A Comparative Study on Efficacy of Intraocular Pressure Lowering of Two Fixed-Dose Antiglaucoma Drug Combination Brinzolamide-Brimonidine Versus Latanoprost-Timolol in Primary Open-Angle Glaucoma and Ocular Hypertension.

Purpose: To compare the efficacy of Brinzolamide-Brimonidine (BB) (1%+0.2%) with the gold standard Latanoprost-Timolol (LT) (0.005%+0.5%) in treating primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Methods: A 1-year prospective study, spanning from May 2022 to May 2023, conducted at a tertiary eye-care hospital. Participants, aged 40-60, with a baseline intraocular pressure (IOP) >21 mm Hg, requiring a >30% reduction, were enrolled. Group A (n = 100) received BB, and Group B (n = 100) received LT. Outcomes were assessed at 1 month (IOP difference from baseline), 3 and 6 months (mean diurnal variations). Results: The mean age at presentation was 55.5 ± 4.5 years in Group A and 54.7 ± 4.2 years in Group B. At 1 month, Group A exhibited a mean IOP of 18.7 mm Hg, while Group B had 17.6 mm Hg, with no statistically significant difference (P = 0.53). No significant diurnal variation was observed in either group (P = 0.07). Target pressure was achieved in 88% of patients in Group A and slightly higher at 92% in Group B. Moreover, no serious side effects were reported, and compliance was higher in Group B (98%) compared to Group A (96%). Conclusion: Although LT showed slightly better and sustained IOP reduction, the difference was not statistically significant. Both BB and LT demonstrated comparable outcomes for managing POAG and OHT.

Topical brimonidine induced acute uveal effusion in a patient with nanophthalmos: a case report.

BACKGROUND: We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine. CASE PRESENTATION: A 42-year-old male patient with nanophthalmos experienced sudden blurred vision in the right eye after using topical brimonidine when picking up tennis balls repeatedly 6 weeks after bilateral YAG peripheral iridotomy. Ocular examination showed wide choroidal and exudative retinal detachment in the temporal and inferior region, involving the macula. Acute uveal effusion in the right, bilateral nanophthalmos was diagnosed. Oral and topical corticosteroids, combined with topical nonsteroids and atropine led to a complete resolution of the uveal effusion after one month. CONCLUSION: This case suggested a possible causal relationship between the topical use of brimonidine and acute uveal effusion in patients with nanophthalmos. Topical brimonidine should be used with caution in nanophthalmic eyes.

Comparisons of efficacy and safety between preserved and preservative-free brimonidine tartrate in glaucoma and ocular hypertension: a parallel-grouped, randomized trial.

This multicenter (four institutions), randomized, investigator-masked, parallel-group clinical trial evaluated and compared the efficacy and safety of preservative-free and preserved brimonidine tartrate 0.15% in open-angle glaucoma and ocular hypertension. Sixty eyes of 60 patients with intraocular pressure (IOP) ≥ 15 mmHg diagnosed with open-angle glaucoma or ocular hypertension were randomized to preserved (n = 31) and preservative-free (n = 29) brimonidine groups. The enrolled eyes received brimonidine monotherapy three times daily. Main outcome measures were corneal/conjunctival staining score, ocular surface disease index, patient satisfaction score, drug tolerance, and drug adherence rate 12 weeks post first administration. Secondary outcome measurements included visual acuity, IOP, drug tolerance, tear-film break-up time, hemodynamic changes including blood pressure and heart rates, and ocular adverse events. After 12 weeks, both preserved and preservative-free groups showed similar IOP reduction, corneal and conjunctival staining scores, drug tolerance, and adherence rates. The preservative-free group showed significantly better tear-film break-up time and higher patient satisfaction regarding drug use and management. Systolic and diastolic blood pressure reductions during the 12 weeks were significantly lower in the preserved group than in the preservative-free group. Preservative-free brimonidine tartrate showed comparable efficacy and safety, better corneal tear film stability, and patient satisfaction than preserved brimonidine.

Ripasudil-Brimonidine Fixed-Dose Combination vs Ripasudil or Brimonidine: Two Phase 3 Randomized Clinical Trials.

PURPOSE: To confirm the superiority of the intraocular pressure (IOP)-lowering effect of the ripasudil-brimonidine fixed-dose combination (RBFC, K-232) to ripasudil 0.4% or brimonidine 0.1% ophthalmic solution. DESIGN: Two prospective multicenter, randomized, double- or single-masked, active-controlled, phase 3 trials. METHODS: Patients with primary open-angle glaucoma or ocular hypertension whose IOP level was ≥18 mm Hg during treatment with ripasudil or brimonidine alone were randomized to 2 groups (RBFC and ripasudil) in a 1:1 ratio in the ripasudil-controlled trial and to 3 groups (RBFC, brimonidine, and ripasudil-brimonidine combination) in a 2:2:1 ratio in the brimonidine-controlled trial. The allocated study drugs were instilled twice daily for 8 weeks. The primary efficacy endpoint was the change in IOP 2 hours after instillation (11 AM) from the baseline to weeks 4, 6, and 8. RESULTS: There were 206 patients randomized in the ripasudil-controlled trial. Changes in IOP were -2.6 and -1.2 mm Hg in the RBFC and ripasudil groups, respectively, with a difference of -1.4 mm Hg (95% CI = -1.8 to -1.0 mm Hg; P < .001). There were 282 randomized patients in the brimonidine-controlled trial. Changes in IOP were -3.4 and -1.5 mm Hg in the RBFC and brimonidine groups, respectively, with a difference of -1.8 mm Hg (95% CI = -2.3 to -1.4 mm Hg; P < .001). The most frequent adverse event was conjunctival hyperemia. CONCLUSIONS: The IOP-lowering effect of RBFC was superior to that of ripasudil or brimonidine.

Efficacy and safety of topical brimonidine in dermatology: A review article.

Brimonidine is a vasoconstrictive agent used to treat several dermatologic disorders. Here, we review the uses of brimonidine in different aspects of dermatology. We searched keywords including rosacea, erythema, topical brimonidine, dermatology, and skin disease in PubMed, Cochrane, and Google Scholar to collect the related published articles. In a review of 15 articles, we found topical brimonidine improved the facial erythema of rosacea. In addition, it reduced the erythema associated with alcohol flushing syndrome, intense pulsed light therapy, and photodynamic therapy. Furthermore, topical brimonidine was used as a hemostatic agent in dermatosurgery procedures such as Mohs surgery and nail surgery to reduce intra-operative and postoperative bleeding. Some side effects such as erythema, flushing, and burning were reported in a few patients. Based on our findings, brimonidine is a beneficial drug that can be used in various dermatologic disorders with negligible side effects.

Brimonidine tartrate ophthalmic solution 0.025% for redness relief: an overview of safety and efficacy.

INTRODUCTION: Ocular redness, or conjunctival hyperemia, is a common ophthalmic sign associated with reduced quality of life. For redness without apparent underlying pathology, topical ophthalmic decongestants have been widely used. AREAS COVERED: Brimonidine tartrate was approved in 2017 as a topical vasoconstrictor at a 0.025% concentration for relief of ocular redness. Since then, investigators have reported on efficacy and safety findings from studies evaluating low-dose brimonidine for reducing ocular redness. EXPERT OPINION: Brimonidine is highly selective for α2-adrenergic receptors. Clinical trials have so far shown that the drug in low doses significantly reduces ocular redness in comparison to vehicle for up to 8 hours. Brimonidine-treated eyes did not present side effects of other vasoconstrictors, such as hypotension, cardiac arrhythmia, or drowsiness. Ocular adverse events, such as allergic reactions and redness rebound, were also minimal. In this review, we examine in detail published literature on the mechanism of brimonidine tartrate and its efficacy and safety in relieving conjunctival hyperemia.

Evaluation of the Use of Brinzolamide-Brimonidine Fixed Combination in Maximum Medical Therapy.

Objectives: To investigate the intraocular pressure (IOP)-lowering efficacy, safety, and treatment tolerability of brinzolamide/brimonidine fixed combination (BBFC) in maximum medical therapy. Materials and Methods: The medical records of 92 patients with glaucoma or ocular hypertension who had previously been treated with a different antiglaucomatous regimen and were switched to a treatment regimen that included BBFC were retrospectively analyzed. Patients were divided into 4 groups including 22, 20, 27, and 23 patients based on previous glaucoma treatment. All patients received maximum medical treatment regimen by adding a combination of beta blocker-prostaglandin analogue therapy along with BBFC. IOP values at baseline and month 1, month 3 and month 6 after starting BBFC and ocular adverse effects at follow-up visits were evaluated. Results: The mean age of all patients was 62.7±16.6 years (range: 18-90). Fifty-two patients (56.5%) were women and 40 (43.5%) were men. Forty-eight (52.2%) patients had primary open-angle glaucoma, 35 (38.0%) had pseudoexfoliation glaucoma, and 9 (9.8%) had ocular hypertension. The IOP of the all eyes was 21.1±4.8 mmHg (range: 17-25) before and 17.6±3.7 mmHg, 17.3±3.4, and 17.0±3.5 mmHg at month 1, 3, and 6 after the introduction of BBFC, respectively (p<0.001 for all time points compared to baseline). In all 4 groups, a significant decrease in IOP was observed at month 1, 3, and 6 follow-ups compared to baseline after the introduction of BBFC. The mean number of antiglaucoma drops was significantly reduced from 2.5±0.6 at baseline to 2 after BBFC (p<0.001). The most frequent ocular adverse event was ocular allergic reactions reported in 8 patients (8.7%), conjunctival hyperemia in 5 patients (5.4%), and ocular discomfort in 2 patients (2.5%). Conclusion: Maximum medical therapy with BBFC provides significant IOP reduction and antiglaucoma therapy simplification with a favorable safety profile in patients with glaucoma.

Carvedilol ameliorates persistent erythema of erythematotelangiectatic rosacea by regulating the status of anxiety/depression.

The treatment of persistent erythema and rosacea flushing is extremely challenging, especially for patients with anxiety. The aim of this study was to verify the efficacy of carvedilol in rosacea patients with persistent erythema and flushing. A total of 156 patients were randomized to use oral carvedilol 5 mg bid (twice per day) (n = 105) or topical brimonidine (n = 51) for a 10-week period with 6 weeks of follow-up. Both the efficacy of carvedilol and the status of anxiety/depression were analyzed by patient self-assessment (PSA), clinician erythema assessment (CEA), generalized anxiety disorder (GAD-7), and patient health questionnaire-9 (PHQ-9). Our study found that carvedilol exerted a dramatic reduction in CEA/PSA scores and sting/burning sensation scores in comparison to topical brimonidine. Additionally, carvedilol treatment dramatically improved telangiectasia, erythema, and pigmentation with no obvious side effects. Patients with carvedilol treatment showed an improvement of depression/anxiety, as reflected by lower GAD-7 and PHQ-9 scores than patients with topical brimonidine. Notably, we found carvedilol treatment had better outcomes among patients under 30 years of age with rosacea younger than 30 years old. Conclusively, our findings reveal that carvedilol could quickly and effectively improve facial erythema, which might stem from the improved the status of anxiety/depression.

The benefit of scratch patch testing to demonstrate ocular contact allergy to brimonidine tartrate.

INTRODUCTION: Ocular allergies to brimonidine are frequent in patients treated for glaucoma. There is variability in reporting due to the lack of diagnostic criteria and the absence of cutaneous testing. Many false-negative patch tests (PT) have been described. Alternative methods, such as strip and scratch PT, have been used without a standardized method. OBJECTIVES: The primary objective is to identify the best method of cutaneous testing and brimonidine concentration for patch testing. The secondary objective is to identify clinical signs and symptoms suggestive of ocular allergy. PATIENTS AND METHODS: A retrospective review of patient files suspected of brimonidine ocular allergy was performed. Patch testing method, brimonidine concentration and clinical symptoms were reviewed. RESULTS: Of the 36 patients identified, half tested positive for brimonidine for at least one of the testing methods. The scratch PT demonstrated 17 positive reactions (94% detection rate). Three patients reacted with strip PT. No positive results were found with standard PT. The 5% brimonidine concentration demonstrated the highest sensitivity. The absence of eyelid pruritus was associated with negative testing. CONCLUSION: In the investigation of ocular allergy to brimonidine, scratch PT proved to be an essential tool. Brimonidine 5% pet. appeared as the most sensitive concentration for scratch PT.

Sustained release of brimonidine from BRI@SR@TPU implant for treatment of glaucoma.

Glaucoma is the leading cause of irreversible vision loss worldwide, and reduction of intraocular pressure (IOP) is the only factor that can be interfered to delay disease progression. As the first line and preferred method to treat glaucoma, eye drops have many shortcomings, such as low bioavailability, poor patient compliance, and unsustainable therapeutic effect. In this study, a highly efficient brimonidine (BRI) silicone rubber implant (BRI@SR@TPU implant) has been designed, prepared, characterized, and administrated for sustained relief of IOP to treat glaucoma. The in vitro BRI release from BRI@SR@TPU implants shows a sustainable release profile for up to 35 d, with decreased burst release and increased immediate drug concentration. The carrier materials are not cytotoxic to human corneal epithelial cells and conjunctival epithelial cells, and show good biocompatibility, which can be safely administrated into rabbit's conjunctival sac. The BRI@SR@TPU implant sustainably released BRI and effectively reduced IOP for 18 d (72 times) compared to the commercial BRI eye drops (6 h). The BRI@SR@TPU implant is thus a promising noninvasive platform product for long-term IOP-reducing in patients with glaucoma and ocular hypertension.

Efficacy and safety of a fixed combination of 1% brinzolamide and 0.1% brimonidine as treatment for glaucoma: a retrospective study focusing on the number of ingredients.

OBJECTIVE: To evaluate the intraocular pressure (IOP)-lowering effect based on the number of ingredients and survival rate due to adverse reactions of brinzolamide (1%)/brimonidine (0.1%) fixed combination (BBFC). METHODS AND ANALYSIS: Among 424 patients newly administered BBFC from June 2020 to May 2021, 406 were retrospectively evaluated for adverse reactions and 299 were evaluated for the IOP-lowering effect of BBFC. Among those evaluated for IOP, group A (n=86) included patients whose treatment was changed to BBFC from other two ingredients, Group B (n=90) included patients who added one ingredient by switching to BBFC, and group C (n=123) included patients who added BBFC in addition to other drugs. RESULTS: The mean IOP (mm Hg) at BBFC initiation and at 3, 6 and 12 months after BBFC initiation was 14.1, 14.0, 14.3 and 13.8 in group A, 15.9, 14.4, 13.8 and 14.5 in group B and 17.2, 14.0, 14.1 and 14.9 in group C, respectively. Group A showed no significant difference in mean IOP from baseline to any time point after BBFC initiation, whereas groups B and C showed significant IOP reductions at all time points. Seventy-three (18%) patients discontinued treatment due to adverse reactions. The survival rate was 72% at 12 months after the start of BBFC when discontinuation due to adverse reactions was defined as failure. CONCLUSION: Using BBFC, sustained IOP or decreasing IOP were observed depending on the number of ingredients. Drop-outs due to the adverse reactions should also be given attention.

Comparing the effects and safety of dorzolamide hydrochloride + timolol maleate versus brimonidine after neodymium-doped yttrium aluminium garnet laser capsulotomy posterior capsule opacification.

AIM: Posterior capsular opacification is treated using neodymium-doped yttrium aluminium garnet laser capsulotomy that leads to increased intraocular pressure. Here, we compare the effects of dorzolamide hydrochloride + timolol maleate versus brimonidine on intraocular pressure. We also investigate their side effects after neodymium-doped yttrium aluminium garnet laser capsulotomy. In these patients, there are no prior studies comparing the results of these two drugs. MATERIALS: Ninety patients with posterior capsule opacification contributed to the study. They received yttrium aluminium garnet laser capsulotomy. After yttrium aluminium garnet laser capsulotomy, they were randomized into three groups. Group 1 received dorzolamide hydrochloride + timolol maleate; Group 2 took brimonidine; and Group 3, the control group, took no drug. Group 1 took dorzolamide hydrochloride + timolol maleate eye drops 1 h before the procedure and on the third hour of the first day and two times per day between the second and the seventh days. Group 2 took brimonidine eye drops 1 h before the procedure and on the third hour of the first day, two times per day between the second and the seventh days. RESULTS: Brimonidine had a similar side effect profile to the fix combination. Intraocular pressure on the first (p = 0.87) and third days (p = 0.124) were similar in Group 1 (dorzolamide hydrochloride + timolol maleate), Group 2 (brimonidine) and the control group. The mean intraocular pressure value of the control group was significantly higher than Groups 1 and 2 because the anti-glaucomatous effects of the drugs become prominent on the seventh day (p = 0.041). In Group 1 and Group 2, intraocular pressure was significantly lower than the control group on the seventh day (p = 0.041). Stinging, itching, hyperemia and Tyndall rates were similar in Group 1, Group 2 and the control group. Watery eyes were less common in the brimonidine group than in the dorzolamide hydrochloride-timolol maleate and the control groups on the seventh day (p = 0.02). Brimonidine also significantly lowered the chemosis rate on the third (p = 0.04) and seventh (p = 0.03) days. CONCLUSION: We suggest that brimonidine and a combination of dorzolamide + timolol are similarly effective at reducing eye pressure for routine cases. In cases where intraocular pressure attacks might be at higher risk, using the dorzolamide + timolol combination would be more appropriate.

Preliminary evaluation of the efficacy and safety of brimonidine for general anesthesia.

BACKGROUND: To determine the hypnotic and analgesic effects of brimonidine, and evaluate its efficacy and safety for general anesthesia. Potentiation of pentobarbital sleeping time following brimonidine administration was observed in mice, as was the analgesic activity of brimonidine. METHODS: The median effective dose (ED50) and lethal dose (LD50) of intraperitoneally injected brimonidine were determined in hypnotized mice. In addition, the LD50 of intravenously injected brimonidine, and ED50 of intravenously, intramuscularly, and intrarectally injected brimonidine in hypnotized rabbits were determined. Finally, the synergistic anesthetic effect of brimonidine and chloral hydrate was evaluated in rabbits. RESULTS: Intraperitoneal injection of 10 mg/kg brimonidine enhanced the hypnotic effect of a threshold dose of pentobarbital. Intraperitoneally injected brimonidine produced dose-related analgesic effects in mice. The ED50 of intraperitoneally administered brimonidine in hypnotized mice was 75.7 mg/kg and the LD50 was 379 mg/kg. ED50 values of intravenous, intramuscular, and intrarectal brimonidine for hypnosis in rabbits were 5.2 mg/kg, 8.8 mg/kg, and 8.7 mg/kg, respectively; the LD50 of intravenous brimonidine was 146 mg/kg. Combined intravenous administration of 0.6 mg/kg brimonidine and 0.03 g/kg chloral hydrate had a synergistic anesthetic effect. CONCLUSIONS: Brimonidine elicited hypnotic and analgesic effects after systemic administration and exhibited safety. Moreover, brimonidine enhanced the effects of other types of narcotics when combined.

Brimonidine related acute follicular conjunctivitis: Onset time and clinical presentations, a long-term follow-up.

ABSTRACT: To evaluate the duration of topical brimonidine therapy before the onset of brimonidine-related allergic conjunctivitis and the clinical characteristics associated with the development of brimonidine allergy.We retrospectively enrolled patients who presented brimonidine allergy from December 1, 2008 to November 30, 2020. The duration of brimonidine treatment, concomitant medications, benzalkonium chloride (BAK) exposure, change in IOP, and season of onset were evaluated.292 patients were included, among which 147 were female and 145 were male. The mean age was 58.3 ± 13.6 years old. The mean (median) duration of brimonidine therapy was 266.6 (196) days, with a peak at 60-120 days. The duration was similar whether the patients received brimonidine monotreatment or in combination with other glaucoma drugs, with or without BAK. The IOP increased by 5.6% after brimonidine allergy (P < .001), which was even higher in the brimonidine monotherapy group (9.2%, P < .001). There was no significant IOP elevation in patients treated with multiple glaucoma medications.Around half of brimonidine allergy occurred within 6 months, with a peak in 2 to 4 months. The duration did not differ in patients receiving brimonidine monotherapy or multiple glaucoma medications. The presence of BAK did not affect the duration either. When brimonidine allergy occurred, there was a loss of IOP control, especially in patients receiving brimonidine monotherapy. It is recommended to switch to other types of glaucoma medications for better IOP control.

The Results of Preoperative Use of Topical Brimonidine in Strabismus Surgery.

Purpose: In this study, we wanted to retrospectively evaluate the effect of the use of topical brimonidine on intraoperative bleeding and surgical hemostasis before strabismus surgery. Methods: Brimonidine tartrate 0.15% (Brimogut, Bilim Ilac, Turkey) eye drops were applied 6 and 3 min before surgery to 44 eyes of 22 patients in group 1 for vasoconstriction. Drops were not applied to 46 eyes of 23 patients in group 2. Preoperative and postoperative photographs and video images were taken. Black-and-white images were used to define the surface areas of the blood vessels. The surface area was calculated by counting the black pixels with ImageJ software. Results: In group 1, redness of eye was observed, on average, at preoperative 339.25 ± 11.52 pixels and intraoperative 247.93 ± 10.63 pixels (P < 0.001). But there was no change in group 2 (preoperative 338.87 ± 8.45 pixels to intraoperative 339.71 ± 9.52 pixels, P > 0.05). The incidence of intraoperative bleeding evaluated by the number of eyes on which cautery was used shows that it was significantly less in group 1 than in group 2 (P < 0.001). Conclusions: The use of topical brimonidine before strabismus surgery facilitates clear monitoring of anatomical structures during surgery by effectively controlling hemorrhage. In the postoperative period, it significantly reduces subconjunctival hemorrhage.