Retinal pigment epithelial tear following intravitreal injection of brolucizumab.

Case Report

A 79-year-old woman received three bilateral monthly intravitreal injections (IVI) of aflibercept 2 mg/0.05 mL (Eylea, Regeneron, New Jersey) for exudative age-related macular degeneration (AMD). Four weeks after her third aflibercept IVI, she had an unresolved foveal pigment epithelial detachment [PED, Fig. 1a] with subretinal hyperreflective material [Fig. 1b]. Due to persistent subretinal fluid, she was switched to brolucizumab 6 mg/0.05 mL (Beovu, Novartis, New Jersey) in her right eye.[ Two weeks following the first brolucizumab IVI, she experienced an acute decline in vision from 20/50 to 20/100 + 2, secondary to a large retinal pigment epithelial tear with subretinal hemorrhage at the border of the PED [Fig. 1c and d]. There was no intraocular inflammation or vasculitis.[

Figure 1:

(a) Fundus photograph (Optos, UK) of retinal pigment epithelial detachment (PED) in the right macula (b) Optical coherence tomography (OCT, Spectralis®; Heidelberg Engineering, Germany) of an elevated PED with RPE corrugation and a prechoroidal cleft at its border (asterisk) (c) Two weeks after brolucizumab IVI, there is subretinal hemorrhage with a curvilinear margin outlining the scrolled edge of RPE (Topcon, NJ) (d) OCT demonstrates a discontinuity in the RPE at the site of the tear in the retinal pigment epithelium (RPE, arrow)

Discussion

Brolucizumab is the most recent anti-vascular endothelial growth factor (anti-VEGF) agent, approved by the Food and Drug Administration (FDA) in October 2019 for exudative AMD.[ Two phase-3 pivotal (HAWK and HARRIER) trials demonstrated noninferiority of visual acuity in treatment-naïve eyes managed for AMD with brolucizumab 6 mg/0.05 mL compared to aflibercept 2 mg/0.05 mL at 48 weeks.[ Secondary outcomes favoring brolucizumab 6 mg/0.05 mL over aflibercept 2 mg/0.05 mL were greater central subfield thickness reduction and extended dosing intervals of every 12 weeks in over half of brolucizumab-treated eyes after 3 monthly loading doses.[ These findings may relate to brolucizumab’s small molecular weight (26kDa), stability, high solubility and tissue penetration, allowing it to achieve 10 times higher molar concentrations than aflibercept.[

RPE tears may develop spontaneously or after anti-VEGFs in eyes with vascularized PEDs, particularly when preceded by a hyporeflective cleft signifying sub-RPE contraction [Fig. 1b].[ In the HAWK and HARRIER trials, RPE tears were reported in 2.5% of brolucizumab 6 mg eyes as compared to 1.1% of aflibercept 2 mg eyes.[ It is unknown if the increased anti-VEGF effect of brolucizumab amplifies contraction of fibrovascular tissue in PEDs hypothesized to produce RPE tears.