2605章糖尿病性黄斑水肿循证治疗进展

循证眼科学中山大学中山眼科中 葛性黄斑水肿的循证治疗进•视网膜病（diabetic是※最主要、最严重的眼部微血管并发 DR是20～64岁人群致盲的主要原•黄斑水（diabeticmacular※引起患者视力受损最常见原原※长期高血糖、高血压、胰岛素的使 高糖化血红蛋白以及蛋白尿等有什么是分局限性单个或小簇微血管的异常渗弥漫性局限弥漫循证医学EBM基本概1992年JAMA杂志了EBM工作组EBM即“遵循的医学1996年著名临床流行病学DavidEBM定义思想是医疗决策应根据现有的最好研究结（）来进行循证医学临床的分2m29s-2m582m29s-2m58DME治疗的循证医学★证明某种疗法有效性和安全性最可靠★RCT和meta-分析是评价临床治疗效果Ⅰ级一个DR治疗的系统评★Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-一个曲安奈德治疗DME的系统评★Intravitrealtriamcinoloneacetonideinjectionfortreatmentofrefractorydiabeticmacularedema:asystematicreview.Ophthalmology,2009;116（5）:902-★ComparisonofIntravitrealTriamcinoloneAcetonidewithIntravitrealBevacizumabforTreatmentofDiabeticMacularEdema:Ameta- ysis.CurrEyeRes.2013;38（5）:578-两个贝伐单抗治疗DME的系统评★Systematicreviewofintravitrealbevacizumabinjectionfortreatmentofprimarydiabeticmacularoedema.ActaOphthalmol.2011;89（8）:709-17.★meta- ysisandreviewontheeffectofbevacizumab macularedema.GraefesArchClinExpOphthalmol.2011;249（1）:15-27.两个雷珠单抗治疗DME的Ⅲ期临床★Ranibizumabfordiabeticmacularedema:resultsfrom2phaseIIIrandomizedtrials:RISEandRIDE.Ophthalmology.2012;119（4）:789-★Intravitrealranibizumabfordiabeticmacularedemawithpromptversusdeferredlasertreatment:three-yearrandomizedtrialresults.2个雷珠单抗联合激光治疗DME★Intravitrealranibizumab（lucentis）forthetreatmentofdiabeticmacularedema:asystematicreviewandmeta- ysisofrandomizedclinicalcontroltrials.CurrEyeRes.2012;37（8）:661-70.治 的控※血糖、血压、血脂控激光治玻璃体手术治曲安奈德（triamcinolone贝伐单抗（bevacizumab,雷珠单抗（ranibizumab联合治的控制血糖控制与DR的关系ⅠⅡⅠ 控制与并发症的研（diabetscontrolandcomplications斯德哥尔摩干预研（theStockholmdiabetesintervention4m39s-54m39s-5降 血血管并发症的性下降DiabetesControlandComplicationsTrial/EpidemiologyofDiabetesInterventionsandComplicationsResearchGroup.Retinopathyandnephropathyinpatientswithtype1diabetesfouryearsafteratrialofintensivetherapy.NEnglJMed,2000;342（6）:381-389.5m01s—5m5m01s—5mⅡ英国前瞻性研（UKprospectivediabetes※从1977年开始启动，1998年最终结强化治疗即空腹血糖糖化血红蛋白微血管病变下降25%白内障下降24%5m01s—5mUKProspectiveDiabetesStudyGroup.Tightbloodpressurecontrolandriskofmacrovascularandmicrovascularcomplicationsintype2diabetes:UKPDS38.BMJ.1998;317（7160）:703-713.5m01s—5m5m5m37s-血糖控糖化血红蛋白每下降1%（如从9%下※发生视网膜病变的就会下降※对视力的影响下降※治疗所需要的激光下降致盲率下降medQ,etal.Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-CheungN,etal.Diabeticretinopathy.Lancet,2010,376（9735）:124-136.血压控高血压是DR发生的重要，收缩压每下降10mmHg（1kPa7.5mmHg）※发生视网膜病变的就会下降※对视力的影响下降※治疗所需要的激光减少高血压药物选※血管紧张素转换酶抑制血管紧张素II受体拮抗medQ,etal.Managementofdiabeticretinopathy:asystematic血脂控血脂异常在DR的发病机制中起到据DCCT※甘油三酯的异常升※高密度脂蛋白的下

与DR的发生有需要激光治疗的DR患者下6m33s-6m33s-LyonsTJ,etal.DiabeticretinopathyandserumlipoproteinsubclassesintheDCCT/EDICcohort.InvestOphthalmolVisSci,2004,45（3）:KeechAC,etal.Effectoffenofibrateontheneedforlasertreatmentfordiabeticretinopathy（FIELDstudy）:arandomizedtrial.Lancet,2007,370（9600）:1687-激光治格栅样光激光光凝是目前DME最主要1985年DR早期治疗研究小组（ETDRS）局部激光治疗可使DME患者3a内中度视力下降的风险从24%下降到12%※制定DME的激光治疗指缺视野变小、视力剧烈下降、玻璃体EarlyTDRS．Photocoagulationfordiabeticmacularedema．Earlytreatmentdiabeticretinopathystudyreportnumber1.ArchOphthalmol,1985,103（12）:1796-1806．玻璃体手术治玻璃体手术治适应※激光治疗无效的难治性黄斑水伴有玻璃体视网膜界面异常（如后部DME患者可能机清除VEGF等促进DME发生的增大液体的流动并增加内层视网膜改善内层视网膜的缺血状态，从而LaidlawD.Vitrectomyfordiabeticmacularoedema.Eye,2008,22（10）:1337-1341.medQ,etal.Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-DR治疗的系统评目标寻找治疗DR包括DME的最方 MEDLINE（1966throughMay EMBASE,Cochrane※theAssociationforResearchinVisionandOphthalmologydatabase theNationalInstitutesofHealthClinicalTrialsDatabase※AllEnglish-languagerandomizedcontrolledtrials（RCTs）withmorethan12monthsoffollow-up medQ,etal.Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-916.DR治疗系统评价-结对于严重非增殖型和增殖型DR，全视网局部光凝能够降低DME患者50~中度视力丧失的风medQ,etal.Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-目标和方目标：难治性DME的视力恢复效※玻璃体腔内注射曲安奈德（IVTA）未治疗※Tenon囊下注射曲安奈德（STTA）方法※Medline（1950–SeptemberWeek2※TheCochraneLibrary（Issue3,※TheTRIPDatabase（uptoSeptember1,※与难治性E相关并且随访时间超过3个月的RCTYilmazT,etal.Intravitrealtriamcinoloneacetonideinjectionfortreatmentofrefractorydiabeticmacularedema:asystematicreview.Ophthalmology.2009;116（5）:902-11.结果和结在4个RCT中，不管是3个月还是6个IVTA组眼压升IVTA对于难治性黄斑水肿的治疗，短一个曲安奈德和贝伐单治疗DME的meta分10m42s—10m42s—目标和方目标比较曲安奈德和贝伐单抗治疗DME的效※玻璃体腔内注射曲安奈德（IVTA）※玻璃体腔内注射贝伐单抗（IVB）方法Medline、TheCochraneLibrary webofScience（直※ ChineseBiomedical（直※剂量：曲安奈德4mg，贝伐单1.25或者※观察指标：视力，黄斑厚※观察时间：治疗后ZhangY,etal.ComparisonofIntravitrealTriamcinoloneAcetonidewithIntravitrealBevacizumabforTreatmentofDiabeticMacularEdema:Ameta-ysis.CurrEyeRes.2013;38（5）:578-87.结果和结共434眼（8个RCT）•黄斑厚度：IVTA组与仅仅在注射后4W时黄斑厚度明显降低，其他时间曲安奈德治疗DME的效果比贝伐单抗好目标和方目标※玻璃体腔内注射贝伐单抗（IVB）黄斑光凝组※贝伐单抗联合曲安奈德方法※Medline※TheCochraneLibrary（Issue4,※EMBASE※TheTRIPDatabase12m36s—12m36s—结果和结视力4W时IVB的效果比MPC好，※视力：6W时IVB的效果比IVB/IVTA好，YilmazT,etal.Systematicreviewofintravitrealbevacizumabinjectionfortreatmentofprimarydiabeticmacularoedema.ActaOphthalmol.2011;89（8）:709-贝伐单抗治疗DMEmeta分目标和方目标评价贝伐单抗治疗DME的效※玻璃体腔内注射贝伐单抗（IVB）曲安奈德（IVT）方法※Medline※CochraneCentralRegisterofControlledTrials（2009）※评价指标：视力和黄斑区视网膜厚结果和结视力仅仅在6和24W时贝伐单抗（IVB）组※在任何时间点，IVT和IVB联合治疗的（IVB）组效果黄斑区视网膜厚度※仅在6W时贝伐单抗（IVB）组能够明显降低黄斑区视网膜厚度雷珠单抗治疗14m26s—14m26s—雷珠单抗治疗TheDiabeticRetinopathyClinicalResearchNetwork（DRCR，临床1,2,3年结TheRISEandRIDEResearch（RISE和RIDE研究组雷珠单抗治疗DME的系统评价和meta分14m45s—14m45s—2007.3~2008.12—2010,2011,201252个单位，583位合作者参加的前瞻性多中心研究691例（854）≥18岁Ⅰ或者Ⅱ型剂量珠单抗—0.5安奈德—4随机分4组★假注射组3-10天后行激光，293★0.5mg雷珠单抗注射3-10天后行激光187★0.5mg雷珠单抗注射24W后行激光188★4mg曲安奈德3-10天后行激光，18652个单位，853名合作ElmanMJ,SloanMD,ButcherTM,StarrJ,GoreN,CoffeyT,SingletaryPV,Salfer-FirestoneDY,AndreaniG,KetnerDJ,SotirakosP,CainT,ChalamKV,GroverS,GuptaSK,SinghTM,KeshavamurthyR,AgarwalS,PhillipsWW,SifritJ,Pa BrarVS,CarpentierJR,MaturiRK,CiullaT,HrisomalosNF,BleauLA,NovakCK,StorieM,SteeleT,MapleA,PostonJL,HarlessA,FriedmanSM,PlousOZ,BlackmerKA,KeyJS,SjoblomK,MaldonadoJ,Walters-TreonS,McKinneyA,GostischaK,CarltonS,BrowningDJ,BrownJC,AntoszykAN,BrooksDR,PriceAK,CowenMK,HeJV,EnnisSA,PierceRE,KarowAS,LailW,PowersME,McClainD,GeorgeRJ,ClarkLM,SchlickerKA,LeotaudPA,VittitowAR,BalasubramaniamUM,DavisLM,McOwenMD,BallardJA,LauerAK,FrancisPJ,BaileyST,HwangTS,FlaxelCJ,PopeSI,ToomeyMD,NolteSK,IraSD,LiesegangT,LundquistAD,SchainM,VahrenwaldDR,HowellCS,RossiJC,WallacePR,WestKL,SteinkampPN,RicePB,PickellSR,StoneTW,KitchensJW,WoodWJ,IsernhagenRD, bDM,CruzJL,SearsCA,VanHooseB,BuckM,WolfeJL,VanArsdallJ,HeathWR,SladeEA,BlevinsST,KiddT,McMillanTA,PerkinsSL,AndersonNG,GoogeJM,HigdonCT,EvansS,MorrisCD,HuntC,MooreM,JohnsonMM,OliverK,SeitzVL,ArnoldA,JacobusM,WhetstoneJK,BlaisPA,OelrichSM,ClarkWL,WellsJA,TaylorMM,CahillCP,GridineMD,McDougalPD,HenryKL,SpiveyR,HendersonML,leyP,OliverLL,HickmanMichelsonJB,TeasleyLA,ManjarrezP,GarciaA,LeeC,SudernoG,KepplerJ,YooP,PaquetteP,DanielsSA,TingTD,RaySK,LeongCJ,AguilosMC,DowellKJ,MarudoGM,MoreciCM,TejadaRJ,NguyenTH,Teshima-McCormickSM,SchrockA,CombsWM,HomN,HughesMD,HanamotoF,DhallaMS,ThompsonWS,AnagnosteS,Brady-LopezJA,FernandezCV,QuinchiaE,MarianoJ,SherleyCM,AramayoP,RitchieML,McHughKL,FernandezBM,LambertHM,WillisAW,KhawlyJA,Diaz-RohenaR,MillerPS,BuschSK,FredricksonD,LazarteVN,DavisKL,MoralesJA,ChaseKJ,LowdDK,MunizJE,SidtAW,BhavsarAR,EmersonGG,EmersonMV,HuynhVT,OlsonTM,BollDJ,YafchakM,HagerCH,PearsonSL,SeldersDL,SmithCM,Chan-TramC,CarliWB,KellsJA,Taylor-ReetzL,SolomonSD,ScottAW,BresslerNM,DoDV,BresslerS,FreyM,WestS,DonohueD,KellnerV,CainD,GraulJ,Mc-DonaldJ,EmmertD,ShahSM,BeltJ,HerringC,FanJT,SutharMB,RauserME,DavidsonCL,SantiagoG,RollinsKE,CorlissCJ,QuesadaCG,KiernanWH,ObispoRG,KnabbJ,BakerCW,CaldwellTM,MartinTR,PalmerMJ,LambertLF,WilliamsTR,TravisAB,DardenDD,BergerBB,ChenE,WongRW,DavisK,LummusJR,ManhartGJ,Clevenger-SmithTL,CallenN,GartnerMT,SunJL,AbeytaGL,OstranderB,RenY,GrossJG,MageeMA,FlowersAM,HenryKL,McDowellAS,ForeCM,LovitHK,RohrerJC,BlandKK,PaulAM,MalletCN,ChristoffR,PriceRL,GottliebJL,BlodiBA,IpMS,BurkeKF,SoderlingBH,OlsonSR,WealtiAM,SomersSF,DietzmanKA,KnutsonGE,KrolnikDA,PetersonJC,NovakMA,ConeyJM,MillerDG,SingermanLJ,StoneL,McNamaraE,NitzscheTM,DuboisKA,TannerV,CunninghamTL,Smith-BrewerSK,DuBoisJC,GreanoffGA,SunJK,AielloLP,SchlossmanDK,ShahST,ArriggPG,SilvaPS,SharukGS,MurthaTJ,StockmanME,BarenholtzJA,KirbyRK,CalderonRM,CavalleranoJD,BuAbbudJC,WeimannES,BestourousL,CavicchiRW,KoplleA,ShamiM,SmithSR,SaldivarY,PusserP,MeeksA,GarciaNR,SquiresL,TarterCL,WentlandtTF,PetersMA,LemleyCA,LeeMS,HandelmanIL,DreyerRF,HobbsS,BrunelleDA,KopferM,RaunigW,WeimannES,BestourousL,CavicchiRW,KoplleA,ShamiM,SmithSR,SaldivarY,PusserP,MeeksA,GarciaNR,SquiresL,TarterCL,WentlandtTF,PetersMA,LemleyCA,LeeMS,HandelmanIL,DreyerRF,HobbsS,BrunelleDA,KopferM,RaunigW,WeimannES,BestourousL,CavicchiRW,KoplleA,ShamiM,SmithSR,SaldivarY,PusserP,MeeksA,GarciaNR,SquiresL,TarterCL,WentlandtTF,PetersMA,LemleyCA,LeeMS,HandelmanIL,DreyerRF,HobbsS,BrunelleDA,KopferM,RaunigW,DurbinG,DanielH,LoganJ,MalletCN,WohlseinH,PieramiciDJ,NasirMA,CaslarinCA,RabenaMD,SmithJ,SterlingAL,HernandezD,AveryK,BasefskyJC,TramelL,BoyerK,RisardSM,GiustM,GrevenCM,SlusherMM,FishJ,EverhartC,LedbetterFM,CookeLN,MillerDT,ClarkMD,TylerM,MarcusDM,SinghH,ZapataGR,McAteerMC,BlairD,LeverettKA,PowellC,HillCM,OvertonKY,CoxvilleJC,IveyK,OldagVL,GhumanTA,WingG,WalkerJP,RaskauskasPA,SharmaAG,GrodinRW,KieselC,FrederickJL,KnipsE,RyanC,PetersCY,BanksJM,DyshanowitzD,SchoemanEC,HamptonRG,TorrisiPF,RutledgeBK,SpaldingSC,GrinnellCJ,ManleyML,KwasniewskiLM,HayPB,CaponeLA,HarrisonKM,NovackRL,BoyerD,TabandehH,TamA,MukarramS,GasparyanT,GilmourJK,SanguinetJ,SierraJ,PaanSE,ProtacioEG,KessingerJ,SmuckerA,HartnettME,MeredithTA,GargS,HoughtonOM,BarnhartCJ,N'DureF,MorckD,CantrellD,EsquejoRL,KinyounJL,VemulakondaGA,RathSA,BurrowsPK,ErnstPK,PettingillJA,CliftonBC,LeslieJD,StephensC,TopTM,ClearyTA,FreeseLA,WilliamsL,HurleyZandPP,CoreyEA,StoneJL,HowardTN,TyR,ChongSG,MosesKL,GrahamM,BennettSA,JonesMC,ScottMH,WiegmanPM,RundeMM,DvorakTR,HumphreyMJ,TebonBL,KimJE,HanDP,WeinbergDV,ConnorTB,WirostkoW,StepienKE,WilliamsVV,GrafJ,PackardKL,RekowS,AlvarezD,Baker-HillR,HalbmaierJ,SmithCW,eHA,RegoE,DuCotyCL,VaradianS,SalinasC,BewiczE,NagleAL,M.CarpenterS,BerryJP,Gentile15m34s—LamancusaAE,FillR,PeaceM,WilliamsDM,PollackJS,MacCumberMM,CiscatoBJ,Lluen-NuneK,KosinskiBM,DroiraC,MuirDW,PleskovichJ,ChaceR,KallayS,DolbecN,StevensK,FlandersJ,BarwickV,BackesDB,BeringerJR,KellerKL,SelchertKJ,HuangSS,WilkerSC,TangJ,MalikA,CarltonK,ClowC,BurkeS,PankhurstG,HarrodMA,FishGE,WangRC,ArnwineJ,TarterCL,SanchezB,ArceneauxS,AguadoH,CummingsK,GrayK,MackensM,HendrixBL,JaramilloD,BruckerAJ,DrossnerSG,DuPontJC,XuW,DevineC,NybergW,WeeneyL,BergerJM,MeinCE,ChicaMA,KirschbaumL,RiffE,TadrosMF,WeinekeCS,NakoskiB,MacCumberMW,Lluen-NunezK,DroiraC,PleskovichJ,NeelyKA,ScottIU,GardnerTW,ChobanoffSM,WalterLE,HersheyM,StrongJD,BennettTJ,LazarusHS,BunchDP,RidgeAD,BoothK,MooreJ,TrimbleM,KuppermannBD,GrijalvaJ,MagallonR,TrumpB,CummingsHL,LongDJ,VermillionJJ,PonceEA,OuA,GuerreroP,GuerreroC,GallardoJM,PerezV,TaiKW,PaaJA,JampolD,MasiniR,WhittenP,Carrasquillo-BoydW,BoydK,ChanCK,SalibDM,LinSG,NuthiAS,WaltherKS,AldanaI,DickersonED,MyersLE,WarrenS,CastilloSU,HuffKM,ChesbroughDJ,BlairM,LimJI,NiecM,JohnsonT,OvandoY,JanowiczM,CarrollC,BravermanJM,CiardellaAP,Quiroz-MercadoH,RymanLS,RhodesRC,MontalvoSI,HarloffSR,BrownDM,KaufmanSR,EstafanousMF,HuffKA,DRCR的一年结视力（与假注射组3-10天后行激光比较0.5mg雷珠单抗注射3-10天和24W后但是4mg曲安奈德3-10天后行激光没4mg曲安奈德3-10天后行激光组中人曲安奈德雷珠单抗并发※3（8%）眼内炎发生在雷珠单抗注射※眼压升高常见于曲安奈德DiabeticRetinopathyClinicalResearchNetwork.Randomizedtrialevaluatingranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2010;117（6）:1064-16m40s—16m40s—16m40s—16m40s—DiabeticRetinopathyClinicalResearchNetwork.Randomizedtrialevaluatingranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2010;117（6）:1064-16m42s—16m42s—不管是雷珠单抗注射310天后还是24W后行激光治疗，其效果比单独行激光治疗要好在人工晶体眼，曲安奈德注射310天后行激光治疗的效果比单独行激光治疗要好DRCR的二年结视力（与假注射组3-10天后行激光比较0.5mg雷珠单抗注射3-10天和24W后行4mg曲安奈德注射3-10天后行激光视力在1-2年随访中，雷珠单抗平均注射2-3黄斑中心凹视网膜厚度≧250μm的%分※单纯激光组：59%；曲安奈德＋激光组：52%；雷珠单抗＋激光组两组：并发3（8%）眼内炎发生在雷珠单抗※眼压升高常见于曲安奈德DiabeticRetinopathyClinicalResearchNetwork.Expanded2-yearfollow-upofranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2011;118（4）:609-DiabeticRetinopathyClinicalResearchNetwork.Expanded2-yearfollow-upofranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2011;118（4）:609-17m56s—17m56s—DRCR的二年结DME的正确性与合理18m8s—18m3318m8s—18m33DRCR三目标比较0.5mg雷珠单抗注射3～10天后方法※391例≥18岁Ⅰ或者Ⅱ型※剂量雷珠单抗—0.5随机分4组0.5mg雷珠单抗注射3-10天后行激144人★0.5mg雷珠单抗注射24W后行激光14718m3318m33s---DRCR的三年结视0.