Fixed-combination brimonidine-timolol versus latanoprost in glaucoma and ocular hypertension: a 12-week, randomized, comparison study.

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

A comparison of long-term intraocular pressure fluctuation in patients treated with bimatoprost or latanoprost.

PURPOSE: To evaluate long-term intraocular pressure (IOP) fluctuation in patients with glaucoma or ocular hypertension treated with bimatoprost or latanoprost. DESIGN: Post hoc analysis of prospectively collected data from a previously reported multicenter, investigator-masked, randomized clinical trial of bimatoprost and latanoprost. METHODS: Patients were treated bilaterally with bimatoprost (n = 133) or latanoprost (n = 136) for six months. IOP measurements were taken at 8 am, 12 pm, and 4 pm at baseline, week 1, and months 1, 3, and 6. Long-term IOP fluctuation during treatment was determined as the standard deviation (SD) of all 12 follow-up measurements. RESULTS: There was no significant between-group difference in short-term daily IOP fluctuation at baseline. Long-term IOP fluctuation over six months of treatment [mean SD (range SD)] was 1.9 (0.5 to 6.3) mm Hg with latanoprost vs 1.7 (0.5 to 3.9) mm Hg with bimatoprost (P = .050). Latanoprost-treated eyes were more likely than bimatoprost-treated eyes to have long-term IOP fluctuation of > or =3 mm Hg (7.8% vs 2.5% of eyes; P = .009). CONCLUSIONS: Bimatoprost-treated eyes demonstrated less long-term fluctuation in IOP compared with latanoprost-treated eyes in this six-month study. Additional studies are needed to confirm these findings and to determine their impact on glaucomatous progression.

Efficacy and safety of brimonidine and dorzolamide for intraocular pressure lowering in glaucoma and ocular hypertension.

BACKGROUND: Brimonidine and dorzolamide are intraocular pressure (IOP)-lowering medications most commonly used in second-line treatment of glaucoma and ocular hypertension. SCOPE: An evidence-based review of comparative clinical trials of brimonidine and dorzolamide was undertaken to determine the relative efficacy and safety of these drugs in reducing IOP. Using the keywords 'brimonidine' and 'dorzolamide', all articles describing such trials from September 1966 to July 2007 were found in MEDLINE and EMBASE. FINDINGS: In all identified studies, brimonidine and dorzolamide were both found to provide significant IOP reduction from treated or untreated baseline levels. Results of eight trials reported to date indicate that brimonidine produced either a lower treated IOP or greater pressure reduction from baseline than dorzolamide at one or more measured timepoints, and provided comparable IOP lowering over all other measurements. Differences between the IOP reductions provided by brimonidine and dorzolamide were more pronounced when the medications were used adjunctively with other classes of drugs. Six other trials showed similar efficacy, and one additional monotherapy study showed lower IOP with dorzolamide treatment. Ocular burning was noted with dorzolamide more than any other adverse event with either drug. Trials ranged widely in duration of therapy and the time of day IOP measurements were taken, and many were too small for sufficient statistical power. CONCLUSION: Brimonidine and dorzolamide are both efficacious and reasonably well tolerated. Possible overall distinctions in efficacy were obscured by differences in study designs and treatment regimens, but adjunctive therapy with brimonidine may reduce IOP as effectively or more effectively than adjunctive or fixed combination dorzolamide therapy. In certain patients with glaucoma and ocular hypertension brimonidine may be a better choice than dorzolamide for second-line treatment.

Central corneal thickness and glaucoma in aphakic and pseudophakic children.

BACKGROUND: The risk of glaucoma among aphakic children is as high as 32%, based primarily on intraocular pressure (IOP) measurements. Although IOP may be falsely elevated by increased central corneal thickness, central corneal thickness (CCT) values have not been reported in this population. METHODS: Patients from the practices of 2 pediatric ophthalmologists and 2 glaucoma specialists had measurements of CCT, IOP, and optic nerve cupping, with visual field analysis when possible. Normal fellow eyes of unilateral aphakes and pseudophakes were included as controls. RESULTS: In 36 aphakic and 6 pseudophakic eyes CCT averaged 660 microns compared with 576 microns for phakic fellow eyes (P < 0.0001). Glaucoma, defined by IOP at least 35 mm Hg or by IOP at least 22 mm Hg associated with optic nerve changes, occurred in 21% of 28 aphakic patients but in no pseudophakic patient. CONCLUSIONS: CCT in aphakic/pseudophakic children is substantially increased compared with control patients. These values may be important in interpreting IOP measurements in these children.

Bimatoprost versus latanoprost in lowering intraocular pressure in glaucoma and ocular hypertension: results from parallel-group comparison trials.

This review evaluated the clinical evidence of the comparative efficacy and safety of bimatoprost and latanoprost in lowering intraocular pressure (IOP) in patients with glaucoma and ocular hypertension. Four head-to-head, randomized, and controlled clinical trials of bimatoprost and latanoprost with treatment periods ranging from 1 to 6 months were identified from searches of the MEDLINE database through February 2004. According to a review and comparison of the results, bimatoprost, when compared with latanoprost, was associated with greater mean reductions in IOP, greater mean increases in the percentage of patients demonstrating target IOP, and greater response rates. The differences between drugs were not always statistically significant. Overall, the between-group differences in mean IOP ranged from 0 to 1.5 mm Hg. In 92% of the IOP measurements, the mean IOP was lower among patients given bimatoprost than among those given latanoprost; in the remaining 8%, the IOP reduction was equal. Transient, mild conjunctival hyperemia was the most frequently reported adverse effect associated with either drug, but it occurred more frequently with bimatoprost. Overall, both drugs were well tolerated. As a 1-mm Hg change in IOP has been shown to reduce the risk of progression in patients with glaucoma (according to the Early Manifest Glaucoma Trial), the greater efficacy demonstrated by bimatoprost in lowering IOP may be clinically significant.

Three-month comparison of brimonidine and latanoprost as adjunctive therapy in glaucoma and ocular hypertension patients uncontrolled on beta-blockers: tolerance and peak intraocular pressure lowering.

PURPOSE: To compare the tolerance and peak intraocular pressure (IOP)-lowering efficacy of brimonidine and latanoprost as adjunctive therapy in patients with ocular hypertension or glaucoma uncontrolled on beta-blockers. DESIGN: A prospective, multicenter, double-masked, parallel-design clinical trial. PARTICIPANTS: One hundred fifteen patients with IOP inadequately controlled on topical beta-blocker monotherapy. METHODS: Patients were randomly assigned to receive brimonidine, 0.2%, twice a day or latanoprost, 0.005%, every day as adjunctive therapy for 3 months. After 1 month of adjunctive treatment, patients who failed to meet a target 15% reduction in IOP at peak drug effect were crossed over to the other study medication. The target sample size of 51/group gave a power of 0.80 to detect a difference of 1 mmHg in mean IOP lowering between groups. MAIN OUTCOME MEASURES: The primary outcome variables were reduction in IOP from baseline at peak drug effect, response rate, and quality of life as measured using the Glaucoma Disability Index. RESULTS: Mean beta-blocker-treated baseline IOP was comparable between treatment groups (approximately 21.3 mm Hg). After 1 month of adjunctive therapy, brimonidine and latanoprost provided comparable IOP lowering (4.88 mmHg [22.8%] with brimonidine and 5.01 mmHg [23.5%] with latanoprost, P = 0.798). Response rates were similar in both groups, with 44 of 54 brimonidine patients and 43 of 53 latanoprost patients achieving the minimum target 15% IOP reduction at peak drug effect at month 1 (P = 0.963). Among patients who were successful at month 1 and continued on the initial study medication, mean IOP reductions were 4.55 mmHg with brimonidine and 5.49 mmHg with latanoprost (P = 0.149) at month 3. There was no significant difference in the ability of brimonidine and latanoprost to maintain at least a 15% additional reduction in IOP for 3 months (28 of 38 patients on brimonidine vs. 30 of 36 patients on latanoprost achieved > or =15% IOP reduction at month 3; P = 0.314). Patients in the latanoprost group were more likely to report negative quality-of-life variables than patients in the brimonidine group. Significantly more latanoprost patients reported watery or teary eyes (34 of 53, 64.2% vs. 23 of 54, 42.6% with brimonidine; P = 0.025) and hands and feet that became cold easily (24 of 53, 45.3% vs. 12 of 54, 22.2% with brimonidine; P = 0.012). CONCLUSIONS: As adjunct therapy with beta-blockers, brimonidine twice daily and latanoprost every day were comparable in lowering IOP at peak effect, but brimonidine was better tolerated, with fewer reports of adverse quality-of-life effects.