A randomized, 36-month, post-marketing efficacy and tolerability study in Sweden and Finland of latanoprost versus non-prostaglandin therapy in patients with glaucoma or ocular hypertension

Comparison of the Intraocular Pressure Lowering Effect of Latanoprost and Carteolol-pilocarpine Combination in Newly Diagnosed Glaucoma

To identify predictors of intraocular pressure (IOP) reduction following selective laser trabeculoplasty (SLT) in patients with high- and low-pressure primary open-angle glaucoma, who are already taking maximally tolerated IOP-lowering medication and need further IOP reduction. In this prospective interventional case series, 157 eyes of 157 open-angle glaucoma patients who were assigned for SLT for further IOP reduction were included. Each patient had diurnal IOP measurements taken before and on average 6months following SLT. The mean of six IOP measurements was compared. The following parameters were analysed for their association with SLT success: age, gender, spherical equivalent, high-pressure or normal-pressure open-angle glaucoma, number and type of pressure-lowering medications, lens status, pre-SLT IOP, IOP at the time of diagnosis, duration of glaucoma, visual field stage and central corneal thickness. The only parameter that was predictive for absolute and relative mean diurnal IOP reduction after SLT was the preoperative mean diurnal IOP. One hundred per cent of the patients with a mean diurnal preoperative IOP of more than 18mmHg had an IOP reduction after SLT. With mean diurnal preoperative values of 14-18mmHg, 83.1% of the patients, and with values below 14mmHg only 64% of the patients, showed an IOP reduction. This difference was statistically significant (>18 compared to 14-18: p=0.002; >18 compared to <14: p=0.001; 14-18 compared to <14: p=0.030). The pressure-lowering effect of SLT can best be predicted by the individual IOP level before treatment. Patients with mean diurnal IOP levels below 14mmHg might not benefit from the procedure at all.

To characterize the 24-hour pattern of intraocular pressure (IOP) in untreated patients with newly diagnosed early glaucomatous changes. Measurements of IOP, blood pressure, and heart rate were taken every 2 hours during a 24-hour period from a group of 24 untreated patients (ages 40-78 years) with newly diagnosed abnormal optic discs and/or abnormal visual fields. In the 16-hour diurnal awake period, IOP was measured sitting and supine, and blood pressure and heart rate were measured supine. In the 8-hour nocturnal sleep period, all measurements were taken in the supine position. Mean diurnal and nocturnal IOP, blood pressure, and heart rate in the glaucoma group were compared with data obtained from an age-matched control group of 24 individuals with healthy eyes. Mean diurnal IOP, either sitting or supine, was significantly higher in the glaucoma group than in the control group. For both subject groups, nocturnal supine IOP was higher than diurnal sitting IOP. However, this diurnal-to-nocturnal increase in IOP was significantly smaller in the glaucoma group. When compared with the diurnal supine IOP, the nocturnal supine IOP was lower in the glaucoma group but higher in the control group. Around normal awakening time, the supine IOP increased in the glaucoma group and did not change in the control group. There was a diurnal-to-nocturnal decrease in mean blood pressure only in the glaucoma group. Compared with healthy eyes, the diurnal IOP is higher, the diurnal-to-nocturnal change of habitual IOP is less, and the posture-independent IOP pattern around normal awakening time is different in eyes with early glaucomatous changes.

Objective:To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%–timolol 0.5% compared with latanoprost 0.005% in patients with glaucoma or ocular hypertension.Research design and methods:This was a prospective, randomized, multicenter, investigator-masked clinical trial. After washout of any previous IOP-lowering medications, patients with IOP of 24 mmHg or higher were randomized to twice-daily fixed-combination brimonidine 0.2%–timolol 0.5% (n = 73) or once-daily latanoprost 0.005% (n = 75, dosed in the evening, with vehicle control in the morning to maintain masking) for 12 weeks. IOP was measured at 8 a.m. (before dosing), 10 a.m., and 3 p.m. at baseline, week 6, and week 12.Clinical trial registration:The trial is registered with the identifier 00811564 at http://www.clinicaltrials.gov.Main outcome measures:The primary efficacy endpoint was diurnal IOP (averaged over 8 a.m., 10 a.m., and 3 p.m.) at week 12. Safety measures included biomicroscopy.Results:There was no statistically significant difference between the treatment groups in mean diurnal IOP at baseline (p = 0.118). At week 12, the mean (SD) diurnal IOP was 17.8 (2.9) mmHg with brimonidine–timolol and 17.9 (3.9) mmHg with latanoprost (p = 0.794). The percentage of patients achieving at least a 20% decrease from baseline diurnal IOP at week 12 was 87.7% in the brimonidine–timolol group and 77.3% in the latanoprost group (p = 0.131). Measured biomicroscopic changes from baseline to week 12 were infrequent in both groups.Conclusions:Fixed-combination brimonidine–timolol was as effective as latanoprost in reducing IOP in patients with glaucoma or ocular hypertension. Both treatments demonstrated favorable ocular tolerability. The duration of the study was 12 weeks, and additional studies will be needed to compare the efficacy and safety of fixed-combination brimonidine–timolol and latanoprost during long-term treatment.

Comparison of latanoprost with fixed-combination dorzolamide and timolol in adult patients with elevated intraocular pressure: An eight-week, randomized, open-label, parallel-group, multicenter study in Latin America

Aims: To evaluate the efficacy and safety of replacing current dual ocular hypotensive therapy with latanoprost 0.005% monotherapy in patients with open angle glaucoma. Methods: This randomised, open label, parallel...

PurposeThe study reported here investigated the efficacy, tolerability, and safety of the preservative-free prostaglandin analog tafluprost 0.0015% in treatment-naive patients.Patients and methodsData were collected in two non-interventional, prospective, multicenter, observational, open-label studies of identical design that were conducted in Germany and the Czech Republic. All subjects received preservative-free tafluprost 0.0015% once daily. Intraocular pressure (IOP) levels were recorded for each eye at untreated baseline and 3 months after initiation of medical treatment. The primary outcome was change in mean IOP from baseline to month 3. In the primary open-angle glaucoma (POAG) and ocular hypertension (OH) patient subgroups, analyses were stratified by the level of baseline IOP: ≥20 to 23 mmHg versus ≥24 mmHg. In addition, responder rates and the achievement of pre-specified IOP levels at month 3 were evaluated. Local tolerance of preservative-free tafluprost was evaluated by the patients at final visit. Overall satisfaction with the medical treatment was evaluated by both patients and physicians. All adverse events were recorded.ResultsA total of 579 treatment-naive patients with POAG (n = 349), OH (n = 105), normal tension glaucoma (n = 71), exfoliative glaucoma (n = 27), or other glaucomas (n = 27) were included in this observational study. Mean IOP level at baseline for all patients was 23.6 ± 4.0 mmHg. Mean IOP at month 3 was 16.8 ± 2.9 mmHg (−28.8% vs baseline). At month 3, significant reductions in mean IOP (P < 0.001) were seen in all patients and all subgroups. Preservative-free tafluprost lowered mean IOP significantly in patients with POAG and OH with IOP levels ≥ 20 to 23 mmHg from 21.9 ± 1.1 mmHg at baseline to 16.5 ± 2.2 mmHg, and in the subgroup with IOP levels ≥ 24 mmHg from 26.2 ± 2.4 mmHg to 17.9 ± 2.4 mmHg. In the subgroups of patients with POAG and OH, an IOP response ≥20%, ≥30%, and ≥40% was achieved by 83.4%, 44.1%, and 12.8%, respectively. Overall, patients with higher baseline IOP values showed a better response than patients with lower baseline IOP levels. Preservative-free tafluprost was well tolerated and safe. After 3 months, 97.9% of all patients remained on therapy.ConclusionIn this real-world observational study, treatment with once-daily preservative-free tafluprost proved efficacious, well tolerated, and safe in treatment-naive patients.

Efficacy and safety of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure

Association between Genetic Polymorphisms of Adrenergic Receptor and Diurnal Intraocular Pressure in Japanese Normal-Tension Glaucoma

ABSTRACTAims: To assess the incremental change in intraocular pressure (IOP) levels in patients with primary open-angle glaucoma or ocular hypertension, insufficiently treated with topical ocular hypotensive monotherapy or combination therapy and changed to the latanoprost/timolol fixed-combination therapy (LTFC).Methods: The glaucoma database of the Glasgow Royal Infirmary was reviewed retrospectively to identify patients ≥ 18 years of age with primary open-angle glaucoma or ocular hypertension in at least one eye who had been switched to LTFC from a previous monotherapy or combination therapy. Ninety patients were identified, and 59 (66%) had changed to LTFC from latanoprost monotherapy (LM). The analysis focused on this subgroup because few patients were changed from any other single therapy. At least one documented patient visit following the change to LTFC was required. The within-subject difference in IOP levels (IOP on LM–IOP on LTFC) was calculated for each case, and the statistical significance of the mean change in IOP was analysed using a 2-sided Student's paired t-test with a 0.05 α level.Results: The mean decrease in IOP after changing to LTFC from LM was 2.6 mmHg (95% confidence interval = 1.6, 3.6), from 21.4 (SD = 3.5) mmHg to 18.8 (SD = 4.2) mmHg (p = 0.002).Conclusions: LTFC provides significant incremental IOP reduction in patients with primary open-angle glaucoma or ocular hypertension who require additional IOP reduction following treatment with LM.

The objective of this study was to compare the effect on intraocular pressure (IOP) of latanoprost 0.005% once daily with timolol 0.5% twice daily in patients with open angle glaucoma or ocular hypertension. The study was designed as a single-centre, randomised, double-masked parallel-group comparison of latanoprost with timolol after 12 weeks of treatment. 60 patients with open angle glaucoma or ocular hypertension with IOP of at least 22 mm Hg were included. Administration of previous ocular hypotensive medication necessitated a wash-out period of 5 to 21 days before the start of the study treatment. The patients were randomised to treatment with latanoprost 0.005% once daily or timolol 0.5% twice daily. Mean diurnal IOP was measured at baseline and after 6 and 12 weeks of treatment. After 6 weeks of treatment, the diurnal IOP reduction (mean± standard error of the mean [SEM]) in the latanoprost group was 12.1±1.1 mm Hg (41%;p&lt;0.001; analysis of covariance [ANCOVA]) and 8.7 ± 1.1 mm Hg (30%; p &lt; 0.001; ANCOVA) in the timolol group. The difference of 3.4 ± 1.6 mm Hg was statistically significant in favour of latanoprost (p = 0.034; ANCOVA). A 30% reduction or more in mean diurnal IOP was achieved by 71 % of patients in the latanoprost group and by 34% of patients in the timolol group. After 12 weeks of treatment, the diurnal IOP reduction (mean± SEM) in the latanoprost group was 11.1±1.2 mm Hg (39%; p &lt; 0.001; ANCOVA) and 9.1 ± 1.1 mm Hg (32%; p &lt; 0.001; ANCOVA) in the timolol group. Most side effects observed were mild and transient and no serious adverse events were reported. Latanoprost 0.005% administered once daily in the evening was at least as effective as timolol 0.5% twice daily in reducing the mean diurnal IOP after 6 and 12 weeks of treatment. Both medications were well tolerated during the study period.

Diurnal Variation in Intraocular Pressure of Normal-tension Glaucoma Eyes

To compare the efficacy and tolerability of latanoprost or brimonidine in patients with elevated intraocular pressure (IOP). This prospective, randomized, masked-evaluator, parallel-group, multicenter study in the United States included patients with primary open angle glaucoma or ocular hypertension. Patients received latanoprost 0.005% once daily (8:00 AM; n = 152) or brimonidine tartrate 0.2% twice daily (8:00 AM and 8:00 PM; n = 151). Patients underwent evaluation at screening, baseline (randomization), and after 0.5, 3, and 6 months of treatment. IOP was measured at 8:00 AM, 10:00 AM, noon, and 4:00 PM at baseline and the months 3 and 6 visits, and at 8:00 AM only at week 2. The main outcome measure was the difference in diurnal IOP change from baseline to month 6 between treatment groups. Adverse events were recorded at each visit. Baseline mean diurnal IOP levels were similar between groups. At month 6, the adjusted mean (+/- SEM) diurnal IOP reduction was 5.7 +/- 0.3 mm Hg in the latanoprost group and 3.1 +/- 0.3 mm Hg in patients receiving brimonidine (P < 0.001). The mean difference in diurnal IOP reduction was 2.5 +/- 0.3 mm Hg (95% CI: 1.9, 3.2; P < 0.001). Five times more patients receiving brimonidine than latanoprost were withdrawn from the study due to adverse events. Latanoprost instilled once daily is more effective and better tolerated than brimonidine administered twice daily for the treatment of patients with glaucoma or ocular hypertension. During therapy, the range of daily fluctuation of IOP is less for latanoprost compared with brimonidine.

IntroductionNew open-angle glaucoma (OAG) and ocular hypertension (OHT) therapies that reduce treatment burden and improve outcomes relative to currently available agents are needed. Netarsudil, a novel Rho kinase inhibitor approved by the US Food and Drug Administration, reduces intraocular pressure (IOP) by increasing trabecular outflow. Two phase 3 superiority studies compared a fixed-dose combination (FDC) of netarsudil and the prostaglandin latanoprost with each active component for IOP-lowering efficacy.MethodsPooled efficacy and safety data were analyzed from MERCURY-1 and -2 studies in patients with OAG or OHT. Patients instilled one drop of netarsudil (0.02%)/latanoprost (0.005%) FDC (n = 483), netarsudil (0.02%, n = 499), or latanoprost (0.005%, n = 486) into each eye once-daily between 20:00 and 22:00. IOP was measured at 08:00, 10:00, and 16:00 at weeks 2, 6, and the primary endpoint at month 3.ResultsBaseline mean diurnal IOP was 23.6, 23.6, and 23.5 mmHg in netarsudil/latanoprost FDC, netarsudil, and latanoprost groups, respectively. Mean diurnal IOP in each group was 15.3, 18.1, and 17.5 mmHg at week 2, 15.7, 18.4, and 17.4 mmHg at week 6, and 15.8, 18.4, and 17.3 mmHg at week 12. The netarsudil/latanoprost FDC met criteria for superiority compared with each active component (p < 0.0001 for all nine time points). At month 3, among patients randomized to netarsudil/latanoprost FDC or latanoprost, 58.4% vs 37.3% (p < 0.0001) achieved IOP ≤ 16 mmHg. Among patients randomized to netarsudil/latanoprost FDC or netarsudil or latanoprost, 30.9% vs 5.9% (p < 0.0001) vs 8.5% (p < 0.0001) achieved at least a 40% reduction from baseline in mean diurnal IOP. Pooled safety results were consistent with individual MERCURY studies.ConclusionOnce-daily netarsudil/latanoprost FDC produced statistically significant and clinically relevant reductions in mean IOP that were statistically superior to IOP reductions achieved by netarsudil and latanoprost monotherapy. Results of the pooled efficacy and safety analyses were consistent with the individual studies.Trial registrationClinicalTrials.gov identifiers, NCT02558400 and NCT02674854.Electronic supplementary materialThe online version of this article (10.1007/s12325-020-01277-2) contains supplementary material, which is available to authorized users.

Individual Variability in the Diurnal Intraocular Pressure Curve