title: Using diurnal intraocular pressure fluctuation to assess the efficacy of fixed-combination latanoprost/timolol versus latanoprost or timolol monotherapy.
abstract: OBJECTIVE
  To evaluate differences in diurnal intraocular pressure (IOP) fluctuation in glaucoma/ocular hypertension patients treated with once-daily fixed-combination latanoprost/timolol, once-daily latanoprost or twice-daily timolol.
  
  
  METHODS
  In two 6-month, double-masked, parallel-group studies, patients received run-in timolol (2-4 weeks) and randomised (1:1:1) to therapy. IOP was measured three times/day at baseline and weeks 2, 13 and 26. In posthoc analyses, diurnal IOP fluctuation = highest daily IOP-lowest daily IOP at baseline and week 26. Fluctuation also was dichotomised: high (>6 mm Hg), low (< or =6 mm Hg).
  
  
  RESULTS
  854 patients were randomised (fixed combination = 278; latanoprost = 287; timolol = 289). Diurnal fluctuation was significantly reduced from baseline to week 26 with the fixed combination (p = 0.002) but not with latanoprost or timolol monotherapy (p = 0.601; p = 0.097). Relative to baseline, the percentage with high diurnal IOP fluctuation at week 26 was reduced by 48% with fixed combination but increased 13% with latanoprost and 48% with timolol. Changes in IOP fluctuation and in mean IOP were significantly correlated for the monotherapies but not the fixed combination.
  
  
  CONCLUSIONS
  Fixed-combination latanoprost/timolol results in lower diurnal IOP fluctuation and significantly fewer patients with a high fluctuation than treatment with latanoprost or timolol monotherapy. The fixed combination may have an independent effect on reducing IOP fluctuation in addition to lowering IOP.
authors.affiliation: Doheny Eye Institute and the Department of Ophthalmology, Keck School of Medicine, University of Southern California, 1450 San Pablo Street, DEI-4900, Los Angeles, CA 90033, USA. rvarma@usc.edu
authors.forename: R
authors.initials: R
authors.lastname: Varma
authors.forename: L-J
authors.initials: LJ
authors.lastname: Hwang
authors.forename: J W
authors.initials: JW
authors.lastname: Grunden
authors.forename: G W
authors.initials: GW
authors.lastname: Bean
mesh_terms: D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002940:Circadian Rhythm / Q000502:physiology; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D005902:Glaucoma, Open-Angle / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects* / Q000502:physiology; D000077338:Latanoprost; D008297:Male; D008875:Middle Aged; D009798:Ocular Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000627:therapeutic use*; D013999:Timolol / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; D011461:Prostaglandins F, Synthetic; D000077338:Latanoprost; D013999:Timolol