Dataset Information

Efficacy and tolerability of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure: a meta-analysis of randomized controlled trials.

ABSTRACT:

Objective

To evaluate the efficacy and tolerability of the fixed combination of Latanoprost/Timolol versus Dorzolamide/Timolol in the treatment of patients with elevated intraocular pressure (IOP).

Methods

A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify randomized clinical trials comparing latanoprost/timolol FC (FCLT) with dorzolamide/timolol (FCDT) in patients with elevated IOP. The efficacy estimates were measured by the weight mean difference (WMD) for the IOP reduction (IOPR) from baseline to end point, including the diurnal mean IOPR, 8 AM IOPR, 12 PM IOPR, and 4 PM IOPR. The tolerability estimates were measured by RR for adverse events. All outcomes were reported with a 95% confidence interval (CI). The data were synthesized by Stata 12.0 SE for Windows.

Results

Eight studies involving 841 patients (841 eyes) were included in the meta-analysis. With a WMD of IOPR in the diurnal mean of 0.16 mmHg (95% CI, -0.31 to 0.63), the FCLT was as effective as FCDT in lowering IOP in patients with elevated IOP (P = 0.51). The WMDs of IOPR were 0.58 mmHg (95% CI: -0.002 to 1.17) at 8 AM, -0.07 mmHg (95% CI: -0.50 to 0.36) at 12 PM, and 0.41 mmHg (95% CI: -0.18 to 1.00) at 4 PM, and there were no signi?cant difference between FCLT and FCDT. FCLT was associated with a significantly lower incidence of eye pain, bitter taste, and irritation/stinging than FCDT, with pooled RRs of 0.34 (95% CI: 0.14 to 0.82), 0.06 (95% CI:0.008 to 0.42), and 0.35 (95% CI: 0.14 to 0.85), respectively.

Conclusion

FCLT was associated with equivalent efficacy in IOP lowering comparing with FCDT. However, FCLT was better tolerated than FCDT.

SUBMITTER: He M

PROVIDER: S-EPMC3859645 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Efficacy and tolerability of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure: a meta-analysis of randomized controlled trials.

He Miao M Wang Wei W Huang Wenyong W

PloS one 20131211 12

<h4>Objective</h4>To evaluate the efficacy and tolerability of the fixed combination of Latanoprost/Timolol versus Dorzolamide/Timolol in the treatment of patients with elevated intraocular pressure (IOP).<h4>Methods</h4>A comprehensive literature meta-analysis was performed according to the Cochrane Collaboration methodology to identify randomized clinical trials comparing latanoprost/timolol FC (FCLT) with dorzolamide/timolol (FCDT) in patients with elevated IOP. The efficacy estimates were me ...[more]

PMID: 24349536

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Project description:BackgroudTo assess the noninferiority of a dorzolamide-timolol fixed combination (DTFC) versus latanoprost in terms of intraocular pressure (IOP) and to compare blood pressure (BP), ocular perfusion pressure (OPP) and diastolic ocular perfusion pressure (DOPP) between the latanoprost and DTFC groups in patients with normal-tension glaucoma (NTG).MethodsProspective, interventional, randomized, single-blinded, crossover design study. Patients with newly diagnosed NTG that had not been treated with a glaucoma medication in the most recent 2 months were recruited. In total, 44 patients with NTG were randomly allocated to one of two groups. Patients in group A were treated with DTFC, lubricant, and latanoprost for 4 weeks each, whereas patients in group B were treated with latanoprost, lubricant, and DTFC for 4 weeks each. Patients were examined on day 1 (without medication), week 4 (under medication), week 8 (without medication), and week 12 (under medication). At weeks 4 and 12, diurnal IOP, systolic and diastolic BP, and OPP were measured at 8:00 AM, 10:00 AM, 12:00 PM, 4:00 PM, and 8:00 PM.ResultsBaseline demographic characteristics showed no difference in terms of age, sex, central corneal thickness, spherical equivalent, or stage of glaucoma between the groups. The between-group difference was -0.19 ± 0.18 mmHg (mean ± SE, upper bound of one-sided 95% CI, 0.12). Diurnal IOP showed no difference between the groups with an average IOP reduction of 13.1% using latanoprost and 12.3% using DTFC. Diurnal systolic and diastolic BP were lower in the DTFC group than the latanoprost group; however, the difference between the groups was not statistically significant. Diurnal OPP and DOPP also showed no statistically significant difference between the groups.ConclusionsIOP lowering efficacy of DTFC was noninferior to that of latanoprost in newly diagnosed NTG patients. There was no difference in BP, OPP, or DOPP between the latanoprost and DTFC groups. This prospective, randomized, single-blinded, crossover study demonstrated the noninferiority of DTFC versus latanoprost in terms of IOP in patients with NTG.Trial registrationClinicalTrials.gov NCT01175902.

Project description:To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity.The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1-30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated.The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4-8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24-30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24-30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs.Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC.

Project description:BACKGROUND:Fixed-combination ocular hypotensives have multiple advantages, but triple-therapy dorzolamide/brimonidine/timolol (dorz/brim/tim) is only available in Latin and South America, and information on its relative efficacy is limited. This study compares the efficacy and tolerability of fixed-combination bimatoprost/timolol (bim/tim) and dorz/brim/tim in Mexican patients with primary open-angle glaucoma or ocular hypertension. METHODS:In this investigator-masked, crossover study, patients with unmet target intraocular pressure (IOP) on once-daily bim/tim or twice-daily dorz/brim/tim received the opposite medication for 3 months before returning to their pre-baseline medication for 3 months. IOP was evaluated before and after morning instillation at months 2, 3, 5 and 6. Primary endpoints were mean IOP change and Ocular Surface Disease Index© (OSDI) score at each visit. The intent-to-treat population was the a priori analysis population, but due to the number of discontinuations, the per-protocol and intent-to-treat populations were used for the primary efficacy and sensitivity analyses, respectively. RESULTS:Seventy-eight and 56 patients were included in the intent-to-treat and per-protocol populations, respectively. At month 3, statistically significant IOP reductions from baseline were observed in the bim/tim (P?<?0.01) and dorz/brim/tim (P?<?0.0001) groups, regardless of assessment time. At month 6, patients returned to bim/tim exhibited no significant IOP increase (regardless of assessment time), but patients returned to dorz/brim/tim exhibited a statistically significant IOP increase (P?<?0.001) when assessed before instillation of study treatment. Results were similar in both intent-to-treat and per-protocol analysis populations. In the per-protocol analysis, 70% of patients on bim/tim at month 3 had an IOP <14 mm Hg, which declined to 58% (P?=?0.0061) at month 6 (ie, after 3 months of dorz/brim/tim treatment). In patients receiving dorz/brim/tim at month 3, 38% had an IOP <14 mm Hg, which remained comparable after return to bim/tim. OSDI scores and incidence of adverse events were similar in both groups. CONCLUSIONS:In this first direct comparison of the efficacy of dorz/brim/tim and bim/tim, patients switched from dorz/brim/tim to bim/tim demonstrated improved/lower IOP; when returned to dorz/brim/tim, IOP increased to levels seen at study initiation, suggesting that once-daily bim/tim may have greater IOP-lowering efficacy. Both bim/tim and dorz/brim/tim were well tolerated with minimal ocular surface damage. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01737853 (registered October 9, 2012).

Project description:ObjectiveTo assess ocular discomfort upon instillation and patient preference for brinzolamide/timolol relative to dorzolamide/timolol, in patients with open-angle glaucoma or ocular hypertension.MethodsThis was a multicenter, prospective, patient-masked, randomized, crossover study. On day 0, patients received one drop of brinzolamide/timolol in one eye and one drop of dorzolamide/timolol in the contralateral eye. On day 1, patients were randomly assigned to receive one drop of either brinzolamide/timolol or dorzolamide/timolol in both eyes; on day 2, patients received one drop of the alternate treatment in both eyes. Measures included a patient preference question on day 2 (primary) and mean ocular discomfort scale scores on days 1 and 2 (secondary). Safety assessments included adverse events, visual acuity, and slit-lamp examinations.ResultsOf 120 patients who enrolled, 115 completed the study. Of these, 112 patients instilled both medications and expressed a study medication preference on day 2. A significantly greater percentage preferred brinzolamide/timolol to dorzolamide/timolol (67.0% versus 30.4%; P < 0.001). The ocular discomfort (expressed as mean [standard deviation]) with brinzolamide/timolol was significantly lower than with dorzolamide/timolol (day 2:1.9 [2.3] versus 3.7 [2.8], respectively [P = 0.0003]; both days combined: 2.1 [2.5] versus 3.5 [2.9], respectively [P = 0.00014]). On day 1, five patients receiving brinzolamide/timolol reported five nonserious adverse events (AEs): flu (n = 1), bitter taste (n = 2), and headache (n = 2). Four events, bitter taste (two events) and headache (two events), were considered related to brinzolamide/timolol. Events were mild in intensity, except bitter taste of moderate intensity reported by one patient. No AEs were reported at day 2. All AEs resolved without additional treatment. No clinically relevant changes from baseline were observed in best-corrected visual acuity or slit-lamp examinations of ocular signs.ConclusionPatients had less discomfort with brinzolamide/timolol than with dorzolamide/timolol, and more expressed a preference for brinzolamide/timolol. Both treatments were generally safe and well tolerated.

Project description:OBJECTIVE:To evaluate the additive intraocular pressure (IOP)-lowering efficacy and safety of fixed-combination brimonidine 0.2%/timolol 0.5% compared with timolol 0.5% at peak and trough effect when used as therapy adjunctive to latanoprost 0.005% in patients with glaucoma or ocular hypertension who require additional IOP lowering. METHODS:In this prospective, randomized, multicenter, investigator-masked, parallel-group study, patients were treated with latanoprost monotherapy for at least four weeks prior to baseline. At baseline on latanoprost, patients with IOP ?21 mmHg in at least one eye were randomized to twice-daily fixed brimonidine-timolol (n = 102) or timolol (n = 102), each adjunctive to latanoprost for 12 weeks. IOP was measured at 8 am and 10 am at baseline, week 6, and week 12 and evaluated in the per protocol population. The primary efficacy endpoint was peak IOP lowering at 10 am, week 12. Safety measures included adverse events. RESULTS:Baseline mean IOP was similar at 10 am in the treatment groups (brimonidine-timolol 23.4 mmHg; timolol 23.0 mmHg). The mean additional reduction from latanoprost-treated baseline IOP was 8.3 mmHg (35.5%) with fixed brimonidine-timolol and 6.2 mmHg (27.0%) with timolol at 10 am, week 12 (P < 0.001). Patients treated with fixed brimonidine-timolol adjunctive to latanoprost were significantly more likely than patients treated with adjunctive timolol to achieve an IOP <18 mmHg (P = 0.028) and a ?20% reduction in IOP from baseline (P = 0.047) at both 8 am and 10 am in week 12. Adverse events occurred in 14.7% of fixed brimonidine-timolol patients and 12.7% of timolol patients. Biomicroscopy findings were similar between the treatment groups after 12 weeks of treatment. CONCLUSION:Fixed-combination brimonidine-timolol reduced IOP significantly more effectively than timolol when used as adjunctive therapy to latanoprost in patients with glaucoma and ocular hypertension. Both fixed brimonidine-timolol and timolol were well tolerated as agents adjunctive to latanoprost.

Dataset Information

Efficacy and tolerability of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure: a meta-analysis of randomized controlled trials.

Objective

Methods

Results

Conclusion

Publications

Efficacy and tolerability of the fixed combinations latanoprost/timolol versus dorzolamide/timolol in patients with elevated intraocular pressure: a meta-analysis of randomized controlled trials.

Similar Datasets

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