Advances in retinal implant technology

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Erick Bates
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1 Advances in retinal implant technology Andrew Kuznetsov Freiburg i.br. 3 May 2012 Rhine-Waal University of Applied Sciences, Emmerich

2 Strategies electronic implants (top-down) subretinal implants epiretinal implant cell implants stem cells gene implants (bottomup) optogenetic therapy (creation of light-sensitive retinal ganglion cells) photoreceptor cells: 95% rods, 5% cones loss of photoreceptor cells in the visual perception channel leads to loss of vision

of light-sensitive retinal ganglion cells) photoreceptor cells: 95% rods, 5%

3 Clinical problems RP dry AMD norm over 25m people around the world are visually impaired and that will rise to 50m by 2020 retinitis pigmentosa (RP) and age-related macular degeneration (AMD) cause a degeneration of the retina

50m by 2020 retinitis pigmentosa (RP) and age-related

4 History of artificial vision the discovery of phosphenes in projects on artificial vision in , Charles LeRoy, visual sensations of light by passing a charge through the eye of a blind man 1929, Ottfricd Foerster, electrical stimulation of the cerebral cortex resulted in phosphenes 1956, Graham Tassiker, subretinal light-sensitive selenium cell transiently restored the blind patient s ability to perceive phosphenes 1997, Rolf Eckmiller, first epiretinal implant... Gerding, 2008

stimulation of the cerebral cortex resulted in phosphenes 1956, Graham Tassiker, subretinal light-sensitive selenium cell

5 The eye and retinal implants human eye epiretinal implants: fixing is difficult don t need intact optics editorial processing subretinal implants: easy fixing need intact optics native stimulation ~100 fold compression: from 131m photoreceptor cells to 1.2m ganglion neurons c - Argus II, d Alpha IMS, f - Boston Retinal Implant Gerding, 2008

optics native stimulation ~100 fold compression: from 131m photoreceptor cells to 1.

6 Boston Retinal Implant Project Joseph Rizzo, John Wyatt subretinal implant 3x5 electrodes 3 pigs, > 7 months Shire et al, 2009

7 Second Sight, Argus II Alan Litke epiretinal implant on the market in spring year clinical trial 23 of 30 patients read large fonts 6x10 electrodes (in future 200, 512 electrodes, diameter 5 µm) (a) scleral band, coil receiving power and data, electronics to process data, ribbon cable passing through the sclera to the implant (b) video camera, transmission coil, control unit reducing the image resolution to 6x10 pixels

coil receiving power and data, electronics to process data, ribbon cable passing through the sclera to the

8 Retina Implant AG, Alpha IMS Eberhart Zrenner subretinal implant microchip and external power supply through a cable micro photodiode array (MPA), 30x50 light sensors implants were removed after 4 months Stingl et al, 2012

array (MPA), 30x50 light sensors implants were removed after 4 months

9 Bionic Eye with IR projection Daniel Palanker array with pillars of 10 µm in diameter and 65 µm in height alternative: cells are attracted by the holes in a newly designed array pillar electrodes (1) penetrating into retina, return electrodes (2) are located on photodiodes rat retina after implantation of the array into a subretinal space. Tops of pillars achieve proximity to cells in the inner nuclear layer Loudin et al, 2007

into retina, return electrodes (2) are located on photodiodes rat retina after implantation of the array

10 Obstacles and development Despite some successes, these electronic implants remain open-loop devices with poorly understood mechanisms of action new image preprocessing methods new systems design How many electrodes are required? 20/80 vision, d < 7 µm, 2.5m electrodes/cm 2 Problems delivery of information about thousands of pixels signal processing that compensates the loss of retinal network placement of electrodes close to target cells interaction between electrodes energy dissipation and electrolysis Early development projects new biocompatible materials (parylene C), nano-structured implants, novel electrodes to exceed 100m/cm 2 ambient light operations in a contact lens

5m electrodes/cm 2 Problems delivery of information about thousands of pixels signal processing that compensates the loss of retinal network placement of electrodes close

11 Cell and gene implants no FDA-approved therapy for the retinitis pigmentosa (RP) Stem cells ophthalmology engineering scaffold to support cell transplants Ocular gene therapy the immune-privileged status of the eye gene transfer mediated by adenoassociated viruses (AAV) transfection of bipolar or ganglion cells induced photosensitivity with channelrhodopsin-2 (Chop2) RetroSense Therapeutics, retina analysis in light and dark conditions Ivanova et al, 2010

by adenoassociated viruses (AAV) transfection of bipolar or ganglion cells induced photosensitivity with

12 Reading and acknowledgements Shire et al., Development and implantation of a minimally invasive, wireless subretinal neurostimulator // IEEE Trans. Biomed. Eng. 2009; 56/10: Humayun et al., Interim Results from the International Trial // Ophthalmology 2012; 119: Sahni et al., Therapeutic Challenges to Retinitis Pigmentosa: From Neuroprotection to Gene Therapy // Current Genomics 2011; 12: Ivanova et al., Retinal channelrhodopsin-2-mediated activity in vivo evaluated with manganese-enhanced magnetic resonance imaging // Molecular Vision 2010; 16: Many thanks for supporting materials to Prof. Gislin Dagnelie, Johns Hopkins Univ. Sch. of Medicine, Baltimore Prof. Kareem Zaghloul, Institute of Neurological Disorders and Stroke, Bethesda Thanks to Prof. Thorsten Brandt suggesting the topic

, Therapeutic Challenges to Retinitis Pigmentosa: From Neuroprotection to Gene Therapy // Current Genomics 2011; 12: 276-84 Ivanova et al.

The Retinal Implant Project

The Retinal Implant Project RLE Group Retinal Implant Research Group Academic and Research Staff Professor John L. Wyatt, Jr. Visiting Scientists and Research Affiliates Joseph F. Rizzo, M.D., Dr. Shawn