectrode arrays in humans blind from photoreceptor loss has shown that ambulatory vision and limited character recognition is possible. To develop an implantable retinal prosthesis that would provide useful vision, these results need to be sustained over a prolonged period of retinal electrical stimulation. As a first step toward this goal, the biocompatibility and the feasibility of surgically implanting an electrically inactive electrode array onto the retinal surface was tested. A 5 x 5 electrode array (25 platinum disc-shaped electrodes in a silicone matrix) was implanted onto the retinal surface using retinal tacks in each of the 4 mixed-breed sighted dogs. Color fundus photography, fluorescein angiography, electroretinography, and visual evoked potentials were obtained preoperatively, at 1-week intervals for 2 weeks postoperatively, then at 2-week intervals up to 2 months postoperatively, and thereafter at 1-month intervals. One dog was killed at 2 months after implantation and a second dog after 3 months of implantation. Histologic evaluation of the retinas was performed. The remaining two dogs continue to be followed beyond 6 months after the implantation surgery. No retinal detachment, infection, or uncontrolled intraocular bleeding occurred in any of the animals. Retinal tacks and the retinal array remained firmly affixed to the retina throughout the follow-up period. Hyperpigmentation of the retinal pigment epithelium was observed only around the site of retinal tack insertion. No fibrous encapsulation of the implant or intraocular inflammation was visible. A- and b-wave amplitudes of the electroretinogram were depressed at the first postoperative week testing but recovered over the ensuing 1 week and were not statistically different from the normal unoperated fellow eye throughout the postoperative period. N1 and P1 wave amplitudes of the visual evoked potentials were not significantly different from the normal fellow eyes at any of the postoperative test intervals. Fluorescein angiography showed that the entire retina including the area under the electrode array remained well perfused. Similarly, histologic evaluation revealed near total preservation of the retina underlying the electrode array. Implantation of an electrode array on the epiretinal side (i.e., side closest to the ganglion cell layer) is surgically feasible, with insignificant damage to the underlying retina. The platinum and silicone arrays as well as the metal tacks are biocompatible. With the success of implanting an electrically inactive device onto the retinal surface for prolonged periods, the effects of long-term retinal electrical stimulation are now ready to be tested as the next step toward developing a prototype retinal prosthesis for human use.Investigative Ophthalmology & Visual Science 09/1999; 40(9):2073-81. · 3.44 Impact Factor
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ABSTRACT: Simple basic visual perception may be restored by epiretinal electrical stimulation in patients that are blind due to photoreceptor loss. To stimulate ganglion cells, epiretinally flat platinum microelectrodes embedded in thin polyimide film were developed and tested in the cat. After removal of the lens and the vitreous body a thin microfilm electrode array was implanted through a corneoscleral incision in the cat eye (n = 4). In two eyes no further attempt was made to fixate the tip of the electrode, which was pressed onto the retinal surface due to the tension of the curved polyimide film. In two eyes the tip of the electrode was fixed with cyanoacrylate adhesive. The exterior part of the microelectrode film was directed under the skin towards the forehead which allowed fixation of the microplug to a head fixation bolt. Retinal stimulation experiments were performed within 1 week after implantation. Success of stimulation was assessed by recording neuronal activities from areas 17 and 18. Retinal microelectrodes were removed 2 weeks or longer after implantation. Intraocular inflammation or retinal detachment were not observed after implantation of the microelectrode film. In two eyes the tip of the microelectrodes dislocated spontaneously within the first few days. The lowest threshold of electrical stimulation was 35 microA, corresponding to a charge transfer of 14 nC per phase. These values were ten times higher than those obtained by needle electrodes used in prior experiments. Intraocular implanted flat microelectrodes made of platinum and polyimide were well tolerated. Because of the flat configuration of the microelectrodes higher stimulation thresholds than for needle electrodes were found, indicating insufficient contact to the retinal surface. An alternative shape and fixation technique is required to minimise electrodes' threshold of stimulation.Albrecht von Graæes Archiv für Ophthalmologie 11/2000; 238(10):840-5. · 1.93 Impact Factor
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ABSTRACT: To report methods for performing epiretinal electrical stimulation with microfabricated electrode arrays and determining perceptual thresholds on awake human volunteers during acute surgical trials. Four hypotheses were tested: (1) epiretinal stimulation can be performed during acute experiments without obviously damaging the retina or degrading vision or the health of the eye; (2) perception can be obtained 50% of the time in blind patients with charge densities below published safety limits; (3) the minimal charge needed to induce perception would be higher in patients with more severe retinal degeneration; and (4) threshold charge would be lower at shorter stimulus durations. Five subjects with severe blindness from retinitis pigmentosa and one with normal vision (who underwent enucleation of the eye because of orbital cancer) were studied. Electrical stimulation of the retina was performed on awake volunteers by placing a single 250-microm diameter handheld needle electrode or a 10-microm thick microfabricated array of iridium oxide electrodes (400-, 100-, or 50-microm diameter) on the retina. Current sources outside the eye delivered charge to the electrodes. Assessment of damage was made by observing the clinical appearance of the eyes, comparing pre- and postoperative visual acuity, obtaining retinal histology in one case, and comparing perceptual thresholds with published safety limits. No clinically visible damage to the eye or loss of vision occurred. Even at sites removed from stimulation, histology revealed swollen photoreceptor inner and outer segments, which were believed to be nonspecific findings. Percepts could not be reliably elicited with 50-microm diameter electrodes using safe charges in one blind patient. With the two larger electrodes, only the normal-sighted patient had thresholds at charge densities below 0.25 and 1.0 millicoulombs (mC)/cm(2) for 400- and 100-microm diameter electrodes, respectively, which is one seemingly reasonable estimate of safety derived from the product of charge per phase and charge density per phase. In blind patients, thresholds always exceeded these levels, although most were close to these limits in patient 6. The range of charge density thresholds with the 400- microm electrode in blind patients was 0.28 to 2.8 mC/cm(2). The normal-sighted patient had a threshold of 0.08 mC/cm(2) with a 400-microm electrode, roughly one quarter of the lowest threshold in the blind patients. Strength-duration curves obtained in two blind patients revealed the lowest threshold charge at the 0.25- or 1.0-ms stimulus duration. Threshold charge densities in severely blind patients were substantially higher than that in a normal-sighted patient. Charge densities in blind patients always exceeded one seemingly reasonable estimate of safe stimulation. The potential adversity of long-term stimulation of the retina by a prosthesis has yet to be determined.Investigative Ophthalmology & Visual Science 01/2004; 44(12):5355-61. · 3.44 Impact Factor