Toxic Conjunctivitis

Cellular Mechanisms

Toxicity implies damage to the structure of the ocular tissues, or disturbance of function, with or without an accompanying inflammatory response. This damage may occur as a direct result of the drug itself, the accompanying preservatives, or from breakdown products of the drug.

Allergic reactions may be of the anaphylactoid (type I) or of the delayed (type IV) hypersensitivity type. The type I reaction is characterized by the union of allergen, IgE antibody, and mast cells, leading to the degranulation of the mast cell and the release of multiple mediators, including histamine, various chemotactic factors, and others. These mediators are responsible for the signs and symptoms of an acute allergic reaction. In the delayed hypersensitivity reaction, drugs act as haptens that conjugate with proteins. This conjugate combines with T lymphocytes, leading to the elaboration of various lymphokines, which mediate the inflammatory response.

Signs and Symptoms

In general, allergic reactions are characterized by chronicity. Repeated exposure to the agent and adequate sensitization time are needed for the reaction to develop. The development of this reaction may require an amount of time ranging from days to years. On the other hand, a toxic reaction, though also often requiring repeated exposure, may occur with the first exposure to the agent.

Conjunctival redness, chemosis, lid or periorbital swelling, mucous discharge, papillary palpebral conjunctival reaction, and itching are common manifestations of an allergy. Itching may be the strongest indication of allergic conjunctivitis. Many of the available topical medications may cause this type of reaction, perhaps the most common being idoxuridine (IDU), gentamicin, atropine, and neomycin. ^,

In allergic conjunctivitis, a papillary reaction of the tarsal conjunctiva may occur, as well as a milky chemosis with hyperemia. Papillary reactions are common in toxic conjunctivitis also, but in addition, a follicular component may be present. Follicles are generally not seen in allergy alone and may be a key sign suggesting toxicity. Table 47.1 lists medications associated with follicular conjunctivitis. ^,

In addition, the hyperemia and chemosis that may occur with toxicity may not be as diffusely distributed on the bulbar conjunctiva as in the allergic reaction, but may spare the superior aspect relatively. It is often more prominent in the inferonasal cornea and conjunctiva from the natural Bell phenomena and the locus of the direct placement of topical drops ( Figs. 47.1–47.3 ).

Allergic conjunctivitis is often associated with a mucous discharge that is typically thin and clear. A more purulent or mucopurulent discharge may be associated with toxicity.

The cornea in allergic conjunctivitis is often unaffected or may show punctate staining with fluorescein, more prominent inferiorly. The cornea in toxic reactions, on the other hand, may demonstrate a broad range of involvement, from mild punctate keratitis to severe ulcerative keratopathy. As described by Wilson, the most common manifestations are coarse and punctate epithelial lesions. Heaps and swirls of opaque epithelium may occur as well, which may lead to large erosions. Pseudodendrites may develop, resembling herpetic dendrites. Schwab and Abbott emphasized the importance of the largely unrecognized problem of toxic ulcerative keratopathy. They described a series of patients with similar findings secondary to inappropriate use of topical medications, including anesthetic abuse. All of these patients had oval epithelial defects located primarily in the inferonasal quadrants, with coarse surrounding keratitis, resembling a “comet’s impact” crater (see Fig. 47.1 ). Mucous threads, intense ciliary flush, papillary tarsal response, chemosis, and marked inferior or inferonasal injection were also common (see Figs. 47.1–47.3 ). The epithelial defects typically demonstrate rolled, but not heaped, margins. These findings were observed in patients with iatrogenic toxic keratopathy as well as in factitious, self-induced keratoconjunctivitis.

Diagnostic Testing

Various clinical tests are available, although not often performed, which may help to distinguish allergy from toxicity. The standard clinical test for the diagnosis of type I hypersensitivity is the intradermal skin test, in which injection of the agent intradermally elicits a wheal and flare reaction within seconds or minutes. The ocular equivalent of this—application of the substance into the conjunctival fornix—may yield a positive result with immediate chemosis, hyperemia, itching, and eyelid swelling. The standard test for type IV hypersensitivity, or contact dermatitis, is the patch test. Here, the substance is applied to the skin and covered. Examination of the skin 24–48 hours later may reveal a contact dermatitis if positive. However, false negatives and false positives may both occur, and a careful history is often more helpful in making this diagnosis. Conjunctival scrapings may show eosinophils in allergic conjunctivitis and not in toxic reactions. In addition, large toxic granules may be present in the cytoplasm of epithelial, mononuclear, and polymorphonuclear cells. These are large basophilic granules that differ from the usual smaller neutrophilic granules. However, they are not specific for toxicity and may be found in allergic responses as well.