山东大学耳鼻喉眼学报 ›› 2021, Vol. 35 ›› Issue (1): 99-103.doi: 10.6040/j.issn.1673-3770.0.2020.250

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增殖性糖尿病视网膜病变术前玻璃体腔应用阿柏西普的时机及其疗效观察

刘志高1,2,王淑雅1,韩旭光2,王玉2,李志伟2,马爱华3,赵博军1,3   

  1. 1. 山东中医药大学 第一临床学院, 山东 济南 250300;
    2. 济南爱尔眼科医院 眼底病科, 山东 济南 250100;
    3. 山东省立医院 眼科, 山东 济南 250000
  • 发布日期:2021-02-01
  • 通讯作者: 赵博军. E-mail:275288825@qq.com
  • 基金资助:
    山东省自然科学基金(ZR2019MH111,ZR2015MH026)

Preoperative timing and the effect of intravitreal aflibercept injection for proliferative diabetic retinopathy patients

LIU Zhigao1,2, WANG Shuya1, HAN Xuguang2, WANG Yu2, LI Zhiwei2, MA Aihua3, ZHAO Bojun1,3   

  1. 1. Department of Ophthalmology, Shandong University of Traditional Chinese Medicine, Jinan 250300, Shandong, China;
    2. Department of Ophthalmology, Jinan Aier Eye Hospital, Jinan 250100, Shandong, China;
    3. Department of Ophthalmology, Provincial Hospital Affiliated to Shandong University, Jinan 250000, Shandong, China
  • Published:2021-02-01

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摘要： 目的 探讨增殖性糖尿病视网膜病变玻璃体腔注射抗-血管内皮生长因子(VEGF)药物阿柏西普的用药时机,观察对玻璃体液中血管内皮生长因子和碱性成纤维细胞生长因子含量的影响。 方法 采用前瞻性随机对照研究设计,选择拟行玻璃体切割手术治疗的增殖性糖尿病视网膜病变(PDR)患者52例52眼,用随机数字表法将患者分为A组(16例16眼)、B组(18例18眼)、C组(18例18眼);A组:单纯玻璃体切割术;B组:玻璃体腔注射阿柏西普2.0 mg(0.05 mL)3 d后行玻璃体切割术;C组:玻璃体腔注射阿柏西普2.0 mg(0.05 mL)6 d后行玻璃体切割术,选择特发性黄斑前膜和特发性黄斑裂孔拟行玻璃体切割术且无糖尿病的患者(15例15眼)作为对照组(D组)。术中抽吸各组受检者玻璃体液0.2~0.3 mL,采用流式细胞学法检测玻璃体液中VEGF、bFGF含量。 结果 与对照组相比,A组、B组及C组患者玻璃体液中VEGF含量升高,差异有统计学意义(P<0.05),bFGF含量升高,差异无统计学意义(P=0.390,P=0.247,P=0.239)。与A组比较,B组、C组患者玻璃体液VEGF含量显著降低,差异有统计学意义(P<0.05),bFGF含量差异无统计学意义(P=0.547,P=0.613)。B组与C组相比,患者玻璃体液中VEGF含量降低,差异无统计学意义(P=0.529);bFGF含量升高,差异无统计学意义(P=0.737)。与A组相比,B组、C组手术时间明显缩短,电凝次数明显减少,术后出血明显减少,医源性裂孔发生率明显降低,硅油填充比例降低,差异有统计学意义(P<0.05),B组与C组比较差异无统计学意义(P>0.05)。 结论 PDR患者玻璃体液中VEGF含量明显升高,PDR患者玻璃体腔注射阿柏西普后3~6 d玻璃体液中VEGF的含量明显降低,视网膜新生血管明显减少,术中出血明显减少,有利于玻璃体切割手术的顺利进行,即PDR患者在阿柏西普注射后3~6 d(最佳注射时机)行玻璃体切割术效果最佳。

关键词: 新生血管, 抗血管内皮生长因子/阿柏西普, 增殖性糖尿病视网膜病变, 细胞因子, 玻璃体切割术

Abstract: Objective To investigate the changes in vitreous inflammatory and angiogenic cytokine levels after administering intravitreal aflibercept(IVA)in the eyes with proliferative diabetic retinopathy(PDR). Methods A prospective comparative study was performed of the clinical data of the PDR patients who had undergone 23-gauge vitrectomy. Patients were divided into three groups: group A(16 eyes of 16 patients), without IVA administered preoperatively; group B(18 eyes of 18 patients), with IVA 2.0 mg administered 3 days preoperatively; and group C(18 eyes of 18 patients), with IVA 2.0 mg administered 6 days preoperatively. A total of 15 patients with idiopathic epiretinal membrane or idiopathic macular hole were selected as controls(group D). The vitreous humor was collected at the beginning of vitrectomy. The vitreal factors, including the vascular endothelial growth factor(VEGF)and basic fibrosis growth factor, were measured using the cytometric bead array. Results Higher levels of VEGF(P<0.05)in groups A, B, and C were observed compared to group D. However, VEGF levels were significantly higher in group A than in groups B and C(P<0.05). Conclusions IVA is effective in reducing the level of VEGF. IVA administered 3 to 6 days preoperatively is optimal and can help reduce complications.

Key words: Neovascularization, Proliferative diabetic retinopathy, Angiogenic and inflammatory cytokines, Vitrectomy, Aflibercept

中图分类号: 

  • R774
[1] 李维业, 黎晓新, 徐国彤. 糖尿病性视网膜病变[M]. 北京: 人民卫生出版社, 2017: 224-225.
[2] Simunovic MP, Maberley DA. Anti-vascular endothelial growth factor therapy for proliferative diabetic retinopathy: a systematic review and meta-analysis[J]. Retina, 2015, 35(10): 1931-1942. doi:10.1097/IAE.0000000000000723.
[3] Bressler SB, Liu DN, Glassman AR, et al. Change in diabetic retinopathy through 2 years: secondary analysis of a randomized clinical trial comparing aflibercept, bevacizumab, and ranibizumab[J]. JAMA Ophthalmol, 2017, 135(6): 558-568. doi:10.1001/jamaophthalmol.2017.0821.
[4] Raczyńska D, Lisowska KA, Pietruczuk K, et al. The level of cytokines in the vitreous body of severe proliferative diabetic retinopathy patients undergoing posterior vitrectomy[J]. Curr Pharm Des, 2018, 24(27): 3276-3281. doi:10.2174/1381612824666180926110704.
[5] Dong F, Yu CY, Ding HY, et al. Evaluation of intravitreal ranibizumab on the surgical outcome for diabetic retinopathy with tractional retinal detachment[J]. Medicine(Baltimore), 2016, 95(8): e2731. doi:10.1097/MD.0000000000002731.
[6] Feng J, Li B, Wen J, et al. Preoperative timing of intravitreal bevacizumab injection for proliferative diabetic retinopathy patients[J]. Ophthalmic Res, 2018, 60(4): 250-257. doi:10.1159/000493640.
[7] Semeraro F, Cancarini A, dell'Omo R, et al. Diabetic retinopathy: vascular and inflammatory disease[J]. J Diabetes Res, 2015, 2015: 582060. doi:10.1155/2015/582060.
[8] Zhao Y, Singh RP. The role of anti-vascular endothelial growth factor(anti-VEGF)in the management of proliferative diabetic retinopathy[J]. Drugs Context, 2018, 7: 212532. doi:10.7573/dic.212532.
[9] Pérez-Argandoña E, Verdaguer J, Zacharías S, et al. Preoperative intravitreal bevacizumab for proliferative diabetic retinopathy patients undergoing vitrectomy-First update[J]. Medwave, 2019, 19(1): e7512. doi:10.5867/medwave.2019.01.7511.
[10] Aleman I, Castillo Velazquez J, Rush SW, et al. Ziv-aflibercept versus bevacizumab administration prior to diabetic vitrectomy: a randomised and controlled trial[J]. Br J Ophthalmol, 2019, 103(12): 1740-1746. doi:10.1136/bjophthalmol-2018-313313.
[11] El-Sabagh HA, Abdelghaffar W, Labib AM, et al. Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: histopathologic findings and clinical implications[J]. Ophthalmology, 2011, 118(4): 636-641. doi:10.1016/j.ophtha.2010.08.038.
[12] Tsubota K, Usui Y, Wakabayashi Y, et al. Effectiveness of prophylactic intravitreal bevacizumab injection to proliferative diabetic retinopathy patients with elevated preoperative intraocular VEGF in preventing complications after vitrectomy[J]. Clin Ophthalmol, 2019, 13: 1063-1070. doi:10.2147/OPTH.S203921.
[13] 刘万智, 陈珺, 樊长春. 康柏西普治疗增生性糖尿病视网膜病变[J]. 山东大学耳鼻喉眼学报, 2018, 32(6): 88-91. doi: 10.6040/j.issn.1673-3770.0.2018.005. LIU Wanzhi, CHEN Jun, FAN Changchun. Clinical study of conbercept in the treatment of-proliferative diabetic retinopathy[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(6): 88-91. doi: 10.6040/j.issn.1673-3770.0.2018.005.
[14] 周学义, 李一鸣, 王美菊, 等. 25+微创玻璃体视网膜手术联合玻璃体腔注射雷珠单抗治疗增生型糖尿病视网膜病变的临床观察[J]. 山东大学耳鼻喉眼学报, 2017, 31(4): 87-89. doi: 10.6040/j.issn.1673-3770.0.2017.023. ZHOU Xueyi, LI Yiming, WANG Meiju, et al. The application of 25-gauge minimally invasive vitreoretinal surgery combined with intravitreal ranibizumab injections in the treatment of proliferative diabetic retinopathy[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2017, 31(4): 87-89. doi: 10.6040/j.issn.1673-3770.0.2017.023.
[15] Lotfy A, Solaiman KAM, Abdelrahman A, et al. Efficacy and frequency of intravitreal aflibercept versus bevacizumab for macular edema secondary to central retinal vein occlusion[J]. Retina, 2018, 38(9): 1795-1800. doi:10.1097/IAE.0000000000001782.
[16] Heier JS, Korobelnik JF, Brown DM, et al. Intravitreal aflibercept for diabetic macular edema: 148-week results from the VISTA and VIVID studies[J]. Ophthalmology, 2016, 123(11): 2376-2385. doi:10.1016/j.ophtha.2016.07.032.
[17] Jiao CH, Eliott D, Spee C, et al. Apoptosis and angiofibrosis in diabeic tractional membranes after vascular endothelial growth factor inhibition: results of a prospective trial. report No. 2[J]. Retina, 2019, 39(2): 265-273. doi:10.1097/IAE.0000000000001952.
[18] Zlotcavitch L, Flynn HW Jr, Avery RL, et al. Progression to macula-off tractional retinal detachment after a contralateral intraoperative intravitreal bevacizumab injection for proliferative diabetic retinopathy[J]. Clin Ophthalmol, 2015, 9: 69-71. doi:10.2147/OPTH.S69466.
[19] Feng J, Li B, Wen J, et al. Preoperative timing of intravitreal bevacizumab injection for proliferative diabetic retinopathy patients[J]. Ophthalmic Res, 2018, 60(4): 250-257. doi:10.1159/000493640.
[20] Sohn EH, He SK, Kim LA, et al. Angiofibrotic response to vascular endothelial growth factor inhibition in diabetic retinal detachment[J]. Arch Ophthalmol, 2012, 130(9): 1127. doi:10.1001/archophthalmol.2012.1611.
[21] Schlingemann RO, van Geest RJ, Lesnik Oberstein SY, et al. A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy[J]. Acta Ophthalmol, 2012. doi:10.1111/j.1755-3768.2012.4723.x
[22] Smith JM, Steel DH. Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy[J]. Cochrane Database Syst Rev, 2011(5): CD008214. doi:10.1002/14651858.cd008214.pub2.
[23] Sohn EH, He S, Kim LA, et al. Angiofibrotic response to vascular endothelial growth factor inhibition in diabetic retinal detachment: report no. 1[J]. Arch Ophthalmol, 2012, 130(9): 1127-1134. doi:10.1001/archophthalmol.2012.1611.
[24] Han XX, Guo CM, Li Y, et al. Effects of bevacizumab on the neovascular membrane of proliferative diabetic retinopathy: reduction of endothelial cells and expressions of VEGF and HIF-1α[J]. Mol Vis, 2012, 18: 1-9. doi: 10.4236/ojog.2014.416149.
[25] Smith JM, Steel DH. Anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity haemorrhage after vitrectomy for proliferative diabetic retinopathy[J]. Cochrane Database Syst Rev, 2015(8): CD008214. doi:10.1002/14651858.CD008214.pub3.
[26] Hueber A, Wiedemann P, Esser P, et al. Basic fibroblast growth factor mRNA, bFGF peptide and FGF receptor in epiretinal membranes of intraocular proliferative disorders(PVR and PDR)[J]. Int Ophthalmol, 1996, 20(6): 345-350. doi:10.1007/BF00176889.
[27] Okada-Ban M, Thiery JP, Jouanneau J. Fibroblast growth factor-2[J]. The International Journal of Biochemistry & Cell Biology, 2000, 32(3): 263-267. doi: 10.1016/S1357-2725(99)00133-8.
[28] Li JK, Wei F, Jin XH, et al. Changes in vitreous VEGF, bFGF and fibrosis in proliferative diabetic retinopathy after intravitreal bevacizumab[J]. Int J Ophthalmol, 2015, 8(6): 1202-1206. doi:10.3980/j.issn.2222-3959.2015.06.22.
[29] Dowlati A, Gray R, Sandler AB, et al. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab: an Eastern Cooperative Oncology Group Study[J]. Clin Cancer Res, 2008, 14(5): 1407-1412. doi:10.1158/1078-0432.CCR-07-1154.
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