Trifluridine, cidofovir, and penciclovir in the treatment of experimental herpetic keratitis.
OBJECTIVE
To compare trifluridine eyedrops, cidofovir eyedrops, and penciclovir ophthalmic ointment for the treatment of herpes simplex virus type 1 keratitis.


METHODS
New Zealand white rabbits were infected with the McKrae strain of herpes simplex virus type 1. Three days after viral inoculation, the rabbits were randomly assigned to treatment with 1% trifluridine, 0.2% cidofovir, 3% penciclovir ointment, or phosphate-buffered saline (for control) on various schedules. The severity of keratitis was graded in a masked manner.


RESULTS
Treatment with any of the antiviral drugs resulted in significantly less severe keratitis than treatment with phosphate-buffered saline. There was no statistically significant difference between eyes given trifluridine 2, 4, or 7 times a day and eyes given cidofovir 2 times a day (P=.06, P=.43, and P=.19, respectively, using the F test of the analysis of variance). Cidofovir given twice a day was significantly more effective than penciclovir given either 2 or 4 times a day (P<.001 and P=.002, respectively). Even with once-a-day dosage, all 3 drugs were significantly more effective than phosphate-buffered saline (P<.001 for all). There was no significant difference between once-a-day trifluridine and cidofovir treatments (P=.17). Trifluridine administered 5 times a day was as effective as 1% cidofovir. A similar degree of punctate keratitis was seen after 4 to 5 days in eyes treated with trifluridine at the highest frequency, 1% cidofovir, or penciclovir ointment.


CONCLUSIONS
Trifluridine treatment was highly effective in this rabbit model, even when given only once a day. Treatment with cidofovir was as effective as that with trifluridine.


CONCLUSIONS
Cidofovir and penciclovir treatments may prove to be effective against epithelial keratitis. Clinical trials of trifluridine, cidofovir, and penciclovir with lower treatment frequencies appear to be warranted.
Kaufman
H E
HE
LSU Eye Center, Louisiana State University Medical Center School of Medicine, New Orleans 70112-2234, USA.
Varnell
E D
ED
Thompson
H W
HW
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000077404:Cidofovir; D003315:Cornea / Q000187:drug effects / Q000473:pathology / Q000821:virology*; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D006147:Guanine; D018259:Herpesvirus 1, Human / Q000187:drug effects; D016849:Keratitis, Herpetic / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009824:Ointments; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000008:administration & dosage* / Q000627:therapeutic use; D011817:Rabbits; D014271:Trifluridine / Q000008:administration & dosage* / Q000627:therapeutic use
D000998:Antiviral Agents; D009824:Ointments; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C053539:penciclovir; D006147:Guanine; D003596:Cytosine; D000077404:Cidofovir; D014271:Trifluridine; D000212:Acyclovir