Understanding Retinal Vasculitis Associated with Brolucizumab: Complex Pathophysiology or Occam’s Razor?

Sharma, Ashish; Kumar, Nilesh; Parachuri, Nikulaa; Singh, Sumit; Bandello, Francesco; Regillo, Carl D.; Boyer, David S.; Nguyen, Quan Dong

doi:10.1080/09273948.2021.1897628

Cited by 22 publications

(20 citation statements)

References 17 publications

(27 reference statements)

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“…The large dose of anti-VEGF probably accounts for the improved efficacy and durability, despite a higher rate of hypersensitivity-like reactions that are rarely reported for other agents [25]. The initial enthusiasm for this new molecule has been somewhat offset by reports of an increased propensity to produce inflammatory side effects, such as hyalitis or vasculitis [14,17,26]. However, due to the limited therapeutic arsenal available in the treatment of nAMD, brolucizumab could be an effective alternative anti-VEGF molecule.…”

Section: Discussionmentioning

confidence: 99%

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Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study

Bilgic¹,

Kodjikian

Srivastava

et al. 2021

JCM

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The present study aimed to determine the efficacy and safety of pro re nata (PRN) intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) without a loading dose in the real-world setting. The PROBE study (Pro Re Nata Brolucizumab for Exudative AMD) is a retrospective, observational, multicentric study that included 27 treatment-naïve patients (27 eyes) with neovascular AMD who received PRN brolucizumab therapy with the treatment interval being at least 8 weeks, should the need for a second consecutive injection arise. The primary outcome measure was changed to best-corrected visual acuity (BCVA) over time. Secondary outcome measures included the determination of change in central subfield thickness (CST) and complications. The mean follow-up was 11.2 ± 1.2 months. The mean baseline and final BCVA were 57.4 ± 4.5 letters and 65.3 ± 3.12 letters, respectively (p = 0.014). The mean gain in letters at the end of follow-up was 7.8 ± 3.5 letters. There was a significant decrease in CST at the end of the follow-up period (p = 0.013). Patients received a mean of 2.2 ± 0.9 injections (in addition to the first mandatory injection) during the follow-up period. There were no adverse events noted. In conclusion, initial PRN brolucizumab for exudative AMD without a loading dose demonstrated significant visual improvement and no adverse events.

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Section: Discussionmentioning

confidence: 99%

“…As the data evolves, the risk of serious adverse events is continuously updated (www.brolucimab.info, accessed on 29 May 2021) [13]. The reported predisposing factors for intraocular inflammation following brolucizumab injection include female gender, multiple past treatments, and frequent injections, among others [14].…”

Section: Introductionmentioning

confidence: 99%

Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study

Bilgic¹,

Kodjikian

Srivastava

et al. 2021

JCM

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“…Different pathogenic hypotheses exist, explaining why Brolucizumab causes a higher rate of intraocular inflammation and retinal vascular occlusion. 4 All of these advocate the generous use of systemic, i.e. intravenous, corticosteroids in this disease.…”

mentioning

confidence: 99%

“…Since recognition of this problem, substantial efforts have been undertaken, primarily driven by Novartis, but also by independent experts to understand this phenomenon 4,[7][8][9] and to provide expert guidelines for its treatment. 2,10,11 Real-world evidence gathered from two large us registries (IRIS and Komodo), together covering 21394 injections, indicates that a history of intraocular inflammation or vascular occlusion in the affected eye results in a tenfold increase in the risk of IOI after Brolucizumab from 0.32-0.41% to 3.97-4.68%.…”

mentioning

confidence: 99%

“…Even in mild uveitis, however, re-treatment with Brolucizumab is not recommendable. 2,4 (3) In instances with a mild primary presentation, timely follow-up is a prerequisite to identifying disease progression towards the posterior segment, whereas preand intra-retinal cells visible in OCT already indicate a more severe affection of the eye (Figure 1). (4) As outlined above, the clinical presentation tends to underrepresent the severity of disease (Figure 2A): Vascular occlusion may be missed in biomicroscopy, whereas its presence has a strong impact on the aggressiveness of the treatment strategy.…”

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confidence: 99%

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Pitfalls in the Interpretation of Intraocular Inflammation in Response to Intravitreal Brolucizumab Injection

Garweg

Hänsli

2021

Ocular Immunology and Inflammation

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Retinal vasculitis after intravitreal aflibercept 8 mg for neovascular age-related macular degeneration

Matsumoto,

Hoshino,

Numaga

et al. 2024

Jpn J Ophthalmol

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Purpose To evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD). Study design Retrospective, interventional case series. Methods We retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8 mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined. Results BCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8 mg (all P < 0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss. Conclusions Intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis.

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Understanding Retinal Vasculitis Associated with Brolucizumab: Complex Pathophysiology or Occam’s Razor?

Cited by 22 publications

References 17 publications

Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study

Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study

Pitfalls in the Interpretation of Intraocular Inflammation in Response to Intravitreal Brolucizumab Injection

Retinal vasculitis after intravitreal aflibercept 8 mg for neovascular age-related macular degeneration

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