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更昔洛韦玻璃体腔注射治疗HSCT术后并发巨细胞病毒性视网膜炎研究进展
陈伟彬
赵明威 [综述]
苗恒 [综述]
作者及单位信息
·
DOI： 10.3760/cma.j.cn115989-20220116-00020
Advances in intravitreal ganciclovir treatment of cytomegalovirus retinitis after hematopoietic stem cell transplantation
Chen Weibin
Zhao Mingwei
Miao Heng
Authors Info & Affiliations
Chen Weibin
Department of Ophthalmology and Clinical Center of Optometry, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing Key Laboratory Diagnosis and Therapy of Retina and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing 100044, China
Zhao Mingwei
Department of Ophthalmology and Clinical Center of Optometry, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing Key Laboratory Diagnosis and Therapy of Retina and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing 100044, China
Miao Heng
Department of Ophthalmology and Clinical Center of Optometry, Peking University People's Hospital, Eye Diseases and Optometry Institute, Beijing Key Laboratory Diagnosis and Therapy of Retina and Choroid Diseases, College of Optometry, Peking University Health Science Center, Beijing 100044, China
·
DOI： 10.3760/cma.j.cn115989-20220116-00020
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摘要

造血干细胞移植术(HSCT)给许多血液病患者带来了延长生存期的可能，但移植术后患者往往因免疫功能低下而并发巨细胞病毒性视网膜炎(CMVR)。更昔洛韦玻璃体腔注射(IVG)是该病的主要治疗手段之一。因HSCT术后CMVR的治疗和随访尚缺乏标准化共识或指南，现存的IVG方案在给药剂量和给药频率上尚存在较大差异。基于房水病毒载量和细胞因子监测的大剂量IVG治疗和随访方案开始被应用于临床，并被证实可显著缩短治疗时长并减少注药次数。IVG造成视网膜毒性的病例报道十分罕见，其治疗HSCT术后CMVR是安全且有效的，但安全剂量范围尚需探索。本文从更昔洛韦的作用机制、系统性应用存在的问题、玻璃体腔注射的治疗方案、玻璃体腔注射的视网膜毒性几个方面就IVG治疗HSCT术后并发CMVR的研究进展进行综述。

造血干细胞移植术;巨细胞病毒性视网膜炎;更昔洛韦;玻璃体腔注射;临床方案
ABSTRACT

Hematopoietic stem cell transplantation (HSCT) brings the possibility to prolong survival for patients with different types of hematological diseases, but patients may be complicated with cytomegalovirus retinitis (CMVR) due to immunocompromised state.Intravitreous injection of ganciclovir (IVG) is a major treatment in CMVR after HSCT, but there are significant differences in the dosage and frequency among existing IVG protocols due to lack of standardized consensus or guidelines.High-dose IVG therapy and a follow-up plan based on aqueous humor virus load and cytokine monitoring have been applied in clinical practice, and it has been reported to shorten treatment duration and reduce number of injections.Reports of retinal toxicity caused by IVG are rare, and more exploration is needed to determine the safe dose range of IVG.This article reviewed the advances in IVG treatment of CMVR after HSCT focusing on the acting mechanism of ganciclovir, the problems in systematic application, the treatment plan involving intravitreal injection, and the retinal toxicity of intravitreal injection.

Hematopoietic stem cell transplantation;Cytomegalovirus retinitis;Ganciclovir;Intravitreal injections;Clinical protocols
Miao Heng, Email: mocdef.aabnisgnuoy_reywas
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引用本文

陈伟彬,赵明威,苗恒. 更昔洛韦玻璃体腔注射治疗HSCT术后并发巨细胞病毒性视网膜炎研究进展[J]. 中华实验眼科杂志,2023,41(10)：1033-1037.

DOI:10.3760/cma.j.cn115989-20220116-00020

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巨细胞病毒性视网膜炎(cytomegalovirus retinitis，CMVR)是由巨细胞病毒(cytomegalovirus，CMV)感染引起的、好发于免疫功能低下人群的机会感染性眼病。CMVR可导致视网膜全层坏死及出血、渗出等改变 [ 1 ]，当病灶累及黄斑时严重损害患者视力，影响患者生活质量。在鸡尾酒疗法应用于人免疫缺陷病毒(human immunodeficiency virus，HIV)感染之后，继发于HIV感染的CMVR患者数量显著下降 [ 2 ]。随着造血干细胞移植术(hematopoietic stem cell transplantation，HSCT)在多种血液疾病治疗中的广泛应用，许多血液系统疾病患者的生存期得以延长，但其特异性免疫功能通常受损严重，容易导致CMVR的发生 [ 3 ]。我国HSCT术后1年CMVR累计发病率为2.3%，但当患者伴有血小板植活时间>100 d、EB病毒血症、顽固CMV血症、急性移植物抗宿主反应等多个危险因素时，移植术后1年CMVR的发病率高达26.2% [ 3 ]。自20世纪80年代更昔洛韦被美国食品药品监督管理局批准用于治疗CMV感染以来，其一直是治疗CMV感染性疾病的一线抗病毒用药 [ 4 ]。由于系统性用药受到眼内药物浓度低、骨髓抑制不良反应等因素的限制，最早在1988年就有研究者报道玻璃体腔注射更昔洛韦(intravitreal injection of ganciclovir，IVG)治疗HIV相关CMVR效果良好 [ 5 ]。而IVG在HSCT术后并发CMVR中的应用最早见于1997年 [ 6 ]，但此后相关研究较少。因HSCT术后并发CMVR的治疗和随访尚缺乏标准化共识或指南，现存的IVG方案在给药剂量和给药频率上尚存在较大差异。本文就IVG治疗HSCT术后并发CMVR的现状及研究进展进行综述。
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备注信息
A
苗恒，Email： mocdef.aabnisgnuoy_reywas
B
所有作者均声明不存在利益冲突
C
感谢龙泽、侯婧对本文内容构思和文献收集做出的贡献
D
国家重点研发计划项目 (2020YFC2008200)
国家自然科学基金项目 (81800847)
北京大学人民医院学术新星基金项目 (RS2018-05)
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