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Feiyan Ma, Su-Na Lee, Huiyuan Hou, James Beadle, William Freeman, Karl Hostetler, Lingyun Cheng; Intravitreal long-lasting micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) for cytomegalovirus retinitis. Invest. Ophthalmol. Vis. Sci. 2013;54(15):3208.
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We have previously shown that micelle formulation of HDP-CDV had a long vitreous half-life and good ocular safety profile. In the current study, we applied a pre-treatment strategy to evaluate the sustained therapeutic effect of hexadecyloxypropyl-cidofovir (HDP-CDV) against a rabbit HSV retinitis model.
Twenty-seven New Zealand pigmented rabbits (27 eyes) received either an intravitreal equal molar concentrations of HDP-CDV (42μg/50μl), CDV (28 μg/50μl) or 5% dextrose (50μl) as controls 5 weeks or 9 weeks before HSV intravitreal inoculation. Intravitreal injection of a 5×10-5 dilution of 108TCID/mL HSV was performed to induce HSV retinitis. After the virus injection, the rabbit eyes were monitored by indirect ophthalmoscopy and the retinitis was graded as 0.5, 1, 2, 3, and 4 as we described previously on day 3, day 6, day 9, and day 14 on which rabbits were sacrificed for pathological evaluation. The retinitis scores were compared among the HDP-CDV, free CDV, and dextrose groups.
HSV retinitis in rabbits is a rapidly spreading retinitis model. It presents on day 4 to 6 after virus inoculation and shows rapid progression between day 6 and day 9 before a complete retinitis on day 14. For the 5-week pretreatment study, the retinitis scores on day 6 and day 9 were pooled and treated as a repeated measurement as ordinary scale to compare the retinitis severity among the three groups. HDP-CDV showed significantly less retinitis than dextrose controls (p=0.0047), though no significant difference from CDV group (p=0.22). For the 9-week pretreatment study, HDP-CDV group showed a significantly less retinitis than CDV group (p=0.0053) and dextrose group (p=0.0097). At week 9, CDV had same severe retinitis as the dextrose injected eyes (p=0.23). On day 14 after the virus inoculation, there were 2 eyes that developed retinitis out of 7 eyes with HDP-CDV, 5 eyes out of 5 eyes with CDV, and 5 eyes out of 5 eyes with dextrose (p=0.0062).
CDV can provide 5 weeks antiviral effect after intravitreal injection. However, HDP-CDV can provide at least 9 weeks antiviral effect following a single intravitreal injection of 42 µg.
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