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Editorial Retina Relating to long-term effects of anti-VEGF agents on the retinal circulation, Mir et al. recently reported a promoting effect on the improvement of retinal nonperfusion in RVO patients following monthly ranibizumab injections. 19 This is an interesting aspect, but up to now, no data on long- term (>36 months) observation exist. As a rationale for combining or switching drugs or therapeutic methods one could mention the risk of cumulative toxicity and tachyphylaxis following repeated monotherapy. Unfortunately, limited evidence for combination therapy exists. Unpublished data (Wirth et al., Aflibercept in Branch Retinal Vein Occlusion – clinical outcome 12 months after changing treatment from bevacizumab/ranibizumab) did show a prolongation of retreatment intervals, as well as beneficial functional and anatomic changes after switching from bevacizumab and/or ranibizumab to aflibercept. Combination of steroids and anti-VEGF agents may be of significance in recalcitrant ME, but its superiority (over anti-VEGF alone) remains to be elucidated. Likewise, up to now, no studies have evaluated the outcome of anti-VEGF injections alone versus anti-VEGF plus laser photocoagulation. Apart from that, panretinal laser photocoagulation 1. Klein R, MS, Meuer SM, Klein BE, The 15-year cumulative incidence of retinal vein occlusion: the Beaver Dam Eye Study, Arch Ophthalmol, 2008;126:513–8. 2. Hayreh SS, Zimmerman B, McCarthy MJ, Podhajsky P, Systemic diseases associated with various types of retinal vein occlusion, Am J Ophthalmol, 2001;131:61–77. 3. Nobre Cardoso J, Keane PA, Sim DA, et al., Systematic evaluation of optical coherence tomography angiography in retinal vein occlusion, Am J Ophthalmol, 2016;163:93–107. 4. Cheung N, Klein R, Wang JJ, et al., Traditional and novel cardiovascular risk factors for retinal vein occlusion: the multiethnic study of atherosclerosis, Invest Ophthalmol Vis Sci, 2008;49:4297–302. 5. Hayreh SS, Zimmerman MB, Podhajsky P, Hematologic abnormalities associated with various types of retinal vein occlusion, Graefes Arch Clin Exp Ophthalmol, 2002;240:180–96. 6. Arsene S, Vierron E, Le Lez ML, et al., Conversion from nonischemic to ischemic retinal vein occlusion: prediction by venous velocity on color Doppler imaging, Eur J Ophthalmol, 2009;19:1009–16. 7. Gutman FA, Macular edema in branch retinal vein occlusion: prognosis and management, Trans Sect Ophthalmol Am Acad Ophthalmol Otolaryngol, 1977;83(3 Pt 1):488–95. 8. Rehak M, Wiedemann P, Retinal vein thrombosis: pathogenesis and management, J Thromb Haemost, 2010;8:1886–94. 9. Deobhakta A, Chang LK, Inflammation in retinal vein occlusion, Int J Inflam, 2013;438412. 10. 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 26 was not found to reduce the total VEGF load in BRVO eyes. 20 However, a recent study indicated that the addition of scatter photocoagulation to ranibizumab may reduce progression of retinal nonperfusion in patients with BRVO. 19 To summarise, the achievement of a potential synergistic effect by combination of different interventions requires further study. According to the SHORE and HORIZON studies, there is no superiority in pro re nata (PRN) versus monthly treatment. 21,22 The treat and extend regimen represents a popular option in clinical practice and has been shown to reduce treatment burden and associated costs. 23 Initiating treatment immediately after diagnosis may provide the highest vision gains. 24 Long-term follow-up data from the RETAIN study demonstrated that 50% of eyes still required anti-VEGF injections in regular intervals. 25 To date, we have no final answer on the required duration of treatment. In conclusion, we are fortunate in having a battery of therapeutic methods available. However, for evidence-based management of BRVO, larger comparative studies are needed to conclusively evaluate different therapeutic options as well as their combinations. n Ophthalmol Vis Sci, 2009;50:1025–32. 11. Noma H, Funatsu H, Yamasaki M, et al., Aqueous humour levels of cytokines are correlated to vitreous levels and severity of macular oedema in branch retinal vein occlusion, Eye (Lond), 2008;22:42–8. 12. 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;118:2041–9. 13. Clark WL, Boyer DS, Heier JS, et al., Intravitreal aflibercept for macular edema following branch retinal vein occlusion: 52-week results of the VIBRANT study, Ophthalmology, 2016;123:330–6. 14. Haller JA, Bandello F, Belfort R Jr, et al., Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results, Ophthalmology, 2011;118:2453–60. 15. 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;127:1101–14. 16. Vujosevic S, Midena E, Controversies in pharmacological treatment of inflammatory component of macular edema, Curr Pharm Des, 2015;21:4688–93. 17. Garweg JG, Zandi S, Retinal vein occlusion and the use of a dexamethasone intravitreal implant (Ozurdex(R)) in its treatment, Graefes Arch Clin Exp Ophthalmol, 2016;254:1257. 18. Wang JK, Su PY, Hsu YR, et al., Comparison of the efficacy of 19. 20. 21. 22. 23. 24. 25. intravitreal aflibercept and bevacizumab for macular edema secondary to branch retinal vein occlusion, J Ophthalmol, 2016;8421940. Mir TA, Kherani S, Hafiz G, et al., Changes in retinal nonperfusion associated with suppression of vascular endothelial growth factor in retinal vein occlusion, Ophthalmology, 2016;123:625–34. Campochiaro PA, Hafiz G, Mir TA, et al., Scatter photocoagulation does not reduce macular edema or treatment burden in patients with retinal vein occlusion: the RELATE trial, Ophthalmology, 2015;122:1426–37. Campochiaro PA, Wykoff CC, Singer M, et al., Monthly versus as-needed ranibizumab injections in patients with retinal vein occlusion: the SHORE study, Ophthalmology, 2014;121:2432–42. 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;119:802– 9. Rush RB, Simunovic MP, Aragon AV 2nd, Ysasaga JE, Treat- and-extend intravitreal bevacizumab for branch retinal vein occlusion, Ophthalmic Surg Lasers Imaging Retina, 2014;45:212–6. Thach AB, Yau L, Hoang C, Tuomi L, Time to clinically significant visual acuity gains after ranibizumab treatment for retinal vein occlusion: BRAVO and CRUISE trials, Ophthalmology, 2014;121:1059–66. Campochiaro PA, Sophie R, Pearlman J, et al., Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab: the RETAIN study, Ophthalmology, 2014;121:209–19. EUR OP EAN OP H TH ALMIC RE VIE W