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Purpose: To study the effect of brimonidine on vascular density and flow index of optic nerve head (ONH) and macula in primary open angle glaucoma (POAG) using optical coherence tomography angiography (OCTA). Methods: Twenty-three brimonidine-naïve POAG patients were started on brimonidine. They underwent OCTA ONH and macula before commencing brimonidine and one month thereafter. Systemic arterial blood pressure (SABP) and intraocular pressure (IOP) were measured at each visit to calculate mean ocular perfusion pressure (MOPP). The OCT angiograms were analyzed using ImageJ software to calculate ONH and macular flow indices. Results: Thirty-seven eyes (23 patients) with a mean age of 56.7 ± 12.49 years were included of whom 60.8% were males. Brimonidine was associated with an increase in the superficial flow index (SFI) (P-value = 0.02) and optic nerve head flow index (ONHFI) (P-value = 0.01). Also, superficial vascular density (SVD) for whole image, superior-hemi and fovea increased (P-value = 0.03, 0.02, 0.03 respectively). ONH inferior-hemi vascular density decreased (P-value = 0.01) despite an increase in inferior quadrant retinal nerve fiber layer thickness (RNFLT) (P-value = 0.03). There was no statistically significant correlation between flow indices and MOPP at baseline and follow-up. A moderate negative correlation was found between SVD and DVD at the fovea and MOPP at baseline and follow-up (P-value = 0.03, 0.05) (P-value = 0.02, 0.01) respectively. Conclusions: Brimonidine was associated with an increase in SFI, ONHFI and SVD indicating improved GCC and RNFL perfusion in POAG. Despite the increase in inferior quadrant RNFLT, the concomitant decrease in inferior-hemi ONHVD precluded a conclusion of hemodynamically-mediated improvement of RNFLT. [ABSTRACT FROM AUTHOR]

Purpose: The ROCK inhibitor ripasudil hydrochloride hydrate was shown to have axonal protective effects in TNF-induced optic nerve degeneration. The α2-adrenoreceptor agonist brimonidine was also shown to exert axonal protection. The current study aimed to elucidate whether additive axonal protection was achieved by the simultaneous injection of ripasudil and brimonidine and examine the association with AMPK activation. Methods: Intravitreal administration was performed in the following groups: PBS, TNF, or TNF with ripasudil, with brimonidine, or with a combination of ripasudil and brimonidine. Axon numbers were counted to evaluate the effects against axon loss. Immunoblot analysis was performed to examine phosphorylated AMPK expression in optic nerves, and immunohistochemical analysis was performed to evaluate the expression levels of p-AMPK and neurofilament in the optic nerve. Results: Both ripasudil alone or brimonidine alone resulted in significant neuroprotection against TNF-induced axon loss. The combination of ripasudil and brimonidine showed additive protective effects. Combined ripasudil and brimonidine plus TNF significantly upregulated p-AMPK levels in the optic nerve compared with the TNF groups. Immunohistochemical analysis revealed that p-AMPK is present in axons and enhanced by combination therapy. Conclusion: The combination of ripasudil and brimonidine may have additive protective effects compared with single-agent treatment alone. These protective effects may be at least partially associated with AMPK activation. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic inflammatory disease with a multifactorial pathogenesis. The wide spectrum of clinical phenotypes, including erythema, telangiectasia, inflammatory papules and pustules, and phyma, demand an individualized approach to treatment. This narrative review offers an updated reference for rosacea management by covering the latest developments in both topical and systemic treatments, including data from newly approved therapies, updates to current treatment modalities and ongoing clinical trials. Although use of benzoyl peroxide as a treatment for rosacea has typically been limited due to irritation, the improved tolerability due to microencapsulation of benzoyl peroxide 5% cream provides a new therapeutic option for patients with rosacea. Minocycline foam and topical ivermectin cream add to our armamentarium of treatment options, particularly for inflammatory papules and pustules. Sarecycline has a narrower spectrum of antibacterial activity, which might reduce the development of antibiotic resistance and disruption of the microbiome compared to other oral antibiotics. Brimonidine gel and oxymetazoline cream provide topical options for redness and flushing. There is emerging evidence about the role of hydroxychloroquine and intradermal botulinum toxin A, which may improve rosacea through their effects on mast cells. The clinical trials pipeline includes agents with a variety of mechanisms, including mast cell stabilization, antimicrobial, anti-inflammatory, and vasoconstrictive effects. However, the clinical pipeline for rosacea appears limited, and there remain important unmet needs for patients with more recalcitrant rosacea or phymatous disease. In addition, there is a need for comparative effectiveness studies to identify the highest value treatment approaches for patients with rosacea. [ABSTRACT FROM AUTHOR]

Introduction: This multicenter, randomized, comparative, and investigator-masked crossover clinical trial sought to compare the efficacy and tolerability of fixed combinations of 0.1% brimonidine/0.5% timolol (BTFC) versus 1% dorzolamide/0.5% timolol (DTFC) as adjunctive therapies to prostaglandin analogues. Methods: A total of 110 patients with open-angle glaucoma or ocular hypertension previously treated with prostaglandin analogue monotherapy were randomized to receive either BTFC or DTFC as adjunctive therapy for 8 weeks. These patients were then crossed over to the alternative treatment arm for another 8 weeks. The reduction in intraocular pressure (IOP) (primary outcome), occurrence of adverse events, ocular discomfort after instillation, and patient preference (secondary outcomes) were recorded through patient interviews. Results: BTFC instillation for 8 weeks reduced IOP by 3.55 mmHg, demonstrating non-inferiority to DTFC instillation (3.60 mmHg; P < 0.0001, mixed-effects model). Although adverse events were rare with both combinations, patients reported greater discomfort with DTFC than with BTFC (P < 0.0001). More patients preferred BTFC (P < 0.0001) over DTFC, as BTFC caused minimal or no eye irritation. Conclusion: As BTFC offered better tolerability than DTFC with comparable reduction in IOP, we recommend it as an alternative for patients who experience ocular discomfort with DTFC-prostaglandin analogue combination therapy. Trial Registration Number: jRCTs051190125. Plain Language Summary: Patients with glaucoma who require further reduction in intraocular pressure while undergoing monotherapy with prostaglandin analogue ophthalmic solution have been prescribed two enhanced treatment options: 0.1% brimonidine/0.5% timolol fixed combination ophthalmic solution (BTFC) and 1% dorzolamide/0.5% timolol fixed combination ophthalmic solution (DTFC). The Aibeta Crossover Study Group in Japan compared the efficacy and tolerability of fixed combinations of BTFC versus DTFC when an additional fixed combination ophthalmic solution was prescribed in patients with open-angle glaucoma or ocular hypertension who had been treated with prostaglandin analogue monotherapy. We recruited 110 patients previously treated with prostaglandin analogue monotherapy at 20 clinical centers in Japan, then randomly assigned them to two alternative treatment groups: the BTFC to DTFC group or the DTFC to BTFC group, as an adjunctive therapy to prostaglandin analogues for total of 16 weeks. We compared the reduction in intraocular pressure, occurrence of side effects, eye discomfort after instillation, and patient preference between BTFC versus DTFC instillations. The intraocular pressure reduction of BTFC instillation was comparable to that of DTFC instillation, showing non-inferiority to DTFC (3.55 mmHg vs. 3.60 mmHg; P < 0.0001, mixed-effects model). Both eye drops caused few side effects; however, patients felt greater eye discomfort with DTFC than with BTFC (P < 0.0001). Because of less eye irritation, more patients preferred BTFC (P < 0.0001) over DTFC. We can recommend using BTFC for patients who feel eye discomfort with DTFC–prostaglandin analogue combination therapy. [ABSTRACT FROM AUTHOR]

Glaucoma is a chronic eye disease in which the pressure inside the eye increases and leads to damage to the optic nerve, and eventually causes blindness. In this disease, it is often necessary to use a multi-drug treatment system. There is a fixed combination of timolol maleate and brimonidine tartrate among the combination drugs in glaucoma treatment. Liposomes are one of the most important targeted drug delivery systems to eye tissue, which leads to improved drug permeability and durability in ocular tissue. In this study, thin layer hydration was used to make liposomal formulations containing timolol maleate (TM) and brimonidine tartrate (BT). After the necessary evaluations, one of the eight initial formulations was selected as an optimization formulation. Then, characteristics such as drug loading percentage, particle size, pH, zeta potential, and drug release were performed on the optimized formulation. The study of reducing intraocular pressure was performed on the optimized formulation. This study in total was performed on 18 rabbits in three groups. Hydroxypropyl methylcellulose (HPMC) polymer was injected into the anterior chamber to experimental induce glaucoma. The selected formulation was within the acceptable range of ocular products in terms of physical properties. HPMC polymer injection successfully induced glaucoma in the animal model, resulting in a 79% increase in intraocular pressure. The results showed that the liposomal formulation significantly reduced the intraocular pressure compared to the simple formulation of the aqueous solution, and both formulations were able to significantly reduce the intraocular pressure compared to the control group (P < 0.001). The results also showed that liposomal formulation has a therapeutic effect in reducing intraocular pressure. It seems that the selected liposomal formulation made by thin layer hydration can act as a suitable drug carrier to increase the effectiveness of the fixed combination of timolol maleate and brimonidine tartrate and be proposed as a new drug formulation for targeted and controlled drug delivery in the treatment of glaucoma. [ABSTRACT FROM AUTHOR]

Glaucoma is a complex disease which when encountered in pregnancy poses a challenge to the woman's obstetrician and her ophthalmologist. The dilemma arises while opting the line of management, either medical or surgical which requires balancing the clinical disease of the mother with the potential threat of therapy to the growing child. Such was our case an elderly primigravida 10 weeks of gestation who had an acute episode of angle closure glaucoma with diminishing vision, who was managed both medically (anti-glaucoma drugs) and surgically (trabeculectomy). She recovered with a normal IOP, improved vision and anomaly scan of the fetus showing a structurally normal fetus. Thus, the fear of uncertain drug teratogenicity should not discourage doctors from prescribing treatments when their expected benefits to the mother are thought to outweigh the risk to the fetus. [ABSTRACT FROM AUTHOR]

Introduction: This study was aimed to compare ocular tissue distribution and systemic exposure of brimonidine and timolol after single topical administration to rabbits of fixed-combination ophthalmic solution of 0.1% brimonidine tartrate and 0.5% timolol and single drugs (0.1% brimonidine tartrate ophthalmic solution or 0.5% timolol ophthalmic solution) or concomitant administration of single drugs. Methods: Rabbits were treated with a single topical administration of each ophthalmic solution or concomitant administration of single drugs. For concomitant administration, 0.1% brimonidine tartrate was administered after 0.5% timolol instillation successively within 10 s (without interval) or with 5-min intervals. Brimonidine and timolol concentrations in the aqueous humor, retina/choroid, vitreous body, and plasma were determined with liquid chromatography-tandem mass spectrometry. Results: The area under the curve values of both drugs in the aqueous humor after fixed-combination administration were comparable to those after concomitant administration. The value of brimonidine was comparable to that after 0.1% brimonidine tartrate administration, whereas the value of timolol was 1.6-fold higher than that after 0.5% timolol administration. The plasma area under the curve value of brimonidine did not differ between fixed-combination and single-drug administrations, but that of timolol was higher after fixed-combination administration than after single-drug administration. Similar concentration-time curves of brimonidine were observed in the posterior ocular tissues in all groups. For concomitant administration, both drug concentrations in the aqueous humor without an administration interval were lower than those with 5-min intervals. Conclusion: There was no difference in the effect of formulation compositions on ocular and systemic pharmacokinetics among the ophthalmic solutions, but brimonidine may alter the ocular and systemic absorption of timolol, which is possibly due to its pharmacologic action. We demonstrated the importance of an administration interval in the concomitant administration of these drugs. This concern could be avoided by using a fixed combination of brimonidine and timolol. [ABSTRACT FROM AUTHOR]

A novel voltammetric method was developed for brimonidine (BRIM) determination in deproteinized aqueous humor, simplifying preparation of biological samples for analysis for stability studies. The differential pulse voltammetric (DPV) method using boron doped diamond electrode (BDDE), based on characteristic oxidation peaks, was proposed and successfully applied. The linearity range was within 5.0 × 10−6 to 5.0 × 10−5 M of brimonidine, and limit of detection and limit of quantitation were 1.94 × 10−6 M and 6.46 × 10−6 M, respectively. Intra-day and inter-day precision and accuracy were evaluated and all results were in accordance with validation ICH guidelines. The best short-term stability study results were obtained for a concentration level of 3.0 × 10−5 M expressed by deviation of + 1.86% between initial and post storage concentrations. A long-term stability study was performed for two concentrations of 3.0 × 10−5 M and 5.0 × 10−5 M and resulted in deviations of + 1.63% and + 3.56%, respectively. A freeze and thaw stability study indicated that samples might be frozen only once. The enhancement of DPV/BDDE method sensitivity gained by modification, for the analysis of immeasurable BRIM quantities in native, untreated aqueous humor, was reached for quantities of 6 or 12 nmol/0.1 mL aqueous humor with acceptable accuracy (up to + 7.5%). The nature of the process—the irreversible one electron oxidation voltammetric peak of BRIM—limited the sensitivity. Only electrochemical pre-treatment of the BDD electrode before each measurement significantly speeded up the whole procedure. The advantages of the proposed method are simplicity, short-time performance, and good specificity/selectivity, as well as satisfactory accuracy, and no chemical modification of BDDE was necessary. [ABSTRACT FROM AUTHOR]

Introduction: Brimonidine bioavailability in the aqueous humor depends on the solution pH following topical administration. The purpose of this study was to investigate the effect of solution pH on brimonidine distribution in the posterior ocular tissues in pigmented rabbits. Methods: The anterior retina/choroid, posterior retina/choroid, and vitreous body of pigmented rabbits were collected 0.67, 1.5, 3, 6, 12, 24, 168, and 360 h after the administration of a single topical dose of 0.2% brimonidine tartrate ophthalmic solution, pH 6.4 (Alphagan®; Allergan Inc., Irvine, CA, USA). Brimonidine concentrations in these tissues were quantified using liquid chromatography/tandem mass spectrometry. Pharmacokinetic parameters were determined using noncompartmental analysis, and the results were compared with tissues from eyes administered 0.1% brimonidine tartrate ophthalmic solution, pH 7.3 (Aiphagan®; Senju Pharmaceutical Co., Ltd., Osaka, Japan) in our previous study conducted using the same procedure. Results: Topically applied brimonidine was distributed rapidly into the posterior tissues of the eye after a single ophthalmic administration of the 0.2% ophthalmic solution. The areas under the curve from time 0 to 360 h following dosing with the 0.2% ophthalmic solution were 500,000, 14,300, and 28.7 ng h/g in the anterior and posterior retina/choroid, and vitreous body, respectively. Conclusion: The differences in the areas under the curve between two ophthalmic solutions were less than the difference in drug concentrations between these two products in any tissues. This finding indicates that the change in the solution pH from 6.4 to 7.3 increases brimonidine bioavailability into the posterior ocular tissues similarly as into the aqueous humor. Funding: Senju Pharmaceutical Co., Ltd. [ABSTRACT FROM AUTHOR]

The purpose of this study is to evaluate the outcome of a series of patients with erythematotelangiectatic rosacea (ETR) affected by persistent erythema and varying degree of telangiectasias being treated with brimonidine alone or combined with a vascular laser based on the type of vascular components preliminarily evaluated by clinical and instrumental observation. Ten patients affected by ETR were enrolled in a pilot, open study. Instrumental evaluation included erythema-directed digital photography by VISIA-CR™ system and X10 dermoscopy. Those patients showing marked background erythema and minimal telangiectasias (group A) were treated with a single application of brimonidine 0.33% gel, while patients showing both marked background erythema and marked telangiectasias (group B) were treated with a session of Nd:YAG laser and reevaluated 1 month later after a single application of brimonidine. An Investigator Global Assessment (IGA) of treatment outcome was performed at the end of treatment in both groups. In group A, 6 h after brimonidine application, a marked reduction of the background erythema was observed in all patients, and IGA was rated as excellent. In group B, 6 h following the application of brimonidine, a marked reduction of the background erythema was observed in all cases, while telangiectasias remained unchanged. A further treatment with brimonidine 1 month after the Nd:YAG laser session determined complete clearing of facial erythema, and IGA was rated as excellent. In conclusion, a preliminary evaluation of the vascular component by erythema-directed digital photography and dermoscopy in ETR may be helpful to select the most appropriate therapeutic strategy. [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy of the fixed combination of brimonidine-timolol (FCBT) and the fixed combination of brinzolamide-timolol (FCBZT) treatments for elevated intraocular pressure (IOP) after phacoemulsification cataract surgery.Methods: A randomised, prospective, double-blinded study was conducted on 277 eyes of 257 patients who underwent phacoemulsification cataract surgery. Patients were divided into three groups based on the medication administered after cataract surgery as follows: FCBT, FCBZT and a control group where no antiglaucoma medications were used. IOP was recorded at preoperative and postoperative hours 6 and 24 and days 3 and 5.Results: No statistical differences were observed among the groups regarding age, sex and baseline IOP levels (p > 0.05). Mean IOP levels were significantly lower in the treatment groups than in the control group at postoperative hours 6 and 24 and days 3 and 5 (p < 0.001). Administration of one drop of FCBT or FCBZT demonstrated similar effects on preventing IOP spikes within 24 h of phacoemulsification cataract surgery. FCBZT more effectively lowered IOP than FCBT at days 3 and 5 (p < 0.05).Conclusions: We demonstrate that the postoperative administration of FCBT or FCBZT is effective in lowering IOP after phacoemulsification cataract surgery; FCBZT more effectively lowered IOP than FCBT at postoperative days 3 and 5. [ABSTRACT FROM AUTHOR]

Purpose: To assess the responses of the superficial peripapillary retinal vessel density (VD) and prelaminar flow index (PLFI) to topical Rho-assisted coiled-coil forming protein kinase (ROCK) inhibitor ripasudil and alpha-2 agonist brimonidine using optical coherence tomography angiography.Methods: This is a prospective, non-randomized, comparative cohort study. We studied the response of optical coherence tomography angiography (OCTA) parameters to drugs in 24 eyes treated with ripasudil and 23 eyes treated with brimonidine at the Sensho-kai Eye Institute. After division by the signal strength (SS), we compared the responses of peripapillary VD/SS and PLFI/unit area (UA)/SS to topical eye drops in eyes with primary open-angle glaucoma (POAG) and ocular hypertension (OH).Results: In the superficial peripapillary retina, VD/SS increased significantly in the ripasudil-treated eyes (12.5 ± 21.7%, P = 0.018), but not in the brimonidine-treated eyes (− 2.0 ± 13.8%, P = 0.484). In the deeper area of the optic disc, the changes in the PLFI/UA/SS in the brimonidine-treated eyes (+ 0.9 ± 8.9%, P = 1.00) and ripasudil-treated eyes (− 1.3 ± 8.5%, P = 0.241) were not significant. Multivariate discriminant analysis showed that the change in the peripapillary VD/SS was the most important parameter (P = 0.0186) for differentiating ripasudil- and brimonidine-treated eyes.Conclusions: The topical ROCK inhibitor ripasudil enhanced the peripapillary VD in POAG and OH, whereas the alpha-2 agonist brimonidine did not. The PLFI did not respond to either drug. [ABSTRACT FROM AUTHOR]

Introduction: This study compared the efficacy and safety of adjunctive brimonidine tartrate 0.1% ophthalmic solution (brimonidine) and timolol maleate 0.5% ophthalmic solution (timolol) in prostaglandin analogue (PGA)-treated normal-tension glaucoma (NTG), assessing the non-inferiority of brimonidine in terms of intraocular pressure (IOP) reduction.Methods: In this multicenter, randomized, investigator-masked, parallel-group, clinical study, adjunctive brimonidine or timolol was administered twice daily for 12 weeks in eyes with NTG that had been treated with PGA for at least 90 days and required additional treatment despite an IOP of 16 mmHg or less. IOP was measured on at least three visits before add-on therapy (mean baseline IOP), and at weeks 4, 8, and 12 after adjunctive administration. Systolic/diastolic blood pressure, pulse rate, and adverse events (AEs) were recorded at each visit.Results: A total of 152 individuals were enrolled and 128 (84.2%) were eligible for efficacy analyses. IOP in both groups at each visit decreased significantly from baseline (P < 0.001). However, the difference in the change from baseline IOP at week 12 between the brimonidine (-1.05 ± 1.81 mmHg) and timolol (-1.41 ± 1.40 mmHg) groups was 0.36 mmHg (95% confidence interval [CI] [-0.21, 0.92]), which exceeded the value of the non-inferiority margin (0.75 mmHg). Baseline systolic/diastolic blood pressure decreased significantly in both groups at certain visits (P < 0.05), while baseline pulse rates decreased significantly in the timolol group (P < 0.001), with no significant differences in the brimonidine group. AE-related treatment discontinuation occurred in 2/71 (2.8%) and 2/75 (2.7%) patients in the brimonidine and timolol groups, respectively.Conclusion: This study demonstrated an add-on effect of brimonidine to PGAs, although non-inferiority of brimonidine to timolol as adjunctive therapy in PGA-treated NTG in terms of IOP reduction was not observed. Brimonidine was associated with no adverse effects on pulse rate.Funding: Senju Pharmaceutical Co., Ltd.Trial Registration: UMIN Clinical Trials Registry identifier, UMIN000014810. [ABSTRACT FROM AUTHOR]

Introduction: Solid facial edema (SFE) is a rare complication of acne vulgaris. To examine the clinical features of acne patients with solid facial edema, and to give an overview on the outcome of previous topical and systemic treatments in the cases so far published. Methods: We report two cases from Switzerland, both young men with initially papulopustular acne resistant to topical retinoids. Results: Both cases responded to oral isotretinoin, in one case combined with oral steroids. Our cases show a strikingly similar clinical appearance to the cases described by Connelly and Winkelmann in 1985 (Connelly MG, Winkelmann RK. Solid facial edema as a complication of acne vulgaris. Arch Dermatol. 1985;121(1):87), as well as to cases of Morbihan's disease that occurs as a rare complication of rosacea. Conclusion: Even 30 years after, the cause of the edema remains unknown. In two of the original four cases, a potential triggering factor was identified such as facial trauma or insect bites; however, our two patients did not report such occurrencies. The rare cases of solid facial edema in both acne and rosacea might hold the key to understanding the specific inflammatory pattern that creates both persisting inflammation and disturbed fluid homeostasis which can occur as a slightly different presentation in dermatomyositis, angioedema, Heerfordt's syndrome and other conditions. [ABSTRACT FROM AUTHOR]

Aims: Diabetic retinopathy is considered a microvascular disease, but recent evidence has underlined early involvement of the neuroretina with interactions between microvascular and neural alterations. Topical administration of somatostatin (SST), a neuroprotective molecule with antiangiogenic properties, prevents diabetes-induced retinal neurodegeneration in animals. The α-adrenergic receptor agonist brimonidine (BRM) decreases vitreoretinal vascular endothelial growth factor and inhibits blood-retinal barrier breakdown in diabetic rats. However, SST and BRM effects on microvascular cells have not yet been studied. We investigated the behaviour of these drugs on the crosstalk between microvasculature and neuroretina. Methods: Expression of SST receptors 1-5 in human retinal pericytes (HRP) was checked. We subsequently evaluated the effects of diabetic-like conditions (high glucose and/or hypoxia) with/without SST/BRM on HRP survival. Endothelial cells (EC) and photoreceptors were maintained in the above conditions and their conditioned media (CM) used to culture HRP. Vice versa, HRP-CM was used on EC and photoreceptors. Survival parameters were assessed. Results: HRP express the SST receptor 1 (SSTR1). Glucose fluctuations mimicking those occurring in diabetic subjects are more damaging for pericytes and photoreceptors than stable high glucose and hypoxic conditions. SST/BRM added to HRP in diabetic-like conditions decrease EC apoptosis. However, neither SST nor BRM changed the response of pericytes and neuroretina-vascular crosstalk under diabetic-like conditions. Conclusions: Retinal pericytes express SSTR1, indicating that they can be a target for SST. Exposure to SST/BRM had no adverse effects, direct or mediated by the neuroretina, suggesting that these molecules could be safely evaluated for the treatment of ocular diseases. [ABSTRACT FROM AUTHOR]

Rosacea is a chronic inflammatory disease with transient and non-transient redness as key characteristics. Brimonidine is a selective α2-adrenergic receptor (AR) agonist approved for persistent facial erythema of rosacea based on significant efficacy and good safety data. The majority of patients treated with brimonidine report a benefit; however, there have been sporadic reports of worsening erythema after the initial response. A group of dermatologists, receptor physiology, and neuroimmunology scientists met to explore potential mechanisms contributing to side effects as well as differences in efficacy. We propose the following could contribute to erythema after application: (1) local inflammation and perivascular inflammatory cells with abnormally functioning ARs may lead to vasodilatation; (2) abnormal saturation and cells expressing different AR subtypes with varying ligand affinity; (3) barrier dysfunction and increased skin concentrations of brimonidine with increased actions at endothelial and presynaptic receptors, resulting in increased vasodilation; and (4) genetic predisposition and receptor polymorphism(s) leading to different smooth muscle responses. Approximately 80% of patients treated with brimonidine experience a significant improvement without erythema worsening as an adverse event. Attention to optimizing skin barrier function, setting patient expectations, and strategies to minimize potential problems may possibly reduce further the number of patients who experience side effects.Funding: Galderma International S.A.S., Paris, France. [ABSTRACT FROM AUTHOR]

Purpose: The p62, also called sequestosome 1 (SQSTM1), plays a crucial role in tumor necrosis factor (TNF)-induced optic nerve degeneration. Brimonidine has been shown to have protective effects on retinal ganglion cell bodies, although its role in their axons remains to be examined. We determined whether brimonidine modulates axonal loss induced by TNF and affects the expression of p62 in the optic nerve. Methods: Experiments were performed on adult male Wistar rats that received an intravitreal injection of 10 ng TNF alone or simultaneous injection of TNF and 2, 20, or 200 pmol of brimonidine tartrate. The expression of p62 in the optic nerve was examined by immunoblot analysis. The effects of brimonidine on axons were evaluated by counting axon numbers 2 weeks after intravitreal injection. Results: Intravitreal injection of brimonidine exerted substantial axonal protection against TNF-induced optic nerve degeneration. Immunoblot analysis showed that p62 was upregulated in the optic nerve after intravitreal injection of TNF, and that this increase was completely inhibited by brimonidine. Treatment with brimonidine alone also significantly decreased p62 protein levels in the optic nerve compared with the basal level. Conclusions: These results suggest that the modulation of p62 levels in the optic nerve by brimonidine may be involved partly in its axonal protection. [ABSTRACT FROM AUTHOR]

To evaluate the role of brimonidine (BMD), an alpha-2 agonist, in the management of clinically significant macular edema (CSME) in diabetic maculopathy with ischemic changes. A prospective, randomized controlled trial including 30 eyes of 30 metabolically stable diabetic patients with CSME showing fundus fluorescein angiography documented ischemic changes. Group I included 17 eyes of patients who received topical BMD (0.2 %) twice daily for 6 months while Group II included 13 eyes of age-matched patients who were kept under observation and acted as controls. The mean change in logMAR visual acuity and any change in the grade of the foveal avascular zone (FAZ) size, outline, capillary non-perfusion, or capillary dilatation was noted in the two groups and compared at the end of 6 months. The FAZ area and radius was significantly less in the study group than the control group. However, no significant difference in FAZ capillary outline, FAZ capillary loss, FAZ capillary dilatation and overall grade of ischemia between the two groups was seen. There was improvement in visual acuity from baseline to 6 months but it was comparable between the two groups ( p = 0.02). BMD may have a role in the treatment of ischemic macula in CSME since the FAZ area and radius were significantly less in the study group. However, a larger sample size and a longer follow-up are needed to further authenticate the results of this pilot study. [ABSTRACT FROM AUTHOR]

Purpose: Preparation of topical ophthalmic formulations containing brimonidine-loaded nanoparticles prepared from various biodegradable polymers-PCL, PLA and PLGA-for sustained release of brimonidine as a once daily regimen for management of glaucoma. Methods: Nanoparticles were prepared using spontaneous emulsification solvent diffusion method then characterized regarding their particle size, zeta potential, morphology and drug contents. Brimonidine-loaded nanoparticles were incorporated into eye drops, temperature-triggered in situ gelling system and preformed gel and characterized regarding their pH, viscosity, uniformity of drug contents, in vitro release study, in vitro cytotoxicity and in vivo intraocular pressure (IOP) lowering effects. Results: The results of optimized brimonidine-loaded PCL-, PLGA- and PLA-NPs respectively, are: particle sizes of 117.33 ± 4.58 nm, 125.67 ± 5.15 nm and 131.67 ± 3.79 nm; zeta potentials of −18.5 ± 2.87 mV, −21.82 ± 2.7 mV and −28.11 ± 2.21 mV; and encapsulation efficiencies of 77.97 ± 1.38%, 68.65 ± 3.35% and 73.52 ± 2.92%. TEM analyses revealed that all NPs have spherical shapes with dense core and distinct coat. In vitro release data showed a sustained release without any burst effect with Higuchi non-Fickian diffusion mechanism. Cytotoxicity studies revealed that all formulations are non-toxic. Also all formulations possessed a sustained IOP lowering effect compared to Alphagan® P eye drops. Conclusions: Our formulations showed prolonged management of glaucoma that should meet with better patient compliance as a once-daily formulation. [ABSTRACT FROM AUTHOR]

We report on two cases of granulomatous conjunctivitis and uveitis related with the use of a brimonidine-timolol fixed combination. Case report and a review of medical literature. A 64-year-old man was diagnosed with marked granulomatous uveitis and a 57-year-old woman was diagnosed with granulomatous conjunctivitis. Both patients were using a topical fixed combination of brimonidine 0.2 %-timolol 0.5 % for open angle glaucoma. Bilateral granulomatous uveitis and conjunctivitis were diagnosed after 16 months of treatment with a fixed combination of brimonidine-timolol in both cases. Granulomatous inflammation resolved with the cessation of antiglaucomatous drugs and topical corticosteroid treatment. When the inflammation had resolved completely, both patients were rechallenged with topical brimonidine in one eye only to determine causality. Conjunctival hyperemia is a common side effect of glaucoma medications and is sometimes overlooked. Hyperemia may be associated with other signs such as iritis and keratic precipitates or conjunctival inflammation. In such cases, granulomatous inflammation may be considered in the differential diagnosis. The fixed-combination of brimonidine-timolol may cause this clinical picture. [ABSTRACT FROM AUTHOR]

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The bioavailability of therapeutic agents from eye drops is usually limited due to corneal barrier functions and effective eye protective mechanisms. Therefore, the current study aims to enhance ocular bioavailability of brimonidine, a potent antiglaucoma drug, through the preparation of ocular inserts. Solvent casting technique was employed to prepare the inserts using polyvinylpyrrolidone K-90 (PVP K-90) as film-forming polymer blended with different viscosity grades of bioadhesive polymers namely hydroxypropyl methycellulose, carbopol, sodium alginate, and chitosan. The prepared ocular inserts were evaluated for various physicochemical parameters, swelling behavior, and in vitro release patterns. Sodium alginate-based ocular inserts revealed the most sustainment in drug release (99% at 6 h), so it was selected for further modifications via coating it, on one side or dual sides, using hydrophobic film composed of either ethylcellulose or Eudragit RSPO. The obtained in vitro release results for the modified ocular inserts revealed that ethylcellulose is superior to Eudragit RSPO in terms of brimonidine release sustainment effect. Ocular inserts composed of 7% PVP K-90, 1.5% low molecular weight sodium alginate with or without ethylcellulose coat were able to sustain the in vitro release of brimonidine. Their therapeutic efficacy regarding intraocular pressure (IOP) lowering effect when inserted in albino rabbits eyes showed superior sustainment effect compared with that of brimonidine solution. Furthermore, due to both the mucoadhesive property and the drug sustainment effect, the one-side-coated ocular insert showed more IOP lowering effect compared with that of its non-coated or dual-side-coated counterpart. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effects of brimonidine 0.2%-timolol 0.5% fixed-combination therapy in the treatment of patients with glaucoma. Methods: To measure the main treatment effects of a fixed combination of brimonidine 0.2%-timolol 0.5%, we conducted three small studies: (1) a comparison of diurnal intraocular pressure (IOP) at baseline and at 6 months after brimonidine/timolol fixed-combination therapy ( n = 81); (2) an assessment of the effects of one drop of the brimonidine/timolol fixed combination on diurnal IOP ( n = 25); and (3) the effects of brimonidine/timolol fixed-combination therapy on the anterior ocular segment over time ( n = 64). Results: (1) After 6 months of treatment with the brimonidine/timolol fixed combination, the mean diurnal IOP in primary open-angle glaucoma (POAG) decreased from 21.4 ± 2.0 to 14.5 ± 3.1 mmHg (32.2%, P < 0.001), and the mean diurnal IOP in normal-tension glaucoma (NTG) decreased from 13.5 ± 2.8 to 10.9 ± 2.0 mmHg (19.3%, P < 0.001). (2) After instillation with one drop of the brimonidine/timolol fixed combination, the IOP in the instilled eye was lowest at 9:00 p.m. and had decreased by 1.7 mmHg compared with the baseline IOP in the instilled eye. The difference in IOP between the instilled eye and untreated fellow eye was largest at 3:00 p.m., measuring 1.7 mmHg ( P = 0.011). (3) Brimonidine/timolol fixed-combination therapy caused significant miosis over time ( P = 0.003). Conclusions: The results of this study suggest that brimonidine/timolol fixed-combination therapy has beneficial IOP-lowering effects and significant effects on pupil size. [ABSTRACT FROM AUTHOR]

The purpose of this research is to investigate the expression of matrix metalloproteinase-9 (MMP-9) in retinal ganglion cells (RGC) and the impact of topically applied brimonidine tartrate 0.2% (BMD) on this expression in an endothelin-1 (ET-1)-induced chronic optic nerve (ON) ischemia model of rabbit. Osmotically driven minipumps were implanted in one eye of 16 New Zealand albino rabbits to deliver ET-1 at the constant rate of 0.5 μl/h for 2 weeks. ET-1 was given with (group 3) and without topical BMD therapy (group 1). Groups 2 and 4 were taken as controls. MMP-9 expression by immunohistochemically and proportion of cells undergoing apoptosis in RGC layer were investigated. The correlation between the MMP-9 immunopositivity and the proportion of cells undergoing apoptosis in the RGC layer was evaluated. MMP-9 immunopositivity was found to be significantly higher in both groups 1 and 3 compared to that of the controls. There was no difference between groups 1 and 3 regarding MMP-9 expression ( p = 0.495). A positive correlation was found between the proportion of cells undergoing apoptosis and MMP-9 expressions in the RGC layer in group 1 ( p = 0.031, r = 0.754). MMP-9 expression in the RGC layer seems to significantly increase in the ET-1-induced chronic ON ischemia model. Topical BMD therapy does not seem to affect this MMP-9 expression. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effects of two commercially available combination topical ophthalmic medications on human ocular surface cells in vitro. Tissue culture plates (96-well) containing immortalized human corneal and conjunctival epithelial cells were divided into five groups. The test solutions examined were: timolol 0.5%+brimonidine 0.2%, containing 0.0050% benzalkonium chloride (BAK); timolol 0.5%+dorzolamide 2%, containing 0.0075% BAK; and preservative-free artificial tears. Balanced salt solution (BSS) was used as the live control, and a fixative solution containing 70% methanol and 0.2% saponin was used as the dead control. Cells were exposed to 100 μL of test or control solution for 25 minutes at 37°C and 5% carbon dioxide (CO2). A live cell assay was used to measure the toxicity of combination treatments compared with BSS controls. Exposure to timolol 0.5%+brimonidine 0.2% resulted in a significantly higher percentage of living conjunctival cells (48%±12%) as compared with timolol 0.5%+dorzolamide 2% (10%±5%, P<0.00001). In corneal cells, testing revealed 12%±3% live cells after timolol 0.5%+brimonidine 0.2% exposure compared with 2%±3% after timolol 0.5%+dorzolamide 2% ( P<0.001). Both combination medications demonstrated a significant reduction in the percentage of live corneal and conjunctival epithelial cells compared with control. However, cell cultures exposed to timolol 0.5%+dorzolamide 2% had significantly fewer live cells compared with cell cultures exposed to timolol 0.5%+brimonidine 0.2%. Further studies are needed to better understand the clinical significance of these findings in patients using these medications for chronic treatment of glaucoma and ocular hypertension. [ABSTRACT FROM AUTHOR]

This paper describes experiments in cell systems that have helped clarify intracellular mechanisms leading to apoptosis. Using the cellular systems described (rat retinal whole mount, rat retinal cell line E1A-NR3, and rat neuronal cell line NG 108-15), it has been possible to demonstrate that intracellular pH change may be the mechanism through which carbonic anhydrases modulate vasodilation and act on retinal blood flow. Intracellular pH can also be used to monitor intracellular changes that precede and occur during apoptosis. The findings also show the potential significance of advanced glycation end products (AGEs) in the glaucomatous process, and the potential for brimonidine and memantine to rescue neuroretinal cells from AGE-induced retinal damage.Eye (2007) 21, S38–S41; doi:10.1038/sj.eye.6702887 [ABSTRACT FROM AUTHOR]

Recent research in the field of neuroprotection in glaucoma has focused on the N-methyl-D-aspartate (NMDA) and the α-2 adrenergic receptor systems. Experimental findings have shown that brimonidine (BMD), a specific α-2 adrenoceptor agonist, can protect against loss in mitochondrial membrane potential during oxidative stress, and preserve anterograde axonal transport. Memantine is a selective blocker of the NMDA-type glutamatergic type ion channel. It has unique open channel blocker properties that result in a preferential inhibition of excessive (excitotoxic) neuronal activation by high levels of glutamate without interfering with the channel's normal functions. In a primate model, memantine was neuroprotective as can be seen from its effect on maintaining/preserving RGCs. Research in Alzheimer's disease has demonstrated that memantine may increase neuronal functionality as well as being protective. Research in a primate glaucoma model shows that memantine protects neurons from shrinking in the lateral geniculate nucleus. Memantine is currently in clinical trials for glaucoma.Eye (2007) 21, S46–S50; doi:10.1038/sj.eye.6702889 [ABSTRACT FROM AUTHOR]

The Low-Pressure Glaucoma Treatment Study is a double-masked, randomized trial comparing the visual outcomes of 190 low-pressure glaucoma patients randomized to intraocular pressure reduction with brimonidine tartrate or timolol maleate. Baseline characteristics of participants are compared to published studies.Eye (2007) 21, S51–S54; doi:10.1038/sj.eye.6702890 [ABSTRACT FROM AUTHOR]

This study was undertaken to evaluate the ocular hypotensive efficacy of brimonidine Purite® 0.15% (Alphagan® P 0.15%; Allergan, Inc., Irvine, Calif) given as adjunctive therapy with latanoprost 0.005% (Xalatan®; Pfizer Inc., New York, NY) to patients with open-angle glaucoma or ocular hypertension. In this multicenter, open-label, prospective evaluation, the intraocular pressure (IOP) of the 43 enrolled patients was ≥18 mm Hg after at least 6 wk of latanoprost monotherapy. The primary outcome measure was IOP at peak drug effect (10 am, or approximately 2 h after the morning dose of brimonidine 0.15%). IOP at trough drug effect (8 am, or approximately 12 h after the evening dose of brimonidine) was also measured. Baseline IOP was 21.9 (±2.3) mm Hg. After 1 mo of treatment, additional mean IOP reductions from latanoprost-treated baseline values were 5.8 mm Hg (26%) at peak drug effect ( P < .001) and 3.3 mm Hg (15%) at trough ( P < .001). At the month 2 visit, additional mean IOP reductions from latanoprost-treated baseline values were 5.1 mm Hg (23%) at peak drug effect ( P < .001) and 2.0 mm Hg (9%) at trough ( P=.002). Brimonidine Purite 0.15% provided statistically significant additional reductions in IOP from latanoprost-Transmission and reproduction of this material in whole or part without prior written approval are prohibited. treated baseline values. These findings suggest that brimonidine Purite 0.15% is an efficacious adjunctive therapy in patients given latanoprost who require additional lowering of IOP. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

AIM:To identify the relative incidence and profile of adverse drug reaction (ADR) to various topical ocular hypotensives in a hospital setting. METHODS:All the patients presenting in outpatients clinic and accident and emergency with an ADR to topical hypotensive agent from August 2000 to January 2001 were included in the study. Details regarding the type date of commencing the treatment, the date of developing ADR, time to resolution of the ADR were noted. RESULTS:Over the period of 6 months, 66 patients presented with 73 ADRs. Brimonidine was the most frequent offending agent. In total, 23 (34.8%) presented with ADR after being commenced on treatment for more than 12 months. In all, 16 (24%) patients had IOP>21 on presentation, eight (12%) patients underwent filtration surgery following the development of ADR. CONCLUSION:Adverse drug reaction to ocular hypotensive agents is not uncommon and can have a major impact on glaucoma management. Delayed presentation and association with raised intraocular pressure presentation emphasise the need for effective patient education to encourage prompt reporting of ADR.Eye (2005) 19, 392-395. doi:10.1038/sj.eye.6701515 Published online 6 August 2004 [ABSTRACT FROM AUTHOR]

Purpose: To compare the effects of brimonidine 0.2% and apraclonidine 1% on intraocular pressure (IOP) and pupil size in patients undergoing laser peripheral iridotomy (LPI). Methods: Forty patients (40 eyes) with occludable angle or angle-closure glaucoma requiring LPI were recruited. Patients were randomized to receive either brimonidine 0.2% or apraclonidine 1% before and after LPI. The IOPs were measured at 1, 2 and 3 h after LPI, and pupil size was measured before and at 45 min after eyedrop instillation. Both parameters were analyzed using the t test. Results: There were 20 patients in each group. The baseline IOP was 17.1 ± 3.2 mmHg for the brimonidine group and 16.7 ± 2.8 mmHg for the apraclonidine group ( P = 0.67) ( t test). The mean IOP 3 h after laser treatment was 18.2 ± 7.8 mmHg for the brimonidine group and 15.7 ± 5.6 mmHg for the apraclonidine group ( P = 0.25) ( t test). There was no statistically significant difference between the two groups in the mean IOP changes at 1, 2, or 3 h after LPI. The mean change in pupil size after brimonidine was −0.33 ± 0.37 mm and after apraclonidine was +0.90 ± 0.87 mm. The difference was significant ( P < 0.001). Conclusion: Brimonidine 0.2% was found to have an efficacy comparable to that of apraclonidine 1.0% in preventing post LPI IOP spikes. Apraclonidine 1.0% tends to have a pupil dilating effect while brimonidine 0.2% tends to constrict the pupil. [ABSTRACT FROM AUTHOR]

PURPOSE: To compare the additive intraocular pressure (IOP)-lowering effects of latanoprost 0.005%and brimonidine 0.2%in primary open-angle glaucoma (POAG) patients uncontrolled on fixed combination of timolol 0.5%and dorzolamide 2%(TDC) alone. METHODS: In all, 80 eyes of 80 POAG patients with IOP inadequately controlled by TDC were randomly assigned to receive either latanoprost 0.005%or brimonidine 0.2%. IOP measurements were recorded at 1000 (peak effect) and 1600 (trough effect) on day 0 (baseline) and at 1 and 3 months. At each stage and time point, the mean IOP reductions from baseline were evaluated for both groups, and success rates (minimum 15%reduction) were determined. RESULTS: At baseline, the mean peak/trough IOPs with TDC were 20.2/21.6 and 19.9/21.4?mmHg in latanoprost and brimonidine groups, respectively. Latanoprost+TDC reduced the mean peak/trough IOP by 4.4/3.4 and 5.2/3.5?mmHg at 1 and 3 months. The corresponding values for brimonidine+TDC were 3.9/2.9 and 4.6/2.9?mmHg. Each of these results represented a significant reduction from baseline (P<0.001 for all); however, the groups’peak/trough reductions from baseline did not differ at any time point (P>0.05 for all). With the latanoprost+TDC combination, the peak/trough success rates at 1 and 3 months were 76.3%/42.1%and 77.1%/40%. The corresponding values with the brimonidine+TDC combination were 71.8%/41%and 77.7%/41.7%. There were no significant differences in the groups’success rates at any time point (P>0.05 for all). CONCLUSION: Addition of latanoprost 0.005%or brimonidine 0.2%to TDC reduces peak/trough IOPs significantly and the effects of these combinations are comparable.Eye (2005) 19, 145-151. doi:10.1038/sj.eye.6701428 Published online 7 May 2004 [ABSTRACT FROM AUTHOR]

AIMS:Since its introduction in 1996, brimonidine tartrate 0.2%ophthalmic solution (Alphagan, Allergan) twice daily has become established as an effective intra ocular pressure-lowering treatment. While the efficacy of Alphagan cannot be questioned, we gained the clinical impression that the drug has an unacceptably high rate of allergy. Of greater concern, we suspected that patients suffering from local Alphagan allergy had a higher rate of allergy to subsequently used topical preparations. We analysed data from a large scale study of glaucoma patients to establish whether our suspicions were correct. SUBJECTS AND METHODS:We have created a database of the entire glaucoma treatment histories for consecutive patients attending a single consultant's clinics (DMIM) at Glasgow Royal Infirmary between May 1999 and September 2001. All have undergone medical treatment for primary open angle glaucoma, ocular hypertension, or normal tension glaucoma. Patients with any other form of glaucoma, and patients in whom a full record of treatment was not available were excluded from the study. RESULTS:Alphagan was discontinued due to allergy on 73 per 100?000 patient treatment days. This was a far higher frequency than for other preparations. In patients allergic to both Alphagan and another preparation (Timoptol, Trusopt and Xalatan), the mean interval between the first and second allergy was shorter when Alphagan allergy occurred first. This was statistically significant in Timoptol and Trusopt cross-reactivity. CONCLUSIONS:Alphagan has high allergenicity, and may increase the likelihood of allergy to subsequently used preparations.Eye (2005) 19, 129-137. doi:10.1038/sj.eye.6701441 Published online 9 July 2004 [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily.Methods: In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period.Results: In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey.Conclusion: Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve. [ABSTRACT FROM AUTHOR]

AIMS:To evaluate the efficacy and safety of latanoprost/timolol maleate fixed combination (LTFC) given once daily vs the concomitant therapy of brimonidine twice daily and latanoprost once daily in primary open-angle glaucoma or ocular hypertensive subjects. METHODS:A prospective, double-masked, active-controlled comparison in which qualified subjects had all glaucoma medicines discontinued for 1 month and then were randomized to either LTFC or brimonidine and latanoprost concomitant therapy for 6 weeks. They were then switched to the other treatment regimen. The intraocular pressure (IOP) was measured at 0800, 1200, and 1600?h at baseline and at the end of Periods 1 and Period 2. RESULTS:In 32 subjects, the diurnal curve of the untreated IOP of 26.0±3.4 decreased to 17.8±2.5 on LTFC and 17.2±2.8?mmHg on brimonidine and latanoprost (P=0.31). At 0800 and 1600 h, the IOPs were statistically similar between the groups (P>0.05). At 1200?h the latanoprost and brimonidine treatment IOP was statistically lower (16.2±3.2) than LTFC (18.0±2.8?mmHg). However, the reduced IOP from untreated baseline was not statistically different at each time point and for the diurnal curve for each therapy (P<0.05). Safety was similar between groups for both solicited and unsolicited side effects (P>0.05). CONCLUSION:This study suggests that LTFC and concomitant therapy of brimonidine and latanoprost provide statistically similar diurnal IOP reduction from an untreated baseline.Eye (2004) 18, 990-995. doi:10.1038/sj.eye.6701375 Published online 19 March 2004 [ABSTRACT FROM AUTHOR]

The tolerability of brimonidine tartrate 0.15%—referred to as bromonidine-Purite® 0.15% in this study—was compared with brimonidine tartrate 0.2% in irritated eyes of healthy volunteers as well as patients with glaucoma or ocular hypertension (N=20) in a 2-week, single-center, randomized, double-masked, crossover study. Participants were evaluated at days 0, 7, 11, and 15. At day 0, they were exposed to a controlled adverse environment (CAE), in which humidity, temperature, and airflow was regulated, for up to 90 minutes. Participants who reported a sufficient level of bilateral ocular discomfort during exposure to the CAE were enrolled in this study and received 1 drop of brimonidine-Purite 0.15% in 1 eye and 1 drop of brimonidine tartrate 0.2% in the contralateral eye. Immediately following instillation, participants were asked to indicate their preference for either study medication. The study medications were not used between days 0 and 7. From day 7 to 10, participants administered either drug bilaterally. On day 11, the treatment was crossed over, and participants were asked to compare the preferred medication with their previous regimen. They continued to administer the drug bilaterally twice daily until day 15, when the preferred medication was again compared with the previous regimen. Following CAE exposure at visit 1, 70.6% of the participants preferred brimonidine-Purite 0.15% over brimonidine tartrate 0.2% and indicated that it was significantly more comfortable than brimonidine tartrate 0.2% ( P=.009). When given brimonidine-Purite 0.15% first before switching to brimonidine tartrate 0.2%, 80% of participants preferred brimonidine-Purite 0.15% ( P=.012). When given brimonidine tartrate 0.2% first before switching to brimonidine-Purite 0.15%, 85% preferred brimonidine-Purite 0.15% (P=.001). The results of this study suggest that brimonidine-Purite 0.15% is significantly more comfortable than brimonidine tartrate 0.2% in patients with irritated eyes. [ABSTRACT FROM AUTHOR]

Two double-masked, randomized, parallel, multicenter trials of similar design were conducted to compare the IOP-lowering efficacy of dual therapy with brimonidine 0.2% and latanoprost 0.005% with the fixed combination of timolol 0.5%/dorzolamide 2% in patients with glaucoma or ocular hypertension. The combination of brimonidine and latanoprost produced significantly greater mean IOP reductions at each visit in both trials. In study 1, the mean reduction at peak drug effect after 6 weeks was 9.2 mm Hg (34.7%) with brimonidine and latanoprost and 6.7 mm Hg (26.1%) with timolol/dorzolamide (P=.024); respective reductions at week 12 were 9.0 mm Hg (33.9%) and 6.5 mm Hg (25.3%) (P=.044). At the month 1 visit in study 2, the mean peak IOP reduction was 10.6 mm Hg (39.0%) with dual therapy and 6.3 mm Hg (25.1%) with the fixed combination (P=.001). After 3 months, reductions were 9.1 mm Hg (33.4%) and 6.6 mm Hg (26.3%) (P=.047). In these studies, the combination of brimonidine and latanoprost provided IOP control superior to that of the fixed combination of timolol/dorzolamide. [ABSTRACT FROM AUTHOR]

This 3-month multicenter, investigator-masked, parallel-group study compared brimonidine Purite and bimatoprost (brimP/bim) with timolol gel-forming solution and latanoprost (tim/latan) in 28 patients with open-angle glaucoma or ocular hypertension. IOP was measured at baseline and 2 hours after morning instillation at weeks 2, 4, and 12. The primary outcome measure was the mean IOP reduction from baseline. Secondary measures were the percentage of patients in each group who achieved specific low target pressures and the incidence of adverse events. Mean IOP at baseline was 24.8 mm Hg in each group. At follow-up visits, mean reductions from baseline ranged from 8.5 to 9.0 mm Hg with brimP/bim and from 7.5 to 7.7 mm Hg with tim/latan. More patients achieved low target pressures with brimP/bim. At week 12, 69.2% of brimP/bim patients and 27.3% of tim/latan patients had IOPs of 16 mm Hg or lower (P = .024). Both regimens were well tolerated, and adverse events were infrequent. The combination of brimonidine Purite and bimatoprost was well tolerated and at least as effective as Timoptic-XE and latanoprost in reducing IOP. More patients achieved low target IOPs with brimonidine Purite and bimatoprost than with Timoptic-XE and latanoprost. A larger study is needed to confirm these results. [ABSTRACT FROM AUTHOR]

This 3-month multicenter, open-label study of 89 geriatric patients with glaucoma evaluated the substitution of brimonidine twice daily for topical beta blockers that had been used for at least 6 months. The primary outcome measures were reduction in intraocular pressure (IOP) from baseline at 2 hours postdose, change in cardiac and respiratory function, quality of life, and patient satisfaction. Patients were queried about adverse events at each visit and completed a quality-of-life questionnaire at the final evaluation. In this cohort with a mean age of 75.4 years, the average duration of topical beta-blocker therapy was 5 years. Brimonidine twice daily produced an additional mean reduction in IOP of 8.2% (1.4 mm Hg; P<.001). Eighty-eight percent of patients (60/68) reported being at least as satisfied with brimonidine as with their previous beta-blocker regimen, and 46% (31/68) reported greater satisfaction with brimonidine. Additionally, 40% of patients (27/68) noted increased energy after the switch, and 43% (29/68) described brimonidine as more soothing than topical beta blockers. In this elderly population, the replacement of topical beta blockers with brimonidine twice daily significantly decreased IOP, improved quality of life, and enhanced patient satisfaction. [ABSTRACT FROM AUTHOR]

A multicenter open-label study investigated the clinical effectiveness and economic feasibility of switching 142 patients from dual therapy to twice-daily monotherapy with brimonidine for glaucoma or ocular hypertension. Evaluations were performed at baseline and 2 (visit 2) and 8 (visit 3) weeks after the switch. Patients completed a questionnaire that rated medication-related visual function and satisfaction (comfort, convenience, vision, ease of remembering to use drops) at each visit. At visit 3, investigators, taking into account IOP measurements, safety, and responses on the questionnaire, recommended whether the patient should remain on brimonidine. A pharmacoeconomic analysis, including the number of visits, cost of medication, and success rates, compared the cost of dual therapy with that of switching to brimonidine monotherapy. Of the 131 patients who completed the study, 77 (59%) had no change or a decrease in IOP from baseline, and 53 (41%) had an increase. Investigators recommended that 77% of the study completers continue to take brimonidine monotherapy. Extending treatment with brimonidine for 12 months would achieve a significant cost savings of 16%. Brimonidine monotherapy is an efficacious and cost-effective alternative to dual therapy for glaucoma and ocular hypertension. Appropriate monotherapy may be as effective as dual therapy for many patients, and a clinically relevant trial such as this may be economically advantageous for testing a switch. [ABSTRACT FROM AUTHOR]

Copyright of Der Ophthalmologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)