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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 32  |  Issue : 1  |  Page : 56-59

Efficacy of brinzolamide 1% / brimonidine 0.2% fixed combination versus brimonidine 0.2% / timolol 0.5% fixed combination in patients with primary open-angle glaucoma: A comparative study


Department of Ophthalmology, Government Medical College, Patiala, Punjab, India

Date of Submission02-Dec-2019
Date of Decision13-Jan-2020
Date of Acceptance27-Jan-2020
Date of Web Publication17-Apr-2020

Correspondence Address:
Dr. Harvinder Nagpal
Department of Ophthalmology, Government Medical College and Hospital, Patiala - 147 001, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/kjo.kjo_83_19

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  Abstract 


Purpose: The aim of the study was to compare the intraocular pressure (IOP)-lowering efficacy of brinzolamide 1%/brimonidine tartrate 0.2% fixed combination versus brimonidine tartrate 0.2%/timolol maleate 0.5% fixed combination.Materials and Methods: A prospective, randomized, comparative, interventional study was conducted on forty patients of primary open-angle glaucoma attending the outpatient department of the department of ophthalmology at a tertiary institution in North India. Patients fulfilling the inclusion criteria and having none of the exclusion criteria were enrolled in the study after obtaining written informed consent. Patients were then randomized into two groups (Groups 1 and 2) with twenty patients in each group. Group 1 patients were given a brinzolamide 1%/brimonidine tartrate 0.2% fixed drug combination (BBFC) one drop twice daily and Group 2 patients were given a brimonidine tartrate 0.2%/timolol maleate 0.5 % fixed drug combination (BTFC) one drop twice daily for 6 weeks, and IOP was recorded at baseline and after 6 weeks at 9 am and 11 am.Results: The mean age was 61.05 years in Group 1 and 60.20 years in Group 2; there were 11 males in Group 1 and 14 males in Group 2, and the rest were female. Baseline mean IOP values were similar among treatment groups at all time points. At 6 weeks, the mean IOP of Group 1 was 18.32 mmHg and Group 2 was 18.45 mmHg with a reduction of 7.58 mmHg (29.26%) and 8.15 mmHg (31.83%) in Group 1 and Group 2, respectively. The difference in the IOP lowering at the end of the study between the two groups was not statistically significant (P > 0.05). Conclusion: Our study shows that BBFC seems to be an effective, safe, noninferior, and β-blocker-free fixed combination.

Keywords: Brimonidine, brinzolamide, fixed combination, open angle


How to cite this article:
Singh G, Nagpal H, Kaur M. Efficacy of brinzolamide 1% / brimonidine 0.2% fixed combination versus brimonidine 0.2% / timolol 0.5% fixed combination in patients with primary open-angle glaucoma: A comparative study. Kerala J Ophthalmol 2020;32:56-9

How to cite this URL:
Singh G, Nagpal H, Kaur M. Efficacy of brinzolamide 1% / brimonidine 0.2% fixed combination versus brimonidine 0.2% / timolol 0.5% fixed combination in patients with primary open-angle glaucoma: A comparative study. Kerala J Ophthalmol [serial online] 2020 [cited 2020 Aug 12];32:56-9. Available from: http://www.kjophthal.com/text.asp?2020/32/1/56/282662




  Introduction Top


Glaucoma is a chronic, progressive, optic neuropathy caused by a group of ocular disorders that lead to damage of the optic nerve with loss of function.[1] It is the second leading cause of preventable blindness worldwide. In 2010 worldwide, approximately 60.5 million people were suffering from primary open-angle glaucoma (POAG) and primary angle-closure glaucoma. This number is estimated to rise up to 79.6 million by 2020. Twelve million people are affected in India accounting for 12.8% of country blindness. Glaucoma is progressive and, if left untreated, will lead to blindness.[2] Raised intraocular pressure (IOP) is one of the strongest risk factors for the development of POAG. Hence, the main aim of the treatment of glaucoma is the control of IOP that delays the development and progression of glaucoma.[3] The choice of therapy for patients who have POAG consists of medications, argon laser trabeculoplasty, filtration surgery, or a combination of these. All these treatment modalities are designed to lower IOP to the point where deterioration of the disc/field ceases with a minimum of side effects.[4],[5] Brimonidine inhibits the enzyme adenylate cyclase through the activation of a G protein-coupled receptor and suppresses the cAMP-dependent formation of aqueous humor. It also increases aqueous outflow through the uveoscleral pathway by increased prostaglandin release due to α-adrenergic stimulation.[6],[7] Recent clinical studies have suggested that topical brimonidine treatment may also have neuroprotective effects, particularly in low-tension glaucoma patients.[8] Brinzolamide-induced carbonic anhydrase (CA)-II blockage in the ciliary epithelial cells reduces bicarbonate ion formation and sodium transport into the posterior chamber, thus lowering the aqueous humor formation and IOP.[9]

BBFC is a fixed combination of brinzolamide 1.0% (CA inhibitor) and brimonidine tartrate 0.2% (alpha-2 adrenergic receptor agonist) in a single-dose bottle. BTFC is a fixed combination of brimonidine tartrate 0.2% (alpha-2 adrenergic receptor agonist) and timolol maleate 0.5% (beta-blocker), as it contains beta-blocker so cannot be used in patients with asthma, severe chronic obstructive pulmonary disease, sinus bradycardia, second- or third-degree heart block, and severe congestive heart failure. There are no studies available on comparison of brinzolamide 1%/brimonidine tartrate 0.2% fixed combination versus brimonidine tartrate 0.2%/timolol maleate 0.5% fixed combination, so this study was conducted to evaluate the efficacy of these drug combinations. The advantage of using these combinations is that they enable treatment with multiple mechanisms of action in a single topical medication, providing additive IOP, lowering efficacy without increasing treatment complexity, or introducing risk of drug washout.


  Materials and Methods Top


A prospective, randomized, comparative, interventional study was conducted on forty patients of POAG attending the outpatient department of the department of ophthalmology at a tertiary institute in North India. Patients fulfilling the inclusion criteria and having none of the exclusion criteria were enrolled in the study after obtaining written informed consent. Patients were then randomized into two groups (Groups 1 and 2) with twenty patients in each group. On day 0, baseline IOP was recorded before starting the treatment. Group 1 patients were given a fixed drug combination of brinzolamide 1%/brimonidine tartrate 0.2% one drop twice daily at 7 am and 6 pm and Group 2 patients were given a fixed drug combination of brimonidine tartrate 0.2%/timolol maleate 0.5% one drop twice daily at 7 am and 6 pm for 6 weeks, and IOP was recorded after 6 weeks at 9 am and 11 am with Goldmann applanation tonometer for all patients by a single observer. Effectiveness of the drugs was calculated in terms of mmHg fall in mean IOP. All the observations thus made will be compiled on a pro forma and subjected to statistical analysis using appropriate tests.


  Results Top


As shown in [Table 1], the mean age in Group 1 was 61.05 years and in Group 2 was 60.20 years. In Group 1, 11 patients were male and 9 were female, and in Group 2, 14 were male and 6 were female [Table 2].
Table 1: Age distribution in both the groups

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Table 2: Gender distribution in both the groups

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As shown in [Table 3], the mean IOP between the two groups at baseline at 9:00 am and 11:00 am was comparable with the difference being statistically insignificant (P > 0.05). IOP recordings were also taken at 3 pm, but measurements were similar to those taken at 11 am.
Table 3: Comparison of mean intraocular pressure of both the groups at baseline at various time points

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As shown in [Table 4], the mean IOP between the two groups at 6 weeks at 9:00 am and 11:00 am was comparable with the difference being statistically insignificant (P > 0.05).
Table 4: Comparison of mean intraocular pressure of both the groups at 6 weeks at various time points

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As shown in [Table 5], IOP reduction with brinzolamide 1%/brimonidine tartrate 0.2% fixed combination and brimonidine tartrate 0.2%/timolol maleate 0.5% fixed combination was clinically significant at 6 weeks when compared with baseline. The IOP lowering at the end of the study was more with brimonidine tartrate 0.2%/timolol maleate 0.5% fixed combination (mean IOP reduction: 8.15 mmHg, 31.83%) than with brinzolamide 1%/brimonidine tartrate 0.2% fixed combination (mean IOP reduction: 7.58 mmHg, 29.26%). The difference in the IOP lowering at the end of the study between the two groups was not statistically significant (P > 0.05).
Table 5: Reduction of mean diurnal intraocular pressure at various visits in the two groups

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  Discussion Top


The management of POAG and ocular hypertension (OHT) has been focused on reducing the IOP. Nguyen et al.[10] in 2013 evaluated the efficacy of BBFC in POAG and OHT patients and calculated the mean IOP decrease of 7 mmHg from baseline that is 27.9%, whereas in a study conducted by Whitson et al.[11] in 2013 in patients of POAG and OHT, the mean IOP reduction from baseline by BBFC was 4.9–8.0 mmHg and the percentage reduction was 20.0%–30.7%. Whereas, a study was done by Gandolfi et al.[12] in 2014 to evaluate the efficacy of BBFC in POAG and OHT patients and calculated the mean IOP decrease of 8.5 mmHg from baseline and the percentage reduction was 32.19%. Thus, a significant reduction in IOP with BBFC given twice daily was seen in our study, as in most of the studies mentioned above. In 2012, Cheng et al.[13] evaluated the mean reduction of IOP by 28.1% from baseline in POAG patients, whereas Giuffre[14] in 2012 evaluated the mean reduction of IOP by 43.57% from baseline in POAG patients. Thus, a significant reduction in IOP with BTFC given twice daily was seen in our study, as in most of the studies mentioned above. In the present study, the mean IOP reduction at the end of 6 weeks was statistically similar between BBFC and BTFC. The mean IOP reduction with BBFC and BTFC after 6 weeks was 7.58 mmHg (29.26%) and 8.15 mmHg (31.83%), respectively. A comparison between the two groups showed that across all time points and visits during the 6-week treatment period, IOP reduction produced with BBFC was comparable with BTFC. The difference in IOP lowering in the two groups was statistically nonsignificant.


  Conclusion Top


Our study shows that BBFC seems to be an effective, safe, noninferior, and β-blocker-free fixed combination.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Allingham RR, Damji KF, Freedman S, Moroi SE, Rhee DJ. Introduction: An Overview of Glaucoma. Shields Textbook of Glaucoma. 6th ed. USA: Lippincott Williams and Wilkins; 2011. p. 110-1.  Back to cited text no. 1
    
2.
Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006;90:262-7.  Back to cited text no. 2
    
3.
Duke Elder S. Introduction to glaucoma In: System of Ophthalmology 1st edn. Henry and Kimpton, London 1969;3:380-89.  Back to cited text no. 3
    
4.
The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. The AGIS Investigators. Am J Ophthalmol 2000;130:429-40.  Back to cited text no. 4
    
5.
Grant WM, Burke JF Jr., Why do some people go blind from glaucoma? Ophthalmology 1982;89:991-8.  Back to cited text no. 5
    
6.
European Glaucoma Society. Terminology and Guidelines for Glaucoma. 3rd ed. Savona, Italy: Editrice Dogma SRL; 2008.  Back to cited text no. 6
    
7.
Adkins JC, Balfour JA. Brimonidine. A review of its pharmacological properties and clinical potential in the management of open-angle glaucoma and ocular hypertension. Drugs Aging 1998;12:225-41.  Back to cited text no. 7
    
8.
Krupin T, Liebmann JM, Greenfield DS, Ritch R, Gardiner S, Low-Pressure Glaucoma Study Group. A randomized trial of brimonidine versus timolol in preserving visual function: Results from the Low-Pressure Glaucoma Treatment Study. Am J Ophthalmol 2011;151:671-81.  Back to cited text no. 8
    
9.
Kaback M, Scoper SV, Arzeno G, James JE, Hua SY, Salem C, et al. Intraocular pressure-lowering efficacy of brinzolamide 1%/timolol 0.5% fixed combination compared with brinzolamide 1% and timolol 0.5%. Ophthalmology 2008;115:1728-34, 1734.e1-2.  Back to cited text no. 9
    
10.
Nguyen QH, McMenemy MG, Realini T, Whitson JT, Goode SM. Phase 3 randomized 3-month trial with an ongoing 3-month safety extension of fixed-combination brinzolamide 1%/brimonidine 0.2%. J Ocul Pharmacol Ther 2013;29:290-7.  Back to cited text no. 10
    
11.
Whitson JT, Realini T, Nguyen QH, McMenemy MG, Goode SM. Six-month results from a Phase III randomized trial of fixed-combination brinzolamide 1%+brimonidine 0.2% versus brinzolamide or brimonidine monotherapy in glaucoma or ocular hypertension. Clin Ophthalmol 2013;7:1053-60.  Back to cited text no. 11
    
12.
Gandolfi SA, Lim J, Sanseau AC, Parra Restrepo JC, Hamacher T. Randomized trial of brinzolamide/brimonidine versus brinzolamide plus brimonidine for open-angle glaucoma or ocular hypertension. Adv Ther 2014;31:1213-27.  Back to cited text no. 12
    
13.
Cheng JW, Cheng SW, Gao LD, Lu GC, Wei RL. Intraocular pressure-lowering effects of commonly used fixed-combination drugs with timolol: A systematic review and meta-analysis. PLoS One 2012;7:e45079.  Back to cited text no. 13
    
14.
Giuffre I. Comparative evaluation of the efficacy of the bimatoprost 0.03%, brimonidine 0.2%, brinzolamide 1%, dorzolamide 2%, and travoprost 0.004%/timolol 0.5%-fixed combinations in patients affected by open-angle glaucoma. Open J Ophthalmol 2012;2:122.  Back to cited text no. 14
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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