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The Bionic Eyeand the Field of Visual ProsthesisBrittney J. PfeiferUniversity of Missouri Saint Louis11 March 2013

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Outline of Todays Presentation:Anatomy of the EyeHereditary Retinal DiseasesMacular Degeneration (AMD)Retinitis Pigmentosa (RP)History of Visual ProsthesisIntroductionTypes of Visual ProsthesesResearch behind Alpha-IMSIntroduction and HypothesisMethodsResultsConclusions of StudyConclusions and Future Outlook

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Anatomy of the EyeSclera white of eyeOptic nerve transmits visual information from retina to brainRetina photoreceptor cells arranged in several layersFovea provides sharpest images

Optic Nerve:--consists of axons of ganglion cells joined togetherRetina:--Photoreceptors: convert light into electrical signals, which process signals within the retina and forward them via ganglion cell axons to visual cortex of the brain for processing. Two types of photoreceptor cells:--Rods: responsible for peripheral vision and night vision--Cones: responsible for central visual acuity and color vision--Other cells located in front of rods and cones are bipolar cells, ganglion cells, horizontal cells, amacrine cellsFovea:--Region in center of retina--Contains only cones

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Macular Degeneration (AMD)Results in gradual destruction of the macula among people age 50+Causes:Loss of vision, but not complete blindnessCan still see using peripheral visionImage is there, but detail is lostTwo types:DryWetDetected by:Visual acuity testDilated eye exam

Macula:--Made up of millions of light-sensing cells that provide sharp, detailed central vision--Most sensitive part of retina located at back of eyeTwo types:--Dry: occurs when light-sensitive cells in macula slowly break down, gradually blurring central vision; most common--Wet: severe stage of dry degeneration that occurs when new blood vessels under macula leak blood and fluid rapidly damaging maculaDetected by:--Visual acuity test: measures how well you can see by reading a Snellen chart--Dilated eye exam: eyes are dilated with drops and then a Binocular Indirect Ophthalmoscope is used to visualize the inside of the eye4

Retinitis Pigmentosa (RP)

Results in loss of photoreceptors during childhood or late 40s to early 50sCauses:Difficulty seeing at night or in dim lightingGradual loss of peripheral visionLoss of central vision (in advanced cases)Incurable blindnessDetected by:Dilated eye examElectroretinography (ERG) test

Detected by:--Dilated eye examDr. will notice clumps of pigment in peripheral retinal called bone-spicules--Electroretinography (ERG) testStudies eyes response to light stimuli; gives information about function of rods and cones in retinaHereditary disease:--X-linked: passed from mother to son--Autosomal recessive: genes required from both parents--Autosomal dominant: gene required from one parentIs often a sex-linked disease, so RP affects males more than females

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History of Visual Prosthesis1929: German neurologist, Otfrid Foerster, discovered electrically stimulating occipital lobe caused patients to see phosphenes1931: Fedor Krause and Heinrich Schum performed same experiment on a patient who had been blind for 8 years1956: Australian, Graham Tassicker, described how a photosensitive cell placed behind retina of a blind patient resulted in phosphenes1960s and 1970s: Giles Brindley and William Dobelle established Field of Visual Prosthesis by implanting electrodes into visual cortex and demonstrating their ability to induce consistent phosphenes1990s to Present: Advances in biomaterials, electronics, and retinal surgery have led to a cascade of developments in the field

Phosphene: spot of light1931:--Confirmed visual cortex does not lose complete function despite years of deprivation.1956:--First idea of an electronic prosthetic device6

IntroductionBlindness affects over 40 million people around the world with 15 million suffering from blindness due to a hereditary retinal diseaseLooking to restore visual function, Field of Visual Prosthesis beganAll visual prostheses must perform these steps:Detect and capture light-based imagesTransduce images into electrical stimuliDeliver stimuli to axons of ganglion cells within optic nerveEvoke a response in visual cortex to induce phosphenesThere are a variety of prostheses:Cortical prosthesisOptic nerve prosthesisRetinal prosthesisWith advancement in surgical techniques and bioengineering, retinal prosthesis is the most advanced visual prosthesis

There are a variety of prostheses categorized by its target site along the visual pathway7

Cortical ProsthesisFirst device to artificially induce phosphenesHowever, because electrode arrays were situated on the cortex it caused:Poor spatial resolutionDiscomfort from stimulationFocal epileptic activityThe Utah Electrode Array (UEA) was developed to counteract these side effectsMain advantage is that they are the only therapeutic treatment for individuals with non-functioning retina or optic nerves

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Optic Nerve ProsthesisUsed for blind patients with functional retinal ganglion cellsMultiple electrodes are inserted onto optic nerveStimulation of electrodes in acute settings have produced phosphenesAchieving focal stimulation and retinotopic distribution are challenging

Retinotopic distribution: organization of the visual pathways and visual area of the brain9

Retinal ProsthesisReplace photoreceptors by producing small, localized currents that alter membrane potential of adjacent retinal neuronsEnergy required by device is derived from:External power sourceIncident light acting through a photoelectric cellSubjects utilizing this device have been subjected to tests demonstrating:Improvements in mobilityMotion detectionObject localization and recognitionGrating identificationRetinal ganglion cells and visual pathways need to be viable for device to functionTwo types categorized according to site of implantation:Epiretinal prosthesisSubretinal prosthesis

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Epiretinal ProsthesesImplanted on inner surface of retinaConsists of three main components:External camera for capturing images Component that transforms images into electrical stimuliComponent that stimulates remaining cells in inner retinaExamples of devices in advanced stages of development:Argus II:Multielectrode array powered by externally worn battery packImages are captured by camera mounted on glassestranslated into pixilated images by visual processing unitdelivered via transscleral cables to implant

--Consists of 60 independently controlled electrodes--Argus I and II are developed by Second Sight Medical Products Inc.--Transscleral: across the white of the eyeAlthough there is growing evidence of useful spatial resolution, there is limited field of vision:--increase field of vision by increasing size of implant11

Epiretinal Prostheses ContinuedEPI-RET3:Consists of an array of 25 electrodes apposed to ganglion cellsImages are captured by mounted camera on glassestransferred wirelessly to receiver unit placed in anterior chambersignal is transmitted via micro cable to implant

--EPI-RET3 was developed by researchers at Fraunhofer Institute for Microelectronic Circuits in Germany--Main difference between EPI-RET3 implant and Argus II is that Argus II has all ocular devices within the globe; there is no wire passing through the sclera12

Subretinal ProsthesesImplanted between retinaAlpha-IMS:Consists of microphotodiode array (MPDA) with 1500 microelectrodes and a direct stimulation (DS) test fieldConsists of three parts:Subretinal: MPDA implant Extraocular: foil strip carrying connection lanes to external connection and reference electrodeSubdermal: silicone cable that leads from implant to behind the ear where it penetrates skin and ends in a plug

Alpha-IMA was developed by Retina Implant AG in Tubingen, GermanyMicrophotodiode array: light sensitive metal-oxide semiconductor chip with 1500 pixel-generating elements on polyimide foil carrying 16 electrodes for direct electrical stimulation; (i.e. it is a replacement of photoreceptors)13

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Epiretinal ProsthesesAdvantagesDisadvantagesEasy surgical insertionMinimal disruption to retinaLocation of implant allows for heat dissipationEasy upgrades can be made without further surgeryCamera is capable of zoomingLong-term stabilityDecoded electrical signal is sent directly to ganglion cells

Only stimulates ganglion cellsEliminates use of natural eye movementsMore sophisticated processing is required

Advantages:--Surgery is well understood and routine and takes only 4 hours--Minimal disruption because implant is housed in the anterior chamber--Location allows for heat dissipation because anterior chamber acts like a sink--Easy upgrades can be made because the microelectronics of the device are located on the extraocular component--Zooming helps magnify and improve visual perceptionDisadvantages:--It bypasses the processing function of bipolar and amacrine cells--Eye movements are important for preventing image fading on the retina by constantly refreshing images during visual perception --More sophisticated processing is required because information captured has to be processed prior to stimulation of the ganglion cells15

Subretinal ProsthesisAdvantagesDisadvantagesStimulates bipolar and amacrine cellsLocation helps keep electrodes in close proximity to viable retinal cellsUses natural eye movementsConfined space limits size of devicePossible chance of thermal injuryLong surgery time (6-8 hours)

Advantages:--Stimulating bipolar and amacrine cells allows for processing of a substantial amount of visual information, such as motion and contrastDisadvantages:--Possible chance of thermal injury due to implants close proximity to neurons, which limits the thermal budget of the implant16

Artificial Vision with Wirelessly Powered Subretinal Electronic Implant Alpha-IMSBy Stingl, Katarina, et al.

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Introduction and HypothesisHypothesis:If it is possible to replace photoreceptive function using a technical device, then there may be a treatment for hereditary retinal diseases.Purpose of Study:Restore visual function in patients by means of a subretinaly implanted microelectronic deviceUses light-sensitive detector arrays and amplifiersConverts light into signals that can stimulate bipolar cell neurons via tiny metal electrodes

This is possible because the remaining visual pathway, from the bipolar cells onwards, remains functionalTransdermal: through the skin18

Methods:The subretinal alpha-IMS visual implantCharacteristics of implant:9 mm2 in size consisting of 1500 pixelsEach pixel contains a:PhotodiodeAmplification circuitElectrode for charge transfer to adjacent retinal layersRecords images at different frequenciesOffers bipolar cells with a point-by-point electrical imageProvides a diamond-shaped visual field of 10 10Energy is provided by an external coil from a battery pack

Photodiodes: analyze the brightness of incoming light--Battery pack has knobs for adjusting amplification and overall brightness and contrast of perception

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Methods Continued:The PatientsCharacteristics of participants:Four femalesFive malesBetween ages 3562 yearsEight patients had RPOne patient had Cone-rod dystrophyReceived subretinal implant in eye with worst visionWritten informed consent was obtained prior to inclusion in study

Cone-rod dystrophy: hereditary disease that causes deterioration of the cone and rod photoreceptor cells; causes complete blindness20

Methods Continued:Efficacy TestingThe following efficacy tests were performed:Standardized screen tasksTable tasks of activities of daily livingLetter recognitionReports of daily life experiencesControl:All tests (except reports of daily life experiences) were administered with implant power source turned ON or OFF in a randomized order Other eye was always occluded during testsTasks were performed over the course of 3 to 9 months

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Test One:Standardized screen tasksLight and motion tests Measures light perception in full field illumination, light source localization, and motion detection with a moving random dot patternBasic grating acuity (BaGA) test Measures spatial frequency resolution in cycles per degree (cpd)Patient had to identify direction of white stripes in a pattern on a black backgroundVisual acuity testMeasures visual acuity using Landolt C-rings

Grating acuity:--Uses a larger field of view than visual acuity test, and therefore, is measured independently of foveal function or recognition of optotypes. Thus, this provides best general description of retinal resolution in artificial vision.Visual acuity test:--Can be measured by optotypes, such as letters, numbers, or Landolt C-rings--Spatial and visual resolutions were calculated for corresponding eye distance--Subject S5 had difficulties if grating pattern and Landolt C-rings were presented on screen, so a paper-grating pattern and paper Landolt C-rings in reverse contrast were used on a table22

Test Two:Table tasks of activities of daily living (ADL)Part One:4 of 6 geometrical objects (square, circle, triangle, rectangle, ring or crescent) were placed on a tablePart Two:4 of 6 tableware objects (small/medium-sized plates, cup, fork, spoon, and knife) were placed around a large plate on a tableSubjects were asked to:Report number of objects (identification)Locate them (localization)Name them (discrimination)Performance scores ranged from 0 to 4 Scores in ON and OFF power supply states were compared

Performance scores for each question ranged from 0 to 4:If score was 3, then they successfully reported, located, or discriminated against three objects23

Test Three:Letter recognitionCorrect reading of alphabet letters was recordedPatients were not given any information regarding letter choiceAll letters were visible within visual field of implant

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Test Four:Patient-reported experiences in daily lifeSubjects were permitted to use implant outdoors, at home, or at work During first trial days, a mobility trainer accompanied subjects during their visual experiences in daily lifeDocumentation of specific spontaneous perception was performed by videotaping experiences or by recording patients' oral reports

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ResultsIn all nine subjects, light-induced voltage changes generated by implant showed reliable signal generationIn several patients, observation period was cut short due to technical instability of implant:Subject (S8) developed post-operative subretinal bleeding in area of implant and IOP increased significantly. Issue was resolved with topical and general medicationDuring implant surgery for Subject (S1), the tip of the implant touched the optic nerve head, which resulted in failure of light perception via the implant

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Results for Standardized Screen TasksSubjects (S2S9) had light perceptionSubjects (S2 and S4-S9) were able to localize lightSubjects (S4 and S6-S9) detected motion of dot patternsGrating acuity was successfully measured in Subjects (S4-S9)Visual acuity was assessed in Subjects (S5 and S8)

Light source localization:--Subject (S3) had trouble, which may have been caused by retinas inability to process electrical signals due to degenerative disease--Frequency was set at 5 Hz for the majority; others preferred 15 Hz for more continuous perception--Subjects (S3 and S7) had implants set at only 12 Hz because their images faded quickly at higher frequencies due to possible variation in neuronal refractory time (i.e. electrical stimulation processing time)Motion detection:Current maximum recognizable speed is 35 per second, which is comparable to a car moving at 22 km/h at a distance of 10 mMotion detection is limited by: (i) not fully restored retinal processing mechanisms (ii) working frequency of deviceVisual acuity:--Measured as 20/546 and was reproducible--Reading without aids: .4--Orientation and navigation: ~0.1--Low vision: below .3--Blindness: