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中华眼科医学杂志(电子版) ›› 2020, Vol. 10 ›› Issue (01) : 13 -19. doi: 10.3877/cma.j.issn.2095-2007.2020.01.003

论著

两种不同诱因所致巨细胞病毒视网膜炎预后的临床观察
孔文君1, 陶勇2,†(), 陈超1, 谢连永1, 杜葵芳1   
  1. 1. 100069　首都医科大学附属北京佑安医院眼科　北京市感染性眼病诊疗中心
    2. 100020　首都医科大学附属北京朝阳医院眼科　北京市感染性眼病诊疗中心
  • 收稿日期:2019-12-11 出版日期:2020-02-28
  • 通信作者: 陶勇
  • 基金资助:
    北京市教育委员会科研计划项目(KM202010025020); 北京朝阳医院"1351人才培养计划"项目(CYXX-2017-21); 国家高技术研究发展计划项目(2015AA020949); 中国初级卫生保健基金会佑安肝病艾滋病基金项目(YNKT20160038); 首都医科大学北京市重点实验室开放性课题(2016YKSJ04)

Comparison of prognosis of cytomegalovirus retinitis induced by AIDS and HSCT postoperation

Wenjun Kong1, Yong Tao2,†(), Chao Chen1, Lianyong Xie1, Kuifang Du1   

  1. 1. Department of Opthalmology, Beijing You′an Hosptial, Capital Medical University, Beijing 100069, China
    2. Department of Opthalmology, Beijing Chaoyang Hosptial, Capital Medical University, Beijing 100020, China
  • Received:2019-12-11 Published:2020-02-28
  • Corresponding author: Yong Tao
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引用本文：

孔文君, 陶勇, 陈超, 谢连永, 杜葵芳. 两种不同诱因所致巨细胞病毒视网膜炎预后的临床观察[J]. 中华眼科医学杂志(电子版), 2020, 10(01): 13-19.

Wenjun Kong, Yong Tao, Chao Chen, Lianyong Xie, Kuifang Du. Comparison of prognosis of cytomegalovirus retinitis induced by AIDS and HSCT postoperation[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2020, 10(01): 13-19.

目的

探讨两种不同病因诱发的巨细胞病毒视网膜炎(CMVR)的预后情况。

方法

观察2015年5月至2019年10月首都医科大学附属北京佑安医院眼科和北京朝阳医院眼科确诊为CMVR患者32例(52只眼)。其中，男性27例(44只眼)，女性5例(8只眼)，平均年龄(25.4±7.8)岁。根据常见病因，分为获得性免疫缺陷综合征(AIDS)组和造血干细胞移植(HSCT)术后组两组。全部患者均行更昔洛韦和(或)膦甲酸钠玻璃体腔注药联合全身治疗，随访6个月。检查并记录治疗前和治疗6个月后患者的最佳矫正视力(BCVA)、眼压、眼底彩色照相、房水中巨细胞病毒脱氧核糖核酸(CMV-DNA)含量及外周血CD4+T淋巴细胞计数等指标。眼压以均数±标准差描述，以t检验进行比较。BCVA、外周血CD4+T淋巴细胞计数、房水CMV-DNA含量以中位数(最小值，最大值)描述，以Wilcoxon秩和检验进行比较。注药次数用频数或率(%)表示，组间比较采用卡方检验。

结果

治疗前AIDS组患者和HSCT术后组患者BCVA分别为0.36(0.02，1.00)和0.21(0.01，0.60)；治疗后AIDS组和HSCT术后组患者BCVA分别为0.53(0.05，1.00)和0.36(0.02，0.80)。经秩和检验，治疗前两组患者BCVA比较，差异无统计学意义(Z＝-0.23，P>0.05)；治疗后AIDS组患者BCVA高于HSCT术后组，差异具有统计学意义(Z＝-2.05，P<0.05)。治疗前AIDS组和HSCT术后组患者眼压分别为(11.9±2.8)mmHg(1 mmHg＝0.133 kPa)和(12.8±2.2)mmHg；治疗后AIDS组和HSCT术后组患者眼压分别为(13.4±2.7)mmHg和(13.9±3.5)mmHg。经t检验，治疗前和治疗后两组患者眼压比较，差异无统计学意义(t＝-0.94，-0.54；P>0.05)。治疗前AIDS组和HSCT术后组患者外周血CD4+T淋巴细胞计数分别为54(0，213)个/μl和47(2，87)个/μl；治疗后AIDS组和HSCT术后组患者外周血CD4+T淋巴细胞计数分别为139(32，371)个/μl和76(21，212)个/μl。经秩和检验，治疗前两组患者外周血CD4+T淋巴细胞计数比较，差异无统计学意义(Z＝-0.65，P>0.05)。治疗后AIDS组患者外周血CD4+T淋巴细胞计数高于HSCT术后组，差异具有统计学意义(Z＝-2.45，P<0.05)。治疗前AIDS组和HSCT术后组患者房水中CMV-DNA含量分别为2.74×104(1.59×103，5.14×105)拷贝/ml和7.18×103(3.17×103，5.89×105)拷贝/ml；治疗后AIDS组和HSCT术后组患者房水中CMV-DNA含量分别为1.24×10(0，2.23×102)拷贝/ml和2.01×10(0，3.45×102)拷贝/ml。经秩和检验，治疗前和治疗后两组患者房水中CMV-DNA含量比较，差异无统计学意义(Z＝-0.68，-0.27；P>0.05)。HSCT术后组患者在抗病毒治疗6个月内有3只眼出现CMVR复发，AIDS组患者在抗病毒治疗6个月内有1只眼出现CMVR复发。HSCT术后组患者玻璃体腔注药次数≥4次者占55%(11只眼/20只眼)，AIDS组患者玻璃体腔注药次数≥4次者占18.8%(6只眼/32只眼)。经卡方检验，HSCT术后组和AIDS组患者玻璃体腔注药次数≥4次者的比较，差异有统计学意义(χ2＝6.231，P<0.05)。

结论

较之于AIDS诱发的CMVR，HSCT术后诱发的CMVR局部联合全身抗病毒治疗后免疫功能恢复慢，视功能较差，可能需要更长时间的眼内抗病毒治疗。

关键词: 巨细胞病毒视网膜炎, 获得性免疫缺陷综合征, 造血干细胞移植术后
Objective

To explore the prognosis of cytomegalovirus retinitis (CMVR) induced by two different etiologies.

Methods

From May 2015 to October 2019, 32 CMVR patients (52 eyes) diagnosed in the department of Ophthalmology of Beijing You′an Hospital and Beijing Chaoyang Hospital affiliated to Capital Medical University. There were 27 males and 5 females, with an average age of (25.4±7.8) years. According to common causes, patients were divided into two groups; one group was acquired immune deficiency syndrome (AIDS) and the other group with the postoperative hematopoietic stem cell transplantation (HSCT) . 32 patients were treated with ganciclovir and (or) sodium phosphonate intravitreal injection combined with systemic therapy and followed up for 6 months. Analysis of the best corrected visual acuity (BCVA), intraocular pressure, fundus and cytomegalovirus virus (CMV)-DNA in anterior chamber, CD4+ T cells in blood was made before and after the treatment. Intraocular pressure was represented as expressed in mean ± SD and compared with t test. BCVA, the number of CD4+ T cells in blood and the content of CMV-DNA in aqueous humor were expressed in median (minimum, maximum) and compared with Wilcoxon rank sum test. Counting data was expressed by frequency or rate (%) and compared with Chi-square test.

Results

Before treatment, the BCVA of patients in the AIDS group and the HSCT postoperative group were 0.36 (0.02, 1.00) and 0.21 (0.01, 0.60). After treatment, the BCVA of patients in the AIDS group and the HSCT postoperative group were 0.53 (0.05, 1.00) and 0.36 (0.02, 0.80). With Wilcoxon rank sum test, there was no significant difference in BCVA between two groups of patients before treatment (Z=-0.23, P>0.05). The BCVA in the AIDS group was higher than that in the HSCT postoperative group after treatment (Z=-2.05, P<0.05). Before treatment, the intraocular pressure of patients in the AIDS group and in the HSCT postoperative group were (11.9±2.8)mmHg (1 mmHg=0.133 kPa) and (12.8±2.2)mmHg. After treatment, the intraocular pressure of patients in the AIDS group and HSCT postoperative group were (13.4±2.7) and (13.9±3.5)mmHg. With t test, there was no significant difference in intraocular pressure between two groups of patients before and after treatment (t=-0.94, -0.54; P>0.05). Before treatment, the peripheral blood CD4+ T cell counts of patients in the AIDS group and HSCT postoperative group were 54 (0, 213) cells/μl and 47 (2, 87) cells/μl. After treatment, the peripheral blood CD4+ T cell counts of patients in the AIDS group and HSCT postoperative group were 139 (32, 371) cells/μl and 76 (21, 212) cells /μl. With Wilcoxon rank sum test, there was no significant difference in the peripheral blood CD4+ T cell counts between two groups of patients before treatment (Z=-0.65, P>0.05). The peripheral blood CD4+ T cell counts in the AIDS group were higher than that in the HSCT postoperative group after treatment (Z=-2.45, P<0.05). Before treatment, the CMV-DNA in the aqueous humor of the AIDS group and the HSCT postoperative group were 2.74×104 (1.59×103, 5.14×105) copies/ml and 7.18×103 (3.17×103, 5.89×105) copies/ml. After treatment, the CMV-DNA in the aqueous humor of the AIDS group and the HSCT postoperative group was 1.24×10 (0, 2.23×102) copies/ml and 2.01×10 (0, 3.45×102) copies/ml. With Wilcoxon rank sum test, there was no significant difference in CMV-DNA in aqueous humor between two groups of patients before and after treatment (Z=-0.68, -0.27; P>0.05). Recurrence of CMVR occurred in 3 eyes within 6 months of antiviral treatment in the HSCT postoperative group, and recurrence of CMVR occurred in 1 eye within six months of antiviral treatment in the AIDS group. Additionally, 55% patients in the HSCT group and only 18.8% patients in the AIDS group underwent intravitreal injections for 4 times and more than 4 times. The analysis of Chi-square test showed that there was a significant difference in the number of intravitreal injections 4 times or more between HSCT and AIDS patients (χ2=6.23, P<0.05).

Conclusions

Compared with AIDS-induced CMVR, CMVR induced by HSCT has more severe visual impairment, slower recovery of immune function during treatment, which requires longer-term intraocular antiviral treatment.

Key words: Cytomegalovirus retinitis, Acquired immune deficiency syndrome, The postoperative hematopoietic stem cell transplantation
图1 巨细胞病毒视网膜炎治疗前后眼底彩色照像　图A示获得性免疫缺陷综合征合并巨细胞病毒视网膜炎患者治疗前眼底周边型巨细胞病毒视网膜炎，左眼视网膜鼻侧和下方可见黄白色渗出及沿血管周围出血，病灶未累及黄斑区。图B示获得性免疫缺陷综合征合并巨细胞病毒视网膜炎患者治疗6个月后左眼视网膜鼻侧原有病灶处出血渗出吸收，形成机化膜，下方原有病灶陈旧瘢痕化。图C示造血干细胞移植术后合并巨细胞病毒视网膜炎患者治疗前右眼中央型巨细胞病毒视网膜炎，视网膜广泛渗出和出血位于视盘和黄斑区，并向下方延伸。图D示造血干细胞移植术后合并巨细胞病毒视网膜炎患者治疗6个月后右眼视网膜病灶吸收，视网膜血管白线并残存黄白色颗粒样结晶
表1 治疗前和治疗6个月后两组患者BCVA、外周血CD4+T淋巴细胞计数及房水CMV-DNA值的比较
组别 眼数 BCVA [M(Min，Max)] CD4+T淋巴细胞计数[M(Min，Max)](个/μl) 房水CMV-DNA值[M(Min，Max)](拷贝/ml)
治疗前 治疗6个月后 治疗前 治疗6个月后 治疗前 治疗6个月后
AIDS组 32 0.36(0.02，1.00) 0.53(0.05，1.00) 54(0，213) 139(32，371) 2.74×104(1.59×103，5.14×105) 1.24×10(0，2.23×102)
HSCT术后组 20 0.21(0.01，0.60) 0.36(0.02，0.80) 47(2，87) 76(21，212) 7.18×103(3.17×103，5.89×105) 2.01×10(0，3.45×102)
Z值   -0.23 -2.05 -0.65 -2.45 -0.68 -0.27
P值   >0.05 <0.05 >0.05 <0.05 >0.05 >0.05
表2 治疗前及治疗6个月后两组患者患眼眼压的比较[±s ，mmHg]
组别 眼数 治疗前 治疗6个月后
AIDS组 32 11.9±2.8 12.8±2.2
HSCT术后组 20 13.4±2.7 13.9±3.5
t值   -0.94 -0.54
P值   >0.05 >0.05
表3 治疗期间两组患者玻璃体腔内注药次数的比较[%(注药眼数/组内总眼数)]
组别 眼数 注药次数<4次 注药次数≥4次
AIDS组 32 81.3(26/32) 18.8(6/32)
HSCT术后组 20 45(9/20) 55(11/20)
χ2值   6.231  
P值   <0.05  
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