restoring vision to the blind: the challenge of sight recovery technologies

PowerPoint Presentation

Restoring Vision to the BlindThe Challenge of Sight Recovery Technologies

Michael Beyeler, Ariel Rokem, Geoffrey M. Boynton, Ione Fine

Blindness Epidemiology285 million people in the world are visually impaired40 million people in the world are totally blind90% of people with visual impairments live in developing countriesMost of the people with visual impairment are older, and females are more at risk at every age, in every part of the world.Every 5 seconds one person in the world goes blind. (WHO, 2002)

Global Causes of Blindness~80% of global blindness causes are preventable / treatable

(WHO, 2002)

Hereditary Retinal DiseasesRetinitis pigmentosagenetic: ~ 1/4,000occurs at 35 40 years oldbegins with death of the rods, deterioration of night visionfollowed by cone death, progressing from mid-periphery to fovea

Age-related macular degeneration (AMD)complex trait with environmental factors and risk allelesoccurs at 70+ years oldbegins with accumulation of extracellular material between choroid and epitheliumfollowed by death of rods and cones200 different gene mutations result in irreversible vision loss

The EyeThe eye transforms light into electrochemical signals

Healthy Retinal CircuitryParallel processing of visual information

to brainincoming light(Field & Chichilnisky, 2007)

Retina Affected by Retinitis PigmentosaStage 1: Photoreceptor stressRods and cones develop neurite extensionsStage 2: Photoreceptor deathComplete loss of photoreceptorsMuller cells seal off retinaStage 3: Neuronal remodelingNeurite extensions fuse into complex tangled microneuromasSome cell classes migrate, others degenerate and dieRetinal remodeling during retinal degeneration

(Jones & Marc, 2005)

Sight Restoration TechnologiesGene therapyReplace faulty genes with functional ones via virus injection

OptogeneticsOptogenetic proteins (or small-molecule photoswitches) used to create novel light sensitive channels in remaining retinal cells

Electrical prosthesesDirectly elicit responses in remaining retinal cells, analogous to a cochlear implant

Electrical Visual ProsthesesArgus II (Second Sight Medical Products)

Electrical Visual Prostheses

The Linear Scoreboard ModelAssumption:Transformation from stimulation to percept is virtually linearStimulating a grid of positions on the retina leads to percept of a grid of luminous dots

The Linear Scoreboard ModelThe scoreboard model is too simple

Electrodes

Patient drawing

Predicted

Challenges of Sight Recovery TechnologiesDegenerate retinal circuitriesWe dont actually know what were stimulatingPlasticity of the adult visual cortexRetinotopic remapping? Cross-modal plasticity?Unnatural stimulation of the retinaUnselective stimulation of hundreds of ganglion cellsStimulation of ganglion cell axonsStatic image on the retinaFactors affecting the perceptual experience

Challenges of Sight Recovery TechnologiesUnselective stimulation of retinal ganglion cells

Challenges of Sight Recovery Technologies

Unselective stimulation of retinal ganglion cells

(Fine & Boynton, 2015)

Challenges of Sight Recovery TechnologiesAxonal stimulation

Visual Angle (deg)-30-20-100102030-30-20-100102030Visual Angle (deg)Optic nerve

(Yue et al., 2016)(Fine & Boynton, 2015)

Virtual PrototypingVirtual patientPredict the perceptual experienceIncorporate perceptual distortionsdue to engineering constraintsdue to neurophysiologyLearn to invert themWhat would the world look like with a bionic eye?

?

Virtual PatientLinear-nonlinear cascade modelSpatial sensitivityWhat would the world look like with a bionic eye?

(Nanduri et al., 2012; Beyeler et al., in prep)

Virtual PatientLinear-nonlinear cascade modelSpatial sensitivityTemporal sensitivityWhat would the world look like with a bionic eye?

(Nanduri et al., 2012; Beyeler et al., in prep)

Virtual PatientBrightnessPredicting the perceptual experience of bionic vision

Frequency @ 20 HzAmplitude @ 1.25x threshold(Nanduri et al., 2012; Beyeler et al., in prep)

Virtual PatientPredicting the perceptual experience of bionic vision

Size(Nanduri et al., 2012; Beyeler et al., in prep)

Virtual PatientBrightness over timePredicting the perceptual experience of bionic vision(Horsager et al., 2009)Pulse width Frequency 0.45ms 20 Hz 0.95ms 20 Hz 0.25ms 40 Hz 0.45ms 40 Hz 0.95ms 40 Hz

01234

Time (s)Brightness

Virtual PatientSpatiotemporal interactions between electrodesPredicting the perceptual experience of bionic vision

Brightness matching task:

Psychometric function:Point of subjectivebrightness match(Horsager et al., 2011)

Virtual PatientPredicting the perceptual experience of bionic vision

(Horsager et al., 2011)Spatiotemporal interactions between electrodes


Human dataSimulation

(Beyeler et al., in prep)




Human dataSimulation



Human dataSimulation(Beyeler et al., in prep)

Virtual PatientThe virtual patient can provide insights into what aspects of visual tests are important for evaluating and comparing devicesArgus II: Predicting visual acuity

Virtual PatientArgus II: Providing realistic estimates of vision quality

Virtual PatientArgus II: Providing realistic estimates of vision quality

Future WorkProblem:Data collection in real patients is tedious, expensiveHow to know what they actually perceive?Potential solution:Collect many input-output mappings using a population of virtual patientsInvert the mapping; e.g., using machine learningUse learned mapping to generate required stimulus for desired perceptUltimate goal: Generate optimal stimulation protocols

Camera inputApplied stimulusPredicted percept:

virtual patient

Predicted perceptStimulus params

machine learning

Desired perceptRequired stimulus

machine learning

Camera input:

Future WorkUltimate goal: Generate optimal stimulation protocols in real time

Desired perceptRequired stimulus

Softwarehttps://github.com/uwescience/pulse2percept

ConclusionsShapeSize & brightnessBrightness over timePerceptual experience of patientsThe virtual patient can predict the patient experience

ConclusionsResearchers / companies:Improve stimulation protocols for existing devicesHelp identify which aspects of the technology need to be improved. Guide new technology development.Provides a test of whether we have a full understanding of the technologyFDA:Provide insights into what sort of visual tests/metrics are important for evaluating Patients:Provide realistic estimates of prosthetic performanceVirtual prototyping crucial for the evaluation and design of current and future technologies

Moore/Sloan FoundationsWashington Research Foundation

Second Sight Medical Products Inc.RO1 EY-014645Research to Prevent Blindness Dana Foundation

Ione Fine (UW)Geoffrey Boynton (UW)Ariel Rokem (UW)

Projects in this talkDevyani Nanduri (USC)Scott Greenwald (USC)Alan Horsager (USC)Chloe DeBalthasar (USC)

Thank you!

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BlindnessLevel of visual impairment measured by:level of distance visual acuitypresenting or best-corrected visual acuityvisual field constrictionBlindness:best-corrected acuity 20/200 in the better-seeing eyeLow vision:best-corrected acuity < 20/40 in the better-seeing eye (but > 20/200)Visual impairment includes blindness as well as low vision

Definition

Snellen chart:

20/20 normal vision: At 20 feet away (6m), a person can separate contours that are roughly 1.75 mm apart. Normal individuals have 6/4 or 20/12.

In the expression 6/x vision, the numerator (6) is the distance in meters between the subject and the chart and the denominator (x) the distance at which a person with 6/6 acuity would discern the same optotype. Thus, 6/12 means that a person with 6/6 vision would discern the same optotype from 12 meters away (i.e. at twice the distance). This is equivalent to saying that with 6/12 vision, the person possesses half the spatial resolution and needs twice the size to discern the optotype.38

restoring vision to the blind: the challenge of sight recovery technologies

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