A patient receiving intravitreal brolucizumab injections for neovascular age-related macular degeneration presents three days after his third injection with blurred vision and floaters. Fundus examination shows retinal arterial occlusion with areas of inner retinal whitening. Which property of brolucizumab accounts for this feared complication compared with other anti-VEGF agents?

• A Its full-length antibody structure triggers complement-mediated endothelial damage
• B It binds VEGF-B and placental growth factor, causing vasoconstriction of arterioles
• C Its small single-chain fragment size permits rapid diffusion into retinal vessels, provoking a pro-inflammatory reaction ✓
• D Its long systemic half-life leads to cumulative vascular toxicity

Explanation

Brolucizumab is the smallest anti-VEGF fragment in clinical use, a 26 kDa single-chain antibody fragment. Reports of intraocular inflammation and retinal artery occlusion have been linked to this small molecular size, which allows deeper penetration into retinal tissue and vessel walls, triggering inflammation and occlusive vasculitis. Option A is wrong because brolucizumab is not a full-length antibody, and option B describes aflibercept and faricimab binding profiles, not brolucizumab, which binds only VEGF-A isoforms.

Reference: Yanoff and Duker Ophthalmology, 5th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.