Effect of bimatoprost on intraocular pressure in prostaglandin FP receptor knockout mice

PURPOSE: To determine the effect of bimatoprost on intraocular pressure in the prostaglandin FP receptor knockout mouse. METHODS: The IOP response to a single 1.2-microg (4 microL) dose of bimatoprost was measured in the treated and untreated fellow eyes of homozygote (FP+/+, n = 9) and heterozygote (FP+/-, n = 10) FP-knockout mice, as well as in wild-type C57BL/6 mice (FP+/+, n = 20). Serial IOP measurements were also performed after topical bimatoprost in a separate generation of homozygous FP-knockout mice and wild-type littermate control animals (n = 4 per group). Aqueous humor protein concentrations were measured to establish the state of the blood-aqueous barrier. Tissue, aqueous humor and vitreous concentrations of bimatoprost, latanoprost, and their C-1 free acids were determined by liquid chromatography and tandem mass spectrometry. RESULTS: A significant reduction in IOP was observed in the bimatoprost-treated eye of wild-type mice at 2 hours, with a mean difference and 95% confidence interval (CI) of the difference in means of -1.33 mm Hg (-0.81 to -1.84). Bimatoprost did not lead to a significant reduction in IOP in either the heterozygous knockout -0.36 mm Hg (-0.82 to +0.09) or homozygous FP-knockout mice 0.25 mm Hg (-0.38 to +0.89). The lack of an IOP response in the FP-knockout mice was not a consequence of blood-aqueous barrier breakdown, as there was no significant difference in aqueous humor protein concentration between treated and fellow eyes. Tissue and aqueous humor concentrations of bimatoprost, latanoprost, and their C-1 free acids indicate that latanoprost, but not bimatoprost, is hydrolyzed in the mouse eye after topical administration. CONCLUSIONS: An intact FP receptor gene is critical to the IOP response to bimatoprost in the mouse eye.     

Effect of latanoprost on intraocular pressure in steroid-induced glaucoma

PURPOSE: To study the effect of monotherapy with latanoprost 0.005% on intraocular pressure (IOP) in a prospective nonrandomized clinical trial of patients newly diagnosed with steroid-induced secondary open-angle glaucoma. PATIENTS AND METHODS: Eight patients (16 eyes) with newly diagnosed steroid-associated secondary open-angle glaucoma were prescribed latanoprost 0.005% once a day in each eye. The initial IOP before treatment served as an internal control for each eye. Intraocular pressure was remeasured after 1 month of monotherapy with latanoprost. Investigators (WJS) were blinded to initial IOP at the time of remeasurement. After discontinuation of steroids, IOP was rechecked. If IOP was stable, latanoprost was discontinued. Intraocular pressure was rechecked 2 to 4 weeks later to confirm an association with steroid use. RESULTS: Intraocular pressure was significantly decreased after treatment with latanoprost (18.3 +/- 2.8 mm Hg) compared with initial IOP (25.3 +/- 9.1 mm Hg). This change represented a 28% decrease in IOP compared with baseline levels. Average IOP after discontinuation of steroids and latanoprost (17.3 +/- 1.4 mm Hg) did not differ from IOP measured during treatment with latanoprost, but it was significantly less than the initial IOP before treatment. No adverse effects were noted. CONCLUSIONS: Monotherapy with latanoprost is safe and effective in patients with steroid-induced glaucoma. Advantages include lack of systemic side effects and convenient once-daily dosing.     

Effects of latanoprost on rodent intraocular pressure

The aim of the present study was to evaluate the effects of the prostaglandin F_2α analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes. Rodents have been increasingly used in glaucoma research; however, conflicting results regarding the actions of prostaglandins on rodent IOP have been published. In Wistar rats, a single dose of latanoprost (60 ng) produced a biphasic change in IOP: an initial rise in pressure (2.1 ± 0.7 mmHg) peaking at 2 h, followed by a prolonged hypotension with a peak reduction in IOP (5.2 ± 0.7 mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose-related with ED₅₀ values of 108 and 5.2 ng, respectively. These responses were antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6 mice, a single dose of latanoprost also produced a biphasic response in IOP with an initial rise in pressure peaking between 1 and 2 h, followed by prolonged hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP response to topical latanoprost is characterized by an initial hypertension followed by a prolonged hypotension. This prolonged hypotension is similar to that measured in monkeys and humans. Taken together, these results support the idea that rodents can serve as in vivo models to study the actions of ocular hypotensive agents, such as prostaglandins.     

Responses of intraocular pressure and the pupil of feline eyes to prostaglandin EP1 and FP receptor agonists.

PURPOSE: Previous studies suggested that FP receptors do not mediate the relaxation of the ciliary muscle and reduction of intraocular pressure in cats by prostaglandin (PG) F2alpha. The present study was undertaken to determine whether the reduction of intraocular pressure in cats induced by PGF2alpha is mediated by FP or other prostaglandin receptors. METHODS: One eye of each cat was treated topically with prostaglandin F2alpha, fluprostenol (FP receptor agonist), or 17-phenyl trinor PGE2 (EP1 receptor agonist) in a dose range of 12.5 to 50 microg. The effects of SC19220 and SC51089 (EP1 receptor antagonists), BWA868c, and SQ29548 (DP and TP receptor antagonists, respectively) on the intraocular response to PGF2alpha were also examined. At intervals up to 6 hours after treatment, intraocular pressure was measured with a pneumotonometer, and pupil diameters were measured with a millimeter ruler. RESULTS: In the dose ranges used, PGF2alpha and 17-phenyl trinor PGE2 decreased intraocular pressure and pupil diameter. The greatest reduction of intraocular pressure by 50.0 microg PGF2alpha was 5.0+/-1.4 mm Hg, whereas that by 50 microg 17-phenyl trinor PGE2 was 6.2+/-1.5 mm Hg. The isopropyl ester of PGF 2alpha at a dose of 1.25 microg reduced intraocular pressure by 3.75+/-0.25 mm Hg at 2 hours. At doses up to 100 microg, fluprostenol did not decrease intraocular pressure but did reduce pupil diameter. SC19220, a weak but selective EP1 receptor antagonist, inhibited the intraocular pressure response to both PGF2alpha and 17-phenyl trinor PGE2. The more potent EP1 receptor antagonist SC51089 had a greater inhibitory effect than SC19220 on the intraocular pressure response to PGF2alpha. Both of these antagonists had a small but non-dose dependent and statistically insignificant effect on the pupil response to PGF2alpha. These observations suggest that in cats, intraocular pressure and pupil responses to PGF2alpha, are mediated by EP1 and FP receptors, respectively. However, SC19220 significantly and dose-dependently inhibited the pupil response to 17-phenyl trinor PGE2alpha suggesting that EP1 receptors mediate pupil response to this agonist. DP and TP receptor antagonists at doses 5- to 20-fold greater than the IC50 values had no effect on the ocular hypotensive response to PGF2alpha. The concurrent administration of 12.5 microg of each of PGF2alpha and 17-phenyl trinor PGE2 did not produce an additive effect on intraocular pressure, indicating that in cats PGF2alpha and 17-phenyl trinor PGE2 act on the same receptor type. CONCLUSIONS: These results suggest that a significant proportion of the ocular hypotensive action of PGF2alpha in cats is mediated by EP1 but not by FP receptor. Evidence was also provided to show that 17-phenyl trinor PGE2 is an ocular hypotensive agent in cats.     

Effects of latanoprost on rodent intraocular pressure

The aim of the present study was to evaluate the effects of the prostaglandin F2 alpha analog, latanoprost, on the intraocular pressure (IOP) in rodent eyes. Rodents have been increasingly used in glaucoma research; however, conflicting results regarding the actions of prostaglandins on rodent IOP have been published. In Wistar rats, a single dose of latanoprost (60 ng) produced a biphasic change in IOP: an initial rise in pressure (2.1+/-0.7 mmHg) peaking at 2 h, followed by a prolonged hypotension with a peak reduction in IOP (5.2+/-0.7 mmHg) at 5 h. Both the hyper and hypotensive actions of latanoprost were dose-related with ED50 values of 108 and 5.2 ng, respectively. These responses were antagonized by pretreatment with 4% pilocarpine. In Brown Norway rats and C57BL/6 mice, a single dose of latanoprost also produced a biphasic response in IOP with an initial rise in pressure peaking between 1 and 2 h, followed by prolonged hypotension from 4 to 8 h. These results demonstrate that in rodents the IOP response to topical latanoprost is characterized by an initial hypertension followed by a prolonged hypotension. This prolonged hypotension is similar to that measured in monkeys and humans. Taken together, these results support the idea that rodents can serve as in vivo models to study the actions of ocular hypotensive agents, such as prostaglandins.     

Effect of latanoprost on diurnal variations of intraocular pressure in normal-tension glaucoma

OBJECTIVES: To study the effect of instillation of latanoprost on the diurnal variation in the intraocular pressure(IOP), blood pressure, and pulse rate in patients with normal-tension glaucoma(NTG). SUBJECTS AND METHODS: The diurnal variation in the IOP was determined in 23 eyes in 23 NTG patients after a washout period of 4 weeks or longer. The diurnal variation in IOP was then remeasured after latanoprost monotherapy of 8 weeks or longer. The IOP was measured by the Goldmann applanation tonometer at 10:00, 13:00, 16:00, 19:00, 22:00, 01:00, 03:00, 07:00, and 10:00 before and after treatment, and the IOP at each time point, mean diurnal IOP, maximum IOP, minimum IOP, and range of variation in IOP were compared before and after treatment. The blood pressure and pulse rate before and after treatment were also measured and compared. RESULTS: The IOP decreased significantly at all time points. The treatment caused significant decreases in the mean diurnal IOP, maximum IOP, minimum IOP, and range of variation in IOP. There were no differences in the blood pressure and pulse rate before and after treatment. CONCLUSIONS: Latanoprost significantly decreases the IOP throughout the day in NTG patients, and has no effects on the blood pressure and pulse rate. It is therefore useful in the treatment of NTG.     

The effect of latanoprost on circadian intraocular pressure

The presence of a circadian variation of both intraocular pressure (IOP) and aqueous humor flow has been demonstrated in several studies. It must therefore be considered important to monitor IOP and evaluate the efficacy of ocular hypotensive drugs over the 24 hours of the day. The efficacy of latanoprost on IOP during both day and night has been evaluated and the most important results from four such studies are reviewed. The studies reviewed here clearly demonstrate that topical administration of latanoprost 0.005% once daily provided a steady reduction of the IOP during both day and night. Given as a single dose to healthy volunteers, latanoprost resulted in a sustained effect with a significant IOP reduction over 24 hours, and the reduction was still present, however less pronounced, even after 48 hours. Latanoprost administered once daily for 4 weeks to patients with glaucoma or ocular hypertension was more effective in reducing the IOP over 24 hours than timolol gel solution 0.5% once daily, timolol aqueous solution 0.5% twice daily, or dorzolamide 2% three times daily. Latanoprost applied once daily thus provided a better effect on the IOP together with a stable and sustained IOP reduction during both day and night.     

Effect of non-steroidal anti-inflammatory ophthalmic solution on intraocular pressure reduction by latanoprost

AIM: To investigate the effects of a non-steroidal anti-inflammatory drug (NSAID) ophthalmic solution on latanoprost induced intraocular pressure (IOP) reduction using normal volunteers. METHODS: This study was conducted as a prospective and observer masked clinical trial. 13 normal volunteers were enrolled. After measurement of basal IOP and ophthalmic examination, latanoprost ophthalmic solution was initially administered to both eyes once daily. Four weeks later, an NSAID ophthalmic solution, sodium 2-amino-3-(4-bromobenzoyl) phenylacetate sesquihydrate (refer to bromfenac sodium hydrate), was co-administered to one randomly selected eye (NSAID group) twice daily for 2 weeks. The other eye was employed as a control (non-NSAID group). After withdrawal of the NSAID ophthalmic solution, latanoprost ophthalmic solution was continuously administered for another 2 weeks and was then withdrawn. After a 4 week washout, only bromfenac sodium hydrate ophthalmic solution was administered to the eyes of the NSAID group for 2 weeks. During the study period, ophthalmic examination, including IOP measurement was performed in an observer masked fashion. RESULTS: Before initiation of bromfenac sodium hydrate, baseline IOPs of the non-NSAID group and the NSAID group were 15.73 (SD 1.97) mm Hg and 15.86 (2.06) mm Hg, respectively (p=0.88). Although latanoprost ophthalmic solution significantly reduced IOP in both groups, co-administration of bromfenac sodium hydrate significantly inhibited latanoprost induced IOP reduction compared with the non-NSAID group. The IOPs of the non-NSAID and NSAID groups were 10.18 (1.17) mm Hg and 11.63 (1.35) mm Hg with a 2 week co-administration, respectively (p <0.01). Withdrawal of bromfenac sodium hydrate ophthalmic solution diminished the difference between the two groups. Re-administration of bromfenac sodium ophthalmic solution only did not affect IOP. CONCLUSION: These results indicate that NSAID ophthalmic solution may interfere with IOP reduction by latanoprost ophthalmic solution in normal volunteers and that we should take this into account when treating patients with glaucoma using latanoprost ophthalmic solution.     

Effect of dorzolamide and latanoprost on intraocular pressure after small incision cataract surgery

PURPOSE: To evaluate the effect of dorzolamide 2% and latanoprost 0.005% on intraocular pressure (IOP) after small incision cataract surgery. SETTING: Department of Ophthalmology, University of Vienna, Vienna, Austria. METHODS: This prospective study comprised 102 eyes of 102 consecutive patients scheduled for small incision cataract surgery. The patients were assigned preoperatively to 1 of 3 groups of 34 each: dorzolamide, latanoprost, and control (no treatment). One drop of the assigned medication was instilled immediately after surgery. Intraocular pressure was measured preoperatively and 6 and 20 to 24 hours postoperatively. RESULTS: Six hours after surgery, the mean increase in IOP was 1.9 mm Hg +/- 3.9 (SD) in the dorzolamide group (P = .004 versus control), 2.2 +/- 3.0 mm Hg in the latanoprost group (P = .005 versus control), and 4.8 +/- 5.2 mm Hg in the control group. Twenty to 24 hours postoperatively, IOP decreased a mean of -0.9 +/- 3.5 mm Hg in the dorzolamide group (P = .012 versus control) and increased a mean of 0.3 +/- 3.6 mm Hg in the latanoprost group (P = 0.24 versus control) and 1.3 +/- 4.2 mm Hg in the control group. One eye in the dorzolamide group, 1 eye in the latanoprost group, and 4 eyes in the control group had an IOP of 30 mm Hg or higher 6 hours postoperatively. CONCLUSION: Six hours postoperatively, dorzolamide and latanoprost were effective in reducing the IOP increase after small incision cataract surgery; however, at 20 to 24 hours, only dorzolamide was effective. Neither drug prevented IOP spikes of 30 mm Hg or higher.     

Prostaglandin FP receptors do not contribute to 24-hour intraocular pressure variation in mice

PURPOSE: It is not known whether the prostaglandin FP receptor plays an important role in endogenous 24-hour regulation of intraocular pressure. The purpose of this study was to compare 24-hour intraocular pressure (IOP) in FP receptor-knockout mice with that of wild-type mice that have normal FP receptor expression. METHODS: The 24-hour IOP profile was determined by rebound tonometry in FP-knockout and wild-type mice. Peak and trough IOP was then measured by microneedle cannulation of the anterior chamber in homozygous (FP(-/-); n = 8), heterozygous (FP(+/-); n = 14), and C57BL/6 background strain mice (FP(+/+); n = 11). To confirm any differences in baseline IOP between genotypes, midafternoon IOP was also measured in a larger, separate group of FP(-/-) mice (n = 20), FP(+/-) mice (n = 49), and FP(+/+) (n = 23) wild-type littermates. RESULTS: Trough IOPs were measured between 10 AM and 12 PM, peak IOPs were measured between 8 and 10 PM. For FP(+/+), FP(+/-), and FP(-/-) mice trough IOP was 16.2, 15.3, and 15.1 mm Hg and peak IOPs were 18.2, 18.4, and 17.7 mm Hg, respectively. There was no significant difference among genotypes for mean peak or mean trough IOP or for peak-trough difference in IOP among genotypes (P > 0.05, ANOVA). In addition, there was no significant difference in midafternoon IOP between genotypes in a larger population (n = 92) of FP-knockout and wild-type mice. CONCLUSIONS: An intact FP receptor does not appear to be critical for normal 24-hour IOP regulation in the mouse eye.     

Effect of 15-keto latanoprost on intraocular pressure and aqueous humor dynamics in monkey eyes

PURPOSE: To compare the ocular hypotensive effects of 15-keto latanoprost (KL) with the commercial preparation of latanoprost (Xalatan; Pfizer, New York, NY) in monkey eyes with laser-induced unilateral glaucoma and to evaluate the effects of topical 0.005% KL on aqueous humor dynamics in normal monkey eyes. METHODS: Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:30 AM on day 1 (untreated baseline); day 2 (vehicle only); and treatment days 1, 3, and 5 (topical, 30 microL of study drug) in the glaucomatous eyes of four to eight monkeys with unilateral laser-induced glaucoma. KL concentrations of 0.0001%, 0.001%, and 0.01% and latanoprost at 0.005% were studied separately, with a minimum washout period of 2 weeks between studies. Tonographic outflow facility (C) and fluorophotometric aqueous humor flow rates (F) were measured in nine normal monkeys before and after a single topical dose of 0.005% KL in one eye, with a vehicle-only control in the fellow eye. RESULTS: When applied once daily to glaucomatous monkey eyes, all three concentrations of KL and a 0.005% concentration of latanoprost produced significant (P < 0.05) reductions in IOP, with the maximum reduction on treatment day 5, regardless of the drug or concentration studied. The maximum reduction (P < 0.001) from vehicle-only baseline IOP was (mean +/- SEM) 3.0 +/- 0.3 mm Hg (9%) for 0.0001% KL, 7.6 +/- 0.6 mm Hg (23%) for 0.001% KL, 6.3 +/- 0.4 mm Hg (18%) for 0.01% KL, and 6.6 +/- 0.6 mm Hg (20%) for 0.005% latanoprost. After application of a single dose of 0.005% KL in nine normal monkey eyes, neither C nor F was altered (P > 0.80) when compared with untreated baseline values or vehicle-treated control eyes. CONCLUSIONS: The reduction in IOP produced by 0.001% KL was equivalent to, and at some measured time points, greater than the effect produced by 0.005% latanoprost. The IOP reduction by KL in normal monkeys appeared to have no effect on aqueous humor production or tonographic outflow facility and may thus indicate a drug-induced increase in uveoscleral outflow.     

Effect of latanoprost on the diurnal variations in the intraocular and ocular perfusion pressure in normal tension glaucoma

PURPOSE: To evaluate the effects of latanoprost on the diurnal variations in the intraocular pressure (IOP) combined with the ocular perfusion pressure (OPP) in patients with normal tension glaucoma (NTG). PATIENTS AND METHODS: Twenty-two eyes from 22 patients with NTG were used for the study. The diurnal variations in the IOP and blood pressure (BP) were measured every 3 hours without therapy, and then the patients were treated with latanoprost (0.005%) once daily for more than 12 weeks. The diurnal variations in the IOP and BP under medication were again measured every 6 hours. The diurnal variation of IOP for 24 hours, mean diurnal IOP, maximum IOP, minimum IOP, range of variation in IOP, OPP, and BP were compared between the baseline and after treatment by means of a paired t test. RESULTS: At 3 months after the start of the latanoprost treatment regimen, the IOP showed a statistically significant decrease at every assessed time point over 24 hours (P<0.001). Latanoprost significantly reduced the mean diurnal IOP, maximum IOP, minimum IOP, and mean range of variation in the IOP values from baseline (P<0.001, <0.001, <0.001, and 0.009, respectively). OPP after treatment showed no significant difference at any assessed time points from the baseline (P>0.1). Latanoprost did not significantly alter the mean diurnal OPP (P>0.1), and BP (P>0.5) from the baseline. CONCLUSIONS: Latanoprost was thus found to significantly reduce IOP over 24 hours, whereas it does not affect OPP and BP in NTG patients. Therefore, it may be a useful medication for NTG.     

Agonist activity of bimatoprost, travoprost, latanoprost, unoprostone isopropyl ester and other prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor.

We have determined the agonist activity of a number of natural prostaglandins and prostaglandin analogs at the FP prostaglandin receptor cloned from a human ciliary body cDNA library using phosphoinositide (PI) turnover assays. Travoprost acid (EC50 = 3.2 +/- 0.6 nM) was the most potent agonist in these cells followed by bimatoprost free acid (17-phenyl-trinor PGF2alpha; EC50 = 5.8 +/- 2.6 nM), fluprostenol (EC50 = 6.1 +/- 1.5 nM), and latanoprost free acid (PHXA85; EC50 = 54.6 +/- 12.4 nM) which was 17-fold weaker (p < 0.001) than travoprost acid. Unoprostone and S-1033 were significantly (p < 0.001) weaker than travoprost acid. The amide prodrug, bimatoprost (EC50 = 694 +/- 293 nM), activated this FP receptor with an intermediate potency. The isopropyl ester prodrugs, travoprost (EC50 = 42.3 +/- 6.7 nM), latanoprost (EC50 = 126 +/- 347 nM) and unoprostone isopropyl ester (EC50 = 9,100 +/- 2,870 nM), also exhibited FP agonist activity. However, other compounds such as PGI2, bradykinin, histamine, and serotonin were inactive. The agonist activities of bimatoprost, unoprostone (UF-021), fluprostenol and acids of travoprost and latanoprost were antagonized by AL-8810 (11beta-fluoro- 15-epi-15-indanyl-PGF2alpha), an FP-receptor-selective antagonist (Ki = 1.0 - 2.1 microM; n = 3). These studies have demonstrated, for the first time, agonist activities of the currently known and marketed ocular hypotensive prostaglandin analogs at the cloned human ciliary body FP prostaglandin receptor.     

Effect of latanoprost/timolol and dorzolamide/tiomolol on intraocular pressure after phacoemulsification surgery

AIM: To evalaute the effect of fixed-combination latanoprost 0.005%/timolol maleate 0.5% and dorzolamide hydrochloride 2%/timolol maleate 0.5% on postoperative intraocular pressure after phacoemulsification cataract surgery. METHODS: This study is a prospective, randomized, double-masked and placebo-controlled. The study included 90 eyes of 90 patients which were scheduled to have phacoemulsification surgery. Patients were randomly assigned preoperatively to 1 of 3 groups (30 eyes of 30 patients). Two hour before surgery, the patients received one drop latanoprost/timolol (group 1), dorzolamide/timolol (group 2) and placebo (group 3, control group). The IOPs were measured at preoperative and postoperative 4, 8, and 24 hours. RESULTS: The preoperative mean intraocular pressure was not statistically significant between both drug groups and control group. In group 1 and 2, the postoperative mean IOP [group1: (14.03±3.15)mmHg and group 2: (14.16±4.43)mmHg] at 24 hours were significantly lower than the control group [(16.93±3.70)mmHg, (P<0.05)]. In addition, the postoperative mean IOP of group 1 [(14.90±3.69)mmHg] at 8 hours was significantly lower than the control group [(17.70±3.89)mmHg, (P<0.05)], but there was no significant difference between group 2 [(16.16±5.23)mmHg] and control group at 8 hours (P>0.05). CONCLUSION: When compared with placebo, the use of preoperative fixed combination of latanoprost/ timolol and dorzolamide/timolol is an effective method for preventing intraocular pressure elevation in 24 hours after phacoemulsification surgery, but did not completely prevent IOP spikes.     

Long term effect of latanoprost on intraocular pressure in normal tension glaucoma

AIM: To determine the long term effect of latanoprost on the intraocular pressure (IOP) of patients with normal tension glaucoma (NTG). METHODS: Newly diagnosed patients with NTG were recruited into the study and had their baseline IOPs measured hourly between 8 am and 5 pm using a handheld electronic Tonopen. Patients with fixation threatening field defects were placed immediately into the treatment group while those with non-fixation threatening field defects were randomised into either the treatment group or the control group (no treatment). Treatment consisted of once daily topical latanoprost 0.005%. After a minimum period of 6 months, the patients underwent a second period of IOP phasing. RESULTS: 76 newly diagnosed patients with NTG were recruited-26 had fixation threatening disease, 25 were randomised to treatment, and 25 randomised to the control group. The average duration of treatment was 11 months. The average and maximum diurnal IOP for the patients randomised to treatment were statistically significantly lower than for the control patients at follow up (p<0.05). The treated group as a whole demonstrated a 17% decrease in the average diurnal IOP and a 19% decrease in the maximum diurnal IOP when compared to baseline IOP. 41% of those treated achieved a decrease of at least 20%, but only 10% of patients achieved a decrease of at least 30%. CONCLUSION: Latanoprost had a sustained hypotensive effect in eyes with NTG and 41% of treated patients achieved a reasonable response. However, in the majority of eyes with NTG, latanoprost monotherapy may be insufficient in producing a desirable 30% reduction in IOP.     

Comparison of the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure

PURPOSE: To compare the nocturnal effects of once-daily timolol and latanoprost on intraocular pressure (IOP) in patients with ocular hypertension or early glaucomatous changes. DESIGN: Prospective, open-label, experimental study with crossover design. METHODS: Eighteen patients with ocular hypertension or early glaucomatous changes (aged 41 to 79 years) each received topical treatments with timolol (0.5% Timoptic-XE), latanoprost (0.005% Xalatan), and no IOP-lowering medication, for at least 4 weeks. Timolol was given once in the morning upon awakening and latanoprost once in the evening at bedtime. At the end of each treatment period, the patient was housed in a sleep laboratory for 24 hours and IOP was measured every 2 hours using a pneumatonometer. Measurements were taken sitting and supine during the 16-hour diurnal/wake period and only supine during the 8-hour nocturnal/sleep period. Mean diurnal and nocturnal IOP levels were compared among the treatments with timolol, latanoprost, and no medication. RESULTS: In the diurnal period, the mean IOP under the timolol or the latanoprost treatment was significantly less than the mean IOP under no medication in both the sitting and the supine positions. There was no statistical difference between the timolol and latanoprost treatments. In the nocturnal period, supine IOP with timolol treatment was not different from the supine IOP with no medication but was significantly higher than supine IOP with the latanoprost treatment. CONCLUSION: Although both once-daily timolol and latanoprost were effective in lowering IOP during the diurnal period, only latanoprost reduced IOP during the nocturnal period.     

Reduction of intraocular pressure in mouse eyes treated with latanoprost.

PURPOSE: To determine whether topical treatment of mouse eyes with latanoprost alters intraocular pressure (IOP). METHODS: In a masked study design, NIH Swiss mice received a 2-microL topical instillation of 0.00015%, 0.0006%, 0.0025%, or 0.01% latanoprost or vehicle (phosphate-buffered saline [PBS]). After 1, 2, or 3 hours, the animals were anesthetized, and a fluid-filled glass microneedle connected to a pressure transducer was inserted through the cornea into the anterior chamber to measure IOP. The reduction of IOP after latanoprost measurement was calculated by the comparison between treated and nontreated eyes in the same mouse. The effect of latanoprost after a single 0.01% dose was also measured at 6, 12, and 24 hours. As in the previous study, the identity of all eye drop solutions was masked. RESULTS: In mouse eyes receiving topical PBS, the mean IOP was 14.8 +/- 2.2 mm Hg (n = 173 males). There was no significant difference in IOP between male and female eyes and between right and left eyes. At 1 hour after topical treatment with 0.00015% or 0.0025% latanoprost, IOP increased by as much as 11% +/- 7%. At 2 and at 3 hours after application, IOP decreased in a dose-dependent manner. These decreases were significant in eyes receiving 0.0025% or 0.01% latanoprost (P < 0.05, Student-Newman-Keuls test) and the largest decrease (14% +/- 8%) was noted 2 hours after treatment with 0.01% latanoprost. At 6, 12, or 24 hours after treatment, there was no difference in latanoprost- and PBS-treated eyes. CONCLUSIONS: Latanoprost reduces mouse IOP in a dose-dependent manner. The mouse may be a useful model for studying the effect of drugs on IOP.     

Additive intraocular pressure lowering effect of various medications with latanoprost

PURPOSE: To determine the additive intraocular pressure reduction of various topical glaucoma agents used adjunctively with latanoprost. DESIGN: Retrospective interventional case series. METHODS: Retrospective evaluation of 73 eyes of 73 patients with glaucoma and inadequate intraocular pressure control on latanoprost alone. Each patient received adjunctive treatment with an additional glaucoma agent (dorzolamide, brimonidine, timolol, or other beta-blockers) for 1 year. RESULTS: When added to latanoprost, dorzolamide lowered intraocular pressure an additional 3.9 mm Hg (19.7%, P <.001); beta-blockers further reduced intraocular pressure by 2.0 mm Hg (12.3%, P <.001), and brimonidine further reduced intraocular pressure by 2.0 mm Hg (9.3%, P =.0011). Dorzolamide dosed twice or three times daily was as effective as adjunctive therapy with latanoprost (P =.92). CONCLUSION: Adjunctive therapy with dorzolamide provided a statistically significant intraocular pressure reduction at 1 year in eyes that were inadequately controlled with latanoprost alone.