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中华眼科医学杂志(电子版) ›› 2022, Vol. 12 ›› Issue (02) : 88 -93. doi: 10.3877/cma.j.issn.2095-2007.2022.02.005

论著

玻璃体腔注射甲氨蝶呤治疗原发性眼内淋巴瘤的临床研究
薛友余1, 王伟2, 陶勇3, 冯婧3,()   
  1. 1. 276000 山东省临沂市人民医院眼科(2019年12月至2020年2月期间本文第1作者在首都医科大学附属北京朝阳医院眼科进修)
    2. 276000 山东省临沂市人民医院眼科
    3. 100020 首都医科大学附属北京朝阳医院眼科
  • 收稿日期:2022-03-06 出版日期:2022-04-28
  • 通信作者: 冯婧
  • 基金资助:
    山东省自然科学基金项目(ZR2020QC083)

The effectiveness of intravitreal methotrexate in the treatment of primary intraocular lymphoma

Youyu Xue1, Wei Wang2, Yong Tao3, Jing Feng3,()   

  1. 1. Department of Ophthalmology, Linyi People′s Hospital of Shandong Province, Linyi 276000, China
    3. Department of Ophthalmology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China
  • Received:2022-03-06 Published:2022-04-28
  • Corresponding author: Jing Feng
引用本文:

薛友余, 王伟, 陶勇, 冯婧. 玻璃体腔注射甲氨蝶呤治疗原发性眼内淋巴瘤的临床研究[J]. 中华眼科医学杂志(电子版), 2022, 12(02): 88-93.

Youyu Xue, Wei Wang, Yong Tao, Jing Feng. The effectiveness of intravitreal methotrexate in the treatment of primary intraocular lymphoma[J]. Chinese Journal of Ophthalmologic Medicine(Electronic Edition), 2022, 12(02): 88-93.

目的

观察玻璃体腔注射甲氨蝶呤(MTX)个体化治疗原发性眼内淋巴瘤(PIOL)的疗效和安全性。

方法

收集2013年4月至2019年12月于首都医科大学附属北京朝阳医院眼科就诊的PIOL患者20例(30只眼)的临床资料进行研究。其中,男性6例(6只眼),女性14例(24只眼)。患者年龄34~81岁,平均年龄(55.9±12.4)岁。所有患者肿瘤性质均为弥漫性大B细胞淋巴瘤。治疗方案为"根据淋巴瘤临床表现"的个体化治疗,所有患眼均接受单次玻璃体腔注射MTX(400 μg:0.1ml)治疗。如出现玻璃体混浊加重、眼底病灶范围扩大或IL-10/IL-6比值增高行再次注射。自治疗开始随访12~30个月。所有患眼均行最佳矫正视力(BCVA)、眼压、裂隙灯显微镜、彩色眼底照相、光学相干断层扫描(OCT)及荧光素眼底血管造影(FFA)检查并行房水或玻璃体IL-10/IL-6浓度检测。BCVA转换为LogMAR视力和眼压的检查数据先行正态性检验。眼压符合正态分布采用±s表示,治疗前后眼压的比较采用配对t检验;BCVA不符合正态分布,采用中位数和上下四分位数表示,治疗前后BCVA的比较采用Wilcoxon配对秩和检验。裂隙灯显微镜检查、彩色眼底照相、OCT、FFA及IL-10/IL-6的比值采用文字形式进行描述。

结果

治疗前后LogMAR视力中位数为0.75(0.47,1.43)和0.4(0.2,0.57),差异具有统计学意义(Z=3.43,P<0.05)。治疗前后眼压分别为(16.56±4.31)mmHg(1 mmHg=0.133 kPa)和(16.13±3.87)mmHg,差异无统计学意义(t=0.40,P>0.05)。所有患者经玻璃体腔注射MTX治疗后玻璃体混浊程度较治疗前好转者有12例(19只眼),占63%(19/30);视网膜下黄白色奶油样浸润灶减轻或消失者有15例(20只眼),占66%(20/30);视网膜色素上皮下的高反射病灶减轻或消失的为13例(18只眼),占60%(18/30)。注射次数为1~8次,平均(3.00±2.37)次。

结论

"根据淋巴瘤临床表现"进行个体化玻璃体腔注射MTX治疗PIOL安全有效,可达到临床缓解。

Objective

To observe the efficacy and safety of intravitreal methotrexate (MTX) in the treatment of primary intraocular lymphoma (PIOL) according to the clinical behavior of the lymphoma.

Methods

The clinical data of 20 patients (30 eyes) with PIOL who visited the Department of Ophthalmology, Beijing Chaoyang Hospital affiliated to Capital Medical University from April 2013 to December 2019 were collected. Among them, there were 6 males (6 eyes) and 14 females (24 eyes) with an average age of (55.9±12.4) years (ranged from 34 to 81 years). All patients were diagnosed with diffuse large B cell lymphoma. The treatment plan is individualized treatment according to the clinical manifestations of lymphoma, and all eyes received a single intravitreal injection of MTX (400 μg∶0.1ml). When the vitreous opacity of patients increased, enlarged fundus lesions or IL-10/IL-6 increased, then re-injection was performed. They were followed up for 12 to 30 months after intraocular chemotherapy. Best corrected visual acuity (BCVA), intraocular pressure, slit lamp microscopy, color fundus photography, optical coherence tomography, fundus fluorescein angiography and the concentration of IL-6 and IL-10 were performed. The measurement data such as BCVA (represented by LogMAR), intraocular pressure (IOP) and other measurement data were tested for normality. IOP conforming to normal distribution were expressed as ±s, and compared by paired t test before and after treatment; BCVA not conforming to normal distribution were expressed as median and quartile, and compared by Wilcoxon paired rank-sum test. Slit lamp microscopy, color fundus photography, optical coherence tomography, fundus fluorescein angiography and IL-10/IL-6 are described in text.

Results

The median LogMAR visual acuity before and after treatment was 0.75 (0.47, 1.43) and 0.4 (0.2, 0.57), and the difference was statistically significant (Z=3.43, P < 0.05). The IOP of patients before and after treatment was (16.56±4.31) mmHg (1 mmHg=0.133 kPa) and (16.13±3.87) mmHg, respectively, and the difference was not statistically significant (t=0.40, P> 0.05). In all patients, there were 12 cases (19 eyes) with improved vitreous opacity after intravitreal injection of MTX, accounting for 63% (19/30), 15 cases (20 eyes) with reduced or disappeared the yellow and white creamy lesions in the subretinal, accounting for 66% (20/30), and 13 cases (18 eyes) with reduced or disappeared the hyperreflexive lesions in the subretinal pigment epithelium, accounting for 60% (18/30). The number of injections ranged from 1 to 8, with an average of (3±2.37).

Conclusions

Intravitreal injection of MTX according to the clinical behavior of the lymphoma is safe and effective in the treatment of PIOL, which could achieve the clinical remission.

图1 原发性眼内淋巴瘤患眼治疗前后视力的变化
表1 患者治疗前后最佳矫正视力和眼压的描述及比较
图2 患者女性,64岁。双眼原发性眼内淋巴瘤患者治疗前后影像学检查图像 图A示治疗前右眼裂隙灯显微镜照相可见团状玻璃体混浊;图B示治疗前左眼裂隙灯显微镜照相可见片状玻璃体混浊;图C和图D分别示治疗前右眼和左眼荧光素眼底血管造影可见斑点状或颗粒状荧光渗漏;图E和图F分别示治疗前右眼和左眼眼底彩色照相可见视网膜下黄白色奶油样浸润灶;图G和图H分别示治疗后右眼和左眼眼底彩色照相可见视网膜下黄白色奶油样浸润灶消失;图I示治疗前右眼OCT未见明显视网膜色素上皮层的高反射病灶;图J示治疗前左眼OCT可见视网膜色素上皮层的高反射病灶;图K示治疗后右眼OCT未见明显视网膜色素上皮层的高反射病灶;图L示治疗后左眼OCT可见视网膜色素上皮层的高反射病灶消失
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