title: Potential mechanism for the additivity of pilocarpine and latanoprost.
abstract: OBJECTIVE
  To determine the ocular hypotensive mechanism underlying the additivity of latanoprost and pilocarpine.
  
  
  METHODS
  This randomized, double-masked study included 30 patients with ocular hypertension on no ocular medications for at least 3 weeks. On each of six visits to the clinic, measurements were taken of aqueous flow and outflow facility by fluorophotometry, intraocular pressure by tonometry, and episcleral venous pressure by venomanometry. Uveoscleral outflow was calculated. Clinic visits were scheduled on baseline day; on day 8 of four times daily pilocarpine (2%) to one eye and vehicle to the other; on day 8 of continued pilocarpine/vehicle treatment plus latanoprost (0.005%) once daily to both eyes; after a 3-week washout period; on day 8 of once-daily latanoprost to one eye and vehicle to the other; and on day 8 of continued latanoprost/vehicle treatment plus pilocarpine four times a day to both eyes. Drug-treated eyes were compared with contralateral vehicle-treated eyes and with baseline day by paired t tests. Combined pilocarpine and latanoprost-treated eyes were compared with individual drug-treated eyes and with baseline day using the Bonferroni test.
  
  
  RESULTS
  Compared with baseline, pilocarpine reduced intraocular pressure from 18.9 to 16.2 mm Hg (P =.001) and increased outflow facility from 0.18 to 0.23 microl per minute per mm Hg (P =.03). No other parameters were affected. Adding latanoprost further reduced intraocular pressure to 13.7 mm Hg (P <.001) and increased uveoscleral outflow from 0.82 to 1.36 microl per minute (P =.02). Latanoprost alone reduced intraocular pressure from 17.6 to 14.3 mm Hg (P <.0001) and increased uveoscleral outflow from 0.89 to 1.25 microl per minute (P =.05). Adding pilocarpine to the latanoprost treatment further reduced intraocular pressure to 12.7 mm Hg (P <.001) and increased outflow facility from 0.21 to 0.30 microl per minute per mm Hg (P =.03).
  
  
  CONCLUSIONS
  Latanoprost and pilocarpine predominantly increase uveoscleral outflow and outflow facility, respectively, when given alone. These drugs are additive because pilocarpine does not inhibit the uveoscleral outflow increase induced by latanoprost.
authors.affiliation: Department of Ophthalmology, University of Nebraska Medical Center, Omaha, Nebraska 68198-5540, USA. CTORIS@UNMC.edu
authors.forename: C B
authors.initials: CB
authors.lastname: Toris
authors.forename: G L
authors.initials: GL
authors.lastname: Zhan
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: C B
authors.initials: CB
authors.lastname: Camras
authors.forename: M E
authors.initials: ME
authors.lastname: Yablonski
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D008916:Miotics / Q000627:therapeutic use*; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009883:Ophthalmic Solutions; D010862:Pilocarpine / Q000627:therapeutic use*; D011461:Prostaglandins F, Synthetic / Q000627:therapeutic use*; D012590:Sclera / Q000503:physiopathology; D014602:Uvea / Q000503:physiopathology
chemical_list: D008916:Miotics; D009883:Ophthalmic Solutions; D011461:Prostaglandins F, Synthetic; D010862:Pilocarpine; D000077338:Latanoprost