Abstract
Abstract: :
Purpose: To investigate the possible involvement of ocular inflammation and the mechanism of conjunctival hyperemia associated with bimatoprost treatment in patients and laboratory animals. Methods: Ocular inflammation was evaluated in bimatoprost–treated glaucoma and OHT patients using laser–flare photometry, biomicroscopy, and histopathologic evaluation of bulbar conjunctival specimens. In–life observations and histopathological assessment of ocular tissues were conducted for multiple–dose chronic safety studies (one–month to 52–weeks) in rabbits, dogs, and monkeys. Vascular effects of bimatoprost were evaluated using the rabbit endothelium–intact and endothelium–denuded precontracted isolated jugular vein preparation. Ocular surface hyperemia grading was performed in dogs dosed topically with bimatoprost in the presence and absence of a nitric oxide synthase inhibitor L–NAME. Results: The conjunctiva and anterior chamber of patients exhibited no signs of ocular inflammation associated with bimatoprost treatment. Similarly, preclinical safety studies showed no evidence of treatment–related inflammation in ocular tissues of rabbits, dogs, and monkeys. Bimatoprost produced weak vasorelaxant responses in the endothelium–intact rabbit jugular vein preparations, but was inactive in preparations where the vascular endothelium had been removed. Conjunctival hyperemia in dogs treated with bimatoprost was significantly inhibited by L–NAME. Conclusions: Conjunctival hyperemia related to bimatoprost treatment is not associated with inflammation, neither intraocular nor at the ocular surface, in patients and laboratory animals. The mechanism of conjunctival hyperemia appears to occur by vasodilatation and involves endothelium–derived nitric oxide. These studies indicate that conjunctival hyperemia is a non–inflammatory, pharmacologically–based vasodilatation, side effect of bimatoprost treatment.
Keywords: conjunctiva • eicosanoids • nitric oxide