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      Brinzolamide ophthalmic suspension: a review of its pharmacology and use in the treatment of open angle glaucoma and ocular hypertension

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          Abstract

          Brinzolamide is a white powder commercially formulated as a 1% ophthalmic suspension to reduce intraocular pressure (IOP). Pharmacologically, brinzolamide is a highly specific, non-competitive, reversible, and effective inhibitor of carbonic anhydrase II (CA-II), able to suppress formation of aqueous humor in the eye and thus to decrease IOP. Several clinical trials have evaluated its safety and the most commonly ocular adverse events are blurred vision (3%–8%), ocular discomfort (1.8%–5.9%), and eye pain (0.7%–4.0%). Brinzolamide has been introduced to treat ocular hypertension and primary open-angle glaucoma. In some clinical studies it has been estimated that brinzolamide reduced IOP by was about 18%. Brinzolamide can be added to beta-blockers and prostaglandins. In the latter combination, because prostaglandin derivatives improve the uveoscleral outflow but also increase the activity of CA in ciliary epithelium with a secondary increase in aqueous humor secretion, and slightly reduce the efficacy of prostaglandin analogues, theoretically topical CA inhibitors (CAI) decrease IOP by inhibiting CA-II, thus improving prostaglandin efficacy as well as lowering IOP. Brinzolamide could have a secondary possible effect on ocular flow too. Some clinical studies showed a mild improvement of ocular blood flow. Theoretically, CAI could give rise to metabolic acidosis, with secondary vasodilatation and improvement of blood flow. Systemic acidosis can occur in the setting of oral CAI therapy, and local acidosis within ocular tissues is theoretically possible with topical CAI therapy, with the potential for a local increase in ocular blood flow. In conclusion, topical CAI treatment has efficacy in IOP-lowering ranging from 15% to 20%. From published data, brinzolamide can be used as first-line medication, even if other medications have a higher efficacy, with few side effects and it is a good adjunctive treatment. In some type of glaucoma patients with a vascular dysregulation, topical CAI could have a double effect: reducing IOP and improving ocular blood flow.

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          Most cited references 43

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          The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators.

            (2000)
          To investigate the association between control of intraocular pressure after surgical intervention for glaucoma and visual field deterioration. In the Advanced Glaucoma Intervention Study, eyes were randomly assigned to one of two sequences of glaucoma surgery, one beginning with argon laser trabeculoplasty and the other trabeculectomy. In the present article we examine the relationship between intraocular pressure and progression of visual field damage over 6 or more years of follow-up. In the first analysis, designated Predictive Analysis, we categorize 738 eyes into three groups based on intraocular pressure determinations over the first three 6-month follow-up visits. In the second analysis, designated Associative Analysis, we categorize 586 eyes into four groups based on the percent of 6-month visits over the first 6 follow-up years in which eyes presented with intraocular pressure less than 18 mm Hg. The outcome measure in both analyses is change from baseline in follow-up visual field defect score (range, 0 to 20 units). In the Predictive Analysis, eyes with early average intraocular pressure greater than 17.5 mm Hg had an estimated worsening during subsequent follow-up that was 1 unit of visual field defect score greater than eyes with average intraocular pressure less than 14 mm Hg (P =.002). This amount of worsening was greater at 7 years (1.89 units; P <.001) than at 2 years (0.64 units; P =.071). In the Associative Analysis, eyes with 100% of visits with intraocular pressure less than 18 mm Hg over 6 years had mean changes from baseline in visual field defect score close to zero during follow-up, whereas eyes with less than 50% of visits with intraocular pressure less than 18 mm Hg had an estimated worsening over follow-up of 0.63 units of visual field defect score (P =.083). This amount of worsening was greater at 7 years (1.93 units; P <.001) than at 2 years (0.25 units; P =.572). In both analyses low intraocular pressure is associated with reduced progression of visual field defect, supporting evidence from earlier studies of a protective role for low intraocular pressure in visual field deterioration.
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            The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group.

            In a companion paper, we determined that intraocular pressure is part of the pathogenesis of normal-tension glaucoma by analyzing the effect of a 30% intraocular pressure reduction on the subsequent course of the disease. We report an intent-to-treat analysis of the study data to determine the effectiveness of pressure reduction. One eligible eye of 145 subjects with normal-tension glaucoma was randomized either to no treatment (control) or to a 30% intraocular pressure reduction from baseline. To be eligible for randomization, the normal-tension glaucoma eyes had to show documented progression of field defects or a new disk hemorrhage or had to have field defects that threatened fixation when first presented for the study. Survival analysis compared time to progression of all randomly assigned patients during the course of follow-up from the initial baseline at randomization. In a separate analysis, data of patients developing cataracts were censored at the time that cataract produced 2 lines of Snellen visual acuity loss. Visual field progression occurred at indistinguishable rates in the pressure-lowered (22/66) and the untreated control (31/79) arms of the study (P = .21). In an analysis with data censored when cataract affected visual acuity, visual field progression was significantly more common in the untreated group (21/79) compared with the treated group (8/66). An overall survival analysis showed a survival of 80% in the treated arm and of 60% in the control arm at 3 years, and 80% in the treated arm and 40% in the controls at 5 years. The Kaplan-Meier curves were significantly different (P = .0018). The analyses gave different results because of a higher incidence of cataract in the group that underwent filtration surgery. The favorable effect of intraocular pressure reduction on progression of visual change in normal-tension glaucoma was only found when the impact of cataracts on visual field progression, produced largely by surgery, was removed. Lowering intraocular pressure without producing cataracts is beneficial. Because not all untreated patients progressed, the natural history of normal-tension glaucoma must be considered before embarking on intraocular pressure reduction with therapy apt to exacerbate cataract formation unless normal-tension glaucoma threatens serious visual loss.
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              Vascular risk factors for primary open angle glaucoma: the Egna-Neumarkt Study.

               L Bonomi (2000)
              To assess the impact of vascular risk factors on the prevalence of primary open angle glaucoma. Population-based cross-sectional study. Four thousand two hundred ninety-seven patients more than 40 years of age underwent a complete ocular examination in the context of the Egna-Neumarkt Glaucoma Study. Ocular examinations were performed by trained, quality-controlled ophthalmologists according to a predefined standardized protocol including medical interview, blood pressure reading, applanation tonometry, computerized perimetry, and optic nerve head examination. Prevalences of ocular hypertension, primary open-angle glaucoma, normal-tension glaucoma, and other types of glaucoma were determined. Correlation coefficients were calculated for the association between systemic blood pressure and age-adjusted intraocular pressure (IOP) and between age and both intraocular and systemic blood pressures. Odds ratios were computed to assess the risk of primary open-angle glaucoma and normal-tension glaucoma in relation to systemic hypertension or antihypertensive medication, blood pressure levels, diastolic perfusion pressure, and a number of other cardiovascular risk factors. A positive correlation was found between systemic blood pressure and IOP, and an association was found between diagnosis of primary open-angle glaucoma and systemic hypertension. Lower diastolic perfusion pressure is associated with a marked, progressive increase in the frequency of hypertensive glaucoma. No relationship was found between systemic diseases of vascular origin and glaucoma. Our data are in line with those reported in other recent epidemiologic studies and show that reduced diastolic perfusion pressure is an important risk factor for primary open-angle glaucoma.
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                Author and article information

                Journal
                Clin Ophthalmol
                Clinical Ophthalmology
                Clinical ophthalmology (Auckland, N.Z.)
                Dove Medical Press
                1177-5467
                1177-5483
                September 2008
                : 2
                : 3
                : 517-523
                Affiliations
                Clinica Oculistica, University of Genoa, Italy
                Author notes
                Correspondence: Michele Iester, Clinica Oculistica, University of Genoa, Viale Benedetto XV, 16132 Genova, Italy, Tel 010 353 7783, Fax 010 353 8494, Email iester@ 123456unige.it
                Article
                co-2-517
                2694021
                19668749
                © 2008 Dove Medical Press Limited. All rights reserved
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                Review

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