角膜移植失败者巨细胞病毒感染的危险因素分析

Risk factors of cytomegalovirus infection in patients with failed corneal grafts

目的探讨角膜移植失败者巨细胞病毒(CMV)感染水平及危险因素。方法病例对照研究。收集2016年1月至2022年5月因角膜移植失败于北京大学第三医院眼科再次行角膜移植手术患者的临床资料576例(576只眼),其中男性305例,女性271例,年龄为44.0(0.7,91.0)岁。依据角膜移植手术中房水或角膜组织病毒DNA的检测结果将患者分为CMV DNA阳性的CMV组和疱疹病毒DNA均为阴性的对照组,以CMV感染率、临床特征以及危险因素为主要研究指标,运用卡方检验和二元logistic回归分析比较两组患者在一般资料、合并全身病、眼部病变、眼部手术史和局部及全身用药等方面的差异,计算各CMV感染危险因素的比值比(OR值)及95%置信区间(CI)。结果患者总体CMV感染率为21.9%(126/576),2016至2021年历年CMV感染率为10.9%~37.7%。根据纳入和排除标准,最终有378例患者被纳入对照试验,其中CMV组126例,对照组252例。两组之间差异存在统计学意义(P<0.05)的主要指标为全身免疫异常相关性角膜病变[CMV组:38例(30.2%),对照组:26例(10.3%)]、局部免疫及炎性角膜病变[CMV组:46例(36.5%),对照组:40例(15.9%)]、先天性角膜混浊[CMV组:46例(36.5%),对照组:48例(19.0%)]、总角膜移植次数(CMV组:178次,对照组:276次)、跨过植片的角膜深层新生血管[CMV组:104例(82.5%),对照组:68例(27.0%)]和严重混浊[CMV组:44例(34.9%),对照组:30例(11.0%)]。二元logistic回归分析结果显示,全身免疫异常相关性角膜病变(OR=4.044,95%CI:1.810~9.033,P<0.001)、局部免疫及炎性角膜病变(OR=3.554,95%CI:1.569~8.052,P<0.05)、先天性角膜混浊(OR=2.606,95%CI:1.216~5.589,P<0.05)、总角膜移植次数(OR=3.206,95%CI:1.753~5.864,P<0.001)、跨过植片的角膜深层新生血管(OR=8.347,95%CI:3.967~17.559,P<0.001)和严重混浊(OR=3.063,95%CI:1.221~7.682,P<0.05)是角膜移植后CMV感染的独立危险因素。结论超过1/5的角膜移植失败者存在CMV感染。角膜移植后的CMV感染可能与免疫排斥反应及眼部炎性反应有关。全身或局部免疫异常相关的炎性角膜病变、先天性角膜混浊和多次角膜移植可能加剧了角膜移植围手术期的炎症因子水平,增加了移植后CMV感染的风险,进而导致了角膜深层新生血管的长入和严重混浊。

Objective To investigate the levels of cytomegalovirus(CMV)infection and associated risk factors in corneal transplant recipients who experienced transplant failure.Methods This was a case-control study.Clinical data from 576 cases(576 eyes)of patients who underwent repeat corneal transplant surgery at the Department of Ophthalmology,Peking University Third Hospital,due to corneal transplant failure from January 2016 to May 2022 were collected.Of these,305 were male and 271 were female,with a median age of 44.0(0.7,91.0)years.The CMV infection rate was analyzed based on the detection of CMV DNA in aqueous humor or corneal tissue during corneal transplant surgery.Patients were divided into the CMV group(CMV DNA positive)and the control group(herpes virus DNA negative).The main research indicators included the CMV infection rate,clinical characteristics,and risk factors in corneal transplant recipients.Chi-square tests and binary logistic analysis were used to compare differences between the two groups in general information,systemic diseases,ocular lesions,ocular surgical history,and local and systemic medications.Odds ratios(OR)and 95%confidence intervals(CI)were calculated for each CMV infection risk factor.Results The overall CMV infection rate was 21.9%(126/576),with annual rates ranging from 10.9%to 37.7%from 2016 to 2021.After applying inclusion and exclusion criteria,378 patients were included in the control trial,with 126 in the CMV group and 252 in the control group.Statistically significant differences between the two groups were observed in systemic immune-related corneal lesions[CMV group:38(30.2%),control group:26(10.3%)],local immune and inflammatory corneal lesions[CMV group:46(36.5%),control group:40(15.9%)],congenital corneal opacity[CMV group:46(36.5%),control group:48(19.0%)]total number of corneal transplants(CMV group:178 times,control group:276 times),corneal deep neovascularization crossing the graft[CMV group:104(82.5%),control group:68(27.0%)]and severe opacity[CMV group:44(34.9%),control group:30(11.0%)].Binary logistic regression analysis showed that systemic immune-related corneal lesions(OR=4.044,95%CI 1.810-9.033,P<0.001),local immune and inflammatory corneal lesions(OR=3.554,95%CI 1.569-8.052,P=0.002),congenital corneal opacity(OR=2.606,95%CI 1.216-5.589,P=0.014),total number of corneal transplants(OR=3.206,95%CI 1.753-5.864,P<0.001),corneal deep neovascularization crossing the graft(OR=8.347,95%CI 3.967-17.559,P<0.001),and severe opacity(OR=3.063,95%CI 1.221-7.682,P=0.017)were independent risk factors for CMV infection after corneal transplant.Conclusions CMV infection was present in more than 1/5 of corneal transplant recipients who experienced transplant failure.CMV infection after corneal transplant may be related to immune rejection reactions and ocular inflammatory responses.Inflammatory corneal lesions associated with systemic or local immune abnormalities,congenital corneal opacity,and multiple corneal transplants may exacerbate the levels of inflammatory factors during the perioperative period of corneal transplant,increasing the risk of post-transplant CMV infection,leading to the infiltration of deep neovascularization and severe opacity in the cornea.