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Review Glaucoma Early Clinical Experiences with Brinzolamide/ Brimonidine Fixed Combination in Open-angle Glaucoma and Ocular Hypertension Stefano A Gandolfi University of Parma, Parma, Italy T he fixed combination of brinzolamide 10 mg/ml and brimonidine 0.2% 2 mg/ml (BBFC; Simbrinza ® ) is an important addition to the glaucoma treatment choices currently available. Glaucoma is an increasingly prevalent disease worldwide, particularly in the elderly, and causes a serious burden of blindness. Fixed combinations of eye drops simplify treatment regimens, improving compliance, which helps maintain intraocular pressure (IOP) reductions. Registration of BBFC in Europe was supported by two phase III trials. In the first (n=560), after 6 months of treatment, BBFC twice daily lowered IOP by -1.4 mmHg more than brinzolamide alone, and by -1.5 mmHg more than brimonidine alone (least squares mean differences, p<0.0001 for both versus BBFC). BBFC was well tolerated with a safety profile similar to its two components. In the other of these trials (n=411), BBFC was non-inferior to brinzolamide and brimonidine given as separate doses concomitantly (B + B). The adverse events were similar in each group, with a slightly higher incidence in the B + B group. In the US, registration of BBFC in glaucoma was supported by three phase III and one phase IV trials, which also showed significantly greater IOP reduction with BBFC compared with its components alone and showed similar safety profiles. Additional phase IV studies are in progress to evaluate the combined use of BBFC with travoprost and timolol. BBFC has been clinically available in the US and Europe for only a short time, but its clinical trial efficacy suggests it will have a positive impact on real-world glaucoma and may have utility for earlier administration than its current third- or fourth-line use. Keywords Alpha-2 agonist, carbonic anhydrase inhibitor, fixed combination, glaucoma, intraocular pressure, ocular hypertension Disclosure: Stefano A Gandolfi has nothing to declare in relation to this article. Acknowledgements: Medical writing support, including preparation of the drafts under the guidance of the author, was provided by Catherine Amey and James Gilbart, Touch Medical Communications. Compliance with Ethics: This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Authorship: All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. Received: 29 November 2017 Glaucoma is the second most common cause of blindness overall, and the leading cause of irreversible blindness, and constitutes a serious worldwide disability burden. 1 In 2015, 57.5 million people globally were affected by open-angle glaucoma (OAG) and this is predicted to increase to 65.5 million by 2020. Prevalence increases sharply with increasing age in all populations with a higher level in men and among Hispanic and Black populations. 2 The primary treatment goal is to reduce intraocular pressure (IOP), which is a risk factor for worsening of glaucoma-related neuropathy and axonal damage leading to vision loss. 3–5 Successful treatment for glaucoma is linked with good compliance/adherence, 6 yet many patients with glaucoma, especially those without symptoms, require multiple medications for adequate IOP control and this requirement may lead to compliance problems and consequently reduced efficacy. Findings from treatment centre studies and database analyses demonstrate this issue, showing a direct correlation between the number of bottles prescribed and reduced patient compliance. 6,7 Typical first-line treatment regimens for IOP reduction include prostaglandin analogues and beta-blockers. These have been used for over 20 years along with other established treatments such as carbonic anhydrase inhibitors (e.g., dorzolamide and brinzolamide), prostaglandins (e.g., latanoprost and travoprost) and alpha-2 adrenergic agonists (e.g., brimonidine). Combining topical therapies in glaucoma or using adjunctive therapies has been shown to increase IOP-lowering effects in various studies. 8–12 Various fixed combinations of these treatments are currently available for topical glaucoma treatment (see Table 1). Accepted: 21 December 2017 Citation: European Ophthalmic Review, 2017;11(2):103–7 Corresponding Author: Stefano A Gandolfi, Ophthalmology Unit, Department of Biotechnical and Translational Biomedical Sciences, University of Parma, Parma, Italy. E: stefano.gandolfi@unipr.it Support: The publication of this article was supported by Novartis/Alcon Europe. The views and opinions expressed in the article are those of the authors and not necessarily those of Novartis/Alcon Europe. TOU CH MED ICA L MEDIA Among the fixed combinations is a product containing the carbonic anhydrase inhibitor brinzolamide 10 mg/ml and the alpha-2 adrenergic agonist, brimonidine 0.2% 2 mg/ml (BBFC; Simbrinza ® , Alcon Laboratories, Inc., Fort Worth, TX, US). This combination is indicated for the reduction of elevated IOP in patients with OAG or ocular hypertension (OH). Each of the two components decreases elevated IOP by suppressing the formation of aqueous humour from the ciliary process in the eye. 13 Brinzolamide acts by inhibiting the enzyme carbonic anhydrase (CA-II) in the ciliary epithelium that reduces the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport across the ciliary epithelium, resulting in decreased aqueous humour formation. The other component, brimonidine, inhibits the enzyme adenylate 103