Efficacy,tolerability and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% in a broad patient population: multicenter,open-label observational study*

ABSTRACT

Objective: To evaluate intraocular pressure (IOP)-lowering efficacy, tolerability, and safety of the fixed combination of bimatoprost 0.03% and timolol 0.5% (Ganfort^?) among German patients.

Methods: Multicenter, observational, open-label study of patients with primary open angle glaucoma or ocular hypertension (n?=?606). As determined by participating physicians, patients had insufficient IOP control and required a medication change. They were switched to once-daily fixed-combination bimatoprost/timolol with no wash-out period. IOP was recorded at treated baseline, 4–6 weeks and 12 weeks after switching. Tolerability was measured using a 4-step scale (excellent, good, moderate, poor) and all adverse events were recorded.

Results: A total of 405 patients switched from monotherapy, 97 switched from other fixed combinations, and 104 switched from non-fixed combinations. Among all patients, 32.5% had used prostaglandin analog (PGA) monotherapy, 8.7% had been using a fixed combination that included a PGA, and 6.9% had been using an adjunctive combination of a PGA and a β-blocker. Mean treated baseline IOP (±SD) for all patients was 20.7?±?3.5?mmHg. Overall, changing medication to fixed-combination bimatoprost/timolol lowered IOP to 16.6?±?2.7?mmHg (p?<?0.001 vs. baseline) after 4–6 weeks and to 16.1?±?2.6?mmHg (p?<?0.001) after 12 weeks; reductions of 19.8% and 22.2%, respectively. Combined bimatoprost/timolol provided an additional IOP reduction versus baseline in most subgroups based on prior treatment. At week 12, patients who had previously used a β-blocker achieved an additional 25.8% decrease from baseline and IOP was reduced by 22.6% in former PGA monotherapy patients. At week 12, 84.6% of all eyes reached a target pressure less than or equal to 18?mmHg. Tolerability of bimatoprost/timolol was rated excellent or good by the physicians for 98.7% of patients and by 96.7% of the patients themselves. Few adverse events occurred during the treatment period.

Conclusions: Although this study was limited by its observational design, our results show that the fixed combination of bimatoprost 0.03%/timolol 0.5% was effective, well tolerated, and safe in a broad patient population.     

Three-month,randomized, parallel-group comparison of brimonidine–timolol versus dorzolamide–timolol fixed-combination therapy

ABSTRACT

Objective: Fixed combinations of 0.2% brimonidine–0.5% timolol and 2% dorzolamide–0.5% timolol are used to lower intraocular pressure (IOP). The objective of this study was to evaluate the IOP-lowering efficacy and ocular tolerability of brimonidine–timolol compared with dorzolamide–timolol when used as monotherapy or as adjunctive therapy to a prostaglandin analog (PGA) in patients with glaucoma or ocular hypertension.

Study design and methods: Pooled data analysis of two randomized, investigator-masked, 3-month, parallel-group studies with identical protocols (ten sites). In all, 180 patients with open-angle glaucoma or ocular hypertension who were in need of lower IOP received topical brimonidine–timolol BID or dorzolamide–timolol BID as monotherapy (n?=?101) or as adjunctive therapy to a PGA (latanoprost, bimatoprost, or travoprost) (n?=?79).

Clinical trial registration: The studies are registered with the identifiers NCT00822081 and NCT00822055 at http://www.clinicaltrials.gov.

Main outcome measures: IOP was measured at 10 a.m. (peak effect) at baseline and at months 1 and 3. Tolerability/comfort was evaluated using a patient questionnaire.

Results: There were no statistically significant between-group differences in patient demographics. Most patients were Caucasian, and the mean age was 68 years. There were also no statistically significant differences between treatment groups in baseline IOP. At month 3, the mean (SD) reduction from baseline IOP for patients on fixed-combination monotherapy was 7.7 (4.2) mmHg (32.3%) with brimonidine–timolol versus 6.7 (5.0) mmHg (26.1%) with dorzolamide–timolol (p?=?0.040). The mean reduction from PGA-treated baseline IOP for patients on fixed-combination adjunctive therapy was 6.9 (4.8) mmHg (29.3%) with brimonidine–timolol versus 5.2 (3.7) mmHg (23.5%) with dorzolamide–timolol (p?=?0.213). Patients on brimonidine–timolol reported less burning (p?<?0.001), stinging (p?<?0.001), and unusual taste (p?<?0.001) than patients on dorzolamide–timolol.

Conclusions: Fixed-combination brimonidine–timolol provided the same or greater IOP lowering compared with fixed-combination dorzolamide–timolol. Both fixed-combination medications were safe and well-tolerated. Brimonidine–timolol received higher ratings of ocular comfort than dorzolamide–timolol. The duration of the studies was 3 months, and additional studies will be needed to compare the efficacy and tolerability of brimonidine–timolol and dorzolamide–timolol during long-term treatment.     

Intraocular pressure reduction with travoprost/timolol fixed combination,with and without adjunctive brinzolamide,in glaucoma

ABSTRACT

Objective: To investigate if combined intraocular pressure (IOP)-lowering medication with travoprost/timolol fixed combination and a carbonic anhydrase inhibitor, brinzolamide, is superior to both travoprost monotherapy and travoprost/timolol fixed-combination therapy in primary open-angle glaucoma and ocular hypertension.

Methods: Following a 4-week wash-out period and using 4-week long treatment periods, 20 primary open-angle glaucoma or ocular hypertension patients were treated with evening travoprost 0.004?%?, then switched to evening travoprost 0.004?%?/timolol 0.5?%?fixed combination, and finally the treatment was combined with adjunctive twice-daily brinzolamide 1?%?ophthalmic suspension. Both eyes were treated, but only one eye per patient (the eye with the higher mean diurnal IOP at baseline), was evaluated. IOP was measured at 8 a.m., 12 noon and 4 p.m. at baseline and at the end of each treatment period.

Results: Mean diurnal IOP (mean (SD)) at baseline was 28.5 (7.3) mmHg which decreased to 22.3 (6.3) mmHg on travoprost, 19.2 (3.4) mmHg on travoprost/timolol fixed combination and 17.3 (3.4) mmHg when the brinzolamide was added to the travoprost/timolol combination (ANOVA, contrast test, p?<?0.003 for all comparisons). The individual time point IOP values showed similar and significant stepwise differences.

Conclusion: Adjunctive brinzolamide medication provided further IOP decrease in patients receiving evening-dosed travoprost/timolol fixed combination. The travoprost/timolol fixed combination was significantly more effective in IOP reduction than travoprost monotherapy, which by itself induced a significant IOP decrease compared to the untreated baseline value. The results of this open label study suggest that combined therapy with travoprost/timolol fixed combination and brinzolamide is clinically useful for IOP-lowering in primary open-angle glaucoma and ocular hypertension.     

Brimonidine purite 0.1% versus brinzolamide 1% as adjunctive therapy to latanoprost in patients with glaucoma or ocular hypertension

ABSTRACT

Objective: To evaluate the efficacy and tolerability of brimonidine purite 0.1% in comparison to brinzolamide 1% when used as adjunctive therapy to latanoprost 0.005% in patients with glaucoma or ocular hypertension.

Methods: Randomized, single-center, investigator-masked, parallel-group clinical study. Patients with IOP?≥?18?mmHg while on once-daily latanoprost were randomized to adjunctive treatment with brimonidine purite TID (n?=?20) or brinzolamide TID (n?=?20) for 3 months. Intraocular pressure (IOP) was measured at 8 a.m., 10 a.m., and 4 p.m. at latanoprost-treated baseline and after 1 and 3 months of latanoprost and adjunctive therapy. A patient questionnaire was administered to evaluate the tolerability of eye drop instillation.

Results: Baseline mean diurnal IOP (± standard deviation, mmHg) on latanoprost was comparable between groups (brimonidine purite: 19.6?±?2.94; brinzolamide: 19.8?±?3.25; p = 0.846). Mean diurnal IOP at Month 3 was 16.3?±?2.63?mmHg with brimonidine purite and 17.8?±?2.19?mmHg with brinzolamide (?p = 0.028). Adjunctive use of brimonidine purite provided greater IOP lowering than brinzolamide at 10 a.m. (?p < 0.001) and 4 p.m. (?p = 0.050) and equivalent IOP lowering to brinzolamide at 8 a.m. (?p = 0.716). Blurred vision at Month 1 and bitter taste at Months 1 and 3 were more common upon instillation of brinzolamide eye drops.

Conclusion: Brimonidine purite 0.1% provided significantly lower IOP compared with brinzolamide 1% when used as adjunctive therapy to latanoprost. Both adjunctive therapies were well tolerated. Limitations of this study include the use of a single site and the sample size. Additional studies are needed to further evaluate these drugs as adjunctive therapy to prostaglandin analogs.     

Evaluation of the effects on choroidal thickness of bimatoprost 0.03% versus a brinzolamide 1.0%/timolol maleate 0.5% fixed combination

Objective: To investigate the effects of two different medical treatment options on choroidal thickness (CT) in cases of open-angle glaucoma (OAG).

Methods: Sixty-seven eyes newly diagnosed with OAG and 52 healthy eyes constituting the control group were included in the study. Glaucomatous eyes were randomly divided into two subgroups; Group I was started on bimatoprost 0.03% and Group II on a brinzolamide 1.0%/timolol maleate 0.5% fixed combination (BTFC). Intraocular pressure (IOP), ocular pulse amplitude (OPA) and subfoveal CT measurements were performed in all eyes in the study before treatment and on weeks 2, 4 and 8 after treatment.

Results: Mean initial IOP values in groups I and II and the control group were 25.5?±?4.7, 25.1?±?5.2 and 16.1?±?2.9?mmHg, mean OPA values were 3.7?±?1, 3.6?±?1.4 and 2.4?±?0.6?mmHg and mean CT values were 269.4?±?83, 264.5?±?84.4 and 320.1?±?56.6?μm, respectively. Eight weeks after treatment, mean IOP values in Groups I and II and the control group were 18.3?±?2.6, 18.1?±?3.4 and 15.7?±?2.9?mmHg, mean OPA values were 2.9?±?1.2, 2.8?±?1.5 and 2.3?±?0.8?mmHg and mean CT values were 290.2?±?87.3, 271.8?±?82.5 and 319.3?±?56.8?μm, respectively. No significant difference was determined in terms of the decrease in IOP and OPA obtained after treatment in Group I and Group II. However, a significant difference was observed between the two groups in terms of choroidal thickening after treatment.

Conclusion: The use of topical ocular hypotensive medication in eyes with OAG results in an increase in CT. This increase is relatively greater with bimatoprost 0.03% therapy compared to BTFC.     

From dorzolamide 2%/timolol 0.5% to brinzolamide 1%/timolol 0.5% fixed combination: a 6-month,multicenter, open-label tolerability switch study

Purpose: To assess ocular surface status and tolerability after switching glaucoma patients from dorzolamide/timolol to brinzolamide/timolol fixed combination (FC).

Methods: Six-month, multicenter, open-label, prospective study that switched 72 patients from dorzolamide/timolol to brinzolamide/timolol FC. Intraocular pressure (IOP), tear film break-up-time (TF-BUT), fluorescein staining and Glaucoma Symptom Scale (GSS) questionnaire were recorded at baseline and after 6 months.

Results: Median interquartile range (IQR) IOP was 16 (IQR 15 – 18) mmHg at baseline and 16 (15 – 17) mmHg and 6 months. TF-BUT significantly improved (p < 0.0001); the regression analysis found a negative association between TF-BUT changes and age at baseline and at month 6 (r = ?0.32; p = 0.0082 and r = ?0.31; p = 0.0085). Patients with no corneal fluorescein staining statistically increased after substitution (p = 0.04). Quality of life – as examined by the GSS symptoms (SYMP) score – statistically improved (p < 0.0001), revealing an association between GSS SYMP score and age [coefficient ?0.67, 95% confidence interval (CI) ?1.13 to ?0.21, p = 0.0005), superficial keratitis (coefficient ?8.26, 95% CI ?15.73 to ?0.80, p = 0.031) and TF-BUT (coefficient 4.94, 95% CI 1.71 to 8.17, p = 0.003).

Conclusion: Brinzolamide/timolol FC is associated with reduced topical discomfort and improved signs of ocular surface disease. The good tolerability and comfort of this FC might contribute to good patient adherence.     

Comparison of the efficacy and safety of travoprost with a fixed-combination of dorzolamide and timolol in patients with open-angle glaucoma or ocular hypertension

ABSTRACT

Purpose: The purpose of this study was to compare travoprost (TRAV; travoprost 0.004%) and the fixed-combination of dorzolamide/timolol (DTFC; dorzolamide 2.0%/timolol maleate 0.5%) ophthalmic solutions for reducing intraocular pressure (IOP) in patients with primary open-angle glaucoma (OAG) or ocular hypertension (OHT).

Methods: This was a randomized single masked, study with parallel controls. The TRAV group (n = 29) dosed once daily at 9:00 PM while the DTFC group (n = 27) dosed twice daily at 9:00 AM and 9:00 PM. IOP was measured at baseline, and following 3 weeks and 6 weeks of treatment at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM.

Results: Mean average IOP reductions from baseline during the course of the day were 7.5 (32.7%) and 7.1 (30.7%)?mmHg for TRAV and 4.8 (23.1%) and 4.5 (21.7%)?mmHg for DTFC at 3 weeks and 6 weeks, respectively. The greater IOP reduction for patients receiving TRAV was statistically significant at both the 3 and 6 week visits when averaged across all four time points (?p < 0.01). The two products were well-tolerated over the course of the 6 week study. Some factors such as taste perversion were reported more often in the DTFC group.

Conclusions: Travoprost monotherapy provided better efficacy in terms of IOP reduction and per-centage of IOP reduction compared to dorzolamide 2.0%/timolol maleate 0.5% fixed combination.     

Switching from concomitant latanoprost 0.005% and timolol 0.5% to a fixed combination of travoprost 0.004%/timolol 0.5% in patients with primary open-angle glaucoma and ocular hypertension: a 6-month,multicenter, cohort study

Purpose: To assess the usefulness and tolerability of systematically switching glaucoma patients from latanoprost 0.005% and timolol 0.5% (Lat + Tim) to a fixed combination of travoprost 0.004%/timolol 0.5% (TTFC), and to record the effects of this switch on tear-film break-up time (TBUT). Main outcome measures: Intraocular pressure (IOP) reduction, patients reaching IOP < 18 mmHg; the rate of discontinuation; TBUT; and the onset of adverse events (AEs). Methods: Multicenter, observational cohort, 6-month study: 309 patients on concomitant Lat + Tim were switched to TTFC (evening dosage). IOP, TBUT, and AEs were recorded at baseline and after 1 and 6 months. Results: IOP was significantly decreased (from 18.3 ± 2.9 to 16.6 ± 2.7 mmHg) after substitution (p < 0.0001). Many patients (82%) reached an IOP < 18 mmHg (p < 0.0001). TBUT improved significantly (from 8.4 ± 3.6 to 9.2 ± 3.8 s, p < 0.0001). A few patients reported AEs (8.7%), which caused discontinuation in a low percentage (4.5%). Conclusion: TTFC appeared useful in this selected population. In this study, patients who underwent a regimen modification to TTFC obtained further reduction in IOP with a lower exposition to preservative toxicity. The low discontinuation rate at 6 months indicates a good tolerability profile.     

Experience with Cosopt,the fixed combination of timolol and dorzolamide,after switch from free combination of timolol and dorzolamide,in Swiss ophthalmologists’ offices

SUMMARY

Purpose: To analyse a response to the therapy switch from the concomitant application of β-blocker and topical carbonic anhydrase inhibitor to the fixed combination of timolol and dorzolamide (Cosopt^*) in glaucoma/ocular hypertensive patients under everyday, office-practice conditions.

Patients and methods: The data source was a survey among practising ophthalmologists in Switzerland assessing their experience with glaucoma patients/ocular hypertensives put for the first time on the fixed combination of timolol and dorzolamide. A total of 98 patients underwent the therapy switch in at least one eye. The intraocular pressure (IOP) change between the baseline visit before switch to the timolol-dorzolamide fixed combination occurred, and the first follow-up control after the switch, served as an indicator of compliance.

Results: The IOP decreased on average from 19.43?±?5.64?mmHg to 17.97?±?3.58?mmHg (p?<?0.01). The time to the follow-up visit ranged from 4 to 354 days, and the magnitude of IOP change demonstrated a significant dependence on the time to the follow-up visit, also when corrected for baseline IOP level. A total of 87 (85.3%) continued on the timolol-dorzolamide fixed combination therapy after the first control visit. In 68 of these 98 patients the contralateral eyes underwent the same therapy switch, and their IOP followed an identical pattern of behaviour.

Conclusion: The average I OP decrease of 1.5?mmHg upon therapy switch to the timolol-dorzolamide fixed combination suggests a better efficacy due to improved compliance. Short-term compliance benefit seems to be more pronounced. The high timolol-dorzolamide fixed combination therapy continuation rate reflects an improvement in compliance and subjectively-perceived convenience.     

Preservative-free versus preserved brimonidine %0.15 preparations in the treatment of glaucoma and ocular hypertension: short term evaluation of efficacy,safety, and potential advantages

Abstract

Purpose: To compare the efficacy, safety, and potential advantages of the preservative-free versus preserved brimonidine %0.15 preparations in patients with primer open-angle glaucoma (POAG) or ocular hypertension (OHT).

Methods: Forty-two eyes of the 21 treatment-naive patients with POAG or OHT were enrolled in this study. Eyes were randomly assigned to receive brimonidine-purite 0.15% or preservative-free brimonidine 0.15% two times daily. Efficacy of the two eye drops was assessed by measuring the intraocular pressure (IOP) at 9–10 am at baseline and week 4. Safety and potential advantages of the drops were evaluated at weeks 4 in terms of ocular symptoms and tear parameters. Ocular symptom values of the patients were evaluated with a scale of 0–4 (0?=?no discomfort and 4?=?severe discomfort).

Results: Both of the brimonidine tartrate formulations resulted in statistically similar IOP reduction (preserved formulation; ?5.2?mmHg [22.9% reduction] preservative-free formulation; ?5.7?mmHg [24.1% reduction], p?=?0.37). It was found that brimonidine tartrate formulations with and without topical preservatives did not produce a statistically significant difference in pain, stinging, and blurred vision at the upon instillation (p?>?0.05). However, the burning sensation was significantly higher in the preservative-free formulation at the first instillation compared to the preserved formulation (p?=?0.01). Also, there was no statistically significant difference between the two formulations in terms of symptoms (itching, burning, tearing, stinging, and photophobia) and tear parameters during the day (p?>?0.05).

Conclusions: Although topical preservative-free brimonidine tartrate treated eyes had a more burning sensation at the first drop, the two formulations were similar in terms of ocular tolerability in the short term period. Also, both formulations were found to reduce IOP at a similar rate.     

Signs and symptoms of ocular surface status in glaucoma patients switched from timolol 0.5% to brinzolamide 1%/timolol 0.5% fixed combination: a 6-month efficacy and tolerability,multicenter, open-label prospective study

Purpose: To examine the impact of switching glaucoma patients from timolol 0.5% to brinzolamide 1%/timolol 0.5% fixed combination (Brinz/Tim FC) on quality of life and on ocular surface status; to assess efficacy after the switch.

Methods: 6-month, multicenter, open-label, prospective, switch study in 119 early to moderate glaucoma patients. Intraocular pressure (IOP), tear film break-up time (TF-BUT), fluorescein staining and Glaucoma Symptom Scale (GSS) questionnaire were recorded at baseline and after 6 months.

Results: Median (interquartile range) IOP significantly decreased from 20 to 16 mmHg, independent of sex and age. Most patients (95.8%) reached an IOP < 18 mmHg. TF-BUT improved, with a negative weak correlation to age at baseline and at 6 months. The percentage of patients with no fluorescein staining improved. The quality of life recorded by GSS also improved, being related both to age and corneal staining.

Conclusion: Brinz/Tim FC is effective and well tolerated. In this study, patients switched to Brinz/Tim FC obtained further reduction in IOP with no effects on ocular surface status and improved quality of life perception: a better quality of life could determine a better adherence to prescribed therapy.     

Concomitant administration of travoprost and brinzolamide versus fixed latanoprost/timolol combined therapy: three-month comparison of efficacy and safety

SUMMARY

Purpose: To compare the efficacy and safety of the concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily with those of a fixed combination of latanoprost 0.005%/timolol 0.5% once daily.

Research, design and methods: Forty-four patients with primary open-angle glaucoma or ocular hypertension with elevated IOP insufficiently responsive to monotherapy were randomly assigned to one of the two treatment groups: concomitant administration of travoprost 0.004% once daily and brinzolamide 0.1% twice daily (TB group: 22 patients) or latanoprost 0.005% plus timolol 0.5% once daily (LT group: 22 patients). Visits were undertaken at screening (current ocular hypotensive therapy was discontinued), baseline (randomization), and after 2 weeks, 1 month, 2 months and 3 months of therapy.

Main outcome measures: IOP was determined at 9 a.m., 12 p.m. and 4 p.m. at each study visit, and diurnal IOP was calculated as the mean of these recordings. Adverse events were recorded at each visit.

Results: IOP at the baseline visit was similar in both groups. Overall mean IOP was significantly lower in the TB as compared to the LT group after 1?month, 2?month and 3?month follow-up; only 9 a.m. measurements were significantly different, reaching a maximum difference (16.9 ± 0.9?mmHg vs 18.4 ± 1.8?mmHg, p < 0.001) at the 3?month check. The percentage of responders (IOP decrease ≥ 30%) was higher in the TB group. Both treatments were well tolerated and there were no cases of withdrawal from treatment.

Conclusions: Travoprost 0.004% and brinzolamide 0.1% concomitant therapy showed a greater efficacy than the fixed latanoprost 0.005%/timolol 0.5% combination in terms of absolute IOP decreases. Travoprost/brinzolamide therapy also offered the advantages of a greater percentage of responders.     

Changes in intraocular pressure following a switch from latanoprost monotherapy to latanoprost/timolol fixed combination therapy in patients with primary open-angle glaucoma or ocular hypertension: results from a clinical practice database

ABSTRACT

Aims: 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.     

24-hour control of intraocular pressure with 2% dorzolamide/0.5% timolol fixed-combination ophthalmic solution in open-angle glaucoma*

ABSTRACT

Objective: To evaluate the 24-hour efficacy and tolerability of 2% dorzolamide/0.5% timolol fixed combination (DTFC) solution in open-angle glaucoma and ocular hypertension.

Research design and methods: Randomized, parallel, doublemasked, multicenter study. Patients with insufficiently controlled intraocular pressure (IOP≥22 mmHg) were randomized to DTFC (N=117) or timolol (N=115). IOP was measured at baseline, 6 weeks, and 8 weeks, with measurements taken at 6 p.m., 8 p.m., 10 p.m., 2 a.m., 6 a.m., 8 a.m., 10 a.m., and 2 p.m.

Main outcome measures: Statistically significant change in IOP from untreated baseline for DTFC at all hours at week 8. Secondary outcome measures included: IOP-lowering at week 6 at all individual time points, change from baseline to 8 weeks in mean daytime IOP (average of 8 a.m., 10 a.m., 2 p.m., 6 p.m., and 8 p.m. IOPs) and night-time IOP (10 p.m., 2 a.m., 6 a.m.), and comparison of DTFC with timolol after 8 weeks.

Results: Patients receiving DTFC had a statistically significant and clinically relevant reduction in IOP at week 8 compared with baseline at all eight time points (p<0.001). Significant IOP reductions were also seen at all time points at week 6 (p<0.001). DTFC significantly lowered mean daytime IOP and night-time IOP (p<0.001 for both). Timolol alone also significantly reduced IOP from baseline at 8 weeks for all diurnal time points, and mean daytime and night-time IOP (p<0.001 for all). Compared with timolol alone, there were significantly greater reductions with DTFC at 10 a.m. (p=0.003) and 2 p.m. (p=0.016), and for mean daytime IOP (p=0.025) at 8 weeks. Significant between-treatment differences were not observed at other time points. Both treatments were well-tolerated, with no differences observed in the safety profiles between the treatment groups.

Conclusions: Both DTFC and timolol provided significant IOP reduction over the entire 24-hour measurement period. timolol during the daytime, but not at night. Although this study was not designed or powered to compare DTFC and timolol, DTFC exhibited greater IOP-lowering than timolol during the daytime, but not at night.

Trial registration: ClinicalTrials.gov identifier: NCT00108017.     

Comparison of allergy rates in glaucoma patients receiving brimonidine 0.2% monotherapy versus fixed-combination brimonidine 0.2%–timolol 0.5% therapy

ABSTRACT

Objective: To evaluate the incidence of ocular allergy in glaucoma patients prospectively treated with 0.2% brimonidine–0.5% timolol fixed combination (Combigan) compared with the incidence of ocular allergy in patients treated with 0.2% brimonidine (Alphagan?) monotherapy.

Study design and methods: This was a comparative, non-randomized, single-site, interventional study involving patients with primary open-angle glaucoma or exfoliation syndrome who had not previously used brimonidine in any formulation and had no history of ocular allergy. In one study arm, 102 patients were prospectively treated with twice-daily 0.2% brimonidine–0.5% timolol fixed combination. In the other study arm, medical charts at the same center were reviewed to identify a control group of 102 patients who had been treated with twice-daily 0.2% brimonidine monotherapy. Follow-up was at 1, 3, 6, 9, 12, 15, and 18 months of treatment.

Main outcome measure: Ocular allergy defined as the presence of follicles and redness severe enough to warrant discontinuation of the medication.

Results: The incidence of ocular allergy over 18 months of treatment was 8.8% (9/102) in the fixed-combination group compared with 17.6% (18/102) in the brimonidine group (?p?=?0.097). Kaplan–Meier survival analysis suggested that ocular allergy may be reduced or delayed in patients treated with the brimonidine–timolol fixed combination (?p?=?0.066).

Conclusions: The brimonidine–timolol fixed combination was associated with a 50% lower incidence in ocular allergy compared with 0.2% brimonidine monotherapy. This difference between treatments was not statistically significant (?p?=?0.097) but is likely to be clinically important. Additional studies are needed to evaluate the incidence of ocular allergy associated with brimonidine–timolol fixed combination treatment.     

Comparison of morning versus evening dosing and 24-h post-dose efficacy of travoprost compared with latanoprost in patients with open-angle glaucoma

ABSTRACT

Objective: To compare the IOP-lowering efficacy of a.m.-dosed travoprost and latanoprost at 24-h post-dose.

Research design and methods: Open-angle glaucoma patients not naïve to prostaglandin therapy and currently controlled on p.m.-dosed (2100) latanoprost (n?=?21) or travoprost (n?=?30) had baseline IOPs measured at 0900. In a randomized, single-masked, crossover design, patients received travoprost (Travatan) or latanoprost (Xalatan) at 0900 for 4?weeks, then were crossed over to receive the second prostaglandin for another 4?weeks. Treatment IOP was measured at 0900 prior to morning dose at both 4 and 8?week visits. Patient dosing preference (a.m./p.m.) was surveyed on exit.

Main outcome measure: Intraocular pressure (IOP).

Results: The mean IOP in the first period when all patients were dosed in the evening was assessed 12?h after dosing at 09:00 and it was similar in the two treatment groups (mean?±?standard deviation: 17.9?±?2.7?mmHg for travoprost versus 17.7?±?2.5?mmHg for latanoprost, p?=?0.812). In the a.m.-dosing crossover comparison, the 24-h post-dose IOP was significantly lower (?p?<?0.001) on travoprost (16.9?±?3.1?mmHg) compared to latanoprost (18.6?±?3.3?mmHg). In the exit survey, 51% of patients preferred a.m.-dosing.

Conclusions: a.m.-dosed travoprost is superior to a.m.-dosed latanoprost by 1.7?mmHg at 24-h post-dose.     

A comparison of the effects of 0.005% latanoprost and fixed combination dorzolamide/timolol on retrobulbar haemodynamics in previously untreated glaucoma patients

ABSTRACT

Objective:?To assess the effects of dorzolamide/timolol fixed combination (DTFC) and latanoprost 0.005% on the retrobulbar haemodynamics and intraocular pressure (IOP) of open-angle glaucoma patients.

Methods:?22 consecutive subjects with newly diagnosed, open-angle glaucoma were included in this prospective, examiner masked, randomized, crossover study. The patients were randomized into two different arms. Peak systolic velocity (PSV), end-diastolic velocity (EDV), Pourcelot's resistance index (RI) and intraocular pressure (IOP) were determined at baseline and after 1 month of medical treatment with DTFC or latanoprost 0.005% in both groups. A 4‐week washout period, without medical treatment, between study arms was carried out. Primary efficacy variables were the PSV, EDV and RI in the ophthalmic artery (OA) and short posterior ciliary artery (SPCA) and intraocular pressure (IOP). Inter- and intra-group comparisons were performed with a one-way ANOVA test and two-tailed paired Student's t-test respectively.

Results:?Intraocular pressure (IOP) and colour Doppler imaging (CDI) measurements were similar at baseline. Compared to baseline and washout measurements, only the fixed combination dorzolamide/timolol significantly increased the EDV in the OA and in the SPCA, p = 0.00012 and p = 0.00012, respectively and decreased the resistance index in the ophthalmic and short posterior ciliary arteries, p = 0.00011 and p = 0.00031, respectively. There were no statistically significant differences in the IOP lowering effect of either treatment.

Conclusion:?Over a treatment period of 1 month, only the fixed combination dorzolamide/timolol seems to have a vascular effect on retrobulbar vessels. Further research is necessary to confirm these results.     

Influence of switching to travoprost on intraocular pressure of uncontrolled chronic open-angle glaucoma patients compliant to previously-used topical medication

ABSTRACT

Objective: To investigate the influence of switching to travoprost on intraocular pressure (IOP) of chronic open-angle glaucoma (COAG) patients.

Research design and methods: Multicentre, open-label, non-comparative, 12‐week, phase IV study conducted at 10 academic and hospital centres in Hungary. Patients’ compliance to use of the pre-study medication was confirmed at a visit 10 days before the baseline measurements, and compliance was monitored throughout the study period.

Results: Of the 203 COAG patients three (1.48%) ceased travoprost medication due to ocular hyperaemia, and one subject was lost from follow-up. Self-reported compliance was optimal except for two patients. For the per-protocol analysis 197 patients were evaluable. IOP of the 37 per-protocol patients receiving additional travoprost medication decreased from 23.1 ± 3.2?mmHg (mean ± SD) to 17.3 ± 2.6?mmHg at week 12 (?p < 0.001). Switching the 121 per-protocol patients from latanoprost to travoprost IOP decrease from 20.8 ± 3.5?mmHg to 17.7 ± 2.4?mmHg (?p < 0.001). IOP of the 11 patients switched from topical non-selective beta-blockers to travoprost decreased from 20.1 ± 2.1?mmHg to 15.7 ± 1.5?mmHg (?p < 0.001). For the whole per-protocol population (n = 197) IOP decreased from 21.0 ± 3.4?mmHg to 17.4 ± 2.4?mmHg (?p < 0.001). Defining responders as having an IOP decrease > 2.0?mmHg or ≥ 5?mmHg at week 12, the responder rate was respectively 62.9% or 31% for the total study population; 86.5% or 54.1% when travoprost was added to the established therapy; 54.5% or 24.0% if latanoprost was switched to travoprost; and 90.9% or 36.4% for those who switched from beta-blockers.

Conclusion: Travoprost provided a clinically and statistically significant IOP decrease in uncontrolled COAG patients whose self-reported compliance to their previous topical medication was optimal. Our results suggest that the IOP reduction found after switching to travoprost is not explainable by improved compliance due to the clinical study situation.     

Fixed combinations of dorzolamide-timolol and brimonidine-timolol in the management of glaucoma

Importance of the field: The emergence of fixed-combination drugs for the treatment of glaucoma has, to some extent, changed the medical management of glaucoma. The potential benefits of these drugs include a reduction in the total number of drops and preservatives instilled per day and improved patient comfort factors, which may contribute to better compliance. Combination medications may also improve therapeutic efficacy and play an important role in controlling medication cost. However, the fixed dosing may be a disadvantage in some cases.

Area covered in this review: This review describes the composition, pharmacokinetics, mode of action, efficacy, side effects, and safety profile of fixed-combination dorzolamide–timolol and fixed-combination brimonidine–timolol.

What the reader will gain: Understanding of the pros, cons, and safety profile of two FDA approved fixed-combination antiglaucoma medication.

Take home message: Fixed-combination medications may be a reasonable adjunct to prostaglandins if a large drop in the intraocular pressure (IOP) is desired and adding only one medication is unlikely to reach the target IOP range. Both mentioned drugs are effective in reducing the IOP and further clinical studies will help identify differences in efficacy between the two. The clinician must make an individualized assessment of the medication's risk-benefit profile for each patient.     

Comparison of the efficacy and safety of travoprost with a fixed-combination of dorzolamide and timolol in patients with open-angle glaucoma or ocular hypertension

PURPOSE: The purpose of this study was to compare travoprost (TRAV; travoprost 0.004%) and the fixed-combination of dorzolamide/timolol (DTFC; dorzolamide 2.0%/timolol maleate 0.5%) ophthalmic solutions for reducing intraocular pressure (IOP) in patients with primary open-angle glaucoma (OAG) or ocular hypertension (OHT). METHODS: This was a randomized single masked, study with parallel controls. The TRAV group (n = 29) dosed once daily at 9:00 PM while the DTFC group (n = 27) dosed twice daily at 9:00 AM and 9:00 PM. IOP was measured at baseline, and following 3 weeks and 6 weeks of treatment at 8:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM. RESULTS: Mean average IOP reductions from baseline during the course of the day were 7.5 (32.7%) and 7.1 (30.7%) mmHg for TRAV and 4.8 (23.1%) and 4.5 (21.7%) mmHg for DTFC at 3 weeks and 6 weeks, respectively. The greater IOP reduction for patients receiving TRAV was statistically significant at both the 3 and 6 week visits when averaged across all four time points (p < 0.01). The two products were well-tolerated over the course of the 6 week study. Some factors such as taste perversion were reported more often in the DTFC group. CONCLUSIONS: Travoprost monotherapy provided better efficacy in terms of IOP reduction and percentage of IOP reduction compared to dorzolamide 2.0%/timolol maleate 0.5% fixed combination.