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PURPOSE: A retrospective study was done of 47 patients who wore frequent-replacement contact lenses on a daily basis and replaced them every 1 day to 12 weeks. The incidence of giant papillary conjunctivitis (GPC) was determined, and potential risk factors that may predispose frequent-replacement contact lens wearers to develop GPC were assessed. METHODS: The records of patients who were fitted with frequent-replacement contact lenses with no prior contact lens experience (September 1993 to February 1997) were reviewed. RESULTS: Forty-seven of 260 patients met the requirement for inclusion in this study. Ten (21.27%) of the patients developed GPC. The incidence varied according to how often the contact lenses were replaced. Incidence was 36% in patients who replaced their lenses at 4 weeks or longer and 4.5% in patients who replaced their lenses at less than 4 weeks. Lenses were coated more often in patients who replaced their lenses at 4 weeks or longer (pi = .23). A significantly greater number of patients in the GPC group incorporated enzyme into their contact lens care system (pi = .0004). A history of allergy was present, significantly more often in patients who developed GPC (pi = .012). There was no significant difference between the groups for age, sex, average daily wearing time, Food and Drug Administration classification of contact lens material, time in contact lenses from fitting to diagnosis or last follow-up period, or the parameters and fitting characteristics of the contact lenses. CONCLUSION: The frequency of contact lens replacement appears to be an important variable in development of GPC. Although frequent-replacement contact lenses do not eliminate GPC, patients on a 1-day to 3-week replacement cycle had a significantly lower risk of developing GPC than patients who replaced their lenses at longer intervals. Coating was present less often on lenses replaced every 1 day to 3 weeks. In patients who are at high risk for GPC, replacing lenses at intervals of 1 day to 2 weeks appears to offer a better strategy in avoiding GPC than incorporating enzymatic cleaning into their care system.