Efficacy of Anti-VEGF Drugs on Visual Acuity in Patients with Macular Edema Secondary to Central Retinal Vein Occlusion: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

 GUOBie-chuan ,  KEMin , TIANZhen , WANGPing , QIAOChen

Zhongnan Hospital of Wuhan University, Wuhan 430071, China;

Corresponding author：

KEMin, Email: keminyk@163.com

Keywords：

Central retinal vein occlusion(CRVO); Macular edema; Vascular endothelial growth factor(VEGF); Systematic review; Meta-analysis; Randomized controlled trial

DOI：

10.7507/1672-2531.20140009

Video：

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Objective To systematically review anti-vascular endothelial growth factor (VEGF) drugs on visual acuity in patients with central vetinal vein occlnsion-macular edema (CRVO-ME). Methods Databases including PubMed, The Cochrane Library (Issue 11, 2012), EMbase, CBM, CNKI, VIP and WanFang Data were electronically searched for the randomized controlled trials (RCTs) about anti-VEGF drugs on visual acuity in patients with CRVO-ME from the date of establishment of the databases to December 2012. Two reviewers independently screened literature according to the inclusion and exclusion criteria, and evaluated the included studies. Then, meta-analysis was performed using RevMan 5.1 software. The quality of evidence was analyzed using GRADEpro 3.6 software. Results A total 9 trials involving 1 072 patients (1 072 eyes) were included. The results of meta-analysis showed that, anti-VEGF injection, compared with sham injection, increased BCVA score measured by ETDRS (MD=16.27, 95%CI 9.98 to 22.55, P < 0.000 01); decreased CFT score measured by OCT (MD=245.25, 95%CI 136.02 to 354.48, P < 0.000 1); gained more than 15 letters in BCVA (OR=4.43, 95% CI 2.23 to 8.83, P < 0.000 1); and the long term anti-VEGF effect index, gained no less than 15 letters in BCVA (OR=2.25, 95% CI 1.56 to 3.23, P < 0.000 1). The score of short term BCVA changes was of intermediate quality, while another three outcomes were of low quality in the GRADE system. Conclusion Current evidence shows that, anti-VEGF drugs could improve the visual acuity of patients with CRVO-ME. The clinicians could recommend this kind of drugs to the patients. Due to the limitations of the included studies, more large-sample multicentre high-quality RCTs are required to verify its effectiveness.

Citation： GUOBie-chuan, KEMin, TIANZhen, WANGPing, QIAOChen. Efficacy of Anti-VEGF Drugs on Visual Acuity in Patients with Macular Edema Secondary to Central Retinal Vein Occlusion: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2014, 14(1): 44-51. doi: 10.7507/1672-2531.20140009 Copy

1.	Rogers S, McIntosh RL, Cheung N, et al. The prevalence of retinal vein occlusion:Pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology, 2010, 117(2):313-319.
2.	Xu L, Cui T, Zhang S, et al. Prevalence and risk factors of lens opacities in urban and rural Chinese in Beijing. Ophthalmology, 2006, 113(5):747-755.
3.	Stem MS, Talwar N, Comer GM, et al. A Longitudinal Analysis of Risk Factors Associated with Central Retinal Vein Occlusion. Ophthalmology, 2013, 120(2):362-370.
4.	Ehlers JP, Fekrat S. Retinal vein occlusion:beyond the acute event. SurvOphthalmol, 2011, 56(4):281-299.
5.	Hayreh SS, Podhajsky PA, Zimmerman MB. Natural history of visual outcome in central retinal vein occlusion. Ophthalmology, 2011, 118(1):119-133.
6.	Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol, 1997, 115(4):486-491.
7.	Glacet-Bernard A, Coscas G, Zourdani A, et al. Steroids and macular edema from retinal vein occlusion. Eur J Ophthalmol, 2011, 21(Suppl 6):S37-44.
8.	Fekrat S, Finkelstein D. Current concepts in the management of central retinal vein occlusion. Curr Opin Ophthalmol, 1997, 8(3):50-54.
9.	ParodiMB. Medicaltreatment of retinal vein occlusions. Semin Ophthalmol, 2004, 19(1-2):43-48.
10.	Hayreh SS. Management of central retinal vein occlusion. Ophthalmologica, 2003, 217(3):167-188.
11.	McAllister IL, Gillies ME, Smithies LA, et al. The central retinal vein bypass study:A trial of laser-induced chorioretinal venous anastomosis for central retinal vein occlusion. Ophthalmology, 2010, 117(5):954-965.
12.	Ip MS, Scott IU, vanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion:The standard care vs. corticosteroid for retinal vein occlusion (SCORE) study report 5. Arch Ophthalmol, 2009, 127(9):1101-1114.
13.	Arevalo JF, Garcia RA, Wu L, et al. Pan-American Collaborative Retina Study Group. Radial optic neurotomy for central retinal vein occlusion:results of the Pan-American Collaborative Retina Study Group (PACORES). Retina, 2008, 28(8):1044-1052.
14.	Berker N, Batman C. Surgical treatment of central retinal vein occlusion. Acta Ophthalmol, 2008, 86(3):245-252.
15.	Heier JS, Campochiaro PA, Yau L, et al. Ranibizumab for Macular Edema Due to Retinal Vein Occlusions:Long-term Follow-up in the HORIZON Trial. Ophthalmology, 2012, 119(4):802-809.
16.	Kaiser PK. Prospective evaluation of visual acuity assessment:A comparison of Snellen versus ETDRS charts in clinical practice. Trans Am Ophthalmol Soc, 2009, 107:311-324.
17.	Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011], The Cochrane Collaboration, 2011.
18.	Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendation. BMJ, 2004, 328(7454):1490.
19.	Epstein DL, Algvere PV, von Wendt G, et al. Benefit from bevacizumab for macular edema in central retinal vein occlusion:Twelve-month results of a prospective, randomized study. Ophthalmology, 2012, 119(12):2587-2591.
20.	Brown DM, Heier JS, Clark WL, et al. IntravitrealAflibercept Injection for Macular Edema Secondary to Central Retinal Vein Occlusion:1-Year Results From the Phase 3 COPERNICUS Study. Am J Ophthalmol, 2013, 155(3):429-437.
21.	Campochiaro PA, Brown DM, Awh CC, et al. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion:Twelve-month outcomes of a phase Ⅲ study. Ophthalmology, 2011, 118(10):2041-2049.
22.	Kinge B, Stordahl PB, Forsaa V, et al. Efficacy of ranibizumab in patients with macular edema secondary to central retinal vein occlusion:results from the sham-controlled ROCC study. Am J Ophthalmol, 2010, 150(3):310-314.
23.	Boyer D, Heier J, Brown DM, et al. Vascular endothelial growth factor trap-eye for macular edema secondary to central retinal vein occlusion. Ophthalmology, 2012, 119(5):1024-1032.
24.	Epstein DL, Algvere PV, von Wendt G, et al. Bevacizumab for macular edema in central retinal vein occlusion:A prospective, randomized, double-masked clinical study. Ophthalmology, 2012, 119(6):1184-1189.
25.	Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for Macular Edema following Central Retinal Vein Occlusion. Ophthalmology, 2010, 117(6):1124-1133.
26.	Wroblewski JJ, Wells JA 3rd, Adamis AP, et al. Pegaptanib Sodium for Macular Edema Secondary to Central Retinal Vein Occlusion. Arch Ophthalmol, 2009, 127(4):374-380.
27.	UK Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes:UKPDS 38. BMJ, 1998, 317(7160):703-713.
28.	Suñer IJ, Kokame GT, Yu E, et al. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD:Validation studies from two phase 3 clinical trials. Invest Ophthalmol Vis Sci, 2009, 50(8):3629-3635.
29.	Guex-Crosier Y. The pathogenesis and clinical presentation of macular edema in inflammatory diseases. Doc Ophthalmol, 1999, 97(3-4):297-309.
30.	Vinores SA, Derevjanik NL, Ozaki H, et al. Cellular mechanisms of blood-retinal barrier dysfunction in macular edema. Doc Ophthalmol, 1999, 97(3-4):217-228.
31.	Nauck M, Karakiulakis G, Perruchoud AP, et al. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol, 1998, 341(2-3):309-315.
32.	Funk M, Kriechbaum K, Prager F, et al. Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Invest Ophthalmol Vis Sci, 2009, 50(3):1025-1032.

1. Rogers S, McIntosh RL, Cheung N, et al. The prevalence of retinal vein occlusion:Pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology, 2010, 117(2):313-319.
2. Xu L, Cui T, Zhang S, et al. Prevalence and risk factors of lens opacities in urban and rural Chinese in Beijing. Ophthalmology, 2006, 113(5):747-755.
3. Stem MS, Talwar N, Comer GM, et al. A Longitudinal Analysis of Risk Factors Associated with Central Retinal Vein Occlusion. Ophthalmology, 2013, 120(2):362-370.
4. Ehlers JP, Fekrat S. Retinal vein occlusion:beyond the acute event. SurvOphthalmol, 2011, 56(4):281-299.
5. Hayreh SS, Podhajsky PA, Zimmerman MB. Natural history of visual outcome in central retinal vein occlusion. Ophthalmology, 2011, 118(1):119-133.
6. Central Vein Occlusion Study Group. Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol, 1997, 115(4):486-491.
7. Glacet-Bernard A, Coscas G, Zourdani A, et al. Steroids and macular edema from retinal vein occlusion. Eur J Ophthalmol, 2011, 21(Suppl 6):S37-44.
8. Fekrat S, Finkelstein D. Current concepts in the management of central retinal vein occlusion. Curr Opin Ophthalmol, 1997, 8(3):50-54.
9. ParodiMB. Medicaltreatment of retinal vein occlusions. Semin Ophthalmol, 2004, 19(1-2):43-48.
10. Hayreh SS. Management of central retinal vein occlusion. Ophthalmologica, 2003, 217(3):167-188.
11. McAllister IL, Gillies ME, Smithies LA, et al. The central retinal vein bypass study:A trial of laser-induced chorioretinal venous anastomosis for central retinal vein occlusion. Ophthalmology, 2010, 117(5):954-965.
12. Ip MS, Scott IU, vanVeldhuisen PC, et al. A randomized trial comparing the efficacy and safety of intravitreal triamcinolone with observation to treat vision loss associated with macular edema secondary to central retinal vein occlusion:The standard care vs. corticosteroid for retinal vein occlusion (SCORE) study report 5. Arch Ophthalmol, 2009, 127(9):1101-1114.
13. Arevalo JF, Garcia RA, Wu L, et al. Pan-American Collaborative Retina Study Group. Radial optic neurotomy for central retinal vein occlusion:results of the Pan-American Collaborative Retina Study Group (PACORES). Retina, 2008, 28(8):1044-1052.
14. Berker N, Batman C. Surgical treatment of central retinal vein occlusion. Acta Ophthalmol, 2008, 86(3):245-252.
15. Heier JS, Campochiaro PA, Yau L, et al. Ranibizumab for Macular Edema Due to Retinal Vein Occlusions:Long-term Follow-up in the HORIZON Trial. Ophthalmology, 2012, 119(4):802-809.
16. Kaiser PK. Prospective evaluation of visual acuity assessment:A comparison of Snellen versus ETDRS charts in clinical practice. Trans Am Ophthalmol Soc, 2009, 107:311-324.
17. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0[updated March 2011], The Cochrane Collaboration, 2011.
18. Atkins D, Best D, Briss PA, et al. Grading quality of evidence and strength of recommendation. BMJ, 2004, 328(7454):1490.
19. Epstein DL, Algvere PV, von Wendt G, et al. Benefit from bevacizumab for macular edema in central retinal vein occlusion:Twelve-month results of a prospective, randomized study. Ophthalmology, 2012, 119(12):2587-2591.
20. Brown DM, Heier JS, Clark WL, et al. IntravitrealAflibercept Injection for Macular Edema Secondary to Central Retinal Vein Occlusion:1-Year Results From the Phase 3 COPERNICUS Study. Am J Ophthalmol, 2013, 155(3):429-437.
21. Campochiaro PA, Brown DM, Awh CC, et al. Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion:Twelve-month outcomes of a phase Ⅲ study. Ophthalmology, 2011, 118(10):2041-2049.
22. Kinge B, Stordahl PB, Forsaa V, et al. Efficacy of ranibizumab in patients with macular edema secondary to central retinal vein occlusion:results from the sham-controlled ROCC study. Am J Ophthalmol, 2010, 150(3):310-314.
23. Boyer D, Heier J, Brown DM, et al. Vascular endothelial growth factor trap-eye for macular edema secondary to central retinal vein occlusion. Ophthalmology, 2012, 119(5):1024-1032.
24. Epstein DL, Algvere PV, von Wendt G, et al. Bevacizumab for macular edema in central retinal vein occlusion:A prospective, randomized, double-masked clinical study. Ophthalmology, 2012, 119(6):1184-1189.
25. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for Macular Edema following Central Retinal Vein Occlusion. Ophthalmology, 2010, 117(6):1124-1133.
26. Wroblewski JJ, Wells JA 3rd, Adamis AP, et al. Pegaptanib Sodium for Macular Edema Secondary to Central Retinal Vein Occlusion. Arch Ophthalmol, 2009, 127(4):374-380.
27. UK Prospective Diabetes Study (UKPDS) Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes:UKPDS 38. BMJ, 1998, 317(7160):703-713.
28. Suñer IJ, Kokame GT, Yu E, et al. Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD:Validation studies from two phase 3 clinical trials. Invest Ophthalmol Vis Sci, 2009, 50(8):3629-3635.
29. Guex-Crosier Y. The pathogenesis and clinical presentation of macular edema in inflammatory diseases. Doc Ophthalmol, 1999, 97(3-4):297-309.
30. Vinores SA, Derevjanik NL, Ozaki H, et al. Cellular mechanisms of blood-retinal barrier dysfunction in macular edema. Doc Ophthalmol, 1999, 97(3-4):217-228.
31. Nauck M, Karakiulakis G, Perruchoud AP, et al. Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol, 1998, 341(2-3):309-315.
32. Funk M, Kriechbaum K, Prager F, et al. Intraocular concentrations of growth factors and cytokines in retinal vein occlusion and the effect of therapy with bevacizumab. Invest Ophthalmol Vis Sci, 2009, 50(3):1025-1032.

Chinese Journal of Evidence-Based Medicine

Efficacy of Anti-VEGF Drugs on Visual Acuity in Patients with Macular Edema Secondary to Central Retinal Vein Occlusion: A Systematic Review

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