IOVS Archives of Disease in Childhood
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(Investigative Ophthalmology and Visual Science. 2001;42:2957-2963.)
© 2001 by The Association for Research in Vision and Ophthalmology, Inc.

Effects of Topical Latanoprost on Optic Nerve Head Circulation in Rabbits, Monkeys, and Humans

Kiyoshi Ishii1, Atsuo Tomidokoro1, Miyuki Nagahara2, Yasuhiro Tamaki2, Mikiko Kanno2, Yasuhiro Fukaya2 and Makoto Araie2

1 From the Eye Clinic, Omiya Red Cross Hospital, Japan; and the 2 Department of Ophthalmology, University of Tokyo School of Medicine, Japan.

PURPOSE. To evaluate the effect of topically administrated latanoprost on optic nerve head (ONH) circulation in Dutch rabbits, cynomolgus monkeys, and normal humans.

METHODS. The ONH tissue blood velocity (NBONH) was determined using the laser speckle method. Latanoprost (0.005%, 30 µl) was instilled into one eye, and vehicle into the other eye as a control. In rabbits, NBONH was measured for 90 minutes after a single instillation and before and after a 7-day once-daily instillation regimen. In monkeys, NBONH was measured before and after 1, 4, and 7 days of a once-daily instillation regimen. The effect of intravenous indomethacin on the latanoprost-induced NBONH change was also studied in rabbits and monkeys. In humans, the time-course changes in NBONH were measured for 4.5 hours before and after a 7-day once-daily instillation regimen. Intraocular pressure (IOP) and systemic parameters were simultaneously studied in each experiment. All measurements were performed by investigators masked to the experimental condition.

RESULTS. Latanoprost significantly increased NBONH 10% to 19% in treated eyes 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 regimen in monkeys, and after a 7-day (P = 0.013) instillation regimen in humans, whereas there were no significant changes in the vehicle-treated eyes in any of the experiments (P > 0.5). Pretreatment with indomethacin (5 mg/kg) abolished the NBONH increase but not the IOP reduction in latanoprost-treated eyes in rabbits and monkeys. IOP remained unchanged in both eyes in rabbits (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 independent of the IOP-reducing effect of latanoprost and probably was associated with local penetration of the drug and the production of endogenous prostaglandins.






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Copyright © 2001 by the Association for Research in Vision and Ophthalmology