CLINICAL CHARACTERISTICS OF ACYCLOVIR-RESISTANT HERPETIC-KERATITIS AND EXPERIMENTAL STUDIES OF ISOLATES

Background: We treated two patients with dendritic keratitis that did not respond to acyclovir (ACV) ointment therapy. Their systemic immune status was normal; however, one patient had a long history of atopic disease and the other had previously undergone topical corticosteroid treatment. HSV-1 was isolated from the patients and inoculated into an imals to investigate its viral pathogenicity and latent infection. Met hods: HSV-1 isolates from the patients were tested for drug sensitivit y to acyclovir, ganciclovir, idoxuridine, trifluridine, foscarnet and interferon-beta in vitro. In in vivo studies, bilateral corneas of two New Zealand white rabbits and 10 BALB/c mice in each of four groups w ere infected by the respective viral isolates. The extent of corneal e pithelial and/or stromal lesions produced by the viruses was evaluated . The trigeminal ganglial tissues of the mice were examined for viral latent infection by co-culture with Vero cells. Results: Herpetic kera titis in both patients was characterized by prolonged clinical course, succeeded by various types of corneal lesions and ocular complication s. In in vitro studies, the two HSV-1 isolates demonstrated cross-resi stance to ACV, ganciclovir and/or idoxuridine. Both strains demonstrat ed weakly virulent corneal epithelial and/or stromal lesions in rabbit s and mice. One isolate displayed delayed advent but prolonged course of epithelial lesions in rabbits. The latent infection incidences of t he isolates in mice trigeminal ganglia were 6.25% (1/16) and 0% (0/18) respectively. Conclusion: Topical immune depression may induce ACV-re sistant HSV-1 infection in the cornea, with a prolonged course in asso ciation with ocular complications. The prolonged infectious course of the viral isolates in the animal study partially supported the clinica l demonstrations in the patient. The existence of latent infection by one ACV-resistant HSV-1 in its animals may indicate the possibility of its recurrence. Trifluridine may be an alternative choice for treatin g corneal epithelial lesions caused by ACV-resistant HSV-1.