ABSTRACT
BACKGROUND: Vaccinia virus keratitis (VACVK) is a complication of smallpox vaccination that can result in blindness. There are no Food and Drug Administration-approved treatments for VACVK, and vaccinia immunoglobulin (VIG) is contraindicated in isolated VACVK. We used a rabbit model of infection to compare several therapeutic options for VACVK. METHODS: Rabbit eyes were infected with 10(5) plaque-forming units of the Dryvax strain of vaccinia virus and scored daily for 28 days using a modified MacDonald-Shadduck scoring system. Animals were treated for 10 days after the onset of keratitis with albumin, VIG, prednisolone acetate, trifluridine, or combinations thereof. Ocular viral titers and vaccinia-specific antibody titers were determined by plaque assay and enzyme-linked immunosorbent assay, respectively. RESULTS: Treatment with intravenous VIG neither exacerbated nor ameliorated VACVK. Topical prednisolone acetate interfered with viral clearance, and ocular disease rebounded in prednisolone-treated groups. The most effective treatment was topical trifluridine alone. CONCLUSIONS: We conclude that (1) VIG did not negatively affect the treatment of isolated keratitis, (2) topical corticosteroids should not be used for treating VACVK, and (3) treatment with topical trifluridine, with or without intravenous VIG, is the preferred therapeutic regimen for treating VACVK.
Subject(s)
Cornea/drug effects , Immunoglobulins/therapeutic use , Keratitis/drug therapy , Smallpox Vaccine/adverse effects , Animals , Anti-Inflammatory Agents/pharmacology , Antibodies, Viral/biosynthesis , Antibodies, Viral/blood , Antiviral Agents/pharmacology , Blindness/etiology , Blindness/prevention & control , Blindness/virology , Chlorocebus aethiops , Cornea/pathology , Cornea/virology , Disease Models, Animal , Drug Therapy, Combination , Enzyme-Linked Immunosorbent Assay , Female , HeLa Cells , Humans , Immunoglobulins/administration & dosage , Infusions, Intravenous , Keratitis/etiology , Keratitis/virology , Prednisolone/analogs & derivatives , Prednisolone/pharmacology , Rabbits , Random Allocation , Trifluridine/pharmacology , Vaccinia virus/immunology , Vaccinia virus/isolation & purification , Vero CellsABSTRACT
PURPOSE: Vaccinia virus keratitis leading to blindness is a severe complication of smallpox vaccination. The clinical manifestations of vaccinia virus keratitis are similar to those of herpes simplex virus keratitis, a well-studied immunopathologic disease. Vaccinia virus keratitis is likely to involve an immunopathologic component, but little is known about the pathogenesis of the disease. The goal of this study was to determine type and kinetics of immune cell infiltration in the cornea during vaccinia virus keratitis. METHODS: Rabbit eyes were trephined and inoculated with 1x10(5) pfu of the Dryvax strain of the vaccinia virus. On days 2, 4, 7, 10, 14, and 28 after infection, the animals were scored for clinical disease and eye sections were stained for B cells, CD4+ cells, CD8+ cells, and neutrophils. The eyelid, ciliary body, cornea, iris, iridocorneal angle, and choroid were examined. RESULTS: Corneal vaccinia virus challenge resulted in the infiltration of B cells, CD4+ cells, CD8+ cells, and neutrophils into the cornea and eyelids. Neutrophils were the predominant cell type on days 2 and 3 after infection, whereas CD4+ cells were the predominant cell type detected in corneas on days 4 through 10. CD8+ cells and B cells peaked on day 10, but at lower levels than CD4+ cells and neutrophils. CONCLUSIONS: These results suggest that sequential migration of neutrophils, then CD4+ cells, plays an important role in vaccinia virus keratitis.
