Efficacy of 9-(2-phosphonylmethoxyethyl)adenine in the therapy of TK⁺and TK⁻herpes simplex virus experimental keratitis

The acyclic nucleoside phosphonate analogue PMEA [9-(2-phosphonylmethoxyethyl)adenine] is a broad spectrum antiviral agent effective against DNA viruses and retroviruses. It is particularly active against the human immunodeficiency virus and, like other phosphonylmethoxyalkyl derivatives, it also inhibits HSV-1, TK- HSV-1 and HSV-2. We have evaluated the therapeutic efficacy of PMEA in the HSV-1 and TK- HSV-1 experimental keratitis models using BVDU (bromovinyldeoxyuridine) as the reference compound. As compared to placebo eyedrops, PMEA 0.2% and BVDU 0.2% eyedrops induced a rapid and significant healing (P less than 0.005) of keratitis caused by TK+ HSV-1. Treatment with PMEA 0.2% eyedrops also reduced the severity of keratitis caused by the TK- HSV-1 (P less than 0.05), whereas BVDU 0.2% eyedrops did not affect the course of TK- HSV-1 keratitis.