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CollagenCrossLinkinginthelimelight: TheUniversalDreamofKeratoconusTreatment AndrewS.Morgenstern,ODFAAO BoozAllenHamiltonContractorat TheVisionCenterofExcellence WhoWeWorkFor MyExperience CXLUSA LeadSiteinChevyChase WashingtonEyePhysiciansandSurgeons RoyRubinfeld,MDover1000patients MostCrossLinkingPatientsat1siteintheUS President,OptometricCrossLinkingSociety www.ocxls.orgGreatPatientVideo InternationalCrossLinkingMeeting,ParkCityUtah OnlyODtoLectureatconference Chair,OCRTSectiononCollagenCrossLinking www.ocrt.org TheLIMElight…..GetIt??? CXLIsInTheFisheyeLensofFDA Currentlyunderinvestigation Notimelineonapproval Insurancewillnotcoverit IsapprovedinallEuropeanUnionCountries Wecansavevision,especiallyinthepediatriccommunity Thereisaraceagainsttime Themanynames… CornealCollagenCrossLinking CollagenCrossLinking CXL HolcombC3R CCL OphthalmologyTanningBed Can’tWeJust? SteveHolcombUSGoldMedalist Driverof4ManBobsled SuffersfromKeratoconus HadCXLBeforeOlympics FactsAboutKeratoconus AccordingtoYaronRabinowitz,MDincidenceinUSisaround1:1500 Int’lCrossLinkingSocietyMeeting2012Utah Whysohighnow? Bilateralbutasymmetric Geneticcomponent Strongfamilyhistory Environmentalcomponent RubbingtheeyesistheENEMYofKCNandCXL qVariableinappearance PMD Ifleftuntreated,itwillusuallyprogressandisnotreversable HistoryofCornealCrossLinking TheoSeiler,MD StudiedMedicine,MathematicsandPhysics ProfessorofPhysics ProfessorandChairofOphthalmology UniversityofDresden UniversityofZurich UniversityofDresdenearly1990’s UsesUVlightandaphotosensitizer(typicallyriboflavin)tostrengthen bondsinthecornea TheDentist TheDentistAppointment 1998Cross‐linking CornealCross‐linking(CXL) §Strengthens/stiffenscorneaswithUVlightandriboflavindrops §98‐99%effective* §Visionlossisprogressive §NotavailableinUS WhyRiboflavin? Manydifferentvehicleswerediscussedandsampledinanimalstudies Aldehydesugars(wewilldiscusslater) Chemicalcrosslinkers Irradiation In1998thefirsthumanwastreatedwithriboflavinandtherewerenoside effects Resultswereconfirmedandtherestishistory Othervehiclesbeingtrialednow DecolinwithUV‐CinReston,Virgina DifferentDevices Avedro‐USA CXLUSA‐USA Peshke IROCInnocross Sooft VegaX‐Link Web‐linksareonthewww.ocxls.orgsite WhichCXLDeviceWillSitOn TheIronThrone? ISITSAFE????? Howdoweknow? HowmuchUV–lightgetsintotheeye? UVAExposureStandards UVAExposureStandards UVAFacialExposure RealWorldUV AllExposedTissues: §170‐200J/cm2/dayin3‐4hrsoutdoors §~60J/cm2/dayofsolarUVA Cornea: §5J/cm2in15‐20mininSummer CXLexposure=3mJ/cm2 YouCANNOTTurnBackTime WEKNOWITWILLGETWORSEIFWEDONOTHING ANYKCNWOULDBEGFORTHEIR10YEAROLDVISIONBACK FACTSABOUTCROSSLINKINGANDTHECORNEA FLEXIBLEELASTIC& NOTCROSSLINKED NOTFLEXIBLE,RIGID&CROSSLINKED HowDoWeKnowUVAgestheBody? Theyounghavetoflexibleandelastic That’swhytheygrowfromthis GUESSWHOTHISIS? TOTHIS… DAMIANLEWISFROMHOMELAND CXLIsEverywhere Wesee CollagenCrossLinkingEVERYWHERE inourworldbut NEVER payattentiontoit OurWaterSupplyisUVTreated CamelbackWaterBottle Tanning(cross‐linking)leatherhasbeenaroundforover6000years. Thiswomanis6000yearsold. CXLWorks! Safeenoughforachild EverGetAManicure? What’sTheTechnique? Howdoyoudoit? “Dresden”Technique §Anestheticdrops §Preparecornea §Riboflavindropsfor30mins §UVlightfor30mins §Bandagecontactlens §PostopCourse:SimilartoPRK Riboflavin0.1%Drops UV‐ALight370nanometerwavelength Patient’sViewofUVLight Letthecookiesbakeat350 For20‐30minutesuntilgoldenbrownanddelicious SoWeKnowitisSafe ButHowDoesitWork? Thecollageninourcorneahaslinksbetweenthelayers UVlightstimulatesstrengtheningbetweenthebonds Takesdecadestodoitnaturally WeareusingUVlightactivatedbyriboflavintostimulatethecreationof morecross‐links Epionvs.EpiOff Epi‐On Longer“loadtime” Latestagetechnique Moreriboneeded Noepidefect Lesschanceofinfectionandhaze qNoreportedcomplications Epi‐Off Shorter“loadtime” Earlyadoptedtechnique Lessriboneeded LargeEpidefect Slowerrecovery Higherriskofinfectionandhaze ReportedComplications NormalCornealEpithelium Barriertoriboflavinpenetrationofstroma? TypicalEpiOffCXL §Worsevisionfor3‐6months §SteeperKs §Morecompactcorneas §Somehaze §SPEs,pseudodendritesifepi‐off Epi‐OffCXLforKCN KeratometryOverTime VisionandKsWorse @3‐6MowithEpiOff EpithelialMigrationPatterninKCN EpiMigration–NoticetheWhirl EpioffCornealUlcer SoallThinCorneasareWeaker,Right??? NotReally… CornealBiomechanicsisfastbecomingthemostimportantvariable CornealBiomechanics Newwaytodeterminethekeratoconic/ectaticstatusofthecornea Notdependentoncurvatureorthicknessbutthestrengthofthecornea. Acorneamaybethinbutbiomechanicallystrong Acorneamaybethickbutstructurallyweak Thinkofhowrebarmakesadifferenceinconstructionofabuilding. OculusCorvisDevice Measuresbiomechanicalpropertiesofthecornea Usesanairpufftofirstdeformthecornea Watchesforthetimetodeformandtherebound Measuresthedampeningandfloppinessofthecornea Objectivetooltodetermineifacorneaisstructurallyweakandatriskfor keratoconusorectasia CorvisbyOculus ImagesfromCynthiaRobertsPh.D. TheOhioStateUniversity ProfessorofOphthalmologyandBiomedicalEngineering WeakeningofCorneafromLASIK CornealHysteresisMeasurement CornealHysteresis SoftCorneaisassociatedwith KeratoconusandPostLASIKectasia StiffCorneaisassociatedwith Older(aged)cornea HighIOP CornealHysteresis MorgensternsRuletoLASIKCandidacy OtherthanRFXandPMHX Checktoseeifyourresidualbedisgreaterthan300 ChecktoseeifyourK’saresteeperthan37and/orflatterthan48ona primaryprocedure ChecktoseeifyourHOAvalueislessthan.60 Checkthebiomechanicalpropertiesofthecorneatomakesurethattheyfall within1.5sdofnormal Pentacamposteriorfloatcenteredandlessthan15micronsandanterior floatcenteredandlessthan10 Nofamilyhistoryofkeratoconus/PKP/ectasia/PMD Alwaysthinkofotheroptions&potentialcomplications OtherApplicationsofCXL: TheUniversalDreams LASIKandCXL PRKandCXL PostRKFluctuations Cornea‐Plastics ScleralCXL OpticNerveHeadCXL Infection Intacs DiabetesandCXL qDiabeticstypicallydonotgetkeratoconus q1999inTheJournalofRefractiveSurgery qSpoerlandSeiler qAldehydesugarsindiabeticsformnaturalcross‐linksbutonlyafter prolongedtime AminetoAldehyde (OxidativeDeamination) AminetoAldehyde WhoIsTheBestCandidate? MildtoModeratePhaseofKeratoconus Littletonocornealscarring BCVAbetterthan20/40withbestopticaldevice Young Typicallytheyoungerandearlierinthedisease,thebetter PostRKrefractivefluctuations PostLASIKectasiawithrefractivefluctuations I’veheardthatVitaminCcantbeusedbeforeCXL? VitaminCSupplements VitaminCnaturallystrengthenscollagen ScurvyisadiseasewherethelackofVitaminCleadstoanenzymatic breakdownofcollagen Asurpluswillpossiblybeanextrabuildingblockforcollagen VitaminCthereforewillhaveasynergisticeffect ManystudiesdonotwanttheirdataaffectedbytheadditionofVitaminC ItisadvisabletohaveyourKCNpatientsthatdonothaveCXLtotakedaily VitC Contraindications CornealThickness Variablebutneverlessthan300‐350 Minimumpachydifferentfromstudytostudy Priorherpeticinfection ReactivationIssues PregnancyorNursing Absolute SevereScarring Nobenefit,betterwithpartialoffullthicknessgraft Poorwoundhealing Autoimmunedisease Relativecontraindication Complications Infection Epi‐offonlyreported CornealHazeandScarring Epi‐Offonlyreported Progressionofdisease Intra‐OcularInflammation Worseningofrefraction Inabilitytotoleratecontactlenses NeedforPKP “MovingPictures”ofCXL LASIKANDCXL LASIKANDCXL “MovingPictures”ofCXL CXLANDINTACS CXLWITH “MovingPictures”ofCXL RKFROMCOLOMBIAc.1988 FELLOWEYEPOSTGRAFT “MovingPictures”ofCXL UNEVENRIBODISTRIBUTION CXL Keratoconus…WhenInDoubt THINKTOLINK