中华眼底病杂志

中华眼底病杂志

关注早产儿视网膜病变抗血管内皮生长因子药物治疗的结局和终点

查看全文

2013年美国儿科杂志发布的专家共识中首次提出对于Ⅰ区3期伴附加病变的早产儿视网膜病变(ROP)可以考虑行抗VEGF药物治疗。但对于ROP,抗VEGF药物治疗较传统激光治疗的利弊、治疗后有无全身与眼部并发症以及当患儿具备哪些指征时应该终止治疗均是值得眼科医生重点关注的问题。结合该共识及众多研究结果,我们建议首次治疗选择抗VEGF药物还是激光治疗应该从疾病控制效果考虑。对于阈值病变和阈值前病变的Ⅱ区病变,抗VEGF药物治疗效果好于Ⅰ区病变且单次有效率高;对于Ⅰ区病变,其疾病变化快,而抗VEGF药物作用较激光快,建议首次治疗时首选抗VEGF药物治疗。重复治疗的选择,应从最终视网膜结构和功能预后考虑。异常血管消退慢及后极部出现异常者补充治疗采取激光为宜,可减少复查次数和延长复查间隔时间;但过早的使用激光干预,对周边视野的影响不可避免。排除上述问题,补充治疗依然可以选择再次抗VEGF药物治疗,大部分患儿经2次抗VEGF药物治疗足以控制病变。当出现附加病变消退,阈值病变、阈值前1型病变控制无复发病变以及血管达Ⅲ区即周边部血管化等指征时应终止抗VEGF药物治疗。

In the expert consensus published by the Pediatrics in 2013, it was first proposed that anti-VEGF drugs can be considered for retinopathy of prematurity (ROP) with stage 3, zone Ⅰ with plus disease. However, there are many problems worth the attention of ophthalmologists, including the advantages and disadvantages of anti-VEGF therapy compared with traditional laser therapy, systemic and ocular complications after anti-VEGF therapy, and what indicators are the end points of anti-VEGF therapy. Combined with this consensus and numerous research findings, we recommend that the first treatment for anti-VEGF or laser therapy should be considered from disease control effects. For the threshold and pre-threshold lesions, the effect of anti-VEGF therapy for zoneⅡ lesions is better than that for zone Ⅰ lesions and the single-time effective rate is high. So, it is suggested that anti-VEGF therapy should be preferred for the first treatment. The choice of repeat treatment should be considered from the final retinal structure and functional prognosis. Laser therapy is advisable for the abnormal vascular regression slower and abnormalities in the posterior pole. It can reduce the number of reexaminations and prolong the interval between re-examinations. However, the premature use of laser has an inevitable effect on peripheral vision field. Excluding the above problems, supplemental therapy can still choose anti-VEGF therapy again. Most of the children with twice anti-VEGF therapy are sufficient to control the disease. Anti-VEGF therapy should be terminated when there are signs such as plus regression, threshold or pre-threshold lesions controlled without recurrence, peripheral vascularization, etc.

关键词: 早产儿视网膜病/药物疗法; 血管生成抑制剂/治疗应用; 抗体,单克隆/治疗应用; 述评

Key words: Retinopathy of prematurity/drug therapy; Angiogenesis inhibitors/therapeutic applications; Antibodies, monoclonal/therapeutic applications; Reviews

引用本文: 姜燕荣. 关注早产儿视网膜病变抗血管内皮生长因子药物治疗的结局和终点. 中华眼底病杂志, 2019, 35(2): 115-118. doi: 10.3760/cma.j.issn.1005-1015.2019.02.002 复制

登录后 ,请手动点击刷新查看全文内容。 没有账号,
登录后 ,请手动点击刷新查看图表内容。 没有账号,
1. Fierson WM, American Academy of Pediatrics Section on Ophthalmology, American Academy of Ophthalmology, et al. Screening examination of premature infants for retinopathy of prematurity[J]. Pediatrics, 2013, 131(1): 189-195. DOI: 10.1542/peds.2012-2996.
2. Zhou Y, Jiang Y, Bai Y, et al. Vascular endothelial growth factor plasma levels before and after treatment of retinopathy of prematurity with ranibizumab[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(1): 31-36. DOI: 10.1007/s00417-015-2996-0.
3. Wu WC, Shih CP, Lien R, et al. Serum vascular endothelial growth factor after bevacizumab or ranibizumab treatment for retinopathy of prematurity[J]. Retina, 2017, 37(4): 694-701. DOI: 10.1097/IAE.0000000000001209.
4. Jin E, Bai Y, Luo L, et al. Serum levels of vascular endothelial growth factor before and after intravitreal injection of ranibizumab or conbercept for neovascular age-related macular degeneration[J]. Retina, 2017, 37(5): 971-977. DOI: 10.1097/IAE.0000000000001274.
5. Early Treatment for Retinopathy of Prematurity Cooperative Group. Revised indications for the treatment of retinopathy of prematurity: results of the early treatment for retinopathy of prematurity randomized trial[J]. Arch Ophthalmol, 2003, 121(12): 1684-1696. DOI: 10.1001/archopht.121.12.1684.
6. Feng J, Qian J, Jiang Y, et al. Efficacy of primary intravitreal ranibizumab for treatment of retinopathy of prematurity in China[J]. Ophthalmology, 2017, 124(3): 408-409. DOI: 10.1016/j.ophtha.2016.10.032.
7. Huang Q, Zhang Q, Fei P, et al. Ranibizumab injection as primary treatment in patients with retinopathy of prematurity: anatomic outcomes and influencing factors[J]. Ophthalmology, 2017, 124(8): 1156-1164. DOI: 10.1016/j.ophtha.2017.03.018.
8. 程湧, 梁建宏, 黎晓新. 康柏西普玻璃体腔注射治疗急进性后极部早产儿视网膜病变的疗效观察[J]. 中华眼底病杂志, 2017, 33(2): 144-147. DOI: 10.3760/cma.j.issn.1005-1015.2017.02.008.
9. Jin E, Yin H, Li X, et al. Short-term outcomes after intravitreal injections of conbbercept versus ranibizumab for the treatment of retinapathy of prematurity[J]. Retina, 2018, 38(8): 1595-1604. DOI: 10.1097/IAE.0000000000001763.8:1.
10. Wu WC, Kuo HK, Yeh PT, et al. An updated study of the use of bevacizumab in the treatment of patients with prethreshold retinopathy of prematurity in Taiwan[J]. Am J Ophthalmol, 2013, 155: 150-158. DOI: 10.1016/j.ajo.2012.06.010.
11. Mintz-Hittner HA, Kennedy KA, Chuang AZ, et al. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity[J]. N Engl J Med, 2011, 364(7): 603-615. DOI: 10.1056/NEJMoa1007374.
12. Krohne TU, Liu Z, Holz FG, et al. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans[J]. Am J Ophthalmol, 2012, 154(4): 682-686. DOI: 10.1016/j.ajo.2012.03.047.
13. Wong RK, Hubschman S, Tsui I. Reactivation of retinopathy of prematurity after ranibizumab treatment[J]. Retina, 2015, 35(4): 675-680. DOI: 10.1097/IAE.0000000000000578.
14. Kychenthal A, Dorta P. Vitrectomy after intravitreal bevacizumab (Avastin) for retinal detachmentin retinopathy of prematurity[J]. Retina, 2010, 30(4 Suppl): S32-36. DOI: 10.1097/IAE.0b013e3181ca146b.
15. Harper CA 3rd, Wright LM, Young RC, et al. Fluorescein angiographic evaluation of peripheral retinal vasculature after primary intravitreal ranibizumab for retinapathy of prematurity[J/OL]. Retina, 2018, 2018: E1[2018-01-03]. http://dx.doi.org/10.1097/IAE.0000000000001996. DOI: 10.1097/IAE.0000000000001996. [published online ahead of print].
16. Lepore D, Quinn GE, Molle F, et al. Intravitreal bevacizumab versus laser treatment in type 1 retinopathy of prematurity: report on fluorescein angiographic findings[J]. Ophthalmology, 2014, 121(11): 2212-2219. DOI: 10.1016/j.ophtha.2014.05.015.
17. Martinez-Castellanos MA, Velez-Montoya R, Price K, et al. Vascular changes on fluorescein angiography of premature infants with low risk of retinopathy of prematurity after high oxygen exposure[J/OL]. Int J Retina Vitreous, 2017, 3: 2[2017-01-16]. https://journalretinavitreous.biomedcentral.com/articles/10.1186/s40942-016-0055-6. DOI: 10.1186/s40942-016-0055-6.
18. Castellanos MA, Schwartz S, García-Aguirre G, et al. Short-term outcome after intravitreal ranibizumab injections for the treatment of retinopathy of prematurity[J]. Br J Ophthalmol, 2013, 97(7): 816-819. DOI: 10.1136/bjophthalmol-2012-302276.
19. Matsuyama K, Ogata N, Matsuoka M, et al. Effects of intravitreally injected bevacizumab on vascular endothelial growth factor in fellow eyes[J]. J Ocul Pharmacol Ther, 2011, 27(4): 379-383. DOI: 10.1089/jop.2010.0194.