2605章糖尿病性黃斑水腫循證治療進(jìn)展

循證眼科學(xué)中山大學(xué)中山眼科中 葛性黃斑水腫的循證治療進(jìn)?視網(wǎng)膜病（diabetic是※最主要、最嚴(yán)重的眼部微血管并發(fā) DR是20～64歲人群致盲的主要原?黃斑水（diabeticmacular※引起患者視力受損最常見原原※長(zhǎng)期高血糖、高血壓、胰島素的使 高糖化血紅蛋白以及蛋白尿等有什么是分局限性單個(gè)或小簇微血管的異常滲彌漫性局限彌漫循證醫(yī)學(xué)EBM基本概1992年JAMA雜志了EBM工作組EBM即“遵循的醫(yī)學(xué)1996年著名臨床流行病學(xué)DavidEBM定義思想是醫(yī)療決策應(yīng)根據(jù)現(xiàn)有的最好研究結(jié)（）來(lái)進(jìn)行循證醫(yī)學(xué)臨床的分2m29s-2m582m29s-2m58DME治療的循證醫(yī)學(xué)★證明某種療法有效性和安全性最可靠★RCT和meta-分析是評(píng)價(jià)臨床治療效果Ⅰ級(jí)一個(gè)DR治療的系統(tǒng)評(píng)★Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-一個(gè)曲安奈德治療DME的系統(tǒng)評(píng)★Intravitrealtriamcinoloneacetonideinjectionfortreatmentofrefractorydiabeticmacularedema:asystematicreview.Ophthalmology,2009;116（5）:902-★ComparisonofIntravitrealTriamcinoloneAcetonidewithIntravitrealBevacizumabforTreatmentofDiabeticMacularEdema:Ameta- ysis.CurrEyeRes.2013;38（5）:578-兩個(gè)貝伐單抗治療DME的系統(tǒng)評(píng)★Systematicreviewofintravitrealbevacizumabinjectionfortreatmentofprimarydiabeticmacularoedema.ActaOphthalmol.2011;89（8）:709-17.★meta- ysisandreviewontheeffectofbevacizumab macularedema.GraefesArchClinExpOphthalmol.2011;249（1）:15-27.兩個(gè)雷珠單抗治療DME的Ⅲ期臨床★Ranibizumabfordiabeticmacularedema:resultsfrom2phaseIIIrandomizedtrials:RISEandRIDE.Ophthalmology.2012;119（4）:789-★Intravitrealranibizumabfordiabeticmacularedemawithpromptversusdeferredlasertreatment:three-yearrandomizedtrialresults.2個(gè)雷珠單抗聯(lián)合激光治療DME★Intravitrealranibizumab（lucentis）forthetreatmentofdiabeticmacularedema:asystematicreviewandmeta- ysisofrandomizedclinicalcontroltrials.CurrEyeRes.2012;37（8）:661-70.治 的控※血糖、血壓、血脂控激光治玻璃體手術(shù)治曲安奈德（triamcinolone貝伐單抗（bevacizumab,雷珠單抗（ranibizumab聯(lián)合治的控制血糖控制與DR的關(guān)系ⅠⅡⅠ 控制與并發(fā)癥的研（diabetscontrolandcomplications斯德哥爾摩干預(yù)研（theStockholmdiabetesintervention4m39s-54m39s-5降 血血管并發(fā)癥的性下降DiabetesControlandComplicationsTrial/EpidemiologyofDiabetesInterventionsandComplicationsResearchGroup.Retinopathyandnephropathyinpatientswithtype1diabetesfouryearsafteratrialofintensivetherapy.NEnglJMed,2000;342（6）:381-389.5m01s—5m5m01s—5mⅡ英國(guó)前瞻性研（UKprospectivediabetes※從1977年開始啟動(dòng)，1998年最終結(jié)強(qiáng)化治療即空腹血糖糖化血紅蛋白微血管病變下降25%白內(nèi)障下降24%5m01s—5mUKProspectiveDiabetesStudyGroup.Tightbloodpressurecontrolandriskofmacrovascularandmicrovascularcomplicationsintype2diabetes:UKPDS38.BMJ.1998;317（7160）:703-713.5m01s—5m5m5m37s-血糖控糖化血紅蛋白每下降1%（如從9%下※發(fā)生視網(wǎng)膜病變的就會(huì)下降※對(duì)視力的影響下降※治療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.血壓控高血壓是DR發(fā)生的重要，收縮壓每下降10mmHg（1kPa7.5mmHg）※發(fā)生視網(wǎng)膜病變的就會(huì)下降※對(duì)視力的影響下降※治療所需要的激光減少高血壓藥物選※血管緊張素轉(zhuǎn)換酶抑制血管緊張素II受體拮抗medQ,etal.Managementofdiabeticretinopathy:asystematic血脂控血脂異常在DR的發(fā)病機(jī)制中起到據(jù)DCCT※甘油三酯的異常升※高密度脂蛋白的下

與DR的發(fā)生有需要激光治療的DR患者下6m33s-6m33s-LyonsTJ,etal.DiabeticretinopathyandserumlipoproteinsubclassesintheDCCT/EDICcohort.InvestOphthalmolVisSci,2004,45（3）:KeechAC,etal.Effectoffenofibrateontheneedforlasertreatmentfordiabeticretinopathy（FIELDstudy）:arandomizedtrial.Lancet,2007,370（9600）:1687-激光治格柵樣光激光光凝是目前DME最主要1985年DR早期治療研究小組（ETDRS）局部激光治療可使DME患者3a內(nèi)中度視力下降的風(fēng)險(xiǎn)從24%下降到12%※制定DME的激光治療指缺視野變小、視力劇烈下降、玻璃體EarlyTDRS．Photocoagulationfordiabeticmacularedema．Earlytreatmentdiabeticretinopathystudyreportnumber1.ArchOphthalmol,1985,103（12）:1796-1806．玻璃體手術(shù)治玻璃體手術(shù)治適應(yīng)※激光治療無(wú)效的難治性黃斑水伴有玻璃體視網(wǎng)膜界面異常（如后部DME患者可能機(jī)清除VEGF等促進(jìn)DME發(fā)生的增大液體的流動(dòng)并增加內(nèi)層視網(wǎng)膜改善內(nèi)層視網(wǎng)膜的缺血狀態(tài)，從而LaidlawD.Vitrectomyfordiabeticmacularoedema.Eye,2008,22（10）:1337-1341.medQ,etal.Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-DR治療的系統(tǒng)評(píng)目標(biāo)尋找治療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治療系統(tǒng)評(píng)價(jià)-結(jié)對(duì)于嚴(yán)重非增殖型和增殖型DR，全視網(wǎng)局部光凝能夠降低DME患者50~中度視力喪失的風(fēng)medQ,etal.Managementofdiabeticretinopathy:asystematicreview.JAMA,2007,298（8）:902-目標(biāo)和方目標(biāo)：難治性DME的視力恢復(fù)效※玻璃體腔內(nèi)注射曲安奈德（IVTA）未治療※Tenon囊下注射曲安奈德（STTA）方法※Medline（1950–SeptemberWeek2※TheCochraneLibrary（Issue3,※TheTRIPDatabase（uptoSeptember1,※與難治性E相關(guān)并且隨訪時(shí)間超過3個(gè)月的RCTYilmazT,etal.Intravitrealtriamcinoloneacetonideinjectionfortreatmentofrefractorydiabeticmacularedema:asystematicreview.Ophthalmology.2009;116（5）:902-11.結(jié)果和結(jié)在4個(gè)RCT中，不管是3個(gè)月還是6個(gè)IVTA組眼壓升IVTA對(duì)于難治性黃斑水腫的治療，短一個(gè)曲安奈德和貝伐單治療DME的meta分10m42s—10m42s—目標(biāo)和方目標(biāo)比較曲安奈德和貝伐單抗治療DME的效※玻璃體腔內(nèi)注射曲安奈德（IVTA）※玻璃體腔內(nèi)注射貝伐單抗（IVB）方法Medline、TheCochraneLibrary webofScience（直※ ChineseBiomedical（直※劑量：曲安奈德4mg，貝伐單1.25或者※觀察指標(biāo)：視力，黃斑厚※觀察時(shí)間：治療后ZhangY,etal.ComparisonofIntravitrealTriamcinoloneAcetonidewithIntravitrealBevacizumabforTreatmentofDiabeticMacularEdema:Ameta-ysis.CurrEyeRes.2013;38（5）:578-87.結(jié)果和結(jié)共434眼（8個(gè)RCT）?黃斑厚度：IVTA組與僅僅在注射后4W時(shí)黃斑厚度明顯降低，其他時(shí)間曲安奈德治療DME的效果比貝伐單抗好目標(biāo)和方目標(biāo)※玻璃體腔內(nèi)注射貝伐單抗（IVB）黃斑光凝組※貝伐單抗聯(lián)合曲安奈德方法※Medline※TheCochraneLibrary（Issue4,※EMBASE※TheTRIPDatabase12m36s—12m36s—結(jié)果和結(jié)視力4W時(shí)IVB的效果比MPC好，※視力：6W時(shí)IVB的效果比IVB/IVTA好，YilmazT,etal.Systematicreviewofintravitrealbevacizumabinjectionfortreatmentofprimarydiabeticmacularoedema.ActaOphthalmol.2011;89（8）:709-貝伐單抗治療DMEmeta分目標(biāo)和方目標(biāo)評(píng)價(jià)貝伐單抗治療DME的效※玻璃體腔內(nèi)注射貝伐單抗（IVB）曲安奈德（IVT）方法※Medline※CochraneCentralRegisterofControlledTrials（2009）※評(píng)價(jià)指標(biāo)：視力和黃斑區(qū)視網(wǎng)膜厚結(jié)果和結(jié)視力僅僅在6和24W時(shí)貝伐單抗（IVB）組※在任何時(shí)間點(diǎn)，IVT和IVB聯(lián)合治療的（IVB）組效果黃斑區(qū)視網(wǎng)膜厚度※僅在6W時(shí)貝伐單抗（IVB）組能夠明顯降低黃斑區(qū)視網(wǎng)膜厚度雷珠單抗治療14m26s—14m26s—雷珠單抗治療TheDiabeticRetinopathyClinicalResearchNetwork（DRCR，臨床1,2,3年結(jié)TheRISEandRIDEResearch（RISE和RIDE研究組雷珠單抗治療DME的系統(tǒng)評(píng)價(jià)和meta分14m45s—14m45s—2007.3~2008.12—2010,2011,201252個(gè)單位，583位合作者參加的前瞻性多中心研究691例（854）≥18歲Ⅰ或者Ⅱ型劑量珠單抗—0.5安奈德—4隨機(jī)分4組★假注射組3-10天后行激光，293★0.5mg雷珠單抗注射3-10天后行激光187★0.5mg雷珠單抗注射24W后行激光188★4mg曲安奈德3-10天后行激光，18652個(gè)單位，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的一年結(jié)視力（與假注射組3-10天后行激光比較0.5mg雷珠單抗注射3-10天和24W后但是4mg曲安奈德3-10天后行激光沒4mg曲安奈德3-10天后行激光組中人曲安奈德雷珠單抗并發(fā)※3（8%）眼內(nèi)炎發(fā)生在雷珠單抗注射※眼壓升高常見于曲安奈德DiabeticRetinopathyClinicalResearchNetwork.Randomizedtrialevaluatingranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2010;117（6）:1064-16m40s—16m40s—16m40s—16m40s—DiabeticRetinopathyClinicalResearchNetwork.Randomizedtrialevaluatingranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2010;117（6）:1064-16m42s—16m42s—不管是雷珠單抗注射310天后還是24W后行激光治療，其效果比單獨(dú)行激光治療要好在人工晶體眼，曲安奈德注射310天后行激光治療的效果比單獨(dú)行激光治療要好DRCR的二年結(jié)視力（與假注射組3-10天后行激光比較0.5mg雷珠單抗注射3-10天和24W后行4mg曲安奈德注射3-10天后行激光視力在1-2年隨訪中，雷珠單抗平均注射2-3黃斑中心凹視網(wǎng)膜厚度≧250μm的%分※單純激光組：59%；曲安奈德＋激光組：52%；雷珠單抗＋激光組兩組：并發(fā)3（8%）眼內(nèi)炎發(fā)生在雷珠單抗※眼壓升高常見于曲安奈德DiabeticRetinopathyClinicalResearchNetwork.Expanded2-yearfollow-upofranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2011;118（4）:609-DiabeticRetinopathyClinicalResearchNetwork.Expanded2-yearfollow-upofranibizumabpluspromptordeferredlaserortriamcinolonepluspromptlaserfordiabeticmacularedema.Ophthalmology,2011;118（4）:609-17m56s—17m56s—DRCR的二年結(jié)DME的正確性與合理18m8s—18m3318m8s—18m33DRCR三目標(biāo)比較0.5mg雷珠單抗注射3～10天后方法※391例≥18歲Ⅰ或者Ⅱ型※劑量雷珠單抗—0.5隨機(jī)分4組0.5mg雷珠單抗注射3-10天后行激144人★0.5mg雷珠單抗注射24W后行激光14718m3318m33s---DRCR的三年結(jié)視0.