Allergy to Ophthalmic Preservatives

Jison Hong; Leonard Bielory


Curr Opin Allergy Clin Immunol. 2009;9(5):447-453. 

In This Article


Thimerosal, in its usual concentrations range from 0.001 to 0.004%, is an organomercurial derivative that acts as a result of the sulfur-removing properties of the mercuric ion. They act by combining with the sulfhydryl groups of proteins to precipitate bacterial proteins by forming proteinates of mercury. The proteinates act as a neoantigen that causes the highest frequency of cell-mediated responses of the ophthalmic preservatives.[10•] It is most commonly found in soft contact lens solutions and may cause ocular delayed hypersensitivity.

Animal Studies

In 1991, a study[16] on ocular hypersensitivity to thimerosal in rabbits documented that the signs and symptoms 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. They found that the IgG tear antibodies increased as a result of increased vascular permeability with the tear IgA titers increasing to a lesser extent than IgG during the ocular challenge. The major class of serum antibodies consisted of IgG, with IgA compromising approximately 5% of serum antibodies. Histologic analysis showed that the ocular inflammatory response was accompanied by both polymorphonuclear (PMN) and mononuclear cell infiltrates into the cornea and conjunctiva. Both serum and tear antibodies correlate with the severity of the ocular inflammatory response and support an immune complex mediated or Arthus type of ocular hypersensitivity to foreign antigens. In another animal study utilizing rat model performed by Becquet et al.,[7] thimerosal application to the eye resulted in hyperplastic changes to the corneo-conjunctival surface with increasing expression of Limbal class II antibody. In this study, anticlass II (RT1b) antibody was found to be the most reliable marker to locate and count inflammatory cells.

Human Studies

Thimerosal has demonstrated in a concentration-dependent manner on human dendritic cells, inhibition of lipopolysaccharide (LPS)-induced proinflammatory cytokines including TNFα, IL-6, and IL-12p70 while having no effect on IL-10. These thimerosal-exposed dendritic cells induced increased TH2 (IL-5 and IL-13) and decreased TH1 (IFNγ) cytokine secretion from the T cells in the absence of additional thimerosal added to the coculture.[17] In addition, there is a potential impact of thimerosal on limbal stem cells as documented in a recent case report.[18]

Tosti and Tosti[3] provides a case report of 36 patients with follicular allergic contact conjunctivitis induced by thimerosal. All of these patients report using eye drops containing thimerosal. Furthermore, 13 patients were soft contact lens wearers who became sensitized to their contact lens solution containing thimerosal. In the majority of these cases, the eyelids were spared. But in five patients, they also developed an allergic contact dermatitis of the eyelids. All of the 36 patients had a positive patch test reaction to thimerosal.