146malesaged22247yearsoldand70femalesaged22225yearsoldNoneofthemhadpreviouscontactlenswearorocularsurgeryhistoryThoroughocularexaminationswerecarriedouttoexcludecaseswithocularpathologye ID: 331652
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ThecorneainyoungmyopicadultsShu-WenChang,I-LunTsai,Fung-RongHu,LukeLong-KuangLin,Yung-FengShihÐTofurtherunderstandtheeectofrefractiveerroronthecornealdimensionsandfunction.ÐCornealcurvature,cornealthickness,andaxiallengthmeasurementswereperformed,aswellasspecularmicroscopyand¯uorophotometry,onpa-tientswithvariousrefractivestatuses.216subjects,meanage22.2(SD4.2)years,wereexamined.Patientswithpreviouscontactlenswearhistory,externaleyediseases,aswellaspreviousocularsur-geries,wereexcluded.ÐThecorneaswere¯atterineyeswithlongeraxiallength(=þ0.22,p=0.003).Eyeswithmoremyopicsphericalequivalenthadlongeraxiallength(þ0.90,p)aswellaslesscornealendothelialdensity(=0.20,p=0.037).Cornealendothelialdensitydecreasedineyeswithlongeraxiallength(=0.24,p=0.019);however,itcorrelatedneitherwithcornealthickness(=þ0.06,p=0.59)norwithcornealcurvature(=þ0.07,p=0.52).Thecorneashadameancornealthicknessof533(SD29)mandwerethinnerinmoremyopiceyes(=0.16,p=0.021).Thecorneastendedtobethinnerineyeswithlongeraxiallength.However,thecorrela-tiondidnotreachstatisticalsigni®cance(=þ0.11,p=0.14).Besides,therewasnosigni®cantcorrelationbetweenthecornealthicknessandthecornealcurvature(þ0.13,p=0.093)andtheendothelialpermeability(=0.042,p=0.69).Thecor-neaswithhigherendothelialdensityhadlargercornealtransfercoecient(=0.26,p=0.024)andhigherpermeabilityto¯uo-resceinmolecules(=0.28,p=0.014).Nevertheless,thecornealendothelialper-meabilitydidnotcorrelatesigni®cantlywitheithertheaxiallength(=þ0.18,p=0.11)orthedegreeofmyopia(=0.12,p=ÐChangesintheanteriorseg-mentsastheeyeballelongatesinmyopiaprogressionincluded¯attercornealcur-vature,decreasedcornealthickness,aswellasdecreasedendothelialdensity.Thesefactorsshouldbeconsideredinrefractivesurgery.BrJOphthalmolMyopiaisnowacommonandalmostinevita-blepathologicchangeoftheeye,especiallyinAsiancountriesundergoingrapiddevelopment.Themyopicprevalencecouldbeashighasto95%inmedicalschoolstudents.Myopicchangesoftheeyesincludeelongatedaxiallength,deeperanteriorcham-berandvitreousdepth,thinnerretinawithlat-ticechangeandhigherprevalenceofretinaldecreasedchoroidcirculation,aswellasdecreasedsclerathicknessandelasticity.910Commonsurgicalprocedurestocorrectmyo-piaincluderadialkeratotomy(RK),photore-fractivekeratectomy(PRK),laserassistedinsitukeratomileusis(LASIK),intracornealringseg-ment(INTAC),andphakicintraocularlens(PIOL).RKisnowmostlyreplacedbyotherrefractivesurgicalproceduresbecauseofitscomplicationsincludingprogressivehyperopicpostoperativeglare,surgeryrelatedcor-nealendothelialcellloss,andtransientchangeinendothelialbarrierfunction,aswellascom-promisedocularintegrity.EyesreceivingPRKarelessvulnerabletoblunttraumarelatedeyeballrupturethaneyesthathaveundergoneRK.InspiteofthefactthatchangesincornealendothelialcelldensityafterPRKmightnotbesigni®cant,thehigherchanceofpostoperativehazerendersPRKlessfavouredinhighlymyopiceyes.1718LASIKhasbeenpreferredoverPRKforitsavoidanceofphotoablationthroughBowman'slayerandmayresultinareducedpostoperativehazecomparedtosurfacePRK.1718Thediismoresigni®cantinhighmyopiccorneasandthushasbeenamajoradvantagesinthesecases.However,LASIKperformedonthincorneasmayresultininadvertentcornealper-forationduringLASIKprocedure1920aswellassubsequentiatrogenickeratoectasia.2122Itisthusimportanttodetermineifmyopiceyeshavethinnercorneasbeforesurgery.PhakicIOLhasbeenadvocatedasanotherchoiceforexcessivelymyopiceyes,withlesschanceofpostoperativeglareinducedbythesmallerlaseropticzoneaswellaslesschanceofinducedcornealectasia.However,thetotalcumulativelossofcentralendothelialcellswas8.37%inpatientsimplantedwithanglesup-portedPIOLforthecorrectionofmyopia7yearsaftersurgery.ThemeancelllossforirisclawPIOLcouldbeashighas13.42%at4years.Becausechancesofcomplicatedcata-racthavenotbeeneliminatedbythePIOLprocedureandendothelialcelllossfollowingcataractsurgerymightbesigni®cant,primaryendothelialchangerelatedtomyopiashouldbedocumented.Therefore,themainaimofthisstudywastofurtherdelineatetheeectofrefractiveerroronthecornealstromaandMaterialsandmethodsAtotalof216subjects,meanage22.2(SD4.2)years,withanaveragedrefractiveerrorofþ4.17(SD5.03)Dwereincluded.TherewereBrJOphthalmolDepartmentofOphthalmology,ChangGungMemorialHospital,ChangGungUniversity,TaiwanS-WChangDepartmentofOphthalmology,TaipeiMunicipalChung-HsinHospital,TaiwanI-LTsaiDepartmentofOphthalmology,NationalTaiwanUniversityHospital,TaiwanF-RHuLL-KLinY-FShihCorrespondenceto:DrShu-WenChang,DepartmentofOphthalmology,ChangGungMemorialHospital,5Fu-HsinStreet,Kwei-ShanHsiang,TaoyuanHsien,Taiwan,333ROCshuwenchang@Acceptedforpublication4January2001www.bjophthalmol.com 146males(aged22.2(4.7)yearsold)and70females(aged22.2(2.5)yearsold).Noneofthemhadpreviouscontactlenswearorocularsurgeryhistory.Thoroughocularexaminationswerecarriedouttoexcludecaseswithocularpathologyexceptrefractiveerrorsandmyopiaassociatedchorioretinalchanges.Therefrac-tiveerrorsaveragedþ4.90(5.14)Dinmalesandþ2.70(4.47)Dinfemales.Theexamina-tionsweredividedintotwoparts.PARTONECycloplegicrefractionandcornealcurvatureweremeasuredwithanautorefractor(TopconRK-3000).CentralcornealthicknesswasmeasuredwithaDGHultrasonicpachymeter(DGHTechnology,Inc,Exton,PA,USA)at2to3pmonthedayofexamination.AxiallengthwasmeasuredwithanA-scanultra-sound(SonomedA-1500).Theendothelialmorphologyofthecentralcorneawasrecordedwithacontactwide®eldspecularmicroscope(KonanSP-5500)adaptedtoavideosystem.Endothelialphotographsofgoodqualityweretakenintothecomputercellanalysissystem(Bio-optics,Bambivideoimageanalysissys-tem).Atleast100cellsweredigitisedinthecomputersystemandanalysed.Themean,standarddeviation,andcoecientofvariation(CV)werecomputedforcellareaafterdigitis-ingtheapicesofeachcell.Finally,abaselinescanningforcornealauto¯uorescencewasper-formedwithFluorotronMasterII¯uoropho-tometer(CoherentMedical)®ttedwithananteriorsegmentadapter.PARTTWOOnaseparateday,atleast3daysafterendothelialphotography,anteriorsegment¯uorophotometrywasperformed.Thepatientswereinstructedtoinstilthreedropsof2%sodium¯uoresceinintoeacheyeat2am,withanintervalof1minutebetweeneverytwoinstillations.Caremustbetakentoremoveanyresidual¯uoresceinaroundtheeyesinthemorningofexamination.FluorotronMasterIIscanning®ttedwithananteriorsegmentadapterwasperformedatanintervalof3hoursstartingfrom8am.Theendothelialpermeabil-ityto¯uoresceinwascalculatedfromthetransfercoecientasfollows:permeability=kc.ca1.6,inwhichkc.caisthecorneatoanteriorchambertransfercoecient,assuggestedintheYablonskiprotocol,CTisthecentralcornealthicknessmeasuredwiththeultrasonicpachymeter,and1.6isthecorneatoanteriorchamberequilibriumdistri-butionratiodeterminedbyJonesandMau-riceandbyOtaetalANALYSISOFDATAWerecordedthefollowingdataofeachpatient(1)centralcornealthickness,(2)cornealendothelialdensity,(3)CVofcellarea,(4)endothelialpermeabilityto¯uorescein,(5)centralcornealcurvaturecalculatedbyaverag-ingthetwomajorkeratometricreadingsseparatedby90,(6)axiallengthoftheeyeball,(7)sphericalequivalentcalculatedbysphericalrefractiveerrorplus0.5cylindricalrefractiveerror.Statisticalanalysisincluded(1)erenceineachparameterstudiedbetweenmalesandfemales,(2)correlationbetweenrefractiveerrorsandtheendothelialcelldensity,axiallength,CVofcellarea,cornealthicknessaswellasendothelialpermeability.MeansofdierentvariablesbetweengroupsweretestedbyStudent'stest.Aprobabilityof0.05wasconsideredstatisticallysigni®cant.CorrelationbetweenparameterswastestedwithaSpearmancoecientofcorrelation.Atwotailedprobabilityof0.05wasconsideredstatisticallysigni®cant.Table1summarisesthepatient'skeratometry,axiallength,cornealthickness,andendothelialmorphologystudyparameters.ThecornealtransfercoecientandpermeabilityformalesandfemaleswassummarisedinTable2.Therewasnosigni®cantdierenceinthemeancornealthickness,endothelialcelldensity,CVinendothelialcellarea,andendothelialperme-abilitybetweenmalesandfemales.Datainbothgroupswerethuspooledtogetherforacorrelationstudy.MORPHOLOGICALSTUDIESMalesubjectshad¯attercornealsurfaceandlongeraxiallength(Table1).CorrelationbetweenmorphologicalandfunctionalstudyparameterswassummarisedinTable3.Thecornealcurvaturewas¯atterineyeswithlongeraxiallength(=þ0.22,p=0.003).Eye-ballswithmoremyopicsphericalequivalenthadlongeraxiallength(=þ0.90,p0.001)aswellaslesscornealendothelialdensity(0.20,p=0.037).TherewaslesscornealendothelialdensityineyeswithlongeraxialTable1Summaryofpatients'keratometry,axiallength,cornealthickness,andendothelialmorphologystudyparameters SexKM(D)AL(mm)Q(m)ECD(/mm)CVMale(146)43.0(1.3)25.7(2.0)536(27)3020(279)0.263(0.033)Female(70)43.8(1.4)24.3(1.8)528(33)3009(194)0.263(0.041)Total(216)43.3(1.4)25.2(2.0)533(29)3017(253)0.263(0.036)pValue0.0910.8330.995KM=averagedkeratometrymeasurementindioptres.AL=axiallengthinmillimetres.Q=centralcornealthicknessbyanultra-soundpachymeter.ECD=centralcornealendothelialdensity.CV=coecientofvariationincellarea.Numbersinparenthesisindicatethecasenumberintheparticulargroup.Table2Summaryofpatients'corneatoanteriorchambertransfercoecientandendothelialpermeability SexKc.caPermMale(146)4.81(2.40)4.09(1.99)Female(70)5.16(1.68)4.33(1.47)Total(216)4.92(2.20)4.17(1.84)pValue0.4760.557Kc.ca=corneatoanteriorchambertransfercoecient.Perm=endothelialpermeability(/cm).Numbersinparenthesesindicatethecasenumberintheparticulargroup.Thecorneainyoungmyopicadultswww.bjophthalmol.com length(=0.24,p=0.019).However,cornealendothelialdensitycorrelatedneitherwithcor-nealthickness(=þ0.06,p=0.59)norwithcornealcurvature(=þ0.07,p=0.52).Therewasacorrelationbetweenthecornealthick-nessandthesphericalequivalent(=0.16,p=0.021).Thecorneaswerethinnerinmoremyopiceyes(Fig1).Thecorneasalsotendedtobethinnerincaseswithlongeraxiallength(Fig2),butthecorrelationdidnotreachasta-tisticalsigni®cance(=þ0.11,p=0.14).Thecornealthicknessdidnotcorrelatewithcornealcurvature(=þ0.13,p=0.093)orendothelialpermeability(=0.042,p=0.69).TheCVofcellareacorrelatedneitherwithaxiallength(=0.24,p=0.82)norwiththesphericalequivalent(=0.21,p=0.83).FUNCTIONALSTUDIESTheresultsofcornealtransfercoecientandpermeabilityaresummarisedinTable2.Thecorneaswithhigherendothelialdensityhadlargercornealtransfercoecient(=0.26,p=0.024)aswellashigherpermeability(=0.28,p=0.014).However,thecornealendothelialpermeabilitydidnotcorrelatesigni®cantlywiththeaxiallength(=þ0.18,p=0.11)ordegreeofmyopia(=0.12,p=0.26).Theeyeballelongatesduringmyopiaprogres-sion.Thismyopiaprogressionnotonlymakestheglobelongerbutalsomakesthesclerathin-1910involvingtheposteriorsegmentmoresigni®cantly.729Inadditiontothedeepeningoftheanteriorchamberfoundinhighermyopia,therearedimensionalchangesintheanteriorsegmentduringmyopiaprogression,buttheyarelesswelldocumented.Gossetalreportedthateyeswithgreatervitreousdepthstendedtohave¯atteranteriorcornealsurfaces.Inthisstudy,wefoundthattheanteriorcornealsurfacewas¯atterineyeswithlongeraxiallength.Presumablytheendothelialsurfaceareawillincreaseastheaxiallengthelongatesandtheanteriorchamberdeepensifthelimbaldimensiondoesnotchange.Becausethereisnomitoticactivityinthecornealendotheliumafterbirth,itisthusconceivablethatthecor-nealendothelialcellswillhaveto¯attentocovertheenlargedsurface.Subsequently,areducedcornealendothelialdensityisex-pected.Inthisstudy,wedid®ndsigni®cantlylesscornealendothelialdensityineyeballswithlongeraxiallength.Sincetheendothelialcellsarecapableofpreservingfunctioninspiteoftremendousenlargement,andgenerallycanmaintaincornealfunctiondowntocelldensi-tiesaslowas300±600cells/mmtherewillbenosigni®cantchangeintheendothelialfunc-tioninthehighermyopiceyes.Inthisstudythecorrelationbetweenthecornealendothelialpermeabilityandaxiallengthwasinsigni®cant.Ifthetotalcorneavolumedoesnotincrease,weexpectthatthecornealstromawillbecomethinnerinasimilarwayasthescleradoesinmyopiaprogression.Wedidnotethatthecorneawasthinnerinthemoremyopiceyesinthisstudy.InLiu'sseries,thecentralcornealpachymetrycorrelatedwiththemeanmanualkeratometricmeasurement,simulatedkeratom-etry,andintraocularpressure,butnocorrelationTable3Summaryofcorrelationbetweenmorphologicalandfunctionalstudyparameters AL(mm)SE(D)Q(m)ECD(/mm)CVK(D)r=þ0.22=0.07=þ0.13=þ0.07=-0.09p=0.003p=0.49p=0.093p=0.52p=0.38AL(mm)=1.00=þ0.90=-0.11=þ0.24=0.24p=p.001p=0.14p=0.019p=0.82ECD(/mm=0.24=0.20=-0.06=1.00=0.02p=0.019p=0.037p=0.59p=p=0.84SE(D)=þ0.90=1.00=0.16=0.20=0.21p.001p=p=0.021p=0.037p=0.83Perm(=þ0.18=0.12=0.042=0.28=0.13p=0.11p=0.26p=0.69p=0.014p=0.28K=cornealcurvature.AL=axiallengthoftheeyeball.ECD=cornealendothelialdensity.SE=sphericalequivalentofrefractionerror.Perm=endothelialpermeability.Q=cornealthickness.CV=coecientvariationofthecornealendotheliumcellarea.Pearson'scorrelationcoecient.p=twotailedstatisticalsigni®cancebyPearson'scorrelationtest.Figure1Therelationbetweencornealthicknessandrefractiveerrors.Thecorneaswerethinnerinmoremyopiceyes(r=0.16,p=0.021). 650550Spherical equivalence (D)Corneal thickness (µm) Ð25 Ð20Ð15Ð10Ð50510 Figure2Therelationbetweencornealthicknessandaxiallength.Thecorneaswerethinnerineyeballswithlongeraxiallength,however,thedierencewasnotstatisticallysigni®cant(r=þ0.11,p=0.14). 650550Axial length (mm)Corneal thickness (µm) 19 2123252729 Chang,Tsai,Hu,etalwww.bjophthalmol.com wasnoticedbetweencentralcornealthicknessandthedegreeofmyopiaincontactlenswearers.Neitherdidthecentralcornealthick-nesscorrelatewithaxiallength,age,sex,horizontalcornealdiameter,andrefractioninPrice'sseries.ChoandLamfoundthatcentralcornealthicknessdecreasedwithincreasingagebutnotwithrefractiveerrororcornealcurva-tures.Incontrast,Tokoroandco-workersfoundthemyopiccorneatobe0.018mmthin-nerthanthenormalcontrols.VonBahrdiscoveredathinnercorneainhighmyopiceyes.InbothLiu'sandPrice'sseries,however,thecornealthicknessweremeasuredincontactlenswearers.Sincegreatindividualvariationwasnotedafterwearingcontactlenses,mightcompoundthestatisticsandpartiallyexplainthelackofcorrelationbetweencornealthicknessandmyopia.Furthermore,thetimewhenthecornealthicknesswasmeasuredwasnotspeci®edintheirstudies.Thismightfurthercompoundtheresults.Thecornealthicknesshasadiurnalvariationwiththethinnestmeasurementat3o'clockintheafternoon.thusdeliberatelymeasuredthecornealthicknessat2±3o'clockintheafternoontoavoidthevari-ationincornealthickness.Inthisstudy,wefoundthecorneaswereslightlythinnerinhighermyopiceyesinnon-contactlenswearers.Thecorrelationbetweencornealthicknessandthecornealcurvaturewasinsigni®cant.ThismightbeattributedtotherelativelyfewercasesAlsbirkdescribedanethnicdierenceincornealthickness.Themeancentralcornealthicknesswas550(33)minPrice'sseriesofwhitepatients.However,wefoundthinnercorneasinourpopulation(mean533(29)m).Thisnotonlycon®rmedtheethnicdienceinthecornealthicknessbutalsoarousedfurtherconsiderationinrefractivesurgery.LyleandJinhavereportedanincidenceashighas26%ofprogressivecornealectasiatermediatrogenickeratoconusfollowinga52%±70%cuttingdepthinhyperopicautomatedlamellarkeratoplasty.InWang'sstudy,posteriorcor-nealbulgefollowingLASIKsurgeryiscorre-latedwiththeresidualcornealbedthicknessandtheriskofectasiamaybeincreasediftheresidualcornealbedisthinnerthan250m.Basedonpreviousexperienceandonthetheo-reticalcalculationsofAndreassenetal,amini-malresidualstromalbedthicknessof250mwasadvocated.Cornealthinningmightbeasgreatas30±50mafterwearingcontactlensfor13years.3346Inhighmyopiceyes,morestromalablationisneededtoachieveopticalcorrection,whichrendersthepostoperativecorneaeventhinner.Becausecornealthinningmightbesigni®cantinhighermyopiceyesandacontactlensisusuallychosenformyopiacor-rection,theupperlimitoflasertreatmentrangewillbefurtherreducedwhenperformingLASIKonanOrientallongtermcontactlenswearer.Yiandcoworkersfoundthecorneal¯apthicknessdecreasedinthinnercorneasandthevisualoutcomewasslightlyworseinthethincorneal¯apsgroup.Althoughathinner¯apisrecommendedtoachievemoreopticalcorrectioninhighermyopiacases,thevisualresultmightthusbemoreguardedintheOri-entalhighermyopiceyesbecauseoftherelativelyhigherchanceofhavingathinner¯apaswellassubsequentcornealstriaeandstriaerelatedvisualdisturbance.ItisnotknownwhethertherefractiveeectofintracornealringsegmentdiersinthethinnerOrientalcorneas.Withahighmyopicrateof20%attheageof18,refractiveproceduresformyopiacorrectionotherthanLASIKmightbemoreimportantintheOrientalpopulationintheSodium¯uoresceinmoleculespassthroughtheintercellularspace.Higherendothelialden-sityhasmoreintercellularcontactareasthatarepermeableto¯uoresceinmolecules.Itwasdocumentedthatthecornealendotheliumismorepermeableincaseswithhigherendothe-lialdensityinnormaleyes.Wefurtherfoundadecreasedcorneatoanteriorchambertrans-fercoecientaswellaspermeabilityincaseswithlessendothelialdensityinthisstudy.Changesinthecornealendothelialmorphol-ogyandbarrierfunctionwerenoticedafterradialkeratotomy.However,itremainsun-knownwhethertheendothelialpermeabilitychangesfollowingexcimerlasersurgery.Inconclusion,changesintheanteriorsegmentsastheeyeballelongatesinmyopiaprogressionincluded¯attercornealcurvature,decreasedcornealthickness,aswellasde-creasedendothelialdensity.Thesefactorsshouldbetakenintoaccountbeforeperform-ingrefractivesurgeries.1LinLL,ShihYF,TsaiCB,etal.EpidemiologicstudyofocularrefractionamongschoolchildreninTaiwanin1995.OptomVisSci2RajanU,TanFT,ChangTK,etal.IncreasingprevalenceofmyopiainSingaporeschoolchildren.In:ChewSJ,WeintraubJ,eds.ProceedingsoftheFifthInternationalConferenceonMyopia.Toronto,Ontario,Canada,22±24June1994.NewYork:MyopiaInternationalResearchFoundation,1995:41±6.3HosakaA.Thegrowthoftheeyeanditscomponents:Japa-nesestudies.ActaOphthalmol(Suppl)(Kbh)4HosakaA.Populationstudies:myopiaexperienceinJapan.ActaOphthalmol(Suppl)(Kbh)5LinLL,ShihYF,LeeYC,etal.ChangesinocularrefractionanditscomponentsamongmedicalstudentsÐa5-yearlongitudinalstudy.OptomVisSci6CurtinBJ.Ocular®ndingsandcomplications.In:myopias:basicscienceandclinicalmanagement.HarperandRow,1985:277±385.7CelorioJM,PruettRC.Prevalenceoflatticedegenerationanditsrelationtoaxiallengthinseveremyopia.AmJOph-8ReinerA,ShihYF,FitzgeraldME.Therelationshipofchoroidalblood¯owandaccommodationtothecontrolofoculargrowth.VisRes9FunataM,TokoroT.Scleralchangeinexperimentallymyopicmonkeys.GraefesArchClinExpOphthalmol10PhillipsJR,McBrienNA.Formdeprivationmyopia:elasticpropertiesofsclera.OphthalmicPhysio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