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.     

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.     

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.     

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.     

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.     

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.     

Efficacy and ocular surface tolerability of preservative-free tafluprost 0.0015%: a 6-month,single-blind,observational study on naïve ocular hypertension or glaucoma patients

Objectives: The aim of this study was to evaluate the safety of preservative-free tafluprost in newly diagnosed patients and to confirm its efficacy in lowering intraocular pressure (IOP).

Methods: Naïve patients were submitted to an ophthalmic examination, including ocular surface status and quality of life evaluation. All examinations were performed at baseline and after 1 and 6 months.

Results: 28 patients were enrolled and treated with tafluprost, once a day, in the evening. TF-BUT changed from 9 (interquartile range (IQR) 6 – 11) s at baseline to 10 (IQR 7 – 10) s at 1 month (p = 0.106) and 9 (IQR 6 – 12) s at 6 months (p = 0.003). No eye developed corneal staining. Quality of life was (median (IQR)) 91.6 (79.2 – 95.8) at baseline and 95.8 (66.7 – 100) at 6 months (p = 0.62). Only a few adverse events occurred during the follow-up period (three patients experienced ocular burning and one developed redness). The mean IOP reduction was 5.5 mm Hg (95% CI 3.8 – 7.2). The median (IQR) baseline IOP was 18.7 (15 – 23.7) mm Hg; 14 (13 – 16) mm Hg and 16 (14 – 16) mm Hg (p < 0.0001) after 1 and 6 months, respectively.

Conclusion: No patient developed ocular surface disease and quality of life perception was preserved. Preservative-free tafluprost is therefore an effective drug that is safe for the ocular surface after 6 months of daily therapy.     

Brinzolamide/timolol fixed combination: a new ocular suspension for the treatment of open-angle glaucoma and ocular hypertension

For the treatment of open-angle glaucoma, the most frequent cause of irreversible visual loss, fixed combinations of different topical intraocular pressure (IOP) lowering molecules have gained an important role in recent years. The use of fixed combinations reduces the number of daily instillations, which promotes adherence to the prescribed medication and diminishes the exposition of the ocular surface to preservatives. The fixed combination of brinzolamide and timolol was recently approved by the European Medicines Agency (EMEA) and is now available in several countries in Europe. It contains two molecules widely used to treat glaucoma: timolol 0.5% (5 mg/ml) and brinzolamide 1% (10 mg/ml) in ophthalmic suspension formulation. This fixed combination is approved for twice-daily instillation to reduce elevated IOP in open-angle glaucoma and ocular hypertension. The brinzolamide/timolol fixed combination provides an approximately 30 – 33% IOP reduction from the untreated baseline IOP of 25 – 27 mmHg; thus, it is more potent than either of its ingredients alone. It is similarly effective but better tolerated than the dorzolamide/timolol fixed combination, which consists of molecules from the same pharmacological classes. The brinzolamide/timolol fixed combination can be used by itself as a separate therapy, but owing to the additivity of its ingredients to IOP-lowering drugs belonging to other classes, it may also be administered adjunctive to other IOP-reducing molecules, most importantly topical prostaglandin analogues. The ocular and systemic tolerance of the brinzolamide/ timolol fixed combination was reported favorable in Phase III studies, but no long-term clinical experience with this preparation is available at present.     

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.     

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.     

Treatment of patients with primary open-angle glaucoma with a fixed combination of brimonidine 0.2%/timolol 0.5%: multicenter,open-label,observational study in Germany*

ABSTRACT

Objective: At the introduction of the fixed-combination of brimonidine/timolol in Germany in 2006, a non-interventional, multicenter, observational, open-label study was initiated to evaluate efficacy, tolerability, and safety of this preparation in a broad patient population.

Methods: The study population comprised patients with bilateral primary open-angle glaucoma or ocular hypertension with insufficient intraocular pressure (IOP) control who participating physicians determined required a change of medication, and who switched to exclusive use of the new fixed-combination brimonidine 0.2%/timolol 0.5%. Patient demographics and information on specific risk factors were collected. IOP readings were recorded for each eye at treated baseline (previous therapy), 4 to 6 weeks, and 12 weeks after changing to twice-daily brimonidine/timolol. Tolerability was measured using a four-step scale ranging from excellent to poor. All adverse events were recorded.

Results: Mean treated baseline IOP (±SD) for all patients (N?=?861) was 20.8?±?3.5?mmHg. Five hundred sixty-five patients switched from monotherapy, 138 patients switched from other fixed combinations, and 158 patients had been using non-fixed combinations of up to four different active agents. The brimonidine/timolol fixed combination provided an additional IOP decrease in most pretreatment subgroups, with an overall reduction to 16.9?±?2.6?mmHg after 4 to 6 weeks and to 16.5?±?2.7?mmHg after 12 weeks. Both of these values were significantly lower than baseline IOP (p?<?0.001). A target pressure of <18?mmHg was achieved in 79.5% of all eyes at week 12. Tolerability of fixed-combination brimonidine/timolol was rated excellent or good by the physicians for 97.1% of patients, and by 93.4% 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 brimonidine 0.2%/timolol 0.5% was effective, well tolerated, and safe in a broad POAG patient population.     

Topical dorzolamide 2%/timolol 0.5%: a review of its use in the treatment of open-angle glaucoma

The nonselective beta-blocker timolol and the carbonic anhydrase inhibitor dorzolamide both lower intraocular pressure (IOP). Timolol and dorzolamide have different mechanisms of action and their effects are additive when administered together. Therefore, the 2 drugs are frequently used concomitantly to treat patients with open-angle glaucoma who have not adequately responded to first-line therapy. A barrier to good compliance with concomitant therapy is the need to administer 5 or 6 drops of medication on 2 or 4 occasions during the day. Timolol 0.5% and dorzolamide 2.0% have therefore been combined in a single formulation, reducing the number of administrations required to 2 per day. Clinical trials in patients with glaucoma have demonstrated that dorzolamide 2%/timolol 0.5% (dorzolamide/timolol) is superior to monotherapy with the individual components. When dorzolamide/timolol administered twice daily was compared with concomitant treatment with dorzolamide 2% and timolol 0.5%, each administered twice daily for 90 days, both regimens resulted in marked lowering of trough IOP (measured just before the morning dose) compared with baseline (reduction in IOP = 4.2mm Hg). The effect of the 2 regimens on IOP at all time points, both before treatment and at peak effect (2 hours after treatment), were virtually indistinguishable. When the combined formulation was compared with a concomitant regimen that included dorzolamide 2% 3 times daily and timolol 0.5% twice daily the concomitant regimen was slightly more efficacious than the combined regimen at trough after 90 days: IOP was lowered by 3.6mm Hg in the combined group versus 4.1 mm Hg in the concomitant group. Dorzolamide/timolol has been compared with concomitant administration of timolol 0.5% and the IOP lowering miotic drug, pilocarpine 2.0%. This non-blind patient-preference study found that both regimens reduced IOP. However, the dorzolamide/timolol combination was preferred by the patients because of reduced frequency and severity of adverse effects and less frequent administration. Dorzolamide/timolol was well tolerated in clinical trials, the adverse effects reflected those of the individual components, and no additional tolerability issues were identified. However, the potential for timolol to cause cardiorespiratory effects must be considered when prescribing this combination. Furthermore, dorzolamide is a sulfonamide and can cause allergic reactions in those who are hypersensitive to this class of drug. CONCLUSIONS: Dorzolamide/timolol is a well tolerated and effective fixed combination for lowering IOP in the treatment of open-angle glaucoma and is likely to be useful in those patients who do not respond adequately to first-line monotherapy. Compared with concomitant therapy with the same 2 drugs the primary advantage is convenience, which may lead to improved compliance. Studies of compliance and comparisons with other currently available combination therapies would be useful to fully define the value of the formulation. Nonetheless, dorzolamide combined with timolol in a single applicator system will be a useful addition to the treatment options for glaucoma, a leading cause of preventable blindness.     

A comparative study on the efficacy, safety, and cost-effectiveness of bimatoprost/timolol and dorzolamide/timolol combinations in glaucoma patients

Aim:

This study was designed to compare the bimatoprost/timolol combination and dorzolamide/timolol combination in glaucoma for efficacy, safety, and cost-effectiveness in a local population of Trichy in the state of Tamilnadu.

Materials and Methods:

Eight-week, randomized, parallel group, open-label study was conducted on 48 patients of open angle glaucoma or ocular hypertension. After initial clinical assessment and baseline investigations, bimatoprost/timolol combination (Group A) was prescribed to 22 patients (2 patients lost after initial assessment) and dorzolamide/timolol combination (Group B) to 24 patients. The patients were reviewed after second and eighth weeks for cure rate and adverse drug reaction monitoring.

Results:

At the end of 8 weeks, the mean reduction in intraocular pressure from baseline was 13.04 mmHg (95% confidence interval (CI): 10.67–14.70) with bimatoprost/timolol combination once daily (P < 0.01) and 9.46 mmHg (95% CI: 7.47–10.5) with dorzolamide/timolol combination twice daily. Both the treatments were safe. Cost-effective range of bimatoprost/timolol combination was lower than that of dorzolamide/timolol combination.

Conclusion:

The fixed combination of bimatoprost/timolol was slightly more effective than that of dorzolamide/timolol combination in reducing IOP, and both treatments were generally well tolerated. Bimatoprost/timolol combination was more cost-effective (cost-effective analysis) than dorzolamide/timolol combination.     

Effect of 2% dorzolamide on retinal blood flow: a study on juvenile primary open-angle glaucoma patients already receiving 0.5% timolol

AIM: To investigate whether dorzolamide modifies peripapillary retinal haemodynamics in juvenile primary open-angle glaucoma (JPOAG) patients treated with timolol. METHODS: In 40 JPOAG subjects, before and after dorzolamide coadministration with timolol, the following examinations were achieved: intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), heart rate (HR), visual field and retinal flowmetry. RESULTS: Adjunctive therapy with dorzolamide induced the following modifications: IOP reduction [1.75 mmHg, 95% confidence interval (CI) 1.23, 2.26; P < 0.05], OPP increase (5.09 mmHg, 95% CI 2.97, 7.20; P < 0.02) and retinal blood flow improvement (35.0 arbitrary units, 95% CI 12.20, 57.80; P < 0.03). BP, HR and visual field indices did not change. CONCLUSIONS: Dorzolamide, in association or in fixed combination with timolol, significantly improves retinal blood flow in JPOAG patients.     

Intraocular pressure lowering effect of dorzolamide/timolol fixed combination in patients with glaucoma who were unresponsive to prostaglandin analogs/prostamides*

ABSTRACT

Objective: To evaluate the intraocular pressure lowering effect of the dorzolamide/timolol fixed combination (DTFC) in non-responder glaucoma patients to prostaglandin analogs/prostamides (prostas).

Patients and methods: All glaucoma patients treated with DTFC, between June 2003 and December 2005, who were unresponsive to prostaglandin analogs/prostamides, were identified through a retrospective medical records review. A non-responder was defined as an intraocular pressure (IOP) lowering effect less than 15% compared with baseline measurement. Two 12?hour IOP diurnal curves, measured between 8:00?a.m. and 8:00?p.m. (8:00?a.m., 10:00?a.m., 12:00?noon, 2:00?p.m., 4:00?p.m., 6:00?p.m. and 8:00?p.m.), were obtained retrospectively from the records of 31 patients, the first while on prostaglandin analogs/prostamides (baseline IOP) and the second while receiving DTFC (DTFC IOP). The study outcomes were the change in mean diurnal IOP and the reduction in IOP fluctuation as a result of receiving DTFC in patients unresponsive to prostas. The IOP was evaluated by intragroup comparisons with a two-tailed paired Student's t?test. A chi-square test was adopted for analysis of categorical variables.

Results: 31 patients were included in this retrospective study. DTFC significantly reduced IOP in the patients overall, from 25.4 (3.5) to 20.2 (1.0)?mmHg, p < 0.0001. The majority of patients were diagnosed with pseudoexfoliative glaucoma (PEX) (58%; 18/31). DTFC reduced the mean IOP fluctuations over 12 hours (highest minus lowest IOP reading within the 12?hours pressure curve) from 8.6 (3.2) to 4.3 (1.4)?mmHg, p < 0.0001. The most common adverse events were ocular burning (16%) and taste perversion (13%). There were no serious treatment-related adverse events.

Conclusion: DTFC significantly reduced the IOP in patients with glaucoma who did not respond to prostaglandin analogs/prostamides. Further research is needed to confirm these results.     

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.     

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.     

Efficacy and safety of tafluprost 0.0015% and timolol maleate 0.5% fixed combination in patients with ocular hypertension or open-angle glaucoma

Introduction: Lowering intraocular pressure (IOP) is at present the only therapeutic approach to the treatment of glaucoma proven to be successful. The choice of therapy must take into account efficacy, tolerability, safety, quality of life, adherence and cost. Monotherapy fails to achieve a satisfactory IOP reduction in 40 – 75% of glaucoma patients after > 2 years of therapy. So far, three prostaglandin/timolol maleate 0.5% fixed combinations (FCs) are available.

Areas covered: This review provides a background on the tafluprost–timolol FC (TTFC, Santen Oy) and its individual compounds. It summarizes the data on efficacy and safety, including comparative data with prostaglandin/timolol FCs already available.

Expert opinion: Tafluprost is a preservative-free prostaglandin analog with a similar IOP efficacy when compared with other prostaglandin analogs. However, its improved adverse effect profile seems to be beneficial in patients sensitive to preservatives. The preservative-free TTFC has no market authorization yet. Only one Phase III trial was published so far, but results are promising in terms of efficacy, tolerability and safety. It is likely that the TTFC will play a role in the treatment of open-angle glaucoma and ocular hypertension.     

From benzalkonium chloride-preserved Latanoprost to Polyquad-preserved Travoprost: a 6-month study on ocular surface safety and tolerability

Background: To evaluate the safety and tolerability of Polyquad-preserved Travoprost (PQ-Travoprost) in patients previously treated with benzalkonium chloride (BAK)-preserved Latanoprost.

Methods: Cohort 6-month study on open-angle glaucoma or ocular hypertension patients. Complete ophthalmic examination, intraocular pressure (IOP) measurement and ocular surface status (tear film break-up time [TF-BUT], corneal staining and ocular surface disease index [OSDI]) were evaluated at baseline and 6 months later.

Results: A total of 44 patients were enrolled. Median (interquartile range [IQR]) baseline IOP was 18 (15.5 – 21) and 16 (14 – 17) mmHg (p < 0.0001) after 6 months. At baseline, 18 (40.9%) patients presented an IOP of < 18 mmHg, 11 (25%) < 16 mmHg, 2 (4.3%) < 14 mmHg and 1 (2.3%) < 12 mmHg; 6 months later the proportions were 36 (81.8%) (p < 0.0001), 21 (47.7%) (p = 0.00075), 8 (18.2%) (p = 0.0143) and 6 (13.6%) (p = 0.0253). Concerning safety, TF-BUT improved from 8 [IQR 6 – 10] to 10 [IQR 8 – 12] s (p < 0.0001). No eye developed corneal staining; punctate keratitis was absent in 13 (29.5%) patients at baseline and in 31 (70.4%) after 6 months (p < 0.001). OSDI changed from 16 (10 – 30) to 9 (2 – 20).

Conclusions: No patient treated with PQ-Travoprost developed ocular surface disease after 6 months of monotherapy, whereas many patients reached a good IOP control with lower IOP values. Ocular surface status statistically improved when examined by TF-BUT and corneal staining.     

Topical dorzolamide 2%/timolol 0.5% ophthalmic solution: a review of its use in the treatment of glaucoma and ocular hypertension

Topically administered dorzolamide 2%/timolol 0.5% (dorzolamide/timolol ophthalmic solution; Cosopt) is a fixed combination of two ocular hypotensive drugs (the carbonic anhydrase inhibitor dorzolamide and the beta-adrenoceptor antagonist timolol) that have an additive effect on lowering intraocular pressure (IOP) when administered together. This product is indicated for the treatment of elevated IOP in patients with open-angle glaucoma or ocular hypertension (OH) who are insufficiently responsive to topical beta-adrenoceptor antagonist monotherapy. As such, it can be considered for use in individuals who, as a consequence of failing to achieve target IOP with beta-adrenoceptor antagonist monotherapy, require the addition or substitution of another class of topical antiglaucoma medication. Clinical trials have demonstrated that dorzolamide/timolol (1 drop per eye twice daily) is an effective and generally well tolerated fixed combination for lowering IOP in patients with open angle glaucoma or OH, including individuals uncontrolled on beta-adrenoceptor antagonist monotherapy. Compared with concomitant therapy with the individual components, the primary advantage of fixed combination dorzolamide/timolol is convenience.