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中华眼科医学杂志(电子版) ›› 2022, Vol. 12 ›› Issue (02) : 76 -81. doi: 10.3877/cma.j.issn.2095-2007.2022.02.003

论著

房水病毒载量和细胞因子检测在急性视网膜坏死诊断与治疗中应用的临床研究
刘夕瑶1, 毛菲菲1, 李丹1, 鲁丹1, 王胜男1, 孙挥宇1,†()   
  1. 1. 100015　首都医科大学附属北京地坛医院眼科　国家传染病医学中心
  • 收稿日期:2021-11-08 出版日期:2022-04-28
  • 通信作者: 孙挥宇
  • 基金资助:
    北京市医院管理中心科研培育计划项目(PX2018061); 北京市医院管理中心人才培养计划"登峰"项目(DFL20191802); 北京市医院管理局临床医学发展专项(ZYLX202126)

The role of aqueous humor viral load and inflammatory cytokines in patients with acute retinal necrosis for the diagnosis and treatment

Xiyao Liu1, Feifei Mao1, Dan Li1, Dan Lu1, Shengnan Wang1, Huiyu Sun1,†()   

  1. 1. Department of Ophthalmology, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
  • Received:2021-11-08 Published:2022-04-28
  • Corresponding author: Huiyu Sun
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刘夕瑶, 毛菲菲, 李丹, 鲁丹, 王胜男, 孙挥宇. 房水病毒载量和细胞因子检测在急性视网膜坏死诊断与治疗中应用的临床研究[J]. 中华眼科医学杂志(电子版), 2022, 12(02): 76-81.

Xiyao Liu, Feifei Mao, Dan Li, Dan Lu, Shengnan Wang, Huiyu Sun. The role of aqueous humor viral load and inflammatory cytokines in patients with acute retinal necrosis for the diagnosis and treatment[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2022, 12(02): 76-81.

目的

探讨房水病毒载量和细胞因子检测在急性视网膜坏死(ARN)诊断治疗中的作用。

方法

回顾性分析2017年3月至2021年7月于北京地坛医院眼科就诊ARN患者10例(13只眼)的病例资料。其中，男性8例(10只眼)，女性2例(3只眼)；年龄24~66岁，平均年龄(35.1±10.2)岁。采集所有患者的房水，明确病毒种类。将患者治疗前房水中病毒载量高于105拷贝/ml定义为高载量组，低于者定义为低载量组。对所有患者均行静脉和玻璃体腔注射更昔洛韦治疗；对视网膜脱离者行玻璃体切除视网膜复位术或视网膜激光光凝术。检查所有患者治疗前后的最佳矫正视力、眼前节及眼底情况。采用聚合酶链式反应检测所有患者治疗前和每次随访时房水的病毒载量；采用流式细胞微球捕获芯片技术检测患者治疗前和随访时房水白细胞介素(IL)-6及IL-8的含量。房水病毒载量的下降速度以log(病毒载量)拷贝/ml表示。最佳矫正视力以例数和百分比表示；注射次数、房水病毒载量、IL-6及IL-8以中位数和四分位数表示。

结果

ARN患者10例(13只眼)均为感染水痘带状疱疹病毒(VZV)导致，治疗后视网膜病变均得到有效控制，玻璃体腔注射次数为2~9次，平均中位数和四分位数6(5，9)次。继发视网膜脱离者4例(5只眼)，占38.46%(5/13)。其中，行玻璃体切除术者3例(3只眼)，占60.00%(3/5)；行视网膜激光光凝术1例(2只眼)，占40.00%(2/5)。患者治疗前房水VZV平均载量的中位数和四分位数为2.69×105(4.27×104，9.26×107)拷贝/ml；治疗2周后病毒载量开始下降，logVZV平均每周下降(0.67±0.30)拷贝/ml；治疗6周后升高者3例(5只眼)，占38.46%(5/13)。患者治疗前房水IL-6和IL-8平均含量的中位数和四分位数分别为2993.3(1655.9，18751.3)pg/ml和253.6(195.8，1682.2)pg/ml；治疗2周后分别为398.1(251.2，2511.8)pg/ml和63.1(15.8，125.9)pg/ml，较治疗前明显下降。高载量组和低载量组患者的病程分别为(14.00±4.47)d和(11.33±8.26)d，前者时间长于后者19.07%。高载量组和低载量组患者平均注射次数的中位数和四分位数分别为7(6，9)和6.5(4，9)。高载量组和低载量组患者终末最佳矫正视力≥0.1者分别为2例(2只眼)和4例(4只眼)，分别占15.38%(2/13)和30.77%(4/13)；<0.1者分别为4例(5只眼)和2例(2只眼)，分别占38.46%(5/13)和15.38%(2/13)。高载量组和低载量组继发视网膜脱离者分别为4例(4只眼)和1例(1只眼)，分别占30.77%(4/13)和7.69%(1/13)。

结论

ARN患眼房水的病毒载量在治疗后，经历平台期和对数下降期，并最终低至可检测阈值以下。房水IL-6和及IL-8含量可以评估眼内炎的严重程度。房水检测可以明确病毒种类，监测炎症反应和治疗效果，对于ARN的诊断与治疗具有重要参考价值。

关键词: 急性视网膜坏死, 聚合酶链式反应, 流式细胞微球捕获芯片技术, 玻璃体注药术, 更昔洛韦
Objective

The aim of this study was to investigate the role of aqueous humor viral loadand inflammatory cytokines in patientswith acute retinal necrosis (ARN) for the diagnosis and treatment.

Methods

10 ARN patients (13 eyes) were collected from Department of Ophthalmology, Beijng Ditan Hospital affiliated to Capital Medical University from March 2017 to July 2021 and retrospectively analyzed. Among of them, there were 8 males (10 eyes) and 2 females (3 eyes), with an average age of (35.1±10.2) years-old (ranged from 24 to 66 years-old). According to the initial viral load in aqueous humor, the group was divided into the high viral load group and the low viral load group with 105 copies/ml as the boundary. All patients received intravenous and intravitreal injection of ganciclovir. Patients with retinal detachment underwent vitrectomy or retinal laser photocoagulation. The best corrected visual acuity (BCVA), anterior segment and fundus of patients were oberserved before and after treatment. The aqueous humor viral load of all patients were detected before and at follow-up using polymerase chain reaction; the aqueous humor interleukin-6 (IL-6), interleukin-8 (IL-8) were detected before and at follow-up using a microsphere-based flow cytometric assay. The rate of decrease in aqueous humor viral load was expressed as log (viral load) copies/ml. The aqueous humor viral load, IL-6, IL-8 were expressed in median and quartile.

Results

10 cases (13 eyes) ARN were caused by varicella-zoster virus (VZV) and effectively controlled after treatment. The vitreous injection frequency was 2 to 9 times with an average of 6(5, 9) times. There were 4 cases (5 eyes) with secondary retinal detachment, accouting for 38.46% (5/13). Among of them, there were 3 cases (3 eyes) treated by vitrectomy and 1 case (2 eyes) treated by retinal laser photocoagulation, accouting for 60.00% (3/5) and 40.00% (2/5), respectively. The aqueous humor VZV load before treatment was 2.69×105(74.27×104, 9.26×107) copies/ml. After treatment for 2 weeks, the aqueous humor viral load of all patients decreased significantly, with an average weekly decrease of (0.67±0.30) copies/ml of log (VZV). After treatment for 6 weeks, there were the aqueous humor viral load of 3 cases (5 eyes) rebounded. Before treatment, the levels of IL-6 and IL-8 in aqueous fluid were 2993.3(1655.9, 18751.3)pg/ml and 253.6(195.8, 1682.2) pg/ml. After treatment for 2 weeks, the levels of IL-6 and IL-8 was 398.1(251.2, 2511.8)pg/ml and 63.1(15.8, 125.9)pg/ml, respectively, which were decreased significantly than that before the treatment for all patients. The course of disease was (14.00±4.47) d in the high load group and (11.33±8.26) d in the low load group, which was 19.07% longer than that in the high load group. The average injections of two groups were 7 (6, 9) times and 6.5 (4, 9) times, respectively. There were 2 cases (2 eyes) and 4 cases (4 eyes) patients with terminal visual acuity ≥0.1 in the high loading group and the low loading group, accounting for 15.38%(2/13) and 30.77%(4/13), respectively. There were 4 cases (5 eyes) and 2 cases (2 eyes) with final visual acuity <0.1, accounting for 38.46%(5/13) and 15.38%(2/13). There were 4 cases (4 eyes) and 1 case (1 eye) with secondary retinal detachment in the high and low load groups, accounting for 30.77%(4/13) and 7.69%(1/13), respectively.

Conclusions

After treatment, the viral load in the intraocular fluid of ARN patients experienced a plateau, a logarithmic decline and finally was below the detection threshold. The level of IL-6 and IL-8 in aqueous humor could be helpful to assess the severity of intraocular inflammation. The aqueous humor detection could identify the type of virus, monitor inflammatory response and treatment effect, which would play an important role in the diagnosis and treatment of ARN.

Key words: Acute retinal necrosis, Polymerase chain reaction, Flow cytometric microsphere-based immunoassays, Vitreous injection, Ganciclovir
表1 10例(13只眼)急性视网膜坏死综合征患者房水病毒检测、并发症及治疗前后的基本情况
序号 性别 年龄(岁) 病程(d) 眼别 病毒种类 治疗前病毒载量(105拷贝/ml) 眼内注射次数(次) 并发症 视网膜脱离处理 治疗前视力 末次视力
1 男 55 25 右 VZV 0.974 3 无   0.07 0.07
2 男 65 20 右 VZV 48.900 5* 视网膜脱离 玻璃体切除术 手动 手动
3 男 24 10 左 VZV 9.260 2* 视网膜脱离 玻璃体切除术 0.8 光感
4 女 39 14 左 VZV 0.413 6 无   0.3 1.0
5 男 48 10 左 VZV 3.860 7 无   0.8 0.5
6 男 36 14 右 VZV 2.690 6 视网膜脱离 玻璃体切除术 0.05 光感
      10 左 VZV 6.280 6 视神经萎缩   0.12 光感
7 女 66 7 右 VZV 0.427 9 视神经萎缩、白内障   手动 手动
      1 右 VZV 0.943 7 无   0.5 0.8
8 男 40 20 右 VZV 0.275 5 无   0.2 0.6
9 男 43 14 右 VZV 18.900 9 视网膜脱离 视网膜激光光凝 0.5 0.8
      5 左 VZV 0.356 9 视网膜脱离 视网膜激光光凝 0.3 0.5
10 男 57 20 右 VZV 71.200 9 视神经萎缩   0.05 手动
图2 9次玻璃体注射3例(4只眼)急性视网膜坏死患者治疗前和治疗期间随访时房水白细胞介素-6和白细胞介素-8含量的动态变化
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