Anatomical and functional responses to single brolucizumab injection in neovascular age-related macular degeneration patients not responding to antiangiogenics: a case series

Authors

  • Silvio Zuccarini Villa Donatello Hospital, Department of Ophthalmology, Florence - Italy
  • Fabrizio Puce Villa Donatello Hospital, Department of Ophthalmology, Florence - Italy
  • Alessandro Crisà Villa Donatello Hospital, Department of Ophthalmology, Florence - Italy

DOI:

https://doi.org/10.33393/dti.2022.2343

Keywords:

Anti-VEGF, Brolucizumab, Case series, Neovascular age-related macular degeneration (nAMD)

Abstract

Introduction: Neovascular age-related macular degeneration (nAMD) is treated with antivascular endothelial growth factor (anti-VEGF) drugs. However, resistance to anti-VEGF therapy is observed in some patients. Brolucizumab is a new-generation anti-VEGF drug for the treatment of nAMD, with proven efficacy in fluid resolution and long-lasting effects.

Methods: We report here a case series of nAMD patients not responding to previous anti-VEGF therapy showing anatomical and functional response to a single intravitreal injection of brolucizumab.

Results: Nine patients with nAMD, undergoing treatment with anti-VEGF therapy (aflibercept, bevacizumab, or ranibizumab) but with either fluid persistence or frequent fluid recurrences in retinal compartments, were switched to intravitreal brolucizumab and examined 4 weeks postinjection. No signs of active disease were observed in all but one patient, with complete retinal fluid resolution in seven patients. Central macular thickness and visual acuity significantly improved, and changes were sustained for up to 12 weeks in a subset of three patients. No adverse reactions were observed.

Conclusions: This new anti-VEGF drug showed great efficacy since the first week from the injection with a significative reduction of subretinal fluid and rapid improvement of visual acuity. In conclusion, brolucizumab administered intravitreally appears to be an effective treatment in nAMD patients, leading to both early anatomical and functional improvements.

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References

Grossniklaus HE, Green WR. Choroidal neovascularization. Am J Ophthalmol. 2004;137(3):496-503. https://doi.org/10.1016/j.ajo.2003.09.042 PMID:15013874 DOI: https://doi.org/10.1016/j.ajo.2003.09.042

Spaide RF, Jaffe GJ, Sarraf D, et al. Consensus nomenclature for reporting neovascular age-related macular degeneration data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group. Ophthalmology. 2020;127(5):616-636. https://doi.org/10.1016/j.ophtha.2019.11.004 PMID:31864668 DOI: https://doi.org/10.1016/j.ophtha.2019.11.004

Schmidt-Erfurth U, Waldstein SM. A paradigm shift in imaging biomarkers in neovascular age-related macular degeneration. Prog Retin Eye Res. 2016;50:1-24. https://doi.org/10.1016/j.preteyeres.2015.07.007 PMID:26307399 DOI: https://doi.org/10.1016/j.preteyeres.2015.07.007

Wykoff CC, Clark WL, Nielsen JS, Brill JV, Greene LS, Heggen CL. Optimizing anti-VEGF treatment outcomes for patients with neovascular age-related macular degeneration. J Manag Care Spec Pharm. 2018 Feb;24(2-a Suppl):S3-S15. https://doi.org/10.18553/jmcp.2018.24.2-a.s3 PMID: 29383980. DOI: https://doi.org/10.18553/jmcp.2018.24.2-a.s3

Rasmussen A, Brandi S, Fuchs J, et al. Visual outcomes in relation to time to treatment in neovascular age-related macular degeneration. Acta Ophthalmol. 2015;93(7):616-620. https://doi.org/10.1111/aos.12781 PMID:26073051 DOI: https://doi.org/10.1111/aos.12781

Real JP, Granero GE, De Santis MO, et al. Rate of vision loss in neovascular age-related macular degeneration explored. Graefes Arch Clin Exp Ophthalmol. 2015;253(11):1859-1865. https://doi.org/10.1007/s00417-014-2885-y PMID:25491161 DOI: https://doi.org/10.1007/s00417-014-2885-y

Arnold JJ, Markey CM, Kurstjens NP, Guymer RH. The role of sub-retinal fluid in determining treatment outcomes in patients with neovascular age-related macular degeneration—a phase IV randomised clinical trial with ranibizumab: the FLUID study. BMC Ophthalmol. 2016;16(1):31. https://doi.org/10.1186/s12886-016-0207-3 PMID:27009515 DOI: https://doi.org/10.1186/s12886-016-0207-3

Lanzetta P, Loewenstein A; Vision Academy Steering Committee. Fundamental principles of an anti-VEGF treatment regimen: optimal application of intravitreal anti-vascular endothelial growth factor therapy of macular diseases. Graefes Arch Clin Exp Ophthalmol. 2017;255(7):1259-1273. https://doi.org/10.1007/s00417-017-3647-4 PMID:28527040 DOI: https://doi.org/10.1007/s00417-017-3647-4

Gillies M, Arnold J, Bhandari S, et al. Ten-year treatment outcomes of neovascular age-related macular degeneration from two regions. Am J Ophthalmol. 2020;210:116-124. https://doi.org/10.1016/j.ajo.2019.10.007 PMID:31606444 DOI: https://doi.org/10.1016/j.ajo.2019.10.007

Chandra S, Arpa C, Menon D, et al. Ten-year outcomes of antivascular endothelial growth factor therapy in neovascular age-related macular degeneration. Eye (Lond). 2020;34(10):1888-1896. https://doi.org/10.1038/s41433-020-0764-9 PMID:31980748 DOI: https://doi.org/10.1038/s41433-020-0764-9

Heier JS, Brown DM, Chong V, et al; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012;119(12):2537-2548. https://doi.org/10.1016/j.ophtha.2012.09.006 PMID:23084240 DOI: https://doi.org/10.1016/j.ophtha.2012.09.006

Guymer RH, Markey CM, McAllister IL, et al; FLUID Investigators. Tolerating subretinal fluid in neovascular age-related macular degeneration treated with ranibizumab using a treat-and-extend regimen: FLUID study 24-month results. Ophthalmology. 2019;126(5):723-734. https://doi.org/10.1016/j.ophtha.2018.11.025 PMID:30502372 DOI: https://doi.org/10.1016/j.ophtha.2018.11.025

Bhandari S, Nguyen V, Arnold J, et al. Treatment outcomes of ranibizumab versus aflibercept for neovascular age-related macular degeneration: data from the Fight Retinal Blindness! Registry. Ophthalmology. 2020;127(3):369-376. https://doi.org/10.1016/j.ophtha.2019.10.006 PMID:31757494 DOI: https://doi.org/10.1016/j.ophtha.2019.10.006

Essex RW, Nguyen V, Walton R, et al; Fight Retinal Blindness Study Group. Treatment patterns and visual outcomes during the maintenance phase of treat-and-extend therapy for age-related macular degeneration. Ophthalmology. 2016;123(11):2393-2400. https://doi.org/10.1016/j.ophtha.2016.07.012 PMID:27554034 DOI: https://doi.org/10.1016/j.ophtha.2016.07.012

Nguyen V, Vaze A, Fraser-Bell S, et al; Fight Retinal Blindness! Study Group. Outcomes of suspending VEGF inhibitors for neovascular age-related macular degeneration when lesions have been inactive for 3 months. Ophthalmol Retina. 2019;3(8):623-628. https://doi.org/10.1016/j.oret.2019.05.013 PMID:31281103 DOI: https://doi.org/10.1016/j.oret.2019.05.013

Rusakevich AM, Zhou B, Wong TP, Wykoff CC. Quarterly anti-vascular endothelial growth factor dosing for neovascular age-related macular degeneration: real-world clinical outcomes. Ophthalmic Surg Lasers Imaging Retina. 2019;50(9):e250-e256. https://doi.org/10.3928/23258160-20190905-17 PMID:31589766 DOI: https://doi.org/10.3928/23258160-20190905-17

Monés J, Singh RP, Bandello F, Souied E, Liu X, Gale R. Undertreatment of neovascular age-related macular degeneration after 10 years of anti-vascular endothelial growth factor therapy in the real world: the need for a change of mindset. Ophthalmologica. 2020;243(1):1-8. https://doi.org/10.1159/000502747 PMID:31743912 DOI: https://doi.org/10.1159/000502747

Gillies MC, Campain A, Barthelmes D, et al; Fight Retinal Blindness Study Group. Long-term outcomes of treatment of neovascular age-related macular degeneration: data from an observational study. Ophthalmology. 2015;122(9):1837-1845. https://doi.org/10.1016/j.ophtha.2015.05.010 PMID:26096346 DOI: https://doi.org/10.1016/j.ophtha.2015.05.010

Binder S. Loss of reactivity in intravitreal anti-VEGF therapy: tachyphylaxis or tolerance? Br J Ophthalmol. 2012;96(1):1-2. https://doi.org/10.1136/bjophthalmol-2011-301236PMID:22157632 DOI: https://doi.org/10.1136/bjophthalmol-2011-301236

Chakravarthy U, Bezlyak V, Sagkriotis A, et al. Effectiveness of continued ranibizumab therapy in neovascular age-related macular degeneration versus switch to aflibercept: real world evidence. Ophthalmol Retina. 2019;3(1):8-15.e1. https://doi.org/10.1016/j.oret.2018.09.001 PMID:30929819 DOI: https://doi.org/10.1016/j.oret.2018.09.001

Nguyen CL, Gillies MC, Nguyen V, et al; Fight Retinal Blindness! Study Group. Characterization of poor visual outcomes of neovascular age-related macular degeneration treated with anti-vascular endothelial growth factor agents. Ophthalmology. 2019;126(5):735-742. https://doi.org/10.1016/j.ophtha.2018.11.036 PMID:30529685 DOI: https://doi.org/10.1016/j.ophtha.2018.11.036

Salcedo-Villanueva G, Feria-Anzaldo E, Romo-Aguas JC, et al. Anti-VEGF treatment switch in neovascular age-related macular degeneration: a comparison of aflibercept versus ranibizumab after a single-dose switch. Int Ophthalmol. 2019;39(9):2023-2031. https://doi.org/10.1007/s10792-018-1038-4 PMID:30386955 DOI: https://doi.org/10.1007/s10792-018-1038-4

Dugel PU, Singh RP, Koh A, et al. HAWK and HARRIER: Ninety-six-week outcomes from the phase 3 trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2021;128(1):89-99. https://doi.org/10.1016/j.ophtha.2020.06.028PMID:32574761

Dugel PU, Koh A, Ogura Y, et al; HAWK and HARRIER Study Investigators. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology. 2020;127(1):72-84. https://doi.org/10.1016/j.ophtha.2019.04.017 PMID:30986442 DOI: https://doi.org/10.1016/j.ophtha.2019.04.017

Sharma A, Kumar N, Parachuri N, et al. Brolucizumab-early real-world experience: BREW study. Eye (Lond). 2021;35(4):1045-1047. https://doi.org/10.1038/s41433-020-1111-xPMID:32709960 DOI: https://doi.org/10.1038/s41433-020-1111-x

Avaylon J, Lee S, Gallemore RP. Case series on initial responses to intravitreal brolucizumab in patients with recalcitrant chronic wet age-related macular degeneration. Int Med Case Rep J. 2020;13:145-152. https://doi.org/10.2147/IMCRJ.S252260 PMID:32494207 DOI: https://doi.org/10.2147/IMCRJ.S252260

Seguin-Greenstein S, Lightman S, Tomkins-Netzer O. A meta-analysis of studies evaluating visual and anatomical outcomes in patients with treatment resistant neovascular age-related macular degeneration following switching to treatment with aflibercept. J Ophthalmol. 2016;2016:4095852. https://doi.org/10.1155/2016/4095852 PMID:27042342 DOI: https://doi.org/10.1155/2016/4095852

Enríquez AB, Baumal CR, Crane AM, et al. Early experience with brolucizumab treatment of neovascular age-related macular degeneration. JAMA Ophthalmol. 2021;139(4):441-448. https://doi.org/10.1001/jamaophthalmol.2020.7085 PMID:33630045 DOI: https://doi.org/10.1001/jamaophthalmol.2020.7085

Bontzos G, Bagheri S, Ioanidi L, et al. Nonresponders to ranibizumab anti-VEGF treatment are actually short-term responders: a prospective spectral-domain OCT study. Ophthalmol Retina. 2020;4(12):1138-1145. https://doi.org/10.1016/j.oret.2019.11.004 PMID:31937473 DOI: https://doi.org/10.1016/j.oret.2019.11.004

Zola M, D’Alessandro E, Sherif M, et al. Refractory neovascular age-related macular degeneration: time-dependent changes of central retinal thickness with anti-VEGF treatment. Graefes Arch Clin Exp Ophthalmol. 2021 Jun;259(6):1477-1486 https://doi.org/10.1007/s00417-020-05000-3 PMID:33245426 DOI: https://doi.org/10.1007/s00417-020-05000-3

Monés J, Srivastava SK, Jaffe GJ, et al. Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology. 2021 Jul;128(7):1050-1059. https://doi.org/10.1016/j.ophtha.2020.11.011 PMID:33207259 DOI: https://doi.org/10.1016/j.ophtha.2021.04.029

Published

2022-03-24

How to Cite

Zuccarini, S. ., Puce, F. ., & Crisà, A. . (2022). Anatomical and functional responses to single brolucizumab injection in neovascular age-related macular degeneration patients not responding to antiangiogenics: a case series. Drug Target Insights, 16(1), 6–11. https://doi.org/10.33393/dti.2022.2343

Issue

Section

Original Research Article
Received 2021-09-24
Accepted 2022-03-16
Published 2022-03-24

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