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Clinical science
Using diurnal intraocular pressure fluctuation to assess the efficacy of fixed-combination latanoprost/timolol versus latanoprost or timolol monotherapy
  1. R Varma1,
  2. L-J Hwang2,
  3. J W Grunden2,
  4. G W Bean3
  1. 1
    Keck School of Medicine, University of Southern California, Los Angeles, California, USA
  2. 2
    Pfizer, New York, New York, USA
  3. 3
    Burkett, Texas, USA
  1. Correspondence to Dr R Varma, 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{at}


Aim: 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 (⩽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.

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  • Funding The research was supported by Pfizer, New York, New York, USA.

  • Competing interests RV and GWB are consultants to Pfizer. L-JW and JWG are employees of Pfizer. Editorial support, including contributing to the first draft of the manuscript, revising the paper based on author feedback and styling the paper for journal submission, was provided by JG Murphy of Zola Associates and was funded by Pfizer.

  • Ethics approval Ethics approval was provided by the institutional review board or ethics committee of each participating centre before study initiation.

  • Patient consent Obtained.

  • Provenance and Peer review Not commissioned; externally peer reviewed.