Experimental thymidine kinase-deficient HSV-1 keratitis: therapeutic attempts

Area of Science:

• Ophthalmology
• Virology
• Pharmacology

Background:

• Herpes simplex virus type 1 (HSV-1) can cause keratitis.
• Thymidine kinase (TK) is crucial for activating antiviral drugs.
• TK-positive (TK+) and TK-deficient (TK-) HSV-1 strains present different treatment challenges.

Purpose of the Study:

• To evaluate the efficacy of trifluridine (TFT) and 5-fluoro-2'-deoxyuridine (FDU) in treating experimental HSV-1 keratitis.
• To compare TFT and FDU with bromovinyldeoxyuridine (BVDU) and placebo.
• To investigate the differential effects on TK+ and TK- HSV-1 strains.

Main Methods:

• Topical administration of 0.2% BVDU, 0.2% TFT, and 0.2% FDU eyedrops in experimental keratitis models.
• Utilized both TK+ and TK- HSV-1 strains.
• Statistical comparison of healing rates against placebo.

Main Results:

• 0.2% BVDU and 0.2% TFT eyedrops significantly healed TK+ HSV-1 keratitis compared to placebo and FDU (P < 0.005).
• 0.2% FDU eyedrops showed no significant difference from placebo for TK+ HSV-1 keratitis.
• No beneficial healing effect was observed for TK- HSV-1 keratitis with any tested drug, despite in vitro inhibition by TFT and FDU.

Conclusions:

• Trifluridine (TFT) is effective for topical treatment of TK+ HSV-1 keratitis.
• The efficacy of TFT and FDU is dependent on the viral thymidine kinase status.
• Further research may be needed for effective treatment of TK- HSV-1 keratitis.