Efficacy of low-release-rate fluocinolone acetonide intravitreal implants to treat experimental uveitis.

Abstract

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.

CONCLUSION:

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

CLINICAL RELEVANCE:

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.

• Authors: Prithvi Mruthyunjaya, Dara Khalatbari, Ping Yang, Sandra Stinnett, Ryotaro Tano, Paul Ashton, Hong Guo, Marty Nazzaro, Glenn J Jaffe
• Journal: Archives of ophthalmology (Chicago, Ill. : 1960) (Arch Ophthalmol) Vol. 124 Issue 7 Pg. 1012-8 (Jul 2006) ISSN: 0003-9950 [Print] United States
• PMID: 16832025 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Drug Implants
• Eye Proteins
• Glucocorticoids
• Fluocinolone Acetonide

Topics

• Animals
• Aqueous Humor (metabolism)
• Disease Models, Animal
• Drug Implants
• Electroretinography
• Eye Proteins (metabolism)
• Fluocinolone Acetonide (administration & dosage, pharmacokinetics)
• Glucocorticoids (administration & dosage, pharmacokinetics)
• Leukocyte Count
• Rabbits
• Treatment Outcome
• Uveitis (drug therapy, metabolism, pathology)
• Vitreous Body