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H. Inoue, M. Ishikawa, K.-H. Sonoda, E. Uchio; Evaluation of Local Ocular Toxicity in Candidate Anti-Adenoviral Agents in vivo. Invest. Ophthalmol. Vis. Sci. 2007;48(13):735.
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Approximately one million people suffer from adenoviral keratoconjunctivitis every year and it is recognized as one of the major pathogens of ophthalmological nosocomial infection in Japan. Although cidofovir may be used systemically for immunocompromised patients in disseminated adenoviral infection, no specific anti-adenoviral agent is established for the treatment of adenoviral infection. However, it has been reported that cidofovir may cause a development of lacrimal duct obstruction when used locally. We have recently reported that among anti-HIV drugs, zalcitabin and stavudine, which are nucleoside reverse transcriptase inhibitors showed significant anti-adenoviral activity in vitro. We further evaluated the side effects of these possible anti-adenoviral agents including cidofovir in eyes and ocular adnexa in an animal model.
Four anti-adenoviral candidate agents, cidofovir, zalcitabin, stavudine and interferon beta 1% solutions and BSS (balanced salt solution) were given as eye drops to healthy female New Zealand white rabbits (5 animals for each agent) four times per day for 14 days. Clinical scores in conjunctiva, cornea and eyelid were recorded and lacrimal irrigation was carried out. Diameter of lacrimal canaliculus was scanned with ultrasonograph (UD-6000® with 20MHz probe UD-1050®, Tomey, Japan). Histopathological analysis was carried out in animals treated by cidofovir.
In animals given cidofovir locally, significant narrowing of lacrimal canaliculus, redness of eyelids, and conjunctival injection were observed. Obstruction of lacrimal duct was not found. Although zalcitabin and stavudine eyedrops induced eyelid redness, no change was observed in lacrimal route and conjunctiva. In animals treated by cidofovir, histology suggested inflammation mainly due to allergic changes.
These results indicate that these drugs may be possible candidates of safe eyedrops for adenoviral conjunctivitis. It is expected that eyedrops for specific treatment of adenoviral conjunctivitis are going to be available in the near future following investigations of therapeutic effect in adenoviral infected animals and clinical trials in humans.
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