|Year : 2018 | Volume
| Issue : 2 | Page : 140-143
Efficacy of three different formulations of brimonidine for control of intraocular pressure in primary open-angle glaucoma: A 6-week randomized trial
Anubha Bhatti1, Gursatinder Singh2
1 Department of Ophthalmology, Sri Guru Ram Das Institute of Medical Sciences and Research, Amritsar, Punjab, India
2 Department of Ophthalmology, Government Medical College, Patiala, Punjab, India
|Date of Web Publication||28-May-2018|
H. No. 3024, Sector - 37D, Chandigarh
Source of Support: None, Conflict of Interest: None
| Abstract|| |
BACKGROUND: To compare the intraocular pressure (IOP)-lowering efficacy and safety of brimonidine (0.2%), brimonidine purite (0.15%), and brimonidine purite (0.1%) in patients of primary open-angle glaucoma (POAG).
MATERIALS AND METHODS: Sixty patients of POAG with IOP >21 mmHg were enrolled into this study for 6-week duration. The patients were randomly divided into three groups with 20 patients in each group. Group A instilled brimonidine 0.2%, Group B instilled brimonidine purite 0.15%, and Group C instilled brimonidine purite 0.1% twice daily. IOP was recorded by applanation tonometry at baseline and subsequently at 2, 4, and 6 weeks at 9:00–10:00 am during each visit around 30 min after instillation of eye drops.
RESULTS: Mean IOP reduction in Group A was from 25.55 ± 2.01 to 19.85 ± 2.05 mmHg at the end of study, thus resulting in fall of 5.70 mmHg (22.30%), in Group B, it decreased from 25.65 ± 2.41 to 19.55 ± 2.43 mmHg, thus resulting in fall of 6.10 mmHg (23.78%), and in Group C, it decreased from 25.80 ± 2.26 mmHg to 19.85 ± 2.16 mmHg, thus resulting in fall of 6.35 mmHg (24.61%). There was no statistically significant difference in IOP-lowering efficacy of study drugs. Conjunctival hyperemia, foreign body sensation, dry eye, and papillary reaction were the important side effects seen with study drugs. Brimonidine 0.2% caused more side effects than brimonidine purite 0.15% and brimonidine purite 0.1%.
CONCLUSION: All the three formulations of brimonidine produced statistically equal lowering of IOP in patients of POAG with reduced systemic and ocular adverse reactions with brimonidine purite 0.15% and 0.1%.
Keywords: Brimonidine 0.2%, brimonidine purite 0.1%, brimonidine purite 0.15%, primary open-angle glaucoma
|How to cite this article:|
Bhatti A, Singh G. Efficacy of three different formulations of brimonidine for control of intraocular pressure in primary open-angle glaucoma: A 6-week randomized trial. Oman J Ophthalmol 2018;11:140-3
|How to cite this URL:|
Bhatti A, Singh G. Efficacy of three different formulations of brimonidine for control of intraocular pressure in primary open-angle glaucoma: A 6-week randomized trial. Oman J Ophthalmol [serial online] 2018 [cited 2019 Dec 14];11:140-3. Available from: http://www.ojoonline.org/text.asp?2018/11/2/140/233324
| Introduction|| |
Elevated intraocular pressure (IOP) is one of the most important risk factors for glaucomatous damage and its lowering is the only proven treatment so far to prevent this glaucomatous damage. Lowering of IOP can be achieved either by reducing the aqueous humor production or by increasing the outflow of aqueous humor through trabecular or uveoscleral pathway. In general, the trabecular outflow in human eyes accounts for approximately 70%–95% of the aqueous humor egress from the eye, with the lower values corresponding to younger eyes and the higher values corresponding to older eyes. The other 5%–30% of aqueous humor leaves primarily by the uveoscleral outflow pathway, with a decline in the contribution of this pathway with age. Equilibrium between production and drainage of aqueous humor enables the maintenance of consistent IOP. Based on this, there are five major groups of drugs used for the treatment of glaucoma; cholinergics, alpha-adrenergic agonists, beta-adrenergic antagonists, carbonic anhydrase inhibitors, and prostaglandin analogs.
α-agonists are drugs which mediate their action through α-receptors, which are of two types; α1-receptors are present postsynaptically and constrict ciliary muscle and decrease aqueous production and α2-receptors are present presynaptically and decrease aqueous production through cyclic adenosine monophosphate. Depending on α2-selectivity, three drugs are available in this group; clonidine, apraclonidine, and brimonidine. All of them also increase uveoscleral outflow.
Brimonidine tartrate is a highly selective α2-adrenergic receptor agonist and is well tolerated ocularly and systemically. It is an effective and safe alternative to beta-blockers in patients at risk of pulmonary or cardiovascular disease. Brimonidine has also demonstrated neuroprotective properties. Glaucoma patients exhibit improved contrast sensitivity on initiation of brimonidine therapy. Shi and Jiang reported that brimonidine is safe and effective in lowering IOP in glaucoma or ocular hypertension and is well tolerated. Brimonidine 0.2% contains 0.05 mg benzalkonium chloride (BAK) at pH of 6.4. At higher concentration, BAK is more toxic than other preservative. BAK is retained in ocular tissue for a lengthy period of time and may induce cell death in dose-dependent manner. A new formulation of brimonidine and brimonidine purite 0.15% has been introduced to enhance safety and tolerability. In this formulation, the preservative has been changed from BAK to purite, and the concentration of active agent has been reduced by 25%. When instilled into the eye, purite is converted into natural tear components; sodium and chloride ions, oxygen, and water. Further efforts to improve safety and tolerability led to an additional reduction in the concentration of brimonidine and hence introduction of brimonidine purite 0.1%. Various studies have shown that 0.15% and 0.1% formulation of brimonidine purite allow decreased exposure to brimonidine, while providing an IOP-lowering effect comparable to that of the 0.2% formulation.,,, These three different formulations have been compared in the present study to check the IOP-lowering efficacy and also to look at systemic and ocular side effects with these three formulations in patients of primary open-angle glaucoma (POAG).
| Materials and Methods|| |
This was a randomized controlled trial. The study was conducted in the Department of Ophthalmology, Government Medical College, Patiala, with the permission of institutional research committee. Sixty patients of POAG were included in this study and informed written consent was taken. These patients were randomly divided into three groups with 20 patients in each group. In patients with bilateral POAG, both eyes were treated, but only one eye was included for analysis. The baseline IOP was >21 mmHg in all patients. Patients who were already on antiglaucoma treatment medication were included in the study after a washout period of 4 weeks. Patients with a history of acute angle-closure glaucoma, history of any intraocular surgery, history of argon laser trabeculoplasty, and pregnant/lactating females, known sensitivity to the study drugs and any ocular inflammation, were excluded from the study. Group A consisted of 20 patients of POAG. The patients in this group instilled 1 drop of brimonidine 0.2% with BAK ophthalmic solution as preservative twice daily at 9:00 am and 9:00 pm. Group B consisted of 20 patients of POAG. Patients in this group instilled 1 drop of brimonidine 0.15% with purite ophthalmic solution twice daily at 9:00 am and 9:00 pm. Group C consisted of 20 patients of POAG. Patients in this group instilled 1 drop of brimonidine 0.1% with purite ophthalmic solution twice daily at 9:00 am and 9:00 pm. The patients were followed at 2, 4, and 6 weeks. IOP was measured with Goldmann applanation tonometer at 9:00–10:00 am at each visit around 30 min after instillation of eye drops.
Statistical analysis used
Statistical analysis was done by paired t-test for comparing IOP at baseline and at 6 weeks, and ANOVA test was used for comparing IOP at each visit among three groups.
| Results|| |
Sixty eyes of 60 patients diagnosed as POAG were randomly assigned into 3 groups of 20 patients each. Demographic profile of these patients is given in [Table 1].
There was no statistically significant difference between the three groups (P > 0.05) regarding all parameters of patient profile, i.e., age, sex, or eye selected for the study.
The mean IOP lowering at the end of 6 weeks in Group A was 5.70 ± 1.30 mmHg (22.30%), 6.1 ± 1.20 mmHg (23.78%) in Group B, and 6.3 ± 1.08 mmHg (24.61%) in Group C. All the three formulations of brimonidine caused significant reduction in IOP (P < 0.001) compared to entry level IOP in patients of POAG; however, there was no statistically significant difference (P > 0.05) in IOP-lowering efficacy of these three formulations of brimonidine as shown in [Table 2].
Treatment-related adverse events were either systemic or ocular/periocular. Drowsiness and fatigue were complained only by one patient in Group A. Twelve side effects in 20 patients from Group A. Conjunctival hyperemia was most common side effect seen in five patients in Group A, three patients in Group B, and two patients in Group C. Dry eye occurred in two patients in Group A only. Foreign body sensation was complained by two patients in Group A, one patient in Group B, and none in Group C. Papillary reaction was seen in two patients in Group A, one patient in Group B, and one patient in Group C [Figure 1].
|Figure 1: Bar diagram showing incidence of ocular adverse effects in all groups|
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| Discussion|| |
Glaucoma is a chronic debilitating disease requiring lifelong treatment. Being the largest cause of bilateral blindness, secondary to cataract; glaucoma is a major public health problem.
Brimonidine tartrate is a highly selective alpha2-adrenergic receptor agonist. It decreases aqueous humor production and increases uveoscleral outflow. The IOP-lowering efficacy and safety of brimonidine 0.2%, brimonidine purite 0.15%, and brimonidine purite 0.1% were compared in this study. Mean reduction in IOP was 5.7 mmHg (22.3%) in Group A, 6.1 mmHg (23.7%) in Group B, and 6.3 mmHg (24.6%) in Group C at 6 weeks of follow-up. The lowering was found to be statistically significant (P < 0.001) in all the groups. However, there was no statistically significant difference (P > 0.05) in IOP reduction among various groups. All the three formulations had nearly equal reduction in IOP. Noecker in a 4-year clinical trial compared IOP-lowering efficacy of brimonidine purite 0.1% and brimonidine tartrate 0.2% in patients of POAG, normal-tension glaucoma, and ocular hypertension. The baseline IOP was 25.1 ± 3.7 mmHg for brimonidine purite 0.1% and 24.1 ± 3.0 mmHg for brimonidine 0.2%. Mean change from baseline IOP at each time point ranged from −5.7 to −6.5 mmHg with brimonidine purite 0.1% and from −5.3 to −6.2 mmHg with brimonidine tartrate 0.2%. Mean change in IOP from baseline at each time point was found to be similar in all types of glaucoma with advantage of reduced side effects. The results are similar to the present study. Katz and Mundorf et al. also compared the efficacy and safety of brimonidine purite 0.15% twice daily with brimonidine 0.2% twice daily in patients with POAG or ocular hypertension., The difference in mean IOP between the brimonidine purite 0.15% and brimonidine 0.2% treatment group was <1 mmHg at all time points. They concluded that brimonidine purite 0.15% provided IOP-lowering comparable with brimonidine 0.2% in patients of POAG or ocular hypertension. These studies indicate that brimonidine purite 0.15% is equally efficacious when compared to brimonidine 0.2% and has added the advantage of reduced side effects. Later, brimonidine purite became available as brimonidine purite 0.1%, and these two formulations, i.e., brimonidine purite 0.15% and brimonidine purite 0.1% were compared by Cantor et al. over 12 months in a randomized clinical trial. They found no significant difference in IOP-lowering efficacy of these two formulations of brimonidine. It is clear from these studies that efficacy of brimonidine purite 0.1%, brimonidine purite 0.15%, and brimonidine 0.2% is similar. In the present study, these three formulations have been compared simultaneously in patients of POAG and found to be equally efficacious in IOP-lowering capacity.
Major ocular side effect noticed in the present study was conjunctival hyperemia seen in 25% in Group A, 15% in Group B, and 10% in Group C. Papillary reaction was seen in 10% in Group A, 5% in Group B, and 5% in Group C. Foreign body sensation was seen in 10% in Group A and 5% in Group B. Dry eye and burning sensation were complained by 10% and 5%, respectively, in Group A only. Systemic adverse effects in the form of drowsiness and fatigue were complained by one patient in Group A. There was no systemic adverse reaction with brimonidine purite 0.15% and brimonidine purite 0.1%. Katz found that allergic conjunctivitis was lower by 41% in patients using brimonidine purite 0.15% compared to patients using brimonidine 0.2%. Mundorf et al. also reported conjunctival hyperemia and allergic conjunctivitis with the use of brimonidine 0.2%. Kim et al. compared efficacy and safety of brimonidine 0.2% versus brimonidine purite 0.15% in Asians with ocular hypertension and found that brimonidine 0.2% causes more allergic conjunctivitis than brimonidine purite 0.15%.
Cantor et al. reported that the incidence of treatment-related allergic conjunctivitis, conjunctival hyperemia, eye discharge, and oral dryness was statistically lower with brimonidine purite 0.1% compared with brimonidine purite 0.15%. The incidence of oral dryness was also significantly less common with brimonidine purite 0.1% compared to brimonidine 0.15%. Both brimonidine purite 0.1% and brimonidine purite 0.15% were associated with a lower overall incidence of treatment-related adverse effects compared with brimonidine 0.2% (41.4%, 49.7%, and 59.1%, respectively).
All the formulations of brimonidine are well tolerated and do not cause any serious side effect requiring discontinuation of the drug; however, brimonidine 0.2% causes more side effects compared to brimonidine purite 0.15% and brimonidine purite 0.1%. These could be related to the presence of BAK, which is more toxic than other preservatives and is retained in ocular tissue for a lengthy period of time and may induce cell death in a dose-dependent manner. In the formulations where the preservative has been changed from BAK to purite and the concentration of active agent has been reduced to 0.15% and 0.1%, the dose-related side effects are also reduced, and hence, brimonidine purite 0.15% and brimonidine purite 0.1% are better choice than brimonidine 0.2% for patients of POAG and ocular hypertension.
| Conclusion|| |
All the three formulations of brimonidine produced statistically equal lowering of IOP in patients of POAG, but brimonidine purite 0.15% and brimonidine purite 0.1% are better choices than brimonidine 0.2% because of better systemic and ocular safety profile, and the use of ocular hypotensive agents with preservative such as purite may have long-term benefits for the ocular surface health of patients requiring chronic use of topical medication.
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Conflicts of interest
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[Table 1], [Table 2]