shows infiltration of neutrophils, eosinophils, and plasma cells. The specific source of this factor has not yet been determined.

Leukotriene C4 has also been reported to be elevated in the tears of patients with GPC. This mediator’s actions on ocular tissues may be in part responsible for conjunctival injection and edema, increased mucoid secretions, and the papillary reaction that occurs in GPC [44].

The elevated levels of tear immunoglobulins, inflammatory mediators, and chemotactic factors (also found in vernal conjunctivitis) provide further evidence of an immunologic basis of GPC.

Coated contact lenses

Contact lenses rapidly develop a complex coating of various substances after insertion onto the eye. Within 30 minutes after lens insertion, 50% of the contact lens is coated, and by 8 hours, approximately 90% of the surface of the lens is coated [45,46]. Even with the best of cleaning regimens, using surfactants and enzymatic treatment, only 75% of the coating is removed. New coating material is constantly built on the surface of the contact lens [47]. Coated contact lenses are a constant feature of GPC, and as the syndrome progresses, lens coating increases. Patients find it increasingly di cult to keep their lenses clean [48]. Lenses with higher water content tend to accumulate more coating than lenses with lower water content [49–51]. Glyceryl methylmethacrylate contact lenses have been shown to accumulate less calcium deposits than HEMA contact lenses, and it is believed that these lenses may tend to coat less than HEMA lenses [52]. Silicone hydrogel contact lenses deposit less lysozyme and total protein than HEMA-based hydrogels but are more prone to lipid deposition [53,54]. Studies have shown that the nature of the deposits on lenses of patients with GPC and asymptomatic individuals are similar [55–60]. Although coating does not necessarily lead to the occurrence of GPC, patients with GPC accumulate more coating on their contact lenses than do patients who do not have GPC [48,61].

There are no morphologic or biochemical findings that can di erentiate the coating on the contact lenses of patients who have GPC from that on the lenses of those who do not have GPC [48]. When coated contact lenses from GPC patients are placed on the eyes of rhesus monkeys, however, the monkeys develop injection, thickening, and a papillary reaction on the upper tarsal conjunctiva, which resembles that seen in GPC (Fig. 9) [62]. In addition, elevated levels of IgE and IgG have been found in the tears of these monkeys who were wearing the coated contact lenses. A biopsy of the tarsal plate shows a cellular infiltrate consisting of eosinophils and plasma cells, which are similar to the infiltrates observed in biopsies from patients with GPC [62]. Contact lenses worn by patients who did not have GPC and new unworn contact lenses did not elicit the inflammatory, histologic, or immunologic changes when placed on the eyes of monkeys. It is

Fig. 9. Upper tarsal conjunctiva of rhesus monkey after being fitted with contact lens from a patient with giant papillary conjunctivitis. Note the marked tarsal injection, thickening, and papillary reaction.

believed this animal model shows the development of GPC secondary to coated contact lenses, and strongly suggests that an antigen does exist on the coated contact lens that can simulate the inflammatory reaction seen clinically as GPC.

Pathophysiology

Although the cause of GPC is unknown, many factors seem to influence its development. The morphologic and histologic similarities between GPC and vernal conjunctivitis have led many investigators to believe that these conditions share a common pathophysiology [27]. Whether GPC is a purely immunologic disease or whether mechanical trauma or irritation are contributing factors is a matter of ongoing debate. The authors’ hypothesis of the pathophysiology of contact lens–associated GPC is as follows. Contact lenses become coated and this coating serves as an antigen stimulus. This stimulation causes the production of tear immunoglobulins, IgE, IgG, and in severe cases IgM. The complement system is also activated by the formation of C3 anaphylatoxin. C3 anaphylatoxin, in addition to IgE and some classes of IgG, can interact with mast cells and basophils, resulting in the release of vasoactive amines. The coated contact lens also cause conjunctival trauma, which results in the release of NCF and other inflammatory mediators, which attract eosinophils, mast cells, and basophils, and lymphocytes and plasma cells to the conjunctiva. These cells interact with IgG, IgE, and C3a, resulting in the release of additional inflammatory