Preventive Inflammation Management with Steroids before Retreatment with Anti-VEGF after Severe Inflammation due to Brolucizumab

Abstract

Purpose We report two successful cases of treatment by steroids after severe inflammation due to an intravitreal injection (IVI) of brolucizumab and their retreatment with another type of anti-vascular endothelial growth factor (VEGF), with steroid treatments to prevent severe inflammatory recurrence in patients with exudative age-related macular degeneration (AMD).

Clinical Cases, Case 1 An 88-year-old woman with exudative AMD in her left eye who had persistent subretinal fluid despite receiving an IVI, including ranibizumab and, subsequently, aflibercept. A switch to brolucizumab was decided. Two weeks after the third dose, she had a visual loss decreasing from 20/40 to counting fingers at 50 cm. Fundus examination revealed retinal whitening and perivenous sheathing. Fluoresceine angiography confirmed retinal arterial occlusion. Differential diagnoses were ruled out. She was treated with intravenous methylprednisolone and prednisolone eye drops. Three months after the treatment, visual acuity improved to 20/80 with no intraocular inflammation but subretinal fluid recurred. IVI of ranibizumab was rescheduled with preventive treatment by oral and local prednisolone without any inflammation recurrence.

Case 2 An 80-year-old man with exudative AMD in his right eye who had persistent subretinal fluid despite an IVI of aflibercept. Switching him to brolucizumab was decided. Two months after the third dose, he had blurred vision with no pain. Visual acuity decreased from 20/20 to 20/25. Examination showed 1+ anterior chamber cells and hyalitis. We confirmed the diagnosis of anterior uveitis with hyalitis. Differential diagnoses were ruled out. Treatment by prednisolone eye drops was initiated every 30 minutes for 1 day with a gradual decrease for 6 weeks. One week later, visual acuity improved to 20/20 with no inflammation. Three weeks later, subretinal fluid due to AMD increased. The patient was retreated by aflibercept with prednisolone eye drops, 48 hours before and after the IVI, with no recurrence of inflammation.

Discussion Brolucizumab is one of the latest FDA-approved anti-VEGF agents for wet AMD. Since its wider use, few cases of severe ocular inflammation have been reported in post-marketing analysis. Because wet AMD recurrences should be expected after intraocular inflammation, insight is needed into treatment tolerance in cases that received further IVI retreatment.

Conclusion Our cases demonstrate that an IVI reinjection with a different anti-VEGF drug for exudative AMD recurrence can be safely reperformed. The use of local steroids could be effective in preventing recurrence of ocular inflammation after severe intraocular inflammation due to brolucizumab.

Zusammenfassung

Wir berichten hier über 2 Fälle von okulärer Toleranz mit einer präventiven Behandlung für eine weitere intravitreale Injektion (IVI) von Anti-VEGF, die für ein Rezidiv der exsudativen altersbedingten Makuladegeneration (AMD) erforderlich ist, die zuvor eine schwere intraokulare Entzündung nach intravitrealer Verabreichung von Brolucizumab aufwies.

Key words

retina - pharmacology - intraocular inflammation

Schlüsselwörter

Retina - Pharmakologie - intraokulare Entzündungen

Publication History

Received: 19 January 2023

Accepted: 23 February 2023

Article published online:
25 April 2023

• References

• 1 Schmidt-Erfurth U, Chong V, Loewenstein A. et al. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol 2014; 98: 1144-1167
• 2 Kodjikian L, Cohen SY, Devin F. et al. Future treatments in the current management of neovascular age related macular degeneration (Place des traitements à venir dans la prise en charge actuelle de la DMLA exsudative en France-Avis dʼexperts). Journal de la SFO 17.03.2021.
• 3 Finger RP, Daien V, Eldem BM. et al. Anti-vascular endothelial growth factor in neovascular age-related macular degeneration – a systematic review of the impact of anti-VEGF on patient outcomes and healthcare systems. BMC Ophthalmol 2020; 20: 294
• 4 Markham A. Brolucizumab: First Approval. Drugs 2019; 79: 1997-2000 DOI: 10.1007/s40265-019-01231-9.
• 5 Dugel PU, Koh A, Ogura Y. HAWK and HARRIER: phase 3, multicenter, randomized, double-masked trials of brolucizumab for neovascular age-related macular degeneration. Ophthalmology 2020; 127: 72-84
• 6 Kilmartin DJ. Literature review and proposal of best practice for ophthalmologists: monitoring of patients following intravitreal brolucizumab therapy. Ir J Med Sci 2023; 192: 447-456 DOI: 10.1007/s11845-022-02929-8.
• 7 Baumal CR, Spaide RF, Vajzovic L. et al. Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab. Ophthalmology 2020; 127: 1345-1359 DOI: 10.1016/j.ophtha.2020.04.017.
• 8 Xu Y, Tan CS. Safety and complications of intravitreal injections performed in an Asian population in Singapore. Int Ophthalmol 2017; 37: 325-332
• 9 Kitchens JW, Do DV, Boyer DS. et al. Comprehensive review of ocular and systemic safety events with intravitreal aflibercept in randomized controlled clinical trials. Ophthalmology 2016; 123: 1511-1520
• 10 Knickelbein JE, Chew EY, Sen HN. Intraocular Inflammation Following Intravitreal Injection of Anti-VEGF Medications for Neovascular Age-Related Macular Degeneration. Ophthalmic Epidemiol 2016; 23: 69-70
• 11 Hahn P, Chung MM, Flynn jr. HW. et al. Postmarketing analysis of aflibercept-related sterile intraocular inflammation. JAMA Ophthalmol 2015; 133: 421-426
• 12 Souied E, Dugel P, Ferreira A. et al. Severe ocular inflammation following ranibizumab or aflibercept injections for age-related macular degeneration: a retrospective claims database analysis. Ophthalmic Epidemiol 2016; 23: 71-79
• 13 Marwa K, Kondamudi NP. Type IV Hypersensitivity Reaction. [Updated 2023 Mar 6]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. Accessed March 23, 2023 at: https://www.ncbi.nlm.nih.gov/books/NBK562228/
• 14 Rajan K. Safety review committee releases report on inflammation events due to brolucizumab [Internet]. American Academy of Ophthalmology; 2020. Accessed March 23, 2023 at: https://www.aao.org/education/headline/safety-review-committee-releases-report-on-inflamm
• 15 Haug SJ, Hien DL, Uludag G. et al. Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration. Am J Ophthalmol Case Rep 2020; 18: 100680 DOI: 10.1016/j.ajoc.2020.100680.
• 16 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; 128: 1050-1059 DOI: 10.1016/j.ophtha.2020.11.011.
• 17 Baumal CR, Bodaghi B, Singer M. et al. Expert Opinion on Management of Intraocular Inflammation, Retinal Vasculitis, and Vascular Occlusion after Brolucizumab Treatment. Ophthalmol Retina 2021; 5: 519-527 DOI: 10.1016/j.oret.2020.09.020.
• 18 Iyer PG, Peden MC, Suñer IJ. et al. Brolucizumab-related retinal vasculitis with exacerbation following ranibizumab retreatment: A clinicopathologic case study. Am J Ophthalmol Case Rep 2020; 20: 100989 DOI: 10.1016/j.ajoc.2020.100989.
• 19 Enríquez AB, Baumal CR, Crane AM. et al. Early Experience With Brolucizumab Treatment of Neovascular Age-Related Macular Degeneration. JAMA Ophthalmol 2021; 139: 441-448 DOI: 10.1001/jamaophthalmol.2020.7085.
• 20 Chakraborty D, Maiti A, Sheth JU. et al. Brolucizumab in Neovascular Age-Related Macular Degeneration – Indian Real-World Experience: The BRAILLE Study – Fifty-Two-Week Outcomes. Clin Ophthalmol 2022; 16: 43034313 DOI: 10.2147/OPTH.S395577.