The efficacy of intravitreal conbercept for macular edema secondary to retinal vein occlusion_Chinese Journal of Ocular Fundus Diseases

Authors：

MaoJianbo , ChuMengqi , ChenYiqi , ZhengBin , ZhangYun ,  ShenLijun

Eye Hospital of Wenzhou Medical University, Whenzhou 325027, China;

Corresponding author：

ShenLijun, Email: 13868302929@139.com

Keywords：

Retinal vein occlusion/drug therapy; Macular edema/drug therapy; Angiogenesis inhibitors/therapeutic use; Antibodies,monoclonal/therapeutic use; Tomography,optical coherence

DOI：

10.3760/cma.j.issn.1005-1015.2016.04.007

Video：

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Objective To investigate the effects of intravitreous injection of conbercept for macular edema secondary to retina1vein occlusion(RVO) during 6 months period. Methods A retrospective clinical study. 34 patients (34 eyes) were included in this study,who were diagnosed with macular edema due to retinal vein occlusion by ophthalmologic examination, fundus photography, optical coherence tomography (OCT), fundus fluorescein angiography and other methods. The best corrected visual acuity (BCVA) was examined using the international standard visual acuity chart, and the results were converted to the logMAR visual acuity. The average logMAR BCVA was 0.90±0.68, and the mean macular central retinal thickness (CMT) was (672.27±227.51) μm before treatment. All subjects received intravitreal injection of 0.5 mg conbercept (0.05 ml) at the first visit. Injections were repeated based on the visual acuity changes and the OCT findings. 34 eyes received 69 times of injection, the average number of injections was 2.03±1.03. BCVA, OCT were examined before and after treatment using the same method. BCVA and CMT changes, drugs and treatments associated cardiac and cerebral vascular accident, intraocular pressure elevation, retinal tears, retinal detachment, endophthalmitis and other complications after treatment were observed. Linear correlation analysis was used to analyze the correlation between prognosis BCVA and baseline BCVA, correlation between prognosis BCVA and baseline CMT, and also correlation between BCVA and CMT at different time points before and after treatment. Results At 1 week and 1, 2,3, 6 months after treatment, the average logMAR BCVA was 0.65±0.61, 0.56±0.61, 0.46±0.55, 0.56±0.71, 0.44±0.48 respectively. During 1, 2, 3, 6 months after treatment, the mean logMAR BCVA were improved with statistically significant difference (Z=34.029, 47.294, 41.338, 43.603;P < 0.05), while 1 week after treatment showed no obvious improvement (Z=21.941,P > 0.05). At 1 week and 1, 2, 3, 6 months after treatment, the average CMT was (285.89±96.69), (256.65±143.39), (278.68±156.92), (290.11±188.17), (217.15±48.04) μm respectively. At 1 week and 1,2,3,6 months after treatment, the mean CMT were all decreased with statistically significant difference (Z=68.500, 98.735, 93.235, 91.132, 109.162; P < 0.05). There was a positive correlation between the prognosis visual acuity and preoperative visual acuity (r=0.682,P < 0.05). However,there was no correlation between the prognosis vision and the degree of macular edema before treatment (r=0.078,P > 0.05). Before and 3, 6 months after treatment, BCVA was negatively correlated with CMT (r=0.491, 0.416, 0.386; P < 0.05), while there was no correlation in other time points (r=0.145, 0.217, 0.177; P > 0.05). Systemic adverse reactions and persistent intraocular pressure elevation, iatrogenic cataract, retinal detachment, retinal tear, endophthalmitis and ocular complications were never found in the follow-up period. Conclusion Intravitreal conbercept is a safe and effective approach for RVO,which can significantly improve visual acuity and reduce CMT.

Citation： MaoJianbo, ChuMengqi, ChenYiqi, ZhengBin, ZhangYun, ShenLijun. The efficacy of intravitreal conbercept for macular edema secondary to retinal vein occlusion. Chinese Journal of Ocular Fundus Diseases, 2016, 32(4): 372-376. doi: 10.3760/cma.j.issn.1005-1015.2016.04.007 Copy

1.	Hirashima T,Chihara T,Bun T,et al.Intravitreal bevacizumab alone or combined with macular laser photcoagu1ation for recurrent or persistent macular edema secondary to branch retinal vein occlusion[J/OL]. J Ophthalmol, 2014,2014:173084[2014-07-07]. http://dx.doi.org/10.1155/2014/173084. DOI:10.1155/2014/173084.
2.	Tan MH,McAllister IL,Gillies ME,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.
3.	王雯秋, 王泓,姜媛,等. 玻璃体腔内注射Bevacizumab联合眼底激光治疗视网膜静脉阻塞继发黄斑水肿的临床观察[J]. 中华眼视光学与视觉科学杂志,2012,14(2):90-94. DOI:10.3760/cma.j.issn.1674-845X.2012.02.007. Wang WQ, Wang H, Jiang Y, et al. Clinical observation of intravitreal Bevacizumab combined with laser photocoagulation for treatment of macular edema secondary to retinal vein occlusion[J].Chin J Ophthalmol Vis Sci, 2012,14(2):90-94. DOI:10.3760/cma.j.issn.1674-845X.2012.02.007.
4.	钱彤, 黎晓新,尹虹,等. 玻璃体腔注射avastin治疗视网膜分支静脉阻塞继发黄斑水肿疗效观察[J].眼科研究,2010,28(1):79-82. DOI:10.3969/j.issn.1003-0808.2010.01.021. Qian T, Li XX, Yin H, et al. The clinical study on intravitreous injection of avastin for macular edema induced by branch retinal vein occlusion[J].Chin Ophthal Res,2010,28(1):79-82. DOI:10.3969/j.issn.1003-0808.2010.01.021.
5.	张军军, 张美霞.湿性年龄相关性黄斑变性治疗方法的新选择[J].中华实验眼科杂志,2012,30(11):961-964.DOI:10.3760/cma.j.issn.2095-0160.2012.11.001. Zhang JJ, Zhang MX. Choice of the treating methods of neovascular age-related macular degeneration[J].Chin J Exp Ophthalmol, 2012,30(11):961-964. DOI:10.3760/cma.j.issn.2095-0160.2012.11.001.
6.	Wang Q, Li T, Wu Z, et al. Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable anti-angiogenesis effect in vivo[J/OL]. PLoS One, 2013,12,8(8):70544[2013-08-12]. http://dx.plos.org/10.1371/journal.pone.0070544. DOI:10.1371/journal.pone.0070544.
7.	Li X, Xu G, Wang Y,et al.Safety and efficacy of conbercept in neovascular age-related macular degeneration:results from a 12-month randomized phase 2 study:AURORA study[J].Ophthalmology, 2014,121(9):1740-1747. DOI:10.1016/j.ophtha.2014.03.026.
8.	Zhang M,Zhang JJ,Yan M,et al. A phase 1 study of KH902,a vascular endothelial growth factor receptor decoy,for exudative age-related macular degeneration[J]. Ophthalmology, 2011, 118(4):672-678.DOI:10.1016/j.ophtha.2010.08.008.
9.	张菁, 蔡小军,陈晓敏,等. 玻璃体腔注射康柏西普联合视网膜激光光凝治疗视网膜分支静脉阻塞继发黄斑水肿疗效观察[J].中华眼底病杂志,2015,31(1):22-26. DOI:10.3760/cma.j.issn.1005-1015.2015.01.007. Zhang J, Cai XJ, Chen XM, et al. A prospective randomized clinical trial on intravitreous injection of Conbercept combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion[J].Chin J Ocul Fundus Dis, 2015, 31(1):22-26. DOI:10.3760/cma.j.issn.1005-1015.2015.01.007.
10.	Timothy L, Jackson M. Manual of ophthalmology[M].Amsterdam:Elsevier Science Health Science div,2011:471-474.
11.	王彬, 贾淑琴,霍建新.视网膜静脉阻塞的诊断与治疗研究进展[J].国际眼科杂志,2014,7(14):1227-1230.DOI:10.3980/j.issn.1672-5123,2014.07.13. Wang B, Jia SQ, Huo JX. Research progress of the diagnosis and treatment for retinal vein occlusion[J].Int Eye Sci,2014,7(14):1227-1230.DOI:10.3980/j.issn.1672-5123,2014.07.13.
12.	Binder S, Aggermann T, Brunner S.Long-term effects of radial optic neurotomy for central retinal vein occlusion consecutive interventional case series[J]. Graefe's Arch Clin Exp Ophthalmol, 2007,245(10):1447-1452.
13.	Papadia M, Misteli M, Jeannin B,et al. The influence of anti-VEGF therapy on present day management of macular edema due to BRVO and CRVO:a longitudinal analysis on visual function, injection time interval and complications[J].Int Ophthalmol,2014, 34(6):1193-1201. DOI:10.1007/s10792-014-0002-1.
14.	Ho AC, Busbee BG, Regillo CD, et al. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascularage-related macular degeneration[J]. Ophthalmology, 2014,121(11):2181-2192.DOI:10.1016/j.ophtha.2014.05.009.
15.	Boyer DS, Heier JS, Brown DM, et al. A phase Ⅲb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration[J]. Ophthalmology, 2009,116(9):1731-1739.DOI:10.1016/j.ophtha.2009.05.024.
16.	Cho HJ, Kim KM, Kim HS,et al.Intravitreal aflibercept and ranibizumab injections for polypoidal choroidal vasculopathy[J]. Am J Ophthalmol, 2016,165:1-6. DOI:10.1016/j.ajo.2016.02.019.
17.	Hikichi T.Individualized ranibizumab therapy strategies in year 3 after as-needed treatment for polypoidal choroidal vasculopathy[J]. BMC Ophthalmol, 2015,10:15-37. DOI:10.1186/s12886-015-0026-y.
18.	Azad SV, Salman A, Mahajan D,et al. Comparative evaluation between ranibizumab combined with laser and bevacizumab combined with laser versus laser alone for macular oedema secondary to branch retinal vein occlusion[J]. Middle East Afr J Ophthalmol, 2014,21(4):296-301.DOI:10.4103/0974-9233.142264.
19.	Brown DM, Wykoff CC, Wong TP, et al. Ranibizumab in preproliferative (ischemic) central retinal vein occlusion:the rubeosis anti-VEGF (RAVE) trial[J]. Retina, 2014,34(9):1728-1735. DOI:10.1097/IAE.0000000000000191.
20.	Ryu CL, Elfersy A, Desai U,et al.The effect of antivascular endothelial growth factor therapy on the development of neovascular glaucoma after central retinal vein occlusion:a retrospective analysis[J/OL]. J Ophthalmol, 2014,2014:317694[2014-04-01]. http://www.hindawi.com/journals/joph/2014/317694/. DOI:10.1155/2014/317694.
21.	Brown DM, Regillo CD. Anti-VEGF agents in the treatment of neovascular age-related macular degeneration:applying clinical trial results to the treatment of everyday patients[J]. Am J Ophthalmol, 2007, 144(4):627-637.
22.	Atmani K, Voigt M, Le Tien V, et al. Ranibizumab for retinal angioma-tous proliferation in age-related macular degeneration[J]. Eye (Lond), 2010,24(7):1193-1198. DOI:10.1038/eye.2010.9.
23.	Mendrinos E, Mangioris G, Papadopoulou D, et al. One year results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration[J/OL]. Invest Ophthalmol Vis Sci, 2011,52:E1[2011-12-13].http://www.ncbi.nlm.nih.gov/pubmed/?term=One+year+results+of+the+effect+of+intravitreal+ranibizumab+on+the+retinal+arteriolar+diameter+in+patients+with+neovascular+age-related+macular+degeneration. DOI:10.1167/iovs.09-3721.[published online ahead of print].
24.	Kriechbaum K, Prager F, Geitzenauer W,et al. Association of retinal sensitivity and morphology during antiangiogenic treatment of retinal vein occlusion overone year[J]. Ophthalmology, 2009,116(12):2415-2421. DOI:10.1016/j.ophtha.2009.05.001.
25.	Busbee BG, Ho AC, Brown DM, et al.Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration[J]. Ophthalmology,2013,120(5):1046-1056. DOI:10.1016/j.ophtha.2012.10.014.
26.	Campochiaro PA, Wykoff CC, Singer M,et al. Monthly versus as needed ranibizumab injections in patients with retinal vein occlusion:the SHORE study[J]. Ophthalmology,2014,121(12):2432-2442.DOI:10.1016/j.ophtha.2014.06.011.
27.	Shah N, Shah UN. Long-term effect of early intervention with single intravitreal injection of bevacizumab followed by panretinal and macular grid photocoagulation in central retinal vein occlusion (CRVO) with macular edema:a pilot study[J]. Eye(Lond), 2011,25(2):239-244. DOI:10.1038/eye.2010.225.
28.	Vujosevic S, Midena E, Pilotto E, et al. Diabetic macular edema:correlation between microperimetry and optical coherence tomography findings[J]. Invest Ophthalmol Vis Sci, 2006,47(7):3044-3051.
29.	Matsumoto Y, Freund KB, Peiretti E, et al.Rebound macular edema following bevacizumab (Avastin) therapy for retinal venous occlusive disease[J]. Retina, 2007,27(4):426-431.

1. Hirashima T,Chihara T,Bun T,et al.Intravitreal bevacizumab alone or combined with macular laser photcoagu1ation for recurrent or persistent macular edema secondary to branch retinal vein occlusion[J/OL]. J Ophthalmol, 2014,2014:173084[2014-07-07]. http://dx.doi.org/10.1155/2014/173084. DOI:10.1155/2014/173084.
2. Tan MH,McAllister IL,Gillies ME,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.
3. 王雯秋, 王泓,姜媛,等. 玻璃体腔内注射Bevacizumab联合眼底激光治疗视网膜静脉阻塞继发黄斑水肿的临床观察[J]. 中华眼视光学与视觉科学杂志,2012,14(2):90-94. DOI:10.3760/cma.j.issn.1674-845X.2012.02.007. Wang WQ, Wang H, Jiang Y, et al. Clinical observation of intravitreal Bevacizumab combined with laser photocoagulation for treatment of macular edema secondary to retinal vein occlusion[J].Chin J Ophthalmol Vis Sci, 2012,14(2):90-94. DOI:10.3760/cma.j.issn.1674-845X.2012.02.007.
4. 钱彤, 黎晓新,尹虹,等. 玻璃体腔注射avastin治疗视网膜分支静脉阻塞继发黄斑水肿疗效观察[J].眼科研究,2010,28(1):79-82. DOI:10.3969/j.issn.1003-0808.2010.01.021. Qian T, Li XX, Yin H, et al. The clinical study on intravitreous injection of avastin for macular edema induced by branch retinal vein occlusion[J].Chin Ophthal Res,2010,28(1):79-82. DOI:10.3969/j.issn.1003-0808.2010.01.021.
5. 张军军, 张美霞.湿性年龄相关性黄斑变性治疗方法的新选择[J].中华实验眼科杂志,2012,30(11):961-964.DOI:10.3760/cma.j.issn.2095-0160.2012.11.001. Zhang JJ, Zhang MX. Choice of the treating methods of neovascular age-related macular degeneration[J].Chin J Exp Ophthalmol, 2012,30(11):961-964. DOI:10.3760/cma.j.issn.2095-0160.2012.11.001.
6. Wang Q, Li T, Wu Z, et al. Novel VEGF decoy receptor fusion protein conbercept targeting multiple VEGF isoforms provide remarkable anti-angiogenesis effect in vivo[J/OL]. PLoS One, 2013,12,8(8):70544[2013-08-12]. http://dx.plos.org/10.1371/journal.pone.0070544. DOI:10.1371/journal.pone.0070544.
7. Li X, Xu G, Wang Y,et al.Safety and efficacy of conbercept in neovascular age-related macular degeneration:results from a 12-month randomized phase 2 study:AURORA study[J].Ophthalmology, 2014,121(9):1740-1747. DOI:10.1016/j.ophtha.2014.03.026.
8. Zhang M,Zhang JJ,Yan M,et al. A phase 1 study of KH902,a vascular endothelial growth factor receptor decoy,for exudative age-related macular degeneration[J]. Ophthalmology, 2011, 118(4):672-678.DOI:10.1016/j.ophtha.2010.08.008.
9. 张菁, 蔡小军,陈晓敏,等. 玻璃体腔注射康柏西普联合视网膜激光光凝治疗视网膜分支静脉阻塞继发黄斑水肿疗效观察[J].中华眼底病杂志,2015,31(1):22-26. DOI:10.3760/cma.j.issn.1005-1015.2015.01.007. Zhang J, Cai XJ, Chen XM, et al. A prospective randomized clinical trial on intravitreous injection of Conbercept combined with laser photocoagulation for macular edema secondary to branch retinal vein occlusion[J].Chin J Ocul Fundus Dis, 2015, 31(1):22-26. DOI:10.3760/cma.j.issn.1005-1015.2015.01.007.
10. Timothy L, Jackson M. Manual of ophthalmology[M].Amsterdam:Elsevier Science Health Science div,2011:471-474.
11. 王彬, 贾淑琴,霍建新.视网膜静脉阻塞的诊断与治疗研究进展[J].国际眼科杂志,2014,7(14):1227-1230.DOI:10.3980/j.issn.1672-5123,2014.07.13. Wang B, Jia SQ, Huo JX. Research progress of the diagnosis and treatment for retinal vein occlusion[J].Int Eye Sci,2014,7(14):1227-1230.DOI:10.3980/j.issn.1672-5123,2014.07.13.
12. Binder S, Aggermann T, Brunner S.Long-term effects of radial optic neurotomy for central retinal vein occlusion consecutive interventional case series[J]. Graefe's Arch Clin Exp Ophthalmol, 2007,245(10):1447-1452.
13. Papadia M, Misteli M, Jeannin B,et al. The influence of anti-VEGF therapy on present day management of macular edema due to BRVO and CRVO:a longitudinal analysis on visual function, injection time interval and complications[J].Int Ophthalmol,2014, 34(6):1193-1201. DOI:10.1007/s10792-014-0002-1.
14. Ho AC, Busbee BG, Regillo CD, et al. Twenty-four-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascularage-related macular degeneration[J]. Ophthalmology, 2014,121(11):2181-2192.DOI:10.1016/j.ophtha.2014.05.009.
15. Boyer DS, Heier JS, Brown DM, et al. A phase Ⅲb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration[J]. Ophthalmology, 2009,116(9):1731-1739.DOI:10.1016/j.ophtha.2009.05.024.
16. Cho HJ, Kim KM, Kim HS,et al.Intravitreal aflibercept and ranibizumab injections for polypoidal choroidal vasculopathy[J]. Am J Ophthalmol, 2016,165:1-6. DOI:10.1016/j.ajo.2016.02.019.
17. Hikichi T.Individualized ranibizumab therapy strategies in year 3 after as-needed treatment for polypoidal choroidal vasculopathy[J]. BMC Ophthalmol, 2015,10:15-37. DOI:10.1186/s12886-015-0026-y.
18. Azad SV, Salman A, Mahajan D,et al. Comparative evaluation between ranibizumab combined with laser and bevacizumab combined with laser versus laser alone for macular oedema secondary to branch retinal vein occlusion[J]. Middle East Afr J Ophthalmol, 2014,21(4):296-301.DOI:10.4103/0974-9233.142264.
19. Brown DM, Wykoff CC, Wong TP, et al. Ranibizumab in preproliferative (ischemic) central retinal vein occlusion:the rubeosis anti-VEGF (RAVE) trial[J]. Retina, 2014,34(9):1728-1735. DOI:10.1097/IAE.0000000000000191.
20. Ryu CL, Elfersy A, Desai U,et al.The effect of antivascular endothelial growth factor therapy on the development of neovascular glaucoma after central retinal vein occlusion:a retrospective analysis[J/OL]. J Ophthalmol, 2014,2014:317694[2014-04-01]. http://www.hindawi.com/journals/joph/2014/317694/. DOI:10.1155/2014/317694.
21. Brown DM, Regillo CD. Anti-VEGF agents in the treatment of neovascular age-related macular degeneration:applying clinical trial results to the treatment of everyday patients[J]. Am J Ophthalmol, 2007, 144(4):627-637.
22. Atmani K, Voigt M, Le Tien V, et al. Ranibizumab for retinal angioma-tous proliferation in age-related macular degeneration[J]. Eye (Lond), 2010,24(7):1193-1198. DOI:10.1038/eye.2010.9.
23. Mendrinos E, Mangioris G, Papadopoulou D, et al. One year results of the effect of intravitreal ranibizumab on the retinal arteriolar diameter in patients with neovascular age-related macular degeneration[J/OL]. Invest Ophthalmol Vis Sci, 2011,52:E1[2011-12-13].http://www.ncbi.nlm.nih.gov/pubmed/?term=One+year+results+of+the+effect+of+intravitreal+ranibizumab+on+the+retinal+arteriolar+diameter+in+patients+with+neovascular+age-related+macular+degeneration. DOI:10.1167/iovs.09-3721.[published online ahead of print].
24. Kriechbaum K, Prager F, Geitzenauer W,et al. Association of retinal sensitivity and morphology during antiangiogenic treatment of retinal vein occlusion overone year[J]. Ophthalmology, 2009,116(12):2415-2421. DOI:10.1016/j.ophtha.2009.05.001.
25. Busbee BG, Ho AC, Brown DM, et al.Twelve-month efficacy and safety of 0.5 mg or 2.0 mg ranibizumab in patients with subfoveal neovascular age-related macular degeneration[J]. Ophthalmology,2013,120(5):1046-1056. DOI:10.1016/j.ophtha.2012.10.014.
26. Campochiaro PA, Wykoff CC, Singer M,et al. Monthly versus as needed ranibizumab injections in patients with retinal vein occlusion:the SHORE study[J]. Ophthalmology,2014,121(12):2432-2442.DOI:10.1016/j.ophtha.2014.06.011.
27. Shah N, Shah UN. Long-term effect of early intervention with single intravitreal injection of bevacizumab followed by panretinal and macular grid photocoagulation in central retinal vein occlusion (CRVO) with macular edema:a pilot study[J]. Eye(Lond), 2011,25(2):239-244. DOI:10.1038/eye.2010.225.
28. Vujosevic S, Midena E, Pilotto E, et al. Diabetic macular edema:correlation between microperimetry and optical coherence tomography findings[J]. Invest Ophthalmol Vis Sci, 2006,47(7):3044-3051.
29. Matsumoto Y, Freund KB, Peiretti E, et al.Rebound macular edema following bevacizumab (Avastin) therapy for retinal venous occlusive disease[J]. Retina, 2007,27(4):426-431.

Chinese Journal of Ocular Fundus Diseases

The efficacy of intravitreal conbercept for macular edema secondary to retinal vein occlusion

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