Latanoprost and physostigmine have mostly additive ocular hypotensive effects in human eyes
C. Linden and A. Alm
Department of Ophthalmology, Umea University, Sweden. christina.linden@ophthal.umu.se
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.
