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To evaluate symptoms and changes in tear function and the ocular surface with interferon and ribavirin therapy for chronic hepatitis C.Nineteen patients with chronic hepatitis C undergoing a course of interferon alfa-2b/ribavirin therapy and 19 age- and sex-matched controls participated in this prospective study. Patients were evaluated for dry eye subjectively (15-symptom assessment questionnaire) and objectively, including ophthalmologic examination, Schirmer test, tear clearance rate (TCR), tear function index (TFI), and nucleus/cytoplasm (N/C) ratio of conjunctival epithelial cell by impression cytology. All tests were performed before antiviral therapy (baseline); at 1, 3, and 6 months after initiation of therapy; and at 3 and 6 months after completing the 6-month course of treatment. All the tear functional tests and impression cytology results in controls were compared with pretreatment baseline of study group, using the Student t test. A paired t test was used to compare mean patient follow-up values with mean patient baseline values.Patients' mean score on the dry eye symptom assessment questionnaire was significantly (P < 0.05) higher than baseline after 1 and 3 months of therapy, peaked after 6 months of therapy, remained significantly elevated at 3 months after completion of therapy, but had decreased to almost baseline by 6 months after cessation of therapy. Compared with baseline, mean Schirmer test values showed a significant change only at 1 month after the start of treatment. In contrast, mean TCR, mean TFI, and mean N/C ratio were significantly different from baseline at every examination, including 6 months after discontinuation of therapy. After 6 months of therapy, 4 patients (21%) had advanced squamous metaplasia (stage 3 or 4), but 2 patients still had mild squamous metaplasia (stage 2) even 6 months after the completion of therapy.Impairment of tear dynamics and squamous metaplastic changes in the ocular surface occurred in patients with chronic hepatitis C treated with interferon alfa-2b and ribavirin. Symptoms of dry eye were mild and reversible; however, abnormalities in tear dynamics and the ocular surface persisted even 6 months after discontinuation of treatment.