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Journal of Ophthalmology 2021Within the clinical setting, some patients have been identified as lacking in response to PGAs. This meta-analysis study aimed to evaluate the responsiveness of... (Review)
Review
AIM
Within the clinical setting, some patients have been identified as lacking in response to PGAs. This meta-analysis study aimed to evaluate the responsiveness of latanoprost, travoprost, bimatoprost, and tafluprost in OAG/OHT patients, latanoprost nonresponders (LNRs), and the IOP-reducing efficacy and safety.
METHODS
A literature search was conducted on PubMed, Embase, and the Cochrane Controlled Trials Register. The primary clinical endpoint was the number of responders at the end of the study. The secondary clinical endpoint was the IOP reduction at the endpoint from baseline. Safety evaluation included five common adverse events: conjunctival hyperemia, hypertrichosis, ocular burning, ocular itching, and foreign-body sensation.
RESULTS
Eleven articles containing ten RCTs were included in this meta-analysis study. The results highlighted that, in the OAG/OHT population, there was no statistically significant difference in the responsiveness of the four PGAs. Bimatoprost had a better IOP-reducing efficacy than latanoprost. There was no significant difference in the IOP-reducing efficacy of travoprost, latanoprost, and tafluprost. In LNRs, the responsiveness of bimatoprost, travoprost, and latanoprost did not show statistical differences. Bimatoprost reduced IOP with a greater extent than latanoprost and travoprost in LNRs, while there was no significant difference in the IOP-reducing efficacy of travoprost and latanoprost. No serious adverse events occurred with the treatment of the four PGAs. The prevalence of conjunctival hyperemia due to bimatoprost or tafluprost was significantly higher than that of latanoprost. Other adverse events had no significant difference between the four drugs.
CONCLUSION
The existing studies cannot prove that latanoprost, travoprost, bimatoprost, and tafluprost have different responsiveness in OAG/OHT patients. Switching to bimatoprost or travoprost cannot achieve a significant improvement in responsiveness in LNRs. Bimatoprost has a better IOP-reducing efficacy than latanoprost and travoprost. No serious adverse events occurred during treatment with any medication we studied.
PubMed: 34123413
DOI: 10.1155/2021/5586719 -
Investigative Ophthalmology & Visual... Mar 2023The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix...
PURPOSE
The purpose of this study was to evaluate the effects of pharmacologically relevant bimatoprost and bimatoprost free acid (BFA) concentrations on matrix metalloproteinase (MMP) gene expression in cells from human aqueous outflow tissues.
METHODS
MMP gene expression by human trabecular meshwork (TM), scleral fibroblast (SF), and ciliary muscle (CM) cells exposed to 10 to 1000 µM bimatoprost or 0.1 to 10 µM BFA (intraocular concentrations after intracameral bimatoprost implant and topical bimatoprost dosing, respectively) was measured by polymerase chain reaction array.
RESULTS
Bimatoprost dose-dependently upregulated MMP1 and MMP14 mRNA in all cell types and MMP10 and MMP11 mRNA in TM and CM cells; in TM cells from normal eyes, mean MMP1 mRNA levels were 62.9-fold control levels at 1000 µM bimatoprost. BFA upregulated MMP1 mRNA only in TM and SF cells, to two- to three-fold control levels. The largest changes in extracellular matrix (ECM)-related gene expression by TM cells derived from normal (n = 6) or primary open-angle glaucoma (n = 3) eyes occurred with 1000 µM bimatoprost (statistically significant, ≥50% change for 9-11 of 84 genes on the array, versus 1 gene with 10 µM BFA).
CONCLUSIONS
Bimatoprost and BFA had differential effects on MMP/ECM gene expression. Dramatic upregulation in MMP1 and downregulation of fibronectin, which occurred only with bimatoprost at high concentrations observed in bimatoprost implant-treated eyes, may promote sustained outflow tissue remodeling and long-term intraocular pressure reduction beyond the duration of intraocular drug bioavailability. Variability in bimatoprost-stimulated MMP upregulation among cell strains from different donors may help explain differential long-term responses of patients to bimatoprost implant.
Topics: Humans; Intraocular Pressure; Matrix Metalloproteinase 1; Glaucoma, Open-Angle; Tonometry, Ocular; Sclera; Bimatoprost
PubMed: 36877514
DOI: 10.1167/iovs.64.3.15 -
Frontiers in Pharmacology 2022Glaucoma is the main cause of irreversible visual loss worldwide, and comprises a group of progressive, age-related, and chronic optic neuropathies. Prostaglandin... (Review)
Review
Glaucoma is the main cause of irreversible visual loss worldwide, and comprises a group of progressive, age-related, and chronic optic neuropathies. Prostaglandin analogs are considered a first-line treatment in the management of glaucoma and have the best efficacy in reducing intraocular pressure. When comparing these therapeutic agents between them, long-term therapy with 0.03% bimatoprost is the most effective followed by treatment with 0.005% latanoprost and 0.004% travoprost. The prevalence of adverse events is lower for latanoprost than for other prostaglandin analogs. However, some patients do not respond to the treatment with prostaglandin analogs (non-responders). Intraocular pressure-lowering efficacy differs significantly between individuals partly owing to genetic factors. Rs1045642 in , rs4241366 in , rs9503012 in , rs10306114 in , rs11568658 in , rs10786455 and rs6686438 in were reported to be positive with the response to prostaglandin analogs in patients with glaucoma. A negative association was found between single nucleotide polymorphisms of (rs11578155 and rs6672484) and the response to prostaglandin analogs in patients with glaucoma. The current review is an analysis of the information relevant to prostaglandin analog treatments based on previous literatures. It describes in detail the clinical pharmacology and pharmacogenetics of drugs belonging to this therapeutical class to provide a sound pharmacological basis for their proper use in ophthalmological clinical practice.
PubMed: 36313286
DOI: 10.3389/fphar.2022.1015338 -
International Journal of Ophthalmology 2021Glaucoma, a leading cause of irreversible blindness, affects more than 64 million people worldwide and is expected to grow in number due to the aging global population... (Review)
Review
Glaucoma, a leading cause of irreversible blindness, affects more than 64 million people worldwide and is expected to grow in number due to the aging global population and enhanced methods of detection. Although topical therapies are often effective when used as prescribed, the drawbacks of current medical management methods include poor patient adherence, local and systemic side effects, and in some cases, limited therapeutic efficacy. Novel ocular drug delivery platforms promise to deliver differentiated drug formulations with targeted delivery leveraging patient-independent administration. Several platforms are in various stages of development with promising pre-clinical and clinical data. The Bimatoprost Sustained Release (SR) intracameral implant was approved in the United States in March of 2020, making it the first long-term injectable therapy available for the treatment of glaucoma. This review aims to provide an update on novel sustained release drug delivery systems that are available today as well as those that might be commercialized in coming years.
PubMed: 33469497
DOI: 10.18240/ijo.2021.01.21 -
Pharmaceuticals (Basel, Switzerland) Apr 2024Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and... (Review)
Review
BACKGROUND
Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and beyond. Originally developed as an ocular hypotensive agent, it has proven highly effective in treating glaucoma and ocular hypertension. Its ability to reduce intraocular pressure has established it as a first-line treatment option, improving management and preventing vision loss. In dermatology, bimatoprost has shown promising results in the promotion of hair growth, particularly in the treatment of alopecia and hypotrichosis. Its mechanism of action, stimulating the hair cycle and prolonging the growth phase, has led to the development of bimatoprost-containing solutions for enhancing eyelash growth.
AIM
The aim of our review is to provide a brief description, overview, and studies in the current literature regarding the versatile clinical use of bimatoprost in recent years. This can help clinicians determine the most suitable individualized therapy to meet the needs of each patient.
METHODS
Our methods involve a comprehensive review of the latest advancements reported in the literature in bimatoprost formulations, which range from traditional eye drops to sustained-release implants. These innovations offer extended drug delivery, enhance patient compliance, and minimize side effects.
RESULTS
The vast literature published on PubMed has confirmed the clinical usefulness of bimatoprost in lowering intraocular pressure and in managing patients with glaucoma. Numerous studies have shown promising results in dermatology and esthetics in promoting hair growth, particularly in treating alopecia and hypotrichosis. Its mechanism of action involves stimulating the hair cycle and prolonging the growth phase, leading to the development of solutions that enhance eyelash growth. The global use of bimatoprost has expanded significantly, with applications growing beyond its initial indications. Ongoing research is exploring its potential in glaucoma surgery, neuroprotection, and cosmetic procedures.
CONCLUSIONS
Bimatoprost has shown immense potential for addressing a wide range of therapeutic needs through various formulations and advancements. Promising future perspectives include the exploration of novel delivery systems such as contact lenses and microneedles to further enhance drug efficacy and patient comfort. Ongoing research and future perspectives continue to shape its role in medicine, promising further advancements and improved patient outcomes.
PubMed: 38794131
DOI: 10.3390/ph17050561 -
Graefe's Archive For Clinical and... Jan 2024PURPOSE : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda) with... (Randomized Controlled Trial)
Randomized Controlled Trial
UNLABELLED
PURPOSE : To compare the efficacy and safety of the fixed-dose combination (FDC) of netarsudil 0.02%/latanoprost 0.005% ophthalmic solution (NET/LAT; Roclanda) with bimatoprost 0.03%/timolol maleate 0.5% (BIM/TIM; Ganfort) ophthalmic solution in the treatment of open-angle glaucoma (OAG) and ocular hypertension (OHT).
METHODS
MERCURY-3 was a 6-month prospective, double-masked, randomized, multicenter, active-controlled, parallel-group, non-inferiority study. Patients (≥ 18 years) with a diagnosis of OAG or OHT in both eyes that was insufficiently controlled with topical medication (IOP ≥ 17 mmHg in ≥ 1 eye and < 28 mmHg in both eyes) were included. Following washout, patients were randomized to once-daily NET/LAT or BIM/TIM for up to 6 months; efficacy was assessed at Week 2, Week 4, and Month 3; safety was evaluated for 6 months. Comparison of NET/LAT relative to BIM/TIM for mean IOP at 08:00, 10:00, and 16:00 h was assessed at Week 2, Week 6, and Month 3. Non-inferiority of NET/LAT to BIM/TIM was defined as a difference of ≤ 1.5 mmHg at all nine time points through Month 3 and ≤ 1.0 mmHg at five or more of nine time points through Month 3.
RESULTS
Overall, 430 patients were randomized (NET/LAT, n = 218; BIM/TIM, n = 212), and all received at least one dose of study medication. Efficacy analyses were performed at Month 3 on 388 patients (NET/LAT, n = 184; BIM/TIM, n = 204). NET/LAT demonstrated non-inferiority to BIM/TIM, with a between-treatment difference in IOP of ≤ 1.5 mmHg achieved at all time points and ≤ 1.0 mmHg at the majority of time points (six of nine) through Month 3. Mean diurnal IOP during the study ranged from 15.4 to 15.6 mmHg and 15.2 to 15.6 mmHg in the NET/LAT and BIM/TIM groups respectively, with no between-group statistically significant difference. No significant differences were observed in key secondary endpoints. No serious, treatment-related adverse events (AEs) were observed, and AEs were typically mild/moderate in severity. The most common treatment-related AEs were conjunctival hyperemia (NET/LAT, 30.7%; BIM/TIM, 9.0%) and cornea verticillata (NET/LAT, 11.0%; BIM/TIM, 0%).
CONCLUSIONS
Once-daily NET/LAT was non-inferior to BIM/TIM in IOP reduction in OAG and OHT, with AEs consistent with previous findings. NET/LAT offers a compelling alternative FDC treatment option for OAG and OHT.
Topics: Humans; Glaucoma, Open-Angle; Timolol; Bimatoprost; Latanoprost; Prospective Studies; Intraocular Pressure; Antihypertensive Agents; Tonometry, Ocular; Ocular Hypertension; Ophthalmic Solutions; Treatment Outcome; Double-Blind Method; Benzoates; beta-Alanine
PubMed: 37615697
DOI: 10.1007/s00417-023-06192-0 -
Experimental Eye Research May 2020Bimatoprost, latanoprost, and unoprostone are prostaglandin F analogs (PGAs) and are used to lower intraocular pressure. We investigated the free acid effects of these...
Effect of prostaglandin analogs: Latanoprost, bimatoprost, and unoprostone on matrix metalloproteinases and their inhibitors in human trabecular meshwork endothelial cells.
Bimatoprost, latanoprost, and unoprostone are prostaglandin F analogs (PGAs) and are used to lower intraocular pressure. We investigated the free acid effects of these three prostaglandin analogs: bimatoprost, latanoprost, and unoprostone on human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMP) in the trabecular meshwork (TM) cells. Immunoblot results show that all three PGAs generally increased MMPs-1,9 and TIMPs-4. Additionally, bimatoprost and latanoprost both increased MMP-3 and TIMP-2, while unoprostone had an indeterminate effect on both. Zymography results show that all three PGAs except unoprostone increased intermediate MMP-1 activity while bimatoprost and latanoprost increased MMP-9 activity. Together, these data suggest that the balance between MMPs and TIMPs correlate to the relative intraocular pressure lowering effectiveness observed in clinical studies of these PGAs.
Topics: Adult; Aged; Antihypertensive Agents; Bimatoprost; Cells, Cultured; Female; Glaucoma, Open-Angle; Humans; Immunoblotting; Latanoprost; Male; Matrix Metalloproteinase Inhibitors; Matrix Metalloproteinases; Middle Aged; Ophthalmic Solutions; Prostaglandins A, Synthetic; Quaternary Ammonium Compounds; Trabecular Meshwork; Young Adult
PubMed: 32222455
DOI: 10.1016/j.exer.2020.108019 -
Journal of Ophthalmic & Vision Research 2020Glaucoma management has changed dramatically over the last decades, through clinical advances and technological revolutions. This review discusses the latest innovations... (Review)
Review
Glaucoma management has changed dramatically over the last decades, through clinical advances and technological revolutions. This review discusses the latest innovations and challenges faced in the field around three major axes: minimally-invasive glaucoma surgery (MIGS), implantable sensors and injectable therapeutics. Indeed, the vast number of recently developed MIGS techniques has not only provided clinicians with a wide range of therapeutic options, but they have also enabled them to adjust their therapies more finely which may have contributed a more patient-centric decision-making process. Yet, despite considerable advances in the field, the wide heterogeneity in clinical trial designs blurs the surgical outcomes, specificities and indications. Thus, more high-quality data are required to make the choice of a specific MIGS procedure more than an educated guess. Beyond the scope of MIGS, the potential of IOP telemetry for self-assessment of IOP-control through implantable sensors is developing into a real option for clinicians and an empowering opportunity for patients. Indeed, providing patients with direct feedback enables them to take control and have a clearer representation of their care, in turn leading to a better control of the disease. However, there are potential issues with self-monitoring of IOP, such as increased anxiety levels induced by measured IOP fluctuations and peaks, leading to patients self-treating during IOP spikes and additional office visits. Furthermore, the advent of implantable therapeutics may soon provide yet another step towards personalized glaucoma treatment, by offering not only an efficient alternative to current treatments, but also a therapeutic option that may better adapt to patients' lifestyle. After several decades of relative stagnation through the last century, glaucoma has now entered what many view as a golden age for the specialty. Like every revolution, this one brings its fair share of uncertainty, clinical questioning and uneasy periods of adaptation to ever-changing expectations. Yet, while it is impossible to guess what the landscape of glaucoma surgery will be like in ten or fifteen years, data suggest a bright outlook both for patients and clinicians.
PubMed: 33133445
DOI: 10.18502/jovr.v15i4.7792 -
Aging Apr 2024The cardiovascular effects of metformin continue to be a subject of debate within the medical community.
BACKGROUND
The cardiovascular effects of metformin continue to be a subject of debate within the medical community.
METHODS
The Mendelian randomization (MR) study used data from genome-wide association studies (GWAS) to explore the causal association with six diseases that are associated with bimatoprost treatment and myocardial infarction, chronic heart failure, atrial fibrillation, hypertrophic and dilated cardiomyopathy, and valvular disease. Genome-wide significant single nucleotide polymorphisms (SNPs), that are associated with metformin use were selected as the instrumental variables. To determine the causal relationship between metformin use and various cardiovascular diseases, MR analysis was conducted, employing methods such as Instrumental Variable Weighting (IVW).
RESULTS
The IVW analysis demonstrated a positive association between metformin treatment and the risk of myocardial infarction (OR = 22.67, 95% CI 3.22-34.01; = 0.002). Conversely, metformin treatment exhibited a negative association with the risk of developing valvular disease (OR = 0.98, 95% CI 0.95-1.00; = 0.046) and hypertrophic cardiomyopathy (OR = 0.01, 95% CI 0.00-0.22; = 0.016). Multiple test correction found that metformin treatment was causally associated with the risk of both hypertrophic cardiomyopathy ( = 0.048) and myocardial infarction ( = 0.012). The analysis revealed limited heterogeneity in the individual results, absence of pleiotropy evidence, and indications of stability in the findings.
CONCLUSION
The MR study discovered from a genetic standpoint that metformin may lower the risk of hypertrophic cardiomyopathy and valvular heart disease, yet it could elevate the risk of myocardial infarction.
Topics: Metformin; Mendelian Randomization Analysis; Humans; Genome-Wide Association Study; Polymorphism, Single Nucleotide; Cardiovascular Diseases; Hypoglycemic Agents; Myocardial Infarction
PubMed: 38683129
DOI: 10.18632/aging.205775 -
Biomedicine & Pharmacotherapy =... Dec 2023Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by...
Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by colistin limits its clinical use. To identify compounds that might ameliorate colistin-induced nephrotoxicity, we obtained 1707 compounds from the Korea Chemical Bank and used a high-content screening (HCS) imaging-based assay. In this way, we found that bimatoprost (one of prostaglandin F2α analogue) ameliorated colistin-induced nephrotoxicity. To further assess the effects of bimatoprost on colistin-induced nephrotoxicity, we used in vitro and in vivo models. In cultured human proximal tubular cells (HK-2), colistin induced dose-dependent cytotoxicity. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, indicative of apoptosis, was higher in colistin-treated cells, but this effect of colistin was ameliorated by cotreatment with bimatoprost. The generation of reactive oxygen species, assessed using 2,7-dichlorodihydrofluorescein diacetate, was less marked in cells treated with both colistin and bimatoprost than in those treated with colistin alone. Female C57BL/6 mice (n = 10 per group) that were intraperitoneally injected with colistin (10 mg/kg/12 hr) for 14 days showed high blood urea nitrogen and serum creatinine concentrations that were reduced by the coadministration of bimatoprost (0.5 mg/kg/12 hr). In addition, kidney injury molecule-1 (KIM1) and Neutrophil gelatinase-associated lipocalin (NGAL) expression also reduced by bimatoprost administration. Further investigation in tubuloid and kidney organoids also showed that bimatoprost attenuated the nephrotoxicity by colistin, showing dose-dependent reducing effect of KIM1 expression. In this study, we have identified bimatoprost, prostaglandin F2α analogue as a drug that ameliorates colistin-induced nephrotoxicity.
Topics: Mice; Animals; Female; Humans; Colistin; Bimatoprost; Dinoprost; Mice, Inbred C57BL; Anti-Bacterial Agents; Kidney; Prostaglandins
PubMed: 37918255
DOI: 10.1016/j.biopha.2023.115446