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Journal of Nanobiotechnology Dec 2021Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging...
BACKGROUND
Oxidative stress contributes to retina ganglion cells (RGCs) loss in variety of ocular diseases, including ocular trauma, ocular vein occlusion, and glaucoma. Scavenging the excessed reactive oxygen species (ROS) in retinal neurovascular unit could be beneficial to RGCs survival. In this study, a polydopamine (PDA)-based nanoplatform is developed to protect RGCs.
RESULTS
The PDA nanoparticles efficiently eliminate multi-types of ROS, protect endothelia and neuronal cells from oxidative damage, and inhibit microglia activation in retinas. In an optic nerve crush (ONC) model, single intravitreal injection of PDA nanoparticles could significantly attenuate RGCs loss via eliminating ROS in retinas, reducing the inflammatory response and maintaining barrier function of retinal vascular endothelia. Comparative transcriptome analysis of the retina implied that PDA nanoparticles improve RGCs survival probably by altering the expression of genes involved in inflammation and ROS production. Importantly, as a versatile drug carrier, PDA nanoparticles could deliver brimonidine (a neuroprotection drug) to synergistically attenuate RGCs loss and promote axon regeneration, thus restore visual function.
CONCLUSIONS
The PDA nanoparticle-based therapeutic nanoplatform displayed excellent performance in ROS elimination, providing a promising probability for treating retinal degeneration diseases.
Topics: Animals; Brimonidine Tartrate; Cell Survival; Disease Models, Animal; Human Umbilical Vein Endothelial Cells; Humans; Hydrogen Peroxide; Indoles; Macrophages; Male; Mice; Mice, Inbred C57BL; Nanoparticles; Nitric Oxide Synthase Type II; Optic Nerve Injuries; Polymers; Reactive Oxygen Species; Retina; Retinal Degeneration; Retinal Ganglion Cells; Transcriptome
PubMed: 34930292
DOI: 10.1186/s12951-021-01199-3 -
Patient Preference and Adherence 2017Brimonidine tartrate is a highly selective alpha 2 agonist that induces direct vasoconstriction of small arteries and veins, thereby reducing vasodilation and edema. (Review)
Review
BACKGROUND
Brimonidine tartrate is a highly selective alpha 2 agonist that induces direct vasoconstriction of small arteries and veins, thereby reducing vasodilation and edema.
OBJECTIVE
To review the current literature regarding the safety, efficacy, and patient acceptability of brimonidine 0.33% gel.
METHODS
A PubMed search was performed using the terms brimonidine 0.33% gel, rosacea, safety, efficacy, and acceptability. Peer-reviewed clinical trials and case reports from 2012 to 2016 were screened for inclusion of safety, efficacy, and/or patient acceptability data.
RESULTS
Brimonidine topical gel 0.33% is associated with mild, transient skin-related adverse reactions. Efficacy may be achieved within 30 minutes of administration with maximal reductions in erythema 3-6 hours after administration. Patient satisfaction with use of brimonidine topical gel is superior to vehicle gel for facial appearance, treatment effect, facial redness, and daily control of facial redness.
LIMITATIONS
Studies were typically limited to 1-year follow-up. Only one study has examined the use of brimonidine topical gel in combination with other rosacea and acne medications.
DISCUSSION
Brimonidine topical gel 0.33% is a safe, effective, and patient-accepted treatment for facial erythema of rosacea.
PubMed: 28740369
DOI: 10.2147/PPA.S115708 -
Journal of Clinical Medicine Jun 2023To evaluate the concentrations of brimonidine and brinzolamide in the vitreous and aqueous humor after instillation of a 0.1% brimonidine tartrate and 1% brinzolamide...
Ocular Distribution of Brimonidine and Brinzolamide after Topical Instillation of a 0.1% Brimonidine Tartrate and 1% Brinzolamide Fixed-Combination Ophthalmic Suspension: An Interventional Study.
PURPOSE
To evaluate the concentrations of brimonidine and brinzolamide in the vitreous and aqueous humor after instillation of a 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension.
METHODS
The present investigation involved patients with macular holes or idiopathic epiretinal membranes who were planning to undergo vitrectomy. One week prior to surgery, the patients received twice-daily topical treatment with 0.1% brimonidine tartrate and 1% brinzolamide fixed-combination ophthalmic suspension. Before vitrectomy, vitreous and aqueous humor samples were collected, and the mean concentrations of brimonidine and brinzolamide were determined through liquid chromatography-tandem spectrometry.
RESULTS
Ten eyes (nine phakic and one pseudophakic eyes; 10 patients) were examined. The concentration of brimonidine in vitreous and aqueous humor samples was 5.02 ± 2.24 and 559 ± 670 nM, respectively. The concentration of brimonidine in the vitreous humor, which is needed to activate α2 receptors, was >2 nM in all patients. The concentration of brinzolamide was 8.96 ± 4.65 and 1100 ± 813 nM, respectively. However, there was no significant correlation between the concentrations of brimonidine in the vitreous and aqueous humor samples.
CONCLUSIONS
Sufficient concentrations of brimonidine were detected in all vitreous samples. The dissociated correlation of the drug concentrations between aqueous and vitreous humors implies the possibility of another pathway to vitreous humor, different from the pathway to aqueous humor.
PubMed: 37445209
DOI: 10.3390/jcm12134175 -
The Cochrane Database of Systematic... Jan 2017Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field... (Review)
Review
BACKGROUND
Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells, and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the most common form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death.
OBJECTIVES
The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults compared with no neuroprotective agent, placebo, or other glaucoma treatment.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 7), Ovid MEDLINE, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE Daily (January 1946 to August 2016), Embase (January 1980 to August 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov), and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 16 August 2016.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG. Minimum follow-up time was four years.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text copies of potentially relevant studies and re-evaluated for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We identified one trial for this review, thus we performed no meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until study investigators provide additional study details. We documented reasons for excluding studies from the review.
MAIN RESULTS
We included one multicenter RCT of adults with low-pressure glaucoma (Low-pressure Glaucoma Treatment Study, LoGTS) conducted in the USA. The primary outcome was progression of visual field loss after four years of treatment with either brimonidine or timolol. Of the 190 adults enrolled in the study, the investigators excluded 12 (6.3%) after randomization; 77 participants (40.5%) did not complete four years of follow-up. The rate of attrition was unbalanced between groups with more participants dropping out of the brimonidine group (55%) than the timolol group (29%).Of those remaining in the study at four years, participants assigned to brimonidine showed less progression of visual field loss than participants assigned to timolol (risk ratio (RR) 0.35, 95% confidence interval (CI) 0.14 to 0.86; 101 participants). Because of high risk of attrition bias and potential selective outcome reporting, we graded the certainty of evidence for this outcome as very low. At the four-year follow-up, the mean IOP was similar in both groups among those for whom data were available (mean difference 0.20 mmHg, 95% CI -0.73 to 1.13; 91 participants; very low-certainty evidence). The study authors did not report analyzable data for visual acuity or any data related to vertical cup-disc ratio, quality of life, or economic outcomes. The most frequent adverse event was ocular allergy to the study drug, which affected more participants in the brimonidine group than the timolol group (RR 5.32, 95% CI 1.64 to 17.26; 178 participants; very low-certainty evidence).
AUTHORS' CONCLUSIONS
Although the only trial we included in this review found less visual field loss in the brimonidine-treated group, the evidence was of such low certainty that we can draw no conclusions from this finding. Further clinical research is needed to determine whether neuroprotective agents may be beneficial for individuals with OAG. Such research should focus on outcomes important to patients, such as preservation of vision, and how these outcomes relate to cell death and optic nerve damage. As OAG is a chronic, progressive disease with variability in symptoms, RCTs designed to measure the effectiveness of neuroprotective agents require a long-term follow-up of five years or longer to detect clinically meaningful effects.
Topics: Adult; Antihypertensive Agents; Brimonidine Tartrate; Disease Progression; Glaucoma, Open-Angle; Humans; Neuroprotective Agents; Optic Nerve; Optic Nerve Diseases; Randomized Controlled Trials as Topic; Retinal Ganglion Cells; Timolol
PubMed: 28122126
DOI: 10.1002/14651858.CD006539.pub4 -
Effects of brimonidine tartrate 0.1% ophthalmic solution on the pupil, refraction, and light reflex.Scientific Reports Jun 2018This study aimed to assess changes in pupil size, uncorrected visual acuity, refraction, and the direct and consensual light reflexes after instillation of brimonidine...
This study aimed to assess changes in pupil size, uncorrected visual acuity, refraction, and the direct and consensual light reflexes after instillation of brimonidine 0.1% in healthy subjects. The investigation comprised 46 eyes of 23 healthy subjects with no eye diseases in whom brimonidine 0.1% was instilled in the right eye. Pupil size was measured quantitatively under photopic and scotopic conditions, uncorrected visual acuity, refraction, and direct and consensual light reflexes before and at 1, 6, and 24 h after instillation. We found No significant change was found in refraction or uncorrected visual acuity (P = 0.999 and P = 0.998, respectively). A significant reduction in pupil size was observed under scotopic conditions at 1 h and 6 h after instillation (P = 0.007 and P = 0.005, respectively). The rate of pupil contraction and constriction speed measured by light reflexes were significantly increased at 1 h and 6 h after instillation (P = 0.021 and P = 0.033, respectively). Brimonidine 0.1% induced a significant reduction in pupil size under scotopic conditions without a significant change in refraction or visual acuity due to suppression of the sympathetic nervous system.
Topics: Adrenergic alpha-2 Receptor Agonists; Adult; Brimonidine Tartrate; Female; Humans; Male; Ophthalmic Solutions; Pupil; Reflex, Pupillary; Refraction, Ocular; Visual Acuity
PubMed: 29899357
DOI: 10.1038/s41598-018-27436-8 -
Nature Communications May 2023Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For...
Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We develop a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) is conjugated to brimonidine, an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction is observed for up to 18 days after a single intracameral injection in rabbits. Further, the cumulative intraocular pressure lowering effect increases ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.
Topics: Animals; Rabbits; Melanins; Drug Delivery Systems; Brimonidine Tartrate; Peptides; Machine Learning
PubMed: 37130851
DOI: 10.1038/s41467-023-38056-w -
The Cochrane Database of Systematic... Feb 2013Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells and ultimately visual field... (Review)
Review
BACKGROUND
Glaucoma is a heterogeneous group of conditions involving progressive damage to the optic nerve, deterioration of retinal ganglion cells and ultimately visual field loss. It is a leading cause of blindness worldwide. Open angle glaucoma (OAG), the commonest form of glaucoma, is a chronic condition that may or may not present with increased intraocular pressure (IOP). Neuroprotection for glaucoma refers to any intervention intended to prevent optic nerve damage or cell death.
OBJECTIVES
The objective of this review was to systematically examine the evidence regarding the effectiveness of neuroprotective agents for slowing the progression of OAG in adults.
SEARCH METHODS
We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 9), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to October 2012), EMBASE (January 1980 to October 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to October 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 16 October 2012.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which topical or oral treatments were used for neuroprotection in adults with OAG. Minimum follow up time was four years.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed titles and abstracts from the literature searches. Full-text copies of potentially relevant studies were obtained and re-evaluated for inclusion. Two review authors independently extracted data related study characteristics, risk of bias, and outcome data. One trial was identified for this review, thus we performed no meta-analysis. Two studies comparing memantine to placebo are currently awaiting classification until additional study details are provided. We documented reasons for excluding studies from the review.
MAIN RESULTS
We included one multi-center RCT of adults with low-pressure glaucoma (Low-pressure Glaucoma Treatment Study, LoGTS) conducted in the USA. The primary outcome was visual field progression after four years of treatment with either brimonidine or timolol. Of the 190 adults enrolled in the study, 12 (6.3%) were excluded after randomization and 77 (40.5%) did not complete four years of follow up. The rate of attrition was unbalanced between groups with more participants dropping out of the brimonidine group (55%) than the timolol group (29%). Of those remaining in the study at four years, participants assigned to brimonidine showed less visual field progression than participants assigned to timolol (5/45 participants in the brimonidine group compared with 18/56 participants in the timolol group). Since no information was available for the 12 participants excluded from the study, or the 77 participants who dropped out of the study, we cannot draw any conclusions from these results as the participants for whom data are missing may or may not have progressed. The mean IOP was similar in both groups at the four-year follow up among those for whom data were available: 14.2 mmHg (standard deviation (SD) = 1.9) among the 43 participants in the brimonidine group and 14.0 mmHg (SD = 2.6) among the 48 participants in the timolol group. Among the participants who developed progressive visual field loss, IOP reduction of 20% or greater was not significantly different between groups: 4/9 participants in the brimonidine group and 12/31 participants in the timolol group. The study authors did not report data for visual acuity or vertical cup-disc ratio. The most frequent adverse event was ocular allergy to study drug, which occurred more frequently in the brimonidine group (20/99 participants) than the timolol group (3/79 participants).
AUTHORS' CONCLUSIONS
Although neuroprotective agents are intended to act as pharmacological antagonists to prevent cell death, this trial did not provide evidence that they are effective in preventing retinal ganglion cell death, and thus preserving vision in people with OAG. Further clinical research is needed to determine whether neuroprotective agents may be beneficial for individuals with OAG. Such research should focus outcomes important to patients, such as preservation of vision, and how these outcomes relate to cell death and optic nerve damage. Since OAG is a chronic, progressive disease with variability in symptoms, RCTs designed to measure the effectiveness of neuroprotective agents would require long-term follow up (more than four years) in order to detect clinically meaningful effects.
Topics: Adult; Antihypertensive Agents; Brimonidine Tartrate; Disease Progression; Glaucoma, Open-Angle; Humans; Neuroprotective Agents; Optic Nerve; Optic Nerve Diseases; Quinoxalines; Randomized Controlled Trials as Topic; Retinal Ganglion Cells; Timolol
PubMed: 23450569
DOI: 10.1002/14651858.CD006539.pub3 -
Journal of Ocular Pharmacology and... Mar 2019We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We...
PURPOSE
We developed a polycaprolactone (PCL) co-delivery implant that achieves zero-order release of 2 ocular hypotensive agents, timolol maleate and brimonidine tartrate. We also demonstrate intraocular pressure (IOP)-lowering effects of the implant for 3 months in vivo.
METHODS
Two PCL thin-film compartments were attached to form a V-shaped co-delivery device using film thicknesses of ∼40 and 20 μm for timolol and brimonidine compartments, respectively. In vitro release kinetics were measured in pH- and temperature-controlled fluid chambers. Empty or drug-loaded devices were implanted intracamerally in normotensive rabbits for up to 13 weeks with weekly measurements of IOP. For ocular concentrations, rabbits were euthanized at 4, 8, or 13 weeks, aqueous fluid was collected, and ocular tissues were dissected. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry.
RESULTS
In vitro studies show zero-order release kinetics for both timolol (1.75 μg/day) and brimonidine (0.48 μg/day) for up to 60 days. In rabbit eyes, the device achieved an average aqueous fluid concentration of 98.1 ± 68.3 ng/mL for timolol and 5.5 ± 3.6 ng/mL for brimonidine. Over 13 weeks, the drug-loaded co-delivery device resulted in a statistically significant cumulative reduction in IOP compared to untreated eyes (P < 0.05) and empty-device eyes (P < 0.05).
CONCLUSIONS
The co-delivery device demonstrated a zero-order release profile in vitro for 2 hypotensive agents over 60 days. In vivo, the device led to significant cumulative IOP reduction of 3.4 ± 1.6 mmHg over 13 weeks. Acceptable ocular tolerance was seen, and systemic drug levels were unmeasurable.
Topics: Animals; Brimonidine Tartrate; Chromatography, Liquid; Drug Delivery Systems; Female; Hydrogen-Ion Concentration; Intraocular Pressure; Kinetics; Male; Ophthalmic Solutions; Polyesters; Rabbits; Tandem Mass Spectrometry; Temperature; Timolol
PubMed: 30615539
DOI: 10.1089/jop.2018.0096 -
Graefe's Archive For Clinical and... Nov 2021To evaluate the effect of brimonidine tartrate 0.025% ophthalmic solution on pupil size under scotopic conditions in healthy adults METHODS: Pupil size was measured in...
PURPOSE
To evaluate the effect of brimonidine tartrate 0.025% ophthalmic solution on pupil size under scotopic conditions in healthy adults METHODS: Pupil size was measured in 56 eyes of 28 volunteer participants using a pupillometer under scotopic conditions. Age, gender, and iris color were recorded. Subjects using any ophthalmic medications other than artificial tears were excluded. The pupil size was subsequently measured again under scotopic conditions 60 min after instillation of brimonidine tartrate 0.025% ophthalmic solution.
RESULTS
Statistically significant miosis was seen after instillation of brimonidine tartrate 0.025% (p = 0.04). Average pupil size prior to brimonidine 0.025% instillation was 7.28 ± 1.05 mm, and average pupil size after instillation of brimonidine 0.025% was 6.36 ± 1.68 mm, a reduction of - 23.7% in pupil area. Subjects with light irides demonstrated a greater miotic effect than subjects with dark irides (1.55 mm vs. 0.67 mm, p < 0.0001), with a pupil area reduction of - 37.6% and - 17.4%, respectively. The amount of miosis was independent of initial pupil size.
CONCLUSIONS
Brimonidine tartrate 0.025% causes significant miosis in scotopic settings, although the effect is not as great in darker colored eyes. Further studies are needed to determine the latency and duration of the effect and whether the amount of miosis is clinically significant.
Topics: Adult; Brimonidine Tartrate; Humans; Lubricant Eye Drops; Miotics; Ophthalmic Solutions; Pupil; Quinoxalines
PubMed: 34251483
DOI: 10.1007/s00417-021-05297-8 -
Hospital Pharmacy Dec 2013Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The...
Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. A drug class review is now published monthly with The Formulary Monograph Service. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service, call The Formulary at 800-322-4349. The December 2013 monograph topics are vortioxetine, mechlorethamine gel, brimonidine tartrate topical gel, obinutuzumab, and miltefosine. The DUE/MUE is on vortioxetine.
PubMed: 24474837
DOI: 10.1310/hpj4811-951