Diurnal and nocturnal variations in aqueous humor dynamics of patients with ocular hypertension undergoing medical therapy

Arch Ophthalmol. 2012 Jun;130(6):677-84. doi: 10.1001/archophthalmol.2011.2573.


Objective: To evaluate the interaction of intraocular pressure(IOP)–lowering medications with physiologic day and night changes in aqueous humor dynamics in participants with ocular hypertension.

Methods: Thirty participants were enrolled in thisdouble-masked, randomized, crossover study. Each participant underwent aqueous humor dynamics measurements at baseline and at 2 weeks of dosing in random order with latanoprost in the evening and placebo in the morning, timolol maleate twice daily, and dorzolamide hydrochloride twice daily. Measurements included central corneal thickness by ultrasound pachymetry, anterior chamber depth by A-scan, seated and habitual IOP by pneumatonometry, blood pressure by sphygmomanometry,episcleral venous pressure by venomanometry,and aqueous flow by fluorophotometry. Outflow facility was assessed by fluorophotometry and by tonography. Uveoscleral outflow was mathematically calculated using the Goldmann equation.

Results: Latanoprost use significantly decreased IOP during the day and night. It increased daytime uveoscleral outflow by a mean (SD) of 0.90 (1.46) μL/min (P=.048), but a nighttime increase of 0.26 (1.10) μL/min (P=.47)did not reach statistical significance. Timolol use decreased IOP during the day by reducing aqueous flow by 25%. Dorzolamide use lowered IOP only at the noon measurement and reduced daytime aqueous flow by 16%. Neither dorzolamide nor timolol use added to the physiologic 47% reduction in nighttime aqueous flow.

Conclusions: The daytime IOP-lowering effects of latanoprost are mediated by an increase in uveoscleral outflow,and those of timolol and dorzolamide are mediated by aqueous flow suppression. Nighttime physiologic changes in uveoscleral outflow limit the nighttime pharmacodynamic efficacy of latanoprost. Aqueous flow suppression with timolol and dorzolamide was ineffective in obtaining IOP lowering at night.

Trial registration: ClinicalTrials.gov NCT00572936.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / administration & dosage
  • Antihypertensive Agents / administration & dosage*
  • Aqueous Humor / physiology*
  • Blood Pressure / drug effects
  • Carbonic Anhydrase Inhibitors / administration & dosage
  • Circadian Rhythm / physiology*
  • Cornea / diagnostic imaging
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Fluorophotometry
  • Humans
  • Intraocular Pressure / drug effects
  • Latanoprost
  • Male
  • Middle Aged
  • Ocular Hypertension / drug therapy*
  • Ocular Hypertension / physiopathology*
  • Prospective Studies
  • Prostaglandins F, Synthetic / administration & dosage
  • Sphygmomanometers
  • Sulfonamides / administration & dosage
  • Thiophenes / administration & dosage
  • Timolol / administration & dosage
  • Tonometry, Ocular
  • Ultrasonography


  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Carbonic Anhydrase Inhibitors
  • Prostaglandins F, Synthetic
  • Sulfonamides
  • Thiophenes
  • Latanoprost
  • Timolol
  • dorzolamide

Associated data

  • ClinicalTrials.gov/NCT00572936