Bozho Todorich, MD, PhD
Pennsylvania Retina Specialists, PC
Camp Hill, PA
Hemorrhagic occlusive retinal vasculitis (HORV) is a rare, yet visually devastating disease entity linked to intracameral vancomycin, used to reduce rate of endophthalmitis associated with cataract surgery. The joint task force by the ASRS and ASCRS established a national registry aimed at increasing our understanding of this visually devastating condition, and the clinical experience and diagnostic guidelines based on the registry have been published earlier this year (Witkin, et al, Ophthalmology, 2017). The mechanism of HORV has been postulated to be a type III hypersensitivity reaction, a form of leukocytoclastic vasculitis, but direct histological evidence of this was lacking.
In the clinical-pathologic correlation study that I presented at the 2017 annual meeting of Retina Society in Boston, we analyzed histological findings in an eye with vancomycin-related hemorrhagic occlusive retinal vasculopathy. The patient presented with a sudden vision loss 3 days following otherwise uncomplicated cataract surgery during which intracameral vancomycin was used and presented with ocular findings seen in the images. His multiple vitreous biopsy bacterial cultures, viral PCRs and universal bacterial primer PCR performed on undiluted vitreous specimen were negative, ruling out alternative etiologies of his vision loss. He rapidly developed blind painful eye and requested enucleation.
Histological examination of this eye demonstrated diffuse retinal necrosis with disorganization of all retinal layers, intraluminal vascular thrombosis, but with no evidence of leukocytoclastic vasculitis. In contrast, there was diffuse choroidal thickening with massive infiltration of inflammatory cells consisting of primarily CD4+ and CD8+ T lymphocytes, B cells, and to a lesser extent plasma cells, eosinophils and mast cells. Of equal importance, there was no detectable immunoglobulin or complement staining. Glomeruloid-like proliferation of endothelial cells in the choroid was also noted in the episclera, and the clinical significance of which is not known. Histologic examination of the anterior segment demonstrated diffuse hemorrhage and necrosis of the ciliary body and iris, which explains severity of this patient’s pain.
In this, to the best of our knowledge, first histologic study of vancomycin-associated hemorrhagic choroidal and retinal vasculopathy, we did not find histologic evidence supporting type III hypersensitivity or leukocytoclastic retinal vasculitis. Rather, the pathology in this eye was grounded in a necrotizing retinal vasculopathy, chronic non-granulomatous choroiditis, and an unusual glomeruloid proliferation of endothelial cells. Considering absence of immunoglobulin and complement staining and largely T-cell driven inflammation, this may represent a type IV hypersensitivity drug reaction.