Speaker: Eberhart Zrenner
Chair Professor of Ophthalmology
Centre for Ophthalmology Institute for Ophthalmic Research
University of Tübingen, Germany
Title: Advances in Subretinal Implants: Technical Developments and Clinical Outcomes
Abstract: In the last decade, about 100 people world-wide have received several kinds of electronic implants to restore visual function lost to retinal degenerations.
Background: Essentially three concepts are being pursued (Ref. 1): a) epiretinal electrode arrays that are controlled by a camera outside the body and a computer that translates the video image into pulses that are sent directly to the retina’s output cells, the ganglion cells and their nerve fibers, and b) the subretinal approach aiming at replacing the photoreceptors by photodiodes at the input side of the degenerated retina, and stimulating bipolar cells, as photoreceptors would normally do; this approach utilizes the natural processing network of the inner retina, and places the stimulation electrodes at the place of the former photoreceptors; c) the suprachoroidal approach, where the electrode array is placed behind the choroid, with some distance to retinal input neurons. Presently three approaches are available to patients, the ARGUS II System (Second Sight, Sylamar USA, 60 epiretinal electrodes, approx. 50 Patients, postmarketing surveillance starting), the Alpha-IMS study (Retina Implant AG, Tübingen/Reutlingen, Germany, 1500 subretinal electrodes, 36 patients) and the study of Bionic Vision Australia (24 suprachoroidal electrodes in 3 patients). Many other groups are also working hard to develop implants for artificial vision in blind people. In the first part of the lecture, the peculiar properties of the various approaches will be discussed from a physiological and clinical viewpoint.
The subretinal approach: To restore useful visual sensations to patients blind from photoreceptor dystrophies, an externally powered photosensitive microphotodiode array with 1500 pixels (Alpha-IMS implant of Retina Implant AG, Reutlingen , Germany) was implanted in the subretinal space, as will be reported in the second part of the lecture (Ref.2). A multicentre trial is presently being performed (www.clinicaltrials.gov, NCT01024803) that includes centres in Tuebingen, London, Oxford, Dresden, Budapest and Hongkong. So far 36 patients have undergone the procedure. Here we report on the pilot trial and the first module of the main trial (Ref.3). All the subjects had successful implantation of the chip and were able to perceive light after implantation of the photodiode chip. The visual experiences ranged from perception of light where there was none before surgery, to the ability to see individual letters 4 cm high at a working distance of 40 cm. Motion detection was possible up to angular speed up to 35 deg/s, grating acuity up to 3.3 cycles per degree. In some cases visual acuity measurement with Landolt C-rings was possible up to Snellen visual acuity of 20/546. Additionally, the identification, localization and discrimination of objects improved significantly in most patients. In repeated tests over a nine month period, several subjects were able to read letters spontaneously, controlled in four alternative forced choice tests. Control tests were performed each time with the implant's power source switched off.
Conclusion: The study has shown proof of concept that a photodiode chip placed in the subretinal space can provide useful vision for many subjects. Selection of patients based on experiences with preoperative OCT analysis, fluorescence angiography and autofluorescence helps to identify patients optimally suited for rehabilitation measures by means of subretinal electronic implants. From these developments and ongoing clinical studies it can be predicted that electronic implants will finally be available for the blind for restitution of visual abilities that are truly useful in daily life.
1. Zrenner E, Artificial vision: solar cells for the blind. Nature Photonics 2012, 6: 344–345
2. Zrenner E, Bartz-Schmidt KU, Benav H, Besch D, Bruckmann A, Gabel VP, Gekeler F, Greppmaier U, Harscher A, Kibbel S, Koch J, Kusnyerik A, Peters T, Stingl K, Sachs H, Stett A, Szurman P, Wilhelm B, Wilke R. Subretinal electronic chips allow blind patients to read letters and combine them to words. Proc Biol Sci. 2011; 278:1489-97
3. Stingl K, Bartz-Schmidt KU, Besch D, Braun A, Bruckmann A, Gekeler F, Greppmaier U, Hipp S, Hörtdörfer G, Kernstock C, Koitschev A, Kusnyerik A, Sachs H, Schatz A, Stingl KT, Peters T, Wilhelm B and Zrenner E. Artificial vision with wirelessly powered subretinal electronic implant alpha-IMS. Proc. R. Soc. B 2013, 280, published online, 20 February 2013
Prof. Dr. med. Eberhart Zrenner trained as an engineer before studying medicine and has become one of the foremost retinal electrophysiologists and psychophysicists. His research interests include retinal physiology and pathophysiology, neuro-ophthalmology, ophthalmic toxicology, retina implants and methods of non-invasive function testing. He also is Principal Investigator of several clinical studies and has developed a subretinal active microphotodiode array (MPDA) to replace degenerated photoreceptors in blind people so far tested in 30 patients in an international multicenter trial. He serves for the German Research Council on several projects and is the recipient of several international awards, author of more than 200 publications and coordinator of several European grants.
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