Effects of topical latanoprost on optic nerve head circulation in rabbits,monkeys, and humans

Purpose. To evaluate the effect of topically administrated latanoprost on o ptic nerve head (ONH) circulation in Dutch rabbits, cynomolgus monkeys, and normal humans. Methods. The ONH tissue blood velocity (NBONH) was determined using the las er speckle method. Latanoprost (0.005%, 30 mul) was instilled into one eye, and vehicle into the other eye as a control. In rabbits, NBONH was measure d for 90 minutes after a single instillation and before and after a 7-day o nce-daily instillation regimen. In monkeys, NBONH was measured before and a fter 1, 4, and 7 days of a once-daily instillation regimen. The effect of i ntravenous indomethacin on the latanoprost-induced NBONH change was also st udied in rabbits and monkeys. In humans, the time-course changes in NBONH w ere measured for 4.5 hours before and after a 7-day once-daily instillation regimen. Intraocular pressure (IOP) and Systemic parameters were simultane ously studied in each experiment. All measurements were performed by invest igators masked to the experimental condition. Results. Latanoprost significantly increased NBONH 10% to 19% in treated ey es after a single instillation (P=0.035) or 7-day instillation regimen (P=0 .035) in rabbits, after a 4-day (P=0.035) or 7-day (P=0.035) instillation r egimen in monkeys, and after a 7-day (P=0.013) instillation regimen in huma ns, whereas there were no significant changes in the vehicle-treated eyes i n any of the experiments (P>0.5). Pretreatment with indomethacin (5 mg/kg) abolished the NBONH increase but not the IOP reduction in latanoprost-treat ed eyes in rabbits and monkeys. IOP remained unchanged in both eves in rabb its (P>0.4), whereas it significantly decreased only in latanoprost-treated eyes in monkeys (P<0.05) and humans (P<0.05). Conclusions. Topical latanoprost significantly increased ONH blood velocity only in treated eyes in rabbits, monkeys, and humans. This effect was inde pendent of the IOP-reducing effect of latanoprost and probably was associat ed with local penetration of the drug and the production of endogenous pros taglandins.