Retinal Vasculopathy and Choroiditis after Pegcetacoplan Injection: Clinicopathologic Support for a Drug Hypersensitivity Reaction.

Purpose: To report the detailed histopathology of 2 enucleated eyes from 2 patients who developed severe visual loss associated with retinal hemorrhages, vessel sheathing, and vascular nonperfusion after administration of an initial dose of intravitreal pegcetacoplan, and propose, with supportive histopathology, the pathogenesis of the clinical syndrome previously termed hemorrhagic occlusive retinal vasculitis.

Design: Case series.

Subjects: Two enucleated eyes from 2 patients treated with intravitreal pegcetacoplan.

Methods: Retrospective, multicenter, consecutive clinical-pathologic analysis.

Main outcome measures: Histopathologic review and immunophenotypic characterization.

Results: Both patients presented with inflammation and significant vision loss 9 days after the initial injection of pegcetacoplan with no subsequent improvement and underwent enucleation for pain control. Histologic examination of the enucleated eyes (patient 1 at 4 months postinjection and patient 2 at 40 days) revealed extensive vascular thrombosis, retinal hemorrhages and necrosis, and a dense inflammatory infiltrate in the uvea and, variably, the optic nerve, episclera, and muscle tendons composed of predominantly of T cells, macrophages, and eosinophils. Notably, the inflammatory infiltrate was absent from the retina. In addition, 1 eye demonstrated multiple foci of glomerular-like vascular proliferations in the uveal tract and thrombosis with focal recanalization of vessels in the optic nerve.

Conclusions: Drug-induced, immune-mediated, retinal vasculopathy and choroiditis (DIRVAC) is a rare complication after pegcetacoplan injection. Although some limitations arise in interpretation of histopathologic findings because of compensatory changes in the eyes over time (before enucleation), the authors propose that the combined clinical, histopathologic, and immunohistochemical findings suggest a mixed-type, delayed hypersensitivity reaction as the mechanism of initial injury.

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