Visual acuity outcomes and anti-VEGF therapy intensity in macular oedema due to retinal vein occlusion: a real-world analysis of 15 613 patient eyes

Thomas Ciulla, John S Pollack, David F Williams, Thomas Ciulla, John S Pollack, David F Williams

Abstract

Background/aims: To assess visual acuity (VA) outcomes and antivascular endothelial growth factor (anti-VEGF) therapy intensity in retinal vein occlusion (RVO)-related macular oedema (ME).

Methods: A retrospective study was completed in treatment-naïve patients with RVO-related ME from 2013 to 2019, using the Vestrum Health Retina Database.

Results: Mean baseline age was 72.4 years and 54% were women. In 6 months, in 8876 eyes with branch retinal vein occlusion (BRVO)-related ME, after a mean of 4.5 anti-VEGF injections, VA increased by 9.4 letters (95% confidence interval (CI) for change in VA +8.94 to +9.78, p<0.001) from a baseline of 55.1 letters. In 6737 eyes with central retinal vein occlusion (CRVO)-related ME, after a mean of 4.6 anti-VEGF injections over 6 months, VA improved by 9.2 letters (95% CI +8.50 to +9.87, p<0.001) from a baseline of 37.2 letters. In 1 year, VA gain was similar (BRVO: 7.4 injections, +8.1 letters, 95% CI +7.55 to +8.57, p<0.001; CRVO: 7.6 injections, +7.1 letters, 95% CI +6.31 to +7.95, p<0.001). In 6 months and 1 year, mean letters gain increased with number of anti-VEGF injections. Patient eyes with baseline VA of 20/40 or better tended to lose VA in 1 year.

Conclusion: Mean change in VA correlates with treatment intensity, but patients with better VA at presentation are susceptible to vision loss, reflecting a ceiling effect. Assessed with the same database, VA gains compare favourably with 1-year VA gains in neovascular age-related macular degeneration and diabetic ME, but exhibit a larger gap when compared with corresponding randomised controlled trials.

Keywords: Macula; Retina; Treatment Medical.

Conflict of interest statement

Competing interests: Drs Pollack and Williams are co-founders of Vestrum Health, whose database was utilised for this study.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Histograms showing distribution of patient eyes with retinal vein occlusion stratified by number of antivascular endothelial growth factor injections received in 6 months and 1 year. BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion.
Figure 2
Figure 2
Graphs showing change in visual acuity (VA) versus antivascular endothelial growth factor injections administered to all patient eyes with retinal vein occlusion in 6 months and 1 year. The 95% CIs are included. Mean VA change tended to increase with greater treatment intensity. BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion.
Figure 3
Figure 3
Graphs showing the mean number of anti-vascular endothelial growth factor injections and mean visual acuity (VA) change in patient eyes with retinal vein occlusion over 6 months and 1 year, overall and stratified by baseline VA. There were ceiling effects related to baseline VA; mean VA change tended to increase in patient eyes with decreased baseline VA, despite similar treatment intensity. BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion.

References

    1. ASRS 2017 . Preferences and trends membership survey . Chicago, IL: American Society of Retina Specialists, 2017.
    1. Ciulla TA, Bracha P, Pollack J, et al. Real-world outcomes of anti-vascular endothelial growth factor therapy in diabetic macular edema in the United States. Ophthalmol Retina 2018;2:1179–1187. 10.1016/j.oret.2018.06.004
    1. Ciulla TA, Huang F, Westby K, et al. Real-world outcomes of anti-vascular endothelial growth factor therapy in neovascular age-related macular degeneration in the United States. Ophthalmol Retina 2018;2:645–653. 10.1016/j.oret.2018.01.006
    1. Ciulla TA, Hussain RM, Pollack JS, et al. Visual acuity outcomes and anti-vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients: a real-world analysis of 49 485 eyes. Ophthalmol Retina 2020;4:19–30. 10.1016/j.oret.2019.05.017
    1. Ciulla TA, Pollack JS, Williams DF. Visual acuity outcomes and anti-VEGF therapy intensity in diabetic macular oedema: a real-world analysis of 28 658 patient eyes. Br J Ophthalmol 2020. Published Online First. 10.1136/bjophthalmol-2020-315933
    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. Gale R, Pikoula M, Lee AY, et al. Real world evidence on 5661 patients treated for macular oedema secondary to branch retinal vein occlusion with intravitreal anti-vascular endothelial growth factor, intravitreal dexamethasone or macular laser. Br J Ophthalmol 2020. 10.1136/bjophthalmol-2020-315836
    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;117:1102–1112 e1. 10.1016/j.ophtha.2010.02.021
    1. Brown DM, Campochiaro PA, Bhisitkul RB, et al. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology 2011;118:p.1594–602. 10.1016/j.ophtha.2011.02.022
    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;123:330–336. 10.1016/j.ophtha.2015.09.035
    1. Campochiaro PA, Clark WL, Boyer DS, et al. Intravitreal aflibercept for macular edema following branch retinal vein occlusion: the 24-week results of the VIBRANT study. Ophthalmology 2015;122:538–44. 10.1016/j.ophtha.2014.08.031
    1. 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:p.2041–9. 10.1016/j.ophtha.2011.02.038
    1. Brown DM, Campochiaro PA, Singh RP, et al. Ranibizumab for macular edema following central retinal vein occlusion: six-month primary end point results of a phase III study. Ophthalmology 2010;117:1124–1133 e1. 10.1016/j.ophtha.2010.02.022
    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;155:429–437 e7. 10.1016/j.ajo.2012.09.026
    1. Korobelnik JF, 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:p.202–208. 10.1016/j.ophtha.2013.08.012
    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:p.2072–2087. 10.1001/jama.2017.4568
    1. Fogli S, Del Re M, Rofi E, et al. Clinical pharmacology of intravitreal anti-VEGF drugs. Eye (Lond) 2018;32:1010–1020. 10.1038/s41433-018-0021-7
    1. Krohne TU, Liu Z, Holz FG, et al. Intraocular pharmacokinetics of ranibizumab following a single intravitreal injection in humans. Am J Ophthalmol 2012;154:682–686 e2. 10.1016/j.ajo.2012.03.047
    1. Stewart MW. What are the half-lives of ranibizumab and aflibercept (VEGF Trap-eye) in human eyes? Calculations with a mathematical model. Eye Rep 2011;1:12–14. 10.4081/eye.2011.e5
    1. Stewart MW, Rosenfeld PJ, Penha FM, et al. Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor Trap-eye). Retina 2012;32:434–57. 10.1097/IAE.0B013E31822C290F
    1. Stewart MW. Pharmacokinetics, pharmacodynamics and pre-clinical characteristics of ophthalmic drugs that bind VEGF. Expert Rev Clin Pharmacol 2014;7:167–80. 10.1586/17512433.2014.884458
    1. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med 2006;355:1432–44. 10.1056/NEJMoa062655
    1. Martin DF, Maguire MG, Ying GS, et al. Ranibizumab and bevacizumab for neovascular age-related macular degeneration. N Engl J Med 2011;364:1897–908. 10.1056/NEJMoa1102673
    1. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012;119:2537–48. 10.1016/j.ophtha.2012.09.006
    1. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med 2006;355:1419–31. 10.1056/NEJMoa054481
    1. Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology 2014;121:2247–54. 10.1016/j.ophtha.2014.05.006
    1. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 2012;119:789–801. 10.1016/j.ophtha.2011.12.039
    1. Wells JA, Glassman AR, Ayala AR, et al. Aflibercept, bevacizumab, or ranibizumab for diabetic macular edema. N Engl J Med 2015;372:1193–203. 10.1056/NEJMoa1414264

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