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S.P. Epstein, Y.Y. Pashinsky, I. Winicov, P.A. Asbell; Topical Cobalt Chelate Ctc-96 for Treatment of Adenovirus Conjunctivitis in a Rabbit Model . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4650.
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Purpose: Adenovirus (Ad), one of the most common external ocular viral infections worldwide, is associated with significant morbidity and visual disturbances and is highly contagious. Currently, there is no topical antiviral treatment available for adenovirus. We have previously shown that topical tetradentate CoIII chelates can be effective against Herpes Simplex Virus (HSV) keratitis in a rabbit model, that human Adenovirus type 5 (Ad5) has the ability to replicate in rabbits and rabbit cells and that CTC-96 is effective against Ad5 in tissue culture. We now look at the efficacy of CTC-96 in treating ocular Ad infections in a rabbit model. Methods: Normal 3-5 lb NZW rabbits were intracorneally infected with Ad5. After 8 days when ocular disease developed, the animals were arbitrarily divided into groups receiving for 21 days: 1) placebo treatment (normal saline), 9x/day ("-"); 2) CTC-96, 50µg/ml, 9x/day ("50/9"); CTC-96, 50µg/ml, 6x/day ("50/6"); CTC-96, 25µg/ml, 6x/day ("25/6"). Animals were followed in a masked/blinded fashion and monitored for severity/resolution of the conjunctivitis via biomicroscropic examination as well as in conjunctival adenovirus cultures followed by a standardized plaque assay. Results: CTC-96 at 50µg/ml was effective against Ad5, eliminating virus by day 10 in both of the dosing frequencies evaluated, whereas viral clearance was not achieved until day 21 in the sham-treated eyes. CTC-96 at 25µg/ml was only marginally effective. Conclusions: 1) In rabbits, infection with Ad5 produced mainly conjunctivitis with rare slight, small changes in the cornea and/or stroma. 2) Iritis was occasionally seen. 3) Conjunctivitis seen in all eyes by day 8 post-innoculum. 4) Resolution fastest in treatment group "50/9" where most animals resolved by day 21 post-treatment initiation (pt): "50/9" > "50/6" > "25/6" > "-". 5) Little corneal or intra-ocular changes noted in any of the groups. In conclusion, cobalt chelates (CTC-96) were effective in reducing the degree and length of conjunctivitis in rabbit eyes infected with Adenovirus.
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