Abstract
Purpose: :
To evaluate bromfenac sodium (BF) 0.1% ophthalmic solution, a non-steroidal anti-inflammatory drug (NSAID) with potent cyclooxygenase (COX) inhibitory activity, in the treatment of acute and chronic uveitis in several rabbit models.
Methods: :
BF 0.1% ophthalmic solution was prepared and tested on Dutch belted and white rabbits. Acute anterior uveitis: a) Lipopolysaccharides (LPS, 10 µg/kg) was injected intravenously into the marginal ear vein. The aqueous flare was continuously measured with a flare cell meter (Kowa) for 8 hrs. One drop of BF was instilled at 1 hr prior to injection or, 1 hr before and every hour for 8 hrs. b) LPS (50 ng) was injected intravitreously. Anterior inflammation was observed using slit lamp and aqueous protein and cells were measured at 24 hrs. BF was instilled every 2 hrs for 24 hrs. Chronic uveitis: Bovine serum albumin (10 µg) was injected intravitreously. Anterior and posterior inflammations were observed for 25 days. Drugs were instilled twice daily.
Results: :
Acute anterior uveitis: Intravenous LPS increased the aqueous flare with peak level occurring at 1 hr. A single drop instillation of BF completely inhibited the increase in aqueous protein production, whereas, the NSAID pranoprofen, demonstrated only 70% inhibition even with 8-times instillation. Intravitreous LPS gradually increased aqueous protein till 24 hrs. BF demonstrated complete inhibition in anterior inflammatory signs and significant inhibition in the polymorphonuclear leukocyte infiltration in the anterior chamber. Betamethasone (BM), a steroid, inhibited the inflammatory signs by 50% and strongly inhibited the elevation of leukocytes. Chronic uveitis: Ocular inflammatory signs induced by BSA reached peak levels between Days 10 to 12. BF decreased the anterior and posterior inflammations by 70% and 50%, respectively. BM inhibited anterior and posterior inflammation by 70 and 80%, respectively.
Conclusions: :
These studies suggest that the COX enzyme is strongly involved in uveitis and endogenously released eicosanoids induce signs of the anterior and posterior inflammation like uveitis. BF was equally efficacious in inhibiting both acute and chronic uveitis in rabbits as BM. These results confirm the efficacy seen in human for anterior uveitis and suggests the possibility for its application and effectiveness in posterior uveitis.
Keywords: drug toxicity/drug effects • uveitis-clinical/animal model • enzymes/enzyme inhibitors