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 animals to investigate its viral pathogenicity and latent infection.


METHODS
HSV-1 isolates from the patients were tested for drug sensitivity 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 were infected by the respective viral isolates. The extent of corneal epithelial 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 keratitis in both patients was characterized by prolonged clinical course, succeeded by various types of corneal lesions and ocular complications. In in vitro studies, the two HSV-1 isolates demonstrated cross-resistance to ACV, ganciclovir and/or idoxuridine. Both strains demonstrated weakly virulent corneal epithelial and/or stromal lesions in rabbits and mice. One isolate displayed delayed advent but prolonged course of epithelial lesions in rabbits. The latent infection incidences of the isolates in mice trigeminal ganglia were 6.25% (1/16) and 0% (0/18) respectively.


CONCLUSIONS
Topical immune depression may induce ACV-resistant HSV-1 infection in the cornea, with a prolonged course in association with ocular complications. The prolonged infectious course of the viral isolates in the animal study partially supported the clinical 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 treating corneal epithelial lesions caused by ACV-resistant HSV-1.
Yao
Y F
YF
Department of Ophthalmology, Osaka University Medical School, Japan.
Inoue
Y
Y
Kase
T
T
Uchihori
Y
Y
Mori
Y
Y
Ohashi
Y
Y
D000212:Acyclovir / Q000494:pharmacology / Q000627:therapeutic use*; D000287:Administration, Topical; D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003315:Cornea / Q000187:drug effects / Q000294:innervation / Q000821:virology; D046508:Culture Techniques; D004195:Disease Models, Animal; D004352:Drug Resistance, Microbial; D019084:Fluorescent Antibody Technique, Indirect; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000302:isolation & purification* / Q000472:pathogenicity; D006801:Humans; D007065:Idoxuridine / Q000494:pharmacology / Q000627:therapeutic use; D007635:Keratitis, Dendritic / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D009824:Ointments; D011817:Rabbits; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000473:pathology / Q000821:virology
D000998:Antiviral Agents; D009824:Ointments; D007065:Idoxuridine; D000212:Acyclovir