Elsevier

Ophthalmology Retina

Volume 5, Issue 6, June 2021, Pages 519-527
Ophthalmology Retina

Original Article
Expert Opinion on Management of Intraocular Inflammation, Retinal Vasculitis, and Vascular Occlusion after Brolucizumab Treatment

https://doi.org/10.1016/j.oret.2020.09.020Get rights and content
Under a Creative Commons license
open access

Purpose

Recent reports have described a spectrum of uncommon findings of intraocular inflammation (IOI), retinal vasculitis, or retinal vascular occlusion in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injection (IVI) of brolucizumab. We present guidance on the clinical presentation of this spectrum and propose recommendations for management of these events.

Design

PubMed literature review and expert opinion panel.

Participants

A working group of international medical experts and Novartis medical personnel.

Methods

The working group deliberated on the clinical presentations and used a 3-pronged approach to develop management recommendations based on (1) critical appraisal of scientific literature; (2) clinical insights from the HAWK and HARRIER trials, postmarketing reports, and assessments from an independent Safety Review Committee (SRC); and (3) their clinical experience.

Main Outcome Measures

Management recommendations for a spectrum of ocular inflammatory events after treatment with brolucizumab or other anti–vascular endothelial growth factors (VEGFs).

Results

Based on insights gained from the available information and the expertise of the contributors, recommendations were proposed for ocular examinations, imaging modalities, and treatment strategies for management of this spectrum of events. Patients should be educated to promptly report any relevant or persistent symptoms after IVI to facilitate timely intervention. Patients diagnosed with IOI should be evaluated for concomitant retinal vasculitis or retinal vascular occlusive events. Clinical examination can be augmented with multimodal imaging techniques, including widefield imaging, fluorescein angiography (with peripheral sweeps), and OCT. Once confirmed, the ongoing brolucizumab treatment should be suspended and intensive treatment with potent corticosteroids (topical, subtenon, intravitreal, or systemic) is recommended, which may be supplemented with other treatment strategies depending on the severity. Based on the clinical outcome of these events, individualized treatment with locally available standard of care should be considered for the underlying nAMD.

Conclusions

These recommendations emphasize the need for early diagnosis, prompt and timely intervention, intensive treatment, and frequent monitoring to minimize the risk of progression of these events. The proposed recommendations may facilitate a consistent management approach of this spectrum of ocular inflammatory events should they arise in nAMD after treatment with brolucizumab or other anti-VEGFs.

Keywords

Anti–vascular endothelial growth factor
Brolucizumab
Intraocular inflammation
Neovascular age-related macular degeneration
Retinal vascular occlusion
Retinal vasculitis

Abbreviations and Acronyms

AE
adverse event
ASRS
American Society of Retinal Specialists
ICGA
indocyanine green angiography
IOI
intraocular inflammation
IVFA
intravenous fluorescein angiography
IVI
intravitreal injection
nAMD
neovascular age-related macular degeneration
OCTA
OCT angiography
SRC
Safety Review Committee
VEGF
vascular endothelial growth factor

Cited by (0)

Supplemental material available at www.ophthalmologyretina.org.

Development of this publication was funded by Novartis Pharma AG, including medical writing.

Disclosure(s): All authors have completed and submitted the ICMJE disclosures form.

The author(s) have made the following disclosure(s): C.R.B.: Consultant -- Genentech, Novartis, Zeiss; Investigator -- Genentech, Ocular Therapeutics.

B.B.: Consultant -- AbbVie-Allergan, Alimera, Novartis, Santen, Thea; Grants -- Alcon, Bayer, Novartis. M.S.: Consultant -- Aerie, Allegro, Allergan, Eyepoint, Genentech, Kodiak, Novartis, Regeneron, Santen; Speaker -- Allergan, Genentech, Mallinckrodt, Novartis, Regeneron, Spark Therapeutics. Contracted Research: Aerie, Allegro, Allergan, DRCR, Genentech, Icon, Ionis, Kalvista, Kodiak Lifesciences, Novartis, Opthea, Optos, Regeneron, Santen, Senju, Sydnexis.

D.J.T.: Employee -- Novartis Pharmaceuticals Corporation, East Hanover, NJ.

A.S.: Consultant -- Novartis, Roche; Speakers Bureau -- Roche.

M.R.J.: Employee -- Novartis Pharmaceuticals UK Limited.

N.F.: Consultant -- Alimera Sciences, Novartis, Roche; Speaker -- Allergan, Alimera, Bayer, Heidelberg Engineering, Novartis, Roche.

R.G.: Consultant -- AbbVie-Allergan, Bayer, Novartis, Roche; Investigator -- AbbVie-Allergan, Bayer, Novartis, Roche.

HUMAN SUBJECTS: Human subjects were included in this study. IRB/Ethics Committee ruled that approval was not required for this study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.

No animal subjects were used in this study.

Author Contributions:

Conception and design: Baumal, Bodaghi, Singer, Tanzer, Seres, Joshi, Feltgen, Gale

Data collection: Baumal, Bodaghi, Singer, Tanzer, Seres, Joshi, Feltgen, Gale

Analysis and interpretation: Baumal, Bodaghi, Singer, Tanzer, Seres, Joshi, Feltgen, Gale

Obtained funding: N/A

Overall responsibility: Baumal, Bodaghi, Singer, Tanzer, Seres, Joshi, Feltgen, Gale