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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 -
Translational Vision Science &... Mar 2020To assess the pharmacokinetic (PK)/pharmacodynamic (PD) relationship following intracameral Bimatoprost sustained-release (SR) implants (8, 15, 30, and 60 µg) in dogs...
PURPOSE
To assess the pharmacokinetic (PK)/pharmacodynamic (PD) relationship following intracameral Bimatoprost sustained-release (SR) implants (8, 15, 30, and 60 µg) in dogs to determine the optimal investigative dose in humans.
METHODS
Forty-four male normotensive beagle dogs were assigned to 1 of 8 groups receiving 8-, 15-, 30-, and 60-µg implants (PD assessment [n = 8/group, 4 groups]; PK assessment [n = 3/group, 4 groups]). Intraocular pressure (IOP) in PD animals and aqueous humor/blood concentrations of bimatoprost and its acid in PK animals were assessed. PK/PD correlation analysis was performed using steady-state data. Residual implants were recovered to assess polymer degradation.
RESULTS
Dose-dependent IOP lowering was observed for all dose groups for at least 3 months postdose. Blood concentrations of bimatoprost and bimatoprost acid were below the limit of quantification (<0.25 ng/mL), whereas dose-dependent concentration-time profiles were observed in the aqueous humor. At steady state, observed and predicted correlation between aqueous humor drug concentration and IOP lowering was similar and translatable to findings in humans following topical bimatoprost eyedrop administration. Implants at all doses were well tolerated and polymer degradation was apparent.
CONCLUSIONS
Dose-dependent IOP lowering with Bimatoprost SR was maintained for at least 3 months in dogs, and the implants were well tolerated. The established PK/PD relationship appears to translate to humans. Doses between 8 and 15 µg appear to provide the best benefit/risk profile for clinical development of the implants.
TRANSLATIONAL RELEVANCE
The close PK/PD relationship between dog and human helps inform which bimatoprost dose should be investigated in clinical studies.
Topics: Animals; Antihypertensive Agents; Aqueous Humor; Bimatoprost; Delayed-Action Preparations; Dogs; Intraocular Pressure; Male
PubMed: 32818107
DOI: 10.1167/tvst.9.4.20 -
Acta Ophthalmologica May 2022Preservative-free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review...
Preservative-free topical medications have been introduced for glaucoma care to reduce ocular adverse events associated with preservatives. This is a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing the efficacy and safety of beta-blockers, or combination using beta-blockers, with and without preservatives. PubMed, EMBASE and Web of Science were examined. Risk of bias was assessed using the Cochrane Handbook for Systematic Reviews. The primary outcome was change in intraocular pressure (IOP) from baseline to final follow-up. Secondary outcomes included ocular and systemic side effects, and other clinical and quality of life outcomes. Of 242 records identified, seven RCTs (1125 patients) were included. The follow-up period ranged from one to 12 months. Timolol was used in five studies, and two studies used a combination (timolol with bimatoprost or dorzolamide). The difference in mean change (MD) in IOP between the preservative-free and the preserved drugs was statistically significant but not clinically relevant: (MD 0.29 mmHg, 95% confidence interval 0.07-0.51 mmHg, p = 0.010; moderate-certainty evidence). Regarding adverse events: Level of evidence for all ocular surface outcome was low or very low and reported in few studies. No significant difference was observed on ocular surface symptoms. Tear break-up time (TBUT) was better with preservative-free drops (p < 0.001). Schirmer's test was better in the preservative-free group (p < 0.001). Level of evidence for all ocular surface outcomes was low or very low. There was no difference in other secondary outcomes. We found no clinically relevant difference in mean change in IOP between the preserved and the preservative-free treatments. Data on adverse events used different methods and were incompletely reported. Although some measures of ocular surface health favoured preservative-free medications, more evidence is needed. The increasing use of preservative-free drops may be associated with better ocular surface and tolerability, but strong evidence from RCTs would be welcome.
Topics: Adrenergic beta-Antagonists; Antihypertensive Agents; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Timolol
PubMed: 34128326
DOI: 10.1111/aos.14926 -
Clinical Ophthalmology (Auckland, N.Z.) 2022Studies comparing the two different formulations of bimatoprost, 0.03% and 0.01%, have shown similar efficacy, but a better adverse effect profile for bimatoprost 0.01%...
PURPOSE
Studies comparing the two different formulations of bimatoprost, 0.03% and 0.01%, have shown similar efficacy, but a better adverse effect profile for bimatoprost 0.01% in patients with primary open-angle glaucoma (POAG) and ocular hypertension (OHT). This study assesses the efficacy and tolerability of switching from bimatoprost 0.01% to 0.03% in a patient population with broader spectrum of diagnoses in a real-world clinical setting.
DESIGN
Single-centre retrospective observational switch study.
METHODS
Selected patients were on initial topical therapy with bimatoprost 0.01% prior to switching to bimatoprost 0.03%. Intraocular pressure (IOP) was collected from their pre-switch visit, 6- and 12-week after switch. Paired two-sample -test was performed to compare IOP at different time points versus baseline. Worsening of hyperemia and other adverse events after the switch were identified. Subgroup analysis was performed for POAG and OHT, secondary open-angle glaucoma (SOAG, including pseudoexfoliative and pigmentary glaucoma), normal tension glaucoma (NTG), and angle closure glaucoma (ACG).
RESULTS
The study population consisted of 248 eyes (143 patients). There was a significant mean IOP reduction of 1.0 ± 3.7 mmHg (p < 0.001, n = 248) from baseline to week-6 and 1.6 ± 4.0 mmHg (p < 0.001, n = 142) from baseline to week-12 after switch. The IOP reduction was statistically significant in patients with POAG and OHT (6-week: 1.0 ± 3.8 mmHg, n = 76; 12-week: 1.5 ± 4.1 mmHg, n = 49), ACG (6-week: 1.5 ± 4.1 mmHg, n = 72; 12-week: 2.3 ± 4.5 mmHg, n = 46), and NTG (6-week: 0.83 ± 2.5 mmHg, n = 42; 12-week: 1.12 ± 2.1 mmHg, n = 25). Patients with SOAG did not show statistically significant reduction in IOP at 6- or 12-week after switch. Forty-two (29%) of 143 patients experienced adverse events, with the most common being hyperemia (16%).
CONCLUSION
Significant reduction in IOP could be seen after switching from bimatoprost 0.01% to bimatoprost 0.03% in various types of glaucoma except SOAG. Intolerance after switch may be experienced, though not in the majority of cases.
PubMed: 35936971
DOI: 10.2147/OPTH.S368214 -
PloS One 2016The intraocular pressure (IOP)-lowering and side effects in response to different prostaglandin F2α analogues can be variable, but, the underlying basis for this...
BACKGROUND AND PURPOSE
The intraocular pressure (IOP)-lowering and side effects in response to different prostaglandin F2α analogues can be variable, but, the underlying basis for this difference remains unknown. This study investigated the differential changes of cellular proteins relevant to IOP-lowering effects of latanoprost and bimatoprost.
METHODS
The human T lymphoblast (MOLT-3) cell line and immortalized human trabecular meshwork (iHTM) cells were studied by quantitative PCR and by immunofluorescence after treatment with either latanoprost or bimatoprost. New Zealand white rabbit eyes were treated topically with each agent and, following euthanasia, anterior segment tissues were studied with immunostaining.
RESULTS
In cultured MOLT-3 cells, mRNA expression of both c-fos and matrix metalloproteinase 9 increased significantly in response to each agent. In addition, there was little change in tissue inhibitor of metalloproteinase (TIMP)-3 mRNA, but a significant decrease in TIMP-4. Fibronectin mRNA in MOLT-3 cells was down-regulated with bimatoprost, but was up-regulated with latanoprost. Immunofluorescence analysis of iHTM cells showed that intracellular fibronectin was significantly decreased by bimatoprost, but was increased by latanoprost. Both latanoprost and bimatoprost increased mRNA expression of NF-кB p65 and decreased that of IкBα. Aquaporin-1 mRNA expression was significantly down-regulated by bimatoprost. Immunostaining also revealed a significant decrease of aquaporin-1 in the ciliary epithelium of New Zealand white rabbits after bimatoprost treatment.
CONCLUSIONS
Similarities in protein expression produced by latanoprost and bimatoprost in vitro may be relevant to the mechanism for their IOP-lowering effects in vivo. Differences in fibronectin expression and in aquaporin-1 expression in response to each agent may contribute to variability in the IOP-lowering efficacy in some studies.
Topics: Animals; Antihypertensive Agents; Aquaporin 1; Bimatoprost; Cell Line; Fibronectins; Gene Expression Regulation; Humans; Intraocular Pressure; Latanoprost; NF-kappa B; Prostaglandins F, Synthetic; Proteolysis; RNA, Messenger; Rabbits; Signal Transduction
PubMed: 27011234
DOI: 10.1371/journal.pone.0151644 -
Archives of Dermatological Research Nov 2023Eyebrows are an important feature of facial identity and communications in human beings as well as an important eye defense shield from dust and foreign bodies. To... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparative study of the efficacy and safety of topical minoxidil 2% versus topical bimatoprost 0.01% versus topical bimatoprost 0.03% in treatment of eyebrow hypotrichosis: a randomized controlled trial.
Eyebrows are an important feature of facial identity and communications in human beings as well as an important eye defense shield from dust and foreign bodies. To compare the efficacy and safety between 0.01%, 0.03% bimatoprost and minoxidil 2% in gel formulations for eyebrow enhancement. Sixty eligible subjects were female or male, aged 18 years or older with eyebrow hypotrichosis, defined as either a Grade 1 or 2 on the Global Eyebrow Assessment (GEBA) scale. Patients were randomized into 3 groups using block randomization. Group a (20 patients) applied topical 0.03% bimatoprost gel once daily onto both eyebrows, group b (20 patients) applied topical 0.01% bimatoprost gel once daily onto both eyebrows while group c (20 patients) applied topical minoxidil 2% gel once daily onto both eyebrows. A significant improvement in GEBA score was reported in all the three groups after treatment (P ≤ 0.001); however, there was no statistically significant difference between the three groups (P1 = 0.091; P2 = 0.102; P3 = 0.663). Bimatoprost is equally efficacious as minoxidil in enhancement of eyebrows with a more favorable response produced by the 0.03% concentration.
Topics: Humans; Male; Female; Bimatoprost; Minoxidil; Eyebrows; Hypotrichosis; Administration, Topical; Treatment Outcome; Double-Blind Method
PubMed: 37517060
DOI: 10.1007/s00403-023-02679-2 -
Clinical Ophthalmology (Auckland, N.Z.) 2015The purpose of this study was to prospectively evaluate and compare intraocular pressure (IOP) reduction efficacy and safety between bimatoprost and latanoprost-timolol...
BACKGROUND
The purpose of this study was to prospectively evaluate and compare intraocular pressure (IOP) reduction efficacy and safety between bimatoprost and latanoprost-timolol fixed combination (LTFC) in Japanese patients with open-angle glaucoma.
METHODS
In this prospective, randomized, non-masked study, after enrolling 70 eyes of 70 Japanese open-angle glaucoma patients who had used latanoprost monotherapy for more than 4 weeks, the subjects were randomly divided into a bimatoprost group or an LTFC group. Both groups were switched from latanoprost to bimatoprost or LTFC for 12 weeks. IOP, conjunctival injection score, corneal epitheliopathy score (area density classification; AD score), tear film break-up time, heart rate, and blood pressure were evaluated at 0, 4, and 12 weeks after switching. The paired t-test and Mann-Whitney U-test were used for the statistical analysis.
RESULTS
After 13 of the 70 patients dropped out, 57 were analyzed for IOP reduction and safety. There was a significant decrease in mean IOP at 4 weeks compared with week 0 in both groups (both P<0.0001). Comparisons between the two groups showed no statistically significant differences. The conjunctival injection score was higher in the bimatoprost group than in the LTFC group at 12 weeks (P=0.0091). There were no statistically significant differences between the two drugs in relation to AD score, tear film break-up time, heart rate, and blood pressure.
CONCLUSION
Bimatoprost and LTFC exhibited similar efficacy for reduction of IOP. Safety results indicated that only the conjunctival injection score at 12 weeks was higher in the bimatoprost group compared with the LTFC group.
PubMed: 26300624
DOI: 10.2147/OPTH.S87613 -
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 -
Drugs Nov 2021To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate the intraocular pressure (IOP)-lowering efficacy and safety of 10 and 15 µg bimatoprost implant in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).
METHODS
This randomized, 20-month, multicenter, masked, parallel-group, phase 3 trial enrolled 528 patients with OAG or OHT and an open iridocorneal angle inferiorly in the study eye. Study eyes were administered 10 or 15 µg bimatoprost implant on day 1, week 16, and week 32, or twice-daily topical timolol maleate 0.5%. Primary endpoints were IOP and IOP change from baseline through week 12. Safety measures included treatment-emergent adverse events (TEAEs) and corneal endothelial cell density (CECD).
RESULTS
Both 10 and 15 µg bimatoprost implant met the primary endpoint of noninferiority to timolol in IOP lowering through 12 weeks. Mean IOP reductions from baseline ranged from 6.2-7.4, 6.5-7.8, and 6.1-6.7 mmHg through week 12 in the 10 µg implant, 15 µg implant, and timolol groups, respectively. IOP lowering was similar after the second and third implant administrations. Probabilities of requiring no IOP-lowering treatment for 1 year after the third administration were 77.5% (10 µg implant) and 79.0% (15 µg implant). The most common TEAE was conjunctival hyperemia, typically temporally associated with the administration procedure. Corneal TEAEs of interest (primarily corneal endothelial cell loss, corneal edema, and corneal touch) were more frequent with the 15 than the 10 µg implant and generally were reported after repeated administrations. Loss in mean CECD from baseline to month 20 was ~ 5% in 10 µg implant-treated eyes and ~ 1% in topical timolol-treated eyes. Visual field progression (change in the mean deviation from baseline) was reduced in the 10 µg implant group compared with the timolol group.
CONCLUSIONS
The results corroborated the previous phase 3 study of the bimatoprost implant. The bimatoprost implant met the primary endpoint and effectively lowered IOP. The majority of patients required no additional treatment for 12 months after the third administration. The benefit-risk assessment favored the 10 over the 15 µg implant. Studies evaluating other administration regimens with reduced risk of corneal events are ongoing. The bimatoprost implant has the potential to improve adherence and reduce treatment burden in glaucoma. CLINICALTRIALS.
GOV IDENTIFIER
NCT02250651.
Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Dose-Response Relationship, Drug; Double-Blind Method; Drug Implants; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Timolol; Young Adult
PubMed: 34724172
DOI: 10.1007/s40265-021-01624-9 -
Clinical Ophthalmology (Auckland, N.Z.) 2017Glaucoma is a leading cause of irreversible blindness worldwide. The reduction of intraocular pressure has been well established as an effective treatment to prevent... (Review)
Review
Glaucoma is a leading cause of irreversible blindness worldwide. The reduction of intraocular pressure has been well established as an effective treatment to prevent both the development and the progression of all forms of glaucoma. Bimatoprost 0.03% ophthalmic solution, introduced in 2001, is a synthetic prostamide with the unique mechanism of improving both uveoscleral and trabecular outflow. Comparative studies with other pharmacotherapies have shown favorable results for bimatoprost as a potent ocular hypotensive agent that is generally well tolerated. Common side effects include conjunctival hyperemia, eyelash growth, iris pigmentation and periorbital changes. Hyperemia rates were reduced following the introduction of bimatoprost 0.01%. Bimatoprost should be used with caution in those with higher risk of developing ocular inflammation and macular edema. However, the perceived risk of bimatoprost in these patient populations is likely greater than the actual risk observed in practice. Bimatoprost is currently in the center of several clinical trials including its use for dermatologic applications and sustained-release therapies for the treatment of ocular hypertension and glaucoma.
PubMed: 28744094
DOI: 10.2147/OPTH.S118689