• Previous studies have suggested that the effect on intraocular pressure resulting from the combined use of timolol and epinephrine might be different when they are administered hours rather than minutes apart. Fourteen patients were randomly assigned to one of two treatment sequences in which 1% epinephrine borate was added either five minutes or three hours after 0.5% timolol maleate. Combined therapy was continued for two weeks, after which epinephrine administration was stopped for a two-week washout period. The patient groups were then crossed over to the other dosage interval. There was an initial enhancement of pressure reduction when epinephrine was added to timolol in both sequences. After crossover, epinephrine was significantly additive to timolol in reducing pressure only when administered three hours after timolol. This additive effect was still present after three months of combined therapy.
Cyrlin MN, Thomas JV, Epstein DL. Additive Effect of Epinephrine to Timolol Therapy in Primary Open Angle Glaucoma. Arch Ophthalmol. 1982;100(3):414-418. doi:10.1001/archopht.1982.01030030416005