3 May 2012 Rhine-Waal University of Applied Sciences, Emmerich

Advances in retinal implant technology

Andrew Kuznetsov

Freiburg i.Br.

Strategies

• electronic implants (top-down)

– subretinal implants

– epiretinal implant

• cell implants

– stem cells

• gene implants (bottom-up)

– 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

Clinical problems

• 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

normRP dry AMD

History of artificial vision

• 1755, Charles LeRoy, visual sensations of light by passing a chargethrough the eye of a blind man

• 1929, Ottfricd Foerster, electrical stimulation of the cerebral cortexresulted 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• ...

22 projects on artificial vision in 2007

the discovery of

phosphenes in 1755

Gerding, 2008

The eye and retinal implants

~100 fold compression:from 131m photoreceptor cellsto 1.2m ganglion neurons

human eye

c - Argus II, d – Alpha IMS, f - Boston Retinal Implant

epiretinal implants:

fixing is difficultdon’t need intact opticseditorial processing

subretinal implants:

easy fixingneed intact opticsnative stimulation

Gerding, 2008

Boston Retinal Implant Project • Joseph Rizzo, John Wyatt• subretinal implant

• 3x5 electrodes

• 3 pigs, > 7 months

Shire et al, 2009

Second Sight, Argus II

• Alan Litke

• epiretinal implant

• on the market in spring 2011• 2-year clinical trial• 23 of 30 patients read large fonts• 6x10 electrodes (in future 200,

512 electrodes, diameter 5 µm)

http://2-sight.eu/

(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

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

http://www.eye.uni-tuebingen.de/retina-implant/videos/2

Stingl et al, 2012

Bionic Eye with IR projection

array with pillars of 10 µm in diameter and 65 µm in height

pillar electrodes (1) penetrating into retina,return electrodes (2) are located on photodiodes

rat retina after implantation of the array intoa subretinal space. Tops of pillars achieveproximity to cells in the inner nuclear layer

alternative:cells are attracted by the holes in a newly designed array

Loudin et al, 2007

Daniel Palanker

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/cm2

• 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/cm2

– ambient light operations in a contact lens

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 adeno-associated viruses (AAV)

– transfection of bipolar or ganglion cells

– induced photosensitivity with channelrhodopsin-2 (Chop2)

– RetroSense Therapeutics, http://www.retro-sense.com/

retina analysis in light and dark

conditionsIvanova et al, 2010

Reading and acknowledgements

• Shire et al., Development and implantation of a minimally invasive, wireless sub-retinal neurostimulator // IEEE Trans. Biomed. Eng. 2009; 56/10: 2502-11

• Humayun et al., Interim Results from the International Trial // Ophthalmology 2012; 119: 779-88

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

• Ivanova et al., Retinal channelrhodopsin-2-mediated activity in vivo evaluated with manganese-enhanced magnetic resonance imaging // Molecular Vision 2010; 16: 1059-1067

• 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