Effect of topical timolol on tissue circulation in optic nerve head

The effects of topical 0.5% timolol on tissue circulation in the albino rabbit optic nerve head (ONH) were investigated using a laser speckle tissue circulation analyzer. In the first experiment, the normalized blur (NB) value, a quantitative index of tissue blood flow velocity in the ONH, intraocular pressure (IOP), blood pressure, and pulse rate were measured under general anesthesia before, and 30, 60, 90, and 120 minutes after a 20 microL instillation of timolol in one eye and the vehicle in the other eye in a masked, randomized manner. In the second experiment, one eye of a rabbit received timolol twice daily for 20 days and the fellow eye received the vehicle in a masked, randomized manner. Every 5 days IOP was measured and the NB in the ONH and IOP were measured before treatment and 2 hours after the last instillation on the 20th day. After a single instillation of timolol, PR showed a maximum reduction of 12% and IOP in the timolol-treated eyes showed a maximum decrease in 25%. NB in the ONH and BP did not show any significant change during the experiment. After a 20-day treatment with timolol, IOP showed a maximum decrease of 25% in the timolol-treated eyes and 16% in the vehicle-treated eyes. The NB in the timolol-treated eyes increased significantly by 16% (P < 0.01), whereas that in the vehicle-treated eyes showed no significant change. It was suggested that long-term topical timolol with a normal drug regimen caused a significant increase in the peripheral blood velocity in the ONH only in the timolol-treated eyes, at least partly, by local penetration of the drug. Ocular penetration of topically applied timolol is thought to be similar between rabbit and human eyes. Therefore, the present results may have clinical implications.