Five-year outcomes of retinal vein occlusion treated with vascular endothelial growth factor inhibitors

Kimberly Spooner, Samantha Fraser-Bell, Thomas Hong, Andrew A Chang, Kimberly Spooner, Samantha Fraser-Bell, Thomas Hong, Andrew A Chang

Abstract

Purpose: Report 5-year outcomes of patients receiving anti-vascular endothelial growth factor (VEGF) for the treatment of macular oedema secondary to retinal vein occlusion (RVO.

Methods: Retrospective review of eyes with RVO which initiated anti-VEGF treatment. Data including age, gender, visual acuity (VA) and injection numbers were obtained from medical records. Optical coherence tomography scans were graded for presence or absence of macular oedema and central foveal thickness (CFT). Macular perfusion was assessed on fundus fluorescein angiography by masked graders.

Results: 68 eyes (31 branch RVO, BRVO; 35 central RVO, CRVO and 2 hemi-RVO) with 5 years of follow-up after initiation of anti-VEGF treatment. Mean change in VA at 5 years was + 9.6 ± 21.6 letters among CRVO eyes and + 14.2 ± 15.6 letters among eyes with BRVO (p=0.001). Vision of 20/40 or better was achieved in 65 % of treated eyes. The proportion of eyes with a three-line improvement of vision (15 letters) at 5 years was 22 %. Mean CFT decreased by 257.6 ± 249.8 µm in eyes with CRVO and 145.6 ± 143.3 µm in eyes with BRVO.

Conclusion: The results confirm good long-term outcomes can be achieved with anti-VEGF therapy for RVO.

Keywords: retina; treatment medical.

Conflict of interest statement

Competing interests: AAC has acted as a consultant for Novartis, Bayer and Alcon. SF-B has acted as a consultant for Bayer, Novartis and Allergan.

Figures

Figure 1
Figure 1
BRVO analysis: (a) mean change in visual acuity and (b) central foveal thickness over 5 years. BRVO, branch retinal vein occlusion; ETDRS, Early Treatment Diabetic Retinopathy Study.
Figure 2
Figure 2
BRVO analysis: mean change in central foveal thickness over 5 years. BRVO, branch retinal vein occlusion.
Figure 3
Figure 3
Injection frequency by patient over 5 years of anti-VEGF therapy. BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion; HVRO, hemi-retinal vein occlusion; VEGF, vascular endothelial growth factor.
Figure 4
Figure 4
CRVO subtype analysis: mean change in CFT in microns from baseline to 5 years follow-up. CFT, central foveal thickness; CRVO, central retinal vein occlusion; HRVO, hemi-retinal vein occlusion.
Figure 5
Figure 5
CRVO subgroup analysis: mean change in visual acuity in ETDRS letters from baseline to 5 years. CRVO, central retinal vein occlusion; ETDRS, Early Treatment Diabetic Retinopathy Study; HRVO, hemi-retinal vein occlusion.

References

    1. Hayreh SS. Ocular vascular occlusive disorders: natural history of visual outcome. Prog Retin Eye Res 2014;41:1–25. 10.1016/j.preteyeres.2014.04.001
    1. Jiang Y, Mieler WF. Update on the use of anti-VEGF intravitreal therapies for retinal vein occlusions. Asia Pac J Ophthalmol 2017;6:546–53. 10.22608/APO.2017459
    1. Li J, Paulus YM, Shuai Y, et al. . New developments in the classification, pathogenesis, risk factors, natural history, and treatment of branch retinal vein occlusion. J Ophthalmol 2017;2017:1–18. 10.1155/2017/4936924
    1. Appiah AP, Trempe CL. Differences in contributory factors among hemicentral, central, and branch retinal vein occlusions. Ophthalmology 1989;96:364–6. 10.1016/S0161-6420(89)32884-3
    1. Deramo VA, Cox TA, Syed AB, et al. . Vision-related quality of life in people with central retinal vein occlusion using the 25-item National Eye Institute visual function questionnaire. Arch Ophthalmol 2003;121:1297–302. 10.1001/archopht.121.9.1297
    1. Awdeh RM, Elsing SH, Deramo VA, et al. . Vision-related quality of life in persons with unilateral branch retinal vein occlusion using the 25-item National Eye Institute visual function questionnaire. Br J Ophthalmol 2010;94:319–23. 10.1136/bjo.2007.135913
    1. Tsukada K, Tsujikawa A, Murakami T, et al. . Lamellar macular hole formation in chronic cystoid macular edema associated with retinal vein occlusion. Jpn J Ophthalmol 2011;55:506–13. 10.1007/s10384-011-0056-9
    1. Karia N. Retinal vein occlusion: pathophysiology and treatment options. Clin Ophthalmol 2010;4:809–16. 10.2147/OPTH.S7631
    1. Noma H, Funatsu H, Yamasaki M, et al. . Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6. Am J Ophthalmol 2005;140:256.e1–256.e7. 10.1016/j.ajo.2005.03.003
    1. Yoshimura T, Sonoda K-hei, Sugahara M, et al. . Comprehensive analysis of inflammatory immune mediators in vitreoretinal diseases. PLoS One 2009;4:e8158 10.1371/journal.pone.0008158
    1. McIntosh RL, Rogers SL, Lim L, et al. . Natural history of central retinal vein occlusion: an evidence-based systematic review. Ophthalmology 2010;117:1113–23. 10.1016/j.ophtha.2010.01.060
    1. Decroos FC, Fekrat S. The natural history of retinal vein occlusion: what do we really know? Am J Ophthalmol 2011;151:739–41. 10.1016/j.ajo.2010.12.012
    1. Avery RL, Castellarin AA, Steinle NC, et al. . Systemic pharmacokinetics following intravitreal injections of ranibizumab, bevacizumab or aflibercept in patients with neovascular AMD. Br J Ophthalmol 2014;98:1636–41. 10.1136/bjophthalmol-2014-305252
    1. Edington M, Connolly J, Chong NV. Pharmacokinetics of intravitreal anti-VEGF drugs in vitrectomized versus non-vitrectomized eyes. Expert Opin Drug Metab Toxicol 2017;13:1217–24. 10.1080/17425255.2017.1404987
    1. Moisseiev E, Waisbourd M, Ben-Artsi E, et al. . Pharmacokinetics of bevacizumab after topical and intravitreal administration in human eyes. Graefes Arch Clin Exp Ophthalmol 2014;252:331–7. 10.1007/s00417-013-2495-0
    1. Korobelnik J-F, Holz FG, Roider J, et al. . Intravitreal Aflibercept Injection for Macular Edema Resulting from Central Retinal Vein Occlusion: One-Year Results of the Phase 3 GALILEO Study. Ophthalmology 2014;121:202–8. 10.1016/j.ophtha.2013.08.012
    1. Thach AB, Yau L, Hoang C, et al. . Time to clinically significant visual acuity gains after ranibizumab treatment for retinal vein occlusion. Ophthalmology 2014;121:1059–66. 10.1016/j.ophtha.2013.11.022
    1. 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. 10.1016/j.ophtha.2015.09.035
    1. Scott IU, VanVeldhuisen PC, Ip MS, et al. . Effect of bevacizumab vs aflibercept on visual acuity among patients with macular edema due to central retinal vein occlusion: the SCORE2 randomized clinical trial. JAMA 2017;317 10.1001/jama.2017.4568
    1. 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.
    1. Campochiaro PA, Sophie R, Pearlman J, et al. . Long-term outcomes in patients with retinal vein occlusion treated with ranibizumab. Ophthalmology 2014;121:209–19. 10.1016/j.ophtha.2013.08.038
    1. Rezar S, Eibenberger K, Bühl W, et al. . Anti-VEGF treatment in branch retinal vein occlusion: a real-world experience over 4 years. Acta Ophthalmologica 2015;93:719–25. 10.1111/aos.12772
    1. Larsen M, Waldstein SM, Boscia F, et al. . Individualized ranibizumab regimen driven by stabilization criteria for central retinal vein occlusion: Twelve-Month results of the crystal study. Ophthalmology 2016;123:1101–11. 10.1016/j.ophtha.2016.01.011
    1. Brown DM, Wykoff CC, Wong TP, et al. . Ranibizumab in preproliferative (ischemic) central retinal vein occlusion: the rubeosis anti-VEGF (RAVE) trial. Retina 2014;34:1728–35. 10.1097/IAE.0000000000000191
    1. Gregori NZ, Feuer W, Rosenfeld PJ. Novel method for analyzing Snellen visual acuity measurements. Retina 2010;30:1046–50. 10.1097/IAE.0b013e3181d87e04
    1. Wirth MA, Becker MD, Graf N, et al. . Aflibercept in branch retinal vein occlusion as second line therapy: clinical outcome 12 months after changing treatment from bevacizumab/ranibizumab—a pilot study. Int J Retin Vitr 2016;2 10.1186/s40942-016-0045-8
    1. Evoy KE, Abel SR. Aflibercept: newly approved for the treatment of macular edema following central retinal vein occlusion. Ann Pharmacother 2013;47:819–27. 10.1345/aph.1R705
    1. Rishi P, Raka N, Rishi E. Analysis of potential ischemic effect of intravitreal bevacizumab on unaffected retina in treatment-naïve macular edema due to branch retinal vein occlusion: a prospective, interventional Case-Series. PLoS One 2016;11:e0162533 10.1371/journal.pone.0162533
    1. Mitry D, Bunce C, Charteris D, et al. . Anti-vascular endothelial growth factor for macular oedema secondary to branch retinal vein occlusion. Cochrane Database of Systematic Reviews 2013;118 10.1002/14651858.CD009510.pub2
    1. Osaka R, Muraoka Y, Miwa Y, et al. . Anti-vascular endothelial growth factor therapy for macular edema following central retinal vein occlusion: 1 initial injection versus 3 monthly injections. Ophthalmologica 2018;239:27–35. 10.1159/000479049
    1. Wecker T, Ehlken C, Bühler A, et al. . Five-year visual acuity outcomes and injection patterns in patients with pro-re-nata treatments for AMD, DME, RVO and myopic CNV. Br J Ophthalmol 2017;101:353–9. 10.1136/bjophthalmol-2016-308668
    1. Khan M, Wai KM, Silva FQ, et al. . Comparison of ranibizumab and bevacizumab for macular edema secondary to retinal vein occlusions in routine clinical practice. Ophthalmic Surg Lasers Imaging Retina 2017;48:465–72. 10.3928/23258160-20170601-04
    1. Sakanishi Y, Lee A, Usui-Ouchi A, et al. . Twelve-month outcomes in patients with retinal vein occlusion treated with low-frequency intravitreal ranibizumab. Clin Ophthalmol 2016;10:1161–5. 10.2147/OPTH.S107594
    1. Brynskov T, Kemp H, Sørensen TL. Intravitreal ranibizumab for retinal vein occlusion through 1 year in clinical practice. Retina 2014;34:1637–43. 10.1097/IAE.0000000000000111
    1. Chatziralli I, Theodossiadis G, Chatzirallis A, et al. . Ranibizumab for retinal vein occlusion: predictive factors and long-term outcomes in real-life data. Retina 2018;38:559–68. 10.1097/IAE.0000000000001579
    1. Kornhauser T, Schwartz R, Goldstein M, et al. . Bevacizumab treatment of macular edema in CRVO and BRVO: long-term follow-up. (BERVOLT study: bevacizumab for RVO long-term follow-up). Graefes Arch Clin Exp Ophthalmol 2016;254:835–44. 10.1007/s00417-015-3130-z
    1. 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. Am J Ophthalmol 2014;157:237–47. 10.1016/j.ajo.2013.08.013
    1. Brown DM, Heier JS, Clark WL, et al. . Intravitreal aflibercept injection for macular edema secondary to central retinal vein occlusion: 1-year results from the phase 3 COPERNICUS study. Am J Ophthalmol 2013;155:429–37. 10.1016/j.ajo.2012.09.026
    1. Hayreh SS, Podhajsky PA, Zimmerman MB. Natural history of visual outcome in central retinal vein occlusion. Ophthalmology 2011;118:e1-2.:119–33. 10.1016/j.ophtha.2010.04.019
    1. Boyd SR, Zachary I, Chakravarthy U, et al. . Correlation of increased vascular endothelial growth factor with neovascularization and permeability in ischemic central vein occlusion. Arch Ophthalmol 2002;120:1644–50. 10.1001/archopht.120.12.1644
    1. Campochiaro PA, Bhisitkul RB, Shapiro H, et al. . Vascular endothelial growth factor promotes progressive retinal nonperfusion in patients with retinal vein occlusion. Ophthalmology 2013;120:795–802. 10.1016/j.ophtha.2012.09.032
    1. Campochiaro PA, Wykoff CC, Shapiro H, et al. . Neutralization of vascular endothelial growth factor slows progression of retinal nonperfusion in patients with diabetic macular edema. Ophthalmology 2014;121:1783–9. 10.1016/j.ophtha.2014.03.021
    1. 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. 10.1016/j.ophtha.2015.10.030
    1. Hayreh SS, Zimmerman MB. Fundus changes in branch retinal vein occlusion. Retina 2015;35:1016–27. 10.1097/IAE.0000000000000418
    1. Rothwell PM. External validity of randomised controlled trials: “To whom do the results of this trial apply?”. The Lancet 2005;365:82–93. 10.1016/S0140-6736(04)17670-8
    1. Winegarner A, Wakabayashi T, Fukushima Y, et al. . Changes in retinal microvasculature and visual acuity after antivascular endothelial growth factor therapy in retinal vein occlusion. Invest Ophthalmol Vis Sci 2018;59:2708–16. 10.1167/iovs.17-23437
    1. DeCroos FC, Ehlers JP, Stinnett S, et al. . Intravitreal bevacizumab for macular edema due to central retinal vein occlusion: perfused vs. ischemic and early vs. late treatment. Curr Eye Res 2011;36:1164–70. 10.3109/02713683.2011.607537
    1. Campochiaro PA, Heier JS, Feiner L, et al. . Ranibizumab for macular edema following branch retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 2010;117:1102–12. 10.1016/j.ophtha.2010.02.021
    1. Varma R, Bressler NM, Suñer I, et al. . Improved vision-related function after ranibizumab for macular edema after retinal vein occlusion: results from the BRAVO and cruise trials. Ophthalmology 2012;119:2108–18. 10.1016/j.ophtha.2012.05.017

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe