• Comprehensive Ophthalmology, Retina/Vitreous

    Review of: Retinal vasculitis and intraocular inflammation after intravitreal injection of brolucizumab

    Baumal C, Spaide R, Vajzovic L, et al. Ophthalmology, in press

    This retrospective study evaluated the features and outcomes of eyes with retinal vasculitis and inflammation after brolucizumab treatment for neovascular AMD.

    Study design

    The study assessed 15 eyes from 12 patients who developed retinal vasculitis and inflammation after receiving brolucizumab (6 mg/0.05 ml) for wet AMD at 10 U.S. ophthalmology centers. The main outcomes included baseline and follow-up visual acuity, prior anti-VEGF injections, clinical presentation, retinal findings, fluorescein angiography and treatment strategies.

    Outcomes

    Retinal vasculitis and intraocular inflammation were diagnosed, on average, 30 days after the last intravitreal injection of brolucizumab. Ten eyes were diagnosed after the first injection and 5 were diagnosed after receiving additional injections. The mean visual acuity was 20/53 at baseline and 20/191 (range 20/25 to 20/1600) at time of retinal vasculitis diagnosis (P=0.008). All eyes had vitreous cells or opacities and the majority (11 eyes) had anterior chamber cells. The vascular findings included variable combinations of focal or elongated segmental sheathing and discontinuity of small and large retinal arteries, sclerotic arteries, regions of vascular nonperfusion, cotton-wool spots, Kyrieleis plaques, irregular venous caliber with dilated and sclerotic segments, perivenular hemorrhages and foci of phlebitis. Fluorescein angiography revealed delayed retinal arterial filling, retinal vascular nonperfusion and variable dye leakage from affected vessels and the optic nerve. Other findings included Descemet folds, cornea edema and mild conjunctival injection.

    Patients were treated with combinations of corticosteroids (systemic, intravitreal, topical) and 2 eyes had vitrectomy without improvement in vision. Overall, vision improved to 20/136 after a mean follow-up of 25 days, which was still reduced compared with baseline vision (P=0.033).

    Limitations

    The true incidence of retinal vasculitis and intraocular inflammation after brolucizumab is not known. This study only included 12 patients and unlike previous studies, these eyes were not treatment-naïve.

    More information regarding inflammation rates and features in treatment-experienced versus treatment-naive patients is necessary because physicians often manage treatment-experienced patients in clinic. Of note, vasculitis was not reported as an adverse event in the pair of phase 3 trials testing brolucizumab in 1,817 patients. More clarity will be seen as new cases emerge, adding to wealth of data regarding this concerning adverse event.

    Clinical significance

    Patients who are receiving intravitreal brolucizumab require careful examination for intraocular inflammation and retinal vasculitis. These findings indicate patients may develop variable occlusion of retinal arteries and perivenular abnormalities that may span from peripheral vasculitis to occlusion of large retinal arteries around the optic nerve or macula with severe vision loss. Vitreous cells may obscure retinal details. These potential complications need to be discussed with patients who are undergoing intravitreal brolucizumab injection.

    Physicians who encounter inflammation after intravitreal brolucizumab injections should report cases to ASRS, the FDA and Novartis.