Diurnal and Nocturnal Variations in Aqueous Humor Dynamics of Patients With Ocular Hypertension Undergoing Medical Therapy

Abstract

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 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.

Circadian Variation of Aqueous Humor Dynamics in Older Healthy Adults

“…If prostaglandin analogs increase uveoscleral flow by a percentage, rather than by a fixed amount, then the nocturnal effect on absolute uveoscleral flow rate would be small, because uveoscleral flow is markedly reduced at night. This small change in absolute uveoscleral flow rate would be more difficult to detect, consistent with the findings of Gulati et al 48 In contrast, outflow facility decreased by only approximately 15% at night in our subjects, which suggests that improving outflow facility may be a possible mechanism for reducing nocturnal IOP. It is possible that prostaglandin analogs, which have persistent nocturnal efficacy, may use this mechanism.…”

“…[41][42][43][44] Prostaglandin analogs, however, may reduce pressure through two actions, one that improves outflow facility (although this has not been a universal finding) and the other that increases uveoscleral flow. [45][46][47] A study by Gulati et al 48 suggested that latanoprost might increase uveoscleral outflow at night, although their study was not sufficiently powered to show a statistically significant difference. If prostaglandin analogs increase uveoscleral flow by a percentage, rather than by a fixed amount, then the nocturnal effect on absolute uveoscleral flow rate would be small, because uveoscleral flow is markedly reduced at night.…”

A Randomised Open Label Comparative Clinical Trial on the Efficacy of Latanoprost and Timolol in Primary Open Angle Glaucoma

“…Gulati V et al, conducted a double masked, randomised, cross over study to evaluate the interaction of antiglaucoma drugs with physiologic day and night changes in aqueous humor dynamics in ocular hypertensive patients [17]. It showed that Latanoprost is better than Timolol in reducing night time intraocular pressure.…”

Relationship Between Daytime Variability of Blood Pressure or Ocular Perfusion Pressure and Glaucomatous Visual Field Progression

“…In doing so, prostaglandin analogues are recommended as the first-line choice of medical treatment since they reduce both daytime and nighttime IOP. 36 Topical beta-blockers should be avoided in these patients as they have the potential for significant systemic side effects including nocturnal hypotension that may be harmful to some NTG patients. 37 Notably, poorer baseline VF function was a significant glaucoma progression predictor in our study population.…”