Ocular hypersensitivity to thimerosal in rabbits

Rabbits were immunized to thimerosal conjugates and challenged with specific antigen-sensitized contact lenses. The symptoms of acute ocular hypersensitivity observed included corneal edema, corneal infiltration and erosion, infiltration of the anterior chamber, iritis, conjunctival edema and hyperemia, and a significant increase in mucous production. Occasional evidence of corneal neovascularization and giant conjunctival papillae were seen. All these parameters were assessed on a five-point scale (0 to +4) and tabulated as an ocular index. The index of ocular hypersensitivity correlated with the titers of the serum antibodies to thimerosal. The major class of serum antibodies consisted of immunoglobulin (Ig) G, with IgA compromising approximately 5% of serum antibodies. During the ocular challenge, the total and IgG tear antibody titers increased as a result of increased vascular permeability. The tear IgA titers increased to a lesser extent than IgG. The influx of serum proteins directly into the tear film was confirmed by a protein-dye tracer technique. Histologic analysis showed that the ocular inflammatory response was accompanied by both polymorphonuclear and mononuclear cell infiltrates into the cornea and conjunctiva. In conclusion, thimerosal-immunized rabbits show an exquisite sensitivity to the minute quantities of thimerosal conjugates adsorbed to contact lenses. Both serum and tear antibodies correlate with the severity of the ocular inflammatory response. This model would appear to simulate an antibody-mediated immune complex or Arthus type of ocular hypersensitivity commonly seen to foreign antigens including preservatives.