Efficacy and related factors of intravitreal injection with conbercept for retinopathy of premature_Chinese Journal of Ocular Fundus Diseases

Authors：

 Zhang Haitao , Wan Suhua , Jin Wei , 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; Antibodies, monoclonal/therapeutic use; Root cause analysis

DOI：

10.3760/cma.j.issn.1005-1015.2019.02.012

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ObjectiveTo observe the effect of intravitreal injection of conbercept in the treatment of retinopathy of premature (ROP) and to analyze the factors related to the therapy.MethodsA retrospective study. A total of 57 patients (57 eyes) with pre-threshold type 1 (30 patients, 30 eyes), threshold ROP (21 patients, 21 eyes) and acute aggressive posterior ROP (APROP, 6 patients, 6 eyes)) from premature infants by retinal screening in Henan Provincial People’s Hospital during October 2017 and June 2018 were enrolled in this study. All children were received routinely intravitreal injected 10 mg/ml conbercept 0.025 ml (0.25 mg) within 24 hours after diagnosis. Fundus examination was performed 7 days after injection. The interval of examination was 1−3 weeks according to fundus conditions. The mean follow-up was 30.1±4.6 weeks. For patients with relapse or no response to treatment, repeated intravitreal injection of conbercept or laser photocoagulation therapy was given. The retinal blood vessels of the affected eyes were observed. Logistic stepwise regression analysis was used for the correlation test of multiple factors.ResultsAmong 57 eyes, 49 eyes and 8 eyes were treated with 1 or 2 times of intravitreal injection of conbercept. After 24 weeks of treatment, in 57 eyes, 26 eyes were cured (45.6%), 22 eyes improved (38.6%), 8 eyes relapsed (14.0%), and 1 eye aggravated (1.8%). The recurrence time was 12.9±4.5 weeks after the first injection, and the corrected gestational age was 49.0±6.7 weeks. There were significant differences in initial injection time, lesion range among the cure, improved and recurrence eyes (F=5.124, 7.122; P＜0.01, ＜0.01). Parameters of ROP condition, including ROP diagnosis (pre-threshold type 1, threshold and APROP), zone (zone 1 and 2), stage (stage 2 and 3) and plus lesions, were significant different among the cure, improved and recurrence eyes (χ²=11.784, 14.100, 6.896, 9.935; P＜0.01, ＜0.01, ＜0.05, ＜0.01). Logistic stepwise regression analysis showed that the recurrence rate was correlated with ROP zone, more likely recurrence at zone 1 than zone 2 (Wald=9.879, OR=27.333, P=0.002). No injection-related complications such as endophthalmitis, cataract and glaucoma were found during treatment and follow-up period.ConclusionsIntravitreal injection of conbercept is effective in the treatment of ROP without obvious adverse reactions. Lesion zoning is associated with recurrence after treatment.

Citation： Zhang Haitao, Wan Suhua, Jin Wei, Xu Yingying. Efficacy and related factors of intravitreal injection with conbercept for retinopathy of premature. Chinese Journal of Ocular Fundus Diseases, 2019, 35(2): 171-175. doi: 10.3760/cma.j.issn.1005-1015.2019.02.012 Copy

1.	Geisen P, Peterson LJ, Mariniuk D, et al. Neutralizing antibody to VEGF reduces intravitreous neovascularization and may not interfere with ongoing intraretinal vascularization in a rat model of retinopathy of prematurity[J]. Mol Vis, 2008, 14(11): 345-357.
2.	Wang H, Yang Z, Jiang Y, et al. Quantitative analyses of retinal vascular area and density after different methods to reduce VEGF in a rat model of retinopathy of prematurity[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 737-744. DOI: 10.1167/iovs.13-13429.
3.	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.
4.	Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors[J]. Early Hum Dev, 2012, 88(12): 937-941. DOI: 10.1016/j.earlhumdev.2012.09.019.
5.	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(1): 150-158. DOI: 10.1016/j.ajo.2012.06.010.
6.	Nicoară SD, Nascutzy C, Cristian C, et al. Outcomes and prognostic factors of intravitreal bevacizumab monotherapy in zone Ⅰ stage 3+ and aggressive posterior retinopathy of prematurity[J/OL]. J Ophthalmol, 2015, 2015: 102582[2015-09-27]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600496/. DOI: 10.1155/2015/102582.
7.	Karkhaneh R, Khodabande A, Riazi-Eafahani M, et al. Efficacy of intravitreal bevacizumab for zone-Ⅱretinopathy of prematurity[J]. Acta Ophthalmol, 2016, 94(6): 417-420. DOI: 10.1111/aos.13008.
8.	VanderVeen DK, Melia M, Yang MB, et al. Anti-vascular endothelial growth factor therapy for primary treatment of type 1 retinopathy of prematurity:a report by the American Academy of Ophthalmology[J]. Ophthalmology, 2017, 124(5): 619-633. DOI: 10.1016/j.ophtha.2016.12.025.
9.	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.
10.	Bai Y, Nie H, Wei S, et al. Efficacy of intravitreal conbercept injection in the treatment of retinopathy of prematurity[J/OL]. Br J Ophthalmol, 2018, 2018: E1[2018-07-20]. http://dx.doi.org/10.1136/bjophthalmol-2017-311662. DOI: 10.1136/bjophthalmol-2017-311662. [published online ahead of print].
11.	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.
12.	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.
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.	Moran S, O’Keefe M, Hartnett C, et al. Bevacizumab versus diode laser in stage 3 posterior retinopathy of prematurity[J]. Acta Ophthalmol, 2014, 92(6): 496-497. DOI: 10.1111/aos.12339.
15.	Gunay M, Sukgen EA, Celik G, et al. Comparison of Bevacizumab,Ranibizumab, and laser photocoagulation in the treatment of retinopathy of prematurity in Turkey[J]. Curr Eye Res, 2017, 42(3): 462-429. DOI: 10.1080/02713683.2016.1196709.
16.	Mueller B, Salchow DJ, Waffenschmidt E, et al. Treatment of type I ROP with intravitreal bevacizumab or laser photocoagulation according to retinal zone[J]. Br J Ophthalmol, 2017, 101(3): 365-370. DOI: 10.1136/bjophthalmol-2016-308375.
17.	Hu Q, Bai Y, Chen X, et al. Recurrence of retinopathy of prematurity in zone Ⅱ stage 3+ after Ranibizumab Treatment: a retrospective study[J/OL]. J Ophthalmol, 2017, 2017: 5078565 [2017-04-09]. https://doi.org/10.1155/2017/5078565. DOI: 10.1155/2017/5078565.
18.	Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical management of recurrent retinopathy of prematurity after intravitreal bevacizumab monotherapy[J]. Ophthalmology, 2016, 123(9): 1845-1855. DOI: 10.1016/j.ophtha.2016.04.028.
19.	Klaassen I, van Geest RJ, Kuiper EJ, et al. The role of CTGF in diabetic retinopathy[J]. Exp Eye Res, 2015, 133: 37-48. DOI: 10.1016/j.exer.2014.10.016.
20.	Hartnett ME. Vascular endothelial growth factor antagonist therapy for retinopathy of prematurity[J]. Clin Perinatol, 2014, 41(4): 925-943. DOI: 10.1016/j.clp.2014.08.011.
21.	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.
22.	Cheng Y, Meng Q, Linghu D, et al. A lower dose of intravitreal conbercept effectively treats retinopathy of prematurity[J]. Sci Rep, 2018, 8(1): 10732. DOI: 10.1038/s41598-018-28987-6.

1. Geisen P, Peterson LJ, Mariniuk D, et al. Neutralizing antibody to VEGF reduces intravitreous neovascularization and may not interfere with ongoing intraretinal vascularization in a rat model of retinopathy of prematurity[J]. Mol Vis, 2008, 14(11): 345-357.
2. Wang H, Yang Z, Jiang Y, et al. Quantitative analyses of retinal vascular area and density after different methods to reduce VEGF in a rat model of retinopathy of prematurity[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 737-744. DOI: 10.1167/iovs.13-13429.
3. 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.
4. Mintz-Hittner HA. Treatment of retinopathy of prematurity with vascular endothelial growth factor inhibitors[J]. Early Hum Dev, 2012, 88(12): 937-941. DOI: 10.1016/j.earlhumdev.2012.09.019.
5. 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(1): 150-158. DOI: 10.1016/j.ajo.2012.06.010.
6. Nicoară SD, Nascutzy C, Cristian C, et al. Outcomes and prognostic factors of intravitreal bevacizumab monotherapy in zone Ⅰ stage 3+ and aggressive posterior retinopathy of prematurity[J/OL]. J Ophthalmol, 2015, 2015: 102582[2015-09-27]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4600496/. DOI: 10.1155/2015/102582.
7. Karkhaneh R, Khodabande A, Riazi-Eafahani M, et al. Efficacy of intravitreal bevacizumab for zone-Ⅱretinopathy of prematurity[J]. Acta Ophthalmol, 2016, 94(6): 417-420. DOI: 10.1111/aos.13008.
8. VanderVeen DK, Melia M, Yang MB, et al. Anti-vascular endothelial growth factor therapy for primary treatment of type 1 retinopathy of prematurity:a report by the American Academy of Ophthalmology[J]. Ophthalmology, 2017, 124(5): 619-633. DOI: 10.1016/j.ophtha.2016.12.025.
9. 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.
10. Bai Y, Nie H, Wei S, et al. Efficacy of intravitreal conbercept injection in the treatment of retinopathy of prematurity[J/OL]. Br J Ophthalmol, 2018, 2018: E1[2018-07-20]. http://dx.doi.org/10.1136/bjophthalmol-2017-311662. DOI: 10.1136/bjophthalmol-2017-311662. [published online ahead of print].
11. 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.
12. 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.
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. Moran S, O’Keefe M, Hartnett C, et al. Bevacizumab versus diode laser in stage 3 posterior retinopathy of prematurity[J]. Acta Ophthalmol, 2014, 92(6): 496-497. DOI: 10.1111/aos.12339.
15. Gunay M, Sukgen EA, Celik G, et al. Comparison of Bevacizumab,Ranibizumab, and laser photocoagulation in the treatment of retinopathy of prematurity in Turkey[J]. Curr Eye Res, 2017, 42(3): 462-429. DOI: 10.1080/02713683.2016.1196709.
16. Mueller B, Salchow DJ, Waffenschmidt E, et al. Treatment of type I ROP with intravitreal bevacizumab or laser photocoagulation according to retinal zone[J]. Br J Ophthalmol, 2017, 101(3): 365-370. DOI: 10.1136/bjophthalmol-2016-308375.
17. Hu Q, Bai Y, Chen X, et al. Recurrence of retinopathy of prematurity in zone Ⅱ stage 3+ after Ranibizumab Treatment: a retrospective study[J/OL]. J Ophthalmol, 2017, 2017: 5078565 [2017-04-09]. https://doi.org/10.1155/2017/5078565. DOI: 10.1155/2017/5078565.
18. Mintz-Hittner HA, Geloneck MM, Chuang AZ. Clinical management of recurrent retinopathy of prematurity after intravitreal bevacizumab monotherapy[J]. Ophthalmology, 2016, 123(9): 1845-1855. DOI: 10.1016/j.ophtha.2016.04.028.
19. Klaassen I, van Geest RJ, Kuiper EJ, et al. The role of CTGF in diabetic retinopathy[J]. Exp Eye Res, 2015, 133: 37-48. DOI: 10.1016/j.exer.2014.10.016.
20. Hartnett ME. Vascular endothelial growth factor antagonist therapy for retinopathy of prematurity[J]. Clin Perinatol, 2014, 41(4): 925-943. DOI: 10.1016/j.clp.2014.08.011.
21. 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.
22. Cheng Y, Meng Q, Linghu D, et al. A lower dose of intravitreal conbercept effectively treats retinopathy of prematurity[J]. Sci Rep, 2018, 8(1): 10732. DOI: 10.1038/s41598-018-28987-6.

Chinese Journal of Ocular Fundus Diseases

Efficacy and related factors of intravitreal injection with conbercept for retinopathy of premature

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