基于水病毒学和炎症细胞因子测定的巨细胞病毒性视网膜炎治疗方案

Q4 Medicine

中华眼底病杂志 Pub Date : 2020-01-25 DOI:10.3760/CMA.J.ISSN.1005-1015.2020.01.001

Yingying Yu, Mingwei Zhao

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引用次数: 2

摘要

目的观察基于巨细胞病毒DNA（CMV-DNA）载量和IL-8测定的方案对异基因造血干细胞移植（HSCT）后巨细胞病毒视网膜炎（CMVR）患者的治疗监测和局部停止治疗的安全性和有效性。方法前瞻性病例系列研究。本研究共涉及2016年1月至2018年12月在北京大学人民医院眼科诊断的14名异基因造血干细胞移植后CMVR患者（22眼）。所有患者在基线时均为CMV-DNA血清阴性，并接受玻璃体内注射更昔洛韦（IVG，3 mg，0.05 ml）治疗，每周两次，诱导期4次，维持期每周一次。在每周第一次IVG期间采集房水样本。分别用实时定量PCR和ELISA检测CMV-DNA和IL-8水平。随访期间，将CMV-DNA阴性（<103/ml）或水样中IL-8水平<30pg/ml设定为局部停止治疗。然后每2周对患者进行一次随访，随访时间至少为6个月。每次就诊均进行BCVA、眼压和眼底检查。BCVA检查使用国际标准视力表进行，将其转换为logMAR视力。通过Student t匹配检验比较基线和最后一次随访时的BCVA和眼压。结果14例（22眼）异基因造血干细胞移植后CMVR患者中，8例（16眼）为双侧，6例（6眼）为单侧。基线时，平均logMAR BCVA为0.814±0.563，眼压为17.2±7.8mmHg（1mmHg=0.133kPa），平均CMV-DNA水负荷为（3.43±4.96）×105/ml，IL-8平均水平为518±541pg/ml。停止局部治疗时，玻璃体内注射的中位次数为5次。9眼房水中CMV-DNA阴性，其中7眼房水中IL-8阴性。CMV-DNA阳性13眼，IL-8阴性13眼。只有一只眼睛的视网膜病变完全安静。局部停止治疗6个月后，平均logMAR BCVA为0.812±0.691，眼压为14.8±5.4mmHg；与基线无显著差异（t=-0.107，1.517；P=0.916，0.137）。其余20只眼睛的视网膜病变逐渐改善并完全消失。22眼中，4眼因治疗期间血小板计数低（<30×109/ml）而发生医源性玻璃体出血。治疗结束6个月后，眼底血肿吸收清晰可见。在诊断CMVR时，有2眼（9%）出现后囊下混浊，这可能是由异基因造血干细胞移植后的全身糖皮质激素治疗引起的。结论CMV-DNA水负荷和IL-8水平可作为定量指标，用于监测HSCT后CMVR的治疗效果和确定局部停药时间。关键词：巨细胞病毒性视网膜炎；房水；病毒学；白细胞介素-8

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Regime for cytomegalovirus retinitis based on aqueous virology and inflammatory cytokine determination

Objective To observe the safety and efficacy of regime that based on aqueous cytomegalovirus-DNA (CMV-DNA) load and IL-8 determination for therapeutic monitoring and local treatment cessation of cytomegalovirus retinitis (CMVR) patients after allogeneic hematopoietic stem cell transplantation (HSCT). Methods A prospective case series study. A total of 14 CMVR patients (22 eyes) after allogeneic HSCT diagnosed in Ophthalmology Department of Peking University People's Hospital between January 2016 and December 2018 were involved in this study. All patients were CMV-DNA seronegative at baseline and were treated with intravitreous injection of ganciclovir (IVG, 3 mg in 0.05 ml) twice per week for 4 times in the induction stage and once a week in the maintenance stage. Aqueous humor sample was collected during the first time of IVG every week. CMV-DNA and the level of IL-8 were measured by real time quantitative PCR and ELISA, respectively. During follow-up, negative CMV-DNA (<103/ml) or level of IL-8<30 pg/ml in aqueous sample was set as local treatment cessation. Then patients were followed every 2 weeks for at least 6 months. BCVA, intraocular pressure and fundus examination were taken for each visit. The BCVA examination was performed using the international standard visual acuity chart, which was converted into logMAR visual acuity. BCVA and intraocular pressure at the baseline and the last follow-up were compared by the Student t matching test. Results Of the 14 CMVR patients (22 eyes) after allogeneic HSCT, 8 patients (16 eyes) were bilateral, 6 patients (6 eyes) were unilateral. At the baseline, the mean logMAR BCVA was 0.814±0.563, the intraocular pressure was 17.2±7.8 mmHg (1 mmHg=0.133 kPa), the mean aqueous CMV-DNA load was (3.43±4.96)×105/ml, the mean level of IL-8 was 518±541 pg/ml. At cessation of local treatment, the median number of intravitreal injections was 5 times. Nine eyes showed negative CMV-DNA in aqueous humor, of which, 7 eyes showed negative IL-8 in aqueous. CMV-DNA could still be detected in 13 eyes, while IL-8 was negative. Only one eye’s retinal lesion was completely quiet. Six months after local treatment cessation, the mean logMAR BCVA was 0.812±0.691, the intraocular pressure was 14.8± 5.4 mmHg; which was not significantly different from baseline (t=-0.107, 1.517; P=0.916, 0.137). Recurrence of CMVR happened in only 1 eye because of systemic EB virus infection. Retinal lesions progressively improved and became completely quiet in all the remaining 20 eyes. In 22 eyes, iatrogenic vitreous hemorrhage occurred due to low platelet count during treatment (<30×109/ml) in 4 eyes. When the treatment was terminated for 6 months, the fundus of hematoma absorption was clearly visible. At the time of CMVR diagnosis, there were 2 eyes (9%) with posterior subcapsular opacity, which may be caused by systemic glucocorticoid therapy after allogeneic HSCT. Conclusion Aqueous CMV-DNA load and level of IL-8 could be used as quantitative variables for monitoring the therapeutic effect and determining time for local treatment cessation for CMVR after HSCT safely and efficiently. Key words: Cytomegalovirus retinitis; Aqueous humor; Virology; Intereukin-8

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来源期刊

中华眼底病杂志 Medicine-Ophthalmology

CiteScore

0.40

自引率

0.00%

发文量

5383

期刊介绍： Chinese Journal of Ocular Fundus Diseases is the only scientific journal in my country that focuses on reporting fundus diseases. Its purpose is to combine clinical and basic research, and to give equal importance to improvement and popularization. It comprehensively reflects the leading clinical and basic research results of fundus disease disciplines in my country; cultivates professional talents in fundus disease, promotes the development of fundus disease disciplines in my country; and promotes academic exchanges on fundus disease at home and abroad. The coverage includes clinical and basic research results of posterior segment diseases such as retina, uveal tract, vitreous body, visual pathway, and internal eye diseases related to systemic diseases. The readers are medical workers and researchers related to clinical and basic research of fundus diseases. According to the journal retrieval report of the Chinese Institute of Scientific and Technological Information, the comprehensive ranking impact factor and total citation frequency of the Chinese Journal of Ocular Fundus Diseases have been among the best in the disciplines of ophthalmology, otolaryngology, and ophthalmology in my country for many years. The papers published have been included in many important databases at home and abroad, such as Scopus, Peking University Core, and China Science Citation Database (CSCD).