Effects of timolol and brimonidine eyedrops on rabbit ocular surface

Abstract

Objective To investigate the effects of two eyedrops containing timolol, brimonidine and their preservatives (thiomersal in timolol, and benzalkonium chloride in brimonidine) respectively, in the histology of rabbit eye surface. Methods A randomized study was conducted in fifteen New Zealand white rabbits allocated three groups: control group (n=3) , the timolol group (group T, n=6) and the brimonidine group (group B, n=6). The rabbits in groups B or T received eyedrop of timolol or brimonidine in the fight eyes and their preservatives (thiomersal or benzalkonium chloride) in the left eyes, twice daily for 30 days. Corneal epithelial damage and grading was evaluated by scanning electron microscopy, and bulbar conjunctival specimens were examined by HE stain as well as counting conjunetival epithelial inflammatory cells. Results Compared with the tidily arranged epithelial layers of conjunctiva in control group, the medicated rabbits showed increased layers and irregular arrangement of the cells. The lymphocyte count was 32.3±8.8 in the control group versus 55.8±6.9 in timolol, 71.0±8.8 in brimonidine, 56.0±7.1 in thiomersal and 62.5±7.1 in benzalkonium chloride (all P 0.05). Conclusions When applied to rabbit eyes for one month, brimonidine, timolol and their preservatives result in corneal damage and conjunctival inflammatory cell infiltration. The preservatives may play a major role in the ocular surface adverse effects. Brimonidine appears to have more influences on ocular surface compared with timolol. Key words: Glaucoma; Cornea; Conjunctiva; Preservatives; pharmaceutical; Drug toxicity