Latanoprost and physostigmine have mostly additive ocular hypotensive effects in human eyes.

OBJECTIVE: To investigate if a pronounced ciliary muscle contraction, induced by physostigmine salicylate, can abolish the ocular hypotensive effect of latanoprost, a prostaglandin analogue, via inhibition of the uveoscleral outflow.

DESIGN: A randomized, crossover study that was double-masked for latanoprost. Physostigmine was the second factor in a 2(2) factorial experiment.

PARTICIPANTS: A total of 20 male and female healthy volunteers (median age, 25 years; age range, 17-30 years).

INTERVENTIONS: Between 7 AM and 7 PM, 1 drop of physostigmine salicylate (8 mg/mL) was instilled in 1 eye every other hour. At 8 AM, 1 drop of either latanoprost (50 mg/L) or placebo was instilled in both eyes. This protocol was repeated a second time with latanoprost administered to previously placebo-treated eyes and vice versa.

MAIN OUTCOME MEASURES: Intraocular pressure differences were measured with Goldmann applanation tonometry hourly for 13 hours.

RESULTS: Latanoprost reduced the intraocular pressure significantly at 3 to 12 hours after application with a maximal effect at 8 hours after the administration of the dose. The reduction that was obtained with physostigmine administered every other hour was more pronounced, was observed at 1 hour after the administration of the first dose, and increased throughout the day. A significant interaction was seen between 3 and 6 PM (i.e., at 7-10 hours after application of latanoprost).

CONCLUSIONS: Latanoprost and physostigmine have a mainly additive ocular hypotensive effect. Thus, high doses of physostigmine did not abolish the eye pressure-lowering effect of latanoprost, but some interaction was seen at low intraocular pressures. It was concluded that any mechanical effect on the uveoscleral flow achieved with physostigmine is short-lasting compared with the effect obtained with latanoprost, and that latanoprost and miotics can be combined.