Believe It or Not! Amazing Eye Tech, Astounding Therapies ...
Transcript of Believe It or Not! Amazing Eye Tech, Astounding Therapies ...
Believe It or Not! �Amazing Eye Tech,
Astounding Therapies, & Pioneering Procedures– Part 1�
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COPE# 51847-PD
Chris Wroten, O.D., Dipl. A.B.O. [email protected]
Disclosures • No financial interest in any product or company discussed • Some past lecturing and/or paid research for Alcon,
Allergan, Bausch & Lomb/Valeant, Pfizer, & Inspire
• Mention of these products in no way implies endorsement by the presenter
• (mention of these products in no way implies expertise on behalf of the presenter either!)
Believe It or Not – Part 1 �
• Pharmaceuticals • Systemic w/ Ocular SE • Ophthalmic • New/Investigational • Regenerative Medicine? • Glaucoma Therapies & Theories • “Repurposed”
• Drug Delivery Systems • 3-D Printing in Healthcare • Diagnostic & Imaging Technologies • Genomics & Biotechnology
SystemicMedswithOcularSE
• Velcade(bortezomib)• Isaninjectable,pro-inflammatorydrug• FortxofMulitpleMyeloma&MantleCellLymphoma• RiskofEyelidChalazia
• Reportedin24patients• MeandurationonVelcade=98days• Usuallymultiplelesions• Favorupperlid• Resolvewithinfewwksofd/cmedication
SystemicMedswithOcularSE
• Pristiq(desvenlafaxine)• Serotonin-NorepinephrineReuptakeInhibitor(SNRI)• ForTxofDepression• Upto10%ofpatientstakingithaveocularsideeffects:
• BlurredVision• EyePain/DryEyes• Mydriasis• Periorbitalswelling• VisualPhenomena(coloredrings)
• Levodopa(L-dopa)-forParkinson’sds.;mayholdpotentialforpreventingortreatingAMD(retrospectivestudiesshowavg.8yrlateronsetAMDvs.withoutL-dopa)
EverythingOldisNewAgain...
• Remicade(infliximab)&Humira*(adalimumab)• Tumornecrosisfactor(TNF)inhibitors• 97%&95%overallresponseratesrespectivelywhenusedfornoninfectiousuveitis
• Adalimumabisamonoclonalantibody&>2xeffectivevsplaceboinmethotrexate-refractorypediatricJIAuveitis
*FDA-approvedfornon-infectiousIntermediate,Posterior,&Pan-Uveitis7/6/16(1st&onlyNon-corticosteroidapprovedforthis!)
EverythingOldisNewAgain...
NonsurgicalTreatmentofPterygia?• Dypyridamole
• Initiallydosedbid,thenqd• After12mos,33%reductioninlesiondiameter&
70%reductioninheight,aswellasmarkedimprovementinsubjectivesymptoms&completeresolutionofconjunctivalhyperemia&vascularization
“Pterygium:NonsurgicalTreatmentUsingTopical
Dipyridamole–ACaseReport”,Ophthalmology,CarlockBHetal.,2014
EverythingOldisNewAgain...
CoenzymeQ10(a.k.a.ubiquinone)• Ubiquitousinmosteukaryoticcells• Resemblesavitamin• Mainlyfoundinmitochondria• Participatesinaerobiccellularrespiration&isafreeradical-
scavengingantioxidant• AdjuvanttopicaldroptherapyforrefractoryKulcers?• 6casestudyfoundmayhelppromoteepithelialwoundhealing
EverythingOldisNewAgain...
TopicalInsulin?• InsulinmixedwithArtificialTears• DosedBID-TID• Completere-epithelializationofRefractoryNeurotrophicK
Ulcersin6patientswithin1-3wks(WangAL,WeinlanderE,MetcalfBM,etal.Useoftopicalinsulintotreat
refractoryneurotrophiccornealulcers.Cornea,2017;July24)
EverythingOldisNewAgain...
SHP640
• Combobroadspectrumantiseptic(betadine?)+corticosteroid• Expectedindicationforinfectiousconjunctivitis(adenoviral&bacterial)• Topical• ForAdults&Children• FDAPhaseIIIasof2017
• ~33%ofpatientstreatedhadcompleteclinicalresolution6daysp-tx• ~80%ofpatientsshowedcompleteviraleradication
New/InvestigationalOphthalmicMeds
Reproxalap(Aldeyra)• Reactivealdehydespecies(RASP)scavengers
• Proprietaryfamilyofaldehydetraps(newchemicalentities) • Sequester&allowfordegradationoffreealdehydes
• Indicatedfor:• DryeEye• Sjogren’s• NoninfectiousAnteriorUveitis• AllergicConjunctivitis
• FavorablycompletedPhaseIIbtrial...Phase3Trials2019
New/InvestigationalOphthalmicMeds
ONL1204(ONLTherapeutics)• Firstinclasssmallmoleculepeptidedesignedtoprotectkeyretinalcells,includingphotoreceptors,againstapoptosis
• Recent$1MgrantfromNEItocontinueadvancement• Indicationforretinaldetachment,aswellaswet/dryAMD,amongotherchronicretinaldiseases
New/InvestigationalOphthalmicMeds
Optina(AmpioPharmaceuticals)
• Ultralow-dosedanazol(syntheticderivativeoftestosterone)• EnhancesendothelialcellbarrierfunctionfortxofDME• Large,late-stageclinicaltrialsunderwayinU.S.• Oral
New/InvestigationalOphthalmicMeds
PAN-9086(PanOptica)• Potent&selectiveinhibitorofVEGF• PreclinicaltrialscompletedbyWilmerEyeInstituteatJohnsHopkins• CompletedPhaseI/IIClinicalTrials• Treatmentof:WetAMD,DiabeticRetinopathy,&MacularEdema• Effectivein50%oftreatedindividuals
• (betterthancurrentintravitrealanti-VEGFs!)• It’sTOPICAL
New/InvestigationalOphthalmicMeds
New/InvestigationalOphthalmicMeds
SF0166(SciFluorLifeSciences)• PhaseIIpositiveresults• TreatmentDME• Topical&dosedBID
BX795(Univ.Illinois-Chicago)• Moleculesoldtolabstouseinexperiments• InhibitsTBK-1
• TBK-1=enzymeinvolvedininnateimmunity&neuroinflammation• TrialswithHSV-1Keratitis
• Smalldoses=infectionpromoter• Highdoses(butstill5x’slessthancurrentanti-virals)=helpedcellsquicklyclearthevirus!• Doesnothingtothevirus;onlyaffectsinfectedhostcells
New/InvestigationalMeds
RegenerativeMedicine?
• Axolotl(akaMexicanSalamander)• Originallynativeto2lakesinCentralMexico• Cancompletelyregenerateseveredlimbs,spinalcord,etc.,inwks• Canalsoregenerate damagedretinaltissue!
• Genomesequenced2018
• Numerousotherdehydratedamnioticmembrane(amnion)manufacturers...
• Eclipse• 10mmor16mm• Singleordoublelayer
• 9,12,or15mmdisc
RegenerativeMedicine?
• Regenesol(BioTissue)• FullTransplantAmnioticMembraneUmbilicalCordDrops• Launchplannedearly2018
• HAMT-EU/AMX(Italy)
• AmnionExtractDrops:• RegenerEyes(Florida)• Genesis(California)• OptiSerum(umbilicalcordextractdrops)• 9,12,or
15mmdisc
RegenerativeMedicine?
Cacicol(Othea)–CEmark,notyetFDA• Orig.tohealchronicskinwoundsinDM• 1stophthalmicmatrixtherapyagent...“triggersREGENERATIONofdamagedtissuesforENHANCEDHEALING”byrestoringcornealmatrixarchitecture
• Canhealcorneainlittleas2dayspost-sx;dose=1-2x/wk• Study:60k-conuspatients,randomtx30eyesp-CCXL
• ByDay2,83%ofeyeshealedwithvs13%without• Alsolesspain/stinging/ephipora/photophobiaintxgroup
RegenerativeMedicine?
BIIB033(Biogen)• Investigationalmonoclonalantibody• Anti-LINGOagent(LINGO-1isaCNS-specificmembrane
glycoproteinthatsuppressesoligodendrocytedifferentiation&myelination)
• Intravenousadministration• Earlyresults:
• ImprovedVEPlatencyinacuteopticneuritis,aswellasfelloweye• Indicatingremyelination!!!• Poss.1sttrueneuroprotectiveagentforopticneuritis?
• NowinPhaseIITrials
RegenerativeMedicine?
FromNatureNeuroscience,7/11/16:• AndrewHuberman&fellowStanfordresearchers:“...HelpMiceWithDestroyedOpticNervesToSeeAgain”
• CombinedVisualStimulation&ViralActivationofthemammaliantargetofrapamycin(mTOR)
• Results:• In70%ofmice,retinalganglioncellaxonsregeneratedallthewaytochiasm&“reconnectedtotheircorrecttargetsinthebrain,”restoringpartialvision!!!
RegenerativeMedicine?
Lumify(Valeant/B&L)• FDA-approvedDec.’17• NewOTCrednessreliever• Brimonidinetartrate0.025%
“New”GlaucomaMeds
Vyzulta(LatanoprosteneBunod):(B&LviaNicox)• Breaksdownintolatanoprostacid&butanediolmononitrate(i.e.Latanoprost&amoleculeofNitricOxide)...NO=signalingmoleculeinIOP-regulation;actsonTM&Schlemm’s
• PhaseIIIendpointsmet(i.e.non-inferioritytoTimololBID)• FDA-approvedNovember2017
“New”GlaucomaMeds
WeinrebRN,RealiniT,VarmaR.USOphthalmicReview,2016;9(2):80-7DOI:https://doi.org/10.17925/USOR.2016.09.02.80.LatanoprosteneBunod,aDual-actingNitricOxideDonatingProstaglandinAnalogforLoweringofIntraocularPressure.
Aerie Pharmaceuticals Rhopressa(netarsudil)
RhoKinaseinhibitor(ROCK)+NorepinephrineTransporterinhibitor(NET)TripleMechanismofActionQDdosageHyperemia(~35%),Drift?,Bestfor<26mmHg?Avg.6mmHgIOPreductionPhaseIIIcompleted2016*NDAaccepted&FDA-approvedDec.2017
NewGlaucomaMeds
Aerie Pharmaceuticals Roclatan(Rhopressa+ProstaglandinAnalog)
QuadrupleMechanismofActionProstaglandinanalog(latanoprost*)QDdosage&34%IOPReductionPhaseIIbcomplete/PhaseIIIresultslookpromisinginEuropeCommerciallyavailable2018?
AR13533-2ndgenROCK/NETinhibitorPotentiallygreaterIOPloweringthan1stgen.Pre-clinicaltrialsunderway
NewGlaucomaMeds?
• Trabodenoson(InotekPharmaceuticals)• HighlyselectiveAdenosineA1mimetic(agonist)• AvtivatesMMPstoactdirectlyonTM• MonotherapyPhaseII:EfficacylikeLatanoprost?• MonotherapyPhaseIII:
• Placeboresponsewassignificantlylargerthaninanyothertrialsodidnotmeetendpoint
• Anti-tachypylaxiseffect(i.e.wasmoreeffectiveatday84thanday14)• COMBOTherapyPHASEII:TRABODENOSON+LATANOPROST
• At1month,wassuperiortolatanoprostalone,buteffectlostafterwards• PhaseIIITrials0for2sofar
NewGlaucomaMeds?/EverythingOldisNewAgain
AnecortaveAcetate(Retaane)–(Alcon)• OriginallyfortxofWetAMD• êIOPwhenadministeredviasub-Tenon’sinjection• 2smallstudies:
• Singledose=meanIOPêfrom31.3to19mmHg(@3,6mos)• SunsettedatPhaseIIbutresearchersstillstudying
NewGlaucomaMeds?/EverythingOldisNewAgain
• Aminoguanidine• OriginallystudiedforDiabeticNephropathy,thensunsetted• iNOSinhibitor• 6monthratstudywithhighIOP:
• Untreatedgrouplost36%ofganglioncells• Treatedgrouplost<10%ofganglioncells
• IOP-independent!• Oral
NewGlaucomaMeds?/EverythingOldisNewAgain
BimatoprostSR• ExtendedReleaseBimatoprost• ExpectedNDA2Q19&Avail.early2020?• Subconjunctivalinjectionx4-9mosduration
“New”GlaucomaMeds?
NB1111• ProdrugofTetrahydrocannabinol(THC)• Beingdevelopedastopicalglaucomatherapy
inconjunctionwithNanomerics(London)June25,2018,FDAapprovedEpidiolex,
ananti-seizuremedicalmarijuana
derivative...DEA:Sched.V
MAN-01(QBIOMed)
• PrimaryCongenitalGlaucoma• 10mutationsinTIE2gene&itsligand,Angiopoietin1
• ActivatesTIE2receptor• Topical• AlsoworkingoninitialProof-of-ConceptonbiologictargetingofTIE2
(willaidincreationofbiologic-basedtherapeuticplatform)• Phase1trials2019
ErythrocyteVelocity?
• OsamahSaeedi,MD(Univ.ofMaryland)• InconjunctionwithHeidelbergEngineering• Newtechnique:labelRBCswithfluorescentdye&measurespeed
• Quanitifiesvascularperfusionofopticnerve• Couldhelpunderstand&perhapsonedayevendiagnoseglaucoma,aswellasretinaldiseases
NewGlaucomaTheory/Therapy?
• ResearchatMIT• Glaucomaasanautoimmunedisease?
• RetinalGanglionCellreplacement?• AnimalmodelsshowRGCsdeliveredintovitreousmigratedto&integratedintoretina,&grewlengthyaxonsdowntheopticnervetothebrain!!
NewGlaucomaTheory/Therapy?• SECO&ASCRS2016
• JohnBerdahl,M.D.:Glaucomanotjustanocularcondition,ratherametabolicconditionwithimbalancebetweenIOP&ICP
• HisresearchrevealedpatientswithglaucomahavelowerICP,(i.e.largerpressuregradientbetweenIOP&ICP),producingopticnervedamage
• ProposedTreatment:BalanceGoggles™(Equinox)toequilibrateIOP/ICPpressureacrosstheopticnerve
NewICPDiagnostic?• NiSonic• AI-directedultrasounddevice• Infirst44patientsstudied,accuratelydiagnosedelevatedICP100%time• Nowto200-patienttrial
MicroPulseLaserTrabeculoplasty(MLT) • MoreeffectivethanSLTforGlaucoma?
• SpecificdiodeLaser• Usesshortmicroburstsofenergy• Nopost-opinflammation• Smallerspotsize• Repeatable
CycloG6MicroPulseP3forGlaucoma(Iridex)
• CyclophotocoagulationofCiliaryBody• Reported>30%IOPreductionupto18monthspost-procedure
CLASS(iOptima)• CO2Laser-AssistedSclerectomySurgery• Minimallyinvasive• SaferthanTrabeculectomybut
aseffective(~50%IOPê)
SurgicalGlaucomaUpdates
GlaukosiStentTitaniumHeparin-coatedtoself-prime1mm“Snorkel”design
SurgicalGlaucomaUpdates:Minimally/Micro-InvasiveGlaucomaSurgery(MIGS)
• 1stFDA-approvedMIGSdevice• Weighs60μg• Issmallestknownmedical
deviceimplantedinhumans!• ~400KimplantedasofAug.2018
InnFocusMicroshunt• Safe,Easy,Effective• ~50%êinIOPwith>80%gttêx3yrs
SurgicalGlaucomaUpdates:MinimallyInvasiveGlaucomaSurgery(MIGS)
AlconExPressShunt
MoresuccessfulthanTrabeculectomy
SurgicalGlaucomaUpdates:MinimallyInvasiveGlaucomaSurgery(MIGS)
Butwait!...
• CyPass voluntarily pulled from market Aug. 2018 r.e. concerns with endothelial cell density (ECD) loss @ 5 yr post-op study!
• >27% pts had >=30% ECD Loss!FDA Advisory Update Oct. 24, 2018...!• Correlation with how far implant extends into AC!
• 3.1% Loss if No Retention Rings Visible!• 8.4% Loss if 1 Retention Ring Visible!• 21.0% Loss if 2 Retention Rings Visible!• 31.4% Loss if 3 Retentaion Rings Visible!
• Surgeons should consider trimming, removing, repositioning!• All patients with Cypass should be periodically evaluated for ECD Loss
Canaloplasty
• Newer(?)surgicalalternativetoêIOP• Microcatheter(currentlyusedinother
ophthalmicapplications)• PlacedinSchlemm’sCanal• Consideredsafe&effective• ABiC=15minuteprocedure• Failurerates*equiv.toTrabeculoplasty• Phacocanaloplasty=<10%failurerate*3yrspost-op!
*IOP>18mmHg(withorw/ogtt)x2consec.visits
TUG (Eye Sonix) • Therapeutic Ultrasound for Glaucoma • Low power, low ���frequency • Enhances outflow • In Clinical Trials: Prelim. 20% IOP ê x 1 yr in 74% with elevated IOP
SurgicalGlaucomaUpdates
Helios(ForSightVision5)
ImplantforGlaucomaRestsonsurfaceofeye,undereyelidDeliversLatanoprost6mosDurationofTreatment?AlsodevelopingforDES&Allerg.Conj.
Evolute (Mati Therapeutics) PunctalPlugDeliverySystemPhaseIII2015Latanoprost,Olopatadine,UnnamedGlcAgent
• Dextenza&Dexamethasone(OcularTherapeutix)Intracanalic.Plug• ReducePain&Inflammationpost-CatSx&forAllergicConjunctivitis• PhaseIIItrialsnow
• Dextenza&Travoprost(OcularTherapeutix)IntracanalicularPlug• ForsustainedreleasetxofGlaucoma;inPhaseIItrials
EverythingOldisNewAgain...
• Miniature,injectable/implantable,sustained-releasedeliverysystems:• ILUVIEN–licensedtoAlimeraSciences;intra-vitrealsteroidforDME;approvedlate‘14
• RETISERT–licensedtoB&L;intravitrealsteroidforposterioruveitis• DURASERT–Pfizer;latanoprostforGlc;subconjinjection• VITRASERT–B&L;GanciclovirforCMVretinitis• MEDIDUR–DryAMD;Uveitis;RVO;trials• TETHADUR-nanotech;trials
pSivida
NanotechContactLensDrugDelivery
AnujChauhan,Ph.D.Chem.Eng.,Univ.Fla.
NanotechCL–Timolol,Ciprofloxacin
Mass.Eye&Ear:CLdeliveryofLatanoprostviadrugpolymerfilmbetterthangtt
Ocular Iontophoresis – Phase IIb studies r.e. mac. edema with EGP-437 soln promising & no serious tx-emerg. adverse events
ElectricitytoHeal?
• Whenwounded,bodyuseselectricalsignalsaroundinjurysitetohelpcellsmigrateaspartofhealingprocess
• UC-DavisStudy:• Diabetesinmice(viageneticengineering,highfatdiet,&drugs)• Cornealabrasions• Foundelectricalcurrents@edgeofabrasionssignif.weakerinDMmicevs.healthycontrols=slowerhealingtime
• Nowdeveloping2treatmentstospeedhealing:• 1)Pharmacologicalagentstoenhanceiontransport&strengthen
endogenouselectricalsignals• 2)ExternalelectricalcurrentapplicationviaCLwithmultipleelectrodes
3-DPrinting:PharmaceuticalApplications?• NationalUniversityofSingapore• 3-Dprinted,multiplemedication,time-releasedtablet
Australian Co. Anatomics/Lab 22 @ CSIRO 3-D printed Ti sternum/rib cage successfully implanted in cancer patient in Spain
3-DPrinting:SurgicalApplications?
3-DPrinting:SurgicalApplications?WakeForestBaptistMedicalCenter:IntegratedTissue&OrganPrintingSystem(ITOP)
MP-3Microperimeter(Nidek)
• Measuresfunctionallocalretinalsensitivity• Visualfieldperformed“directlyontheretina”• Resultsdisplayedsuperimposedoncolor
fundusimage
VIS-OCT• Bascom-Palmer&FloridaInternationalUniversity• VisiblelightOCTcapableofimagingrhodopsin• Mapshealth/functionofphotoreceptors
RTVueXRAvantiwithAngioVuesoftware(OptoVue)• Non-invasive,dyeless• Hi-res,3-Dvisualizationofretinalvasculature• ImagesmotionofscatteringparticlessuchasRBCsusingsequentialcross-sectionalOCTb-scan
• OCT-AFDA-approvedforsaleinU.S.asof2016
AngioPlex(Zeiss)• Ultra-Clear,3Danddye-freevisualization
ofmicrovascularbloodflowinasinglescan
• ImagesmotionofscatteringparticlessuchasRBCsusingsequentialcross-sectionalOCTb-scans
• FDA-approvedinU.S.2016
PlexElite9000(Zeiss)• FirstFDA-Approved
(2017)Swept-SourceOCTtoimagepost.seg.
• Mainlyforresearchnow,butnextgenerationcoming
SweptSourceOCT:TopconDRIOCTTriton• FDA-approvedFeb.2018• 100KA-scans/sec(vs.~80KwithSD-OCT)• Axialresolution=8μ• Bettersub-RPEvisualizationthanSD-OCT
• ZeissPlexElite9000awaitingFDA-approval
OptovueAvanti-EpithelialThicknessMapping
• FDA-ApprovedJune2018• PredictiveforKeratoconus?• OtherKdisease?
CornealConfocalMicroscopy(CCM)• Examinesunmyelinatedcornealnervefibers@highmag,usinglaser-scanningCCMtoimagecornealsub-basalnerveplexus
• PredictsinsipientperipheralneuropathyinType1DM(63%Sensitive;74%Specific)
• ReducedCornealNFLlength&Cornealsensitivity=increasedseveritydiabeticperipheralneuropathy
• PreviousstudiesdemonstrateutilityforCCMinotherneuropathies
NewStudies:PredictiveforMultiple
Sclerosis?
• UsingLensFluorescenceBiomicroscopecalibratedwithstandardstraceabletoNationalInstituteofStandardsandTechnology(NIST):
• Type2DMDetection(viaAGEsonlens)• Sensitivity=67%,Specificity=94%(HemoglobinA1C:Sens.=44%,Spec.=79%)(FastingPlasmaGluc.:Sens.=50%,Spec.=95%)
• Takes6secs,non-invasive,doesn’trequirefasting
LensAutofluorescence
SightSync• JeffreyKrall,O.D.(SouthDakota)• Patientscansufferfromocularmisalignment&convergenceinsufficiency(CI)
leadingtoheadache&symptomsmirroringdryeye• Linkbetweenneurology&visionasHAtriggeronlyrecentlydiscovered• Isolatesperipheral¢ralvisiontothoroughlyassess
totalbinocularvision&measuringamountofcompensationatnear&atopticalinfinity
• NeuroLenstechnologyincorporatespatient’sindividualrx• Progressiveprismlensthatcompensatesfordifferencesin
fixationalignmentfromdistancetonear
BloodTestforConcussion?
BrainTraumaIndicatorTest• FDA-approvedFeb.2018• Testsforbiomarkersreleaseduponinjurytobrain• Canbetakenwithin12hoursofinjury(3-4hourprocessingtime)
PortableConcussionDetectionDevices
IndianaUniversitySchoolofOptometry• Eye-trackingGoggles&abalanceplatform(Wii-like)• Comparesathlete’sbaselinenumbersvs.post-blow
PortableConcussionDetectionDevices
Eye-Sync(bySyncThink)• JustFDA-approved• Usesinfraredcameras&VRgogglestotrack&compareeyemovements
• Claimstodxconcussionin1minute
Examples of Vision Skills Trends: Top Amateur Baseball Players to the Top 1% of Major League Baseball Players
Vision Skills Make All The Difference
myVisionTrack(a.k.a.mVT)fromVitalArtandScience• FDA-approved• Rxonly,free
download*• Homemonitor• AMD&DR
*Chargetosharedatawithdoctor
23andME• FDA-approved• Direct-to-consumergenotyping• 36conditionscurrently(Sjogren’s,SickleCell)• Glaucoma?,AMD?,RP?,ColorDeficiency?• Salivarysample
Natalis• Cheekswabgenetictestingfornewborns,children,adults• Allconditionstestedforhavemedicalinterventionsavailable• Screensfor193conditions• Alsoscreensforvariantsin10genesassoc.with
sensitivity/sideeffectsto38diff.commonlyrx’dmeds• $649(includesconsultwithgeneticcounselor)• Canorderindividualtestsa-la-carte
• ReportcoverageacrossmostinsurancesthruMountSinaipayerrelationships• ComprehensiveVisionLossPanel
• Includes249genesforretinaldisease,albinism,developmentaleyeds.,&cataractamongothers
Epigenetics
• Obtaingenetictesting• Seekstomodifygenesviacustomized:
• Nutrition• Nutriceuticals• HormoneReplacement