陨灶贼允韵责澡贼澡葬造皂燥造熏灾燥造援 1熏晕燥援 3袁 Sept援18袁圆园园8www.IJO.cn 栽藻造押8629原愿圆圆源缘员苑圆 8629-83085628 耘皂葬蚤造押陨允韵援圆园园园岳员远猿援糟燥皂 窑ClinicalResearch窑 砸蚤泽噪枣葬糟贼燥则泽枣燥则糟燥则灶藻葬造早则葬枣贼枣葬蚤造怎则藻葬灶凿则藻躁藻糟贼蚤燥灶 蚤灶责藻灶藻贼则葬贼蚤灶早噪藻则葬贼燥责造葬泽贼赠

云燥怎灶凿葬贼蚤燥灶蚤贼藻皂押 NationalNaturalScienceFoundationofChina graftrejection;riskfactor 渊No.30471855冤 DepartmentofOphthalmology,GeneralHospitalofChinesePLA, YangYF,HuangYF,WangLQ,YinDF,ZhangK.Riskfactorsfor Beijing100853,China cornealgraftfailureandrejectioninpenetratingkeratoplasty. 悦燥则则藻泽责燥灶凿藻灶糟藻贼燥押 Yan-FengYang.DepartmentofOphthal 2008;1(3):253-256 mology,GeneralHospitalofChinesePLA,Beijing100853,China. [email protected] 陨晕栽砸韵阅哉悦栽陨韵晕 Received:2008-06-22Accepted:2008-07-18 espitethecontinuousevolvementofnewsurgicaltech- D niques,suchasdeeplamellarkeratoplasty(DLEK)[1], 粤遭泽贼则葬糟贼 penetratingkeratoplasty(PK)remainstobethemostcom- ·AIM:Toevaluateriskfactorsofgraftfailureandallograft monformofcornealtransplantation [2].Furthermore,owing rejectionafterpenetratingkeratoplasty(PK). tothedevelopmentofmicrosurgicalinstrumentationsand ·METHODS:ClinicaldataofPKson224eyes(212patients) postoperativemanagementinrecentyears,indicationsfor from1996to2006werestudiedretrospectively.Thegraft PKhavebeenextendedcontinuously.Inthisstudy,the survivalrateandrejection-freesurvivalrateover10years authorsanalyzedretrospectivelythegraftsurvivalrateand wereestimatedwithKaplan-Meir'slifetable,anddifferences rejection-freegraftsurvivalratetothemaincornealdiseases betweenlevelsofeachfactorwerecomparedwithlog-rank inasinglecenteranddeterminedthepreoperativerisk test.Coxregressionwasalsoperformedtofurtherassess factorsleadingtoapooroutcomeofpenetratingkeratoplasty. theimpactofrelatedclinicalfactorsontheprognosisofthe 酝粤栽耘砸陨粤蕴杂粤晕阅酝耘栽匀韵阅杂 cornealgraft. 孕葬贼蚤藻灶贼泽 FromNovember1996toOctober2006,236PKs ·RESULTS:Theoverallratesofgraftsurvivalandrejec- wereperformedin222patients(144males,78females)at tion-freegraftsurvivalat10yearsafterPKwere81.4%and theDepartmentofOphthalmologyinGeneralHospitalof 78.2%respectively.Relativelyhigherriskofgraftfailure ChinesePLA.The12casesthatlackedcomplete wasassociatedwithcornealvascularization,regraft,aphakia informationondependentvariablesusedinthisanalysis orpseudophakia,presenceofanteriororposteriorsynechia, wereexcludedfromthestudy.Finally,thisanalysiswas long( 90minutes)operationtimeandolder( 60years) 逸 逸 carriedoutonatotalof224PKsof212patients(138males, ageofrecipient.Relativelyhigherriskofrejectionwasasso- 74females).Themeanagewas36.6 ± 16.7(2-83)years. ciatedwithcornealvascularizationandlongoperationtime. Thepreoperativediagnosesincludedcornealleucomadueto Coxregressionanalysisshowedcornealvascularization（ =2.46, =0.04）,regraft( =5.67, <0.01),aphakia( trauma(mechanicalorchemical,87,39%),keratoconus(36, =3.64, <0.05),orpseudophakia ( =6.83, <0.01), 16%),herpeskeratitis(14,6%),bacterialandfungalkeratitis presenceofanterior ( =2.76, =0.05)orposterior (12,5%),cornealdystrophiesanddegenerations (48,21%), synechia( =3.12, =0.05)wereindependentriskfactors bullouskeratopathy(16,7%)andothers(11,5%).Demographic forcornealgraftfailure. dataforthe224PKsareshowninTable1. ·CONCLUSION:TheriskfactorsforgraftfailureafterPK 杂怎则早蚤糟葬造 P燥糟藻凿怎则藻泽葬灶凿 P燥泽贼燥责藻则葬贼蚤增藻 M藻凿蚤糟葬造 T则藻葬贼鄄 werecornealvascularization,regraft,aphakiaorpseu- 皂藻灶贼 Donoreyeswereenucleatedasepticallyandthen dophakia,presenceofanteriororposteriorsynechia.The maintainedinpreservationmedia.Transplantationswere riskfactorsafterPKforallograftrejectionwerecorneal performedwithin24hoursinmostofthecases.Thedonor vascularizationandlongoperationtime. buttonswerepunchedoutoftheendothelialsideby ·KEYWORDS:penetraingkeratoplasty;graftfailure;allo- trephineswithadiameterequalto0.25to0.50mmlarger 253 Riskfactorsforcornealgraftfailure

Table 1 Analyzed factors for 224 penetrating keratoplasty (n ,%) Factors Factors levels Number of eyes (%) Regraft Presence 39(17) Absence 185(83) Corneal 0 102(46) vascularization 1 46(21) 2 54(24) ≥3 22(9) Lens status Phakia 165(74) Aphakia 35(15) Pseudophakia 24(11) Figure1Kaplan-Meirsurvivalrateindifferentcornealdis原 Anterior synechia Absence 182(81) eases Presence 42(19) Posterior synechia None 196(88) andwasdeterminedclinicallybyusingaslit-lampbiomicro- Positive 28(12) scope.Graftrejectionwasdefinedasanedematousgraft Suture technique Interrupt 146(65) occurredmorethan2weeksafterthesurgeryandshowedat Continuous 62(28) leastoneofthefollowingsigns: ① anendothelialrejection Combined 16(7) line, ② infiltratingkeraticprecipitates,and ③ anteriorseg- Graft size <8mm 182(81) mentinflammation [3].Theextentofcornealvascularization ≥8mm 42(19) wasgradedintofourstages:0,novesselsinanyquadrant;1, Operation time <90min 117(52) vesselswithinonequadrant;2,vesselsintwoquadrants;and ≥90min 107(48) 3,vesselsinthreeormorequadrants. Recipient age <60years 168(75) 杂贼葬贼蚤泽贼蚤糟alAnalysis Datawerepresentedasmean-SEMfor ≥60years 56(25) continuous variablesandasabsolutefrequenciesfor categoricalvariables.Graftsurvivalrateandrejection-free thanthatoftherecipient.Themeandiameterofthegraft graftsurvivalratewereestimatedbyKaplan-Meier'smethod was7.34 0.50(6.00-10.00)mm,andthediameterofthe andcomparedamongdifferentfactor-levelswithlog-rank 依 cornealgraftwas0.25-0.50mmlargerthanthatoftherecip- test.Coxregressionwasperformedtofurtherassessthe ientcornea.Thegraftsweresuturedtotherecipientcorneas impactofrelatedclinicalfactorsontheprognosisofthe withpreplacedsuturesat3,6,9and12o'clockfollowedby cornealgraft.Statisticalsignificancewassetas <0.05,and sixteencontinuousordiscontinuous10-0nylonsutures. analyzedusingSPSS10.0software. Lensectomy,anteriorvitrectomyorintraocularlensimplan- 砸耘杂哉蕴栽杂 tationwereperformedwhennecessary.Patientsreceiveda Theoverallestimatedgraftsurvivalrateover10yearsafter subconjunctivalinjectionofdexamethasoneandgentamicin PKwas81.4%.Therespectivesurvivalratesofdifferent attheendofsurgery.Topicaltreatmentincludingantibi- preoperativediagnosesareshowninFigure1,withthe otics,corticosteroidsandcyclosporinAeyeointmentor highestinkeratoconus(100%)andthelowestincorneal eyedropswasusedroutinelyinallpatients.Prednisonewas leucomaduetotrauma(76.4%).Theoverallestimatedrejection- takenorallyatthedoseof1mg/(kg·d)for1monthandthen freegraftsurvivalrateover10yearsafterPKwas78.2%. taperedatthediscretionofthetreatingphysician.The Therespectivegraftsurvivalrateandrejection-freegraft cornealsutureswereusuallyremovedat6-12monthsafter survivalrateover10yearsfordifferentpatientgroupsacor- surgery. dingtotheirfactorlevelsareshowninTable2andTable3. 孕葬贼蚤藻灶贼 F燥造造燥憎原怎责葬灶凿 T则葬灶泽责造葬灶贼 O怎贼糟燥皂藻 Patients Therespectiveestimatedrelativerisksofgraftfailureand werefollowedupevery1to2monthsduringthefirstyear rejection-freegraftfailurearealsoshowninTable2and aftersurgery,andthenonceat3-12months.Themean Table3.Factorsassociatedwithgraftfailureincludecorneal follow-uptimewas54.6 38.4(10-131)months.Graftfailure vascularization,regraft,aphakiaorpseudophakia,posterior 依 wasdefinedasanirreversiblelossofcentralgraftclarity oranteriorsynechia,long 90minutes)operationtime, (逸 254 陨灶贼允韵责澡贼澡葬造皂燥造熏灾燥造援 1熏晕燥援 3袁 Sept援18袁圆园园8www.IJO.cn 栽藻造押8629原愿圆圆源缘员苑圆 8629-83085628 耘皂葬蚤造押陨允韵援圆园园园岳员远猿援糟燥皂 Table 2 Graft survival rates in 10a after PK and relative risks (RR) andolder( 60years)recipientage.Factorsassociatedwith 逸 Survival Log-rank graftrejectionincludescornealvascularizationandlong( Factors Factor levels P RR 逸 rate (%) value 90minutes)operationtime.Coxregressionmodelshowed Regraft Presence 66.8 19.6 <0.001 1 onlycornealvascularization （ =2.46, =0.04）,regraft Absence 82.4 1.89 Corneal 0 86.4 17.3 <0.001 1 ( =5.67, <0.01),aphakia( =3.64, <0.05)orpseu- vascularization dophakia( =6.83, <0.01),presenceofanterior（ = 1 78.3 1.60 2.76, =0.05）orposteriorsynechia( =3.12, =0.05) 2 71.2 2.12 wereindependentriskfactorsforcornealgraftfailure.There 57.6 3.12 ≥3 wasnosignificantassociationbetweengraftfailureor Lens status Phakia 84.2 24.2 <0.001 1 allograftrejectionandgraftsizeorsuturetechnique, Aphakia 67.4 2.06 respectively. Pseudophakia 56.2 2.77 Anterior synechia Absence 86.2 25.4 <0.001 1 阅陨杂悦哉杂杂陨韵晕 Presence 58.4 Cornealtransplantationhasbeenthemostsuccessfulonein Posterior synechia Absence 82.3 18.8 <0.001 1 humanorgantransplantations,mainlybecauseofthe Presence 58.4 3.01 existenceoftheimmuneprivilegeofthecornea [4].However, Suture technique Interrupt 76.6 1.64 0.42 graftfailurestilloccursinabout3%-20%ofPKs,withthe Continuous 80.4 [3,5-7] Combined 81.6 allograftrejectionasthemajorcause .Thereportedrisk Graft size <8mm 81.6 0.04 0.85 factors,besidesthevitalityofthedonorgraftperse,for ≥8mm 78.4 graftfailureinclude:cornealvascularization,previous Operation time <90min 83.8 18.4 <0.001 1.95 transplantnumbers,suturetechnique,preoperativeglaucoma, ≥90min 68.4 presenceofanteriororposteriorsynechiaofiris,presenceof Recipient age <60years 84.4 16.6 1 aphakiaorpseudophakia,graftsize,operationtime,blood ≥60years 71.2 1.85 groupABOincompatibility,andhumanleukocyteantigens incompatibility.RiskfactorsforrejectioninPKwere T able 3 Rejection-free graft survival rates in 10a after PK and relative risks (RR) reportedtobecornealvascularization,previoustransplant [6-8] Rejection-free Log-r numberandsuturetechnique .Inthisstudy,usingboththe Factors Factor levels graft ank P RR lifetablemethodandthestratifiedanalysismethodinthe survival (%) value Coxmultipleregressionmodel,wetriedtoanalyzethe Regraft Presence 68.2 3.84 <0.001 Absence 72.4 majorfactorswhichmightaffectthesurvivalrateofPK Corneal 0 87.0 21.3 <0.001 1 amongvariousfactorssuspectedofworseningtheoutcome vascularization ofpenetratingkeratoplasty.However,becauseitisnota 1 72.3 2.13 routineinourclinicalworktoexamineboththedonor'sand 2 70.2 2.29 ≥3 59.6 3.11 therecipient'sABObloodtypeandHLAantigens,wecould Lens status Phakia 77.2 0.68 <0.001 notevaluatethesetwofactors.Inaddition,postoperative Aphakia 82.4 medicationandmanagementalsoexertgreatinfluenceon Pseudophakia 76.8 theoutcome ofgraftsurvivalrate, especiallythe Anterior synechia Absence 79.6 0.54 <0.001 occurrenceofgraftrejection.Nevertheless,theadministration Presence 76.2 Posterior synechia Absence 78.3 0.18 <0.001 ofcorticosteriodsandcyclosporine,includingthedosage, Presence 77.4 routeandcoursewassimilarinourpatientsofPK,sowe Suture technique Interrupt 77.6 0.64 0.42 didnotanalyzethisfactoreither. Continuous 75.8 Combined 80.2 Inthecurrentstudy,wefoundthatcornealvascularization, Graft size <8mm 81.6 2.12 0.85 regraft,presenceofanteriororposteriorsynechiaofirisand ≥8mm 75.4 presenceofaphakiaorpseudophakiawereindependentrisk Operation time <90min 82.8 7.62 <0.001 1 factorsofpostoperativecornealgraftsurvivalrate，whichis 65.1 2.03 ≥90min consistentwiththeresultsofmostofthepreviousreports. Recipient age <60years 78.8 0.53 However,usingmultivariateanalysis,wedidnotfindgraft ≥60years 81.2 size,suturetechniqueoroperationtime,andtherecipient’s

255 Riskfactorsforcornealgraftfailure agehadindependenteffectonthelongtimesurvivalrateof failure.Surgeonsmusttaketheseriskfactorsinto cornealgraft. considerationtoobtainabetterprognosisforkeratoplasty. Comparedwithmostofthepreviousreports,theestimated 砸耘云耘砸耘晕悦耘S overall10years'survivalrateof81.4%inourstudyis 1TerryMA,OusleyPJ.DeeplamellarendothelialkeratoplastyinthefirstUnited relativelylow.Thereasonsmaybemultifactorial.Thereisa Statespatients:earlyclinicalresults. 2001;20:239-243 2SugerA,SugarJ.Techniquesinpenetratingkeratoplasty.Aquartercenturyof relativelyhigherpercentageofpatientswithhighrisk development. 2000;19:603-610 factors, suchaspostoperativevascularizationand 3InoueK,AmanoS,OshikaT,TsuruT.Riskfactorsforcornealgraftfailureand retransplantation,inourstudysubjects.Ontheotherhand,it rejectioninpenetratingkeratoplasty. 2001;79:251-255 iswellestablishedthattheprimarycauseofcornealdisease 4IwamotoT,SmelserGK.Electronmicroscopestudiesonthemastcellsand isthemajorfactorinfluencingtheoutcomeofthegraft,for bloodandlymphaticcapillariesofthehumancorneallimbus. 1965;4:815-834 example,keratoconushasbeeninvariablyshowntohavethe 5WilliamsKA,MuhelbergSM,LewisRF,CosterDJ.Howsuccessfuliscorneal [2] highestgraftsurvivalrate .However,onlyarelatively transplantation?AreportfromtheAustralianCornealGraftRegister. 1995; smallproportionofourpatientshasprognosticallyfavorable 9:219-227 diagnostic indicationssuchaskeratoconusorherpes 6MaguireMG,StarkWJ,GottschJD,StultingRD,SugarA,FinkNE,Schwartz keratitis,which,atleastinpart,mayalsoaccountforthe A.Riskfactorsforcornealgraftfailureandrejectioninthecollaborativecorneal relativelypooroutcomeofourpatients. transplantationstudies. 1994;101:1536-1547 7PriceFW,WhitsonWE,JohnsS,GonzalesJS.Riskfactorsforcornealgraft Insummary,wefoundcornealvascularization,regraft, failure. 1996;12:134-147 aphakiaorpseudophakia,presenceofanteriororposterior 8BraudeLS,ChandlerJW.Cornealallograftrejection:theroleofthemajorhis- synechiawereindependentriskfactorsforcornealgraft tocompatibilitycomplex. 1983;27:290-305

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