Retinal vasculopathy and choroiditis after pegcetacoplan injection: clinicopathologic support for a drug hypersensitivity reaction.

Purpose: To report the detailed histopathology of two enucleated eyes from two 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 to propose, with supportive histopathology, the pathogenesis of the clinical syndrome previously termed hemorrhagic occlusive retinal vasculitis (HORV).

Design: Case series.

Subjects: Two enucleated eyes from two 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 nine days following the initial injection of pegcetacoplan with no subsequent improvement and underwent enucleation for pain control. Histologic examination of the enucleated eyes (patient one at 4 months post-injection and patient two 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, one eye demonstrated multiple foci of glomerular-like vascular proliferations in the uveal tract and thrombosis with focal recanalization of vessels in the optic nerve.

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