Clinical research of Lucentis combined with fortify spleen for fluid retention removement recipe in the treatment of retinal vein occlusion macular edema
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摘要:
目的 探讨雷珠单抗联合自拟健脾利水方治疗视网膜静脉阻塞黄斑水肿(RVO-ME)的疗效和预后预测指标。 方法 选取2021年10月—2022年10月于浙江中医药大学附属第一医院就诊的60例RVO-ME患者，根据随机数字法分为联合治疗组和常规治疗组，各30例。2组均连续3个月进行玻璃体内雷珠单抗注射，联合治疗组口服自拟健脾利水方免煎颗粒，常规治疗组口服安慰剂。比较2组治疗前后外周血炎症指标、最佳矫正视力(BCVA)、OCT图像中高反射信号(HRF)、黄斑中心厚度(CMT)、视网膜下液(SRF)和黄斑囊样水肿(CME)情况。根据疗效将患者分为水肿复发组20例和水肿未复发组40例，比较2组治疗前后指标。 结果 治疗后联合治疗组全身免疫炎症指数(SII)、中性粒细胞/淋巴细胞比值(NLR)、HRF和CMT显著低于常规治疗组(P＜0.05)。联合治疗组的SRF消退率(88.9% vs. 50.0%)和CME消退率(63.0% vs. 25.0%)均较常规治疗组升高(P＜0.05)；联合治疗组RVO-ME复发率(20.0% vs. 46.7%)较常规治疗组降低(P＜0.05)。水肿未复发组治疗后HRF和CMT较治疗前降低数值显著高于复发组(P＜0.05)。ROC曲线提示基线CMT＜497.50 μm(P=0.010)和HRF＜15.5个(P=0.021)患者黄斑水肿复发率较低, 视力较好。 结论 雷珠单抗联合自拟健脾利水方治疗RVO-ME能提升疗效，减少复发。治疗前CMT＜497.50 μm和HRF≤15个的患者预后较好。 -
关键词:
- 视网膜静脉阻塞黄斑水肿 /
- 光学相干断层成像 /
- 治疗反应 /
- 中药颗粒剂 /
- 炎症指标
Abstract:Objective To explore the clinical effects of Lucentis combined with fortify spleen for fluid retention removement recipe and its prognostic indicators in the treatment of retinal vein occlusion macular edema (RVO-ME). Methods A total of 60 patients with RVO-ME visiting the First Affiliated Hospital of Zhejiang Chinese Medical University from October 2021 to October 2022 were randomly divided into a combination treatment group and a conventional treatment group. Each included 30 cases. All patients were given intravitreal injection of Ranibizumab for three months. The combined treatment group was given oral granules administration of self-prepared Chinese medicine recipe for fortifying spleen to remove fluid retention, while the control group was treated with placebo granules. The inflammatory markers of peripheral blood, best corrected visual acuity (BCVA), high reflection signal (HRF) in OCT images, macular central thickness (CMT), sub-retinal fluid (SRF), and cystoid macular edema (CME) before and after the treatment in the two groups were compared. Those indexes were also compared between patients with and without recurrent ME, The group with recurrent ME included 20 patients, while the group without recurrent ME included 40 patients. Results After 3 months of treatment, the systemic immune inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), HRF, and CMT in the combined treatment group were significantly lower than those in the conventional treatment group (P < 0.05). The combined treatment group has significantly higher resolution rates of SRF (88.9% vs. 50.0%) and CME (63.0% vs. 25.0%, P < 0.05). The RVO-ME recurrence rate in the combined treatment group was 20.0%, significantly lower than the conventional group (46.7%, P < 0.05). HRF and CMT descended more significantly in patients without recurrent ME than those with recurrent ME (P < 0.05). The ROC curve indicates patients with baseline CMT < 497.50 μm (P=0.010) and HRF < 15.5 (P=0.021) had a lower probability of edema recurrence and better BCVA. Conclusion Combined treatment of Lucentis with self-prepared Chinese medicine granules improves the efficacy and reduces recurrence in the treatment of RVO-ME. Patients with CMT < 497.50 μm and HRF≤15 before treatment have a better prognosis. -
图 1 治疗前OCT形态指标预测RVO-ME复发的ROC曲线
Figure 1. ROC curve of OCT morphological biomarkers predicting RVO-ME recurrence prior to treatment
表 1 联合治疗组和常规治疗组RVO-ME患者治疗前后实验室检查指标比较[M(P25, P75)]
Table 1. Comparison of laboratory test indicators before and after treatment in the combined and the conventional treatment group for patients with RVO-ME[M(P25, P75)]
组别 例数 SII 治疗前 治疗后 差值 联合治疗组 30 554.81 (329.50, 859.45) 412.77 (293.65, 559.68) -104.71(-180.92, 29.57) 常规治疗组 30 567.67 (401.91, 798.07) 567.67 (401.91, 798.07) -6.36(-118.16, 101.93) Z值 -0.562 -2.114 -2.114 P值 0.574 0.035 0.035 组别 例数 NLR 治疗前 治疗后 差值 联合治疗组 30 2.24 (1.53, 3.56) 1.96 (1.46, 2.89) -0.29(-0.66, 0.08) 常规治疗组 30 2.51 (1.93, 4.37) 2.65 (1.99, 3.97) 0.03(-0.44, 0.48) Z值 -1.124 -2.247 -2.025 P值 0.261 0.025 0.043 组别 例数 BCVA(LogMAR) 治疗前 治疗后 差值 联合治疗组 30 0.52 (0.35, 1.00) 0.52 (0.28, 1.00) -0.17(-0.40, 0.00) 常规治疗组 30 1.00 (0.30, 1.30) 0.46 (0.30, 1.08) -0.08(-0.60, 0.10) Z值 -1.073 0.248 -0.651 P值 0.283 0.805 0.515 组别 例数 CMT(μm) 治疗前 治疗后 差值 联合治疗组 30 451.00 (345.50, 800.75) 243.00 (200.00, 336.50) -156.00(-448.00, -58.50) 常规治疗组 30 639.50(447.25, 895.25) 388.50 (279.00, 609.25) -101.50(-363.50, 34.75) Z值 -1.604 -3.048 -0.970 P值 0.109 0.002 0.332 组别 例数 HRF(个) 治疗前 治疗后 差值 联合治疗组 30 15.00 (9.00, 21.00) 10.00(6.00, 16.75) -3.00(-5.75, -2.00) 常规治疗组 30 17.50 (10.75, 23.25) 17.50 (10.75, 23.25) -2.00(-3.00, 0.00) Z值 -1.391 -2.017 -2.166 P值 0.164 0.044 0.030 
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表 2 联合治疗组与常规治疗组RVO-ME患者治疗前后OCT图像特征比较[例(%)]
Table 2. Comparison of OCT imaging characteristics before and after treatment in the combined and the conventional treatment group [cases(%)]
OCT形态变化 联合治疗组 常规治疗组 χ2 P值 CME 8.054 0.004 消退 17(63.0) 7(25.0) 未消退 10(37.0) 21(75.0) SRF 0.028a 消退 16(88.9) 9(50.0) 未消退 2(11.1) 9(50.0) 注：a为采用Fisher精确检验。
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表 3 水肿复发组和水肿未复发组治疗前后的炎症指标及OCT形态指标比较[M(P25, P75)]
Table 3. Comparison of inflammatory markers and OCT morphological biomarkers before and after treatment between the groups with and without recurrent edema[M(P25, P75)]
组别 例数 SII 治疗前 治疗后 差值 水肿复发组 20 486.25(375.56，748.85) 502.15(280.37, 754.26) -50.54(-145.51, 64.01) 水肿未复发组 40 612.80(337.93, 836.94) 430.42(358.91, 727.71) -66.57(-200.94, 58.09) Z值 -0.612 0.047 0.674 P值 0.541 0.962 0.500 组别 例数 NLR 治疗前 治疗后 差值 水肿复发组 20 2.45(1.76, 3.35) 2.30(1.50, 3.44) -0.02(-0.43, 0.37) 水肿未复发组 40 2.35(1.80, 4.41) 2.28(1.61, 3.28) -0.15(-0.80, -0.28) Z值 0.486 0.157 -0.957 P值 0.627 0.875 0.339 组别 例数 BCVA(LogMAR) 治疗前 治疗后 差值 水肿复发组 20 1.00(0.40, 1.30) 0.82(0.52, 1.30) 0.00(-0.18, 0.12) 水肿未复发组 40 0.70(0.30, 1.00) 0.40(0.22, 0.76) -0.21(-0.60, -0.08) Z值 1.192 3.163 -2.625 P值 0.233 0.002 0.009 组别 例数 CMT(μm) 治疗前 治疗后 差值 水肿复发组 20 733.00(553.25, 928.00) 588.50(463.00, 906.00) -17.00(-375.00, 40.25) 水肿未复发组 40 434.50(329.00, 767.25) 248.00(202.00, 320.00) -156.00(-454.00, -82.00) Z值 2.634 5.180 -2.194 P值 0.008 ＜0.001 0.028 组别 例数 HRF(个) 治疗前 治疗后 差值 水肿复发组 20 21.50(15.25, 23.75) 18.00(12.00, 24.00) -2.00(-3.00, 3.00) 水肿未复发组 40 15.00(9.00, 21.00) 10.00(6.75, 16.00) -3.00(-5.25, -1.00) Z值 2.392 2.963 2.195 P值 0.017 0.003 0.028
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表 4 水肿复发组和水肿未复发组治疗前OCT图像特征比较(例)
Table 4. Comparison of OCT imaging characteristics before treatment between the groups with and without recurrent edema(cases)
治疗前OCT 复发(n=20) 未复发(n=40) χ2值 P值 椭圆体带 0.036 0.850 完整 13 25 不完整 7 15 外界膜 0.159 0.829 完整 15 31 不完整 5 9 CME 0.159a 是 20 35 否 0 5 SRF 0.313 0.576 是 13 23 否 7 17 注：a为采用Fisher精确检验。
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