【作者】 安洋；

【导师】 范斌；

【作者基本信息】 吉林大学 ， 临床医学硕士（专业学位）， 2023， 硕士

【摘要】 目的:采用系统综述的方式找出致使息肉状脉络膜血管病变(Polypoidal choroidal vasculopathy,PCV)发生大面积黄斑下出血(Submacular hemorrhage,SMH)或玻璃体积血(Vitreous hemorrhage,VH)的原因;并通过meta分析,比较有关PCV导致大面积(≥4个视盘直径)SMH的治疗方式的疗效及差异。做出客观的临床评价。旨在为临床医师对评估PCV进展的严重程度以及大面积SMH治疗选择提供一些循证医学证据。方法:通过计算机对Pub Med、Embase、Cochrane、知网、万方、维普、CBM七个数据库进行全面检索。检索内容主要包含:PCV、SMH、VH以及玻璃体切除术(Pars plana vitrectomy,PPV)的相关资料。随后进行文献筛选和质量评价。最后进行基线资料及结局指标的提取,并通过meta分析得出结果。本研究主要观察治疗后最佳矫正视力(Best corrected visual acuity,BCVA)连续数值改变量、BCVA上升或下降率以及中央视网膜厚度(Central retinal thickness,CRT)的改变量。使用STATA14.0统计软件处理数据,合并计算各项观察指标的标准平均差(Standard mean difference,SMD)、率值(Rate,R)及其95%可信区间(Confidence interval,CI)以进行meta分析。结果:第一部分出血原因分析的相关研究中共纳入了28篇文献。通过系统评价得出:一、未治疗导致出血的原因中:ARMS2 A69S基因型、视网膜色素上皮层脱离(Pigment epithelial detachment,PED)且为纤维血管性PED或出血性PED、大面积SMH、出血性视网膜脱离、簇状息肉、外周血CD11b+单核细胞比例增加、年龄大、服用抗凝药以及患者高血压病史等因素与SMH或突破性VH相关。二、在所有因治疗导致出血的原因中:抗血管内皮生长因子(Vascular endothelial growth factor,VEGF)治疗对于引起突破性VH的风险较大;光动力疗法(Photodynamic therapy,PDT)治疗对于引发大面积SMH的风险较大。第二部分大面积SMH治疗的研究中共纳入了10篇文献。通过meta分析得出:一、治疗对于BCVA(用Log MAR表示)改变量方面:1.治疗后3、6、12个月以及末次随访(至少大于6个月)时,SMD及95%CI分别为:-0.37(-0.66,-0.08)、-0.61(-0.94,-0.28)、-0.58(-0.83,-0.32)、-0.74(-1.05,-0.43),P值均<0.05,提示含有或不含有PPV的治疗均可使BCVA改善;2.治疗后1个月SMD及95%CI为:-0.49(-1.02,0.09),P=0.073>0.05,其中含有组织纤溶酶原激活剂(Tissue-type plasminogen activator,t-PA)的治疗组SMD及95%CI为:-1.36(-1.80,-0.92),P<0.05,而不含tPA的治疗组SMD及95%CI为:-0.03(-0.44,0.38),P=0.88>0.05。说明了含有t-PA的治疗可改善治疗后1个月的BCVA,而不含t-PA的治疗组则未能使BCVA得到改善。二、治疗对于末次随访(至少大于6个月)时BCVA上升/下降率的影响方面:1.上升率方面:综合治疗、PPV组及非PPV组治疗的R及95%CI分别为:0.60(0.49,0.70)、0.74(0.64,0.85)、0.52(0.44,0.60),P值均<0.05,说明了综合治疗、PPV组及非PPV组治疗下BCVA的改善率分别为:60%、74%、52%。2.下降率方面:综合治疗、PPV组及非PPV组治疗的R及95%CI分别为:0.093(0.032,0.174)、0.031(0.000,0.146)、0.151(0.076,0.243),即综合治疗、PPV组及非PPV组治疗下BCVA的恶化率分别为:9.3%、3.1%、15.1%。三、治疗对于CRT改变方面:治疗后1、6个月及末次随访(至少大于6个月)时SMD及95%CI分别为:-1.65(-1.98,-1.32)、-1.91(-2.97,-0.84)、-1.89(-2.69,-1.09),P值均<0.05,提示非PPV组治疗下CRT均可获得改善。结论:1、AMRS2 A69S基因、簇状息肉、外周血CD11b+单核细胞比例增加、服用抗凝药、高血压病史以及PDT治疗与PCV患者发生黄斑下出血有关;AMRS2 A69S基因、年龄大、存在PED且为纤维血管性PED或出血性PED、大面积SMH以及抗VEGF治疗与PCV患者发生突破性玻璃体积血有关。2、对于PCV引起的大面积SMH患者,PPV与非PPV治疗方式对BCVA在短期及长期的改善均有效。3、在至少6个月的随访中,关于BCVA上升/下降率这一指标,PPV治疗显示出了优于非PPV治疗的特点。4、非PPV治疗对于改善CRT有效。5、t-PA治疗对于短期BCVA改善有效,对于长期BCVA改善意义较小。更多还原

【Abstract】 Objective:Systematic review was performed to identify the causes of massive macular submacular hemorrhage(SMH)or breakthrough vitreous hemorrhage(VH)in polypoidal choroidal vasculopathy(PCV).Meta-analysis was conducted to compare the therapeutic effects and differences between massive(no less than 4 disk diameter)SMH caused by PCV,and to make an objective clinical evaluation.The aim of this study was to provide some evidencebased medical evidence for clinicians to assess the severity of PCV progression and to choose treatment for massive SMH.Methods:Pub Med,Embase,Cochrane,CNKI,Wanfang Data,VIP and CBM databases were searched for studies on PCV,SMH,VH and vitrectomy.Subsequently,literature screening and quality assessment were conducted according to the inclusion and exclusion criteria.Finally,baseline and outcome data were extracted from selected literatures,and the results were obtained through meta-analysis.The main objective of this study was to observe the continuous numerical change of best corrected visual acuity(BCVA),the improvement or decline rate of BCVA,and the change of central retinal thickness(CRT)after treatment.STATA14.0 statistical software was used to process the data,and the standard mean difference(SMD),rate(R)and 95% confidence interval(CI)of each observation index were pooled for meta-analysis.Results:A total of 28 articles were included in the first part of the analysis of hemorrhage causes.The systematic review concluded that: 1.Among the causes of hemorrhage without treatment: ARMS2 A69 S genotype,pigment epithelial detachment(PED)with fibrovascular PED or hemorrhagic PED,large SMH,hemorrhagic retinal detachment and hemorrhagic retino-choroidal detachment,clustered polyps,increased proportion of CD11b+ monocytes in peripheral blood,older age,use of anticoagulants and history of hypertension were associated with SMH or breakthrough VH.2.Among all the causes of hemorrhage due to treatment,anti-VEGF therapy had a higher risk of causing breakthrough vitreous hemorrhage;PDT had a high risk of inducing massive SMH.In the second part,a total of 10 articles were included for the studies of moderate and large SMH treatment.The results of meta-analysis were as follows:1.The change of BCVA(expressed as Log MAR)after treatment :1.The SMDs(95%CI)at 3,6,12 months after treatment and at the last follow-up(≥ 6 months)were:-0.37(-0.66,-0.08),-0.61(-0.94,-0.28),-0.58(-0.83,-0.32),-0.74(-1.05,-0.43),and P<0.05,indicating that BCVA improved after treatment with or without PPV.2.The SMD(95%CI)at 1 month after treatment was-0.49(-1.02,0.09)(P=0.073>0.05),among which the SMD(95%CI)of the treatment group containing tissue-type plasminogen activator(t-PA)was-1.36(-1.80,-0.92)(P<0.05)and of the non-t-PA group was-0.03(-0.44,0.38)(P=0.88>0.05),indicating that BCVA improved in the t-PA-containing group but not in the non-t-PA group at 1-month follow-up.2.The effect of treatment on the rate of BCVA increase/decrease at the last follow-up(at least more than 6 months):1.In terms of the rate of increase,Rates(95%CI)of the overall treatment,the PPV group and the non-PPV group were: 0.60(0.49,0.70),0.74(0.64,0.85),0.52(0.44,0.60),and P<0.05,indicating that the improvement rates of BCVA under the overall treatment,the PPV group and the non-PPV group were: 60%,74%,52%,respectively.2.In terms of the rate of decline: Rates(95%CI)of overall treatment,PPV group and nonPPV group treatment was: 0.093(0.032,0.174),0.031(0.000,0.146),0.151(0.076,0.243),indicating that the deterioration rates of BCVA under the overall treatment,PPV group and non-PPV group were 9.3%,3.1%,15.1%,respectively.3.In terms of CRT change,SMDs(95%CI)at 1 month,6 months and the last follow-up(at least 6 months)after treatment were:-1.65(-1.98,-1.32),-1.91(-2.97,-0.84),-1.89(-2.69,-1.09),and P<0.05,indicating that CRT could be improved under non-PPV treatment.Conclusion:1.AMRS2 A69 S gene,clustered polyps,increased proportion of CD11b+ monocytes in peripheral blood,taking anticoagulants,history of hypertension and PDT treatment are associated with SMH in PCV patients;AMRS2 A69 S gene,older age,presence of PED and fibrovascular PED or hemorrhagic PED,large area of SMH and anti-VEGF therapy are associated with breakthrough vitreous hemorrhage in PCV patients.2.For patients with moderate and large SMH caused by PCV,PPV and non-PPV treatment methods are effective in improving BCVA in the short and long term.3.PPV treatment is superior to non-PPV treatment with respect to the rate of BCVA improvement / decline at a minimum follow-up of 6 months.4.Non-PPV treatment is effective for improving CRT.5.t-PA treatment is effective for short-term BCVA improvement,but it has little significance for long-term BCVA improvement.更多还原