Clinical evaluation of local ocular toxicity in candidate anti-adenoviral agents in vivo.
BACKGROUND
Adenovirus causes ophthalmological nosocomial infections. Although cidofovir may be used systemically for immunocompromised patients in disseminated adenoviral infections, no specific anti-adenoviral agent has been established for the treatment of adenoviral ocular infection. It has been reported that cidofovir may cause lacrimal duct obstruction when used locally. We have reported that zalcitabine and stavudine showed anti-adenoviral activity in vitro. We now evaluate the side effects of these agents in eyes and ocular adnexa in an animal model.


METHODS
Cidofovir, zalcitabine and stavudine 1% solutions and balanced salt solution were given as eye drops to healthy female Japanese albino rabbits 4 times a day for 14 days. Clinical scores in the conjunctiva and eyelid were recorded, and lacrimal irrigation was carried out. The diameter of the lacrimal canaliculus was scanned with an ultrasonograph. Histopathological analysis was carried out in the cidofovir group.


RESULTS
In the cidofovir group, significant narrowing of lacrimal canaliculus, redness of eyelids and conjunctival injection were observed, but no obstruction of the lacrimal duct was found. Histology showed eosinophils, suggesting an allergic inflammation. Although zalcitabine and stavudine induced eyelid redness and conjunctival injection, no change was observed in the lacrimal pathway.


CONCLUSIONS
These drugs may be possible candidates as eye drops for adenoviral conjunctivitis but further study is required to prove its safety.
Inoue
Hirotoshi
H
Department of Ophthalmology, Fukuoka University School of Medicine, Fukuoka, Japan. hiro_fuk_un@yahoo.co.jp
Sonoda
Koh-hei
KH
Ishikawa
Makoto
M
Kadonosono
Kazuaki
K
Uchio
Eiichi
E
D000257:Adenoviridae Infections / Q000188:drug therapy* / Q000821:virology; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000633:toxicity*; D000077404:Cidofovir; D003228:Conjunctiva / Q000187:drug effects* / Q000473:pathology / Q000821:virology; D003236:Conjunctivitis, Viral / Q000188:drug therapy* / Q000821:virology; D003596:Cytosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004195:Disease Models, Animal; D005143:Eyelids / Q000187:drug effects* / Q000473:pathology; D005260:Female; D007765:Lacrimal Apparatus / Q000187:drug effects* / Q000473:pathology; D009883:Ophthalmic Solutions; D063065:Organophosphonates / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits
D000998:Antiviral Agents; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D003596:Cytosine; D000077404:Cidofovir