异基因骨髓造血干细胞移植后并发巨细胞病毒视网膜炎患眼房水病毒载量变化的初步研究

Changes of aqueous cytomegalovirus DNA in patients with cytomegalovirus retinitis after allogeneic bone marrow hematopoietic stem cell transplantation

目的观察异基因骨髓造血干细胞移植(Allo-HSCT)后巨细胞病毒(CMV)性视网膜炎(CMVR)患眼房水中CMV-DNA载量,初步探讨其影响因素。方法回顾性临床研究。2016年1月至2020年7月于北京大学人民医院眼科检查确诊的Allo-HSCT后CMVR患者19例28只眼纳入研究。其中,男性8例12只眼,女性11例16只眼;中位年龄28岁;单眼10例,双眼9例。患者治疗及随访过程中血液CMV-DNA持续保持阴性状态。患者均给予玻璃体腔注射60 mg/ml更昔洛韦0.05 ml(含更昔洛韦3 mg)治疗。诱导期为2次/周,共4次;维持期为1次/周。每次玻璃体腔注射更昔洛韦(IVG)前抽取房水测定其中CMV-DNA载量。从第4次IVG开始,若房水CMV-DNA载量转阴则终止治疗,并连续随访至少6个月。依据治疗过程中患眼房水CMV-DNA载量是否存在一过性升高,将患眼分为持续下降组和非持续下降组。观察并分析两组间房水CMV-DNA载量及眼部检查表现的差异。房水CMV-DNA载量与IVG次数和治疗时长相关性采用Pearson线性回归分析。结果治疗终止时,患眼IVG中位次数为7(4,9)次。相关性分析结果显示,患眼房水CMV-DNA载量与治疗次数[R2=0.385,P<0.0001,B=-0.237 log10拷贝/(ml·次)]、治疗时长[R2=0.394,P<0.0001,B=-0.301 log10拷贝/(ml·周)]均呈负相关。28只眼中,持续下降组13只眼(46.4%,13/28);非持续下降组15只眼(53.6%,15/28)。持续下降组、非持续下降组患眼基线视力(t=-1.223)、眼压(t=1.538)、房水CMV-DNA载量(t=-0.109)、视网膜炎病灶面积(Z=-0.308)、病变累及象限个数(Z=-0.024)以及是否累及黄斑(Z=-1.826)、合并眼前节炎症反应(Z=-0.499)、合并高眼压(Z=-1.342)、终末视力(t=-0.845)、眼压(t=-0.068)、总IVG次数(Z=0.907)、年龄(Z=-0.832)、性别构成(Z=-1.074)等比较,差异均无统计学意义(P>0.05)。结论Allo-HSCT后CMVR患眼治疗过程中房水CMV-DNA载量每周下降约50%;房水CMV-DNA载量治疗过程中出现一过性升高不影响治疗过程和临床预后。

Objective To observe aqueous cytomegalovirus(CMV)DNA load in patients with cytomegalovirus retinitis(CMVR)after allogeneic hematopoietic stem cell transplantation(Allo-HSCT),and to explore influencing factors for transient elevation of CMV-DNA load during the treatment.Methods A retrospective study.From January 2016 to July 2020,28 eyes of 19 patients with CMVR after Allo-HSCT diagnosed in the Department of Ophthalmology of Peking University People's Hospital were included in the study.Among them,there were 8 males with 12 eyes,11 females with 16 eyes;the mean age was 28 years;10 patients were unilateral and 9 patients were bilateral.During the course of treatment and follow-up,the blood CMV-DNA remained negative.All patients were treated with intravitreal injection of 60 mg/ml ganciclovir 0.05 ml(containing ganciclovir 3 mg),twice a week for two weeks in induction phase and weekly injection in maintenance phase.Aqueous humor sample was collected during injection of ganciclovir(IVG)and CMV-DNA load was determined by real-time quantitative polymerase chain reaction.Intravitreal treatment was terminated if aqueous CMV-DNA load turned negative after the fourth or later intravitreal injection.The patients were followed up every 2 weeks for at least 6 months.Serum CMV-DNA was negative in all patients during treatment and follow-up.All the eyes were divided into continuous decline group and non-continuous decline group depending on whether there was transient elevation of aqueous CMV-DNA load,and data between two groups were compared.Pearson linear regression analysis was used to analyze the correlation between aqueous CMV-DNA load and injection times or treatment duration.Results At the end of treatment,the median number of IVG in the affected eye was 7(4,9).The results of correlation analysis showed that the aqueous humor CMV-DNA load of the affected eye was related to the number of treatments[R2=0.385,P<0.0001,B=-0.237 log10 copies/(ml·time)],and the duration of treatment[R2=0.394,P<0.0001,B=-0.301 log10 copies/(ml·week)]were negatively correlated.Among the 28 eyes,13 eyes(46.4%,13/28)in the continuous decline group and 15 eyes(53.6%,15/28)in the non-sustained decline group.Baseline visual acuity(t=-1.223),intraocular pressure(t=1.538),aqueous humor CMV-DNA load(t=-0.109),retinitis lesion area(Z=-0.308)in the continuous decline group and the non-continuous decline group),the number of quadrants involved(Z=-0.024)and whether the macula was involved(Z=-1.826),combined with anterior segment inflammation(Z=-0.499),combined with high intraocular pressure(Z=-1.342),terminal visual acuity(t=-0.845),intraocular pressure(t=-0.068),total IVG times(Z=0.907),age(Z=-0.832),gender composition(Z=-1.074),etc.The difference was not statistically significant(P>0.05).Conclusion The CMV-DNA load in aqueous humor decreases by about 50%every week during the treatment of CMVR eyes after Allo-HSCT;the transient increase in the CMV-DNA load in the aqueous humor during treatment does not affect the treatment process and clinical prognosis.