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BMC Ophthalmology Apr 2024Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of...
BACKGROUND
Myopia is becoming a huge burden on the world's public health systems. The purpose of this study was to explore the effect of brimonidine in the treatment of form-deprivation myopia (FDM) and the relationship between intraocular pressure (IOP) and myopia development.
METHODS
Monocular form deprivation myopia (FDM) was induced in three-week-old pigmented male guinea pigs. They were treated with 3 different methods of brimonidine administration (eye drops, and subconjunctival or intravitreal injections). Four different concentrations of brimonidine were tested for each method (2µg/µL, 4µg/µL, 20µg/µL, and 40µg/µL). All treatments continued for a period of 21 days. Tonometry, retinoscopy, and A-scan ultrasonography were used to monitor intraocular pressure, refractive error and axial length (AL), respectively.
RESULTS
Treatment with subconjunctival brimonidine at 40µg/µL, and intravitreal brimonidine at 2µg/µL and 4µg/µL, inhibited the development of FDM. The myopic refraction, excessive axial length, and elevation of IOP were significantly decreased. Brimonidine in eye drops was ineffective.
CONCLUSION
Brimonidine at appropriate doses significantly reduced the development of FD myopia in guinea pigs. The IOP may change with FD myopia.
Topics: Male; Animals; Guinea Pigs; Brimonidine Tartrate; Myopia; Refractive Errors; Refraction, Ocular; Ophthalmic Solutions; Sensory Deprivation; Disease Models, Animal
PubMed: 38605375
DOI: 10.1186/s12886-024-03433-6 -
International Ophthalmology Apr 2024The ROCK inhibitor ripasudil hydrochloride hydrate was shown to have axonal protective effects in TNF-induced optic nerve degeneration. The α2-adrenoreceptor agonist...
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.
Topics: Humans; Brimonidine Tartrate; Up-Regulation; AMP-Activated Protein Kinases; Optic Atrophy; Axons; Nerve Degeneration; Isoquinolines; Sulfonamides
PubMed: 38598101
DOI: 10.1007/s10792-024-03095-9 -
Scientific Reports Apr 2024Ripasudil-brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular...
Ripasudil-brimonidine fixed-dose combination (K-232) simultaneously targets three different intraocular pressure (IOP) lowering mechanisms, increasing trabecular meshwork outflow and uveoscleral outflow, and reducing aqueous humor production Vascularly, ripasudil induces transient vasodilation, brimonidine transient vasoconstriction. Investigating effects on IOP, aqueous dynamics, and EVP in mice eyes by microneedle and constant-pressure perfusion methods, and on cytoskeletal and fibrotic proteins changes in HTM cells by a gel contraction assay and immunocytochemistry. Ripasudil, K-232, and brimonidine droplets significantly reduced IOP at 30 min, with K-232 sustaining the effect at 60 min. For EVP, only K-232 exhibited reduced EVP until 60 min after instillation. In vitro, ripasudil inhibited gel contractility and TGFβ2-induced fibrotic changes, whereas brimonidine did not. K-232 significantly lowered IOPs in mice by combining the effects of ripasudil and brimonidine. Brimonidine alone also showed IOP reductions with enhanced outflow facility, and the drug did not interfere with the effects of ripasudil on the trabecular meshwork outflow; K-232 and ripasudil alone both significantly lowered the EVP and enhanced outflow facility, demonstrating that K-232 efficiently reduces IOPs.
Topics: Animals; Mice; Brimonidine Tartrate; Aqueous Humor; Intraocular Pressure; Trabecular Meshwork; Isoquinolines; Sulfonamides
PubMed: 38570526
DOI: 10.1038/s41598-024-58212-6 -
Oman Journal of Ophthalmology 2024A 32-year-old male, with juvenile open-angle glaucoma on chronic antiglaucoma therapy and recently introduced brimonidine eye drops to the treatment regimen, developed...
A 32-year-old male, with juvenile open-angle glaucoma on chronic antiglaucoma therapy and recently introduced brimonidine eye drops to the treatment regimen, developed bilateral follicular conjunctivitis with subepithelial infiltrates (SEIs) initially resembling common infectious keratoconjunctivitis entities. The persistent nature of the conjunctivitis, the lack of positive conjunctival cultures, the absence of systemic symptoms, the full resolution of the condition upon discontinuation of antiglaucoma drops, and the commencement of topical steroids, along with the reappearance of SEIs upon reintroducing brimonidine; suggested an immune-mediated drug reaction secondary to a Benzalkonium chloride (BAK) preserved brimonidine tartrate 0.2% formulation. The interval between the initiation of brimonidine and the onset of the drug reaction was 13 months and shortened to 1 week upon re-exposure to the drug. The condition fully resolved without further sequelae off brimonidine. Brimonidine is notoriously known for causing ocular allergic reactions, the most common being follicular conjunctivitis, but very few reports exist describing its adverse effects on the cornea. This case highlights that brimonidine may directly or indirectly induce an immune reaction affecting the cornea in the form of SEIs. Brimonidine is, thus, capable of mimicking more commonly recognized infectious disease entities causing keratoconjunctivitis. This is the second report of a similar manifestation linked to its use.
PubMed: 38524330
DOI: 10.4103/ojo.ojo_99_23 -
Journal of Medical Case Reports Mar 2024This case report is applicable to the field of ophthalmology because there is a paucity of medical literature related to the clinical presentation, diagnosis, and...
BACKGROUND
This case report is applicable to the field of ophthalmology because there is a paucity of medical literature related to the clinical presentation, diagnosis, and management of uveal effusion syndrome. This is an urgent concern because there are severe complications associated with this disease, including non-rhegmatogenous retinal detachment, angle closure glaucoma, and possible blindness. This report will fill clinical knowledge gaps using a patient example.
CASE PRESENTATION
A 68-year-old white male with multiple cardiovascular risk factors initially presented to the Eye Institute Urgent Care Clinic with new onset visual symptoms, including eye pain, eye lid swelling, redness, and tearing of his left eye. He had experienced a foreign body sensation in the left eye and bilateral floaters weeks prior to his presentation. The patient was examined, and vision was 20/30 in both eyes, and intraocular pressure was 46 in the right eye and 36 in the left eye. After initial assessment, including compression gonioscopy, intermittent angle closure glaucoma was suspected. He received oral diamox 500 mg, one drop of alphagan in both eyes, one drop of latanoprost in both eyes, one drop of dorzolamide in both eyes, and one drop of 2% pilocarpine in both eyes. There was only slight response in intraocular pressure. Owing to the bilateral angle closure, he underwent laser peripheral iridotomy to decrease intraocular pressure and open the angle that was found closed on gonioscopy. The patient was discharged on oral and topical glaucoma drops and scheduled for the glaucoma clinic. When he presented for follow-up in the glaucoma clinic, he was evaluated and noted to have bilateral narrow angles and intraocular pressure in the mid-twenties. A brightness scan (B-scan) was performed and was noted to have bilateral choroidal effusions, confirmed by Optos fundus photos. He was started on prednisone at 60 mg once per day (QD) with taper, continuation of oral and topical glaucoma medications, and a retina evaluation. Evaluation with a retina specialist showed resolving choroidal effusion in the left eye. He continued the prednisone taper as well as glaucoma drops as prescribed. Follow-up in the glaucoma clinic revealed a grade 3 open angle. He continued the prednisone taper, cosopt twice per day in both eyes, and discontinued brimonidine. The magnetic resonance imaging (MRI) that was performed showed results that were remarkable. No hemorrhage or mass was present. Follow-up with the retina specialist found that the choroidal effusions had resolved completely.
CONCLUSION
This case report emphasizes the value in early detection, keen diagnostic evaluation, and cross-collaboration between multiple ophthalmology specialists to optimize healthcare outcomes for patients with uveal effusion syndrome.
Topics: Humans; Male; Aged; Glaucoma, Angle-Closure; Prednisone; Uveal Effusion Syndrome; Intraocular Pressure; Eye; Brimonidine Tartrate
PubMed: 38509616
DOI: 10.1186/s13256-024-04496-1 -
Journal of Pharmacological Sciences Apr 2024To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons...
PURPOSE
To determine whether combination of topical ripasudil and brimonidine has more effective neuroprotection on retinal ganglion cells (RGCs) following injury to axons composing the optic nerve.
METHODS
Topical ripasudil, brimonidine, or mixture of both drugs were administered to adult mice after optic nerve injury (ONI). The influence of drug conditions on RGC health were evaluated by the quantifications of surviving RGCs, phosphorylated p38 mitogen-activated protein kinase (phospho-p38), and expressions of trophic factors and proinflammatory mediators in the retina.
RESULTS
Topical ripasudil and brimonidine suppressed ONI-induced RGC death respectively, and mixture of both drugs further stimulated RGC survival. Topical ripasudil and brimonidine suppressed ONI-induced phospho-p38 in the whole retina. In addition, topical ripasudil suppressed expression levels of TNFα, IL-1β and monocyte chemotactic protein-1 (MCP-1), whereas topical brimonidine increased the expression level of basic fibroblast growth factor (bFGF).
CONCLUSIONS
Combination of topical ripasudil and brimonidine may enhance RGC protection by modulating multiple signaling pathways in the retina.
Topics: Mice; Animals; Brimonidine Tartrate; Optic Nerve Injuries; Neuroprotection; Drug Combinations; Isoquinolines; Sulfonamides
PubMed: 38485351
DOI: 10.1016/j.jphs.2024.02.011 -
Drug Design, Development and Therapy 2024Nicotine is a major component of cigarette smoke with various detrimental cardiovascular effects, including increased oxidative stress in the heart. Agonism of...
INTRODUCTION
Nicotine is a major component of cigarette smoke with various detrimental cardiovascular effects, including increased oxidative stress in the heart. Agonism of α-adrenergic receptors (ARs), such as with dexmedetomidine, has been documented to exert cardioprotective effects against oxidative stress and related apoptosis and necroptosis. α-ARs are membrane-residing G protein-coupled receptors (GPCRs) that primarily activate Gi/o proteins. They are also subjected to GPCR-kinase (GRK)-2-dependent desensitization, which entails phosphorylation of the agonist-activated receptor by GRK2 to induce its decoupling from G proteins, thus terminating αAR-mediated G protein signaling.
OBJECTIVE
In the present study, we sought to examine the effects of nicotine on αAR signaling and effects in H9c2 cardiomyocytes exposed to HO to induce oxidative cellular damage.
METHODS AND RESULTS
As expected, treatment of H9c2 cardiomyocytes with HO significantly decreased cell viability and increased oxidative stress, as assessed by reactive oxygen species (ROS)-associated fluorescence levels (DCF assay) and superoxide dismutase activity. Both HO effects were partly rescued by αAR activation with brimonidine in control cardiomyocytes but not in cells pretreated with nicotine for 24 hours, in which brimonidine was unable to reduce HO-induced cell death and oxidative stress. This was due to severe αAR desensitization, manifested as very low Gi protein activation by brimonidine, and accompanied by GRK2 upregulation in nicotine-treated cardiomyocytes. Finally, pharmacological inhibition of adenylyl cyclase (AC) blocked HO-dependent oxidative damage in nicotine-pretreated H9c2 cardiomyocytes, indicating that αAR activation protects against oxidative injury via its classic coupling to Gai-mediated AC inhibition.
DISCUSSION/CONCLUSIONS
Nicotine can negate the cardioprotective effects of αAR agonists against oxidative injury, which may have important implications for patients treated with this class of drugs that are chronic tobacco smokers.
Topics: Humans; Nicotine; Myocytes, Cardiac; Hydrogen Peroxide; Receptors, Adrenergic, alpha-2; Oxidative Stress; Apoptosis; Brimonidine Tartrate
PubMed: 38229917
DOI: 10.2147/DDDT.S432453 -
American Journal of Ophthalmology Case... Dec 2023To report a case of pressure-induced interlamellar stromal keratitis (PISK) 10 years after laser assisted in situ keratomileusis (LASIK).
PURPOSE
To report a case of pressure-induced interlamellar stromal keratitis (PISK) 10 years after laser assisted in situ keratomileusis (LASIK).
OBSERVATIONS
A case of a 36-year-old man who underwent LASIK and presented with PISK 10 years later. Before presenting to our department he consulted elsewhere for red eye, decreased visual acuity, foreign body sensation, and pain on the RE for 1 week. He was then prescribed topical prednisolone six times per day and was lost to follow-up. On examination and after 1 month of continuous use of steroids uncorrected distance visual acuity (UCDV) was 20/400 in the right eye (RE) and 20/20 in the left eye (LE). Best corrected visual acuity was 20/80 on the RE. The Goldmann intraocular pressure (IOP) was 26 and 17 mmHg in the RE and LE, respectively. Slit lamp biomicroscopy revealed fluid in the interface and epithelial ingrowth. Fundoscopic examination results were normal in both eyes. Treatment was initiated with topical brimonidine tartrate 0.2%, timolol 0.5%, and dorzolamide 2.0% BID. Once the pressure was controlled the patient was scheduled for mechanical debridement of the epithelial ingrowth with significant improvement of UCVA (20/25).
CONCLUSIONS
Refractive surgeons should be aware of PISK as a potential complication of LASIK even years after the procedure. Intraocular pressure can be misleading, and diligent and careful examination are key to diagnosis and treatment of this potentially blinding complication.
PubMed: 38161519
DOI: 10.1016/j.ajoc.2023.101874 -
PloS One 2023The purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits.
PURPOSE
The purpose of this study was to investigate the effect of a 1% brinzolamide and 0.1% brimonidine fixed combination (BBFC) on ONH blood flow (BF) in rabbits.
METHODS
A crossover study was conducted on pigmented rabbits; a physiological saline solution, brinzolamide, or BBFC was administered for eight days. ONH BF, intraocular pressure (IOP) and systemic parameters were measured before the eighth day's first dose and at 6, 9, 12, and 14 hours after the dose. ONH BF was assessed using laser speckle flowgraphy, and mean blur rate (MBR) values were calculated. The percentage against baseline of each parameter was calculated, and intergroup comparisons were performed at each time point.
RESULTS
There were no significant differences in the percentage change in systemic parameters. At 6 hours after administration, the BBFC group showed a significantly higher percentage change in large vessel area-MBR (%MV) compared to the control group (98.6±16.8%MV vs. 81.3±7.9%MV, P = 0.03). On the other hand, the brinzolamide group did not show a significant difference. Both the brinzolamide and BBFC groups had significantly lower percentage change in IOP (%IOP) compared to the control group (90.6±5.0%IOP, 93.3±2.9%IOP, and 99.2±1.7%IOP, respectively, P < 0.01).
CONCLUSION
BBFC effectively reduces IOP and mitigates diurnal fluctuation-induced decreases in ONH BF.
Topics: Animals; Rabbits; Brimonidine Tartrate; Optic Disk; Glaucoma, Open-Angle; Ocular Hypertension; Cross-Over Studies; Intraocular Pressure; Blood Flow Velocity; Regional Blood Flow
PubMed: 38051718
DOI: 10.1371/journal.pone.0295122 -
BMC Ophthalmology Oct 2023We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine.
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.
Topics: Male; Humans; Adult; Microphthalmos; Brimonidine Tartrate; Choroid; Choroid Diseases; Ophthalmologic Surgical Procedures
PubMed: 37814274
DOI: 10.1186/s12886-023-03107-9