This study examined the interaction of IOP-lowering medications with physiologic day and night changes in aqueous humor dynamics in individuals with ocular hypertension. Latanoprost significantly decreased IOP during the day and night, while timolol and dorzolamide lowered IOP during the day but not at night. The authors found that the daytime IOP-lowering effects of latanoprost are mediated by an increase in uveoscleral outflow, and those of timolol and dorzolamide by aqueous flow suppression. Nighttime physiologic changes in uveoscleral outflow limit the nighttime pharmacodynamic efficacy of latanoprost, while aqueous flow suppression with timolol and dorzolamide was ineffective at lowering IOP at night.
There has been recent controversy over which IOP-lowering agents are efficacious at night. Prostaglandins are the only clearly demonstrated agent at present. Other components to the controversy include a lack of any study of associated glaucomatous progression with nocturnal or 24-hour IOP measurements.
Thirty participants were enrolled in this double-masked, randomized, crossover study, which was published in June in the Archives of Ophthalmology. Each participant underwent aqueous humor dynamics measurements at baseline and at two 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 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 tonography.
Latanoprost use increased daytime uveoscleral outflow by a mean (SD) of 0.90 (1.46) μL/min (P = 0.048), but a nighttime increase of 0.26 (1.10) μL/min (P = 0.47) did not reach statistical significance. Timolol use decreased IOP during the day by reducing aqueous flow by 25 percent. Dorzolamide use lowered IOP only at the noon measurement and reduced daytime aqueous flow by 16 percent. Neither dorzolamide nor timolol use added to the physiologic 47 percent reduction in nighttime aqueous flow.
Studies of this type vary by two significant factors: whether nocturnal IOP measurements are supine versus upright, and by the type of study subject. Patients without glaucoma appear to have different nocturnal flow dynamics than patients with glaucoma. No study of naive glaucoma patients has been done looking at nocturnal IOP. Also the method of IOP measurement, which was pneumotonometry in this study, may or may not have a role.
The authors conclude that significant nocturnal physiologic changes in aqueous humor dynamics affect the efficacy of commonly used glaucoma drugs. They recommend additional studies of the mediating pathways for nocturnal changes in order to develop more effective ways of controlling IOP and glaucoma.