Mean Diurnal Intraocular Pressure Research Articles

Bimatoprost and Bimatoprost/Timolol Fixed Combination in Patients with Open-Angle Glaucoma and Ocular Hypertension

To investigate the intraocular pressure (IOP) lowering effect of bimatoprost (BIM) 0.03% and the potential additional effect of the BIM 0.03%/timolol 0.5% fixed combination (BTFC) in eyes with ocular hypertension, primary open-angle glaucoma, or exfoliation glaucoma. Following an appropriate washout period that varied with previous medication, participants with ocular hypertension, primary open-angle glaucoma, or exfoliation glaucoma were treated with evening-dosed BIM for 5 weeks. They were then given evening-dosed BTFC for another 5 weeks. One randomly selected eye was evaluated. Goldmann applanation tonometry was performed by the same investigator at 8 a.m., 12 noon, 4 p.m., and 8 p.m. at baseline and at the end of each treatment period. Thirty-three participants completed the study. Three patients discontinued because of local adverse effects during the BIM treatment period. The mean diurnal IOP (mean ± SD) at baseline, on BIM, and on BTFC were 24.8 ± 5.4, 17.3 ± 3.5, and 14.9 ± 3.1 mmHg, respectively (repeated measures analysis of variance, P < 0.001 for all pairwise comparisons). The individual time-point IOP values showed similar significant reductions. The percentage of IOP reduction from baseline was 30.2% for BIM and 39.9% for the BTFC. The mean ± SD diurnal fluctuation at baseline was 6.8 ± 3.2 mmHg, which decreased to 4.0 ± 3.1 and 2.9 ± 1.4 mmHg on BIM and BTFC, respectively (P < 0.05 for both treatments versus baseline). Both BIM 0.03% and the BTFC were effective in lowering IOP in eyes with ocular hypertension and open-angle glaucoma. However, the fixed combination provided an additional statistically significant reduction in IOP compared with BIM 0.03%.

Control of Intraocular Pressure and Fluctuation With Fixed-Combination Brimonidine–Timolol Versus Brimonidine or Timolol Monotherapy

To evaluate control of intraocular pressure (IOP) and IOP fluctuation in patients with ocular hypertension or glaucoma treated with fixed-combination brimonidine-timolol compared with brimonidine or timolol monotherapy. Post hoc analysis of data from 2 identical, 12-month, randomized, double-masked, multicenter trials. Patients were treated bilaterally with fixed brimonidine-timolol twice a day (n = 385), brimonidine tartrate 0.2% 3 times a day (n = 382), or timolol 0.5% twice a day (n = 392). Diurnal IOP was measured at follow-up visits at weeks 2 and 6 and months 3, 6, 9, and 12. IOP fluctuation was defined as the standard deviation of IOP measurements. The percentage of patients with mean diurnal IOP <18 mm Hg and short-term (daily) IOP fluctuation ≤2 mm Hg was statistically significantly higher in the brimonidine-timolol group than in the brimonidine or timolol group at each follow-up visit (at month 12, brimonidine-timolol 43.0%; brimonidine 18.9%, timolol 33.5%, P ≤ .017). At each hour (8 AM, 10 AM, 3 PM, and 5 PM), the percentage of patients with mean IOP <18 mm Hg and long-term (intervisit) IOP fluctuation ≤2 mm Hg was statistically significantly higher with brimonidine-timolol than with brimonidine or timolol alone (at 8 AM, brimonidine-timolol 41.0%, brimonidine 11.3%, timolol 23.7%, P < .001). Patients treated with fixed-combination brimonidine-timolol were more likely than patients treated with either brimonidine or timolol alone to achieve a combination of low mean IOP and low short-term (daily) or long-term (intervisit) IOP fluctuation.

Effects of brimonidine 0.2%-timolol 0.5% fixed-combination therapy for glaucoma

To evaluate the effects of brimonidine 0.2%-timolol 0.5% fixed-combination therapy in the treatment of patients with glaucoma. To measure the main treatment effects of a fixed combination of brimonidine 0.2%-timolol 0.5%, we conducted three small studies: (1) a comparison of diurnal intraocular pressure (IOP) at baseline and at 6 months after brimonidine/timolol fixed-combination therapy (n = 81); (2) an assessment of the effects of one drop of the brimonidine/timolol fixed combination on diurnal IOP (n = 25); and (3) the effects of brimonidine/timolol fixed-combination therapy on the anterior ocular segment over time (n = 64). (1) After 6 months of treatment with the brimonidine/timolol fixed combination, the mean diurnal IOP in primary open-angle glaucoma (POAG) decreased from 21.4 ± 2.0 to 14.5 ± 3.1 mmHg (32.2%, P < 0.001), and the mean diurnal IOP in normal-tension glaucoma (NTG) decreased from 13.5 ± 2.8 to 10.9 ± 2.0 mmHg (19.3%, P < 0.001). (2) After instillation with one drop of the brimonidine/timolol fixed combination, the IOP in the instilled eye was lowest at 9:00 p.m. and had decreased by 1.7 mmHg compared with the baseline IOP in the instilled eye. The difference in IOP between the instilled eye and untreated fellow eye was largest at 3:00 p.m., measuring 1.7 mmHg (P = 0.011). (3) Brimonidine/timolol fixed-combination therapy caused significant miosis over time (P = 0.003). The results of this study suggest that brimonidine/timolol fixed-combination therapy has beneficial IOP-lowering effects and significant effects on pupil size.

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

To evaluate the relationship between genetic polymorphisms of the adrenergic receptor (ADR) and diurnal intraocular pressure (IOP) in Japanese normal-tension glaucoma (NTG) patients. Prospective, comparative case series. Ninety-two untreated NTG patients. The IOP of both eyes was measured at 3-hour intervals from 0600 to 2400 hours over 2 consecutive days. We used IOP data from the eye with the greater visual field defect for statistical analysis. The mean IOP over 2 days was used for each time point. Genetic polymorphisms in α1A-, α2A-, α2B-, α2C-, β1-, β2-, and β3-ADR were determined mainly by direct DNA sequencing. The relationship between IOP and genetic polymorphisms was analyzed. The IOP and genotypes of genetic polymorphisms. Diurnal mean IOP of the subjects was 14.8 ± 2.1 mmHg (mean value ± standard deviation). For Del 301-303 in α2B-ADR, insertion/insertion (I/I) had a significantly higher diurnal mean IOP (P = 0.017), peak IOP (P = 0.038), and trough IOP (P = 0.046) than deletion (D) carriers. For Del 322-325 in α2C-ADR, I/I had a significantly lower diurnal mean IOP (P = 0.037) and peak IOP (P = 0.029) than D carriers. For S49G (A/G) in β1-ADR, A/A had a significantly higher diurnal mean IOP (P = 0.023), peak IOP (P = 0.019), and trough IOP (P = 0.014) than G carriers. For these 3 polymorphisms, repeated measures analysis of variance showed that the major homozygotes and minor carriers had parallel diurnal IOP curves, but significantly different diurnal IOP levels. Polymorphisms of the ADR gene may alter the untreated IOP level of patients with NTG.

A 12-Week, Randomized, Double-Masked Study of Fixed Combination Latanoprost/Timolol versus Latanoprost or Timolol Monotherapy

To evaluate the efficacy and safety of fixed combination latanoprost/timolol versus latanoprost or timolol monotherapy. This 12-week, randomized, double-masked study was designed to overcome potential shortcomings of previous trials. We enrolled 788 subjects with open-angle glaucoma or ocular hypertension treated with a beta-blocker for > or = 4 weeks before screening. After washout, 500 subjects with a baseline mean intraocular pressure (IOP) > or = 26 and < 37 mmHg were randomized to fixed combination latanoprost-timolol in the evening (n = 170), latanoprost monotherapy in the evening (n = 165), or timolol monotherapy in the morning (n = 165). At weeks 2, 6, and 12, each subject's IOP level was measured in triplicate at 8 AM (predose), 10 AM, and 4 PM in each eye. Adverse events were monitored throughout. The statistical superiority of the fixed combination for the 18 pairwise comparisons with the 2 monotherapies was evaluated (analysis of variance). RESULTS. The statistical superiority of the fixed combination was demonstrated at 7/9 time points versus latanoprost and 9/9 time points versus timolol. Mean diurnal IOP levels were similar at baseline but significantly lower with the fixed combination than with either monotherapy at weeks 6 and 12 (each p < 0.05). Patients treated with the fixed combination were significantly more likely than those treated with either monotherapy to reach prespecified percent IOP reductions at the upper thresholds and to achieve very low target diurnal IOP levels. All therapies were well tolerated. CONCLUSIONS. Fixed combination latanoprost/timolol safely reduces IOP levels in patients with glaucoma or ocular hypertension, though only slightly more than does latanoprost monotherapy.

Meta-analysis of the Efficacy and Safety of α2-Adrenergic Agonists, β-Adrenergic Antagonists, and Topical Carbonic Anhydrase Inhibitors With Prostaglandin Analogs

To perform a meta-analysis to estimate the intraocular pressure (IOP)-lowering efficacy and safety of alpha(2)-adrenergic agonists (AAs), beta-adrenergic antagonists (BBs), and topical carbonic anhydrase inhibitors (TCAIs) when used in combination with a prostaglandin analog (PGA). MEDLINE, Embase, and the Cochrane Controlled Trials Register were systematically searched for relevant articles in April 2009. Ten observer-masked randomized clinical trials that reported baseline IOP while receiving PGA monotherapy and follow-up IOP while receiving combination therapy were identified. The pooled IOP-lowering efficacy achieved with each class of adjunctive agent was calculated using random-effects models. The frequencies of adverse events were pooled across studies and compared using Fisher exact test. Mean diurnal IOP reduction achieved in all 3 groups was statistically similar (P = .22). At trough, IOP reduction was greater in the TCAI (P < .001) and BB (P < .001) groups than in the AA group. Peak IOP reduction was similar in the 3 groups (P = .66). Eye or eyelid pain or burning and xerostomia were significantly more common in the AA group. Fatigue, weakness, or dizziness was more common in the AA and BB groups compared with the TCAI group. Taste disturbance was significantly more common in the TCAI group. All 3 classes are similarly effective in lowering mean diurnal IOP when used in combination with PGAs. The AA class is statistically significantly less effective in reducing IOP at trough compared with BBs and TCAIs. The types of adverse events that were identified varied among the different classes of adjunctive therapies.

Influence of Selective Laser Trabeculoplasty on 24-Hour Diurnal Intraocular Pressure Fluctuation in Primary Open-Angle Glaucoma: A Pilot Study

To investigate the influence of selective laser trabeculoplasty on mean diurnal intraocular pressure (IOP) and diurnal IOP fluctuation in primary open-angle glaucoma. After washout from intraocular pressure-lowering drugs, a baseline diurnal IOP curve was obtained for 26 eyes of 13 patients before selective laser trabeculoplasty. The IOP curve was repeated at 3 and 6 months. In five eyes, office time (8:00 a.m. to 12:00 p.m.) IOP decreased by 20% or more. No similar decrease was seen in mean diurnal IOP in any case. IOP-lowering drugs were required for 11 eyes before the 3-month visit. Baseline diurnal IOP was higher for these eyes than for the others (P = .002). Compared with baseline values, a significant decrease was seen in mean IOP at the 6-month visit (P = .017) and in IOP fluctuation at both visits (P < .001 and P = .004, respectively) for the eyes without drug treatment. Although no eyes showed mean diurnal IOP reduction of 20% or more, selective laser trabeculoplasty resulted in a significant decrease in the amplitude of diurnal IOP fluctuation.

Comparison of ocular hypotensive actions of fixed combinations of brimonidine/timolol and dorzolamide/timolol

Objective:To compare brimonidine/timolol fixed combination (BrTFC; Combigan with dorzolamide/timolol fixed combination (DTFC; Cosopt in terms of ability to lower intraocular pressure (IOP) in primary open-angle glaucoma (POAG).Methods:This was a prospective, randomized, double-masked, crossover study. After 6 weeks of therapy with timolol maleate 0.5% twice daily, patients were randomized to BrTFC twice daily or DTFC twice daily for 6 weeks, before being crossed over to the other treatment arm for a further 6 weeks. At all follow-up visits, IOP was measured at 09.00 (pre-instillation) 12.00 and 16.00.The primary outcome measure was change in mean diurnal IOP from baseline at 6 weeks. The secondary outcome was percentage of patients with IOP <18 mmHg at 6 weeks. Data were analyzed from all patients who completed the study.Results:Twenty-five patients were randomized and 20 completed the study. Mean diurnal IOP (mean ± standard deviation [SD]) was 20.28 ± 2.03 mmHg at timolol-treated baseline. After 6 weeks, mean diurnal IOP was 16.28 ± 2.07 mmHg following BrTFC and 17.23 ± 2.29 mmHg following DTFC (difference: 0.95 mmHg, 95% CI 0.10–1.80, p = 0.03). Mean IOP at 09.00 was 20.95 ± 2.31 mmHg at baseline. This was reduced to 15.85 ± 2.56 mmHg following BrTFC and 17.55 ± 2.67 mmHg following DTFC (difference: 1.70, 95% CI 0.80–2.60, p = 0.001). For the 12.00 and 16.00 timepoints, the mean changes from baseline in the two arms were comparable. Percentages of patients achieving a target IOP of <18 mmHg were 85% following BrTFC and 60% following DTFC (p = NS [not significant]). No treatment-related adverse events were reported with either therapy. Key limitations include the small size of the study population and the 6-week duration of treatment periods, which prevents drawing conclusions regarding long-term therapy.Conclusion:Reductions from baseline in mean diurnal IOP and morning IOP were greater with BrTFC than with DTFC.

Fixed Combination of Latanoprost and Timolol vs Individual Components for Primary Open-Angle Glaucoma or Ocular Hypertension

To assess the efficacy and safety of fixed-combination latanoprost-timolol (FCLT) vs latanoprost or timolol monotherapy. This 12-week, randomized, double-masked, parallel-group study included patients with open-angle glaucoma or ocular hypertension treated with a beta-blocker and with baseline intraocular pressure (IOP) of 26 through 36 mm Hg. Following washout, eligible patients were randomized to once-daily FCLT in the evening, latanoprost in the evening, or timolol in the morning. Postbaseline IOP assessments at 8 am, 10 am, and 4 pm at weeks 2, 6, and 12; statistical superiority of FCLT for the 18 pairwise comparisons between FCLT and the 2 monotherapies, using analysis of variance. All therapies resulted in significant IOP reductions from baseline. Pairwise comparisons favored FCLT at all time points. When the 18 comparisons were tested simultaneously, FCLT was statistically superior to latanoprost at 7 of 9 time points and at all 9 time points when compared with timolol. In addition, FCLT was associated with greater percentage reductions in diurnal IOP levels and a greater likelihood of achieving lower mean diurnal IOP levels. Diurnal IOP reductions of 30% or more from baseline to week 12 were achieved by 73.5%, 57.5%, and 32.8% of those treated with FCLT, latanoprost, and timolol, respectively (P = .007 for FCLT vs timolol; P < .001 for FCLT vs latanoprost). All therapies were well tolerated. Fixed-combination latanoprost-timolol therapy is as safe and effective in lowering IOP in patients with either ocular hypertension or glaucoma as monotherapy with latanoprost or timolol. Combination therapy can be used to treat patients for whom monotherapy does not provide sufficient IOP reduction. The simplicity, efficacy, and tolerability of FCLT contribute to its utility in clinical practice. clinicaltrials.gov Identifier NCT00277498.

Diurnal IOP-lowering efficacy and safety of travoprost 0.004% compared with tafluprost 0.0015% in patients with primary open-angle glaucoma or ocular hypertension

Purpose:To compare the diurnal intraocular pressure (IOP)-lowering efficacy and safety of travoprost 0.004% and tafluprost 0.0015% administered to patients with primary open-angle glaucoma or ocular hypertension.Methods:This was a randomized, double-masked, active-controlled, crossover design trial, in which patients were randomized to either travoprost or tafluprost monotherapy administered once daily in the evening for six weeks and then crossed over to the alternative treatment for another six weeks. Diurnal IOP was measured (8 am to 8 pm, every two hours) and a solicited symptom survey was administered at the end of both six-week periods, as was conjunctival hyperemia and visual acuity assessment, slit-lamp biomicroscopy, and adverse event solicitation.Results:Fifty-one patients were randomized and 48 patients completed the study. The 12-hour mean diurnal IOP was significantly lower with travoprost therapy than with tafluprost therapy (P = 0.01), and a significantly lower IOP was also reported for travoprost at five of the seven individual time points (P < 0.05). Neither therapy produced a significant increase from baseline in any of the individual patient-reported symptom scores, except for hyperemia (P ≤ 0.01), which was increased with both treatments. Investigator-observed hyperemia was also increased from baseline with both therapies (P < 0.01), although the increase with travoprost therapy was significantly smaller than with tafluprost (P < 0.01). No additional safety concerns were noted from slit-lamp biomicroscopy or visual acuity results, and no difference was noted in patient-reported tolerability of the two medications.Conclusion:Travoprost 0.004% monotherapy produced lower diurnal IOP than tafluprost 0.0015% in patients with primary open-angle glaucoma or ocular hypertension and exhibited a similar safety profile.

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

To compare the effect of time on therapy, efficacy, tolerability and resource utilization of latanoprost or non-prostaglandin analogues (non-PGs) in patients who required a change in intraocular pressure (IOP)-lowering monotherapy. This open-label, multicentre study (Sweden, 19 sites; Finland, seven sites) included adults with glaucoma or ocular hypertension with mean diurnal IOP > or = 21 mmHg on ocular hypotensive monotherapy. Patients were randomized to latanoprost monotherapy or non-PG therapy (commercially available therapy other than a PG) and followed for 36 months. End-points included: time to treatment failure (baseline to visit with a change in/addition to treatment); diurnal IOP (mean of 08.00, 12.00 and 16:00 hr measurements) at months 6, 12, 24 and 36; tolerability; and resource utilization, where analyses used Swedish and Finnish 2006 unit costs. Three hundred and twenty-six patients received >or = 1 dose of latanoprost (n = 162) or non-PGs (n = 164). Median time to treatment failure was longer for latanoprost (36 months) than for non-PGs (12 months; p < 0.001); 51% and 24% of patients remained on randomized therapy after 36 months, respectively (p < 0.001). Decreases in mean diurnal IOP from baseline were significantly greater for latanoprost than for non-PGs at months 6 and 12 (p < 0.01). No serious adverse events were judged to be treatment-related. Mean total 36-month direct costs were similar in patients initiated with latanoprost and non-PGs. Patients who failed previous monotherapy remained on therapy longer when switched to latanoprost. Latanoprost's IOP-reducing effect and tolerability were sustained over the long term. Resource utilization and costs were generally similar in those initiating latanoprost or non-PG therapy.

Efficacy and safety of travoprost/timolol vs dorzolamide/timolol in patients with open-angle glaucoma or ocular hypertension

To compare the intraocular pressure- (IOP-) lowering efficacy of fixed combinations travoprost 0.004%/timolol 0.5% and dorzolamide 2%/timolol 0.5% in patients with ocular hypertension or open-angle glaucoma. In this prospective, multicenter, double-masked, randomized clinical trial, 319 qualifying patients received either travoprost/timolol once daily in the morning (n = 157) or dorzolamide/timolol twice daily (n = 162). IOP was assessed morning and evening at 2 and 6 weeks. The primary outcome measure was mean diurnal IOP. Baseline mean IOP values were similar between groups. Mean pooled diurnal IOP was significantly lower in the travoprost/timolol group (16.5 mmHg +/- 0.23) than in the dorzolamide/timolol group (17.3 mmHg +/- 0.23; P = 0.011). Mean IOP was significantly lower in the travoprost/timolol group compared to the dorzolamide/timolol group at the 9 AM time point both at Week 2 (P = 0.006) and Week 6 (P = 0.002). The travoprost/timolol combination produced mean IOP reductions from baseline of 35.3% to 38.5%, while the dorzolamide/timolol combination produced mean IOP reductions from baseline of 32.5% to 34.5%. The fixed combination travoprost 0.004%/timolol 0.5% dosed once daily in the morning demonstrated superior mean diurnal IOP-lowering efficacy compared to dorzolamide 2%/timolol 0.5% dosed twice daily in patients with ocular hypertension or open-angle glaucoma.

Diurnal Intraocular Pressure Fluctuation and Associated Risk Factors in Eyes with Angle Closure

To investigate diurnal intraocular pressure (IOP) fluctuation in eyes with angle closure in comparison with normal subjects and to look for associated risk factors for IOP fluctuation. Prospective, cross-sectional study. Ninety-eight eyes of 98 Asian subjects with angle closure (consisting of 32 primary angle-closure suspects [PACS], 34 subjects with primary angle closure [PAC], and 32 subjects with primary angle-closure glaucoma [PACG]) and 21 eyes of 21 normal control subjects. All angle-closure subjects were enrolled after laser peripheral iridotomy but before commencement of any medical or surgical treatment. Ophthalmic examination, including dynamic gonioscopy and automated perimetry, were performed, and diurnal IOP measurements were obtained using noncontact air-puff tonometry at hourly intervals between 8:00 am and 5:00 pm. Mean diurnal IOP, peak diurnal IOP, trough IOP, and IOP fluctuation (peak IOP-trough IOP) were compared between groups. Multiple linear regression analysis was performed to study the association of IOP fluctuation with clinical variables such as age, extent of peripheral anterior synechiae (PAS), central corneal thickness, vertical cup-to-disc ratio, and pattern standard deviation (PSD) on automated perimetry. Mean diurnal IOP, peak IOP, and IOP fluctuation. Most subjects were Chinese (89.1%) and female (61.3%). Intraocular pressure fluctuation was significantly higher in PACG (5.4+/-2.4 mmHg) and PAC (4.5+/-2.3 mmHg) subjects compared with PACS subjects (3.7+/-1.2 mmHg) and normal controls (3.8+/-1.1 mmHg; P = 0.005), with highest IOP found in the early morning. The combined PACG and PAC group had more than twice the risk (odds ratio, 2.38; 95% confidence interval, 1.1-5.1; P = 0.025) of having IOP fluctuation of more than 3 mmHg compared with the combined PACS and normal group. Extent of PAS (Pearson's correlation coefficient, r = 0.37; P = 0.0001) and visual field PSD (r = 0.34; P = 0.0002) were found to be associated with greater IOP fluctuation. The PACG and PAC eyes showed diurnal IOP fluctuation of 4 to 5 mmHg, and this fluctuation was higher than in PACS subjects and normal controls. The degree of PAS and visual field loss were associated with IOP fluctuation in PAC and PACG eyes.

A Comparison of Bimatoprost 0.03% Versus the Fixed-Combination of Latanoprost 0.005% and Timolol 0.5% in Adult Patients With Elevated Intraocular Pressure: An Eight-Week, Randomized, Open-Label Trial

Bimatoprost and the fixed combination of latanoprost with timolol maleate are 2 medications widely used to treat glaucoma and ocular hypertension (OHT). The aim of the study is to compare the efficacy of these 2 drugs in reducing intraocular pressure (IOP) after 8 weeks of treatment in patients with primary open angle glaucoma (POAG) or OHT. In this randomized, open-label trial, 44 patients with POAG or OHT were allocated to receive either bimatoprost (1 drop QD) or latanoprost/timolol (1 drop QD). Primary outcome was the mean diurnal IOP measurement at the 8th week, calculated as the mean IOP measurements taken at 8:00 am, 10:00 am, and 12:00 pm Secondary outcomes included the baseline change in IOP measured 3 times a day, after the water-drinking test (performed after the last IOP measurement), and the assessment of side effects of each therapy. The mean IOP levels of latanoprost/timolol (13.83, SD = 2.54) was significantly lower than of bimatoprost (16.16, SD = 3.28; P < 0.0001) at week 8. Also, the change in mean IOP values was significantly higher in the latanoprost/timolol group at 10:00 am (P = 0.013) and 12:00 pm (P = 0.01), but not at 8:00 am (P = ns). During the water-drinking test, there was no significant difference in IOP increase (absolute and percentage) between groups; however, there was a significant decrease in mean heart rate in the latanoprost/timolol group. Finally, no significant changes in blood pressure and lung spirometry were observed in either groups. The fixed combination of latanoprost/timolol was significantly superior to bimatoprost alone in reducing IOP in patients with POAG or OHT. Further studies with large sample sizes should be taken to support the superior efficacy of latanoprost/timolol, as well as to better assess its profile of side effects.

Efficacy and tolerability of bimatoprost versus travoprost in patients previously on latanoprost: a 3-month, randomised, masked-evaluator, multicentre study

Aim:To evaluate the efficacy and safety of replacing latanoprost with another prostaglandin analogue (PGA) in patients with glaucoma or ocular hypertension requiring additional intraocular pressure (IOP) lowering while on latanoprost.Methods:Prospective,...

Effects of brinzolamide vs timolol as an adjunctive medication to latanoprost on circadian intraocular pressure control in primary open-angle glaucoma Japanese patients

To study the effect of the concomitant use of brinzolamide and latanoprost on the 24-hour variation in intraocular pressure (IOP) in primary open-angle glaucoma (POAG) patients first treated with timolol and latanoprost. We studied 30 eyes from 30 POAG patients previously treated with latanoprost monotherapy. After a washout of four weeks in both eyes, all patients were treated with 0.5% timolol and latanoprost. Three months after the initiation of treatment with timolol and latanoprost, the 24-hour IOP variation was measured. Thereafter, all patients were treated with concomitant 1% brinzolamide and latanoprost. Three months after changing the therapeutic regimen, the 24-hour IOP variation was measured a second time. Latanoprost was administered once a day, and timolol and brinzolamide were twice a day. IOP was measured with a noncontact tomometer. On treatment with brinzolamide and latanoprost, a significant decrease in IOP compared to timolol and latanoprost was observed at all time points except at 3 PM and 6 PM. As a group, the patients had a significantly lower diurnal mean IOP and nocturnal mean IOP during treatment with brinzolamide and latanoprost than with timolol and latanoprost. Treatment of POAG with a combination of brinzolamide and latanoprost demonstrated improved hypotensive effects compared with timolol and latanoprost during a 24-hour period.

A 12-week Study Evaluating the Efficacy of Bimatoprost 0.03% in Patients with Pseudoexfoliative and Open-Angle Glaucoma

To evaluate the control of diurnal intraocular pressure (IOP) and the safety profile of bimatoprost in pseudoexfoliative glaucoma (PXG) compared to primary open angle glaucoma (POAG). A prospective, observer-masked, nonrandomized study was performed. Seventy consecutive patients with either POAG (35 eyes) or PXG (35 eyes) drug-naive for glaucoma were assigned to receive bimatoprost 0.03% once daily for 12 weeks. Diurnal IOP was measured at baseline and after 12 weeks at three time points (8 AM, noon, and 4 PM). Main outcomes were diurnal IOP control and achievement of target IOP (CIGTS criteria). Mean diurnal IOP, hour-by-hour IOP measurements, and safety, including serious adverse events, were also evaluated. A significant IOP reduction from baseline was found in both groups (p<0.001). Mean and hour-by-hour IOP differences between groups were not statistically significant (NS). The observed IOP values and percentages of IOP reduction were 17.0 mmHg (31.5%) and 16.4 mmHg (31.9%) in PXG and POAG eyes, respectively; the differences were not statistically significant. Six eyes (1 POAG and 5 PXG, respectively) responded with a <20% IOP reduction (NS). Twenty-seven POAG (77.1%) and 23 PXG (65.7%) eyes achieved target IOP. Consequently,20 eyes (8 POAG and 12 PXG, respectively) were classified as unable to achieve the IOP target values (NS). Bimatoprost was effective and safe in lowering IOP both in open angle and pseudoexfoliative glaucoma, achieving target pressure in most patients. However, long-term efficacy in PXG must be evaluated.

Efficacy and Tolerability of Latanoprost Compared to Dorzolamide Combined with Timolol in the Treatment of Patients with Elevated Intraocular Pressure: A Meta-Analysis of Randomized, Controlled Trials

The aim of this study was to evaluate the efficacy and tolerability of latanoprost, compared with the combination of dorzolamide and timolol, in the treatment of patients with elevated intraocular pressure (IOP). Pertinent randomized, controlled trials were identified through systematic searches of the Cochrane Library, PubMed, EMBASE, Chinese Biomedicine Database, and internet searches of meeting abstracts and the manufacturers' databases. The main efficacy measures were the IOP reduction (IOPR), including diurnal mean IOPR, and 10:00 IOPR. The main tolerability measure was withdrawal due to adverse events and individual adverse events. Fourteen (14) studies involving 2149 patients were included in the meta-analysis. Latanoprost was significantly more effective in lowering diurnal mean IOP than combined dorzolamide and timolol in patients with IOP insufficiently controlled by timolol alone, with a weighted mean difference (WMD) for the diurnal mean IOPR% of 3.12 (95% confidence interval, 0.47-5.78) at 3 months, and latanoprost was as effective as the combination of dorzolamide and timolol in patients without baseline timolol treatment. The combination of dorzolamide and timolol was associated with numerically greater reductions in 10:00 IOP, compared with latanoprost in patients with or without timolol treatment at baseline: only the result in patients with baseline timolol treatment at 1 month was statistically significant (WMD -4.14: range, -5.78 to -2.50). The combination of dorzolamide and timolol was less tolerated than latanoprost, with pooled relative risk for withdrawals due to adverse events being 0.34 (range, 0.13-0.84). Latanoprost was associated with significantly greater efficacy in lowering diurnal mean IOP than combined dorzolamide and timolol in patients with IOP insufficiently controlled by timolol alone, and latanoprost was as effective as combined dorzolamide and timolol in patients without baseline timolol treatment. The combination of dorzolamide and timolol was less tolerated than latanoprost.

Intraocular Pressure and Conjunctival Hyperaemia with Bimatoprost Every 48 Hours Versus Every 24 Hours

Purpose To evaluate the efficacy and tolerability of a reduced rate of bimatoprost administration. Methods Diurnal intraocular pressure (IOP) was recorded at 10 a.m., 2 p.m. and 6 p.m. in 40 eyes of twenty Caucasian patients (age range 56-75 years), with ocular hypertension or primary open angle glaucoma, at baseline and four weeks later. The right eye received daily bimatoprost, and in the left eye bimatoprost was administered every 48 hours at 8 p.m. Bulbar conjunctival hyperaemia was assessed by direct observation by a masked observer at baseline and at week 4 and was graded as none, minimal, mild, or moderate or severe (0 to 4). Results Baseline mean diurnal IOP in the right eye significantly ( P<0.001) decreased from 25.4±2.8 to 17.8±1.8 mmHg 14 to 22 hours after daily bimatoprost. Baseline mean diurnal IOP in the left eye significantly ( P<0.001) decreased from 25.2±2.0 to 19.0±1.7 mmHg 38 to 46 hours post-dose. The reduction in the right eye was significantly greater than in the left ( P=0.02). The average conjunctival hyperaemia after bimatoprost every 24 and 48 hours was graded as 2.4±1.0 and 1.8±0.8 respectively and this difference was significant ( P<0.01). Conclusion Bimatoprost every 48 hours was less effective than daily bimatoprost (24.6 vs. 30% IOP decrease), but caused less short term conjunctival hyperaemia. This off label dose schedule may be proposed to patients complaining of ocular redness especially in the first weeks of treatment.

An Eight-week, Multicentric, Randomized, Interventional, Open-label, Phase 4, Parallel Comparison of the Efficacy and Tolerability of the Fixed Combination of Timolol Maleate 0.5%/Brimonidine Tartrate 0.2% Versus Fixed Combination of Timolol Maleate 0.5%/Dorzolamide 2% in Patients With Elevated Intraocular Pressure

To compare the efficacy and tolerability of the fixed combination of timolol maleate 0.5%/brimonidine tartrate 0.2% versus fixed combination of timolol maleate 0.5%/dorzolamide 2% in patients with elevated intraocular pressure (IOP) over 8 weeks. This 8-week, multicentric, interventional, randomized, open-label, parallel group study was conducted at 4 centers in Brazil and 1 center in Argentina. Patients with open-angle glaucoma or ocular hypertension were randomized to receive bilaterally fixed combination of brimonidine/timolol maleate 0.5% or fixed combination of dorzolamide 2%/timolol 0.5% twice daily at 8:00 AM and 8:00 PM. A modified diurnal tension curve (8:00 AM, 10:30 AM, 02:00 PM, and 4:00 PM) followed by the water drinking test (WDT), which estimates IOP peak of diurnal tension curve, were performed in the baseline and week-8 visits. Adverse events data were recorded at each visit. A total of 210 patients were randomized (brimonidine/timolol, n=111; dorzolamide/timolol, n=99). Mean baseline IOP was 23.43+/-3.22 mm Hg and 23.43+/-4.06 mm Hg in the patients treated with brimonidine/timolol and dorzolamide/timolol, respectively (P=0.993). Mean diurnal IOP reduction after 8 weeks were 7.02+/-3.06 mm Hg and 6.91+/-3.67 mm Hg, respectively (P=0.811). The adjusted difference between groups (analysis of covariance) at week 8 was not statistically significant (P=0.847). Mean baseline WDT peak was 27.79+/-4.29 mm Hg in the brimonidine/timolol group and 27.68+/-5.46 mm Hg in the dorzolamide/timolol group. After 8 weeks of treatment, mean WDT peaks were 20.94+/-3.76 mm Hg (P<0.001) and 20.98+/-4.19 (P<0.001), respectively. The adjusted difference between groups (analysis of covariance) was not statistically significant (P=0.469). No statistical difference in terms of adverse events was found between groups. Both fixed combinations were capable of significantly reducing the mean diurnal IOP, mean diurnal peak, and mean WDT peak after 8 weeks of treatment. Also, both fixed combinations are well tolerated with few side effects.