Microphotodiode Array Research Articles

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.

Electrical Properties of Micro-Photodiode Arrays for Use as Artificial Retina Implant

Micro-photodiode arrays have been developed which are intended to eventually replace the function of degenerated photoreceptor cells in the retina. Electric current generated by tiny micro-photodiodes is delivered to the neuronal network in the retina via micro-electrodes. Since the coupling between electrode and tissue is capacitive of nature, only transient signals may be used for stimulation. Therefore, high capacitance of the interface between electrodes and tissue is an important prerequisite for efficient charge transfer. In addition, the electrical properties of the micro-photodiodes as are reflected in current/voltage traces have a profound influence on the charge delivery. For the first time the electrical properties of the entire system consisting of micro-photodiode array, electrode/electrolyte interface and tissue were studied. Our results indicate charged balanced operation of the device and the presence of a non-zero electrode polarization. The latter may be avoided, if an active current sink is employed in order to draw current to discharge the electrode capacitance.

Can subretinal microphotodiodes successfully replace degenerated photoreceptors?

The idea of implanting microphotodiode arrays as visual prostheses has aroused controversy on its feasibility from the moment it appeared in print. We now present results which basically support the concept of replacing damaged photoreceptors with subretinally implanted stimulation devices. Network activity in degenerated rat retinae could be modulated through local electrical stimulation in vitro. We also investigated the long term stability and biocompatibility of the subretinal implants and their impact on retinal physiology in rats. Ganzfeld electroretinograms and histology showed no significant side effect of subretinal implants on retinal function or the architecture of the inner retina.

Optimizing photodiode arrays for the use as retinal implants

The basic function of photoreceptors in the human eye is very similar to that of solar cells, namely delivering potential changes upon illumination. Solar cell or photodiode arrays may therefore serve for replacing natural photoreceptors, the progressive degeneration of which often results in a complete loss of vision in diseases like retinitis pigmentosa. Based on amorphous silicon, we have recently developed ultrathin and flexible microphotodiode arrays for subretinal implantation. We now report on the functional optimization of these devices, finally aiming at the recovery of vision in favour of the handicapped patients. The main topic of this study is the enhancement of stimulation power by the additional conversion of near infrared radiation, because the visible light alone will not be able to generate a sufficiently high charge transfer to the retina cells. Our concept is to use an amorphous silicon photoconductor for local light-induced enabling of the stimulation current, which is driven by a crystalline silicon solar cell acting as an infrared receiver. A proof of this concept is presented. First results indicate how the performance of our devices can be improved by minimizing the band discontinuities between amorphous and crystalline silicon, and by a proper optimization of doping levels and buffer layers.

Towards a Retina Prosthesis Model: Neurons on Microphotodiode Arrays In Vitro

Various neurodegenerative diseases of the retina lead to blindness. Since no pharmacological or gene therapy is available, the alternative concept of neuroprostheses has stimulated the development of micromachined photovoltaic devices. One strategy aims to replace degenerated photoreceptors by microphotodiode arrays (MPDA). MPDAs in the subretinal space shall transform light stimuli into electrical current for the stimulation of still unhampered retinal neurons. MPDAs were fabricated as silicon based multilayered PIN microstructures comprising titanium nitride stimulation electrodes of an area of 8 × 8 μm2. In an effort to develop meaningful tools to evaluate functional MPDA biocompatibility, a novel in vitro system was designed. Retinal cells were cultured on MPDAs, while current generation in MPDAs as in the eye was imitated by light emitting diodes (LED) operating at different wavelengths. For analysis epifluorescence and scannning electron microscopy was employed. MPDAs displayed increasing current delivery with increasing illumination. Surface modification of MPDAs including oxygen plasma treatment and adsorption of polyanions together with laminin were found to render the MPDA surface permissive for cell adhesion. Cell vitality tests using fluorescence markers revealed no adverse effects of optoelectric stimulation via LED/MPDAs. In addition, neurite formation and the expression of differentiation antigen 2A10 were unaffected after stimulation. Optoelectric stimulation allowed regular differentiation of various retinal cell types. In summary, the data provide the first evidence that optoelectric stimulation via MPDAs does not hamper cellular integrity under the experimental conditions chosen. The results support the concept of microphotodiodes as a retinal prosthesis.

Subretinal Semiconductor Microphotodiode Array

To examine the function of a semiconductor microphotodiode array (SMA) surgically implanted in the subretinal space. 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. 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. SMAs can be successfully implanted into the subretinal space and will generate current in response to light stimulation during an extended period of time.

The development of subretinal microphotodiodes for replacement of degenerated photoreceptors.

There are presently several concepts to restore vision in blind or highly visually handicapped persons by implanting electronic devices into the eye in order to partially restore vision. Here, the approach to replace retinal photoreceptors by a subretinally implanted microphotodiode array (MPDA) is summarized. A survey is given on the present state of the development of MPDAs, the possibility of in vitro and in vivo tests as well as first results on biocompatibility and histology. Additionally, electrophysiological recordings in rabbits and rats are presented which have received such subretinal implants.