UWDept ofBioengineering

AcknowledgementsWashingtonNationalPrimateResearchCenter

NIHGrant#P51OD010425.

UWMedicineEyeInstitute

Purpose:Tostudyaqueousoutflowsystemresponsestoatranscleral µPlaser(IridexTM)inanexvivosystemusingvisuallyguidedpositioning&realtimeobservationoftissueresponses.

Background:PhysicaltissueresponsesarehighlyrelevantbecauseoutflowsystemtissueconfigurationdeterminesaqueousflowandIOP,parametersthatbecomeabnormalinglaucoma.

Conclusions:Atranscleral 810nmµPlasercaninduceCMshortening,SSrotation,TMmovementandSC∆s,typesofoutflowpathwayanatomicchangesthoughttoimproveaqueousflowthatinturnreducesIOP.Thispiloteffortsuggeststhatsystematicstudiescandetermineoptimalparametersnecessaryforprovidinganon-incisionalglaucomasurgical(NIGS)proceduretoalteraqueousflow&IOP.

Discussion:TranscleralµPlaserinducescontractionoftheCM,awell-characterizedmuscleresponsetouP lasers.1,2 CMshorteningcausesposteriorandinwardmovementoftheSSchangingTMandaqueousoutflowpathwayshape.Currentlyusedclinicalparametersaresufficienttoinduceoutflowsystempathway∆sgenerallyassociatedwithimprovedaqueousflow.3 Theabovedescribedsystempermitssystematicassessmentofprobelocationposteriortothelimbus,power,durationandfocaldepth,allparameterssubjecttooptimization.

MaterialsandMethods:Microscope,videosystem,micrometer,1mmthickradiallimbalsegmentsfrom4quadrants(Q)ofprimate(M.fasc.),cornea,sclera,ciliarybodypinnedtoparaffinbaseinPetriedish,micromanipulator,Singlepulseof810nmµPlaser,DutyCycle31.3%.Pairedparametersofstepwisepower;range:500-3000mWandstepwiseduration;range:125-3,000msec.Resultantenergylevelrange:0.08-2.35joules.(Clinically~1.59joulesareappliedpersinglelocation).Videocaptureduringpulse.MotionquantitatedfromstillframeswithImageJ.

Results:SeeVideos:www.youtube.com/user/ibmurrayCiliarymuscle(CM)contraction&relaxationwasvisibleat≥0.08JintheIN&SNQbutat≥0.16JintheITandSTQ.CMcontractioncausedtheCMfacingtheACtotransientlymoveinward&posteriorlyat≥0.75JoulesinallQ,Fig.A.Thescleralspur(SS),andtrabecularmeshwork(TM)movedposteriorlywithachange(∆)inSchlemm’scanalshape.Aftercontraction,theCMrelaxed/recoveredtonearitspreµPconfigurationatlowenergieswithaprogressivereductionintherecoveryresponseasenergyincreased,Fig.B.E.g.intheSNQ,CMbundlesturnedwhiteat2.35jouleswithalackofrecoil/relaxationresultinginapersistent∆inCB,SS&TMconfiguration,Fig.C.

TranscleralLaserInducesAqueousOutflowPathwayMotionandReorganization

MurrayJohnstone1;RuikangWang2 StevenPadilla1,KimikaWen1DepartmentofOphthalmology1,DepartmentofBioengineering2,UniversityofWashington,Seattle,WA

TemperatureRiseBuildsThroughoutDeliveryInterval

TemperatureRiseAlteredbyReduced“On”Time

TimeforCoolingBetweenPulses

TemperatureRiseCanBeModulated

ContinuousWaveLaser

MicropulseLaser

A

B

C

CoagulativeDisruption

TissueShrinkage

Duty Cycle≈HeatBuildupTotalonTime100%

1.1ms

1.6ms

Total“ON” Time~31.3%

2,500msec2,000msec

CWExposureDuration

Time Time

MicropulseExposureDuration

Pulse“OFF”

DutyCycle

0.5msPulse“ON”

MicropulsetoReduceHeatDamage

BeforeLaserPulse After2.35JLaserPulse

LaserTip

Cornea

Sclera

CiliaryMuscle

TM

LaserLightPath

CMBundlesShrinkWhiten&NoRecoil

MicropulseLaserEffectsonCiliaryMuscle&ScleralSpur

NoEvidenceofCiliaryEpitheliumMotionorDamage(WhiteArrows)

C VideoofRealTimeMotion:AccessbyQRCode→Or:www.youtube.com/user/ibmurray

ContactInfo:MurrayJohnstoneEmail:johnstone.murray@gmail.com

ContactInfoQRCode**************************************************

References:1.ChoiM,YoonJ,ChoiC.Label-freeopticalcontrolofarterialcontraction.JBiomedOpt2010;15:015006.

2.YoonJ,ChoiM,KuT,ChoiWJ,ChoiC.Opticalinductionofmusclecontractionatthetissuescalethroughintrinsiccellularamplifiers.JBiophotonics 2014;7:597-606.

3.XinC,WangRK,SongS,ShenT,WenJ,MartinE,JiangY,PadillaS,JohnstoneM.Aqueousoutflowregulation:Opticalcoherencetomographyimplicatespressure-dependenttissuemotion.Exp EyeRes2016.

4.XinC,JohnstoneM,WangN,WangRK.OCTStudyofMechanicalPropertiesAssociatedwithTrabecularMeshworkandCollectorChannelMotioninHumanEyes.PLoS One2016;11:e0162048.

5.JohnstoneM.Intraocularpressurecontrolthroughlinkedtrabecularmeshworkandcollectorchannelmotion.In:SamplesJR,KnepperPA,eds.GlaucomaResearchandClinicalAdvances:2016to2018.Amsterdam:KuglerPublications,2016

6.CarreonT,vanderMerweE,Fellman RL,JohnstoneM,BhattacharyaSK.Aqueousoutflow- Acontinuumfromtrabecularmeshworktoepiscleralveins.Prog Retin EyeRes2016

7.HaririS,JohnstoneM,JiangY,PadillaS,ZhouZ,Reif R,WangRK.Platformtoinvestigateaqueousoutflowsystemstructureandpressure-dependentmotionusinghigh-resolutionspectraldomainopticalcoherencetomography.JBiomedOpt2014;19:106013.

8.LiP,Reif R,Zhi Z,MartinE,ShenTT,JohnstoneM,WangRK.Phase-sensitiveopticalcoherencetomographycharacterizationofpulse-inducedtrabecularmeshworkdisplacementinexvivononhumanprimateeyes.JBiomedOpt2012;17:076026.

Clinical Settings100%

150%

50%

TMmotion1st Measureable