玻璃体腔注射雷珠单抗联合地塞米松治疗视网膜中央静脉阻塞继发黄斑水肿的临床研究

doi:10.3877/cma.j.issn.2095-2007.2022.01.005

目的

探讨玻璃体腔注射抗血管内皮生长因子(VEGF)药物雷珠单抗联合地塞米松治疗视网膜中央静脉阻塞(CRVO)继发黄斑水肿的临床疗效和安全性。

方法

收集2014年6月至2020年6月就诊于山东第一医科大学附属青岛眼科医院的CRVO继发黄斑水肿患者51例(51只眼)的临床资料进行研究。其中，男性27例(27只眼)，女性24例(24只眼)，年龄21~83岁，平均年龄(54.7±13.4)岁。所有患者接受了玻璃体腔穿刺注射雷珠单抗联合地塞米松注射液，术后根据黄斑水肿情况按需治疗。检查并记录全部患者术前、术后1周、术后1个月的最佳矫正视力(BCVA)、黄斑中心视网膜厚度(CMT)、重复治疗的次数及间隔时间，同时记录眼部和全身并发症的情况。BCVA及CMT符合正态分布，以均数±标准差表示。治疗前后不同时间点患者的BCVA及CMT的差异采用配对t检验进行两两比较。其中，重点对首次治疗后1周、1个月和末次随访三个时间点的BCVA提高、CMT恢复、随访半年治疗次数、整体随访期间的重复治疗次数及治疗时间间隔进行分析，并与单独注射雷珠单抗注射液或单独注射地塞米松磷酸钠注射液治疗CRVO继发黄斑水肿的相关研究进行比较。治疗前及前三次治疗后BCVA与终末BCVA的相关性，采用Pearson相关系数进行评价。

结果

患者基线的BCVA为(29.43±17.99)个ETDRS字母，首次玻璃体穿刺注药术后1周和1个月时分别为(43.36±21.85)个ETDRS字母和(46.88±20.79)个ETDRS字母，均较基线视力提高，其差异均具有统计学意义(t＝10.94，10.32；P<0.05)；末次随访时患者的BCVA为(45.00±19.10)个ETDRS字母，较基线BCVA提高(15.53±15.34)个ETDRS字母，其差异具有统计学意义(t＝13.50，P<0.05)；末次随访与基线比较，有32只眼的BCVA提高，有14只眼的BCVA稳定，有2只眼的BCVA下降。基线CMT为(695.33±204.90)μm，首次治疗术后1周和1个月时分别为(317.00±71.05)μm和(315.34±66.80)μm，均较基线CMT下降，其差异均具有统计学意义(t＝14.12，13.43；P<0.05)；末次随访时患者的CMT为(236.51±63.95)μm，较基线CMT降低(458.82±216.83)μm，其差异具有统计学意义(t＝16.76，P<0.05)。平均治疗次数(7.19±3.95)次，重复治疗的平均间隔时间为(62.24±22.30)d。所有患者均未出现白内障明显进展、眼内感染及心脑血管并发症等严重不良事件。

结论

玻璃体腔注射雷珠单抗联合地塞米松治疗CRVO继发的黄斑水肿能提高视力，减轻黄斑水肿，减少重复治疗次数，延长治疗的间隔时间且安全性良好。

关键词: 视网膜中央静脉阻塞, 黄斑水肿, 地塞米松, 抗血管内皮生长因子

Objective

The aim of this study was to investigate the efficacy and safety of intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent——ranibizumab in combination with dexamethasone for cystoid macular oedema (CMO) secondary to central retina vein occlusion (CRVO).

Methods

51 patients (51 eyes) with CMO secondary to CRVO diagnosed at Qingdao Eye Hospital of Shandong First Medical University from June 2014 to June 2020 were enrolled. Among of them, 27 cases (27 eyes) were male and 24 cases (24 eyes) were female with the average age of (54.65±13.37)years (ranged from 21 to 83 years) . All of the eyes underwent intravitreous injection of ranibizumab combined with dexame-thasone and performed as needed after treatments according to the extent of CMO. Fundoscopy, best corrected visual acuity (BCVA) and central retinal thickness (CMT) were performed before treatment and after treatment for 1 week, 1 month. Treatment frequency, interval time of repeat treatments and complications were recorded. BCVA and CMT were expressed by ±s. The paired t test was used to compare the changes of BCVA and CMT before and after treatment. Much more attentions were paid to analyze the changes of BCVA, CMT, treatment number during 6 months, repeated measurement data, interval time after treatment for 1 week, 1 months and last follow-up, and compare the efficacy of intravitreal injection of ranibizumab or dexamethasone alone in previous literature reports. Pearson correlation coefficient was used to evaluate the correlation of terminal BCVA and BCVA before and after the first three treatments.

Results

The baseline BCVA was (29.43±17.99)ETDRS letters. BCVA of patients after the first vitreous injection for one week and one month was (43.36±21.85)ETDRS letters and (46.88±20.79)ETDRS letters, respectively, which were both improved. The difference was statistically significant (t=10.94, 10.32; P<0.05). The final BCVA was (45.00±19.10)ETDRS letters, which was improved (15.53±15.34)ETDRS letters than baseline. The difference was statistically significant (t=13.50, P<0.05 ). There were 32 eyes of patients improved in BCVA, 14 eyes stabilized, and 2 eyes decreased. The mean CMT of baseline, and after the first intravitreal injection for 1 week, 1 month was (695.33±204.90)μm, (317.00±71.05)μm, (315.34±66.80)μm, respectively. Compared with the baseline CMT, the difference was statistically significant (t=14.12, 13.43; P<0.05). CMT of patients was (236.51±63.95)μm at final follow-up, which was decreased (458.82±216.83)μm than baseline and the difference was statistically significant (t=16.76, P<0.05). The average number of treatments was (7.19±3.95) and mean interval between injections was (62.24±22.30) d. Serious adverse events such as significant progression of cataracts, intraocular infections, cardiovascular complications were not observed.

Conclusions

Intravitreous injection of Anti-VEGF agent combined with dexamethasone for the treatment of CMO secondary to CRVO was safe and effective in improving BCVA and decreasing CMT. The combined therapy also helps to reduce the treatment frequency and prolong the interval of repeated therapy.

Key words: Central retina vein occlusion, Macular oedema, Dexamethasone, Anti-vascular endothelial growth factor

图1 玻璃体注射雷珠单抗联合地塞米松治疗前后最佳矫正视力的变化图

图2 玻璃体注射雷珠单抗联合地塞米松治疗视网膜静脉阻塞继发黄斑水肿治疗前后最佳矫正视力变化图　注：n-pre，第n次注射前；n-1w，第n次注射术后1周；n-1m，第n次注射后1个月

图3 治疗前视力及第三次治疗后1个月视力与末次随访视力的相关性

图4 玻璃体注射雷珠单抗联合地塞米松治疗前后黄斑中心视网膜厚度的变化图

图5 玻璃体注射雷珠单抗联合地塞米松治疗视网膜中央静脉阻塞激发黄斑水肿治疗前后黄斑中心视网膜厚度变化图　注：n-pre，第n次注射前；n-1w，第n次注射术后1周；n-1m，第n次注射后1个月

图6 患者女性，52岁。视网膜中央静脉阻塞继发黄斑水肿的患者治疗前后的眼底彩色照像和相干光断层扫描检查图像　治疗前患者最佳矫正视力为29个ETDRS字母，黄斑中心视网膜厚度为621 μm；首次治疗后1周时最佳矫正视力为50个ETDRS字母，黄斑中心视网膜厚度为397 μm；首次治疗后1个月时最佳矫正视力为54个ETDRS字母，黄斑中心视网膜厚度为347 μm；经过11次玻璃体腔注射，末次随访距离最后一次注射8个月时，最佳矫正视力为68个ETDRS字母，黄斑中心视网膜厚度为311 μm。　图A示治疗前眼底彩色照像；　图B示治疗前相干光断层扫描检查图像；　图C示治疗后1周时相干光断层扫描检查图像；　图D示末次随访时眼底彩色照像；　图E示治疗后1个月时相干光断层扫描检查图像；　图F示末次随访时相干光断层扫描检查图像

表1 CRVO继发黄斑水肿患眼首次接受联合治疗后重复治疗的间隔时间表

治疗次数	眼数(只眼)	间隔时间^*(d)	中位天数(d)
第1次	51
第2次	47	54.83±20.91	57
第3次	39	57.25±18.41	60
第4次	31	64.10±16.44	60
第5次	23	67.65±15.96	73
第6次	20	67.45±19.25	70
第7次	14	69.71±19.98	70

表1 CRVO继发黄斑水肿患眼首次接受联合治疗后重复治疗的间隔时间表

治疗次数	眼数(只眼)	间隔时间^*(d)	中位天数(d)
第1次	51
第2次	47	54.83±20.91	57
第3次	39	57.25±18.41	60
第4次	31	64.10±16.44	60
第5次	23	67.65±15.96	73
第6次	20	67.45±19.25	70
第7次	14	69.71±19.98	70

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The efficacy of ranibizumab combined with dexamethasone for macular oedema secondary to central retina vein occlusion

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The efficacy of ranibizumab combined with dexamethasone for macular oedema secondary to central retina vein occlusion