Expert consensus on intravitreal injection of anti-vascular endothelial growth factor drugs for retinopathy of prematurity_Chinese Journal of Ocular Fundus Diseases

Authors：

 Pediatric Retinology Group of Ophthalmology Professional Committee of Cross-Strait Medical and Health Exchange Association , Fundus Disease Group of Chinese Medical Association Ophthalmology Branch

Corresponding author：

Pediatric Retinology Group of Ophthalmology Professional Committee of Cross-Strait Medical and Health Exchange Association, Email: zhaopeiquan@xinhuamed.com.cn

Keywords：

Retinopathy of prematurity; Angiogenesis inhibitors; Consensus

DOI：

10.3760/cma.j.cn511434-20210916-00530

Video：

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Abstract Full text Figures/Tables Video References Cited by

With the deepening understanding of the pathogenesis of retinopathy of prematurity (ROP) and the continuous development of new drugs, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has gradually become an important treatment of ROP. Therefore, it is of great significance to standardize the operation of ROP intravitreal injection in order to make sure that infants receive safe and effective treatment. Based on the actual situation of the diagnosis and treatment of ROP in China, and after careful, comprehensive and full discussion on the indications and contraindications, injection requirements, operation precautions and post-treatment precautions of intravitreal injection of anti-VEGF drugs in the treatment of ROP, Pediatric Retinology Group of Ophthalmology Professional Committee of Cross-Strait Medical and Health Exchange Association form an expert consensus, and it is reviewed and modified by Fundus Disease Group of Chinese Medical Association Ophthalmology Branch for ophthalmologists' reference in clinical work.

Citation： Pediatric Retinology Group of Ophthalmology Professional Committee of Cross-Strait Medical and Health Exchange Association, Fundus Disease Group of Chinese Medical Association Ophthalmology Branch. Expert consensus on intravitreal injection of anti-vascular endothelial growth factor drugs for retinopathy of prematurity. Chinese Journal of Ocular Fundus Diseases, 2021, 37(11): 836-840. doi: 10.3760/cma.j.cn511434-20210916-00530 Copy

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2.	赵培泉, 张琦, 许宇. 提高小儿视网膜疾病的认知水平, 推动我国小儿视网膜疾病研究的深入开展[J]. 中华眼底病杂志, 2014, 30(1): 1-5. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.001.Zhao PQ, Zhang Q, Xu Y. The diagnosis and treatment of pediatric retinal disease[J]. Chin J Ocul Fundus Dis, 2014, 30(1): 1-5. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.001.
3.	赵培泉, 费萍. 早产儿视网膜病变诊断治疗研究现状、问题及展望[J]. 中华眼底病杂志, 2012, 28(1): 3-7. DOI: 10.3760/cma.j.issn.1005-1015.2012.01.002.Zhao PQ, Fei P. Screening and treatment of retinopathy of prematurity: current status, problems and prospects in China[J]. Chin J Ocul Fundus Dis, 2012, 28(1): 3-7. DOI: 10.3760/cma.j.issn.1005-1015.2012.01.002.
4.	Good WV, Early Treatment for Retinopathy of Prematurity Cooperative Group. Final results of the early treatment for retinopathy of prematurity (ETROP) randomized trial[J]. Trans Am Ophthalmol Soc, 2004, 102: 233-248.
5.	Mintz-Hittner HA, Kennedy KA, Chuang AZ. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity[J]. N Engl J Med, 2011, 364(7): 603-615. DOI: 10.1056/NEJMoa1007374.
6.	Stahl A, Lepore D, Fielder A, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled study[J]. Lancet, 2019, 394(10208): 1551-1559. DOI: 10.1016/S0140-6736(19)31344-3.
7.	Feng J, Qian J, Jiang Y, et al. Efficacy of primary intravitreal ranibizumab for retinopathy of prematurity in China[J]. Ophthalmology, 2017, 124(3): 408-409. DOI: 10.1016/j.ophtha.2016.10.032.
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.Chen Y, Lian JH, Li XX. Intravitreal injection of conbercept for aggressive posterior retinopathy of prematurity[J]. Chin J Ocul Fundus Dis, 2017, 33(2): 144-147. DOI: 10.3760/cma.j.issn.1005-1015.2017.02.008.
9.	许宇, 张琦, 季迅达, 等. 玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab联合激光光凝治疗急进性后部型早产儿视网膜病变的疗效观察[J]. 中华眼底病杂志, 2014, 30(1): 28-32. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.008.Xu Y, Zhang Q, Ji XD, et al. Combination of intravitreal injection of ranibizumab and laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity[J]. Chin J Ocul Fundus Dis, 2014, 30(1): 28-32. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.008.
10.	Xu Y, Zhang Q, Kang X, et al. Early vitreoretinal surgery on vascularly active stage 4 retinopathy of prematurity through the preoperative intravitreal bevacizumab injection[J/OL]. Acta Ophthalmol, 2013, 91(4): e304-310[2013-05-07]. https://pubmed.ncbi.nlm.nih.gov/23647944/. DOI: 10.1111/aos.12055.
11.	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.
12.	Lyu J, Zhang Q, Jin H, et al. Aqueous cytokine levels associated with severity of type 1 retinopathy of prematurity and treatment response to ranibizumab[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(8): 1469-1477. DOI: 10.1007/s00417-018-4034-5.
13.	陈宜, 冯婧, 孟宪芬, 等. 玻璃体腔注射雷珠单抗治疗早产儿视网膜病变疗效观察[J]. 中华眼底病杂志, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.Chen Y, Feng J, Meng XF, et al. Effects of ranibizumab in zone Ⅰ and zone Ⅱ retinopathy of prematurity patients[J]. Chin J Ocul Fundus Dis, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.
14.	Zhang Q, Qi Y, Chen L, et al. The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: clinical and laboratory evidence[J]. Br J Ophthalmol, 2016, 100(10): 1443-1450. DOI: 10.1136/bjophthalmol-2015-308199.
15.	Honda S, Hirabayashi H, Tsukahara Y, et al. Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246(7): 1061-1063. DOI: 10.1007/s00417-008-0786-7.
16.	Huang Q, Zhang Q, Xu Y, et al. Asymmetric outcomes of type 1 retinopathy of prematurity after bilateral intravitreal ranibizumab treatment[J/OL]. J Ophthalmol, 2017, 2017: 1741386[2017-03-29].https://pubmed.ncbi.nlm.nih.gov/28465833/. DOI: 10.1155/2017/1741386.
17.	Chiang MF, Quinn GE, Fielder AR, et al. International classification of retinopathy of prematurity, third edition[J/OL]. Ophthalmology, 2021: 128(10): e51-e68[2021-07-08]. https://pubmed.ncbi.nlm.nih.gov/34247850/. DOI: 10.1016/j.ophtha.2021.05.031.
18.	黎晓新. 我国早产儿视网膜病变特点和筛查指南[J]. 中华眼底病杂志, 2004, 20(6): 384-386. DOI: 10.3760/j.issn:1005-1015.2004.06.020.Li XX. Characteristics and screening guidelines of retinopathy of prematurity in my country[J]. Chin J Ocul Fundus Dis, 2004, 20(6): 384-386. DOI: 10.3760/j.issn:1005-1015.2004.06.020.
19.	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): 1684-1694. DOI: 10.1001/archopht.121.12.1684.
20.	Van Geest RJ, Lesnik-Oberstein SY, Tan HS, 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]. Br J Ophthalmol, 2012, 96(4): 587-590. DOI: 10.1136/bjophthalmol-2011-301005.
21.	Avery RL, Pieramici DJ, Rabena MD, et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration[J]. Ophthalmology, 2006, 113(3): 363-372.e5. DOI: 10.1016/j.ophtha.2005.11.019.
22.	Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration[J]. Retina, 2006, 26(4): 383-390. DOI: 10.1097/01.iae.0000238561.99283.0e.
23.	Salman AG, Said AM. Structural, visual and refractive outcomes of intravitreal aflibercept injection of high-risk prethreshold type 1 retinopathy of prematurity[J]. Ophthalmic Res, 2015, 53(1): 15-20. DOI: 10.1159/000364809.
24.	Sukgen EA, Kocluk Y. Comparision of clinical outcomes of intravitreal ranibizumab and aflibercept treatment for retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2019, 257(1): 49-55. DOI: 10.1007/s00417-018-4168-5.
25.	Cheng Y, Meng Q, Linghu D, et al. A lower dose of intravitreal conbercept effectively treats retinopathy of prematurity[J/OL]. Sci Rep, 2018, 8(1): 10732[2018-07-16]. https://pubmed.ncbi.nlm.nih.gov/30013230/. DOI: 10.1038/s41598-018-28987-6.
26.	Cheng Y, Zhu X, Linghu D, et al. Comparison of the effectiveness of conbercept and ranibizumab treatment for retinopathy of prematurity[J/OL]. Acta Ophthalmol, 2020, 98(8): e1004-e1008[2020-05-08].https://pubmed.ncbi.nlm.nih.gov/32385940/. DOI: 10.1111/aos.14460.
27.	中华医学会眼科学分会眼底病学组. 我国视网膜病玻璃体腔注药术质量控制标准[J]. 中华眼科杂志, 2015, 51(12): 892-895. DOI: 10.3760/cma.j.issn.0412-4081.2015.12.005.Fundus Disease Group of Chinese Medical Association Ophthalmology Branch. Quality control standards for intravitreal injection of retinopathy in China[J]. Chin J Ophthalmol, 2015, 51(12): 892-895. DOI: 10.3760/cma.j.issn.0412-4081.2015.12.005.

1. 中华医学会眼科学分会眼底病学组. 中国早产儿视网膜病变筛查指南 (2014年)[J]. 中华眼科杂志, 2014, 50(12): 933-935. DOI: 10.3760/cma.j.issn.0412-4081.2014.12.017.Fundus Disease Group of Chinese Medical Association Ophthalmology Branch. Chinese guidelines for screening retinopathy of prematurity (2014)[J]. Chin J Ophthalmol, 2014, 50(12): 933-935. DOI: 10.3760/cma.j.issn.0412-4081.2014.12.017.
2. 赵培泉, 张琦, 许宇. 提高小儿视网膜疾病的认知水平, 推动我国小儿视网膜疾病研究的深入开展[J]. 中华眼底病杂志, 2014, 30(1): 1-5. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.001.Zhao PQ, Zhang Q, Xu Y. The diagnosis and treatment of pediatric retinal disease[J]. Chin J Ocul Fundus Dis, 2014, 30(1): 1-5. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.001.
3. 赵培泉, 费萍. 早产儿视网膜病变诊断治疗研究现状、问题及展望[J]. 中华眼底病杂志, 2012, 28(1): 3-7. DOI: 10.3760/cma.j.issn.1005-1015.2012.01.002.Zhao PQ, Fei P. Screening and treatment of retinopathy of prematurity: current status, problems and prospects in China[J]. Chin J Ocul Fundus Dis, 2012, 28(1): 3-7. DOI: 10.3760/cma.j.issn.1005-1015.2012.01.002.
4. Good WV, Early Treatment for Retinopathy of Prematurity Cooperative Group. Final results of the early treatment for retinopathy of prematurity (ETROP) randomized trial[J]. Trans Am Ophthalmol Soc, 2004, 102: 233-248.
5. Mintz-Hittner HA, Kennedy KA, Chuang AZ. Efficacy of intravitreal bevacizumab for stage 3+ retinopathy of prematurity[J]. N Engl J Med, 2011, 364(7): 603-615. DOI: 10.1056/NEJMoa1007374.
6. Stahl A, Lepore D, Fielder A, et al. Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): an open-label randomised controlled study[J]. Lancet, 2019, 394(10208): 1551-1559. DOI: 10.1016/S0140-6736(19)31344-3.
7. Feng J, Qian J, Jiang Y, et al. Efficacy of primary intravitreal ranibizumab for retinopathy of prematurity in China[J]. Ophthalmology, 2017, 124(3): 408-409. DOI: 10.1016/j.ophtha.2016.10.032.
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.Chen Y, Lian JH, Li XX. Intravitreal injection of conbercept for aggressive posterior retinopathy of prematurity[J]. Chin J Ocul Fundus Dis, 2017, 33(2): 144-147. DOI: 10.3760/cma.j.issn.1005-1015.2017.02.008.
9. 许宇, 张琦, 季迅达, 等. 玻璃体腔注射抗血管内皮生长因子单克隆抗体ranibizumab联合激光光凝治疗急进性后部型早产儿视网膜病变的疗效观察[J]. 中华眼底病杂志, 2014, 30(1): 28-32. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.008.Xu Y, Zhang Q, Ji XD, et al. Combination of intravitreal injection of ranibizumab and laser photocoagulation for the treatment of aggressive posterior retinopathy of prematurity[J]. Chin J Ocul Fundus Dis, 2014, 30(1): 28-32. DOI: 10.3760/cma.j.issn.1005-1015.2014.01.008.
10. Xu Y, Zhang Q, Kang X, et al. Early vitreoretinal surgery on vascularly active stage 4 retinopathy of prematurity through the preoperative intravitreal bevacizumab injection[J/OL]. Acta Ophthalmol, 2013, 91(4): e304-310[2013-05-07]. https://pubmed.ncbi.nlm.nih.gov/23647944/. DOI: 10.1111/aos.12055.
11. 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.
12. Lyu J, Zhang Q, Jin H, et al. Aqueous cytokine levels associated with severity of type 1 retinopathy of prematurity and treatment response to ranibizumab[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(8): 1469-1477. DOI: 10.1007/s00417-018-4034-5.
13. 陈宜, 冯婧, 孟宪芬, 等. 玻璃体腔注射雷珠单抗治疗早产儿视网膜病变疗效观察[J]. 中华眼底病杂志, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.Chen Y, Feng J, Meng XF, et al. Effects of ranibizumab in zone Ⅰ and zone Ⅱ retinopathy of prematurity patients[J]. Chin J Ocul Fundus Dis, 2015, 31(1): 6-9. DOI: 10.3760/cma.j.issn.1005-1015.2015.01.003.
14. Zhang Q, Qi Y, Chen L, et al. The relationship between anti-vascular endothelial growth factor and fibrosis in proliferative retinopathy: clinical and laboratory evidence[J]. Br J Ophthalmol, 2016, 100(10): 1443-1450. DOI: 10.1136/bjophthalmol-2015-308199.
15. Honda S, Hirabayashi H, Tsukahara Y, et al. Acute contraction of the proliferative membrane after an intravitreal injection of bevacizumab for advanced retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2008, 246(7): 1061-1063. DOI: 10.1007/s00417-008-0786-7.
16. Huang Q, Zhang Q, Xu Y, et al. Asymmetric outcomes of type 1 retinopathy of prematurity after bilateral intravitreal ranibizumab treatment[J/OL]. J Ophthalmol, 2017, 2017: 1741386[2017-03-29].https://pubmed.ncbi.nlm.nih.gov/28465833/. DOI: 10.1155/2017/1741386.
17. Chiang MF, Quinn GE, Fielder AR, et al. International classification of retinopathy of prematurity, third edition[J/OL]. Ophthalmology, 2021: 128(10): e51-e68[2021-07-08]. https://pubmed.ncbi.nlm.nih.gov/34247850/. DOI: 10.1016/j.ophtha.2021.05.031.
18. 黎晓新. 我国早产儿视网膜病变特点和筛查指南[J]. 中华眼底病杂志, 2004, 20(6): 384-386. DOI: 10.3760/j.issn:1005-1015.2004.06.020.Li XX. Characteristics and screening guidelines of retinopathy of prematurity in my country[J]. Chin J Ocul Fundus Dis, 2004, 20(6): 384-386. DOI: 10.3760/j.issn:1005-1015.2004.06.020.
19. 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): 1684-1694. DOI: 10.1001/archopht.121.12.1684.
20. Van Geest RJ, Lesnik-Oberstein SY, Tan HS, 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]. Br J Ophthalmol, 2012, 96(4): 587-590. DOI: 10.1136/bjophthalmol-2011-301005.
21. Avery RL, Pieramici DJ, Rabena MD, et al. Intravitreal bevacizumab (Avastin) for neovascular age-related macular degeneration[J]. Ophthalmology, 2006, 113(3): 363-372.e5. DOI: 10.1016/j.ophtha.2005.11.019.
22. Spaide RF, Laud K, Fine HF, et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration[J]. Retina, 2006, 26(4): 383-390. DOI: 10.1097/01.iae.0000238561.99283.0e.
23. Salman AG, Said AM. Structural, visual and refractive outcomes of intravitreal aflibercept injection of high-risk prethreshold type 1 retinopathy of prematurity[J]. Ophthalmic Res, 2015, 53(1): 15-20. DOI: 10.1159/000364809.
24. Sukgen EA, Kocluk Y. Comparision of clinical outcomes of intravitreal ranibizumab and aflibercept treatment for retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2019, 257(1): 49-55. DOI: 10.1007/s00417-018-4168-5.
25. Cheng Y, Meng Q, Linghu D, et al. A lower dose of intravitreal conbercept effectively treats retinopathy of prematurity[J/OL]. Sci Rep, 2018, 8(1): 10732[2018-07-16]. https://pubmed.ncbi.nlm.nih.gov/30013230/. DOI: 10.1038/s41598-018-28987-6.
26. Cheng Y, Zhu X, Linghu D, et al. Comparison of the effectiveness of conbercept and ranibizumab treatment for retinopathy of prematurity[J/OL]. Acta Ophthalmol, 2020, 98(8): e1004-e1008[2020-05-08].https://pubmed.ncbi.nlm.nih.gov/32385940/. DOI: 10.1111/aos.14460.
27. 中华医学会眼科学分会眼底病学组. 我国视网膜病玻璃体腔注药术质量控制标准[J]. 中华眼科杂志, 2015, 51(12): 892-895. DOI: 10.3760/cma.j.issn.0412-4081.2015.12.005.Fundus Disease Group of Chinese Medical Association Ophthalmology Branch. Quality control standards for intravitreal injection of retinopathy in China[J]. Chin J Ophthalmol, 2015, 51(12): 892-895. DOI: 10.3760/cma.j.issn.0412-4081.2015.12.005.

Chinese Journal of Ocular Fundus Diseases

Expert consensus on intravitreal injection of anti-vascular endothelial growth factor drugs for retinopathy of prematurity

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