The efficacy of brimonidine in preventing intraocular pressure elevation in the provocative test for primary angle-closure glaucoma.

The purpose of this study was to evaluate the efficacy of 0.2% brimonidine tartrate in preventing intraocular pressure (IOP) elevation in the dark-prone provocative test for primary angle-closure glaucoma (PACG). Twenty-two eyes from 22 patients with angle-closure glaucoma were enrolled in this study. Each of the selected eyes had previously tested positive in a recent dark-prone test. One drop of 0.2% brimonidine tartrate was then instilled in each eye 2 hours prior to a second dark-prone test. An IOP elevation of greater than 8 mmHg was regarded as a positive result. The IOP elevation in the first dark-prone test was 11.91 +/- 5.17 (range: 5.7 - 27.3) mmHg, while the IOP only increased 5.70 - 2.96 (range: 2.9 - 12.2) mmHg in the second dark-prone test that was pre-treated with 0.2% brimonidine tartrate (p < 0.001). A significant difference was also noted in the pre-test IOP (15.59 +/- 3.86 mmHg vs. 13.33 +/- 3.65 mmHg, p = 0.008) as well as in the post-test IOP (27.62 +/- 7.27 mmHg vs. 19.03 +/- 3.50 mmHg, p < 0.001) in the two sequential dark-prone tests. All but three of the initially positive dark-prone tests (86.46%) converted to negative tests after pre-treatment with brimonidine. There was a significant effect of 0.2% brimonidine tartrate in the prevention of IOP elevation in PACG patients previously found to test positive in the dark-prone provocative test.     

Long-term brimonidine therapy in glaucoma patients with apraclonidine allergy

PURPOSE: To report the use of brimonidine in patients with a documented ocular allergy to apraclonidine. METHODS: We conducted a prospective, open-label study on the use of long-term brimonidine therapy in 57 patients with chronic glaucoma with documented allergy to apraclonidine. The study patients were placed on brimonidine tartrate 0.2%, 1 drop three times daily in one or both eyes, either as additive therapy to a medical regimen devoid of apraclonidine for further lowering of intraocular pressure (25 patients) or as a replacement for apraclonidine at the time of diagnosis of apraclonidine ocular allergy for maintenance of intraocular pressure control (32 patients). Clinical symptoms and signs of ocular allergy to brimonidine were monitored for up to 18 months. RESULTS: During the treatment period of up to 18 months, six (10.5%) of 57 patients developed slit-lamp biomicroscopic findings and subjective symptoms of an ocular allergic reaction that led to discontinuation of brimonidine treatment. All six patients developed ocular allergy to topical brimonidine 0.2% during the first 4 months of therapy. The addition of brimonidine 0.2% topical medication or the replacement of apraclonidine with brimonidine resulted in a significant decrease in mean intraocular pressure from 20.5+/-5.3 to 16.5+/-4.2 mm Hg (P < .0001) at the mean treatment period of 10.6+/-4.6 months (range, 0.5 to 18.0 months in all 57 patients: 5 to 18 months in the 51 patients without brimonidine allergy and 0.5 to 3.8 months in the six patients who developed brimonidine allergy. CONCLUSIONS: The incidence of ocular allergy after the use of brimonidine 0.2% topical medication for up to 18 months was 10.5% in patients with a documented history of apraclonidine allergy. Therefore, it is generally safe as well as efficacious to administer brimonidine to patients with an ocular allergy to apraclonidine.     

Safety and efficacy of oral Triclofos in the ophthalmic evaluation of children with pediatric glaucoma: An observational study

Purpose:Oral Triclofos is widely used as a sedative agent in children. However, the role of Triclofos as a sedative agent in children undergoing ophthalmological procedures has not been adequately studied. The aim of this study was to determine the safety and efficacy of oral Triclofos in children suffering from pediatric glaucoma who were undergoing ocular examination.Methods:80 children aged less than 5 years were assessed for eligibility for the trial after taking hospital ethical committee approval. The children were administered 80 mg/kg of oral Triclofos and Ramsay sedation score was measured every 5 min starting from 20 min after administration of the drug. If the child was not adequately sedated after 30 min, additional dose of 05 mg/kg was administered every 5 min till 60 min of drug administration. The procedure was considered a failure and general anesthesia (GA) administered if Ramsay sedation score was ≤4 after 60 min of initial drug administration. Heart rate and arterial oxygen saturation were measured throughout the period of sedation. The duration of sedation and incidence of side effects was also noted.Results:A total of 73 patients underwent the study. The mean age of children was 23.4 months (SD – 14.72) and mean weight was 12 kg (SD – 3.84). The mean dose of Pedicloryl (Triclofos) used was 83.8 mg/kg and the median duration of onset was 25 min. 64 children completed examination successfully, 2 children had to be administered GA during the procedure. There were no major side effects.Conclusion:Administration of oral Triclofos in a dose of 80 mg/kg body weight was safe and effective in children less than 5 years of age undergoing ocular examination.     

A 3-month comparison of efficacy and safety of brimonidine-purite 0.15% and brimonidine 0.2% in patients with glaucoma or ocular hypertension.

PURPOSE: To compare the efficacy and safety of brimonidine Purite 0.15% (ALPHAGAN P) BID with brimonidine 0.2% (ALPHAGAN) BID in patients with glaucoma or ocular hypertension. METHODS: 3-month, multicenter, randomized, double-masked trial. Eligible patients were taking brimonidine 0.2% BID for at least 6 weeks prior to study entry and their intraocular pressure (IOP) was < or = 21 mm Hg. Patients were randomly assigned to receive either brimonidine Purite 0.15% BID (n = 203) or brimonidine 0.2% BID (n = 204). Scheduled visits were prestudy, baseline, and weeks 2, 6 and 12. IOP was measured at hour 0 and hour 2 to evaluate efficacy. Safety was measured by monitoring adverse events. Patient satisfaction and comfort were also evaluated at all visits. RESULTS: There was no statistically significant difference between the brimonidine 0.2% and brimonidine Purite 0.15% groups with respect to mean IOP at baseline. The IOP-lowering efficacy of brimonidine Purite 0.15% was equivalent to that of brimonidine 0.2% and both study treatments maintained IOP-lowering effects of brimonidine 0.2%. There were no significant between-group differences in mean IOP. The differences in the mean IOPs were < or = 0.26 mm Hg and the mean change from baseline IOP was < or = 0.35 mm Hg at all follow-up time points. There were no statistically significant differences between the two groups in the overall incidence of adverse events. The most commonly reported treatment-related adverse events were conjunctival hyperemia and allergic conjunctivitis: both were mild in severity. CONCLUSION: Brimonidine Purite 0.15% dosed BID provides equal IOP-lowering efficacy to brimonidine 0.2% BID. Patients previously controlled on brimonidine 0.2% can be successfully switched to brimonidine Purite 0.15%.     

Safety and efficacy of overnight orthokeratology in myopic children.

BACKGROUND: This prospective case series was conducted to describe the safety and efficacy of orthokeratology with the Emerald Contact Lens for Overnight Orthokeratology (Oprifocon A; Euclid Systems Corporation, Herndon, Virginia) among young myopes. METHODS: Twenty subjects (ages 10 to 16) were enrolled in the 6-month pilot study. Subjects were fit empirically with overnight orthokeratology lenses and evaluated at 1 day, 1 week, 1 month, 2 months, 3 months, and 6 months. RESULTS: Sixteen subjects completed the study. The mean baseline spherical equivalent refraction (SER) was -2.06 diopters (D) (+/-0.75). The mean SER at 6 months was -0.16 D (+/-0.38). The mean baseline uncorrected acuity was 0.78 (+/-0.28) logarithmic minimum angle of resolution (logMAR) equivalent (20/100 Snellen). The mean logMAR equivalent at 6 months was -0.03 +/- 0.12 (<20/20 Snellen). On average, 40% of eyes showed some type of corneal staining between the 1-week and 6-month visits. No serious adverse events occurred during the study. CONCLUSIONS: In contrast to previously published studies that reported maximum results at 2 weeks, subjects reached maximum reduction in myopia at the 1-week visit and, on average, obtained a 92.2% reduction in spherical equivalent refractive error at 6 months. This pilot study lends to a growing body of evidence that short-term correction of mild to moderate myopia with overnight orthokeratology is safe and efficacious in children and adolescents.     

Twenty-four hour efficacy with the dorzolamide/timolol-fixed combination compared with the brimonidine/timolol-fixed combination in primary open-angle glaucoma

Aim

The aim of this study is to compare the 24-hour efficacy of dorzolamide/timolol-fixed combination (DTFC) and brimonidine/timolol-fixed combination (BTFC) in primary open-angle glaucoma (POAG).

Methods

One eye each of 77 POAG patients was included in this prospective, observer-masked, crossover comparison. Following a 2-month timolol run-in period, patients had three intraocular pressure (IOP) measurements at 1000, 1200 and 1400 h while on timolol treatment. Patients showing at least a 20% IOP reduction on timolol were randomised to 3 months of therapy with DTFC or BTFC, and then were crossed over to the opposite therapy.

Results

Sixty POAG patients completed the study. The mean 24-hour IOP was significantly reduced with both the fixed combinations compared with the timolol-treated diurnal IOP (P<0.001). When the two fixed combinations were compared directly, DTFC demonstrated a lower mean 24-hour IOP level as compared with BTFC (mean difference: −0.7 mm Hg, 95% confidence interval (CI): (−1.0, −0.3), P<0.001). At two individual time points, DTFC significantly reduced IOP more than BTFC: at 1800 h (−1.0 mm Hg, 95% CI (−1.6,−0.5), P=0.001) and at 0200 (−0.9 mm Hg, 95% CI: (−1.4,−0.5), P=0.001). No significant difference existed for the other time points.

Conclusion

Both the fixed combinations significantly reduce 24-hour IOP in POAG. DTFC provided significantly better 24-hour efficacy.     

Comparison of the safety and efficacy of dorzolamide 2% and brimonidine 0.2% in patients with glaucoma or ocular hypertension

PURPOSE: To compare the intraocular pressure (IOP) reduction between dorzolamide 2% and brimonidine 0.2% in primary open-angle glaucoma (POAG) or ocular hypertension (OHT). METHODS: This study was a prospective, double-masked, randomized, crossover comparison of dorzolamide 2% (Trusopt) and brimonidine 0.2% (Alphagan), three times daily during two six-week study periods. The primary endpoint was mean change from baseline in trough IOP and secondary endpoints were mean change from baseline in IOP one and three hours after dosing. T-tests and a repeated-measures ANOVA were used to statistically evaluate the data. RESULTS: Of 43 patients enrolled, 41 completed the first treatment and 38 completed both treatments. Baseline IOP for dorzolamide was 24.3 mm Hg and brimonidine, 24.6 mm Hg (P = 0.9). Mean IOP reduction at trough was similar for both agents, 3.0 mm Hg (P = 0.96). Reductions at one and three hours were comparable (P = ns). Both agents were well tolerated with adverse events consistent with the package inserts. Dorzolamide was associated with more frequent stinging (P = 0.017) and burning (P < 0.001), while brimonidine was associated with more frequent dry eye (P = 0.04). CONCLUSIONS: Dorzolamide and brimonidine, as monotherapy, produced equivalent IOP-lowering efficacy at trough and at one and three hours after instillation, and both were well tolerated.     

Adherence with brimonidine in patients with glaucoma aware and not aware of electronic monitoring

Purpose: To assess the impact of open versus masked adherence monitoring on adherence with topical brimonidine using two different dosing schedules. Methods: Thirty‐seven patients with glaucoma or ocular hypertension were enroled in a prospective, observational cohort study. Patients were randomly assigned to open or masked adherence monitoring and to brimonidine twice daily (BID) or three times daily (TID). Patients received conventional brimonidine eye drops with attached electronic monitoring devices for 4 weeks with weekly intraocular pressure measurements. Adherence calculations comprised dosing intervals, adherence rate and time covered. Subgroup analysis with anova included the factors masking, regimen, diagnosis and age. Results: Among 36 individually analysed patients, 12 (33%) had adherence rates above 75%, therein two (5%)>90%. The mean adherence rate in 19 patients aware of adherence measurements was 70 ± 17% for brimonidine BID and 65 ± 14% for TID, not significantly different to the rates of 17 patients not informed about adherence measurements (77 ± 6% BID, 62 ± 9% TID, p = 0.24). On average, patients with brimonidine TID achieved significantly lower adherence rates (64 ± 12%) than patients on BID (73 ± 13%, p = 0.02). Still, patients on TID applied brimonidine more often (TID 1.9 ± 0.3, BID 1.5 ± 0.1 mean applications per day). The median coverage was 70% and showed no statistically significant difference between patients on BID and TID (p = 0.36). Conclusion: The study findings suggest that adherence measurements are not significantly altered by open adherence monitoring, which may simplify future adherence studies. Adherence with brimonidine eye drops was insufficient for most patients. These results demonstrate the necessity to develop new strategies to improve compliance in glaucoma therapy.     

Allergic reactions to brimonidine in patients treated for glaucoma

BACKGROUND: Allergic reactions to ophthalmic drugs have not been studied extensively in ophthalmology. We performed a study to estimate the incidence of allergy to brimonidine in patients treated for glaucoma. METHODS: We identified all patients in a private glaucoma practice who started therapy with brimonidine between Mar. 19, 1998, and Aug. 14, 1999. We recorded the patient's diagnosis, age, sex, concomitant glaucoma medication, previous allergy to glaucoma medication and allergy to brimonidine. Allergy was defined as allergic contact dermatoconjunctivitis or follicular conjunctivitis. RESULTS: Of the 140 patients identified, 36 (25.7%) had had an allergic reaction to brimonidine. Contact dermatoconjunctivitis was noted in 19 patients (52.8%) and follicular conjunctivitis in 18 (50.0%). The rate of development of those two manifestations was linear and almost parallel throughout the study period. In logistic regression analysis previous allergy to a topically given antiglaucoma medication (t = -5.13) and concurrent use of levobunolol (t = 3.46) were retained as the most probable predictor variables of allergy to brimonidine. Life-table analysis showed a fairly linear curve, with no peak in allergy rate. Allergic reactions occurred throughout the year, with a small peak in March. INTERPRETATION: We found a rate of allergy to brimonidine of 25.7%. Concomitant levobunolol use and allergy to another glaucoma medication were associated with a higher allergy rate.     

Effect of brimonidine tartrate on basophil activation in glaucoma patients

AIM: To evaluate the mechanism of which brimonidine tartrate 0.15% causes clinical hypersensitivity. METHODS: A prospective case-control study comparing 8 glaucoma patients with clinical hypersensitivity to brimonidine to a control group consisting 13 healthy volunteers. Blood samples were stimulated with brimonidine 0.15%, timolol 0.5% or brimonidine tartrate/timolol maleate 0.2%/0.5%. Premixed antibodies (CD63/FITC and aIgE/PE) were added for direct staining and whole-blood samples were lysed, fixed and analyzed by a flow cytometer. The basophil population was defined by high IgE cell expression. Degranulation was identified by the expression of the activation molecule CD63. RESULTS: Basophil activation was not significant when comparing percent of activated basophils of patients and healthy controls after exposure to brimonidine (2.58%, 2.45%, respectively, P=0.72). There was a significant suppression of basophil activation when a combination of brimonidine-timolol (0.87%) was compared to timolol (2.27%; P=0.012) and to brimonidine alone (2.58%; P=0.017). CONCLUSION: The results of our study do not support the hypothesis that brimonidine induces an immediate allergic reaction. Basophil activation was suppressed by the presence of β-blockers in patients hypersensitive to brimonidine and in healthy individuals. This finding indicates that timolol suppress brimonidine drug reaction by a different mechanism.     

Twelve-month evaluation of brimonidine-purite versus brimonidine in patients with glaucoma or ocular hypertension

PURPOSE: To compare the efficacy and safety of brimonidine-Purite (Alphagan; Allergan, Irvine, CA) 0.15% and 0.2% three times daily with brimonidine (Alphagan) 0.2% three times daily in patients with glaucoma or ocular hypertension. PATIENTS AND METHODS: In this 12-month, randomized, multicenter, double-masked, parallel-group study, patients were randomly assigned to receive brimonidine-Purite 0.15% (n = 381), brimonidine-Purite 0.2% (n = 383), or brimonidine 0.2% (n = 383) three times daily. Visits were conducted before the study, at baseline, at weeks 2 and 6, and at months 3, 6, 9, and 12. Diurnal intraocular pressure was measured at 8 am, 10 am, 3 pm, and 5 pm at baseline, week 6, and at months 3, 6, and 12. Intraocular pressure was also measured at 8 and 10 am at week 2 and month 9. Safety was evaluated by adverse events and other ocular and systemic measures. RESULTS: At baseline, mean intraocular pressure was similar in the three treatment groups. During follow-up, there were no statistically significant among-group differences in mean intraocular pressure or mean changes from baseline intraocular pressure (at peak or trough). The difference in mean intraocular pressure between the brimonidine-Purite-0.15% and brimonidine-0.2% treatment group was less than 1 mm Hg at all time points. The relative percent difference in allergic conjunctivitis was 41% lower in the brimonidine-Purite 0.15% group compared with the brimonidine 0.2% group. The comfort and satisfaction rating significantly favored brimonidine-Purite 0.15%. CONCLUSIONS: Over 12-months, brimonidine-Purite 0.15% and 0.2% provided intraocular pressure lowering comparable with brimonidine 0.2% in patients with glaucoma or ocular hypertension. Brimonidine-Purite 0.15% showed the most favorable safety and tolerability profile with a reduced incidence of allergic conjunctivitis and better satisfaction and comfort rating.     

The short-term effect of adding brimonidine 0.2% to timolol treatment in patients with open-angle glaucoma.

Brimonidine, a highly selective alpha(2)-adrenoceptor agonist, was studied to determine its ocular hypotensive effect and side effects in patients with elevated intraocular pressure (IOP) while on continuing therapy with timolol. This was a prospective, randomized, placebo-controlled study in 15 patients with primary open-angle or pseudoexfoliation glaucoma on therapy receiving timolol 0.5% twice daily, with IOP greater than or equal to 22 mm Hg in one eye. IOP measurements, blood pressure and pulse rate were assessed on 2 days at a baseline and 1, 2, 4, 6 and 8 h later. A single drop of brimonidine 0.2% or placebo was added to treatment with timolol. The reductions in IOP at all time intervals observed with brimonidine + timolol were significantly greater than those with timolol + placebo. The maximum mean net decrease in IOP was 19.23 +/- 10.60% at 4 h. Statistically significant decreases in systemic blood pressure and pulse rate without clinical symptoms were observed in the group receiving brimonidine + timolol. This study suggests that a combination of brimonidine and timolol may have potential in the treatment of glaucoma. Further clinical trials with brimonidine are indicated to assess its further role as adjunctive agent.     

Meta-analysis of randomized controlled trials comparing timolol with brimonidine in the treatment of glaucoma

This paper aims to compare the efficacy and tolerability of timolol versus brimonidine in the treatment of glaucoma. Comprehensive searches were performed using Medline, Embase and the Cochrane Controlled Trials Register for randomized controlled trials comparing timolol and brimonidine. Two reviewers independently assessed trials for eligibility and quality and extracted data. A random effects model was used to combine studies. Outcome was defined as the absolute mean intraocular pressure (IOP) reduction from baseline to end-point for efficacy, and relative risk (RR) for adverse events. Subgroup analysis and meta-regression were used to explore heterogeneity according to trial design and quality. Ten publications reporting on eight trials with 2387 participants were included in the meta-analysis. Two further trials were commented on qualitatively. IOP reduction was not significantly different between timolol and brimonidine. Weighted mean difference (WMD) of IOP reduction was 0.24 mmHg (favouring brimonidine) with a 95% confidence interval of -0.57 to 1.04 mmHg. There was significant heterogeneity between studies (chi(2) (13) = 73.75, P < 0.00001, I(2) = 91%). Subgroup analysis showed no significant WMD for studies where data were analysed from end-points >/=6 months or <6 months. Meta-regression analysis showed increased WMD IOP reduction in favour of brimonidine with increased trial quality (t(3) = -4.58, P = 0.01), but no significant association with trial duration (t(3) = 0.73, P = 0.51) or size (t(3) = -0.59, P = 0.57). The RR of ocular allergy was much lower with timolol than brimonidine (RR = 0.08, 95% confidence interval 0.01 to 0.47). Publication bias was not evident on a funnel plot, although the number of studies was small. The conclusion is that both drugs are equally effective in lowering IOP. Brimonidine is associated with a higher rate of allergy.     

Comparison of the efficacy and safety of dorzolamide 2% when added to brimonidine 0.2% or timolol maleate 0.5% in patients with primary open-angle glaucoma.

OBJECTIVE: To determine the ocular hypotensive efficacy and safety of dorzolamide when added to brimonidine or timolol in patients with uncontrolled primary open-angle glaucoma (POAG). PATIENTS AND METHODS: This is a 1-year prospective open-label clinical trial of 48 consecutive POAG patients with inadequate intraocular pressure (IOP) control while using brimonidine 0.2% (23 patients) and timolol 0.5% (25 patients), 2 times daily. Patients were assigned to receive dorzolamide 2% as adjunctive therapy, added 3 times daily to brimonidine or timolol. IOP was measured on week 2, and months 3, 6, 9, and 12. RESULTS: A significant reduction in IOP from the baseline was observed after dorzolamide use in both groups at visits during that year (P < 0.001). Overall, mean IOP reduction was 5.6 +/- 1.9 mmHg with the brimonidine-dorzolamide combination, and 6.8 +/- 1.7 mmHg with timolol-dorzolamide after 1 year of treatment; the difference was significant (P = 0.029). No statistical differences existed between the groups for adverse events (P < 0.05). CONCLUSION: The addition of dorzolamide to brimonidine or timolol has significant IOP-lowering efficacy during 1 year in patients with POAG whose IOPs were inadequately controlled with brimonidine or timolol alone. The IOP-lowering effect of the timolol-dorzolamide combination at 1 year was more pronounced than brimonidine-dorzolamide. Both combinations were well-tolerated by the patients.     

Safety and efficacy of combined trabeculectomy for primary angle closure glaucoma with persistent ocular hypertension

Purpose:To investigate the safety and efficacy of combined trabeculectomy for primary acute angle closure glaucoma with persistent ocular hypertension.Methods:A total of 36 patients (40 eyes) with primary acute angle closure glaucoma,who were treated with combined trabeculectomy in the Ophthalmology Unit of our hospital,were selected.Before the procedure,patients were assigned to ocular hypertension group( ≥ 40 mm Hg) or control group(＜ 40 mm Hg) based on intraocular pressure.These two groups were followed up for one year,and compared for post-operative visual acuity,intraocular pressure, filtering bleb,anterior chamber depth, and the occurrence of complications.Results:At 1 week,6 months,and 12 months after the procedure,intraocular pressure was controlled in both the ocular hypertension group and the control group,without significant differences between the two groups (P＞0.05).At 1 week,6 months,and 12 months after the procedure,all of the patients,in both groups,had improved in terms of visual acuity,with a significant difference before and after the procedure for the ocular hypertension group (P＜0.05).After follow-up at 12 months,the two groups presented no statistically significant differences in anterior chamber depth,filtering bleb survival,or the incidence of post-operative complications (P＞0.05 for all).Conclusion:It is feasible,safe,and effective to perform combined trabeculectomy on patients with primary acute angle closure glaucoma complicated by persistent ocular hypertension.