Download Collagen Cross Linking in the limelight: The Universal Dream of

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