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BMC Ophthalmology Dec 2020Anterior uveitis secondary to topical brimonidine administration is rare and not well-defined. In glaucoma patients using brimonidine, one must consider this phenomenon...
BACKGROUND
Anterior uveitis secondary to topical brimonidine administration is rare and not well-defined. In glaucoma patients using brimonidine, one must consider this phenomenon to avoid mis-diagnosis and over-treatment with topical steroids which in turn may increase intraocular pressure (IOP). This is the largest case series including the longest patient follow-up in the current literature.
METHODS
Sixteen patients (26 eyes) with consultant diagnosed brimonidine-associated anterior uveitis in a tertiary referral glaucoma clinic presenting between 2015 and 2019 were included in this retrospective case series. Clinical records were taken for descriptive analysis. Main outcome measures were the key clinical features, and disease course (therapy, IOP control, patient outcome).
RESULTS
Key features were conjunctival ciliary injection and mutton fat keratic precipitation in all eyes. The findings were bilateral in 10 patients. Time between initiation of brimonidine treatment and presentation was 1 week to 49 months. Glaucoma sub-types were mostly pseudo-exfoliative and primary open angle glaucoma. Brimonidine treatment was stopped immediately. Additionally, topical corticosteroids were prescribed in 18 eyes and tapered down during the following 4 weeks. Thirteen eyes did not need surgical or laser treatment (median follow-up time 15 months). No patient showed recurrence of inflammation after cessation of brimonidine.
CONCLUSIONS
This type of anterior uveitis is an uncommon but important manifestation which should always be considered in glaucoma patients on brimonidine treatment. Although treatable at its root cause, problems may persist, especially with respect to IOP control. The latter may necessitate glaucoma surgery after the resolved episode of the uveitis.
Topics: Administration, Ophthalmic; Adrenergic alpha-2 Receptor Agonists; Aged; Aged, 80 and over; Antihypertensive Agents; Brimonidine Tartrate; Female; Follow-Up Studies; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Retrospective Studies; Uveitis, Anterior
PubMed: 33334316
DOI: 10.1186/s12886-020-01762-w -
AAPS PharmSciTech Dec 2011In the present study, an effort was made to design prolonged release Eudragit nanoparticles of brimonidine tartrate by double emulsion-solvent evaporation technique for...
In the present study, an effort was made to design prolonged release Eudragit nanoparticles of brimonidine tartrate by double emulsion-solvent evaporation technique for the treatment of open-angle glaucoma. The effect of various formulation variables like initial drug amount, lecithin proportion, phase volume and pH, secondary emulsifier and polymer proportion were studied. Various process variables like energy and duration of emulsification, lyophilization on the characteristics of nanoparticles and in vitro drug release profile were studied. The selected formulations were subjected to in vivo intraocular pressure-lowering efficacy studies by administering aqueous dispersion of nanoparticles into the lower cul de sac of glaucomatous rabbits. The prepared Eudragit-based nanoparticles were found to have narrow particle size range and improved drug loading. The investigated process and formulation variables found to have significant effect on the particle size, drug loading and entrapment efficiency, and in vitro drug release profile of nanoparticles. The selected formulations upon in vivo ocular irritability and tolerability tests were found to be well tolerated with no signs of irritation. In vivo pharmacodynamic efficacy studies revealed that the selected nanoparticle formulations significantly improved the therapy as area under the ∆IOP vs. time curve [AUC((∆IOP vs. t))] showed several fold increase in intensity and duration of intraocular pressure (IOP) decrease. All the selected nanoparticle formulations were found to prolong the drug release in vitro and prolong IOP reduction efficacy in vivo, thus rendering them as a potential carrier in developing improved drug delivery systems for the treatment of glaucoma.
Topics: Acrylic Resins; Administration, Ophthalmic; Adrenergic alpha-2 Receptor Agonists; Animals; Brimonidine Tartrate; Chemistry, Pharmaceutical; Delayed-Action Preparations; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Carriers; Drug Compounding; Drug Stability; Glaucoma; Hydrogen-Ion Concentration; Intraocular Pressure; Kinetics; Nanoparticles; Nanotechnology; Quinoxalines; Rabbits; Solubility; Technology, Pharmaceutical
PubMed: 21879393
DOI: 10.1208/s12249-011-9675-1 -
Drug Delivery Dec 2019Brimonidine tartrate (BRT) is a hydrophilic α adrenergic agonist used for the treatment of glaucoma. Glaucoma is an ocular disease affecting the anterior segment of the...
Proniosomal gel-derived niosomes: an approach to sustain and improve the ocular delivery of brimonidine tartrate; formulation, in-vitro characterization, and in-vivo pharmacodynamic study.
Brimonidine tartrate (BRT) is a hydrophilic α adrenergic agonist used for the treatment of glaucoma. Glaucoma is an ocular disease affecting the anterior segment of the eye requiring lifetime treatment. Owing to the obstacles facing ocular delivery systems and hydrophilicity of BRT, frequent administration of the eye drops is required. Niosomes have been widely used to improve the ocular bioavailability of the topically applied drugs and to enhance the ocular residence time. However, they have drawbacks as physical instability, aggregation, and loss of the entrapped drug. For this reason, BRT proniosomes were prepared to overcome niosomal instability issues. A D-optimal design was utilized to determine the optimum conditions for preparation of the proniosomal gels. Independent variables were amount of surfactant, surfactant:cholesterol ratio, and type of surfactant used. The dependent variables were entrapment efficiency (EE%), particle size, percentage of drug released after 2 h (Q), and percentage of drug released after 24 h (Q). The optimum formula was suggested with desirability 0.732 and the composition of 540 mg Span 60 and 10:1 surfactant:cholesterol ratio. The results obtained after reconstitution were; EE% of 79.23 ± 1.12% particle size of 810.95 ± 16.758 nm, polydispersity index (PDI) 0.6785 ± 0.213, zeta potential 59.1 ± 0.99 mV, Q40.98 ± 1.29%, Q 63.35 ± 6.07%, and Q = 91.11 ± 1.76%. Transmission electron microscope imaging of the formula showed the typical spherical shape of niosomes. In-vivo pharmacodynamic study assured the improved ocular bioavailability of BRT selected formula when compared with AlphaganP with relative AUC of 5.024 and 7.90 folds increase in the mean residence time (MRT). Lack of ocular irritation of the formula was assured by Draize test.
Topics: Animals; Brimonidine Tartrate; Drug Compounding; Drug Delivery Systems; Eye; Gels; Glaucoma; Intraocular Pressure; Liposomes; Male; Particle Size; Rabbits; Surface Properties
PubMed: 31090464
DOI: 10.1080/10717544.2019.1609622 -
Pharmacology Research & Perspectives Oct 2022α2-adrenoceptors, (α2A, α2B and α2C-subtypes), are Gi-coupled receptors. Central activation of brain α2A and α2C-adrenoceptors is the main site for α2-agonist...
α2-adrenoceptors, (α2A, α2B and α2C-subtypes), are Gi-coupled receptors. Central activation of brain α2A and α2C-adrenoceptors is the main site for α2-agonist mediated clinical responses in hypertension, ADHD, muscle spasm and ITU management of sedation, reduction in opiate requirements, nausea and delirium. However, despite having the same Gi-potency in functional assays, some α2-agonists also stimulate Gs-responses whilst others do not. This was investigated. Agonist responses to 49 different α-agonists were studied (CRE-gene transcription, cAMP, ERK1/2-phosphorylation and binding affinity) in CHO cells stably expressing the human α2A, α2B or α2C-adrenoceptor, enabling ligand intrinsic efficacy to be determined (binding K /Gi-IC ). Ligands with high intrinsic efficacy (e.g., brimonidine and moxonidine at α2A) stimulated biphasic (Gi-Gs) concentration responses, however for ligands with low intrinsic efficacy (e.g., naphazoline), responses were monophasic (Gi-only). ERK1/2-phosphorylation responses appeared to be Gi-mediated. For Gs-mediated responses to be observed, both a system with high receptor reserve and high agonist intrinsic efficacy were required. From the Gi-mediated efficacy ratio, the degree of Gs-coupling could be predicted. The clinical relevance and precise receptor conformational changes that occur, given the structural diversity of compounds with high intrinsic efficacy, remains to be determined. Comparison with α1 and β1/β2-adrenoceptors demonstrated subclass affinity selectivity for some compounds (e.g., α2:dexmedetomidine, α1:A61603) whilst e.g., oxymetazoline had high affinity for both α2A and α1A-subtypes, compared to all others. Some compounds had subclass selectivity due to selective intrinsic efficacy (e.g., α2:brimonidine, α1:methoxamine/etilefrine). A detailed knowledge of these agonist characteristics is vital for improving computer-based deep-learning and drug design.
Topics: Animals; Brimonidine Tartrate; CHO Cells; Cricetinae; Cricetulus; Humans; Ligands
PubMed: 36101495
DOI: 10.1002/prp2.1003 -
Brimonidine Ophthalmic Solution 0.025% for Reduction of Ocular Redness: A Randomized Clinical Trial.Optometry and Vision Science : Official... Mar 2018The α2-adrenergic receptor agonist brimonidine has been reported to induce conjunctival blanching in cataract, strabismus, laser refractive, and filtration procedures.... (Randomized Controlled Trial)
Randomized Controlled Trial
SIGNIFICANCE
The α2-adrenergic receptor agonist brimonidine has been reported to induce conjunctival blanching in cataract, strabismus, laser refractive, and filtration procedures. Clinicians are often faced with red eyes with no apparent underlying pathology. Low-dose brimonidine reduced ocular redness in such subjects with efficacy maintained over 1 month and negligible rebound redness.
PURPOSE
The aim of this study was to evaluate the safety and efficacy of brimonidine tartrate ophthalmic solution 0.025% for the treatment of ocular redness.
METHODS
In this single-center, double-masked, phase 3 clinical trial, adult subjects with baseline redness of more than 1 unit in both eyes (0- to 4-unit scale) were randomized 2:1 to brimonidine 0.025% or vehicle. A single dose was administered in-office (day 1); thereafter subjects instilled treatment four times a day for 4 weeks, with clinic visits on days 15, 29, and 36 (7 days post-treatment). Efficacy end points included investigator-evaluated redness 5 to 240 minutes post-instillation on day 1 (primary); investigator-evaluated change from baseline 1, 360, and 480 minutes post-instillation on day 1, and 1 and 5 minutes post-instillation on days 15 and 29; total clearance of redness, and subject-assessed redness. Safety/tolerability measures included adverse events, rebound redness, and drop comfort.
RESULTS
Sixty subjects were randomized (n = 40 brimonidine, n = 20 vehicle). Investigator-assessed redness was lower with brimonidine versus vehicle over the 5- to 240-minute post-instillation period (mean [SE], 0.62 [0.076] vs. 1.49 [0.108]; P < .0001) and at each time point within that period (P < .0001). At 1, 360, and 480 minutes post-instillation, respectively, the mean differences (95% confidence interval) between treatments were -0.73 (-1.05 to -0.41), -0.57 (-0.84 to -0.29), and -0.39 (-0.67 to -0.10), respectively. No tachyphylaxis was evident with brimonidine on days 15 and 29, and minimal rebound redness was observed following discontinuation. Adverse events were infrequent, and brimonidine was rated as very comfortable.
CONCLUSIONS
Brimonidine 0.025% appeared safe and effective for reduction of ocular redness, with an 8-hour duration of action, no evidence of tachyphylaxis, and negligible rebound redness.
Topics: Administration, Ophthalmic; Adrenergic alpha-2 Receptor Agonists; Adult; Aged; Brimonidine Tartrate; Conjunctiva; Conjunctival Diseases; Double-Blind Method; Female; Humans; Hyperemia; Male; Middle Aged; Ophthalmic Solutions; Young Adult
PubMed: 29461408
DOI: 10.1097/OPX.0000000000001182 -
Journal of Glaucoma 2014The effects of brimonidine on daytime and nighttime intraocular pressure (IOP) and aqueous humor dynamics were evaluated in volunteers with ocular hypertension (OHT). (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The effects of brimonidine on daytime and nighttime intraocular pressure (IOP) and aqueous humor dynamics were evaluated in volunteers with ocular hypertension (OHT).
PATIENTS AND METHODS
Thirty participants with OHT (58.6±1.7 years old, mean±SEM) were enrolled into this randomized, double-masked, cross-over study. For 6 weeks, participants self-administered 0.2% brimonidine or placebo 3 times daily. During daytime and nighttime visits, measurements included aqueous flow (Fa) by fluorophotometry, outflow facility (C) by tonography, episcleral venous pressure (Pev) by venomanometry, and seated and supine IOP by pneumatonometry. Uveoscleral outflow (U) was calculated mathematically.
RESULTS
When treated with placebo, nighttime supine Pev (11.2±0.25 mm Hg) was higher (P<0.05) compared with daytime seated Pev (10.2±0.25 mm Hg), and Fa and U were significantly reduced at night. Brimonidine significantly lowered seated IOP at 9:00 AM and 11:00 AM, 9:00 PM and 11:00 PM and supine IOP at 9:00 AM and 11:00 AM. Brimonidine increased U at 9 AM and 11 AM (P<0.01) and had no effect on daytime and nighttime Fa, C, or Pev.
CONCLUSIONS
In subjects with OHT, brimonidine treatment for 6 weeks significantly reduces seated IOP during the day by increasing uveoscleral outflow. The lack of IOP effect at night can be explained by failure to overcome a normal nighttime reduction of uveoscleral outflow.
Topics: Adrenergic alpha-2 Receptor Agonists; Aqueous Humor; Brimonidine Tartrate; Circadian Rhythm; Corneal Pachymetry; Cross-Over Studies; Double-Blind Method; Female; Fluorophotometry; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Prospective Studies; Quinoxalines; Supine Position; Tonometry, Ocular; Venous Pressure
PubMed: 24886701
DOI: 10.1097/IJG.0000000000000051 -
Medicine Jul 2021To evaluate the duration of topical brimonidine therapy before the onset of brimonidine-related allergic conjunctivitis and the clinical characteristics associated with...
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.
Topics: Antihypertensive Agents; Brimonidine Tartrate; Conjunctivitis, Allergic; Drug Administration Schedule; Female; Follow-Up Studies; Glaucoma; Humans; Intraocular Pressure; Longitudinal Studies; Male; Middle Aged; Ophthalmic Solutions; Retrospective Studies
PubMed: 34398046
DOI: 10.1097/MD.0000000000026724 -
Acta Neurochirurgica Jun 2023There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly,...
BACKGROUND
There is an urgent need for easy-to-perform bedside measures to detect residual consciousness in clinically unresponsive patients with acute brain injury. Interestingly, the sympathetic control of pupil size is thought to be lost in states of unconsciousness. We therefore hypothesized that administration of brimonidine (an alpha-2-adrenergic agonist) eye drops into one eye should produce a pharmacologic Horner's syndrome if the clinically unresponsive patient is conscious, but not if the patient is unconscious. Here, in a first step to explore this hypothesis, we investigated the potential of brimonidine eye drops to distinguish preserved sympathetic pupillary function in awake volunteers from impairment of sympathetic tone in patients in a coma.
METHODS
We enrolled comatose patients admitted for acute brain injury to one of the intensive care units (ICU) of a tertiary referral center, in whom EEG and/or neuroimaging for all practical purposes had ruled out residual consciousness. Exclusion criteria were deep sedation, medications with known drug interactions with brimonidine, and a history of eye disease. Age- and sex-matched healthy and awake volunteers served as controls. We measured pupils of both eyes, under scotopic conditions, at baseline and five times 5-120 min after administering brimonidine into the right eye, using automated pupillometry. Primary outcomes were miosis and anisocoria at the individual and group levels.
RESULTS
We included 15 comatose ICU patients (seven women, mean age 59 ± 13.8 years) and 15 controls (seven women, mean age 55 ± 16.3 years). At 30 min, miosis and anisocoria were seen in all 15 controls (mean difference between the brimonidine-treated pupil and the control pupil: - 1.31 mm, 95% CI [- 1.51; - 1.11], p < 0.001), but in none (p < 0.001) of the 15 ICU patients (mean difference: 0.09 mm, 95% CI [- 0.12;0.30], p > 0.99). This effect was unchanged after 120 min and remained robust in sensitivity analyses correcting for baseline pupil size, age, and room illuminance.
CONCLUSION
In this proof-of-principle study, brimonidine eye drops produced anisocoria in awake volunteers but not in comatose patients with brain injury. This suggests that automated pupillometry after administration of brimonidine can distinguish between the extremes of the spectrum of consciousness (i.e., fully conscious vs. deeply comatose). A larger study testing the "intermediate zone" of disorders of consciousness in the ICU seems warranted.
Topics: Humans; Female; Middle Aged; Aged; Adult; Brimonidine Tartrate; Coma; Anisocoria; Ophthalmic Solutions; Miosis; Brain Injuries
PubMed: 37014450
DOI: 10.1007/s00701-023-05569-8 -
Clinical Ophthalmology (Auckland, N.Z.) 2014To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine) as add-on therapy in...
BACKGROUND
To evaluate the efficacy and safety of newly formulated brimonidine (0.1% brimonidine tartrate preserved with sodium chlorite: brimonidine) as add-on therapy in on-treatment Japanese normal-tension glaucoma (NTG) patients.
METHODS
Brimonidine was added to on-treatment NTG patients with intraocular pressures (IOP) of between 13 mmHg and 16 mmHg after three consecutive IOP measurements. The time courses of IOP, conjunctival hyperemia, superficial punctate keratitis, and adverse events were examined at 4, 8, and 12 weeks after brimonidine instillation.
RESULTS
Though 75 of 83 patients (31 males and 52 females; mean age: 63.4±11.6 years) completed the study, six patients discontinued because of side effects and two patients withdrew. The mean IOP after brimonidine addition at week 4 (12.6±1.8 mmHg, P<0.001), week 8 (12.4±1.7 mmHg, P<0.001), and week 12 (12.6±1.8 mmHg, P<0.001) was significantly decreased compared with that before the addition of brimonidine (13.9±1.2 mmHg). No significant changes in superficial punctate keratitis or conjunctival hyperemia scores were observed throughout the study. Dizziness, sleepiness, eye pain, and itching (mild to moderate) were noted in five, four, three, and three patients, respectively.
CONCLUSIONS
The addition of newly formulated brimonidine to on-treatment Japanese NTG patients with IOP of 13-16 mmHg further reduced the levels of IOP with minimal side effects and adverse events.
PubMed: 25214761
DOI: 10.2147/OPTH.S67366 -
Advances in Therapy Jan 2012To examine the comparative short-term effects of brimonidine/timolol and dorzolamide/timolol on ocular perfusion pressure and retrobulbar blood flow in patients with... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
To examine the comparative short-term effects of brimonidine/timolol and dorzolamide/timolol on ocular perfusion pressure and retrobulbar blood flow in patients with primary open angle glaucoma (OAG).
METHODS
In a prospective, randomized, double-blind, crossover study, intraocular pressure (IOP), blood pressure (BP), ocular perfusion pressure (OPP), and retrobulbar hemodynamics were assessed in 15 patients with OAG (mean age 68.1 years, eight women) with well controlled IOP. IOP was measured by Goldman applanation tonometery and color Doppler imaging was utilized to assess the retrobulbar blood vessels before and 1 month after treatment with topical brimonidine/timolol and dorzolamide/timolol. Statistical analysis was performed by Friedman two-way analysis of variance by ranks and post-hoc Wilcoxon signed rank test for multiple comparisons with Holm's sequential Bonferroni procedure. P values <0.05 were considered statistically significant.
RESULTS
The Friedman test and subsequent post-hoc analysis indicated that IOP, BP, OPP, and retrobulbar blood flow velocities did not significantly differ between brimonidine/timolol and dorzolamide/timolol after 1-month treatment administration in patients with OAG and well controlled IOP.
CONCLUSION
In this cohort of patients with OAG, short-term treatment with brimonidine/timolol and dorzolamide/timolol results in similar effects on OPP and retrobulbar blood flow velocities.
Topics: Administration, Ophthalmic; Aged; Antihypertensive Agents; Blood Pressure; Brimonidine Tartrate; Cross-Over Studies; Double-Blind Method; Drug Combinations; Eye; Female; Glaucoma, Open-Angle; Hemodynamics; Humans; Intraocular Pressure; Male; Quinoxalines; Sulfonamides; Thiophenes; Timolol; Tonometry, Ocular
PubMed: 22246943
DOI: 10.1007/s12325-011-0092-3