The combination therapy of subtenon triamcinolone acetonide injection and intravitreal brolucizumab for brolucizumab-related intraocular inflammation

Abstract

Rationale: Brolucizumab is a novel anti-vascular endothelial growth factor agent with clinical trials demonstrating excellent efficacy for neovascular age-related macular degeneration (AMD) in both visual and anatomic outcomes. However, there is concern of intraocular inflammation (IOI), and we propose concurrent subtenon triamcinolone acetonide (STTA) to prevent IOI. Patient concern: A 73-year-old man was treated with aflibercept for neovascular AMD in his right eye. Despite 11 months of monthly intravitreal aflibercept injections, optical coherence tomography demonstrated persistent exudation. Ten days following his second brolucizumab injection, the patient presented with decreased vision due to vitritis in his right eye Diagnosis: Brolucizumab-related IOI in neovascular AMD refractory to aflibercept. Interventions: A combination therapy involving of intravitreal brolucizumab and STTA Outcomes: The anti-vascular endothelial growth factor inhibitor was changed back to aflibercept; however, exudation persisted. Therefore, a combination therapy involving STTA (5 mg/0.5 mL) and intravitreal injection of brolucizumab (6.0 mg/0.05 mL) was performed to treat the exudation and as prophylaxis to recurrent IOI. Combination therapy achieved no recurrent IOI and resolution of exudation with 8-week treatment intervals. Lessons: This case might indicate that STTA is not only an optimal treatment option for brolucizumab-related IOI but also a preventive agent for this condition.

A Treat-and-Extend Regimen of Intravitreal Brolucizumab for Exudative Age-Related Macular Degeneration Refractory to Aflibercept: A 12-Month Result

“…This study's treatment interval significantly extended from the first to the last interval at 12 months (from 6.15 ± 2.40 to 6.87 ± 2.92, p = 0.045). Several studies have reported the efficacy of brolucizumab for refractory exudative AMD in short-term results in the real-world [41,49,[56][57][58][59][60][61][62].…”

“…In phase 3 clinical trial of HAWK/HARRIER, intravitreal administration of (6.0 mg/0.05 mL) brolucizumab demonstrated similar visual gains to and better morphological improvement than the intravitreal administration of (2.0 mg/0.05 mL) aflibercept [35,36]. Although there remain safety concerns including intraocular inflammation (IOI), retinal vasculitis, and retinal vascular occlusion after intravitreal administration of brolucizumab, there is mounting evidence regarding incidence, treatment, and prophylaxis of intraocular inflammation [37][38][39][40][41][42][43][44][45][46]. Though these data from animal experiments and clinical trials suggest the possible advantage of brolucizumab over other anti-VEGF agents, few data reveal the efficacy of switching to brolucizumab from other anti-VEGF agents for neovascular AMD with persistent exudation, including SRF and IRF, despite multiple intravitreal injections.…”

A case of intraocular inflammation after intravitreal brolucizumab injection monitored by laser flare-cell photometer

“… 14 Treatment with corticosteroids in the early phase has reportedly been proposed for patients with IOI after IVbr. 17 , 19 In the current case, we were able to perform early intensive treatment with STTA due to the prompt recognition of IOI showing an LFP value of 51.2 pc/ms. We were also able to monitor the efficacy of STTA based on the reduction in the LFP value to 30.3 pc/ms after 3 days and 17.9 pc/ms after 2 weeks from STTA.…”

“…IOI is well known to potentially occur after IVbr. 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 Although IOI has been reported to occur in 4.6% of patients after injections in the HAWKS and HARRIER studies, it tends to be seen more frequency in Japanese patients by approximately 15% to 20%. 15 , 18 , 23 We should be alert for the occurrence of IOI and promptly diagnose early-phase IOI should it develop after the use of brolucizumab.…”

“…Recently, the occurrence of intraocular inflammation (IOI) and retinal vasculitis with or without occlusion after brolucizumab administration has been reported. 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 However, the correct diagnosis of the degree of inflammation from an objective perspective is considerably difficult. A laser flare-cell photometer (LFP) can non-invasively evaluate inflammation with numerical information.…”