Brolucizumab Decreases Pigment Epithelial Detachment Height Rapidly

Brolucizumab reduced PED maximum height faster than aflibercept, but raised risk for intraocular inflammation.

Stronger and potentially longer-acting than previously-approved intravitreal biologics, brolucizumab has shown in large trials that it can decrease subretinal pigment epithelial (sub-RPE) fluid as, or more effectively than aflibercept. A report now shows that  brolucizumab also decreases maximum height of pigment epithelial detachment (PED) in a shorter interval than aflibercept, as reported in BMC Ophthalmology.

The retrospective analysis included all patients — 83 eyes of 83 individuals, treatment-naïve for neovascular age-related macular degeneration (nAMD) and diagnosed with type 1 macular neovascularization (MNV) at a Japanese academic hospital’s ophthalmology department from June 2015 to January 2021. 

Participants were divided into 2 groups; 49 eyes that received intravitreal aflibercept (IVA) and 34 that received brolucizumab (IVBr) therapy. No significant baseline differences existed between the 2 groups for PED maximum height, PED type, or demographic factors of sex or age. The loading phase treatment involved 3 monthly injections.

In the aflibercept cohort, pretreatment PED mean maximum height of 228±169 μm regressed after 1 month to 180±150 μm (P =.2558). In the same period, the patients in the IVBr group’s baseline height of 307±254 μm diminished to 183±150 μm (P =.0113). 

We did observe IOI in 5 of our patients, but the visual function improved in 2 cases, was preserved in 2 cases, and slightly worsened in 1 case.

At 2 months, the IVA group’s maximum heights further decreased to 165±140 μm (P =.0962). In contrast, PED heights with IVBr lessened to 139±114 μm (P =.0003). Ultimately, in 3 months the IVA patients’ maximum height levels fell to 150±129 μm (P =.0284). PED height measurement in the IVBr cohort dropped to 125±126 μm (P <.0001).

No large group differences emerged regarding change in mean diameter of PED or retinal hemorrhage; and macular dryness was also comparable. However, RPE tears occurred in 3% of those receiving IVBr, and for 10% of IVA patients. This finding differs from prevalent thought that rapid PED reduction creates greater risk for a tear, so researchers speculate RPE tear may result from “the force of contraction of the MNV multiplied by time.” Of concern, 5 participants receiving IVBr, vs 0 in the IVA group developed intraocular inflammation (IOI, P =.0096). 

In prior studies, IOI incidence after brolucizumab treatment has been an important issue, with the potential for occlusive retinal vasculitis. No occlusive vasculitis appeared in the present cohort. “We did observe IOI in 5 of our patients, but the visual function improved in 2 cases, was preserved in 2 cases, and slightly worsened in 1 case (20/32 to 20/40),” the investigators explain, adding that prompt detection and urgent intervention for IOI is vital during IVBr treatment.

Previous research also demonstrates IVBr may offer a greater degree of polyp occlusion than IVA. An analysis found that with aflibercept monotherapy, the rate of polyp occlusion was 55.0%, as opposed to an earlier paper by the current authors which presented a 78.9% occlusion after induction therapy with IVBr — thus, investigators hypothesize brolucizumab is also robust to decrease PED.

Limitations of this analysis include a relatively small sample, and brolucizumab’s recent launch in 2020. Although, this real-world investigation builds on prior clinical trials that show brolucizumab therapy can reduce sub-RPE fluid and smaller studies which demonstrate it may decrease PED in stubborn cases.


Mukai R, Matsumoto H, Nagai K, Akiyama H. Comparison of the regressive effects of aflibercept and brolucizumab on pigment epithelial detachment. BMC Ophthalmol. Published online on September 29, 2022. doi:10.1186/s12886-022-02617-2