Intraocular pressure fluctuations in response to the water-drinking provocative test in patients using latanoprost versus unoprostone.

Impairment of outflow facility in glaucoma causes large intraocular pressure (IOP) fluctuations that have been shown to be a risk factor for disease progression. The water-drinking provocative test (WDT) has been proposed as an indirect measurement of outflow facility to compare intraocular pressure responses of glaucoma eyes to different drugs. This study was a double-masked, randomized, parallel-group clinical trial comparing the IOP fluctuations in response to the WDT in patients using latanoprost versus unoprostone. After completing a wash-out of ocular hypotensive medications, patients with primary openangle glaucoma or ocular hypertension were randomized to receive either latanoprost (N=40) or unoprostone (N=42). IOP was measured before treatment and at 8 weeks after treatment (baseline IOP for WDT), followed by the WDT. IOP fluctuations and maximum IOP after water ingestion were compared between the two groups. Analysis of covariance was used to adjust for the effects of baseline IOP and treatment efficacy. The mean percentage reduction of IOP was 27% in patients using latanoprost, as compared to 13% in patients using unoprostone (p<0.001). Patients on treatment with latanoprost had significantly less IOP fluctuations in response to the WDT, compared to patients using unoprostone. From an overall baseline IOP of 20.0 mmHg and an overall treatment efficacy of 20%, the mean+/-standard error of the mean (SEM) of the IOP fluctuation during the WDT was 5.3+/-0.4 mmHg in the unoprostone group, and 3.6+/-0.4 mmHg in the latanoprost group (p=0.005, ANCOVA). This could represent an additional benefit of latanoprost over unoprostone in controlling the intraocular pressure of glaucomatous patients.     

Latanoprost and cholinergic agonists in combination

Latanoprost, a prodrug of a prostaglandin F(2alpha) analog, is a potent ocular hypotensive agent, reducing intraocular pressure (IOP) primarily by increasing aqueous humor drainage through the uveoscleral outflow pathway. Initial assessments in animals found that high concentrations of cholinergic agonists reduced drainage through this pathway and attenuated the effects of a PGF(2alpha) analog. This raised the question of whether latanoprost would be effective when added to the treatment regimen of patients on pilocarpine or strong miotics. In published clinical studies, latanoprost was additive to the maximally tolerated medical therapy (which included cholinergic agonists) of glaucoma patients. Multiple doses of physostigmine in healthy volunteers did not block the effect of a single drop of latanoprost during a 1-day study. One study attempting to find the optimal timing of administration of latanoprost and pilocarpine claimed to show that additivity was best when pilocarpine was given one hour after latanoprost in the evening. Two other studies found that the timing of the doses was not important. To explain the additivity of latanoprost and pilocarpine, aqueous humor dynamics were assessed in ocular hypertensive patients treated for 1 week with each drug alone and then for one week in combination. The results showed that latanoprost increased uveoscleral outflow, pilocarpine increased outflow facility, and pilocarpine did not block or attenuate the uveoscleral outflow effect of latanoprost. The result was greater IOP reduction when these drugs were used in combination than when either drug was used alone. All available evidence demonstrates that addition of latanoprost to the treatment regime of patients already taking cholinergic agonists is an effective, although not necessarily the preferred, combination of medications for the treatment of elevated IOP.     

Aqueous humor dynamics in monkeys with laser-induced glaucoma.

This study determines the effects of laser-induced glaucoma on aqueous humor dynamics of 18 cynomolgus monkeys. Baseline measurements of 12 monkeys included intraocular pressure (IOP) by pneumatonometry, aqueous flow by fluorophotometry and outflow facility by tonography. Beginning 4 to 14 days later, the trabecular meshwork of one eye was treated repeatedly with laser photocoagulation until elevated IOP was induced. Thirty-six to 75 days after the last laser treatment, all measurements were repeated. Between 1.7 and 11.4 years after laser treatment, the same 12 monkeys plus 6 additional monkeys underwent IOP and aqueous flow measurements. In addition, outflow facility was determined with fluorophotometry, and uveoscleral outflow was both calculated (n=18) and measured with an intracameral tracer (n=7). In glaucoma eyes compared to control eyes (n=12), IOP was increased (p<0.04) by at least 8 mmHg at Time 1 (1 to 3 months) or Time 2 (3 to 4 years) after laser treatment; aqueous flow was reduced (p=0.0007) by 46% at Time 1 but returned to baseline levels at Time 2; tonographic outflow facility was reduced (p=0.0008) by 71% at Time 1. In lasered eyes compared to control eyes, fluorophotometric outflow facility was reduced (p=0.0008; n=18) by 63%, and uveoscleral outflow was increased (p<0.05), whether calculated or measured with tracers at least 1 year after laser treatment. The increased IOP in monkeys with laser-induced glaucoma was caused by a sustained reduction in outflow facility. The uveoscleral outflow increase was not enough to prevent the rise in IOP.     

The effect of latanoprost on intraocular pressure during 12 months of treatment for normal-tension glaucoma

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering efficacy of latanoprost in normal-tension glaucoma (NTG). METHODS: One-hundred and seventeen eyes of 63 NTG patients treated with 0.005% latanoprost once a day were enrolled in this study. Of these, 85 eyes of 47 patients were treated for 12 months. Mean IOPs were analyzed, and the mean IOP reductions from the untreated baseline were assessed after two weeks and after 1, 3, 6, 9, and 12 months of treatment. RESULTS: The mean untreated baseline IOP was 15.0 +/- 2.7 mmHg. After two weeks of latanoprost treatment, the mean IOP reduction from the baseline value was 2.6 +/- 0.2 mmHg (17.3%, p<0.05), and after 6 and 12 months, the reduction was 2.4 +/- 0.2 mmHg (16.0%, p<0.05) and 2.4 +/- 0.2 mmHg (16.0%, p<0.05), respectively. Patients with a baseline IOP of > or = 15 mmHg achieved significantly higher IOP reductions than those with a baseline IOP of <15 mmHg at all follow-ups (p<0.05). CONCLUSIONS: Latanoprost was found to be well tolerated and to significantly reduce IOP in NTG patients.     

Intraocular pressure-lowering efficacy of latanoprost in patients with normal-tension glaucoma or primary open-angle glaucoma.

We investigated the intraocular pressure (IOP)-lowering potential of latanoprost in patients with normal-tension glaucoma (NTG) or primary open-angle glaucoma (POAG). This prospective study included 59 NTG and 20 POAG patients treated with the following four dosing regimens of latanoprost: patients on no previous medication received latanoprost as initial therapy (Group 1, n=31), patients on beta-blocker therapy received latanoprost as adjunctive therapy (Group II, n=9), patients on unoprostone monotherapy were switched to latanoprost monotherapy (Group III, n=14), and patients previously on dual therapy with isopropyl unoprostone and beta-blocker were switched to a combined treatment of latanoprost and beta-blocker (Group IV, n=25). IOP significantly decreased 8 weeks after initiation of latanoprost therapy by 19.9% in Group I, 20.5% in Group II, 16.6% in Group III, and 12.2% in Group IV. In Groups I and II, there was a significant positive correlation between the magnitude of IOP reduction induced by latanoprost and the IOP level before latanoprost therapy. The IOP level before latanoprost therapy is a contributing factor in the IOP-lowering efficacy of latanoprost. Latanoprost is more effective in lowering IOP than isopropyl unoprostone.     

Effect of pilocarpine 4% in combination with latanoprost 0.005% or 8-iso prostaglandin E2 0.1% on intraocular pressure in laser-induced glaucomatous monkey eyes.

PURPOSE: To compare the effect of pilocarpine, an agent that reduces uveoscleral outflow, on the ocular hypotensive efficacy of latanoprost and 8-iso prostaglandin E2 (PGE2). METHODS: Each of the two treatment groups was composed of the same eight monkeys with unilateral laser-induced glaucoma. Intraocular pressure (IOP) was measured hourly for 6 hours beginning at 9:00 AM on the baseline day (Thursday before treatment week) and on treatment days 1, 3, and 5 (Monday, Wednesday, and Friday). On all five treatment days, one drop of pilocarpine 4% was administered at 9:00 AM and 3:00 PM and one drop of latanoprost 0.005% or 25 microL of 8-iso PGE2 0.1% was administered at 10:00 AM and 4:00 PM. RESULTS: One hour after pilocarpine instillation on day 1, the reduction of IOP was similar (P > 0.90) in both treatment groups, 7.6 +/- 1.1 mm Hg (mean +/- standard error of the mean ) in the latanoprost group and 7.4 +/- 0.8 mm Hg in the 8-iso PGE2 group. However, the IOP effects of the two treatment groups became significantly different (P < 0.05) beginning 2 hours after dosing with latanoprost or 8-iso PGE, on day 1. A difference (P < 0.05) between the two groups persisted at all subsequent measurements. The reduction of IOP lessened with repeated dosing in the latanoprost and 8-iso PGE2 groups. Three hours after dosing with pilocarpine and two hours after dosing with the prostanoids, the IOP reduction was 8.3 +/- 0.9 mm Hg in the latanoprost group and 9.9 +/- 0.6 mm Hg in the 8-iso PGE2 group on day 1, and 2.1 +/- 1.0 mm Hg in the latanoprost group and 7.3 +/- 0.9 mm Hg in the 8-iso PGE1 group on day 5. CONCLUSIONS: The smaller reductions in IOP with pilocarpine and latanoprost than with pilocarpine and 8-iso PGE2 show that pilocarpine blocks much more of the ocular hypotensive effect of latanoprost than of 8-iso PGE2. The results also indicate that pilocarpine and latanoprost are mutually antagonistic. Enhancement of uveoscleral outflow appears to account for most of the ocular hypotensive effect of latanoprost and for much less of the ocular hypotensive effect of 8-iso prostaglandin E2.     

A three-year prospective, randomized and open comparison between latanoprost and timolol in Japanese normal-tension glaucoma patients

PURPOSE: To compare the longitudinal effects of treatment on intraocular pressure (IOP) and visual field performance in Japanese normal-tension glaucoma (NTG) between latanoprost and timolol. PATIENTS AND METHODS: This is an open-label, randomized, study. A total of 62 NTG patients were prospectively, consecutively enrolled. All study subjects were randomly assigned to 0.005% latanoprost instillation once daily in the morning or 0.5% timolol instillation twice daily for a prospective 3-year follow-up, and underwent a routine ocular examination every month. Automated perimetry was performed every 6 months using Humphrey field analysers. Stereophotographs of optic discs were also obtained every 6 months. RESULTS: Percentage of IOP reduction or the magnitude of IOP reduction showed no intergroup differences either at any time point (13-15%). In the visual field, the estimated rate of change in the MD value (dB/year) was -0.34+/-0.17 (SE) for the latanoprost group, and -0.10+/-0.18 (SE) for the timolol group. The estimated rate of change in MD showed no significant difference from zero in both groups, and there were no statistical intergroup differences. No changes in the optic nerve head topography in the vertical cup-to-disc ratio and rim area measured by image-analysis techniques were observed in either group. There were no patients who dropped out due to the side effects of treatment regimens. CONCLUSION: Both latanoprost and timolol single treatments reduced IOP by 13-15% at their trough effects for 3 years in Japanese NTG patients; both showed similar effects on visual field performance.     

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.     

Involvement of nitric oxide in the ocular hypotensive action of nipradilol

PURPOSE: To evaluate the role of nitric oxide (NO) in the mechanism of the ocular hypotensive action of nipradilol, a beta-blocker with alpha( 1)-blocking activity. METHODS: Change in intraocular pressure (IOP) of albino rabbits was measured after a single application of carboxy-PTIO (c-PTIO), an NO trapping agent. Next, IOP change was measured every hour for 5 hours after the instillation of 0.25% nipradilol into one of the eyes with and without c-PTIO pretreatment of both eyes. IOP change induced by desnitro-nipradilol was also examined. The outflow facility and uveoscleral outflow were determined by two-level constant pressure and anterior chamber perfusion methods before and at 3 hours after the application of nipradilol with and without c-PTIO pretreatment. RESULTS: Topical administration of c-PTIO showed no significant effect on IOP. Unilateral instillation of nipradilol reduced IOP significantly compared with control eyes with a maximum reduction of 3.6 mmHg and effect duration of 3 hours. Pretreatment with c-PTIO partially inhibited the reduction during an earlier period (1 approximately 2 hours) and completely at 3 hours. IOP change by desnitro-nipradilol was similar to that by nipradilol with c-PTIO pretreatment. Nipradilol increased both outflow facility and uveoscleral outflow at 3 hours, whereas pretreatment with c-PTIO inhibited both of these outflows. CONCLUSIONS: Results indicate that ocular hypotensive action by nipradilol during the relatively late period may be mainly due to enhancement of aqueous humor outflow by NO at least in the rabbits.     

Effects of topical nipradilol, a beta blocking agent with alpha blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans

AIMS: To study the effects of topical nipradilol, a non-selective beta blocker with alpha blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension. METHODS: Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0. 5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks. RESULTS: Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period. CONCLUSION: Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new antiglaucoma drug.     

Additive IOP-reducing effect of latanoprost in patients insufficiently controlled on timolol

PURPOSE: To evaluate the effect on intraocular pressure (IOP) of switching from timolol to latanoprost or adding latanoprost to timolol in patients with open angle glaucoma or ocular hypertension where IOP is not adequately controlled with timolol. METHODS: This was a 6-week, double-masked, randomised multi-centre study. 53 patients with primary open angle glaucoma, capsular glaucoma, or ocular hypertension with an IOP of at least 21 mmHg on current therapy were recruited. After a run-in period of at least 2 weeks on timolol, 5 mg/ml twice daily, patients were randomised to one of three groups. One group continued on timolol, one switched from timolol to latanoprost, 50 microg/ml once daily, and a third group received latanoprost in addition to timolol. The efficacy was evaluated by comparing IOP at 9 AM at baseline and after 6 weeks of treatment. RESULTS: IOP at baseline and after 6 weeks of treatment (mean +/- SEM) were 24.2 +/- 0.9 and 23.8 +/- 1.0 mmHg (n = 16) for patients continuing on timolol, 26.3 +/- 1.2 and 19.6 +/- 1.1 mmHg (n = 17) for patients switching to latanoprost, and 23.2 +/- 1.0 and 17.5 +/- 0.8 mmHg (n = 17) for patients with combined treatment. Adding latanoprost to timolol reduced IOP with 5.9 +/- 0.9 mmHg (p < 0.001) and switching from timolol to latanoprost reduced IOP with 5.0 +/- 0.9 mmHg (p < 0.001), which caused in each group a significant IOP reduction of about 25%. CONCLUSIONS: The effect of latanoprost was additive to that of timolol, and a good effect on IOP reduction was also achieved by switching from timolol to latanoprost, suggesting that a switch in many patients is an effective alternative to combination treatment.     

Comparison of latanoprost monotherapy and combined therapy of 0.5% timolol and 1% dorzolamide in chronic primary angle-closure glaucoma (CACG) in Japanese patients.

To compare the efficacy, adverse effects, and patient compliance of latanoprost monotherapy with unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of chronic primary angle-closure glaucoma (CACG), 36 Japanese patients with CACG following laser iridotomy (LPI) were treated for 12 weeks with instillation of latanoprost alone or with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. After 12 weeks of treatment, latanoprost reduced intraocular pressure (IOP) from 22.2 +/- 2.0 mmHg to 14.8 +/- 1.9 mmHg (33% reduction); timolol maleate and dorzolamide hydrochloride also reduced IOP from 22.5 +/- 2.2 mmHg to 17.1 +/- 2.7 mmHg (24% reduction). Latanoprost monotherapy significantly lowered IOP compared with unfixed combination therapy of 0.5% timolol maleate and 1% dorzolamide hydrochloride. Furthermore, a systemic adverse effect of bradycardia was not observed in the latanoprost monotherapy group. Concerning compliance, no significant difference was observed between the two groups. Thus, latanoprost monotherapy is more effective than unfixed combination therapy with 0.5% timolol maleate and 1% dorzolamide in the treatment of CACG following relief of pupillary block in Japanese patients.     

Changes in intraocular pressure and ocular perfusion pressure after latanoprost 0.005% or brimonidine tartrate 0.2% in normal-tension glaucoma patients

OBJECTIVE: To evaluate and compare the effects of latanoprost 0.005% once daily and brimonidine tartrate 0.2% twice daily in patients with normal-tension glaucoma (NTG). DESIGN: A randomized, open-label, crossover study. PARTICIPANTS: Twenty-eight NTG patients with progressive visual field defects/optic disc excavation, new disc hemorrhage, or field defects that threatened fixation. INTERVENTION: Patients were randomly allocated to one of two groups. Patients in group 1 were treated with latanoprost, lubricant, and brimonidine for 4 weeks each, whereas patients in group 2 were treated with brimonidine, lubricant, and latanoprost for 4 weeks each. MAIN OUTCOME MEASURES: Intraocular pressure (IOP), pulse rate, and blood pressure were measured at 8 am, 12 noon, and 4 pm after each 4-week treatment. Ocular perfusion pressure (OPP) was calculated. RESULTS: Latanoprost and brimonidine reduced the average IOP by 3.6 +/- 1.9 mmHg (P < 0.001) and 2.5 +/- 1.3 mmHg (P < 0.001), respectively, with a significant difference between the two regimens (P = 0.009). Both drugs significantly reduced IOP at each time point. Latanoprost decreased IOP significantly more than did brimonidine at 8 am (11.7 +/- 2.2 mmHg vs. 13.7 +/- 2.1 mmHg, P = 0.004) and 4 pm (11.4 +/- 2.1 mmHg vs. 13.2 +/- 2.9 mmHg, P = 0.004), but IOP was equal between the two agents at 12 noon (11.5 +/- 2.6 mmHg vs. 11.5 +/- 2.3 mmHg, P = 0.967). IOP was maintained at 12 mmHg or lower in 18 (66.7%) of 27 patients after treatment with latanoprost and in 9 (33.3%) of 27 patients after treatment with brimonidine. Latanoprost monotherapy reduced IOP by 30% in 8 patients (29.6%), but brimonidine monotherapy did not reduce IOP by that much in any of the patients. OPP increased after latanoprost treatment (P < 0.001) but did not increase after brimonidine treatment (P = 0.355). There was no significant change in pulse rate or blood pressure. CONCLUSIONS: Both latanoprost and brimonidine reduce IOP in NTG patients. Brimonidine has a peak IOP-lowering effect equal to that of latanoprost but produces a higher mean diurnal IOP than does latanoprost because of its shorter effect. Latanoprost might favorably alter optic disc blood perfusion by increasing OPP.     

Predicting intraocular pressure change before initiating therapy: timolol versus latanoprost

Purpose: To study intraocular pressure (IOP) reductions with timolol and latanoprost reached in clinical practice, taking into account data that are routinely collected by the ophthalmologist; to predict IOP reduction from these variables. Methods: A cohort of patients with primary open‐angle glaucoma (suspect) or ocular hypertension was recruited from nine Dutch centres. Mean absolute and relative IOP reduction was calculated in order to compare timolol to latanoprost. IOP reduction was calculated by comparing patients with certain characteristics to those who had none. Results: One hundred and fifty‐six persons started on timolol and 76 started on latanoprost monotherapy. Mean [95% confidence interval (CI)] absolute reduction was 7.2 mmHg (7.9; 6.5) for timolol and 6.9 mmHg (8.0; 5.8) for latanoprost. Mean relative reduction (95% CI) was 27.2% (29.3; 25.1) for timolol and 26.6% (30.2; 22.9) for latanoprost. No significant difference in IOP reduction between timolol and latanoprost was found when adjusting for data that are routinely collected by the ophthalmologist. At the time of starting treatment, none of these items normally used for the management of glaucoma, except IOP at baseline, could predict change in IOP. Conclusion: In clinical practice, timolol and latanoprost achieve similar IOP reductions that are comparable to those achieved in randomized trials. No clinically relevant information for glaucoma management can be used to predict IOP reduction accurately.     

A Comparative Study of Latanoprost (Xalatan) and Isopropyl Unoprostone (Rescula) in Normal and Glaucomatous Monkey Eyes

Latanoprost (PhXA41, Xalatan) and isopropyl unoprostone (UF-021, unoprostone, Rescula) two new prostanoid derivatives, have been shown to reduce intraocular pressure (IOP) significantly in patients with glaucoma or ocular hypertension. This study was designed to compare the ocular hypotensive effects of latanoprost and unoprostone in cynomologus monkeys with glaucoma and characterizes the prostanoid’s mechanisms of action in normal cynomolgus monkey eyes. Intraocular pressure was measured daily at 0, 0.5, and 1 hour and hourly for 5 additional hours during 1 baseline day, 1 vehicle-treated day, and 5 days of therapy with either 0.005% latanoprost or 0.12% unoprostone applied twice daily, at 9:30 am and 3:30 pm, to the glaucomatous eye of eight monkeys with unilateral laser-induced glaucoma. Outflow facility was measured in six normal monkeys 3 hours prior to dosing and 1 hour after unilateral dosing with either drug. Aqueous humor flow rates were measured in six normal monkeys hourly for 4 hours on 1 baseline day and on 1 treatment day beginning 1 hour after administration of either drug to one eye. Intraocular pressure was significantly (P < 0.005) reduced after the first application for 4 hours with latanoprost and for 2 hours with unoprostone, up to 5.4±0.8 mm Hg (mean ± SEM) (latanoprost) and 3.8 ± 0.5 mm Hg (unoprostone). Intraocular pressure was significantly (P < 0.005) reduced for at least 18 hours following each pm dose of latanoprost. Intraocular pressure was not reduced (P > .05) 18 hours after each pm dose of unoprostone. An enhancement of the ocular hypotensive effect was observed from day 1 to day 5 with repeated dosing of either drug. Latanoprost produced a greater magnitude of IOP reduction for a longer duration of time than unoprostone after each application. Neither drug altered outflow facility or aqueous humor flow rates. Latanoprost and unoprostone appear to reduce IOP in monkeys by enhancing uveoscleral outflow. Latanoprost appears to be more efficacious and potent than unoprostone in reducing IOP in glaucomatous monkey eyes.     

The effect of substituting latanoprost 0.005% for unoprostone 0.12%

PURPOSE: To evaluate the effect of substituting latanoprost(LAT) 0.005% for unoprostone(UNO) 0.12% after a trial of unilateral treatment. METHODS: We treated 30 patients with primary open-angle glaucoma(n = 8), ocular hypertension (n = 1), or normal-tension glaucoma(n = 21) with UNO for 4 weeks in one eye and then substituted LAT for UNO. Four weeks later we measured the intraocular pressure(IOP) in the ipsilateral eye. RESULTS: The mean baseline IOP level was 18.6 +/- 3.8(mean +/- standard deviation) mmHg. The mean IOP levels(reduction rates) after UNO and LAT therapy were 16.7 +/- 3.1 mmHg (16.6%) and 14.1 +/- 3.2 mmHg (28.9%), respectively(p < 0.001). All patients who responded to UNO also responded to LAT; however, 55% of those who did not respond to UNO responded to LAT. CONCLUSIONS: If LAT is substituted for UNO, it can be predicted that 63.3% of the patients will respond.     

Peak pressures: crossover study of timolol and latanoprost

PURPOSE: To compare the diurnal efficacy and action on peak intraocular pressures (IOP) of 0.005% latanoprost and 0.5% timolol as primary therapy in 60 eyes having dark brown irides with primary open angle glaucoma (POAG). METHODS: A prospective, comparative, observer-masked, crossover, interventional trial including the mean of both eyes of 30 patients with POAG who were randomly started on either latanoprost once daily or timolol twice daily. Three months after treatment with one drug, the second drug was substituted. A masked observer carried out diurnal assessments of IOP before the start of therapy and at 3 and 7 months. The fourth month was the washout period for the first drug. RESULTS: The average baseline IOP was 23.36 +/- 2.14 mm Hg, which was reduced by 8.8 +/- 2.2 mmHg with latanoprost (p < 0.01) and by 6.75 +/- 1.9 mm Hg with timolol (p = 0.01). The reduction was greater for latanoprost (p < 0.005). The average peak IOP at baseline was 27.6 +/- 2.22 mmHg. The effective fall in IOP at the time of new peaks in subsequent diurnal recordings of IOP compared to the baseline diurnal curve was 8.9 mm Hg with latanoprost (p < 0.005) and 5.77 mm Hg with timolol (p < 0.01). This difference in IOP reduction between the two drugs was statistically significant (p < 0.01). Latanoprost had a lower efficacy in peak IOP reduction in eyes with evening peak of IOP than in those with morning peak (p < 0.005). The efficacy of timolol was lower overall compared to latanoprost, but was similar in all circadian rhythms. The shift in timing of IOP peak was greater with latanoprost compared to timolol (4.34 hours vs -0.72 hours, p < .01). A total of 90% of patients on latanoprost and 33.3% on timolol achieved a reduction of > 30% in baseline mean IOP. The average of the trough IOP recorded in each of the individual baseline IOP curves was 19.05 +/- 2.05 mm Hg. CONCLUSIONS: Greater mean and peak IOP reduction was achieved with latanoprost compared to timolol. Dampening of the circadian rhythm was better with latanoprost. Latanoprost appears to be more effective than timolol at all points in time with greater efficacy in eyes with morning peaks compared to evening peaks.     

Positive ibopamine provocative test in normal-tension glaucoma suspects

BACKGROUND: Ibopamine is an alpha-adrenergic agent and causes an elevation of intraocular pressure in eyes with increased outflow resistance. It has been proposed as a test substance for the detection of early ocular hydrodynamic disorders. PATIENTS AND METHODS: A total of 64 normal-tension glaucoma suspect eyes without anti-hypertensive treatment were enrolled. A daily pressure curve was registered with measurements at 7:00 am, 8:00 am, 12:00 am, 17:00 pm using an applanation tonometer and a contour tonometer followed by instillation of ibopamine 2% in both eyes. Tonometry was performed every 15 minutes during the following hour. An IOP increase of > 2.0 mmHg was considered positive. RESULTS: The positive test group showed a significant pressure increase from 18.04 to 22.06 mmHg. Ocular pulse amplitude increased from 2.96 to 3.97 mmHg and was positively correlated with the pressure. Intraocular pressure was unchanged in the negative test group. Central corneal thickness was not significantly different in the two groups (p = 0.32). CONCLUSIONS: Ibopamine 2% eye drops have a positive pressure effect in 50% of suspected normal-tension glaucoma eyes and may differentiate between eyes with normal trabecular outflow capacity and eyes with increased resistance in the trabecular meshwork that are prone to pressure peaks and deterioration to glaucoma.     

Circadian changes of intraocular pressure and ocular perfusion pressure after timolol or latanoprost in Caucasians with normal-tension glaucoma

Purpose To evaluate the circadian effects on intraocular pressure (IOP) and ocular perfusion pressure (OPP) of 0.5% timolol or 0.005% latanoprost in Caucasian patients affected by normal-tension glaucoma (NTG). Patients and methods In this crossover trial, 30 consecutive NTG subjects underwent three 24-hour assessments of IOP, blood pressure (BP), heart rate (HR), and OPP [calculated according to the formula OPP = (1/3 systolic BP + 2/3 diastolic BP) x 2/3 – IOP]: at baseline, and after 1-month treatment with timolol or latanoprost. These parameters were recorded at 4 a.m., 8 a.m., noon, 4 p.m., 8 p.m., and midnight. Results Both timolol and latanoprost reduced IOP (p < 0.001), with a difference in favour of latanoprost of 1.3 mmHg (95% CI 0.9, 1.6; p < 0.001). After timolol, BP and HR decreased with respect to baseline (p < 0.001). Latanoprost increased mean OPP (3.6 mmHg, 95% CI 2.9, 4.3; p < 0.001), whereas timolol did not improve it. Conclusions Latanoprost induces an IOP reduction greater than timolol, also achieving a better circadian flattening of the IOP curve. Only latanoprost significantly increased mean 24-hour OPP. The management of Caucasian NTG patients should be critically realized, considering the 24-hour influence of each IOP-lowering drug on the ocular blood perfusion.     

Effects of brinzolamide on aqueous humor dynamics in monkeys and rabbits.

This study examines the mechanisms by which brinzolamide reduces intraocular pressure (IOP) in healthy rabbits and in monkeys with unilateral ocular hypertension. Intraocular pressures were measured by pneumatonometry and aqueous flow was determined by fluorophotometry before and after three twice-daily drops of 1% brinzolamide to both eyes per monkey and after similar treatment to one eye per rabbit. In monkeys, outflow facility was determined by fluorophotometry and uveoscleral outflow was calculated. In rabbits, outflow facility was determined by two-level constant pressure infusion and uveoscleral outflow was measured by an intracameral tracer technique. Compared with contralateral vehicle-treated rabbit eyes, IOP was reduced in brinzolamide-treated eyes by 2.5 +/- 1.9 mmHg (mean +/- standard deviation; p =.006) at four hours after the second dose. Aqueous flow was reduced by 0.50 +/- 0.65 microl/min (p =.02). This effect was found in rabbits previously treated with brinzolamide but not in naive rabbits. Treated hypertensive eyes of monkeys had a reduction in IOP of 7.3 +/- 8.8 mmHg (p = 0.01) and aqueous flow of 0.69 +/- 1.10 microL/min (p = 0.05) when compared with baseline. Brinzolamide did not affect outflow facility or uveoscleral outflow in either rabbits or monkeys. It is concluded that, in normotensive eyes of rabbits and hypertensive eyes of monkeys, brinzolamide reduces IOP by reducing aqueous flow and not by affecting aqueous humor drainage.