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International Ophthalmology

, Volume 39, Issue 4, pp 891–901 | Cite as

The short-term efficacy of intravitreal ranibizumab, aflibercept and dexamethasone implant in the treatment of macular edema due to non-ischemic central retinal vein occlusion

  • Ozlem Eski YucelEmail author
  • Hakki Birinci
  • Yuksel Sullu
Original Paper
  • 295 Downloads

Abstract

Purpose

To assess and compare the efficacy over 6 months of intravitreal ranibizumab (IR), aflibercept (IA) and dexamethasone implant (IDI) in eyes with macular edema (ME) secondary to non-ischemic central retinal vein occlusion (CRVO).

Methods

This is a retrospective single-center study. Patients who received pro re nata treatment of IR 0.5 mg, IA 2 mg or IDI 0.7 mg (as Group 1, Group 2, and Group 3, respectively) for the treatment of ME due to non-ischemic CRVO were included in the study. Efficacy outcomes were considered as the changes in mean best-corrected visual acuity (BCVA) and central macular thickness (CMT) from baseline over 6 months.

Results

Eighteen patients (Group 1) received IR, 16 patients received (Group 2) IA, and 24 patients (Group 3) received IDI. The mean numbers of injections were 2.56 ± 1.0, 2.68 ± 0.9, and 1.62 ± 0.5 in Group 1, 2, and 3, respectively (p = 0.000). In Groups 1 and 2, the mean BCVA values increased significantly after the treatment (p < 0.001). However, in Group 3, no increase in mean BCVA was statistically significant in any month (p = 0.061). The proportion of eyes gaining at least three lines in BCVA was 33.3% in Group 1, 43.8% in Group 2, and 33.3% in Group 3 (p = 0.762). In all groups, significant improvements were observed in CMT after treatment (p < 0.001). At month 6, the mean changes in CMT were − 162.7 ± 186.5 µm in Group 1, − 310.1 ± 345.9 µm in Group 2, and − 193.8 ± 228.3 µm in Group 3, with no significant difference among groups (p = 0.474). Cataract formation and IOP increase were higher in the IDI group, but the differences were not statistically significant (p = 0.054 and p = 0.392, respectively).

Conclusions

IR and IA may be preferred treatment for ME due to non-ischemic CRVO as visual improvement remains the primary ophthalmological objective. The most important advantages of IDI are its effect on CMT and the need for fewer injections. The increase in IOP and the formation of cataract may be observed more in IDI-treated eyes.

Keywords

Aflibercept Central retinal vein occlusion Dexamethasone implant Macular edema Ranibizumab Retinal vein occlusion 

Notes

Acknowledgments

We thank Ozlem Terzi, M.D. for assistance in clinical information analysis.

Compliance with ethical standards

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Ethical standards

This study was approved by the Ondokuz Mayis University Clinical Research Ethics Committee.

References

  1. 1.
    Rogers S, McIntosh RL, Cheung N, Lim L, Wang JJ, Mitchell P, Kowalski JW, Nguyen H, Wong TY, International Eye Disease Consortium (2010) The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia. Ophthalmology 117:313–319.  https://doi.org/10.1016/j.ophtha.2009.07.017 CrossRefGoogle Scholar
  2. 2.
    Miller JW, Le CJ, Strauss EC, Ferrara N (2013) Vascular endothelial growth factor A in intraocular vascular disease. Ophthalmology 120:106–114.  https://doi.org/10.1016/j.ophtha.2012.07.038 CrossRefGoogle Scholar
  3. 3.
    Hayreh SS, Podhajsky PA, Zimmerman MB (2011) Natural history of visual outcome in central retinal vein occlusion. Ophthalmology 118:119–133.  https://doi.org/10.1016/j.ophtha.2010.04.019 CrossRefGoogle Scholar
  4. 4.
    The Central Vein Occlusion Study Group (1995) Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. Ophthalmology 102:1425–1433CrossRefGoogle Scholar
  5. 5.
    Epstein DL, Algvere PV, von Wendt G, Seregard S, Kvanta A (2012) Bevacizumab for macular edema in central retinal vein occlusion: a prospective, randomized, double-masked clinical study. Ophthalmology 119(6):1184–1189.  https://doi.org/10.1016/j.ophtha.2012.01.022 CrossRefGoogle Scholar
  6. 6.
    Brown DM, Campochiaro PA, Singh RP, Li Z, Gray S, Saroj N, Rundle AC, Rubio RG, Murahashi WY, CRUISE Investigators (2010) Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 117(6):1124–1133.  https://doi.org/10.1016/j.ophtha.2010.02.022 CrossRefGoogle Scholar
  7. 7.
    Boyer D, Heier J, Brown DM, Clark WL, Vitti R, Berliner AJ, Groetzbach G, Zeitz O, Sandbrink R, Zhu X, Beckmann K, Haller JA (2012) Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology 119(5):1024–1032.  https://doi.org/10.1016/j.ophtha.2012.01.042 CrossRefGoogle Scholar
  8. 8.
    Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Can Res 57(20):4593–4599Google Scholar
  9. 9.
    Ferrara N, Damico L, Shams N, Lowman H, Kim R (2006) Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 26:859–870CrossRefGoogle Scholar
  10. 10.
    Holash J, Davis S, Papadopoulos N, Croll SD, Ho L, Russell M, Boland P, Leidich R, Hylton D, Burova E, Ioffe E, Huang T, Radziejewski C, Bailey K, Fandl JP, Daly T, Wiegand SJ, Yancopoulos GD, Rudge JS (2002) VEGF-trap: a VEGF blocker with potent antitumor effects. Proc Natl Acad Sci USA 99:11393–11398CrossRefGoogle Scholar
  11. 11.
    Papadopoulos N, Martin J, Ruan Q, Rafique A, Rosconi MP, Shi E, Pyles EA, Yancopoulos GD, Stahl N, Wiegand SJ (2012) Binding and neutralization of vascular endothelial growth factor (VEGF) and related ligands by VEGF Trap, ranibizumab and bevacizumab. Angiogenesis 15:171–185.  https://doi.org/10.1007/s10456-011-9249-6 CrossRefGoogle Scholar
  12. 12.
    Ip MS, Scott IU, VanVeldhuisen PC, Oden NL, Blodi BA, Fisher M, Singerman LJ, Tolentino M, Chan CK, Gonzalez VH, SCORE Study Research Group (2009) 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 127(9):1101–1114.  https://doi.org/10.1001/archophthalmol.2009.234 CrossRefGoogle Scholar
  13. 13.
    Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jacques ML, Jiao J, Li XY, Whitcup SM, OZURDEX GENEVA Study Group (2010) Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion. Ophthalmology 117(6):1134–1146.  https://doi.org/10.1016/j.ophtha.2010.03.032 CrossRefGoogle Scholar
  14. 14.
    Jain N, Stinnett SS, Jaffe GJ (2012) Prospective study of a fluocinolone acetonide implant for chronic macular edema from central retinal vein occlusion: thirty-six-month results. Ophthalmology. 119(1):132–137.  https://doi.org/10.1016/j.ophtha.2011.06.019 CrossRefGoogle Scholar
  15. 15.
    Felinski EA, Antonetti DA (2005) Glucocorticoid regulation of endothelial cell tight junction gene expression: novel treatments for diabetic retinopathy. Curr Eye Res 30(11):949–957CrossRefGoogle Scholar
  16. 16.
    Nauck M, Karakiulakis G, Perruchoud AP, Papakonstantinou E, Roth M (1998) Corticosteroids inhibit the expression of the vascular endothelial growth factor gene in human vascular smooth muscle cells. Eur J Pharmacol 341(2–3):309–315CrossRefGoogle Scholar
  17. 17.
    Ehlers JP, Fekrat S (2011) Retinal vein occlusion: beyond the acute event. Surv Ophthalmol 56:281–299.  https://doi.org/10.1016/j.survophthal.2010.11.006 CrossRefGoogle Scholar
  18. 18.
    Kinge B, Stordahl PB, Forsaa V, Fossen K, Haugstad M, Helgesen OH, Seland J, Stene-Johansen I (2010) Efficacy of ranibizumab in patients with macular edema secondary to central retinal vein occlusion: results from the sham-controlled ROCC study. Am J Ophthalmol 150(3):310–314.  https://doi.org/10.1016/j.ajo.2010.03.028 CrossRefGoogle Scholar
  19. 19.
    Heier JS, Campochiaro PA, Yau L, Li Z, Saroj N, Rubio RG, Lai P (2012) Ranibizumab for macular edema due to retinal vein occlusions: long-term follow-up in the HORIZON trial. Ophthalmology 119(4):802–809.  https://doi.org/10.1016/j.ophtha.2011.12.005 CrossRefGoogle Scholar
  20. 20.
    Heier JS, Clark WL, Boyer DS, Brown DM, Vitti R, Berliner AJ, Kazmi H, Ma Y, Stemper B, Zeitz O, Sandbrink R, Haller JA (2014) Intravitreal aflibercept injection for macular edema due to central retinal vein occlusion: two-year results from the COPERNICUS study. Ophthalmology 121(7):1414–1420.  https://doi.org/10.1016/j.ophtha.2014.01.027 CrossRefGoogle Scholar
  21. 21.
    Joshi L, Yaganti S, Gemenetzi M, Lightman S, Lindfield D, Liolios V, Menezo V, Shao E, Taylor SR (2013) Dexamethasone implants in retinal vein occlusion: 12-month clinical effectiveness using repeat injections as-needed. Br J Ophthalmol 97(8):1040–1044.  https://doi.org/10.1136/bjophthalmol-2013-303207 CrossRefGoogle Scholar
  22. 22.
    Querques L, Querques G, Lattanzio R, Gigante SR, Del Turco C, Corradetti G, Cascavilla ML, Bandello F (2013) Repeated intravitreal dexamethasone implant (Ozurdex®) for retinal vein occlusion. Ophthalmologica 229(1):21–25.  https://doi.org/10.1159/000342160 CrossRefGoogle Scholar
  23. 23.
    Hoerauf H, Feltgen N, Weiss C, Paulus EM, Schmitz-Valckenberg S, Pielen A, Puri P, Berk H, Eter N, Wiedemann P, Lang GE, Rehak M, Wolf A, Bertelmann T, Hattenbach LO, COMRADE-C Study Group (2016) Clinical efficacy and safety of ranibizumab versus dexamethasone for central retinal vein occlusion (COMRADE C): a European label study. Am J Ophthalmol 169:258–267.  https://doi.org/10.1016/j.ajo.2016.04.020 CrossRefGoogle Scholar
  24. 24.
    Nghiem-Buffet S, Fajnkuchen F, Buffet M, Ayrault S, Le Gloahec-Lorcy A, Grenet T, Delahaye-Mazza C, Quentel G, Cohen SY (2014) Intravitreal ranibizumab and/or dexamethasone implant for macular edema secondary to retinal vein occlusion. Ophthalmologica 232(4):216–222.  https://doi.org/10.1159/000365639 CrossRefGoogle Scholar
  25. 25.
    Brown DM, Heier JS, Clark WL, Boyer DS, Vitti R, Berliner AJ, Zeitz O, Sandbrink R, Zhu X, Haller JA (2013) Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol 155(3):429–437.  https://doi.org/10.1016/j.ajo.2012.09.026 CrossRefGoogle Scholar
  26. 26.
    Campochiaro PA, Brown DM, Awh CC, Lee SY, Gray S, Saroj N, Murahashi WY, Rubio RG (2011) Sustained benefits from ranibizumab for macular edema following central retinal vein occlusion: twelve-month outcomes of a phase III study. Ophthalmology 118(10):2041–2049.  https://doi.org/10.1016/j.ophtha.2011.02.038 CrossRefGoogle Scholar
  27. 27.
    Haller JA, Bandello F, Belfort R Jr, Blumenkranz MS, Gillies M, Heier J, Loewenstein A, Yoon YH, Jiao J, Li XY, Whitcup SM, Ozurdex GENEVA Study Group (2011) Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results. Ophthalmology 118(12):2453–2460.  https://doi.org/10.1016/j.ophtha.2011.05.014 CrossRefGoogle Scholar
  28. 28.
    Chatziralli I, Theodossiadis G, Moschos MM, Mitropoulos P, Theodossiadis P (2017) Ranibizumab versus aflibercept for macular edema due to central retinal vein occlusion: 18-month results in real-life data. Graefes Arch Clin Exp Ophthalmol 255(6):1093–1100.  https://doi.org/10.1007/s00417-017-3613-1 CrossRefGoogle Scholar
  29. 29.
    Channa R, Smith M, Campochiaro PA (2011) Treatment of macular edema due to retinal vein occlusions. Clin Ophthalmol 5:705–713.  https://doi.org/10.2147/OPTH.S7632 Google Scholar
  30. 30.
    Pielen A, Feltgen N, Isserstedt C, Callizo J, Junker B, Schmucker C (2013) Efficacy and safety of intravitreal therapy in macular edema due to branch and central retinal vein occlusion: a systematic review. PLoS ONE 8(10):e78538.  https://doi.org/10.1371/journal.pone.0078538 CrossRefGoogle Scholar
  31. 31.
    Ford JA, Shyangdan D, Uthman OA, Lois N, Waugh N (2014) Drug treatment of macular oedema secondary to central retinal vein occlusion: a network meta-analysis. BMJ Open 4(7):e005292.  https://doi.org/10.1136/bmjopen-2014-005292 CrossRefGoogle Scholar
  32. 32.
    The Central Vein Occlusion Study Group (1997) Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol 115(4):486–491CrossRefGoogle Scholar
  33. 33.
    Hayreh SS, Zimmerman MB, Podhajsky P (1994) Incidence of various types of retinal vein occlusion and their recurrence and demographic characteristics. Am J Ophthalmol 117:429–441CrossRefGoogle Scholar
  34. 34.
    Wykoff CC, Brown DM, Croft DE, Major JC Jr, Wong TP (2015) Progressive retinal nonperfusion in ischemic central retinal vein occlusion. Retina 35(1):43–47.  https://doi.org/10.1097/IAE.0000000000000277 CrossRefGoogle Scholar
  35. 35.
    Singer M, Tan CS, Bell D, Sadda SR (2014) Area of peripheral retinal nonperfusion and treatment response in branch and central retinal vein occlusion. Retina 34(9):1736–1742.  https://doi.org/10.1097/IAE.0000000000000148 CrossRefGoogle Scholar
  36. 36.
    Campochiaro PA, Bhisitkul RB, Shapiro H, Rubio RG (2013) Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion. Ophthalmology 120(4):795–802.  https://doi.org/10.1016/j.ophtha.2012.09.032 CrossRefGoogle Scholar

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© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Ophthalmology, Medical FacultyOndokuz Mayis UniversitySamsunTurkey

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