糖尿病黄斑水肿患者抗VEGF治疗的长期疗效观察及其与视网膜前膜的关系

The Long-Term Efficacy of Anti-Vascular Endothelial Growth Factor Therapy in Diabetic Macular Edema Patients and Relationship of Epiretinal Membrane

摘要: 目的：观察糖尿病黄斑水肿(DME)患者行玻璃体腔内注射抗血管内皮生长因子(VEGF)药物康柏西普治疗后的长期疗效，探讨其与视网膜前膜的相互影响。方法：对2018年3月~2021年3月在青岛大学附属医院接受抗VEGF治疗的120例DME患者的166只眼的临床资料进行回顾性研究。所有患眼均行玻璃体腔注射康柏西普(0.05 ml/0.5mg)治疗，每一个月1次，连续3次，若发现视力下降或CMT ≥ 300 μm则需继续每月注射，直至视力稳定。记录患者治疗前、治疗后1月、3月、6月、12月的最佳矫正视力(BCVA)、黄斑中心视网膜厚度(CMT)及玻璃体黄斑界面异常(VMIA)发生情况。结果：治疗前DME患者logMAR BCVA为0.68 ± 0.38，CMT为(478.96 ± 140.62) μm，治疗后1月、3月、6月、12月logMAR BCVA分别为0.56 ± 0.31 (Z = −3.207, P = 0.001)、0.46 ± 0.34 (Z = −6.635, P < 0.001)、0.51 ± 0.35 (Z = −4.208, P < 0.001)、0.53 ± 0.36 (Z = −3.980, P < 0.001)，CMT分别为(349.94 ± 86.15) μm (Z = −6.777, P < 0.001)、(351.59 ± 115.86) μm (Z = −5.901, P < 0.001)、(408.77 ± 142.14) μm (Z = −2.419, P = 0.032)、(415.77 ± 118.63) μm (Z = −2.271, P = 0.023)，与基线相比，BCVA均显著提高，CMT显著下降。治疗前伴有ERM的DME患者基线logMAR BCVA为0.75 ± 0.31，CMT为(481.20 ± 102.75) μm，经抗VEGF治疗后1月、3月、6月、12月logMAR BCVA分别为0.68 ± 0.29 (Z = −2.115, P = 0.034)、0.58 ± 0.31 (Z = −3.132, P = 0.002)、0.62 ± 0.28 (Z = −2.359, P = 0.018)、0.67 ± 0.30 (Z = −2.558, P = 0.011)，CMT分别为(381.56 ± 71.28) μm (Z = −3.245, P = 0.001)、(363.19 ± 82.67) μm (Z = −2.587, P = 0.010)、(412.92 ± 118.80) μm (Z = −2.436, P = 0.012)、(418.33 ± 109.36) μm (Z = −2.106, P = 0.039)，与基线相比，BCVA均显著提高，CMT显著下降，差异均有统计学意义(P < 0.05)。DME患者治疗前ERM发生率为25.90% (43只眼)，经抗VEGF药物治疗后1、3、6、12月时，ERM的发生率分别为31.3% (52只眼)、41.6% (69只眼)、46.4% (77只眼)、48.2% (80只眼)，差异具有统计学意义(2 = 111.352, P < 0.001)。与治疗前ERM的发生率比较，除治疗后1月差异无统计学意义(P = 0.431)，治疗后3、6、12月差异均有统计学意义(P < 0.001)。结论：抗VEGF药物治疗可有效降低DME患者CMT，提高BCVA，治疗后3~6月视力最佳，12月时视力有所下降，但仍明显优于治疗前；抗VEGF治疗可增加ERM的发生率，可能是影响其长期疗效的原因之一。

Abstract: Objective: To investigate the long-term efficacy of intravitreal injections of anti-vascular endothelial growth factor drug conbercept in diabetic macular edema patients and interaction with epiretinal membrane. Method: The present study was a retrospective observational case series, including 166 eyes from 120 patients with DME, who were diagnosed and treated at Ophthalmology, the Affiliated Hospital of Qingdao University, between April 2018 and March 2021. All patients completed three consecutive monthly intravitreal injections of conbercept 0.5 mg. Monthly injections have to be continued if a decrease in BCVA due to DME or CMT ≥ 300 μm were observed investigator’s opinion and were continued until stable visual acuity was reached. Morphological characteristics potentially associated with prognosis were assessed at baseline, month 1, month 3, month 6 and years 1 of follow-up. Results: The BCVA (log MAR) at baseline was 0.68 ± 0.38 and 0.56 ± 0.31 (Z = −3.207, P = 0.001), 0.46 ± 0.34 (Z = −6.635, P < 0.001), 0.51 ± 0.35 (Z = −4.208, P < 0.001)、0.53 ± 0.36 (Z = −3.980, P < 0.001) at 1, 3, 6, 12 months, respectively. Similarly, CMT reduced from (478.96 ± 140.62) m to (349.94 ± 86.15) μm (Z = −6.777, P < 0.001), (351.59 ± 115.86) μm (Z = −5.901, P < 0.001)、(408.77 ± 142.14) μm (Z = −2.419, P = 0.032), (415.77 ± 118.63) μm (Z = −2.271, P = 0.023) at 1, 3, 6, 12 months, respectively. The BCVA (log MAR) at baseline in DME patients with ERM was 0.75 ± 0.31 and 0.68 ± 0.29 (Z = −2.115, P = 0.034)、0.58 ± 0.31 (Z = −3.132, P = 0.002), 0.62 ± 0.28 (Z = −2.359, P = 0.018), 0.67 ± 0.30 (Z = −2.558, P = 0.011) at 1, 3, 6, 12 months, respectively. Similarly, CMT reduced from (481.20 ± 102.75) m to (381.56 ± 71.28) μm (Z = −3.245, P = 0.001), (363.19 ± 82.67) μm (Z = −2.587, P = 0.010), (412.92 ± 118.80) μm (Z = −2.436, P = 0.012), (418.33 ± 109.36) μm (Z = −2.106, P = 0.039) at 1, 3, 6, 12 months, respectively. Significant differences all could be found after treatment, while the visual prognosis was poorer in DME patients with ERM at baseline. ERM was identified in 43 (25.90%) eyes at baseline, 52 (31.3%, P = 0.431) eyes at 1 month, 69 (41.6%, P < 0.001) eyes at 3 months, 77 (46.4%, P < 0.001) eyes at 6 months and 80 (48.2%, P < 0.001) eyes at 12 months. Significant probabilities for differences were considered after Bonferroni correction (alpha = 0.05/10 = 0.005). The study showed that the incidence of ERM increased with an increasing number of injections (2 = 111.352, P < 0.001). Conclusion: Anti-VEGF therapy is effective in the DME treatment, as demonstrated by BCVA improvement and CMT decrease. Better visual prognosis could be obtained at 3 to 6 months after treatment, followed by 12 months. Intravitreal anti-VEGF therapy was associated with ERM development and progression, that it may be one of the reasons affecting long-term efficacy.