Compound subretinal prostheses with extra-ocular parts designed for human trials: successful long-term implantation in pigs
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Subretinal implants aim to replace photoreceptor function in patients suffering from degenerative retinal disease like retinitis pigmentosa by topically applying electrical stimuli in the subretinal space. This study—as a last step before upcoming human trials—explored a newly developed surgical technique for permanent implantation of complex subretinal implants with extra-ocular parts.
The implant consisted of a microphotodiode array (MPDA) with 1,550 electrodes and a 4×4 array of gold electrodes for direct electrical stimulation; both were mounted onto a polyimide foil for transscleral placement into the subretinal space. The foil carried connection lanes to a silicone cable that was implanted under the skin and led to a stimulator box in the animal’s neck. Surgery was performed in 11 domestic pigs. Improved vitreo-retinal surgical technique consisted of a 180° peripheral retinotomy and use of diathermy to penetrate the choroid in order to avoid choroidal haemorrhage. Subretinal forceps were used to place the implant safely onto the retinal pigment epithelium before the retina was flattened, peripheral laser photocoagulation was applied and the eye was filled with silicon oil. The implant was stabilized by a scleral fixation patch, use of a metal clamp with bone screws on the animal’s skull and a tissue ring under the animal’s skin in the neck. Behaviour was observed in the freely moving animals after direct subretinal electrical stimulation and funduscopy, optical coherence tomography, fluorescein angiography and histology were performed.
All implants were successfully placed subretinally. In three animals a proliferative vitreo-retinopathy was observed after approximately 2 weeks. Otherwise, funduscopy and OCT demonstrated complete retinal attachment and FA showed no retinal vascular abnormalities over and around the implant. The animals showed clear behavioural reactions to electrical stimulation over the whole examination period. Histological examination failed to show any voltage-induced alteration in the cellular architecture of the retina overlying the stimulation electrodes.
This study demonstrates the feasibility of a new surgical procedure for highly safe and controlled implantation of complex subretinal devices with extra-ocular parts. The new implant design proved to be safely implantable in free-moving pigs for an observation period of 4 weeks.
KeywordsRetina Prosthesis Subretinal Implant Retinitis pigmentosa Photodiode Retinal degeneration
The study was supported in part by Retina Implant AG, Markwiesenstrasse 55, 72770 Reutlingen, Germany. We gratefully acknowledge the help of our project partners (Retina Implant AG: W. G. Wrobel, R. Rubow, H. Sailer, A. Harscher, S. Meine; Institute for Microelectronics, Stuttgart; Institute for Physical Electronics, Stuttgart: H.G. Graf, H. Gruber; all Germany). Helmut Sachs gave us friendly advice from his experience with subretinal implant surgery. Our veterinarians K. Pressler and S. Burgsmüller were outstanding in caring for our animals in the postoperative period. Gabi Fuchs and Annette Wagner were extremely helpful in surgery, as was A. Bezirgiannidis in providing help in installing the animal operation theatre. Without the excellent technical assistance and animal care provided by the team of the Hohenheim animal experimental unit (C. Fischinger, M. Mecchelem, W. Dunne, D. Günther, and J. Bzyl) this study would not have been possible. Regina Hofer contributed excellent graphics for Fig. 2. The German Ministry for Education and Research (BMBF) (grant no. 01KP0401) and the Ewald + Karin Hochbaum-Stiftung have once more generously supported our work.
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