Side Effects of Brolucizumab


Age-related macular degeneration and its complication, subretinal neovascularization, are common causes of progressive, irreversible impairment of central vision. Antivascular endothelial growth factor (anti-VEGF) therapy has improved the visual outcome and provided an evolution in the treatment of retinal disease. The current four anti- VEGF drugs – pegaptanib, ranibizumab, aflibercept, and bevacizumab – have been administered for many years. A new anti-VEGF agent, brolucizumab, was approved by the U.S. Food and Drug Administration (FDA) in late 2019 for the treatment of wet agerelated macular degeneration. Brolucizumab is a novel single-chain fragment variable antibody that inhibits all isoforms of VEGF-A and has been suggested to have more tissue penetration. Despite all the benefits, there are some reports of serious side effects that need to be understood in managing patients. Brolucizumab has been reported to cause occlusive retinal vasculitis in the setting of intraocular inflammation, which has not been seen in other anti-VEGF medications. A PubMed and Scopus search was performed and all article types were included. In the present article, we have reviewed the reported side effects of brolucizumab.


Anti-vascular Endothelial Growth Factor, Brolucizumab, Wet Age-related Macular Degeneration

1. Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health 2014;2:e106–e116.

2. Gragoudas ES, Adamis AP, Cunningham ET, Jr, Feinsod M, Guyer DR, Group VISiONCT. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med 2004;351:2805–2816.

3. Comparison of Age-related Macular Degeneration Treatments Trials Research G, Writing C, Martin DF, Maguire MG, Fine SL, Ying GS, et al. Ranibizumab and bevacizumab for treatment of neovascular age-related macular degeneration: two-year results. Ophthalmology 2020;127:S135–S145.

4. Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology 2012;119:2537–2548.

5. Rofagha S, Bhisitkul RB, Boyer DS, Sadda SR, Zhang K, Group S-US. Seven-year outcomes in ranibizumabtreated patients in ANCHOR, MARINA, and HORIZON: a multicenter cohort study (SEVEN-UP). Ophthalmology 2013;120:2292–2299.

6. Maguire MG, Martin DF, Ying GS, Jaffe GJ, Daniel E, Grunwald JE, et al. Five-year outcomes with anti-vascular endothelial growth factor treatment of neovascular age-related macular degeneration: the comparison of age-related macular degeneration treatments trials. Ophthalmology 2016;123:1751–1761.

7. Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Cortez R, et al. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol 2015;99:220–226.

8. Sharma A, Parachuri N, Kumar N, Sharma R, Bandello F, Kuppermann BD, et al. Brolucizumab-another anti-VEGF or beyond. Eye 2020;34:1499–1500.

9. Gaudreault J, Gunde T, Floyd HS, Ellis J, Tietz J, Binggeli D, et al. Preclinical pharmacology and safety of ESBA1008, a single-chain antibody fragment, investigated as potential treatment for age-related macular degeneration. Invest Ophthalmol Vis Sci 2012;53:3025.

10. Sharma A, Kumar N, Kuppermann BD, Bandello F. Brolucizimab-leading an era of structural revolution for long-term VEGF suppression. Eye 2020;34:611–613.

11. Mohammadi SS, Hosseinzadeh F, Nejatollahi F. Production of specific anti-EGFR single chain antibodies: a promising strategy in the immunotherapy of EGFR expressing tumor tissues. Int J Cancer Manag 2017;10:e6666.

12. Hosseinzadeh F, Mohammadi S, Nejatollahi F. Production and evaluation of specific single-chain antibodies against CTLA-4 for cancer-targeted therapy. Rep Biochem Mol Biol 2017;6:8–14.

13. Kholodenko RV, Kalinovsky DV, Doronin II, Ponomarev ED, Kholodenko IV. Antibody fragments as potential biopharmaceuticals for cancer therapy: success and limitations. Curr Med Chem 2019;26:396–426.

14. Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, et al. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2020;127:72–84.

15. American Society of Retina Specialists (ASRS). Beovu update for ASRS members [Internet]. Chicago, IL: ASRS; 2020. Available from: clinical-updates

16. Haug SJ, Hien DL, Uludag G, Ngoc TTT, Lajevardi S, Halim MS, et al. Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. Am J Ophthalmol Case Rep 2020;18:100680.

17. Jain A, Chea S, Matsumiya W, Halim MS, Yasar C, Kuang G, et al. Severe vision loss secondary to retinal arteriolar occlusions after multiple intravitreal brolucizumab administrations. Am J Ophthalmol Case Rep 2020;18:100687.

18. Baumal CR, Spaide RF, Vajzovic L, Freund KB, Walter SD, John V, et al. Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab. Ophthalmology 2020;127:1345–1359.

19. Witkin AJ, Hahn P, Murray TG, Arevalo JF, Blinder KJ, Choudhry N, et al. Occlusive retinal vasculitis following intravitreal brolucizumab. J Vitreoretin Dis 2020;4:269– 279.

20. Novartis. US FDA approves updated Novartis Beovu label, to include additional safety information [Internet]. Novartis; 2020 [cited 2021 Mar 1]. Available from: use-and-safety-beovu-patients-wet-amd

21. Rajan K. Safety review committee releases report on inflammation events due to brolucizumab [Internet]. American Academy of Ophthalmology; 2020 [cited 2021 Mar 1]. Available from: safety-review-committee-releases-report-on-inflamm

22. Mones J, Srivastava SK, Jaffe GJ, Tadayoni R, Albini TA, Kaiser PK, et al. Risk of inflammation, retinal vasculitis, and retinal occlusion-related events with brolucizumab: post hoc review of HAWK and HARRIER. Ophthalmology 2020;128:1050–1059.

23. Sharma A, Kumar N, Parachuri N, Sadda SR, Corradetti G, Heier J, et al. Brolucizumab-early real-world experience: BREW study. Eye 2020;35:1045–1047.

24. Narayanan R, Tyagi M, Gupta SR, Nayaka A, Jayadev C. Immediate onset of sterile endophthalmitis with hypopyon after intravitreal Brolucizumab in a case of polypoidal choroidal vasculopathy. Indian J Ophthalmol 2021;69:469–470.

25. Iyer PG, Peden MC, Suner IJ, Patel N, Dubovy SR, Albini TA. Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: a clinicopathologic case study. Am J Ophthalmol Case Rep 2020;20:100989.

26. Kondapalli SSA. Retinal vasculitis after administration of brolucizumab resulting in severe loss of visual acuity. JAMA Ophthalmol 2020;138:1103–1104.

27. Dugel PU, Jaffe GJ, Sallstig P, Warburton J, Weichselberger A, Wieland M, et al. Brolucizumab versus aflibercept in participants with neovascular age-related macular degeneration: a randomized trial. Ophthalmology 2017;124:1296–1304.

28. Beovu® (brolucizumab). Dafety of Beovu® (brolucizumab) [Internet]. Novartis; n.d. [cited 2021 Mar 19]. Available from:

29. Gonzalez S, Rosenfeld PJ, Stewart MW, Brown J, Murphy SP. Avastin doesn’t blind people, people blind people. Am J Ophthalmol 2012;153:196–203.e1.

30. Cox JT, Eliott D, Sobrin L. Inflammatory complications of intravitreal anti-VEGF injections. J Clin Med 2021;10:981. 31. Greenberg JP, Belin P, Butler J, Feiler D, Mueller C, Tye A, et al. Aflibercept-related sterile intraocular inflammation outcomes. Ophthalmol Retina 2019;3:753–759.

32. Sharma A, Kumar N, Parachuri N, Singh S, Bandello F, Kuppermann BD, et al. Brolucizumab-related retinal vasculitis: emerging disconnect between clinical trials and real world. Eye 2020;35:1292–1294.