Retinal arterial occlusive vasculitis following intravitreal brolucizumab administration

Abstract

Purpose: To describe retinal arterial occlusion and vasculitis following intravitreal brolucizumab administration in a patient with neovascular age-related macular degeneration (nAMD).

Observation: An 88-year-old Caucasian woman with neovascular age-related macular degeneration (nAMD) complained of painless loss of vision with light sensitivity in both eyes (OU) four weeks after bilateral intravitreal brolucizumab. Upon examination, her visual acuity decreased to 20/40 in the right eye (OD) and 20/50 in the left eye (OS). Examination revealed 0.5+ and 1+ anterior chamber cells in OD and OS, respectively. The patient was treated with 1% prednisolone acetate eyedrops in both eyes, and after several weeks, the anterior chamber cells resolved. However, the patient still reported a decline in visual acuity (VA). Fluorescein angiography (FA) revealed retinal arterial occlusion, vasculitis, and optic nerve inflammation in the left eye. Retinal intra-arterial grayish materials were also detected. Laboratory evaluations were performed for common infectious and inflammatory causes and were normal or negative. A delayed inflammatory reaction to brolucizumab was suspected as the cause of the ocular inflammation and retinal vasculitis. An intravitreal dexamethasone implant was inserted into the left eye to treat the inflammation. One week after the dexamethasone implant, VA improved to 20/40 in OU; FA showed improvement, but residual peri-vascular leakage remained.

Conclusion: Medication-associated uveitis is a rare adverse effect that can lead to vision loss. The index report illustrates a case of intraocular inflammation, retinal arterial vaso-occlusion and vasculitis associated with intravitreal brolucizumab. The delay in developing uveitis suggests that the inflammation is due to a delayed hypersensitivity reaction which can occur several days or weeks after administration of the inciting agent. Recently, several cases of uveitis and vasculitis associated with brolucizumab have been presented and those cases have similar features compared to the index case (1). Therapy with steroids (either intraocular or systemic), after infectious etiologies have been excluded, may be beneficial in halting inflammation and preventing further vision loss.

Keywords: Age-related macular degeneration; Brolucizumab; Intraocular inflammation; Occlusive vasculitis; Retinal vasculitis.

Fig. 1

Optical coherence tomography (Spectralis; Heidelberg Engineering, Heidelberg, Germany) of the right (OD) and left (OS) eyes. Before intravitreal brolucizumab injection in both eyes (row A), after 4 weeks (row B), after 6 weeks (row C), after 8 weeks and before intravitreal dexamethasone implant in OS (row D), two weeks post-intravitreal dexamethasone implant (row E).

Fig. 2

Fundus photos and fluorescein angiography of the right eye (RE) 8 weeks after intravitreal brolucizumab (top row), one weeks later (middle row) and two weeks later (bottom row) showing area of pigmentary changes (A and C), supratemporal retinal vessel sheathing (black arrow-A). Staining of a segment of the superior arcade retinal arterial (white arrow) is noted in the late phase, (C and F) which resolved spontaneously after 2 weeks (I).

Fig. 3

Fundus photos and fluorescein angiography of the left eye 8 weeks after intravitreal brolucizumab and before intravitreal dexamethasone implant (top row), showing discrete intraarterial grayish materials (gold arrows-A), retinal vessel sheathing and superior optic nerve edema (blue arrow-A) and vasculitis with vascular and superior optic nerve leakage (white arrow-C). One week after dexamethasone implant (middle row), sheathing of temporal retinal arcade and superior optic nerve edema (blue arrow-D) were still present. Much improved but persistent peri-vascular and optic disc leakage, and temporal retinal vaso-obliteration in the late phase (white arrow-F) with visible intraarterial grayish materials (black arrow-F). At two weeks (bottom row) the inferior temporal retinal artery showed delayed filling (red arrow-H) compared to the superior temporal retinal artery (green arrow-H) and intraarterial blockages in late phase (black arrow-I). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)