Efficacy of low-release-rate fluocinolone acetonide intravitreal implants to treat experimental uveitis.
OBJECTIVE
To determine the efficacy of 0.5-mg and 0.1-mg sustained-release fluocinolone acetonide intravitreal implants to inhibit ocular inflammation in a rabbit model of severe uveitis.


METHODS
The in vitro pharmacokinetic profile of both the 0.5-mg and 0.1-mg sustained-release fluocinolone intravitreal implants was determined during a 10-day period. A sustained-release fluocinolone acetonide intravitreal implant with a release rate of either 0.5 microg/d (n = 16) or 0.1 microg/d (n = 16) was implanted into the vitreous cavity of the right eye in albino rabbits after a subcutaneous injection of tuberculin antigen. Control animals (n = 14) received empty devices. Uveitis was induced with an intravitreal tuberculin antigen injection. A masked observer graded anterior chamber flare, anterior chamber cells, vitreous opacity, and inflammation on histologic sections.


RESULTS
In vitro, the drug was released from both devices in a linear manner. In vivo, treated eyes were significantly less inflamed than untreated eyes (P< or =.02). Inflammation was suppressed to a greater degree with the 0.5-microg/d implant compared with the 0.1-microg/d implant.


CONCLUSIONS
Sustained-release fluocinolone intravitreal implants suppress ocular inflammation in a rabbit model of severe uveitis.


CONCLUSIONS
The efficacy demonstrated with the 0.1-microg/d implant provides the rationale for future human studies with lower-release-rate implants than are currently used in noninfectious uveitis clinical trials.
Mruthyunjaya
Prithvi
P
Department of Ophthalmology, Duke University Eye Center, Erwin Road, Durham, NC 27710, USA.
Khalatbari
Dara
D
Yang
Ping
P
Stinnett
Sandra
S
Tano
Ryotaro
R
Ashton
Paul
P
Guo
Hong
H
Nazzaro
Marty
M
Jaffe
Glenn J
GJ
D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D004195:Disease Models, Animal; D004343:Drug Implants; D004596:Electroretinography; D005136:Eye Proteins / Q000378:metabolism; D005446:Fluocinolone Acetonide / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007958:Leukocyte Count; D011817:Rabbits; D016896:Treatment Outcome; D014605:Uveitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D014822:Vitreous Body
D004343:Drug Implants; D005136:Eye Proteins; D005938:Glucocorticoids; D005446:Fluocinolone Acetonide