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Laboratory Science |

Trifluridine, Cidofovir, and Penciclovir in the Treatment of Experimental Herpetic Keratitis

Herbert E. Kaufman, MD; Emily D. Varnell, BS; Hilary W. Thompson, PhD
Arch Ophthalmol. 1998;116(6):777-780. doi:10.1001/archopht.116.6.777.
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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.

Conclusion  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.

Clinical Relevance  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.

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Figure 1.

Comparison of the severity of keratitis (on a scale of 0-4 [see the "Methods" subsection for an explanation of the grades on the scale]) in rabbits infected with the McKrae strain of herpes simplex virus type 1 in both eyes and treated with 1 of the 3 drugs on various dosage schedules. Treatment was begun after the evaluation on postinfection day 3 and continued through day 9. Treatments with 1% trifluridine drops, 0.2% cidofovir solution, or 3% penciclovir ointment were administered in a coded manner, and all grading was done in a masked manner.

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Figure 2.

Comparison of the severity of keratitis (on a scale of 0-4 [see the "Methods subsection for an explanation of the grades on the scale]) in rabbits infected with the McKrae strain of herpes simplex virus type 1 in both eyes and treated with 1 of the 3 drugs on a once-a-day schedule. Treatment was begun after the evaluation on postinfection day 3 and continued through day 9. Treatments with 1% trifluridine drops, 0.2% cidofovir solution, or 3% penciclovir ointment were administered once a day, in a coded manner, and all grading was done in a masked manner.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Comparison of the severity of keratitis (on a scale of 0-4 [see the "Methods subsection for an explanation of the grades on the scale]) in rabbits infected with the McKrae strain of herpes simplex virus type 1 in both eyes and treated with 1% cidofovir twice a day or 1% trifluridine 5 times a day. Treatment was begun on postinfection day 3 and continued through day 7. Drug treatments were coded, and all grading was done in a masked manner.

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