雷珠单抗联合地塞米松玻璃体内植入剂治疗视网膜分支静脉阻塞继发黄斑水肿的效果

doi:10.3969/j.issn.1674-490X.2024.05.003

摘要/Abstract

摘要： 目的观察雷珠单抗联合地塞米松玻璃体内植入剂治疗视网膜分支静脉阻塞继发黄斑水肿(macular edema secondary to branch retinal vein occlusion, BRVO-ME)的效果。方法纳入2020年1月至2022年5月保定市第一中心医院眼科确诊为BRVO-ME且临床资料完整的患者67例67只眼,按照治疗方法的不同将患者分为单药组及联合组,其中单药组37例37只眼,联合组30例30只眼。所有患者行玻璃体腔注射雷珠单抗注射液0.05 mL治疗,联合组于雷珠单抗治疗1周后行地塞米松玻璃体内植入剂0.7 mg玻璃体腔注射;分别于治疗前和治疗后4周检测最佳矫正视力(best corrected visual acuity, BCVA),应用相干光断层扫描成像(optical coherence tomography, OCT)分析黄斑中心凹厚度(central macular thickness, CMT)变化,相干光断层扫描血管成像(optical coherence tomography angiography, OCTA)分析黄斑区浅层视网膜血管灌注密度(vessel perfusion density, VPD)及血管长度密度(vessel length density,VLD)变化。依据患者复诊的情况判断是否需要再次治疗,如果随访复查时OCT的黄斑区域出现视网膜内液或视网膜下液,CMT≥300 μm或BCVA持续下降,需再次接受雷珠单抗注射者则终止观察。结果初诊时联合组和单药组BCVA、CMT比较差异无统计学意义(P>0.05),治疗后2组BCVA、CMT较治疗前均降低(P<0.05)且治疗后联合组BCVA、CMT低于单药组(P<0.05)。而2组患者治疗前后黄斑区浅层毛细血管中心、内环、外环及完整的VLD及VPD均无明显变化(P>0.05)。2组治疗前后结果进行组间比较,VLD、VPD结果均无统计学意义(P>0.05)。结论玻璃体腔内注射雷珠单抗联合地塞米松玻璃体内植入剂治疗BRVO-ME可降低黄斑水肿,改善视力及黄斑区结构和功能,并且疗效可持续。但二者早期疗效相似,协同作用不明显。

关键词: 视网膜分支静脉阻塞, 黄斑水肿, 地塞米松, 抗血管内皮生长因子, 相干光断层扫描血管成像

Abstract: Objective To observe the effcts of intravitreal of ranibizumab and DEX implant in macular edema secondary to branch retinal vein occlusion(BRVO-ME). Methods 67 cases with BRVO-ME in the Department of Ophthalmology of Baoding No.1 Central Hospital were included from January 2020 to May 2022. According to the different methods of treatment,all patients were divided into ranibizumab group and combined treatment group, 37 cases of 37 eyes in the ranibizumab group and 30 cases of 30 eyes in the combined treatment group. All patients were treated with intravitreal injection of ranibizumab,and the combined treatment group was treated with ranibizumab and 1 week later with 0.7 mg DEX implant. The best corrected visual acuity(BCVA), the central macular thickness(CMT)and the vessel perfusion density(VPD), vessel length density(VLD)were evaluated detected with optical coherence tomography(OCT and OCTA)before and after treatment. Depending on the patient's follow-up, the following situation occurs would stop observing. If intra-retinal/sub-retinal accumulation fluid appeared in the macular area, the BCVA continued to decline, or the CMT≥300 μm, with the increase in CMT. Results There was no significant difference in BCVA and CMT between the combination group and the single drug group at the first diagnosis(P>0.05). After treatment, the BCVA and CMT of the two groups were lower than those before treatment(P<0.05), and the BCVA and CMT of the combination group were lower than those of the single drug group after treatment(P<0.05).While no significant difference was found in VPD and VLD at the central, inner, otuer, full region in the superficial retinal capillary plexus within 6 mm×6 mm of macular area before and after treatment(P>0.05). Conclusion In eyes with BRVO-ME, treatment with an anti-VEGF agent plus DEX implant could provide a predictable duration of effect, as well as significant improvements in BCVA and CMT. However, the early efficacy of the two is similar, and the synergistic effects are not obvious.

Key words: branch retinal vein occlusion, macular edema, dexamethasone, anti-vascular endothelial growth factor, optical coherence tomography angiography

中图分类号:

杨娜, 温晓英, 张月玲. 雷珠单抗联合地塞米松玻璃体内植入剂治疗视网膜分支静脉阻塞继发黄斑水肿的效果[J]. 医学研究与教育, 2024, 41(5): 19-29.

参考文献

[1] URIAS E A, URIAS G A, MONICKARAJ F, et al. Novel therapeutic targets in diabetic macular edema: beyond VEGF[J]. Vision Res, 2017, 139: 221-227. DOI: 10.1016/j.visres.2017.06.015.
[2] ZHOU J Q, XU L, WANG S, et al. The 10-year incidence and risk factors of retinal vein occlusion: the Beijing eye study[J]. Ophthalmology, 2013, 120(4): 803-808. DOI: 10.1016/j.ophtha.2012.09.033.
[3] LI J, PAULUS Y M, SHUAI Y L, et al. New developments in the classification, pathogenesis, risk factors, natural history, and treatment of branch retinal vein occlusion[J]. J Ophthalmol, 2017, 2017: 4936924. DOI: 10.1155/2017/4936924.
[4] CUGATI S, WANG J J, ROCHTCHINA E, et al. Ten-year incidence of retinal vein occlusion in an older population: the Blue Mountains Eye Study[J]. Arch Ophthalmol, 2006, 124(5): 726-732. DOI: 10.1001/archopht.124.5.726.
[5] KLEIN R, MOSS S E, MEUER S M, et al. The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study[J]. Arch Ophthalmol, 2008, 126(4): 513-518. DOI: 10.1001/archopht.126.4.513.
[6] BERGER A R, CRUESS A F, ALTOMARE F, et al. Optimal treatment of retinal vein occlusion: Canadian expert consensus[J]. Ophthalmologica, 2015, 234(1): 6-25. DOI: 10.1159/000381357.
[7] ROGERS S, MCINTOSH R L, CHEUNG N, et al. The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia[J]. Ophthalmology, 2010, 117(2): 313-319. DOI: 10.1016/j.ophtha.2009.07.017.
[8] 雍红芳,戚卉,吴瑛洁,等.视网膜静脉阻塞继发黄斑水肿发病机制及黄斑水肿影响视功能的研究进展[J].国际眼科杂志, 2019, 19(11): 1888-1891. DOI: 10.3980/j.issn.1672-5123.2019.11.17.
[9] CHATZIRALLI I, THEODOSSIADIS G, PARIKAKIS E, et al. Long-term anatomical and functional outcomes in patients with ischemic central retinal vein occlusion treated with anti-vascular endothelial growth factor agents[J]. Ophthalmic Res, 2017, 58(4): 203-208. DOI: 10.1159/000462976.
[10] CELIK E, DOG ˇAN E, TURKOGLU E B, et al. Serous retinal detachment in patients with macular edema secondary to branch retinal vein occlusion[J]. Arq Bras Oftalmol, 2016, 79(1): 9-11. DOI: 10.5935/0004-2749.20160004.
[11] IIJIMA H. Mechanisms of vision loss in eyes with macular edema associated with retinal vein occlusion[J]. Jpn J Ophthalmol, 2018, 62(3): 265-273. DOI: 10.1007/s10384-018-0586-5.
[12] NOMA H, MINAMOTO A, FUNATSU H, et al. Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion[J]. Graefe's Arch Clin Exp Ophthalmo, 2006, 244(3): 309-315. DOI: 10.1007/s00417-004-1087-4.
[13] TARALLO V, FALCO S D. The vascular endothelial growth factors and receptors family: up to now the only target for anti-angiogenesis therapy[J]. Int J Biochem Cell Biol, 2015, 64: 185-189. DOI: 10.1016/j.biocel.2015.04.008.
[14] XIA J P, WANG S, ZHANG J S. The anti-inflammatory and anti-oxidative effects of conbercept in treatment of macular edema secondary to retinal vein occlusion[J]. Biochem Biophys Res Commun, 2019, 508(4): 1264-1270. DOI: 10.1016/j.bbrc.2018.12.049.
[15] SIVAPRASAD S, AMOAKU W M, HYKIN P, et al. The Royal College of Ophthalmologists Guidelines on retinal vein occlusions: executive summary[J]. Eye, 2015, 29(12): 1633-1638. DOI: 10.1038/eye.2015.164.
[16] PULIDO J S, FLAXEL C J, ADELMAN R A, et al. Retinal vein occlusions preferred practice pattern(^®)guidelines[J]. Ophthalmology, 2016, 123(1): 182-208. DOI: 10.1016/j.ophtha.2015.10.045.
[17] 中华医学会眼科学分会眼底病学组,中国医师协会眼科医师分会眼底病专业委员会.中国视网膜静脉阻塞临床诊疗路径专家共识[J].中华眼底病杂志, 2024, 40(3): 175-185. DOI: 10.3760/cma.j.cn511434-20240201-00056.
[18] 陈露璐,陈有信.2019年《EURETINA视网膜静脉阻塞诊疗指南》解读[J].中华实验眼科杂志, 2020, 38(1): 60-63. DOI: 10.3760/cma.j.issn.2095-0160.2020.01.012.
[19] MYUNG J S, AAKER G D, KISS S. Treatment of noninfectious posterior uveitis with dexamethasone intravitreal implant[J]. Clin Ophthalmol, 2010, 4: 1423-1426. DOI: 10.2147/OPTH.S15696.
[20] BOYER D S, YOON Y H, BELFORT R, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema[J]. Ophthalmology, 2014, 121(10): 1904-1914. DOI: 10.1016/j.ophtha.2014.04.024.
[21] MISHRA S K, GUPTA A, PATYAL S, et al. Intravitreal dexamethasone implant versus triamcinolone acetonide for macular oedema of central retinal vein occlusion: quantifying efficacy and safety[J]. Int J Retina Vitreous, 2018, 4: 13. DOI: 10.1186/s40942-018-0114-2.
[22] BUDZINSKAYA M V, SHELANKOVA A V, PLUKHOVA A, et al. The role of steroids in the management of macular edema from retinal vein occlusion[J]. Ophthalmol Russ, 2019, 16(1): 95-101. DOI: 10.18008/1816-5095-2019-1-95-101.
[23] TAN M H, MCALLISTER I L, GILLIES M E, et al. Randomized controlled trial of intravitreal ranibizumab versus standard grid laser for macular edema following branch retinal vein occlusion[J]. Am J Ophthalmol, 2014, 157(1): 237-247. DOI: 10.1016/j.ajo.2013.08.013.
[24] SHIRAKATA Y, FUKUDA K, FUJITA T, et al. Pars plana vitrectomy combined with internal limiting membrane peeling for recurrent macular edema due to branch retinal vein occlusion after antivascular endothelial growth factor treatments[J]. Clin Ophthalmol, 2016, 10: 277-283. DOI: 10.2147/OPTH.S85751.
[25] HAHN P. Successful treatment of neovascular age-related macular degeneration following single bevacizumab failure using aflibercept in a vitrectomized eye[J]. Clin Ophthalmol, 2014, 8: 2129-2131. DOI: 10.2147/OPTH.S73265.
[26] FLAXEL C J, ADELMAN R A, BAILEY S T, et al. Retinal vein occlusions preferred practice pattern(^®)[J]. Ophthalmology, 2020, 127(2): 288-320. DOI: 10.1016/j.ophtha.2019.09.029.
[27] SINGER M A, JANSEN M E, TYLER L, et al. Long-term results of combination therapy using anti-VEGF agents and dexamethasone intravitreal implant for retinal vein occlusion: an investigational case series[J]. Clin Ophthalmol, 2017, 11: 31-38. DOI: 10.2147/OPTH.S119373.
[28] IU L P, ZHAO P, YEUNG I Y, et al. Sequential therapy with ranibizumab and dexamethasone intravitreal implant is better than dexamethasone monotherapy for macular oedema due to retinal vein occlusion[J]. Br J Ophthalmol, 2015, 99(2): 210-214. DOI: 10.1136/bjophthalmol-2014-305661.
[29] AL-KHERSAN H, HARIPRASAD S M, SALEHI-HAD H. Dexamethasone and anti-VEGF combination therapy for the treatment of diabetic macular edema[J]. Ophthalmic Surg Lasers Imaging Retina, 2019, 50(1): 4-7. DOI: 10.3928/23258160-20181212-01.
[30] QIAN T, ZHAO M, XU X. Comparison between anti-VEGF therapy and corticosteroid or laser therapy for macular oedema secondary to retinal vein occlusion: a meta-analysis[J]. J Clin Pharm Ther, 2017, 42(5): 519-529. DOI: 10.1111/jcpt.12551.
[31] MANOUSARIDIS K, PETER S, MENNEL S. Outcome of intravitreal dexamethasone implant for the treatment of ranibizumab-resistant macular edema secondary to retinal vein occlusion[J]. Int Ophthalmol, 2017, 37(1): 47-53. DOI: 10.1007/s10792-016-0226-3.
[32] COSCAS G, AUGUSTIN A, BANDELLO F, et al. Retreatment with Ozurdex for macular edema secondary to retinal vein occlusion[J]. Eur J Ophthalmol, 2014, 24(1): 1-9. DOI: 10.5301/ejo.5000376.
[33] FASSBENDER ADENIRAN J M, JUSUFBEGOVIC D, SCHAAL S. Common and rare ocular side-effects of the dexamethasone implant[J]. Ocul Immunol Inflamm, 2017, 25(6): 834-840. DOI: 10.1080/09273948.2016.1184284.
[34] ZHAO L Q, CHENG J W. A systematic review and meta-analysis of clinical outcomes of intravitreal anti-VEGF agent treatment immediately after cataract surgery for patients with diabetic retinopathy[J]. J Ophthalmol, 2019, 2019: 2648267. DOI: 10.1155/2019/2648267.