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Ophthalmology Jan 2016Primary open-angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the... (Meta-Analysis)
Meta-Analysis Review
TOPIC
Primary open-angle glaucoma (POAG) is a highly prevalent condition worldwide and the most common cause of irreversible sight loss. The objective is to assess the comparative effectiveness of first-line medical treatments in patients with POAG or ocular hypertension through a systematic review and network meta-analysis, and to provide relative rankings of these treatments.
CLINICAL RELEVANCE
Treatment for POAG currently relies completely on lowering the intraocular pressure (IOP). Although topical drops, lasers, and surgeries can be considered in the initial treatment of glaucoma, most patients elect to start treatment with eye drops.
METHODS
We included randomized controlled trials (RCTs) that compared a single active topical medication with no treatment/placebo or another single topical medication. We searched CENTRAL, MEDLINE, EMBASE, and the Food and Drug Administration's website. Two individuals independently assessed trial eligibility, abstracted data, and assessed the risk of bias. We performed Bayesian network meta-analyses.
RESULTS
We included 114 RCTs with data from 20 275 participants. The overall risk of bias of the included trials is mixed. The mean reductions (95% credible intervals) in IOP in millimeters of mercury at 3 months ordered from the most to least effective drugs were as follows: bimatoprost 5.61 (4.94; 6.29), latanoprost 4.85 (4.24; 5.46), travoprost 4.83 (4.12; 5.54), levobunolol 4.51 (3.85; 5.24), tafluprost 4.37 (2.94; 5.83), timolol 3.70 (3.16; 4.24), brimonidine 3.59 (2.89; 4.29), carteolol 3.44 (2.42; 4.46), levobetaxolol 2.56 (1.52; 3.62), apraclonidine 2.52 (0.94; 4.11), dorzolamide 2.49 (1.85; 3.13), brinzolamide 2.42 (1.62; 3.23), betaxolol 2.24 (1.59; 2.88), and unoprostone 1.91 (1.15; 2.67).
CONCLUSIONS
All active first-line drugs are effective compared with placebo in reducing IOP at 3 months. Bimatoprost, latanoprost, and travoprost are among the most efficacious drugs, although the within-class differences were small and may not be clinically meaningful. All factors, including adverse effects, patient preferences, and cost, should be considered in selecting a drug for a given patient.
Topics: Antihypertensive Agents; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 26526633
DOI: 10.1016/j.ophtha.2015.09.005 -
BMC Ophthalmology Dec 2021Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The...
BACKGROUND
Topical application of β-blocker eye drops induces damage to the ocular surface in clinical. However, the mechanism involved remains incompletely understood. The purpose of this study was to investigate the influence and mechanism of β-blocker eye drops on corneal epithelial wound healing.
METHODS
Corneal epithelial wound healing models were constructed by epithelial scraping including in the limbal region and unceasingly received eye drops containing 5 mg/mL β-blocker levobunolol, β1-adrenoceptor (β1AR)-specific antagonist atenolol or β2-adrenoceptor (β2AR)-specific antagonist ICI 118, 551. For the migration assay, the murine corneal epithelial stem/progenitor cells (TKE2) were wounded and subsequently incubated with levobunolol, atenolol, or ICI 118, 551. The proliferation and colony formation abilities of TKE2 cells treated with levobunolol, atenolol, or ICI 118, 551 were investigated by CCK-8 kit and crystal violet staining. The differentiation marker Cytokeratin 3 (CK3), the stem cell markers-Cytokeratin 14 (CK14) and Cytokeratin 19 (CK19), and corneal epithelium regeneration-related signaling including in Ki67 and the phosphorylated epithelial growth factor receptor (pEGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) were assessed by immunofluorescence staining.
RESULTS
Levobunolol and ICI 118, 551 impaired corneal wound healing, decreased the expressions of CK3, CK14, and CK19 after limbal region scraping in vivo and reduced the migration and proliferation of TKE2 in vitro, whereas atenolol had no significant effect. Moreover, levobunolol and ICI 118, 551 inhibited corneal wound healing by mediating the expression of Ki67, and the phosphorylation of EGFR and ERK1/2 in the limbal and regenerated corneal epithelium.
CONCLUSION
β-blocker eye drops impaired corneal wound healing by inhibiting the β2AR of limbal stem cells, which decreased corneal epithelial regeneration-related signaling. Therefore, a selective β1AR antagonist might be a good choice for glaucoma treatment to avoid ocular surface damage.
Topics: Adrenergic beta-Antagonists; Animals; Epithelium, Corneal; Limbus Corneae; Mice; Ophthalmic Solutions; Receptors, Adrenergic; Stem Cells
PubMed: 34863129
DOI: 10.1186/s12886-021-02186-w -
The British Journal of Ophthalmology Apr 1987Topical levobunolol 0.5% was compared with topical metipranolol 0.6% for efficacy, safety, and comfort in 46 patients with open angle glaucoma or ocular hypertension.... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Topical levobunolol 0.5% was compared with topical metipranolol 0.6% for efficacy, safety, and comfort in 46 patients with open angle glaucoma or ocular hypertension. The study was of parallel design, randomised, double-masked, and of three months' duration. After a washout interval the study medications were instilled twice daily in both eyes. The overall mean decrease in intraocular pressure (IOP) was approximately 7 mmHg in both groups. More than 90% of patients in both groups successfully completed the study. Both agents caused slight decreases in heart rate and blood pressure. More complaints of burning and stinging were reported in the metipranolol group than in the levobunolol group. This three-month, 46-patient study showed levobunolol 0.5% and metipranolol 0.6% to be similarly effective ocular hypotensive agents.
Topics: Administration, Topical; Adult; Aged; Blood Pressure; Double-Blind Method; Glaucoma, Open-Angle; Heart Rate; Humans; Intraocular Pressure; Levobunolol; Metipranolol; Middle Aged; Ocular Hypertension; Propanolamines; Random Allocation
PubMed: 2883990
DOI: 10.1136/bjo.71.4.250 -
Medicine Sep 2022Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic...
BACKGROUND
Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis.
METHODS
Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified.
RESULTS
Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma.
CONCLUSION
This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.
Topics: Ajmaline; Aminoglutethimide; Asthma; Bethanechol; Biomarkers; Cefaclor; Computational Biology; Cytokines; Dimenhydrinate; Ethionamide; Gene Expression Profiling; Humans; Iloprost; Indoprofen; JNK Mitogen-Activated Protein Kinases; Levobunolol; Mimosine; Mitogen-Activated Protein Kinases; Myeloid Differentiation Factor 88; NF-kappa B; NLR Proteins; Neutrophils; Receptors, Cytokine; Toll-Like Receptor 2; Trapidil; Triggering Receptor Expressed on Myeloid Cells-1
PubMed: 36197221
DOI: 10.1097/MD.0000000000030661 -
The British Journal of Ophthalmology Dec 1988Fifty-one patients with raised intraocular pressure (IOP) were treated for up to four years with one of three ophthalmic solutions: 0.5% levobunolol, 1% levobunolol, or... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Fifty-one patients with raised intraocular pressure (IOP) were treated for up to four years with one of three ophthalmic solutions: 0.5% levobunolol, 1% levobunolol, or 0.5% timolol. The study was conducted as a double-masked, randomised trial in which medications were administered twice daily to both eyes. Levobunolol and timolol were equally effective in reducing overall mean IOP; reductions were greater than 8.8 mmHg in all three treatment groups. The study showed levobunolol to be as safe and effective as timolol in the long-term control of raised IOP.
Topics: Aged; Blood Pressure; Double-Blind Method; Female; Glaucoma; Heart Rate; Humans; Intraocular Pressure; Levobunolol; Male; Middle Aged; Timolol; Visual Fields
PubMed: 3067745
DOI: 10.1136/bjo.72.12.892 -
Clinical Interventions in Aging 2014An 88-year-old man was admitted with fatigue, dizziness, and heart palpitations. Both the electrocardiogram and Holter confirmed the existence of sinus bradycardia and...
An 88-year-old man was admitted with fatigue, dizziness, and heart palpitations. Both the electrocardiogram and Holter confirmed the existence of sinus bradycardia and sinus arrest. One hour prior to the onset of symptoms, he received levobunolol hydrochloride solution topically. The levobunolol hydrochloride solution was discontinued and the bradycardia resolved. He was diagnosed as having intermittent sinus bradycardia and sinus arrest, induced by topical β-blocker therapy. Levobunolol hydrochloride solution is an effective therapy for ocular hypertension, probably by reducing aqueous fluid production. However, it can induce cardiac side effects such as bradyarrhythmia and should be used with caution in elderly patients or patients with cardiac disease.
Topics: Adrenergic beta-Antagonists; Aged, 80 and over; Bradycardia; Electrocardiography, Ambulatory; Heart Rate; Humans; Levobunolol; Male; Ocular Hypertension; Ophthalmic Solutions; Sinus Arrest, Cardiac
PubMed: 25342892
DOI: 10.2147/CIA.S69420 -
Ophthalmology Jun 1988The prophylactic effect of topical 0.5% levobunolol on intraocular pressure (IOP) elevations after neodymium:YAG (Nd:YAG) laser posterior capsulotomies and extracapsular... (Clinical Trial)
Clinical Trial
The prophylactic effect of topical 0.5% levobunolol on intraocular pressure (IOP) elevations after neodymium:YAG (Nd:YAG) laser posterior capsulotomies and extracapsular cataract extractions (ECCEs) was investigated in two separate, double-masked, placebo-controlled studies. In study 1, 42 patients received either levobunolol or vehicle 1 hour before a unilateral Nd:YAG laser posterior capsulotomy. Elevated IOP (greater than or equal to 10 mmHg) occurred in up to 38% of those in the vehicle group and none in the levobunolol group. Mean IOP increased up to 6 mmHg in the vehicle group, whereas it decreased up to 3 mmHg in the levobunolol group. In study 2, 41 patients received either levobunolol or vehicle immediately after a unilateral ECCE involving the use of a viscoelastic preparation and the implantation of a posterior chamber intraocular lens (PC IOL). The incidence of IOP elevations (greater than or equal to 10 mmHg) was up to 40% in the vehicle group and 19% in the levobunolol group. Mean IOP increased up to 9 mmHg in the vehicle group and up to 2 mmHg in the levobunolol group. Thus, marked elevations in IOP after posterior capsulotomies or ECCEs may be minimized by prophylactic treatment with levobunolol.
Topics: Cataract Extraction; Humans; Intraocular Pressure; Laser Therapy; Lens Capsule, Crystalline; Lens, Crystalline; Levobunolol; Postoperative Complications; Postoperative Period
PubMed: 3062528
DOI: 10.1016/s0161-6420(88)33124-6 -
The British Journal of Ophthalmology May 2022To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
To assess the comparative efficacy of latanoprostene bunod (LBN), a novel prostaglandin analogue (PGA), to other medications for open-angle glaucoma and ocular hypertension on lowering intraocular pressure (IOP).
METHODS
A systematic literature review adapted from the Li (Ophthalmology, 2016) study was conducted. Medline, Embase and PubMed were searched for randomised controlled trials published between 1 January 2014 and 19 March 2020. Studies had to report IOP reduction after 3 months for at least two different treatments among placebo, PGAs (bimatoprost 0.01%, bimatoprost 0.03%, latanoprost, LBN, tafluprost, unoprostone) or apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide, levobunolol, timolol, travoprost. A Bayesian network meta-analysis was performed to provide the relative effect in terms of mean difference (95% credible interval) of IOP reduction and ranking probabilities. Surface under the cumulative ranking curve (SUCRA) was generated.
RESULTS
A total of 106 trials were included with data for 18 523 participants. LBN was significantly more effective than unoprostone (-3.45 (-4.77 to -2.12)). Although relative effect was not significative, compared with other PGAs, LBN numerically outperformed latanoprost (-0.70 (-1.83 to 0.43)) and tafluoprost (-0.41 (-1.87 to 1.07)), was similar to bimatoprost 0.01% (-0.02(-1.59 to 1.55)) and was slightly disadvantaged by bimatoprost 0.03% (-0.17 (-1.42 to 1.07)). LBN was significantly more efficient than the beta-blockers apraclonidine, betaxolol, brimonidine, brinzolamide, carteolol, dorzolamide and timolol. According to SUCRA, LBN was ranked second after bimatoprost 0.03%, followed by bimatoprost 0.01%.
CONCLUSION
LBN was significantly more effective than the PGA unoprostone and most of the beta-blockers. Compared with the most widely used PGAs, LBN numerically outperformed latanoprost and travoprost and was similar to bimatoprost 0.01%.
Topics: Amides; Antihypertensive Agents; Bayes Theorem; Betaxolol; Bimatoprost; Brimonidine Tartrate; Carteolol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Network Meta-Analysis; Ocular Hypertension; Prostaglandins A; Prostaglandins F, Synthetic; Timolol; Travoprost
PubMed: 33397657
DOI: 10.1136/bjophthalmol-2020-317262 -
Experimental Eye Research Nov 1993Using an in vitro culture system, we investigated the effects of five antiglaucoma drugs on growth and morphologic characteristics of bovine trabecular meshwork cells....
Using an in vitro culture system, we investigated the effects of five antiglaucoma drugs on growth and morphologic characteristics of bovine trabecular meshwork cells. Epinephrine hydrochloride (55-550 microM) and pilocarpine hydrochloride (0.8-16 mM), when added to the cultures for 3 days, inhibited trabecular cell growth in a dose-dependent manner. The lowest concentration at which the inhibitory effect was observed was 109 microM and 0.8 mM, respectively, for epinephrine and pilocarpine. Dipivefrin hydrochloride (26-260 microM), timolol maleate (116-1160 microM), and levobunolol hydrochloride (150-1500 microM) were also added to the cells for 3 days. These drugs caused a reduction in cell density, respectively, at concentrations higher than 103, 460, and 616 microM. Cell elongation was seen in cultures treated with epinephrine and dipivefrin, whereas levobunolol and timolol induced the cells to adopt a rounded appearance. Cells that had been exposed to pilocarpine were enlarged with numerous vacuoles. By scanning electron microscopic techniques, epinephrine, timolol, and levobunolol were found to retard the phagocytosis of latex beads by trabecular meshwork cells. Immunostaining with the use of antibodies to vimentin and actin revealed disorganization and condensation of cytoskeletal fibers in trabecular meshwork cells after treatment with epinephrine and dipivefrin. Little change was seen with comparable concentrations of a preservative, benzalkonium chloride, and a vehicle, Liquifilm tears. These results showed that antiglaucoma drugs, depending on their concentrations, may profoundly influence the growth and activity of trabecular meshwork cells.
Topics: Actins; Animals; Cattle; Cell Survival; Cells, Cultured; Cytoskeleton; Dose-Response Relationship, Drug; Epinephrine; Glaucoma; Levobunolol; Phagocytosis; Pilocarpine; Timolol; Trabecular Meshwork; Vimentin
PubMed: 8282042
DOI: 10.1006/exer.1993.1160