Development of very large electrode arrays for epiretinal stimulation (VLARS)

BioMedical Engineering OnLine

Florian Waschkowski²  Stephan Hesse⁴  Anne Christine Rieck⁴  Tibor Lohmann⁴  Claudia Brockmann¹  Thomas Laube¹  Norbert Bornfeld¹  Gabriele Thumann³  Peter Walter⁴  Wilfried Mokwa²  Sandra Johnen⁴  Gernot Roessler⁴ 

[1] Department of Ophthalmology, University Hospital Essen, Hufelandstr 55, 45147 Essen, Germany

[2] Institute for Materials in Electrical Engineering I, RWTH Aachen University, Sommerfeldstr 24, 52074 Aachen, Germany

[3] Hôpitaux universitaires de Genève, Service d’ophtalmologie, Rue Alcide-Jentzer 22, CH-1211 Genève 14, Suisse

[4] Department of Ophthalmology, University Hospital Aachen, RWTH Aachen University, Pauwelsstr 30, 52074 Aachen, Germany

关键词: Neurostimulation;    Polyimide;    Silicon wafer Technology;    Vitreoretinal surgery;    Rehabilitation;    Blindness;    Retinitis pigmentosa;    Artificial vision;    Retinal prosthesis;   

Others  :  797197
DOI  :  10.1186/1475-925X-13-11

 received in 2013-08-20, accepted in 2014-01-29,  发布年份 2014

【 摘 要 】

Background

Retinal implants have been developed to treat blindness causing retinal degenerations such as Retinitis pigmentosa (RP). The retinal stimulators are covering only a small portion of the retina usually in its center. To restore not only central vision but also a useful visual field retinal stimulators need to cover a larger area of the retina. However, large area retinal stimulators are much more difficult to implant into an eye. Some basic questions concerning this challenge should be answered in a series of experiments.

Methods

Large area retinal stimulators were fabricated as flexible multielectrode arrays (MEAs) using silicon technology with polyimide as the basic material for the substrate. Electrodes were made of gold covered with reactively sputtered iridium oxide. Several prototype designs were considered and implanted into enucleated porcine eyes. The prototype MEAs were also used as recording devices.

Results

Large area retinal stimulator MEAs were fabricated with a diameter of 12 mm covering a visual angle of 37.6° in a normal sighted human eye. The structures were flexible enough to be implanted in a folded state through an insertion nozzle. The implants could be positioned onto the retinal surface and fixated here using a retinal tack. Recording of spontaneous activity of retinal neurons was possible in vitro using these devices.

Conclusions

Large flexible MEAs covering a wider area of the retina as current devices could be fabricated using silicon technology with polyimide as a base material. Principal surgical techniques were established to insert such large devices into an eye and the devices could also be used for recording of retinal neural activity.

【 授权许可】

   
2014 Waschkowski et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Daiger SP, Bowne SJ, Sullivan LS: Perspective on genes and mutations causing retinitis pigmentosa. Arch Ophthalmol 2007, 125:151-158.
• [2]Aldahmesh MA, Abu Safieh L, Alkuraya H, Al-Rajhi A, Shamseldin H, Hashem M, Alzahrani F, Khan AO, Alqahtani F, Rahbeeni Z, Alowain M, Khalak H, Al-Hazzaa S, Meyer BF, Alkuraya FS: Molecular characterization of retinitis pigmentosa in Saudi Arabia. Mol Vis 2009, 15:2464-2469.
• [3]Bunker CH, Berson EL, Bromley WC, Hayes RP, Roderick TH: Prevalence of retinitis pigmentosa in Maine. Am J Ophthalmol 1984, 97:357-365.
• [4]Humayun MS, de Juan E, Dagnelie G Jr, Greenberg RJ, Propst RH, Philips DH: Visual perception elicited by electrical stimulation of retina in blind humans. Arch Ophthalmol 1996, 114:40-46.
• [5]Hornig R, Laube T, Walter P, Velikay-Parel M, Bornfeld N, Feucht M, Akguel H, Rössler G, Alteheld N, Lütke Notarp B, Wyatt J, Richard G: A method and technical equipment for an acute human trial to evaluate retinal implant technology. J Neural Eng 2005, 2:129-134.
• [6]Keserü M, Feucht M, Bornfeld N, Laube T, Walter P, Rössler G, Velikay-Parel M, Hornig R, Richard G: Acute electrical stimulation of the human retina with an epiretinal electrode array. Acta Ophthalmol 2012, 90:e1-e8.
• [7]Yanai D, Weiland JD, Mahadevappa M, Greenberg RJ, Fine I, Humayun MS: Visual performance using a retinal prosthesis in three subjects with retinitis pigmentosa. Am J Ophthalmol 2007, 143:820-827.
• [8]Roessler G, Laube T, Brockmann C, Kirschkamp T, Mazinani B, Goertz M, Koch C, Krisch I, Sellhaus B, Trieu HK, Weis J, Bornfeld N, Rothgen H, Messner A, Mokwa W, Walter P: Implantation and explantation of a wireless epiretinal retina implant device: observations during the EPIRET3 prospective clinical trial. Invest Ophthalmol Vis Sci 2009, 50:3003-3008.
• [9]Benav H, Bartz-Schmidt KU, Besch D, Bruckmann A, Gekeler F, Greppmaier U, Harscher A, Kibbel S, Kusnyerik A, Peters T, Sachs H, Stett A, Stingl K, Wilhelm B, Wilke R, Wrobel W, Zrenner E: Restoration of useful vision up to letter recognition capabilities using subretinal microphotodiodes. Conf Proc IEEE Eng Med Biol Soc 2010, 1:5919-5922.
• [10]Menzel-Severing J, Laube T, Brockmann C, Bornfeld N, Mokwa W, Mazinani B, Walter P, Roessler G: Implantation and explantation of an active epiretinal visual prosthesis: 2-year follow-up data from the EPIRET3 prospective clinical trial. Eye (Lond) 2012, 26(4):501-509.
• [11]Eckmiller R: Learning retina implants with epiretinal contacts. Ophthalmic Res 1997, 29:281-289.
• [12]Stieglitz T, Beutel H, Keller R, Blau C, Meyer JU: Development of flexible stimulation devices for a retina implant system. Conf Proc IEEE Eng Med Biol Soc 1997, 5:2307-2310.
• [13]Mokwa W, Goertz M, Koch C, Krisch I, Trieu HK, Walter P: Intraocular epiretinal prosthesis to restore vision in blind humans. Conf Proc IEEE Eng Med Biol Soc 2008, 1-8:5790-5793.
• [14]Patel KS, Kohl PA, Bidstrup Allen SA: Dual capacitor technique for measurement of through-plane modulus of thin polymer films. J Polym Sci B 2000, 38(12):1634-1644.
• [15]Koch C, Fassbender H, Nolten U, Goertz M, Mokwa W: Fabrication and assembly techniques for a 3rd generation wireless epiretinal prosthesis. Aachen, Germany: Proc. of MME 2008, 19th Workshop on Micromachining, Micromechanics and Microsystems; 2008:365-368. ISBN: 978-3-00-025529-8
• [16]Mokwa W, Görtz M, Koch C, Krisch I, Trieu HK, Walter P: Intraocular epiretinal Prothesis to restore vision in blind humans. In Proc. of the 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, Vancouver. Piscataway, NJ, USA: EMBS; 2008:5790-5793.
• [17]Rodger DC, Fong AJ, Li W, Ameri H, Ahuja AK, Gutierrez C, Lavrov I, Zhong H, Menon PR, Meng E, Burdick JW, Roy RR, Edgerton VR, Weiland JD, Humayun MS, Tai YC: Flexible parylene-based multielectrode array technology for high-density neural stimulation and recording. Sens Actuators B 2008, 132(2):449-460. ISSN 0925-4005, http://dx.doi.org/10.1016/j.snb.2007.10.069 webcite
• [18]Wessling B, Mokwa W, Schnakenberg U: RF-sputtering of iridium oxide to be used as stimulation material in functional medical implants. J Micromech Microeng 2006, 16(6):S142-S148.
• [19]Drasdo N, Fowler CW: Non-linear projection of the retinal image in a wide-angle schematic eye. Br J Ophthalmol 1974, 58:709.
• [20]Eckhorn R, Wilms M, Schanze T, Eger M, Hesse L, Eysel UT, Kisvarday ZF, Zrenner E, Gekeler F, Schwahn H, Shinoda K, Sachs H, Walter P: Visual resolution with retinal implants estimated from recordings in cat visual cortex. Vision Res 2006, 46(17):2675-2690.
• [21]Walter P, Kisvárday ZF, Görtz M, Alteheld N, Rossler G, Stieglitz T, Eysel UT: Cortical activation via an implanted wireless retinal prosthesis. Invest Ophthalmol Vis Sci 2005, 46(5):1780-1785.
• [22]Ameri H, Ratanapakorn T, Ufer S, Eekhardt H, Humayun MS, Weiland JD: Toward wide-field retinal prosthesis. J Neural Eng 2009, 1:6(3).
• [23]Villalobos J, Allen PJ, McCombe MF, Ulaganathan M, Zamir E, Ng DC, Shepherd RK, Williams CE: Development of a surgical approach for a wide-view suprachoroida retinal prosthesis: evaluation of implantation trauma. Graefes Arch Clin Exp Ophthalmol 2012, 250:399-407.
• [24]Klauke S, Goertz M, Rein S, Hoehl D, Thomas U, Eckhorn R, Bremmer F, Wachtler T: Stimulation with a wireless intraocular epiretinal implant elicits visual percepts in blind humans. Invest Ophthalmol Vis Sci 2011, 52:449-455.
• [25]Walter P, Szurman P, Vobig M, Berk H, Ludtke-Handjery HC, Richter H, Mittermayer C, Heimann K, Sellhaus B: Successful long-term implantation of electrically inactive epiretinal microelectrode arrays in rabbits. Retina 1999, 19:546-552.
• [26]Menzel-Severing J, Sellhaus B, Laube T, Brockmann C, Bornfeld N, Walter P, Roessler G: Surgical results and microscopic analysis of the tissue reaction following implantation and explantation of an intraocular implant for epiretinal stimulation in minipigs. Ophthalmic Res 2011, 46:192-198.
• [27]Laube T, Brockmann C, Roessler G, Walter P, Krueger C, Goertz M, Klauke S, Bornfeld N: Development of surgical techniques for implantation of a wireless intraocular epiretinal retina implant in Göttingen minipigs. Graefes Arch Clin Exp Ophthalmol 2012, 250:51-59.
• [28]Ando F, Kondo J: A plastic tack for the treatment of retinal detachment with giant tear. Am J Ophthalmol 1983, 95:260-261.
• [29]de Juan E, Machemer R: Retinal tacks. Am J Ophthalmol 1985, 99:272-274.
• [30]Majji AB, Humayun MS, Weiland JD, Suzuki S, D’Anna SA, de Juan E Jr: Long-term histological and electrophysiological results of an inactive epiretinal electrode array implantation in dogs. Invest Ophthalmol Vis Sci 1999, 40:2073-2081.
• [31]Ahuja AK, Yeoh J, Dorn JD, Caspi A, Wuyyuru V, McMahon MJ, Humayun MS, Greenberg RJ, Dacruz L: Factors affecting perceptual threshold in Argus II retinal prosthesis subjects. Transl Vis Sci Technol 2013, 2(4):1. Epub 2013 Apr 12
• [32]Roessler G, Klee D, Mokwa W, Alteheld N, Harwardt M, Koch C, Hungar K, Sellhaus B, Walter P: Development of biochemically modified inactive retinal implants for fixation testing in animal experiments [abstract]. Invest Ophthalmol Vis Sci 2006, 47:3175. ARVO E-Abstract
• [33]Tunc M, Humayun M, Xuanghong C, Ratner BD: A reversible thermosensitive adhesive for retinal implants. Retina 2008, 28:1338-1343.
• [34]Margalit E, Babai N, Luo J, Thoreson WB: Inner and outer retinal mechanisms engaged by epiretinal stimulation in normal and rd mice. Vis Neurosci 2011, 28:145-154.
• [35]Fried SI, Lasker ACW, Desai NJ, Eddington DK, Rizzo JF: Axonal sodium-channel bands shape the response to electric stimulation in retinal ganglion cells. J Neurophysiol 2009, 101:1972-1987.
• [36]Jensen RJ, Rizzo JF, Ziv R, Grumet A, Wyatt J: Thresholds for activation of rabbit retinal ganglion cells with an ultrafine, extracellular microelectrode. Invest Ophthalmol Vis Sci 2003, 44:3533-3543.