Comparison of the effect of intravitreal injection of conbercept with different doses in the treatment of retinopathy of prematurity_Chinese Journal of Ocular Fundus Diseases

Authors：

 Zhang Haitao , Yang Xin , Wan Suhua , Xu Yingying

Henan Provincial People's Hospital, Henan Eye Hospital, Henan Eye Institute, People's Hospital of Zhengzhou University, School of Medicine Henan University, Zhengzhou 450003, China;

Corresponding author：

Zhang Haitao, Email: zhanght525@163.com

Keywords：

Retinopathy of prematurity/drug therapy; Angiogenesis inhibitors/therapeutic use

DOI：

10.3760/cma.j.cn511434-20200219-00066

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Objective To observe the effect of intravitreal injection of Conbercept with two different doses in the treatment of retinopathy of prematurity (ROP）and explore the clinical feasibility of ROP treatment by lower dose conbercept.Methods This was a prospective study. The premature infants were enrolled with pre-threshold type 1, threshold and acute aggressive posterior retinopathy of prematurity (AP-ROP) from March 2018 to June 2019, who received fundus screening in neonatal intensive care unit (NICU) of Henan Provincial People's Hospital, Henan Eye Hospital. They were randomly divided into two groups. The group A (lower dose group) were received intravitreal injection of conbercept with 0.15 mg/0.015 ml, and those in group B (control group) were received intravitreal injection of conbercept with 0.25 mg/0.025 ml. We checked and recorded the lesion area, stage, scope (according to the clock range), additional lesion (plus), etc. Fundus examination should be performed with the pediatric wide-field fundus imaging system within 7 days after treatment. It was used to observe the plus disese, ridge, regression of neovascularization on ridge, and development of retinal vessels to serrated edge or scarring. The follow-up period was at least 24 weeks. The effect evaluation was divided into recovery, improvement, recurrence and aggravation.Results The 43 ROP subjects (84 eyes) were enrolled including 21 cases (40 eyes) in group A and 22 (44 eyes) in group B. There was no significant difference between the two groups in gender (χ²=1.169), birth age (t=0.283), birth weight (t=0.547), hospitalization days in NICU (t=1.187), first examination time (t=1.811), first injection time (t=0.492), follow-up time (t=0.899) and ROP condition (χ²=0.854) (P>0.05). In group A, 21 eyes (52.5%) were cured, 17 eyes (42.5%) were improved, 2 eyes (5.0%) were recurred, and no aggravating cases were found. In group B, 24 eyes (54.5%) were cured, 14 eyes (31.8%) were improved, 6 eyes (13.6%) were recurred, and no aggravating cases were found. There was no significant difference of the cure rate (χ²=2.210, P>0.05) and effective (recovery and improvement) rate (χ²=1.814, P=0.269）between two groups after the first injection.Conclusion Intravitreal injection of conbercept with the two doses should be effective in the treatment of ROP.

Citation： Zhang Haitao, Yang Xin, Wan Suhua, Xu Yingying. Comparison of the effect of intravitreal injection of conbercept with different doses in the treatment of retinopathy of prematurity. Chinese Journal of Ocular Fundus Diseases, 2020, 36(8): 595-599. doi: 10.3760/cma.j.cn511434-20200219-00066 Copy

1.	Huang CY, Lien R, Wang NK, et al. Changes in systemic vascular endothelial growth factor levels after intravitreal injection of aflibercept in infants with retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(3): 479-487. DOI: 10.1007/s00417-017-3878-4.
2.	Kong L, Bhatt AR, Demny AB, et al. Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity[J]. Invest Ophthalmol Vis Sci, 2015, 56(2): 956-961. DOI: 10.1167/iovs.14-15842.
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.	Sankar MJ, Sankar J, Chandra P. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity[CD]. Cochrane Database Syst Rev, 2018, 1(1): CD009734[2018-01-08]. http://europepmc.org/article/MED/29308602. DOI: 10.1002/14651858.CD009734.pub3.
5.	Wu AL, Wu WC. Anti-VEGF for ROP and pediatric retinal diseases[J]. Asia Pac J Ophthalmol(Phila), 2018, 7(3): 145-151. DOI: 10.22608/APO.201837.
6.	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.
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.	Stahl A, Krohne TU, Eter N, et al. Comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity: a randomized clinical trial[J]. JAMA Pediatr, 2018, 172(3): 278-286. DOI: 10.1001/jamapediatrics.2017.4838.
9.	Bai Y, Nie H, Wei S, et al. Efficacy of intravitreal conbercept injection in the treatment of retinopathy of prematurity[J]. Br J Ophthalmol, 2019, 103(4): 494-498. DOI: 10.1136/bjophthalmol-2017-311662.
10.	Jin E, Yin H, Li X, et al. Short-term outcomes after intravitreal injections of conbercept versus ranibizumab for the treatment of retinopathy of prematurity[J]. Retina, 2018, 38(8): 1595-1604. DOI: 10.1097/IAE.0000000000001763.
11.	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.Cheng Y, Liang 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.
12.	张海涛, 万素华, 靳玮, 等. 康柏西普玻璃体腔注射治疗早产儿视网膜病变的疗效观察及其影响因素分析[J]. 中华眼底病杂志, 2019, 35(2): 171-175. DOI: 10.3760/cma.j.issn.1005-1015.2019.02.012.Zhang HT, Wan SH, Jin W, et al. Efficacy and related factors of intravitreal injection with conbercept for retinopathy of premature[J]. Chin J Ocul Fundus Dis, 2019, 35(2): 171-175. DOI: 10.3760/cma.j.issn.1005-1015.2019.02.012.
13.	International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited[J]. Arch Ophthalmol, 2005, 123(7): 991-999. DOI: 10.1001/archopht.123.7.991.
14.	Harder BC, von Baltz S, Jonas JB, et al. Intravitreal low-dosage bevacizumab for retinopathy of prematurity[J]. Acta Ophthalmol, 2014, 92(6): 577-581. DOI: 10.1111/aos.12266.
15.	Hillier RJ, Connor AJ, Shafiq AE. Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series[J]. Br J Ophthalmol, 2018, 102(2): 260-264. DOI: 10.1136/bjophthalmol-2017-310408.
16.	Han J, Kim SE, Lee SC, et al. Low dose versus conventional dose of intravitreal bevacizumab injection for retinopathy of prematurity: a case series with paired-eye comparison[J]. Acta Ophthalmol, 2018, 96(4): 475-478. DOI: 10.1111/aos.13004.
17.	Wallace DK, Kraker RT, Freedman SF, et al. Assessment of lower doses of intravitreous bevacizumab for retinopathy of prematurity: a phase 1 dosing study[J]. JAMA Ophthalmol, 2017, 135(6): 654-656. DOI: 10.1001/jamaophthalmol.2017.1055.
18.	Wallace DK, Dean TW, Hartnett ME, et al. A dosing study of bevacizumab for retinopathy of prematurity: late recurrences and additional treatments[J]. Ophthalmology, 2018, 125(12): 1961-1966. DOI: 10.1016/j.ophtha.2018.05.001.
19.	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://www.nature.com/articles/s41598-018-28987-6. DOI: 10.1038/s41598-018-28987-6.

1. Huang CY, Lien R, Wang NK, et al. Changes in systemic vascular endothelial growth factor levels after intravitreal injection of aflibercept in infants with retinopathy of prematurity[J]. Graefe's Arch Clin Exp Ophthalmol, 2018, 256(3): 479-487. DOI: 10.1007/s00417-017-3878-4.
2. Kong L, Bhatt AR, Demny AB, et al. Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity[J]. Invest Ophthalmol Vis Sci, 2015, 56(2): 956-961. DOI: 10.1167/iovs.14-15842.
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. Sankar MJ, Sankar J, Chandra P. Anti-vascular endothelial growth factor (VEGF) drugs for treatment of retinopathy of prematurity[CD]. Cochrane Database Syst Rev, 2018, 1(1): CD009734[2018-01-08]. http://europepmc.org/article/MED/29308602. DOI: 10.1002/14651858.CD009734.pub3.
5. Wu AL, Wu WC. Anti-VEGF for ROP and pediatric retinal diseases[J]. Asia Pac J Ophthalmol(Phila), 2018, 7(3): 145-151. DOI: 10.22608/APO.201837.
6. 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.
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. Stahl A, Krohne TU, Eter N, et al. Comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity: a randomized clinical trial[J]. JAMA Pediatr, 2018, 172(3): 278-286. DOI: 10.1001/jamapediatrics.2017.4838.
9. Bai Y, Nie H, Wei S, et al. Efficacy of intravitreal conbercept injection in the treatment of retinopathy of prematurity[J]. Br J Ophthalmol, 2019, 103(4): 494-498. DOI: 10.1136/bjophthalmol-2017-311662.
10. Jin E, Yin H, Li X, et al. Short-term outcomes after intravitreal injections of conbercept versus ranibizumab for the treatment of retinopathy of prematurity[J]. Retina, 2018, 38(8): 1595-1604. DOI: 10.1097/IAE.0000000000001763.
11. 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.Cheng Y, Liang 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.
12. 张海涛, 万素华, 靳玮, 等. 康柏西普玻璃体腔注射治疗早产儿视网膜病变的疗效观察及其影响因素分析[J]. 中华眼底病杂志, 2019, 35(2): 171-175. DOI: 10.3760/cma.j.issn.1005-1015.2019.02.012.Zhang HT, Wan SH, Jin W, et al. Efficacy and related factors of intravitreal injection with conbercept for retinopathy of premature[J]. Chin J Ocul Fundus Dis, 2019, 35(2): 171-175. DOI: 10.3760/cma.j.issn.1005-1015.2019.02.012.
13. International Committee for the Classification of Retinopathy of Prematurity. The International Classification of Retinopathy of Prematurity revisited[J]. Arch Ophthalmol, 2005, 123(7): 991-999. DOI: 10.1001/archopht.123.7.991.
14. Harder BC, von Baltz S, Jonas JB, et al. Intravitreal low-dosage bevacizumab for retinopathy of prematurity[J]. Acta Ophthalmol, 2014, 92(6): 577-581. DOI: 10.1111/aos.12266.
15. Hillier RJ, Connor AJ, Shafiq AE. Ultra-low-dose intravitreal bevacizumab for the treatment of retinopathy of prematurity: a case series[J]. Br J Ophthalmol, 2018, 102(2): 260-264. DOI: 10.1136/bjophthalmol-2017-310408.
16. Han J, Kim SE, Lee SC, et al. Low dose versus conventional dose of intravitreal bevacizumab injection for retinopathy of prematurity: a case series with paired-eye comparison[J]. Acta Ophthalmol, 2018, 96(4): 475-478. DOI: 10.1111/aos.13004.
17. Wallace DK, Kraker RT, Freedman SF, et al. Assessment of lower doses of intravitreous bevacizumab for retinopathy of prematurity: a phase 1 dosing study[J]. JAMA Ophthalmol, 2017, 135(6): 654-656. DOI: 10.1001/jamaophthalmol.2017.1055.
18. Wallace DK, Dean TW, Hartnett ME, et al. A dosing study of bevacizumab for retinopathy of prematurity: late recurrences and additional treatments[J]. Ophthalmology, 2018, 125(12): 1961-1966. DOI: 10.1016/j.ophtha.2018.05.001.
19. 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://www.nature.com/articles/s41598-018-28987-6. DOI: 10.1038/s41598-018-28987-6.

Chinese Journal of Ocular Fundus Diseases

Comparison of the effect of intravitreal injection of conbercept with different doses in the treatment of retinopathy of prematurity

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