Brolucizumab for the Treatment of Diabetic Macular Edema

Blanche L. Kuo; Rishi P. Singh


Curr Opin Ophthalmol. 2022;33(3):167-173. 

In This Article

Abstract and Introduction


Purpose of Review: To review the available data supporting the use of brolucizumab in the treatment of diabetic macular edema (DME).

Recent Findings: Brolucizumab is a humanized single- chain variable antibody fragment (scFv), the smallest functional subunit of an antibody approved for intravitreal use. Three phase III studies demonstrate that at 52 weeks, brolucizumab has statistically superior anatomical outcomes of reducing retinal thickness (54.0–57.5% of brolucizumab treated eyes achieved central subfield thickness <280 μm compared to 40.1 – 41.4% of aflibercept treated eyes) and retinal fluid (present in 54.2–60.3% of brolucizumab treated eyes compared to 72.9–78.2% of aflibercept treated eyes). Brolucizumab also demonstrated a prolonged durability up to 16 weeks, thus reducing treatment burden. The visual outcomes appear noninferior to current anti-VEGF agents with an increased risk for intraocular inflammatory events (0.3–4.7% compared to 0.6–1.7%).

Summary: Results from recent phase III trials showing the efficacy and safety of brolucizumab presents an additional therapeutic option in the DME treatment landscape. It can reduce treatment burden in DME with increased inter-treatment intervals while conferring efficacy in both functional and anatomical outcomes. Caution should be taken regarding the risks of intraocular inflammation, retinal vasculitis, and retinal vascular occlusion.


Diabetic macular edema (DME) is a vision threatening complication in patients with diabetes mellitus. With the unprecedented global rise is diabetes, DME presents an increasing public health burden. Currently, over 34 million people, or more than 10% of the population, have diabetes in the United States.[1] Antivascular endothelial growth factor (VEGF) agents have emerged as first line therapy in treating DME, with landmark trials showing efficacy of these agents over the previous standard of care, focal laser photocoagulation therapy.[2–9] These agents target proangiogenic VEGF molecules, preventing interactions with their receptors. In turn, the endothelial cell proliferation, neovascularization, and vascular permeability that lead to blood retinal barrier breakdown and DME development are suppressed.[10] The introduction of intravitreal use of anti-VEGF agents has drastically changed the landscape of DME management.

However, even with the advent of anti-VEGF agents, there remain several shortcomings of the current DME treatment landscape. Best outcomes in DME management with anti-VEGF agents require frequent intravitreal injections, causing heavy treatment burden and high socioeconomic costs to clinicians, patients, and the healthcare system.[11,12] Much of this stems from the short effect duration of current anti-VEGF treatments, which have led to a threefold increase in clinic visits since the era of laser therapy in an effort to sustain drug efficacy.[13] Moreover, current treatment regimens are often individualized based on disease activity that must be assessed routinely to determine treatment intervals, thus requiring frequent clinic visits and further burdening the healthcare system. Additionally, patients diagnosed with DME often have multiple diabetes-related comorbidities that require additional healthcare services. These challenges result in treatment fatigue, potentially leading to discontinuation of treatments, loss to follow up, and, in extreme cases, subsequent vision loss.

Consequently, real world clinical outcomes are suboptimal compared to the efficacy achieved in clinical trials that require rigid treatment regimens.[14] Ciulla et al.[15] showed in a real world setting, DME patients receive an average of 6.4 injections in the first year of initiating intravitreal anti-VEGF treatments, which is significantly less than patients who were enrolled in registered clinical trials for aflibercept (9.2), bevacizumab (9.7) and ranibizumab (9.4). In addition, in order to see a meaningful improvement in vision from baseline, more than four injections within the first year are required. These studies accentuate the unmet need of current treatment regimens in addressing the high treatment burden of DME.

Not only are frequent intravitreal anti-VEGF injections uncomfortable, but the cumulative exposure of intravitreal injections (IVI) can also result in adverse effects with long term use,[16,17] such as increased risk of endophthalmitis, subconjunctival hemorrhage, retinal pigment epithelial tears, and retinal detachment.[18–20] Even recent studies showcasing the efficacy of brolucizumab for use in nAMD demonstrate risks for intraocular inflammation (IOI), with rates as high as 4.6%.[21] As such, new treatment options are needed to alleviate the treatment burden on patients and healthcare systems while optimizing treatment efficacyand safety.