Purpose
To assess the efficacy and safety of dexamethasone sodium phosphate Visulex system (DSP-V) with various dosing regimens in treating intermediate and posterior uveitis in New Zealand white (NZW) rabbit.
Methods
Fifteen NZW rabbits were assigned to 5 groups according to DSP concentration, dosing, and Visulex application time (see table). Uveitis was induced in NZW rabbits by subcutaneous injections of complete Freund’s adjuvant and an IVT injection of H37 RA antigen as described by Cheng, et. al. After induction, DSP treatment was given to the right eye of each rabbit by DSP-V except the control group. Efficacy and safety of DSP-V were evaluated daily by indirect ophthalmoscopy (IO) and at the end of the study by histopathological examinations (HE) to evaluate the pathology and inflammatory cell infiltration (ICI) into the eye tissues including both anterior (conjunctiva, cornea, anterior chamber) and posterior sections (vitreous, choroid, retina).
Results
The control group exhibited significant inflammation in the vitreous, choroid, and retina; and slight or no inflammation in the conjunctiva, cornea, anterior chamber, and iris. All treatments with DSP-V showed effectiveness in the reduction of vitreous opacity (VO) and ICI of the vitreous, choroid, and retina. The VO of the control group indicate that uveitis occurred within 24 h after induction and remained throughout the 29 day study. After Day 3, there was a clear differentiation between the control and the 10 and 15 min treatment groups. By Day 10, the highest dosing regimen (Group 2) showed complete resolution of the vitreal inflammation and by Day 21, the lowest dosing regimen (Group 5) was also completely clear. With the exception of the 8% single dose treatment, there appears to be a DSP dose-efficacy relationship. As for the safety of DSP-V, the differences in inflammation scores between the treatment and control groups would imply DSP-V is a safe modality for uveitis treatment. The HE also supports the safety aspect of DSP-V treatment.
Conclusions
DSP-V containing 8% to 15% DSP administered for 5 to 15 min is well tolerated and highly efficacious in this chronic intermediate and posterior uveitis model. Even a single dose of 8% DSP can suppress intermediate and posterior uveitis for 29 days.
Keywords: 746 uveitis-clinical/animal model •
557 inflammation •
503 drug toxicity/drug effects