Visual evoked potentials to infrared stimulation in normal cats and rats.

The absence of effective treatments for retinal degenerative diseases has inspired several laboratories to pursue the development of a retinal prosthetic. In our laboratory, we have focused on the subretinal approach, using an array of photodiodes housed within a silicon chip. These photodiodes generate electrical current in response to wavelengths ranging from 500-1100 nm. Because the native retina is traditionally thought to be insensitive to wavelengths beyond approximately 750 nm, we and others have attempted to isolate implant-mediated electrophysiological responses from those of the native retina by using longer wavelength stimuli in the near infrared range. Evoked potentials recorded over the visual cortex in response to infrared stimuli have been reported as evidence of a functional subretinal implant due to the typical physiological characteristics of the waveform: a direct relationship between amplitude and intensity, increased amplitude over the visual cortex, and repeatability of the response. However, these results should be interpreted with caution since here we report an unappreciated sensitivity of the native retina to infrared light under dark-adapted conditions.

Implantation of silicon chip microphotodiode arrays into the cat subretinal space.

There are currently no therapies to restore vision to patients blinded by photoreceptor degeneration. This project concerns an experimental approach toward a semiconductor-based subretinal prosthetic designed to electrically stimulate the retina. The present study describes surgical techniques for implanting a silicon microphotodiode array in the cat subretinal space and subsequent studies of implant biocompatibility and durability. Using a single-port vitreoretinal approach, implants were placed into the subretinal space of the right eye of normal cats. Implanted retinas were evaluated post-operatively over a 10 to 27 month period using indirect ophthalmoscopy, fundus photography, electroretinography, and histology. Infrared stimulation was used to isolate the electrical response of the implant from that of the normal retina. Although implants continued to generate electrical current in response to light, the amplitude of the implant response decreased gradually due to dissolution of the implant's gold electrode. Electroretinograms recorded from implanted eyes had normal waveforms but were typically 10-15% smaller in amplitude than those in unimplanted left eyes. The nonpermeable silicon disks blocked choroidal nourishment to the retina, producing degeneration of the photoreceptors. The laminar structure of the inner retinal layers was preserved. Retinal areas located away from the implantation site appeared normal in all respects. These results demonstrate that silicon-chip microphotodiode-based implants can be successfully placed into the subretinal space. Gold electrode-based subretinal implants, however, appear to be unsuitable for long-term use due to electrode dissolution and subsequent decreased electrical activity.

Subretinal semiconductor microphotodiode array.

BACKGROUND AND OBJECTIVE: To examine the function of a semiconductor microphotodiode array (SMA) surgically implanted in the subretinal space. MATERIALS AND METHODS: Positive-intrinsic layer-negative (PiN) or negative-intrinsic layer-positive (NiP) SMAs were surgically placed into the subretinal space of rabbits through a pars plana incision and a posterior retinotomy. The implants required no external connections for power and were sensitive to light over the visible and infrared (IR) spectrum; IR stimuli were used to isolate implant-mediated responses from the activity of native photoreceptors. A stimulator ophthalmoscope was used to superimpose IR stimuli on the implant and adjacent retinal areas, and responses were recorded during the postoperative recovery period. SMA responses were also evaluated in vitro. The animals were given lethal anesthetic overdoses, and the retinas were examined histologically. RESULTS: The in vitro implant response consisted of an electrical spike, followed by a small-amplitude DC offset that followed the time course of the IR stimulation, and an overshoot at the stimulus offset. The SMAs placed in the subretinal space retained a stable position and continued to function throughout the postoperative period. The SMA responses recorded in vivo included additional slow-wave components that were absent from the in vitro recordings. These responses reverted to the in vitro configuration following the death of the animal. There was a significant loss of retinal cells in areas overlying the implant, and the retina appeared normal away from the implant and surgical site. CONCLUSION: SMAs can be successfully implanted into the subretinal space and will generate current in response to light stimulation during an extended period of time.

Subretinal electrical stimulation of the rabbit retina.

A number of disorders results in photoreceptor degeneration, yet spare the inner retinal layers. We are investigating the possibility that retinal function may be restored in such a situation by electric current applied from the subretinal space. In the present study, bipolar strip electrodes receiving electric current from external photodiodes were implanted into the subretinal space of adult rabbits. Recordings were made from the scalp overlying the visual cortex in response to photic flash stimulation of one eye before surgery. This was compared to the visual cortex response caused by subretinal electrical stimulation of the same eye from an implanted strip electrode. Electric current to the strip electrode was provided by an externally connected photodiode that was stimulated at a remote location with a photoflash. The electrical stimulus was recordable as a brief electrical implant spike during stimulation. In addition, after the implant spike, cortical responses were obtained in response to subretinal electrical stimulation that resembled closely the normal light induced visual evoked potential produced by the pre-implanted eye. These results indicate that the visual system can be activated by electrical stimulation from the subretinal space and indicate that this approach may provide a means to restore vision to eyes blinded by outer retinal disease.