Abstract
Purpose:
To compare the anti-inflammatory effects of a suprachoroidal injection of CLS-TA, triamcinolone acetonide injectable suspension with clinically relevant doses of oral prednisone in a porcine model of acute uveitis.
Methods:
Twenty-four hours after the induction of acute posterior uveitis by intraocular lipopolysaccharide (LPS) injection (Day 0) into the vitreous, 50 µL of balanced salt solution (BSS, Group 1) or CLS-TA (2 mg, Group 3) was injected into the suprachoroidal space (SCS). In Groups 2 and 4, oral prednisone (1 mg/kg/day, Group 2 or 0.1 mg/kg/day, Group 4) was dosed on Day 0, and repeated every 24 hours until euthanasia on day 3. The doses chosen for this study reflect the doses typically used to treat patients with uveitis, for initial dose (1 mg/kg/day) and maintenance dose (0.1 mg/kg/day). Only the right eye of each animal was used in the study and the left eye was unaltered (n=4/group). Eyes were examined daily, which included measuring inflammation scores (modified Hackett-McDonald) and intraocular pressure (IOP). Safety assessments and histopathology were performed on all eyes.
Results:
Following induction with LPS, mean inflammation scores for all groups increased significantly compared with pre-induction scores. After treatment, mean inflammation scores decreased in all groups. On Days 1 and 2 only, Group 3 (suprachoroidal CLS-TA) had mean cumulative inflammation scores significantly lower than Group 1 (p≤0.04), the BSS, or untreated control group. By day 3, Group 2 (high dose oral prednisone) and Group 3 (CLS-TA) had significantly lower mean cumulative inflammation scores than Group 1 (BSS) treated eyes (p<0.034). In Group 4 (low dose oral prednisone), mean cumulative inflammation scores were not significantly different than BSS treated eyes at any treatment time (p>0.05). Mean histologic inflammation scores of the anterior and posterior segment with CLS-TA (Group 3) were significantly lower than eyes treated with BSS (Group 1).
Conclusions:
These results suggest that suprachoroidal injection of CLS-TA resulted in more rapid anti-inflammatory effect than oral prednisone (Day 1 vs Day 3), was as effective as high dose oral prednisone (Day 3), and was superior to low dose prednisone in its anti-inflammatory effect in this porcine model of acute uveitis.