International Ophthalmology

, Volume 34, Issue 6, pp 1193–1201 | Cite as

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

  • Marina Papadia
  • Marie Misteli
  • Bruno Jeannin
  • Carl P. Herbort
Original Paper


The purpose of this study was to evaluate the impact of intravitreal bevacizumab injections on the management and outcome of patients affected by retinal vein occlusions, their effectiveness on morphological and functional parameters, the modalities of long-term management and the need for additional laser treatment due to ischemic retinal evolution. Patients diagnosed with branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) had a comprehensive work-up including complete ophthalmic examination, fluorangiography (FA), optical coherence tomography (OCT), visual field testing (VFT), microperimetry (MP), and laser flare photometry (LFP). In case of BRVO, intraocular bevacizumab injection was performed if significant macular edema/visual deficit was still present 3 months after onset of occlusion and injections were started at presentation in case of CRVO. Post-injection follow-up examination including best corrected visual acuity (BCVA), intraocular pressure (IOP), LFP, OCT, MP, and VFT were performed monthly and recorded at the end of follow-up. Follow-up FA was performed between 12 and 18 months after diagnosis. Injections were repeated in case of recurrence of a significant central macular edema. Patients were subdivided into 2 groups according to number of injections: 1–4 injections or more than 4 injections. The proportion of resolved cases (no recurrence after a minimum follow-up of 12 months) was calculated and correlated with number of injections. In patients needing sustained injections, management modalities were recorded. The proportion of patients having needed laser photocoagulation treatment because of significant ischemic signs was recorded. Fifty-one patients were diagnosed with retinal vein occlusion between 2006 and 2012 at the Centre for Specialized Ophthalmic Care (COS) in Lausanne, Switzerland. Forty-four had enough data and were included in the study. Nine eyes were affected by CRVO and 35 were affected by BRVO. Mean BCVA at presentation was 0.24 ± 0.2 and improved to 0.81 ± 0.38 (p < 0.01) at 48 months. MP improved from 184.9 ± 92 to 362.5 ± 56.2 (p < 0.01) at 42 months follow-up. The number of injections varied from 1 to 25 (mean 5.5 ± 5.43). 31/44 eyes received 1–4 injections (group 1) of which all were recurrence free, with a follow-up of at least 1 years in all. 13/44 eyes received more than 5 injections (group 2) with functional and morphological parameters maintained in 9/13 but only 1/13 patients showed resolution. Rhythm of injection varied from one patient to another but 8/13 patients needing continuous injections had a constant time interval between injections. In 8/44 patients, laser photocoagulation had to be performed due to ischemic complications. The visual outcome using bevacizumab intravitreal injection was exceptionally good and functional parameters such as BCVA, MP, and VFT improved significantly. In about two-thirds of patients, resolution was obtained after 1–4 injections. In one-third of patients, continuous injections were necessary but a constant rhythm for re-injection for each patient could be established allowing to reduce to a minimum follow-up visits. The absence of significant side effects allowed to re-treat apparently without limitation achieving maintained visual function. FA monitoring for the detection of ischemic complications should not be neglected especially in cases where bevacizumab could be discontinued.


Branch retinal vein occlusion (BRVO) Central retinal vein occlusion (CRVO) Bevacizumab Optical coherence tomography (OCT) Microperimetry (MP) Fluorescein angiography (FA) Individual injection time interval 


  1. 1.
    Yau JW, Lee P, Wong TY, Best J, Jenkins A (2008) Retinal vein occlusion: an approach to diagnosis, systemic risk factors and management. Intern Med J. 38(12):904–910PubMedCrossRefGoogle Scholar
  2. 2.
    Royal College of Ophthalmologists. Retinal vein occlusion guidelines. Royal College of Ophthalmologists Web site. Accessed 30 July 2009
  3. 3.
    Klein R, Klein BE, Moss SE, Meuer SM (2000) The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc 98:133–141PubMedCentralPubMedGoogle Scholar
  4. 4.
    The Branch Vein Occlusion Study Group (1984) Argon laser photocoagulation for macular edema in branch vein occlusion. Am J Ophthalmol 98:271–282CrossRefGoogle Scholar
  5. 5.
    The Central Vein Occlusion Study Group (1997) Natural history and clinical management of central retinal vein occlusion. Arch Ophthalmol 115:486–491CrossRefGoogle Scholar
  6. 6.
    Finkelstein D (1996) Laser therapy for central retinal vein obstruction. Curr Opin Ophthalmol 7(3):80–83PubMedCrossRefGoogle Scholar
  7. 7.
    Opremcak EM, Bruce RA, Lomeo MD, Ridenour CD, Letson AD, Rehmar AJ (2001) Radial optic neurotomy for central retinal vein occlusion: a retrospective pilot study of 11 consecutive cases. Retina 21(5):408–415PubMedCrossRefGoogle Scholar
  8. 8.
    Chung EJ, Lee H, Koh HJ (2008) Arteriovenous crossing sheathotomy versus intravitreal triamcinolone acetonide injection for treatment of macular edema associated with branch retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 246(7):967–974PubMedCrossRefGoogle Scholar
  9. 9.
    Weiss JN, Bynoe LA (2001) Injection of tissue plasminogen activator into a branch retinal vein in eyes with central retinal vein occlusion. Ophthalmology 108(12):2249–2257PubMedCrossRefGoogle Scholar
  10. 10.
    Schumann M, Hansen LL, Janknecht P, Witschel H (1993) Isovolemic hemodilution in central retinal vein occlusion in patients less than 50 years of age. Klin Monbl Augenheilkd 203(5):341–346PubMedCrossRefGoogle Scholar
  11. 11.
    Parodi MB (2004) Medical treatment of retinal vein occlusions. Semin Ophthalmol 19(1–2):43–48PubMedCrossRefGoogle Scholar
  12. 12.
    Asano S, Miyake K, Miyake S, Ota I (2007) Relationship between blood-aqueous barrier disruption and ischemic macular edema in patients with branch or central retinal vein occlusion: effects of sub-tenon triamcinolone acetonide injection. J Ocul Pharmacol Ther 23(6):577–584PubMedCrossRefGoogle Scholar
  13. 13.
    Greenberg PB, Martidis A, Rogers AH, Duker JS, Reichel E (2002) Intravitreal triamcinolone acetonide for macular oedema due to central retinal vein occlusion. Br J Ophthalmol 86(2):247–248PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Ip MS, Kumar KS (2002) Intravitreous triamcinolone acetonide as treatment for macular edema from central retinal vein occlusion. Arch Ophthalmol 120(9):1217–1219PubMedGoogle Scholar
  15. 15.
    Jonas JB, Kreissig I, Degenring RF (2002) Intravitreal triamcinolone acetonide as treatment of macular edema in central retinal vein occlusion. Graefes Arch Clin Exp Ophthalmol 240(9):782–783PubMedCrossRefGoogle Scholar
  16. 16.
    Kaiser PK (2005) Steroids for branch retinal vein occlusion. Am J Ophthalmol 139(6):1095–1096PubMedCrossRefGoogle Scholar
  17. 17.
    Kiddee W, Trope GE, Sheng L, Beltran-Agullo L, Smith M, Strungaru MH, Baath J, Buys YM (2013) Intraocular pressure monitoring post intravitreal steroids: a systematic review. Surv Ophthalmol 58(4):291–310PubMedCrossRefGoogle Scholar
  18. 18.
    Carnahan MC, Goldstein DA (2000) Ocular complications of topical, peri-ocular, and systemic corticosteroids. Curr Opin Ophthalmol 11(6):478–483PubMedCrossRefGoogle Scholar
  19. 19.
    Thompson JT (2006) Cataract formation and other complications of intravitreal triamcinolone for macular edema. Am J Ophthalmol 141(4):629–637PubMedCrossRefGoogle Scholar
  20. 20.
    Stahl A, Agostini H, Hansen LL, Feltgen N (2007) Bevacizumab in retinal vein occlusion-results of a prospective case series. Graefes Arch Clin Exp Ophthalmol 245(10):1429–1436PubMedCrossRefGoogle Scholar
  21. 21.
    Wu L, Martínez-Castellanos MA, Quiroz-Mercado H, Arevalo JF, Berrocal MH, Farah ME, Maia M, Roca JA, Rodriguez FJ (2008) Pan American Collaborative Retina Group (PACORES). Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results of the Pan-American Collaborative Retina Study Group (PACORES). Graefes Arch Clin Exp Ophthalmol 246(1):81–87PubMedCrossRefGoogle Scholar
  22. 22.
    Hayreh SS (1983) Classification of central retinal vein occlusion. Ophthalmology 90(5):458–474PubMedCrossRefGoogle Scholar
  23. 23.
    Glacet-Bernard A, Mahdavi KN, Coscas G, Zourdani A, Fardeau C (1994) Macular grid photocoagulation in persistent macular edema due to central retinal vein occlusion. Eur J Ophthalmol. 4(3):166–174PubMedGoogle Scholar
  24. 24.
    Parodi MB, Di Stefano G, Ravalico G (2008) Grid laser treatment for exudative retinal detachment secondary to ischemic branch retinal vein occlusion. Retina 28(1):97–102PubMedCrossRefGoogle Scholar
  25. 25.
    McIntosh RL, Mohamed Q, Saw SM, Wong TY (2007) Interventions for branch retinal vein occlusion: an evidence-based systematic review. Ophthalmology 114(5):835–854 Epub 2007 Mar 30PubMedCrossRefGoogle Scholar
  26. 26.
    Ohashi H, Oh H, Nishiwaki H, Nonaka A, Takagi H (2004) Delayed absorption of macular edema accompanying serous retinal detachment after grid laser treatment in patients with branch retinal vein occlusion. Ophthalmology 111(11):2050–2056PubMedCrossRefGoogle Scholar
  27. 27.
    Mohamed Q, McIntosh RL, Saw SM, Wong TY (2007) Interventions for central retinal vein occlusion: an evidence-based systematic review. Ophthalmology. 114(3):507-19, 524Google Scholar
  28. 28.
    The Central Vein Occlusion Study Group (1995) Evaluation of grid pattern photocoagulation for macular edema in central vein occlusion. The central vein occlusion study group M report. Ophthalmology 102:1425–1433CrossRefGoogle Scholar
  29. 29.
    Russo V, Barone A, Conte E, Prascina F, Stella A et al. (2009) Bevacizumab compared with macular laser grid photocoagulation for cystoid macular edema in branch retinal vein occlusion. Retina (Phila, Pa) 29: 511–515Google Scholar
  30. 30.
    Smith GC, Pell JP (2003) Parachute use to prevent death and major trauma related to gravitational challenge: systematic review of randomised controlled trials. BMJ 327(7429):1459–1461PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Mitry D, Bunce C, Charteris D (2013) Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database Syst Rev 31:1Google Scholar
  32. 32.
    Brown DM, Campochiaro PA, Bhisitkul RB, Ho AC, Gray S, Saroj N, Adamis AP, Rubio RG, Murahashi WY (2011) Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology 118(8):1594–1602PubMedCrossRefGoogle Scholar
  33. 33.
    Schmucker C, Ehlken C, Agostini HT, Antes G, Ruecker G et al (2012) A safety review and meta-analyses of bevacizumab and ranibizumab: off-label versus goldstandard. PLoS One 7:e42701PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Campochiaro PA, Sophie R, Pearlman J, Brown DM, Boyer DS, Heier JS, Marcus DM, Feiner L (2014) Patel A; RETAIN Study Group. Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN Study. Ophthalmology 121(1):209–219PubMedCrossRefGoogle Scholar
  35. 35.
    Epstein DL, Algvere PV, Von Wendt G, Seregard S, Kvanta A (2012) Benefit from bevacizumab for macular edema in central retinal vein occlusion: twelve-month results of a prospective, randomized study. Ophthalmology 119:2587–2591PubMedCrossRefGoogle Scholar
  36. 36.
    Gokce G, Sobaci G, Durukan AH, Erdurman FC (2013) Intravitreal triamcinolone acetonide compared with bevacizumab for the treatment of patients with macular edema secondary to central retinal vein occlusion. Postgrad Med 125(5):51–58PubMedCrossRefGoogle Scholar
  37. 37.
    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):1040–1044PubMedCrossRefGoogle Scholar
  38. 38.
    Dunavoelgyi R, Sacu S, Eibenberger K, Palkovits S, Leydolt C, Pruente C, Schmidt-Erfurth U (2012) Retreatment with anti-vascular endothelial growth factor therapy based on changes in visual acuity after initial stabilization of neovascular age-related macular degeneration: 3-year follow-up results. Retina 32(8):1471–1479PubMedCrossRefGoogle Scholar
  39. 39.
    Yuan A, Ahmad BU, Xu D, Singh RP, Kaiser PK, Martin DF, Sears JE, Schachat AP, Ehlers JP (2014) Comparison of intravitreal ranibizumab and bevacizumab for the treatment of macular edema secondary to retinal vein occlusion. Int J Ophthalmol 7(1):86–91PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2014

Authors and Affiliations

  • Marina Papadia
    • 1
    • 2
  • Marie Misteli
    • 1
  • Bruno Jeannin
    • 1
  • Carl P. Herbort
    • 1
    • 3
  1. 1.Centre for Ophthalmic Specialized Care (COS)LausanneSwitzerland
  2. 2.Ospedale Antero MiconeGenoaItaly
  3. 3.University of LausanneLausanneSwitzerland

Personalised recommendations