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

Vikas Gulati, Shan Fan, Min Zhao, Matthew A. Maslonka, Chiraag Gangahar, Carol B Toris

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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 this double-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 amean (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 Identifier: NCT00572936.

Original languageEnglish (US)
Pages (from-to)677-684
Number of pages8
JournalArchives of Ophthalmology
Volume130
Issue number6
DOIs
StatePublished - Jun 1 2012

Fingerprint

dorzolamide
latanoprost
Ocular Hypertension
Aqueous Humor
Intraocular Pressure
Timolol
Fluorophotometry
Therapeutics
Venous Pressure
Anterior Chamber
Cross-Over Studies
Placebos
Blood Pressure

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Diurnal and nocturnal variations in aqueous humor dynamics of patients with ocular hypertension undergoing medical therapy. / Gulati, Vikas; Fan, Shan; Zhao, Min; Maslonka, Matthew A.; Gangahar, Chiraag; Toris, Carol B.

In: Archives of Ophthalmology, Vol. 130, No. 6, 01.06.2012, p. 677-684.

Research output: Contribution to journalArticle

@article{17de1a38fa144e7da7853920ca57fcd3,
title = "Diurnal and nocturnal variations in aqueous humor dynamics of patients with ocular hypertension undergoing medical therapy",
abstract = "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 this double-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 amean (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 Identifier: NCT00572936.",
author = "Vikas Gulati and Shan Fan and Min Zhao and Maslonka, {Matthew A.} and Chiraag Gangahar and Toris, {Carol B}",
year = "2012",
month = "6",
day = "1",
doi = "10.1001/archophthalmol.2011.2573",
language = "English (US)",
volume = "130",
pages = "677--684",
journal = "JAMA Ophthalmology",
issn = "2168-6165",
publisher = "American Medical Association",
number = "6",

}

TY - JOUR

T1 - Diurnal and nocturnal variations in aqueous humor dynamics of patients with ocular hypertension undergoing medical therapy

AU - Gulati, Vikas

AU - Fan, Shan

AU - Zhao, Min

AU - Maslonka, Matthew A.

AU - Gangahar, Chiraag

AU - Toris, Carol B

PY - 2012/6/1

Y1 - 2012/6/1

N2 - 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 this double-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 amean (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 Identifier: NCT00572936.

AB - 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 this double-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 amean (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 Identifier: NCT00572936.

UR - http://www.scopus.com/inward/record.url?scp=84862199855&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862199855&partnerID=8YFLogxK

U2 - 10.1001/archophthalmol.2011.2573

DO - 10.1001/archophthalmol.2011.2573

M3 - Article

C2 - 22332206

AN - SCOPUS:84862199855

VL - 130

SP - 677

EP - 684

JO - JAMA Ophthalmology

JF - JAMA Ophthalmology

SN - 2168-6165

IS - 6

ER -