Treatment of Giant Papillary Conjunctivitis

Mathea R. Allansmith

Contact lenses have become so familiar that both patients and physicians are likely to think of them as innocuous objects. They are widely prescribed for cosmetic reasons as well as to correct a variety of conditions that impair sight. But even the best tolerated contact lens is a prosthetic device on the surface of the eye and, like all prostheses, is foreign to the body. The tissues of the eye and its adnexa therefore mobilize normal responses to foreign bodies. For many contact lens wearers, the result may be minor inconvenience and relatively inconsequential problems with lens tolerance. For others, however, erythema, itching, increased mucus production, and formation of giant papillae on the upper tarsal conjunctiva may make prolonged wearing of contact lenses impossible. This disease related to wearing contact lenses and other ocular prostheses is now recognized as giant papillary conjunctivitis (GPC).

It is estimated that GPC affects 1 to 5 percent of the 12 million wearers of soft contact lenses in the United States and perhaps 1 percent of the 8 million wearers of rigid contact lenses. The prevalence of GPC among wearers of hard [polymethylmethacrylate (PMMA)] contact lenses in one large contact lens practice was carefully studied. Of the 200 subjects wearing PMMA contact lenses, 21 (10.5%) had elevated papillae larger than 0.3 millimeters in diameter. Of the control group of 500 non-lens-wearing subjects, only 3 (0.6%) showed elevated papillae larger than 0.3 millimeters in diameter (and two of these were later found to have the early stages of vernal conjunctivitis).

The age distribution of GPC patients is difficult to determine because it is a function of (1) who wears contact lenses, (2) how long they wear them, and (3) what type they wear. Contact lens wearers are usually in their second or third decade. The average length of time patients have worn



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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium Treatment of Giant Papillary Conjunctivitis Mathea R. Allansmith Contact lenses have become so familiar that both patients and physicians are likely to think of them as innocuous objects. They are widely prescribed for cosmetic reasons as well as to correct a variety of conditions that impair sight. But even the best tolerated contact lens is a prosthetic device on the surface of the eye and, like all prostheses, is foreign to the body. The tissues of the eye and its adnexa therefore mobilize normal responses to foreign bodies. For many contact lens wearers, the result may be minor inconvenience and relatively inconsequential problems with lens tolerance. For others, however, erythema, itching, increased mucus production, and formation of giant papillae on the upper tarsal conjunctiva may make prolonged wearing of contact lenses impossible. This disease related to wearing contact lenses and other ocular prostheses is now recognized as giant papillary conjunctivitis (GPC). It is estimated that GPC affects 1 to 5 percent of the 12 million wearers of soft contact lenses in the United States and perhaps 1 percent of the 8 million wearers of rigid contact lenses. The prevalence of GPC among wearers of hard [polymethylmethacrylate (PMMA)] contact lenses in one large contact lens practice was carefully studied. Of the 200 subjects wearing PMMA contact lenses, 21 (10.5%) had elevated papillae larger than 0.3 millimeters in diameter. Of the control group of 500 non-lens-wearing subjects, only 3 (0.6%) showed elevated papillae larger than 0.3 millimeters in diameter (and two of these were later found to have the early stages of vernal conjunctivitis). The age distribution of GPC patients is difficult to determine because it is a function of (1) who wears contact lenses, (2) how long they wear them, and (3) what type they wear. Contact lens wearers are usually in their second or third decade. The average length of time patients have worn

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium contact lenses before developing GPC is 8 months for soft contact lenses and 8 years for hard contact lenses. Patients who develop GPC secondary to their wearing contact lenses for purely cosmetic reasons could, albeit reluctantly, change from contact lenses to wearing eyeglasses. But the proper care of patients who must wear contact lenses (e.g., in the event of keratoconus of high myopia) requires a range of hygienic and medical interventions to manage the possible adverse reactions to wearing contact lenses and to prevent the onset of GPC. As early as 1950 allergic reactions to wearing plastic contact lenses were reported (MacIvor, 1950). Spring (1974) noted the similarity of a contact-lens-associated disease to vernal conjunctivitis. Complications have been associated with the introduction of hydrogel lenses (Binder, 1980). Lens deposits have been identified as a major complication of extended-wear soft contact lenses (Binder, 1979) and a possible contributing factor to GPC (Allansmith and Ross, 1987). The relationship between lens deposits and GPC, however, is not clear. There is no completely successful treatment of contact-lens-associated GPC (Donshik et al., 1984). Removal of the lenses and application of topical corticosteroids and cromolyn sodium have been recommended. We are beginning to understand enough about the pathophysiology of GPC to propose a program for the total management of the disease. DESCRIPTION OF GPC The most salient feature of GPC is the presence of giant papillae on the upper tarsal conjunctiva. Giant papillae are arbitrarily defined as papillae with a diameter greater than 1.0 millimeters (Korb et al., 1980). Macropapillae (papillae with a diameter of 0.3 to 1.0 millimeters) are also abnormal. GPC shows features of being an immediate type 1, IgE-mediated hypersensitivity and a type IV delayed reaction. The immediate hypersensitivity is mediated by specific IgE bound to mast cells in the conjunctival, but the nature of the specific antigen or antigens has not been discovered. The delayed inflammatory reaction is mediated by sensitized lymphocytes, reacting with antigen to release lymphokines, with resultant tissue inflammation and tissue damage. Cellular infiltration of the conjunctival epithelium with mast cells, eosinophils, basophils, and polmorphonuclear leukocytes, as well as an occasional lymphocyte, is regularly observed in GPC. Eosinophils are present in conjunctival scrapings in somewhat less than one-fourth of individuals with GPC. The involvement of mast cells, basophils, or eosinophils in abnormal positions in the conjunctival tissue reflects the disturbed nature of the immune apparatus in GPC. All GPC patients examined had one of the following abnormalities: mast cells in the epithelium, eosinophils in the

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium epithelium or substantia propria, or basophils in the epithelium or substantia propria (Allansmith et al., 1978). Meisler and colleagues (1981) found a high percentage of IgE-containing plasma cells (27%) in patients with GPC associated with wearing an ocular prosthesis. Tear IgE levels have been found to be significantly elevated in patients with GPC, and tear IgE and IgG levels were higher in the more symptomatic eye of the patient (Donshik and Ballow, 1983). In 8 of the 18 symptomatic patients studied, tear IgM levels were measurable. In asymptomatic contact lens wearers and control subjects, no IgM could be measured. Immediate hypersensitivity of IgE-dependent anaphylactic mechanisms alone cannot account for the histologic picture in GPC. The degree of mast cell degranulation and tissue edema and the increase in eosinophils seen in IgE anaphylactic reactions (Allansmith et al., 1981) do not include such features of GPC as increased tissue mass, presence of many inflammatory cells, extensive infiltration with eosinophils, increased number of mast cells in the substantia propria and epithelium, and the presence of basophils. The cellular infiltrate of giant papillary conjunctivitis and vernal conjunctivitis suggests a common immunologic basis for the two diseases (Allansmith et al., 1979). The mechanism of GPC is probably a basophil-rich delayed hypersensitivity (similar to cutaneous basophilic hypersensitivity) with a possible IgE humoral component. In (genetically) predisposed individuals, irritation caused by the foreign body combined with grinding the antigen repeatedly against the conjunctiva is thought to trigger a hypersensitivity response. Mechanical trauma is important in the pathogenesis of GPC. The condition is nearly universally present in patients with ocular prosthesis in whom excess mucous production can be observed. Abrasion of the upper palpebral conjunctiva by exposed suture ends (suture barb giant papillary conjunctivitis) has been reported and resolves with removal or trimming of the offending sutures (Jolson and Jolson, 1984; Nirankari et al., 1983). Studies of the ultrastructure of tissues from GPC patients and vernal conjunctivitis patients (Henriquez et al., 1981) disclosed that patients with vernal conjunctivitis have more mast cells in the epithelium and substantia propria of the conjunctiva than do patients with GPC and that the mast cells are more completely degranulated. The greater number of mast cells in vernal conjunctivitis can explain the further findings of greater mediator-associated changes: higher tear histamine levels, more eosinophils, greater itching and inflammation, and more corneal pathology. Buckley (1985), however, has suggested on the basis of histologic evidence that there might be two types of GPC. One type closely resembles vernal keratoconjunctivitis and is found among atopic patients. A second form of GPC, unlike the first, is characterized by epithelial hyperplasia, nonspecific cellular infiltrates, and the absence of eosinophils. Although

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium two forms of the disease may exist, the fact that mast cells within the conjunctival epithelium play a major role in the pathophysiology gives an important clue to effective treatment. DIAGNOSIS OF GPC Early diagnosis is an essential component of the treatment of GPC. But, unfortunately, the earliest clues to the development of GPC in soft lens wearers are minor and are usually dismissed by patients as inconsequential: increased mucus in the nasal corner of the eye on arising and itching immediately after removing the lens. Patients, thinking that these minor signs and symptoms are “normal,” may never report them to their physicians. In more severe stages of GPC, patients may complain of mild blurring of vision after hours of wearing the lens (from deposits on the lens and not corneal edema), readily apparent excess mucus, and movement of the lens on blinking. In advanced stages of GPC, patients cannot tolerate the foreign body sensation of pain associated with wearing the contact lens. Sheets or strings of mucus are present, sufficient sometimes to glue the eyes shut on waking in the morning. At this stage, the lenses are visibly clouded by mucus soon after they are inserted. Abnormal amounts of deposits on the soft lenses are a constant feature of the syndrome. Deposits on the lens are most easily seen by drying the lens slightly and looking through it against a light. Although some asymptomatic wearers of soft contact lenses may also produce heavy deposits on their soft lenses, all symptomatic wearers do. Usually patients report the symptoms of GPC long before the appearance of definitive clinical signs. Furthermore, patients vary widely in how much ocular discomfort they will tolerate from various degrees of GPC. Some patients may continue wearing their soft contact lenses despite scores of giant papillae covering both upper tarsal plates. Other patients may stop wearing their soft contact lenses because of the itching and increased mucus, although the only definitive sign of GPC is conjunctival thickening. Such patients will complain of lens intolerance even though no giant papillae are apparent. Early in the clinical stage of GPC, the normally small papillae become obscured by more elevated ones. Small normal papillae do not enlarge to become giant papillae; new abnormal papillae begin to grow from the substructure of the deep conjunctival or tarsal area. At this point there is a generalized thickening of the conjunctiva. The conjunctiva has a translucent rather than transparent appearance, and the vasculature of the plate becomes more visible. The conjunctiva may appear hyperemic. In the more aggravated stage of GPC, the conjunctiva loses translucency to become more opaque (due to cellular infiltration), and it is possible to observe the earliest demar-

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium cations of macropapillae (0.3 to 1.0 millimeters) or giant papillae (1.0 millimeters or greater). As the disorder progresses, giant papillae increase in size and elevation. The surface flattens to produce a mushroom appearance devoid of remnants of the small papillary pattern. As the number and size of giant papillae increase, they may almost completely cover zones 1 and 2 with papillae ranging in size from 0.6 to 1.75 millimeters in diameter, with most approximately 0.75 to 1.0 millimeters in diameter. Papillae and follicles resemble each other in some respects, and both are signs of active inflammation in the palperbral conjunctiva. Giant papillae are distinguished from follicles, however, by the presence of blood vessels in the centers of the follicles as well as around the edges. Follicles are more commonly observed in the inferior palpebral conjunctiva and the inferior fornix. Papillae are more commonly observed in the upper palpebral conjunctiva. The side walls of papillae are often perpendicular to the plane of the tarsal plate and not pyramidal-like follicles. Papillae may have white heads resembling scars. These white, scar-like areas usually regress as the papillae regress. Some patients with GPC may have Horner-Trantas dots (Meisler et al., 1980). A network of fine dilated blood vessels may be observed in GPC. The disease may also be confined to the limbus in some patients, with no infiltration of the lid. TREATMENT OF GPC The goal of treatment is to allow the GPC patient to continue wearing contact lenses or to tolerate an ocular prosthesis with the benefit of the most effective and least obtrusive therapeutic program (Molinari, 1982). Nonetheless, the treatment of GPC is complex, requires carefully sequenced clinical divisions, and can be both tedious and expensive for the patient and the physician. Six conditions favor the development or exacerbation of GPC: increased deposits on the lenses, increased time per day that lenses are worn, use of lenses consistently for months or years, individual reactivity to wearing a particular lens type, larger lens and therefore broader area of adhering antigenic material, and genetic constitution of the patient. The treatment of GPC depends on three therapeutic strategies: teaching the patient to clean the lens, finding the best tolerated lens, and treating the conjunctival inflammation.

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium Cleaning the Lens Lens Care Patients must clean the lens thoroughly, preferably using cleaning agents that are free of preservatives (e.g., thimersol). The lens should be rinsed and stored in fresh saline. Cold disinfecting solutions preserved with chlorhexidine should not be used. Three methods of sterilizing the lens are currently available: cold disinfection, heat disinfection, and treatment with hydrogen peroxide. In cold disinfection the lenses remain overnight in the unheated disinfecting solution. Heat disinfection is effective, but the heat bakes the deposits on the surface of the lens. Hydrogen peroxide treatment depends on the disinfecting power of hydrogen peroxide, which is then neutralized by contact with a platinum disc. Of the three commercially available methods, treatment with hydrogen peroxide seems to be the best tolerated by the inflamed or potentially inflamed conjunctiva. Deposits Patients should clean their lenses with a proteolytic enzyme at least once a week. For some patients daily cleaning with a proteolytic enzyme is recommended. Of the two enzyme preparations on the market —the proteolytic enzyme papain and a pancreatic enzyme containing lipases and proteolytic enzymes—the papain enzymatic cleaner seems to be more effective in removing deposits and quieting the GPC. Type of Contact Lens Lens of the Same Design In many patients GPC can be controlled by reestablishing good cleaning practices, a new lens of the same design, and replacing the contact lenses every 6 to 12 months. The patient should then be instructed to clean the lens thoroughly and to use enzymatic cleaning as described above. Lens of a Different Design If proper care and cleaning of the lens and regular replacement do not resolve the GPC, a new contact lens of a different design should be prescribed. A lens of a different design and a polymer different from the one worn when the GPC developed (i.e., change manufacturers) should be prescribed.

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium A lens of a lower water content also can be prescribed. We have initial evidence that non-hydroxyethylmethacrylate (HEMA) lenses may be better tolerated by patients with GPC than HEMA-containing lenses. Patients should be instructed to clean the new lens following the procedure described above. Lenses of Different Design for Each Eye A third maneuver in discovering a tolerable lens design is to prescribe lenses of different design for each eye. For example, one might prescribe a Hydrocurve lens for one eye and a CSI for the other, avoiding the polymer and design that had been associated with exacerbation of the GPC. Rigid Gas-Permeable Lens A fourth option is to prescribe a rigid gas-permeable (RGP) lens rather than a soft (hydrogel) lens. RGP lenses are smaller and thus have less surface to hold deposits. The edge of a gas-permeable lens can be reshaped to be less traumatic to the conjunctiva. Finally, deposits are more easily removed from RGP lenses than from hydrogel lenses. The Conjunctiva Irrigation GPC patients can often tolerate their lenses if they irrigate the conjunctiva with unpreserved saline two or three times a day. Withdrawal of Lenses Contact lenses must be withdrawn under certain pathologic conditions: (1) staining of the tops of the giant papillae when fluorescein is introduced to the tear film, (2) heavy mucus observed on the papillary conjunctiva, (3) significant tarsal hyperemia, and (4) increased lens movement (decentering of the lens) when the patient blinks. Lenses should not be reintroduced until the patient has been free of symptoms for 3 to 5 days and the hyperentia has resolved. Partial resolution of certain signs is acceptable. For example, the large papillae need not decrease in size, but they must be completely healed (as disclosed by failure of fluorescein to stain the tops of the papillae). Itching and heavy mucous production must be resolved.

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium Cromolyn Sodium If GPC symptoms recur after this hygienic program has been followed, cromolyn sodium 4 percent ophthalmic solution may be applied four times daily. Cromolyn sodium may be applied with the contact lens in place. We have found no difficulty in using benzalkonium chloride preserved cromolyn sodium solution while the contact lens is being worn. Donshik and colleagues (1984) carried out a carefully controlled study of the effects of changing various lens parameters and the use of topical cromolyn sodium in the treatment of patients with GPC. Of one group of patients (N = 22), 17 GPC patients (77 percent) found relief by being fitted with new lenses of a different type, but 5 patients suffered a recurrence of symptoms within an average of less than 6 months. Of a second group of patients (N = 17) refitted with the same type of lens, 11 GPC patients (65%) were relieved of symptoms, but 6 patients suffered a recurrence of symptoms. A group of the patients for whom hygienic measures failed to give relief (N = 9) was treated with 2 percent cromolyn sodium. Of this group of difficult cases, 7 patients (78 percent) were relieved of symptoms when treated with cromolyn sodium and were able to resume wearing their contact lenses. The average follow-up period was 7.7 months (range of 5–12 months). The authors reported that there had not been any adverse effect from cromolyn sodium on the contact lens. Matter et al. (1984) reported the results of a 6-week, double-blind, placebo-controlled study of cromolyn sodium in the treatment of contact-lens-associated GPC in 37 actively symptomatic GPC patients. The authors reported the clinical and statistical (p < 05) superiority of cromolyn sodium over placebo in relieving the dryness, grittiness, and abnormal lens movement associated with GPC. Clinical signs were likewise improved after treatment with cromolyn sodium. Cromolyn sodium reduced hyperemia in the bulbar conjunctiva and upper and lower tarsal conjunctiva, diffuse infiltration and size of palpillae in the upper tarsal conjunctiva, and mucous production in the lower tarsal conjunctiva and fornix. In addition to the effectiveness of cromolyn sodium in the treatment of active GPC, its safety makes it valuable as a drug for treating the earliest signs of disease and as a prophylactic agent. We have found it useful in the very early stages of GPC. Cromolyn sodium is also helpful in resolving early (stage 1) symptoms of GPC—increased mucous production and mild itching without giant papillae forming in the upper tarsal conjunctiva. It is not effective, however, in the treatment of the final stages of GPC. However, it is well worth considering use of it as a daily drop to prevent emergence of symptoms in a high-risk, high-need patient.

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium REFERENCES Allansmith, M.R., and R. N. Ross 1987 Giant papillary conjuctivitis. Pp. 1–10 T. Duane, ed., Clinical Opthalmology, Vol. 4 . Philadelphia: Harper & Row Allansmith, M.R., D.R. Korb, and J.V. Greiner 1978 Giant papillary conjunctivitis induced by hard or soft contact lens wear: quantitative histology. Transactions of the American Academy of Opthalmology and Otolaryngology 85:766–778. Allansmith, M.R., R.S. Baird, and J.V. Greiner 1979 Vernal conjunctivitis and contact lens-associated giant papillary conjunctivitis compared and contrasted. American Journal of Ophthalmology 87:544–555. Allansmith, M.R., K.J. Bloch, R.S. Baird, and K. Sinclair 1981 Ocular anaphylaxis: induction by local injection of antigen. Immunology 44:623–627. Binder, P.S. 1979 Complications associated with extended wear of soft contact lenses Ophthalmology 86:1093–1101. 1980 The physiologic effects of extended wear soft contact lenses. Ophthalmology 87:745–749. Buckley, R.J. 1985 Allergic diseases of the eye and use of cromolyn sodium: the British experience. In The First Cromolyn Sodium in Ophthalmology Symposium ( I.H. Lass, ed). Excerpta Medica . Donshik, P.C., and M. Ballow 1983 Tear immunoglobulins in giant papillary conjunctivitis induced by contact lenses. American Journal of Ophthalmology 96:460–466. Donshik, P.C., M. Ballow, A. Luistro, and L. Samartino 1984 Treatment of contact lens-induced giant papillary conjunctivitis Contact Lens Association of Ophthalmologists Journal 10:346–350. Henriquez, A.S., K.R. Kenyon, and M.R. Allansmith 1981 Mast cell ultrastructure: comparison in contact lens-associated giant papillary conjunctivitis and vernal conjunctivitis. Archives of Ophthalmology 99:1266–1272. Jolson, A.S., and S.C. Jolson 1984 Suture barb giant Papillary conjunctivitis. Ophthalmic Surgery 15:139–140. Korb, D.R., M.R. Allansmith, J.V. Greiner, A.S. Henriquez, P.P. Richmond, and V.M. Finnemore 1980 Prevalence of conjunctival changes in wearers of hard contact lenses American Journal of Ophthalmology 90:336–341. MacIvor, J. 1950 Contact allergy to plastic artificial eyes: preliminary report. Canadian Medical Association Journal 62:164–166.

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Considerations in Contact Lens Use Under Adverse Conditions: Proceedings of a Symposium Matter, M., A.H.S. Rahi, and R.J. Buckley 1984 Sodium cromoglycate in the treatment of contact lens-associated giant papillary conjunctivitis. Proc VII Congress of the European Society of Ophthalmology , Helsinki, Finland, 21–25 383–384 Meisler, D.M., C.R. Zaret, and E.L. Stock 1980 Trantas dots and limbal inflammation associated with soft contact lens wear. American Journal of Ophthalmology 89:66–69. Meisler, D.M., J.H. Krachmer, and J.A. Goeken 1981 An immunopathologic study of giant papillary conjunctivitis associated with an ocular prosthesis. American Journal of Ophthalmology 92:368– 371 Molinari, J.F. 1982 Giant papillary conjunctivitis management in hydrogel contact lens wearers. Journal of the British Contact Lens Association 5:94–99. Nirankari, V.S., J.V. Karesh, and R.D. Richards 1983 Complications of exposed monofilament sutures. American Journal of Ophthalmology 95:515–519. Spring, T.F. 1974 Reaction to hydrophilic lenses. Medical Journal of Australia 1:449–450.