The AAO – FDA Task Force on Premium IOL’s:

Accommodating, MF, EDOF IOL’s

Scott MacRae MD Flaum Eye Institute

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AAOTaskForceAAOmembers:•  Chair,JackHolladay,MD•  AdrianGlasser,PhD•  Sco:MacRae,MD•  SamuelMasket,MD•  WalterStark,MD

FDA members: •  Malvina Eydelman, MD •  Don Calogero, MS •  Gene Hilmantel, OD, MS •  Tieuvi Nguyen, PhD, RAC •  Eva Rorer, MD •  Michelle Tarver, MD, PhD

DevelopingNovelEndpointsforPremiumIntraocularLenses

§  FDA/AAOWorkshopheld–3/28/14

§  Primarygoals:»  ToimprovetheregulatoryscienceforevaluaOngpremium

IOLs,

»  Todevelopbe:erstandardizedmethodstomoreefficientlyevaluatepremiumIOL’sandacceleratestudies.

WorkshopRecomendaCons•  SubjecCveAssessmentsforAccommodaCon/DepthofFocus

TesCng»  ProposedmethodstoreducetesOngbias(e.g.,standardizingcomputerized

VAchartswithle:errandomizaOon,standardluminance,etc.)

•  ExtendedDepthofFocus»  Minimumcriterion:atleast0.5Dgreaterdepthoffocusthanamonofocal

IOLcontrol(at0.2logMAR)»  DevelopnewpreclinicaltesOngtomoreaccuratelymodeltheclinical

environment

•  ObjecCveAssessmentofAccommodaCon»  OpOcalorbiometricmethodsacceptableifappropriatelyvalidated

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WorkshopRecommendaCons(cont’d)

•  Adverseevents(AEs)forsafetyandperformanceendpoints(SPE)inclinicaltrials»  ClarifydefiniOons»  AddnewAE’s(e.g.,dysphotopsias,malposiOons)»  EvaluatepubliclyavailablePMAdatabytypeofIOLforapprovedpremiumIOLs

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WorkshopRecommendaCons(cont’d)

•  PaCent-ReportedOutcome(PRO)Measures»  DeveloppaOent-focuseddefiniOonsandimagesforsymptomareas,includingdysphotopsias

»  EvaluaOonofvisualfuncOontailoredforpaOentswithhighervisualfuncOoningandupdatedfornewertasks(e.g.,smartphoneusage)andIOLdesigngoals(e.g.,intermediatevision)

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Optical Symptoms Classified

Dysphotopias

•  Negative Dysphotopia •  Positive Dysphotopia

Entopic Phenomenon

•  Floaters •  Blue entopic phenonenon

–WBC’s •  Flashing Lights

The Dysphotopsias •  SubjecOve(Undesired)OpOcalImagesAssociatedwithOtherwiseUncomplicatedIOLSurgery–PhoOcPhenomena» PosiOve(PD)lightstreaks,arcs,flashes,starbursts» NegaOve(ND)temporaldarkshadow» MulOfocal(DiffracOve)–halos,rings

Dysphotopsia •  PosiOveDysphotopsia

» PaOentreportslightstreaks,halos,centralflashesthatinterferewithvisionlasOngmorethan3monthspostop

»  Excludingentopicphenomena

•  NegaOveDysphotopsia» PaOentreportsatemporaldarkcrescentlasOngmorethan3monthsagersurgery

Positive Dysphotopsia •  BrightarOfacts:

» Arcs»  Streaks» Rings» Halos» OnreOnacentrallyormidperipherally

Negative Dysphotosia •  Notedwith“PerfectSurgery”•  Ogendescribeashaving“horseblinders”•  SymptomsabatewithpupildilaOon•  Ascociatedwith:

» HighindexofrefracOonIOLs» NasallocaOonofthepupil»  Sharpedgedesign(toinhibitPCO)

Post Surgical Entopic Phenomenon

•  FromGreekἐντός“within”ὀπτικός“visual”meaningthesourceiswithintheeyeitself.

IndustryEngagement•  TheMedicalDeviceManufacturersAssociaOon(MDMA)distributedthefollowingforcomment(10/14):»  Whatshouldthestandardthresholdbeforadefocuscurvethatwould

permitanIOLtoachieveaclaimasanEDFIOL?»  WhatisanappropriatecriteriontousetocorrelateopOcalbenchdatato

actualclinicalresultsfortheEDFIOLs?•  CollaboraOononthedevelopmentoftoolstobe:ermeasurepaOent-reportedoutcomes

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Task Force Progress: Extended Depth of Focus IOLs §  CriteriaforExtendedDepthofFocusIOLs:

» Nostandardizedmonofocalcontrol,thereforeintermediateacuityperformancecriteriawasaddedtocriteriarecommendedatworkshop:50%shouldachieveatleast0.2logMAR(20/32)at67cm

» Distanceacuitynon-inferiortomonofocalcontrol

§  DevelopedspecificmethodologyforEDFdefocuscurvetesOng

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Task Force Progress: Extended Depth of Focus IOLs §  Recommenduseofcomputerizedvisionchartswithrandomizedle:erstominimizebiasduetomemorizaOon

§  Non-clinicallaboratorytesOngforEDF:MTFopOcalbenchwithwhitelightusingamodeleye

§  DragfordisseminaOontoindustry

– Optical Compromises of Multifocal Designs – Loss of Distance Image Quality – (Compared to a Monofocal IOL)

0.4

0.6

0.8

1.0

-1 0 1 2 3 4 5

Imag

e Q

ualit

y M

etric

(CC

)

Defocus [D]

4mm Pupil Size SN60AT

SN6AD1

SN6AD3

ZM900

NXG1

– monofocal

– ReSTOR

– Tecnis

– ReZoom

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-4 -2 0 2 4

Focus(D)

NoaberraOon

– Near – Beyond ∞ – Distance

–  Hyperopia ß Defocus (D) à Myopia – -2 – -1.5 – -1 – -0.5 – 0 – 0.5 – 1 – 1.5 – 2 – No aberration

– Zernike SA shifts subjective refraction.

– No SA – Defocus Curve

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-4 -2 0 2 4

Focus(D)

NoaberraOon

PosiOveSA

– Near – Beyond ∞ – Distance

–  Hyperopia ß Defocus (D) à Myopia – -2 – -1.5 – -1 – -0.5 – 0 – 0.5 – 1 – 1.5 – 2

– +SA

– No aberration

– Zernike SA shifts subjective refraction.

– Positive SA à Hyperopic shift

– More IOL power

– No SA – Defocus Curve

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-4 -2 0 2 4

Focus(D)

NoaberraOon

PosiOveSA

NegaOveSA

– Near – Beyond ∞ – Distance

–  Hyperopia ß Defocus (D) à Myopia – -2 – -1.5 – -1 – -0.5 – 0 – 0.5 – 1 – 1.5 – 2

– -SA

– +SA

– No aberration

– Zernike SA shifts subjective refraction.

– Negative SA à Myopic shift

– Less IOL power

– Positive SA à Hyperopic shift

– More IOL power

– No SA – Defocus Curve

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Extend Depth of Focus - Spherical Aberration -

–  beyond infinity ß distance à near – -2 – -1.5 – -1 – -0.5 – 0 – 0.5 – 1 – 1.5 – 2 – Defocus (D):

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Adverse Events

§  SPErate(SafetyandPerformanceEndpoint):PercentofsubjectswithAE

§  BenchmarksfortheperformanceofnewIOLsbasedonhistoricalmonofocalIOLclinicaltrialdata

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Current SPE AEs CumulaOveAEs:§ EndophthalmiOs§  Lensdislocatedfromposteriorchamber/anteriorchamber

§ Pupillaryblock§ Hypopyon§ ReOnaldetachment§ Cystoidmacularedema

§  SecondarysurgicalintervenOon(excludesposteriorcapsulotomies)

PersistentAEs:§ Cornealstromaedema§  IriOs§ RaisedIOPrequiringtreatment

§ Cystoidmacularedema

AsymmetricRefracCve

Mplus,OculenCs

distance focus

near focus

– McAlinden et al. (2011)

DiffracCveBifocal

ReSTOR,Alcon

DiffracCveTrifocal

MicroF,FineVision

– Gatinel et al. (2011)

ZonalRefracCve

ReZoom,AMO

– Far– Near

– Presbyopic Correction: Multifocal Approaches – Extending Depth of Focus (IOL)

Tecnis,AMO

ATLisa,CarlZeiss

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Task Force Progress: Clinical - Adverse Events

§  IdenOfiedneweventstobeincludedassafetyandperformanceendpoints(SPE)inclinicaltrialsofpremiumIOLs

§  DevelopedAEdefiniOonsforstandardizaOon

§  DragfordisseminaOontoindustry

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Patient-Reported Outcome (PRO) Questionnaire Development

§  DysphotopsiasarenotadequatelyassessedwithcurrentPROmeasures

§  RecommenddevelopingaquesOonnairetobe:ermeasuredysphotopsiasfollowingcataractsurgerywithIOLimplantaOon

MedicalDeviceDevelopmentTools(MDDT)Program

§  Purpose:ToqualifytoolsthatareusedinthedevelopmentandevaluaOonofmedicaldevicesoutsideoftheregulatorysubmission

•  DragguidancepublishedonNovember2013»  h:p://www.fda.gov/medicaldevices/deviceregulaOonandguidance/

guidancedocuments/ucm374427.htm

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MedicalDeviceDevelopmentTools

MDDTQualificaCon

ClinicalOutcomeAssessments*

BiomarkerTests

NonclinicalAssessmentModels

Qualification is a regulatory conclusion that within a specified context of use, the results of an assessment that uses an MDDT can be relied upon to support device development and regulatory decision-making

subjecOvemeasuresofhowapaOentfeelsorfuncOons,ormeasuresbasedonsubjecOveclinicaldecision-making.alabtest,medicalimagingmethod,orotherobjecOveclinicalassessmentmethodusedtodetectormeasureabiomarker.anonclinicaltestmethodormodel.

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FDAQualifiedMDDT•  TheDeviceindustrydoesnotneedtoreconfirmthesuitabilityofaqualifiedMDDT

•  Deviceindustryusersmayneedtodemonstratethetoolisusedaccordingtothespecifiedcontextofuse

Device or Product

Area

Specific Role of the

MDDT

Stage of Develop-

ment Contextofusedefinestheboundarieswithinwhichevidence&jusCficaConsupportstooluse

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BenefitstoMedicalDeviceManufacturers&FDA

•  QualificaOonwillfacilitate:»  MorepredictableproductevaluaCon.MedicaldeviceindustrycanusequalifiedtoolswithouttheneedtoreconfirmvalidityinindividualsubmissionstoFDA,potenOallyreducingOmeandotherresourcesneededtodevelopnewproducts

»  MoreefficientregulaCon.FDA’seffortstoqualifyoneMDDTcouldbysurpassedbytheOmeandresourcessavedwhentheMDDTisappliedtoseveraldevicesubmissionsordevicedevelopmentprograms

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PRO Development

§  ResourcesrequiredfromallstakeholderstodevelopPROmeasures

§  H.DunbarHoskinsCenterforQualityEyeCareservesasneutralforumtorequestandbringtogetherfinancialresourcesandexperOsefromdifferentstakeholderscollecOvelytofacilitatePROmeasuredevelopment» Contact:FloraLum,M.D.-flum@aao.org

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Task Force Deliverables

§  Developdragconsensusstatementsforcomments

§  SubmitfinalconsensusstatementsforpublicaOoninOphthalmology

§  Developapsychometrically-evaluatedPROmeasure» AcceptedintoPilotProgramforQualificaOonofMedicalDeviceDevelopmentTools(h:ps://www.federalregister.gov/arOcles/2014/08/15/2014-19360/pilot-program-for-qualificaOon-of-medical-device-development-tools)

Thank you!