Wilson and colleagues1- 3 reported an association between Mooren ulcer and chronic infection with hepatitis C virus (HCV) in 4 patients. Interferon alfa-2b, an effective therapy for some patients with HCV, caused at least a temporary remission of eye disease in their 4 subjects.3 We report another case of keratitis responsive to treatment with interferon alfa-2b in which a focused medical evaluation revealed HCV infection.
A 54-year-old white man was referred for a corneal degeneration. His medical history included abnormal findings on liver function tests, diabetes mellitus, vitiligo, and Graves disease that had been treated with radioactive iodine. The patient described bilateral redness and discomfort over the previous 5 years that was responsive to treatment with topical corticosteroids. Best-corrected acuity was 20/20 OD and 20/60 OS. Both eyes had diffuse conjunctival hyperemia. The right cornea demonstrated mild thinning in the superior and inferior peripheries. The left eye had vasodilated and thickened nasal conjunctiva. There was 300° of peripheral, corneal thinning. Neovascularization extended onto the nasal cornea. The epithelium was intact. A posterior subcapsular cataract was present on the left cornea. There was no evidence of blepharitis or meibomian gland dysfunction.
A medical evaluation disclosed no clinical evidence of rheumatologic disease. Heptatis C virus antibodies were detected as was HCV RNA by polymerase chain reaction techniques (HCV Amplicor Assay, Roche, Inc, Branchburg, NJ). Laboratory tests included elevated values for alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, and direct bilirubin. Total complement and C3 complement levels were reduced. An ultrasound showed a coarsened liver texture and hepatosplenomegaly that were suggestive of cirrhosis and portal hypertension. Data from other laboratory tests included normal or negative values for erythrocyte sedimentation rate, complete blood cell count, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibodies, VDRL, purified protein derivative (tuberculin), total bilirubin, alkaline phosphatase, and hepatitis B surface antigen.
We prescribed 3 million units of interferon alfa-2b subcutaneously 3 times a week. Several days after initiating therapy, conjunctival vasodilation diminished, and he discontinued the topical corticosteroid regimen. The interferon alfa-2b was given empirically for 8 months, but 5 months after discontinuation of this treatment, bilateral vasodilation, peripheral corneal infiltrates, and progressive stromal thinning recurred (Figure 1).
Five months after discontinuing treatment with interferon alfa-2b. Left, In the right eye, there is thinning of the superior and inferior, peripheral cornea. Peripheral infiltrates are present from the 6-o'clock to 8-o'clock positions. Right, The left eye has circumferential, peripheral thinning as demonstrated by poor visualization of the peripheral iris detail. A peripheral infiltrate is present inferotemporally.
This case demonstrates a milder form of keratitis than previously described in association with HCV, but it shares the features of bilaterality, chronicity, inflammation, a lack of evident systemic autoimmune disease, and a transient response to treatment with interferon alfa-2b. Possible mechanisms for keratitis include antigenic mimicry, in which host immunity against hepatitis C antigens cross-reacts with epitopically similar autoantigens,2 or immunoreactivity directed against exogenous viral antigens absorbed into the cornea. The concentration of HCV RNA in tear fluid can be higher than that in plasma,4 so the exposure of the ocular surface to a relatively high viral antigen load is possible.
As in any constellation of concurrent clinical findings, the clinician must maintain caution in linking presumptive causes with clinical signs or symptoms. Until the association between HCV and keratitis is either definitively established or found to be coincidental, we recommend that all patients with inflammatory peripheral keratitis without systemic rheumatologic disease be tested for HCV. In cases of suspected staphylococcal marginal keratitis, HCV testing would also be reasonable in atypical presentations or recalcitrant disease.
This study was supported in part by Research to Prevent Blindness, Inc, New York, NY.
Reprints: Keith H. Baratz, MD, Mayo Clinic, 200 First St, SW, Rochester, MN 55902 (e-mail: firstname.lastname@example.org).
Baratz KH, Fulcher SFA, Bourne WM. Hepatitis C–Associated Keratitis. Arch Ophthalmol. 1998;116(4):529-530. doi: