bimatoprost and tafluprost

Topics: Animals; Antihypertensive Agents; Bimatoprost; Drug Discovery; Glaucoma; Humans; Prostaglandins; Prostaglandins F; Travoprost; Treatment Outcome

To systematically review the efficacy and tolerability of 4 prostaglandin analogues (PGAs) as first-line monotherapies for intraocular pressure (IOP) lowering in adult patients with primary open-angle glaucoma or ocular hypertension.. A literature search was performed in PubMed (1965-June 2013) and the Cochrane Library (1980-June 2013) using the search terms ocular hypertension, open-angle glaucoma, prostaglandin analogues, bimatoprost, latanoprost, tafluprost, and travoprost. Additional studies were searched from the reference lists of identified publications.. In all, 32 randomized controlled trials comparing between PGAs (bimatoprost 0.03%, latanoprost 0.005%, tafluprost 0.0015%, and travoprost 0.004%) or PGA with timolol were selected.. A network meta-analysis was conducted. Using timolol as reference, the relative risks (RRs) of achieving treatment success, defined as the proportion of patients achieving at least 30% IOP reduction, with 95% CIs, were as follows: bimatoprost, 1.59 (1.28-1.98); latanoprost, 1.32 (1.00-1.74); travoprost, 1.33 (1.03-1.72); and tafluprost, 1.10 (0.85-1.42). The mean IOP reductions after 1 month were 1.98 (1.50-2.47), 1.01 (0.55-1.46), 1.08 (0.59-1.57), and 0.46 (-0.41 to 1.33) mm Hg, respectively, and the results were sustained at 3 months. Bimatoprost was associated with the highest risk of developing hyperemia, whereas latanoprost had the lowest risk, with RRs (95% CI) of 4.66 (3.49-6.23) and 2.30 (1.76-3.00), respectively.. Bimatoprost achieved the highest efficacy in terms of IOP reduction, whereas latanoprost had the most favorable tolerability profile. This review serves to guide selection of the optimal PGA agent for individual patient care in clinical practice.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Randomized Controlled Trials as Topic; Timolol; Travoprost

Hypotensive effect to prostaglandins analogs (latanoprost, travoprost, tafluprost) means to increase uveoscleral outflow by action to FP receptors who generated extracellular matrix changes and intermuscular spaces changes. Syntetic prostamides analogs (bimatoprost) have a particulary action with a receptors most and intensive studied. The bimatoprost effect is the consequences to preferated stimulations on the specific receptors who have action only the tissue with prostaglandins activity is important to specify what the bimatoprost have dual effect: to uveoscleral outflow and classic outflow by increase hidraulic conductivity.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Drug Therapy, Combination; Humans; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Prostaglandins; Prostaglandins F; Prostaglandins F, Synthetic; Receptors, Prostaglandin; Travoprost

Bimatoprost-timolol (bimatoprost 0.03%-timolol 0.5% fixed-dose combination [FDC]) and tafluprost-timolol (tafluprost 0.0015%-timolol 0.5% FDC) eye drops are currently the only topical intraocular pressure (IOP)-reducing therapies available as preservative-free (PF) prostaglandin and timolol FDC. The aim of this study was to investigate changes to ocular signs and symptoms when patients with ocular hypertension (OH) or open-angle glaucoma (OAG) switched from PF or benzalkonium chloride (BAK)-preserved bimatoprost-timolol to PF tafluprost-timolol eye drops.. This was a 12-week, open-label, phase IV study.. Sixteen centres in Finland, Germany, Italy and the UK.. Patients with OH or OAG (IOP on medication ≤21 mm Hg), treated with PF or BAK-preserved bimatoprost-timolol for ≥4 weeks before screening, and presenting with conjunctival hyperaemia and ≥1 ocular symptom.. Patients were switched to PF tafluprost-timolol once daily in the treated eye(s).. The primary endpoints were change from screening to week 12 in conjunctival hyperaemia and worst ocular symptom. The secondary outcome measures were changes from screening in ocular signs (other than conjunctival hyperaemia) and symptoms at week 12.. Of 123 enrolled patients, 121 were included in the intention-to-treat dataset, of which all were Caucasian and 54.5% were female; 76 patients used BAK-preserved bimatoprost-timolol and 45 used PF drops. Conjunctival hyperaemia and severity of worst ocular symptom following switch to PF tafluprost-timolol significantly reduced from screening to week 12 in all patients (p<0.001). The percentage of patients with ocular signs and symptoms was significantly reduced at week 12 compared with screening (p<0.001). IOP was not affected by the change of treatment.. Switching from BAK-preserved or PF bimatoprost-timolol to tafluprost-timolol reduced both signs and symptoms of ocular surface disease with no clinically relevant effect on IOP.. EudraCT2014-005273-37; Results.

Topics: Adult; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Drug Administration Schedule; Drug Combinations; Female; Glaucoma, Open-Angle; Humans; Intention to Treat Analysis; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F; Quality of Life; Timolol

To compare the ocular hypotensive effect of tafluprost with prostaglandin analogues (PGAs) in glaucoma patients.. 89 primary open-angle glaucoma patients treated with bimatoprost, latanoprost, or travoprost for at least 3 months complaining for ocular discomfort were switched to tafluprost. IOP was assessed at baseline and 3 months after switching the therapy by daily curve. Primary outcome was to compare the mean daily IOP of tafluprost with PGAs.. The mean daily IOP was 16 ± 2.1 and 16.6 ± 2.0 mm Hg at baseline and after switching to tafluprost, respectively (P > 0.05). When analysis was carried out between tafluprost and each previous PGAs, the comparison between latanoprost and tafluprost and travoprost and tafluprost did not show any statistically significant difference in mean daily IOP and at each time point. The comparison between bimatoprost and tafluprost showed a statistically significant difference in mean daily IOP (P < 0.05) and at each time point (P < 0.05).. After 3 months of switching tafluprost showed an overall IOP lowering effect similar to others PGAs. When each PGA was compared with tafluprost, bimatoprost showed to provide a statistically significant additional IOP lowering effect.

Topics: Aged; Amides; Bimatoprost; Cloprostenol; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Time Factors; Travoprost; Treatment Outcome

To compare the drug efficacy of four prostaglandin analogues (PGAs) by bilateral treatment in normal subjects.. Three consecutive studies comparing latanoprost to three other PGAs (travoprost, tafluprost and bimatoprost) were performed in 24 healthy subjects. Each study was separated by a washout period of over 6 weeks. In each study, two drugs were randomly assigned to one eye of each subject. Study subjects instilled the assigned medication at 9:00 p.m. every day for 2 weeks. The same masked investigator measured intraocular pressure (IOP) at 9:00 a.m., 1:00 p.m. and 5:00 p.m. at baseline and repeated measurements on days 7 and 14. The differences in IOP reduction were compared between the drugs.. Mean diurnal IOP reduction with latanoprost on days 7 and 14 was similar to that with travoprost and tafluprost, but was significantly lower than that with bimatoprost. The association of the mean diurnal IOP reduction between latanoprost and bimatoprost on day 14 (r (2) = 0.25) was weak, in remarkable contrast to the strong association between latanoprost and travoprost (r (2) = 0.81) and between latanoprost and tafluprost (0.82).. The short-term bilateral treatment revealed a different IOP-lowering efficacy of bimatoprost compared to other PGAs in healthy subjects.

Topics: Adult; Amides; Antihypertensive Agents; Bimatoprost; Circadian Rhythm; Cloprostenol; Female; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Tonometry, Ocular; Travoprost; Treatment Outcome

The VISIONARY study demonstrated statistically significant intraocular pressure (IOP) reductions with the preservative-free fixed-dose combination of tafluprost 0.0015% and timolol 0.5% (PF tafluprost/timolol FC) in open-angle glaucoma (OAG) or ocular hypertension (OHT) patients, sub-optimally controlled with topical prostaglandin analogue (PGA) or beta-blocker monotherapy. Current subanalyses have examined these data according to the baseline monotherapy.. A European, prospective, observational study included adults (aged ≥ 18 years) with OAG or OHT, who were switched to the PF tafluprost/timolol FC from PGA or beta-blocker monotherapy. Treatment outcomes were reported according to prior monotherapy subgroup: beta-blocker, preserved latanoprost, PF-latanoprost, bimatoprost, tafluprost, and travoprost. Endpoints included the mean change from baseline regarding IOP, conjunctival hyperemia, and corneal fluorescein staining (CFS) at Week 4 and Week 12, and at Month 6.. The subanalysis included 577 patients. All prior monotherapy subgroups demonstrated statistically significant IOP reductions from baseline at Week 4, that were maintained through Month 6 (p < 0.001). Mean (SD) IOP change at Month 6 was 6.6 (4.16), 6.3 (4.39), 5.6 (3.67), 4.9 (2.97), 4.6 (4.39), and 4.7  (3.64) mmHg for prior beta-blocker, preserved latanoprost, PF-latanoprost, tafluprost, bimatoprost, and travoprost subgroups, respectively. The largest IOP change was observed in the preserved latanoprost subgroup for each of the ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% IOP reduction categories at Month 6, demonstrating respective reductions of 8.06, 9.20, 10.64, and 11.55 mmHg. CFS was significantly reduced at Month 6 in the prior bimatoprost subgroup (p = 0.0013). Conjunctival hyperemia severity was significantly reduced at each study visit for prior preserved latanoprost users (p < 0.001).. PF tafluprost/timolol FC therapy provided statistically and clinically significant IOP reductions from Week 4 over the total 6-month period, in patients with OAG/OHT, regardless of the type of prior PGA or beta-blocker monotherapy used. Conjunctival hyperemia severity and CFS decreased significantly in prior bimatoprost and preserved latanoprost users, respectively.. European Union electronic Register of Post-Authorization Studies (EU PAS) register number: EUPAS22204.

Topics: Adult; Antihypertensive Agents; Bimatoprost; Drug Combinations; Glaucoma; Glaucoma, Open-Angle; Humans; Hyperemia; Intraocular Pressure; Latanoprost; Ocular Hypertension; Prospective Studies; Prostaglandins A; Prostaglandins F; Timolol; Travoprost

The origin, isolation, and characterization of (Z)-isopropyl 7-((1R, 2R, 3R, 5S)-2-((1E, 3Z)-3-fluoro-4-phenoxybuta-1, 3-dienyl)-3, 5-dihydroxycyclopentyl) hept-5-enoate, an impurity found in the preparation of an anti-glaucoma agent-Tafluprost has been described in this study.. Further, an enantiospecific synthesis of (Z)-isopropyl 7-((1R, 2R, 3R, 5S)-2-((1E, 3Z)- 3-fluoro-4-phenoxybuta-1, 3-dienyl)-3, 5-dihydroxycyclopentyl) hept-5-enoate has been revealed using deoxofluorination as a key transformation of the strategy.. Moreover, the impurity showing anti-glaucoma properties in docking studies with respect to bimatoprost has been described.. The extention of our work towards docking studies and the present impurity molecule showed almost the same biological activity with respect to Tafluprost.

Topics: Bimatoprost; Glaucoma; Humans; Prostaglandins F

The distribution of prostaglandin-associated periorbitopathy (PAP) graded using the Shimane University PAP Grading System (SU-PAP) among glaucoma/ocular hypertension subjects using a topical FP or EP2 receptor agonist was reported. A 460 consecutive 460 Japanese subjects (211 men, 249 women; mean age ± standard deviation, 69.9 ± 14.5 years) who had used either a FP agonist (0.005% latanoprost, 0.0015% tafluprost, 0.004% travoprost, 0.03% bimatoprost, or fixed combinations of these) or EP2-agonist (0.002% omidenepag isopropyl) for more than 3 months in at least 1 eye were retrospectively enrolled. Age, sex, prostaglandin, intraocular pressure (IOP) measured by Goldmann applanation tonometry (IOPGAT) and iCare rebound tonometry (IOPRBT), difference between IOPGAT and IOPRBT (IOPGAT-RBT), PAP grade, and PAP grading items were compared among groups stratified by PAP grade or prostaglandins. Of the study patients, 114 (25%) had grade 0 (no PAP), 174 (38%) grade 1 (superficial cosmetic PAP), 141 (31%) grade 2 (deep cosmetic PAP), and 31 (7%) grade 3 (tonometric PAP). The IOPGAT was significantly higher in grade 3 (17.5 ± 5.4 mm Hg) than grades 0 (15.0 ± 5.1 mm Hg, P = .032) and 1 (14.5 ± 4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ± 3.2 mm Hg) than the other 3 grades (1.3-1.9 mm Hg, P < .001 for all comparisons); the IOPRBT was equivalent among the 4 grades. The PAP grade was significantly higher associated with travoprost (2.0 ± 0.8) and bimatoprost (2.0 ± 0.7) than latanoprost (1.0 ± 0.8, P < .001 for both comparisons) and tafluprost (1.0 ± 0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ± 0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard β = 0.11), travoprost (0.53, referenced by latanoprost) and bimatoprost (0.65) were associated with higher PAP grades, while tafluprost (-0.18) and omidenepag (-0.73) were associated with lower PAP grades. The PAP graded using SU-PAP reflects the degree of overestimation of the IOPGAT and different severities of PAP among the different prostaglandins. SU-PAP, the grade system constructed based on the underlining mechanisms of PAP, is a simple grading system for PAP that is feasible for use in a real-world clinical situation.

Topics: Age Factors; Aged; Aged, 80 and over; Antihypertensive Agents; Bimatoprost; Cloprostenol; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Manometry; Middle Aged; Ocular Hypertension; Orbital Diseases; Prostaglandins F; Prostaglandins, Synthetic; Retrospective Studies; Severity of Illness Index; Sex Factors; Travoprost

We evaluated the recovery of patients with PAPS for whom the treatment regimen switched from conventional prostaglandin F2α analogues to a new selective prostaglandin-EP2 agonist: omidenepag isopropyl.. From November 2018 to July 2019, we prospectively evaluated 11 patients who had been using conventional PGF2α drugs. Digital photographs of the patients were taken before the start of omidenepag isopropyl therapy and ~3 and 6 months after. Three independent observers used the photographs to judged recovery according to the 5 signs of PAPS: deepening of the upper eyelid sulcus (DUES), flattening of the lower eyelid bags, upper eyelid ptosis, ciliary hypertrichosis, and periorbital skin hyperpigmentation.. The mean age of patients was 61, and 7 patients were female. The original PGF2α drugs were bimatoprost, latanoprost, travoprost, and tafluprost. The mean duration of PGF2α treatment was 65 months. PAPS signs were evaluated in 10 patients after 3 months and in all 11 patients after 6 months: After 3 and 6 months, DUES improved in 3 and 3 patients, respectively; flattening of the lower eyelid bags improved in 1 and 2 patients, respectively; upper eyelid ptosis did not improve in any patients; ciliary hypertrichosis improved in 0 and 2 patients, respectively; and eyelid pigmentation improved in 2 and 8 patients, respectively. The 3 patients who showed improvement in DUES at 6 months had all previously used bimatoprost.. Some PAPS signs improved after patients started taking omidenepag isopropyl. Our findings will be useful for patients taking antiglaucoma eye drops.

Topics: Aged; Antihypertensive Agents; Bimatoprost; Drug Substitution; Eyelid Diseases; Female; Glycine; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Orbital Diseases; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Pyrazoles; Pyridines; Syndrome; Travoprost

The aim of this study was to evaluate the in vivo effects at 3 years of preservative-free tafluprost on corneal health. It was a prospective, masked, study on consecutive patients with a new prescription of preservative-free (PF) tafluprost (naïve-N or switched-S, 44 and 14 patients), and preserved (P) bimatoprost 0.003% or travoprost 0.004% (P-group, 35 patients). A complete ophthalmic examination and an in vivo corneal confocal microscopy evaluation were performed at baseline and every 6 months for 3 years. Ninety-three patients were enrolled, clinical parameters were similar in the groups at baseline, apart from intraocular pressure (IOP) which was lower in the S-group (p = 0.012). Both at baseline and over time, confocal microscopy parameters had different trends. At baseline, keratocyte activation was similar in the three groups (p = 0.43) but over the next months naïve patients treated with PF-tafluprost presented a significant (p = 0.004) reduction in keratocyte activation. Sub-basal nerves tended to increase in patients switched to PF-tafluprost (p = 0.07) while were stable in the other two groups (p = 0.11 in PF and 0.40 in P group). Grade of tortuosity was stable over time in the three groups. Beading-like formations were stable over time for the P- and the PF-group, while significantly increased in the S-group (p = 0.027). Endothelial density values were statistically different at baseline (p = 0.007), they decreased both in PF-group and in S-group (p = 0.048 and 0.001, respectively), while increased in P-group (p = 0.006). Our study is the first to show that a PF-tafluprost formulation does not significantly alter the corneal structures as examined by confocal microscopy after 36 months of topical daily therapy, while improving corneal alterations due to chronic preserved therapies.

Topics: Aged; Bimatoprost; Corneal Keratocytes; Female; Glaucoma; Humans; Intraocular Pressure; Male; Microscopy, Confocal; Middle Aged; Prospective Studies; Prostaglandins F; Travoprost

To perform patient preference-based comparative effectiveness and cost-utility (cost-effectiveness) analyses to evaluate topical bimatoprost 0.01%, latanoprost 0.005%, travoprost 0.004%, tafluprost 0.0015%, and timolol 0.5% for the treatment of open-angle glaucoma (OAG).. Value-Based Medicine. Bimatoprost conferred a mean 2.56 QALY gain (22.9% patient quality-of-life gain) for the average OAG patient, while latanoprost for the average OAG patient, while latanoprost conferred a 2.00 QALY gain (17.8% quality-of-life gain), tafluprost a 1.99 QALY gain (17.9% quality-of-life gain), travoprost a l.92 QALY gain (17.2% quality-of-life gain), and timolol a 1.42 QALY gain (12.8% quality-of-life gain). The ophthalmic cost-perspective, incremental cost-utility ratio of bimatoprost referent to travoprost was $6,034/QALY, to latanoprost was $27,973/QALY, and to timolol was $16,063/QALY. Bimatoprost dominated tafluprost, meaning that it conferred greater patient value for lesser cost than tafluprost.. Topical bimatoprost delivers greater patient value than the other prostamides and topical timolol for the treatment of OAG. Bimatoprost is incrementally cost-effective referent to the other prostamides and timolol.

Topics: Bimatoprost; Cost-Benefit Analysis; Glaucoma, Open-Angle; Health Care Costs; Humans; Intraocular Pressure; Latanoprost; Patient Preference; Prostaglandins F; Timolol; Travoprost; Visual Acuity

For primary open angle glaucoma (POAG), laser treatment or surgery is used when the target intraocular pressure (IOP) cannot be achieved by pharmacological agents, such as prostaglandin (PG) analogs; these drugs also have varied effects. We retrospectively reviewed the medical records of 74 POAG patients (74 eyes) whose IOP was inadequately controlled by PG analogs (bimatoprost [13 eyes], latanoprost [34 eyes], tafluprost [11 eyes], and travoprost [16 eyes]) and underwent primary trabeculectomy. The proportion of patients with no recurrent IOP elevation within 24 months post-trabeculectomy was significantly (P < 0.001) lower in the bimatoprost group (31.3%) than in the latanoprost (83.2%), tafluprost (45.5%), or travoprost groups (65.6%). Deepening of the upper eyelid sulcus (DUES) was observed before trabeculectomy in 18 of 74 eyes (24.3%) treated with bimatoprost (9 eyes; 50.0%), latanoprost (3 eyes; 16.7%), tafluprost (1 eye; 5.5%) and travoprost (5 eyes; 27.8%). The proportion of patients with no recurrent IOP elevation up to 24 months post-trabeculectomy was significantly (P < 0.0001) lower in the DUES(+) group (34.7%) than in the DUES(-) group (74.3%). Multivariate stepwise logistic regression analysis, with no recurrent IOP elevation used as dependent variable, and bimatoprost, latanoprost, travoprost, tafluprost, β-blocker, carbonic anhydrase inhibitor, brimonidine, gender, age, preoperative IOP, mean deviation, duration of PG analog use before surgery, and the number of ophthalmic solutions used as independent variables, identified only bimatoprost as a significant independent factor (P = 0.0368). Thus, the outcome of trabeculectomy varied depending on the PG analog used preoperatively, and bimatoprost use was associated with a high risk of recurrent IOP elevation up to 2 years post-trabeculectomy. This may indicate that the incidence of DUES differed with the PG analog used. Patients with glaucoma who are treated with bimatoprost should be monitored for DUES, and when these patients undergo trabeculectomy, the postoperative course of IOP should be followed carefully.

Topics: Aged; Analysis of Variance; Bimatoprost; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Logistic Models; Male; Middle Aged; Multivariate Analysis; Preoperative Care; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Recurrence; Retrospective Studies; Trabeculectomy; Travoprost; Treatment Outcome

The aim of this study was to investigate the effects of prostaglandin analogs on blood flow in the ophthalmic artery of clinically healthy rabbits.. Fifty-five clinically healthy New Zealand white rabbits were divided into six groups, and the left eyes were treated for four weeks with the preservative benzalkonium chloride (BAK) only or a topical formulation of different prostaglandin analogs (bimatoprost BAK, tafluprost BAK-free, travoprost BAK, travoprost POLYQUAD, and latanoprost BAK). Color Doppler imaging was performed before and after the treatments. The mean values of the peak systolic velocity (PSV) and end diastolic velocity and the resistive index (RI) were calculated. Statistical analysis was performed to compare the differences pre- and post-treatment for each drug and post-treatment among the drugs.. The prostaglandin analogs did not affect PSV. Bimatoprost BAK, travoprost POLYQUAD, and latanoprost BAK did not change RI. Tafluprost BAK-free and travoprost BAK therapy resulted in similar reductions in RI. No significant differences pre- and post-treatment were found when BAK was administered alone.. The prostaglandin analogs tafluprost BAK-free and travoprost BAK improved blood flow in the ophthalmic artery in healthy New Zealand white rabbits, which suggests that these drugs enhance the prevention of the progression the progression of glaucoma.

Topics: Animals; Antihypertensive Agents; Benzalkonium Compounds; Bimatoprost; Blood Flow Velocity; Female; Glaucoma; Latanoprost; Male; Ophthalmic Artery; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Random Allocation; Reference Values; Reproducibility of Results; Travoprost; Ultrasonography, Doppler, Color; Vascular Resistance

Differences in the increase in matrix metalloproteinase (MMP) and decrease in tissue inhibitor of metalloproteinase (TIMP) activity may contribute to the different characteristics observed clinically on decreased intraocular pressure in patients with glaucoma or ocular hypertension. The purpose of this study was to investigate differences in the expression profiles of MMPs and TIMPs induced by the prostaglandin analogs bimatoprost, latanoprost, and tafluprost in human non-pigmented ciliary epithelial cells (HNPCECs).. HNPCECs were cultured for 24 h with 0, 10, 100, or 1000 μM of the free acid forms of bimatoprost, latanoprost, and tafluprost. We measured the expression levels of MMPs and TIMPs using real-time polymerase chain reaction, and compared the results. Enzyme activities of MMP-2 and -9 in conditioned media were measured by gelatin zymography.. All prostaglandin analogs we examined dose-dependently increased expression levels of MMP-1, -2, -3, -9, and -17, whereas expression levels of TIMP-1 and -2 decreased with increasing concentrations of each analog. Each prostaglandin analog induced different levels of increases in MMPs and decreases in TIMPs.. Unique expression profiles of MMPs and TIMPs induced by bimatoprost, latanoprost, and tafluprost, as shown in HNPCECs, may contribute to clinically different effects on intraocular pressure decreases in patients with glaucoma or ocular hypertension.

Topics: Antihypertensive Agents; Bimatoprost; Cell Line; Ciliary Body; Dose-Response Relationship, Drug; Epithelial Cells; Gene Expression Regulation, Enzymologic; Humans; Latanoprost; Matrix Metalloproteinases; Prostaglandins F; Prostaglandins F, Synthetic; Real-Time Polymerase Chain Reaction; RNA, Messenger; Tissue Inhibitor of Metalloproteinases

Primary (or chronic) open-angle glaucoma (POAG or COAG) may be asymptomatic but causes progressive optic nerve damage with significant loss of visual field. Treatments aim to lower intraocular pressure (IOP) by reducing the production of aqueous humour and/or increasing its drainage. Here we update our previous articles to reflect new drugs, preservative-free preparations and fixed-dose drug combinations for POAG.

Topics: Adrenergic beta-Antagonists; Adult; Bimatoprost; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Prostaglandins F; Prostaglandins F, Synthetic

To determine the equilibrium binding constant (EB) values of bimatoprost and tafluprost drug product formulations in contact with lotrafilcon A soft contact lenses and to characterize the importance of drug molecule hydrophobicity in controlling the binding interactions.. Bimatoprost Ophthalmic Solution and Tafluprost Ophthalmic Solution (Saflutan) were incubated with lotrafilcon A lens material for timed intervals at 25°C and 37°C. Aliquots were withdrawn, filtered, and tested using reverse-phase ultrahigh-performance liquid chromatography with respect to [bimatoprost] or [tafluprost] remaining in the solution. A series of homologous dialkyl phthalate esters and a series of homologous p-hydroxybenzoic acid alkyl esters were also tested as reference compounds.. Bimatoprost and tafluprost were rapidly (within 15 min) absorbed from the solution by lotrafilcon A lenses, reaching an equilibrium within 60 min. At any lens:solution (w/v) ratio, the extent of drug binding to lens material was greater for tafluprost than for bimatoprost. The log(EB) values correlated with solute octanol:water partition coefficient (logP) values, indicating that hydrophobic interactions are important in controlling solute partitioning into the lens material.. This study established the quantitative relationships between tafluprost and bimatoprost binding to lotrafilcon A lenses. The fraction of bimatoprost or tafluprost that binds to lotrafilcon A increases with increasing lens:solution (w/v) ratio. For a 60 µL dose volume applied to a single contact lens, 16% of initially present bimatoprost remains in the solution, whereas only 6% of initially present tafluprost remains in the solution. These calculations clearly demonstrate that both drugs partition extensively into lotrafilcon A contact lens material. Although the clinical implications of such binding can only be surmised, it would seem prudent to caution contact lens wearers to remove the lenses before administering either prostaglandin drug.

Topics: Amides; Antihypertensive Agents; Bimatoprost; Chromatography, High Pressure Liquid; Cloprostenol; Contact Lenses, Hydrophilic; Hydrogels; Ophthalmic Solutions; Prostaglandins F; Silicones

Prostaglandin analogues (PGA) are ocular hypotensive agents used for the treatment of glaucoma. Hypertrichosis of the eyelashes has been reported in humans as a side effect. Eyelash growth was investigated with clinical trials in people using bimatoprost. Scattered reports of eyelash growth during the treatment of glaucoma with other PGA are also found in the literature. We investigated the effect of 4 different topical PGA on eyelash length.. Forty New Zealand white rabbits were divided into 4 groups and received daily topical application of bimatoprost, tafluprost, travoprost, and latanoprost in the left eye for 4 weeks. The right eye received no treatment. Eyelash length was measured in both eyes before and after treatment using a stainless steel digital caliper.. Bimatoprost and tafluprost groups had significant increases in eyelash length. We did not observe significant eyelash growth in rabbits receiving travoprost and latanoprost after 1 month of treatment.. Today, only bimatoprost is approved for growing eyelashes, and our research shows that tafluprost could be further explored by the cosmetic and pharmaceutical industry. Additional research using travoprost and latanoprost as agents for eyelash growth should be performed in the future using prolonged treatment periods to determine whether or not these PGA induce eyelash growth, and investigate other possible side effects.

Topics: Administration, Topical; Amides; Animals; Antihypertensive Agents; Bimatoprost; Cloprostenol; Eyelashes; Female; Hypertrichosis; Latanoprost; Male; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Travoprost

To investigate the effect of prostaglandin F2α (PGF2α), latanoprost, travoprost, bimatoprost, and tafluprost on human orbital preadipocyte differentiation and intracellular lipid storage, and to reveal the potential mechanisms by which topical prostaglandin analogs induce orbital fat volume reduction and cause deep superior sulcus syndrome.. Human orbital adipose precursors were treated in vitro for 24 h (day 1) with PGF2α, latanoprost, travoprost, bimatoprost, and tafluprost in their commercial formulations (1:100 dilution). Expressions of adipogenic transcription factor, peroxisome proliferator-activated receptor-gamma (PPARγ), and CCAAT-enhancer-binding protein α (C/EBPα) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) at day 7. At 14 days, cells were stained with oil red O, intracellular lipid accumulation was evaluated by lipid absorbance, and adipocyte expression marker [Lipoprotein lipase (LPL)] was determined by real-time RT-PCR.. Our results showed that PGF2α and topical prostaglandin analogs down-regulated the expression of PPARγ and C/EBPα, and inhibited accumulation of intra-cytoplasmic lipid droplets and expression of LPL compared with the untreated control. Comparison between the 4 drugs showed that latanoprost had the weakest antiadipogenic effect, and bimatoprost induced the most significant reduction of adipogenesis.. Latanoprost, travoprost, bimatoprost, and tafluprost inhibited human preadipocyte differentiation and intracellular lipid accumulation. Morphologic and metabolic changes in orbital adipocytes caused by PGF2α analogs are a possible pathophysiologic explanation of superior eyelid deepening in patients with glaucoma.

Topics: Adipocytes; Adipogenesis; Adult; Amides; Antihypertensive Agents; Bimatoprost; CCAAT-Enhancer-Binding Protein-alpha; Cloprostenol; Dinoprost; Humans; In Vitro Techniques; Latanoprost; Lipoprotein Lipase; Orbit; PPAR gamma; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost; Young Adult

We investigated the appearance frequency of eyelid pigmentation and eyelash bristles after the use of five types of prostaglandin (PG) analogs.. This study included 250 eyes from 250 patients diagnosed with primary open-angle glaucoma or ocular hypertension who were treated with either latanoprost, travoprost, tafluprost, bimatoprost, or isopropyl unoprostone for >3 months in only one eye. Photographs of both eyes were obtained, and the images were assessed by three ophthalmologists who were masked to treatment type. The existence of eyelid pigmentation and eyelash bristles was judged, and images of the left and right eyes were compared. Subjective symptoms regarding the existence of eyelid pigmentation and eyelash bristles were investigated through a questionnaire.. There was no significant difference between the five types of medications with regard to eyelid pigmentation (P=0.537). Use of isopropyl unoprostone resulted in a significantly lower incidence of eyelash bristles (P<0.0001). The questionnaire investigation showed that eyelid pigmentation and eyelash bristles were significantly more frequent with travoprost (42.0% and 42.0%, respectively) and bimatoprost (58.0% and 60.0%, respectively) than with other three medications (P<0.0001).. The appearance frequency of eyelid pigmentation was similar among the five types of PG analogs studied, and eyelash bristles appeared less frequently with isopropyl unoprostone use. Patients are conscious of eyelash bristles; therefore, these adverse effects should be sufficiently explained to patients before PG administration.

Topics: Adult; Aged; Aged, 80 and over; Amides; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Eyelashes; Eyelid Diseases; Female; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Ocular Hypertension; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Skin Pigmentation; Surveys and Questionnaires; Travoprost

This in-vitro study compared the toxicity of bimatoprost 0.01% containing benzalkonium chloride (BAK) 0.02% with other commercial BAK-free or BAK-containing prostaglandin analogs.. Six test solutions were evaluated: travoprost 0.004% with polyquaternium-1 0.001% (PQ), PQ, bimatoprost 0.01% with BAK 0.02%, latanoprost 0.005% with BAK 0.02%, tafluprost 0.0015% preservative free (PF), and BAK 0.02%. Phosphate-buffered saline (PBS) was the live control and 70% methanol was the dead control. Confluent human corneal epithelial cells were incubated with test solutions (diluted 1:5 or 1:10 with PBS) or control solutions for 10 or 25 min, after which cells were fluorescently labeled to distinguish live and dead cells. Data were expressed as a percentage of PBS live-cell fluorescence for automated readouts. Live and dead cells were manually counted for numeric analyses.. For 1:5 and 1:10 dilutions using automated readout, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significant reductions in the live cell signal compared with PBS, travoprost with PQ, and PQ alone (all P < 0.001). They also demonstrated significantly greater toxicity than tafluprost PF for 1:5 dilutions (all P < 0.001) and 1:10 dilutions (P ≤ 0.02), except for 1:10-diluted bimatoprost with BAK (P = 0.41). For 1:5 dilutions using manual cell count, cells exposed to bimatoprost with BAK demonstrated significant reductions in the percentage of live cells compared with PBS (P = 0.02). For 1:10 dilutions using manual cell count, cells exposed to bimatoprost with BAK, latanoprost with BAK, and BAK alone demonstrated significantly greater toxicity than PBS, travoprost with PQ, PQ alone, and tafluprost PF (all P ≤ 0.03). No significant differences were observed among PBS, travoprost with PQ, and PQ alone under any test conditions (P ≤ 0.63).. This study demonstrated that BAKcontaining solutions, including bimatoprost 0.01% with BAK, were toxic to human corneal epithelial cells, whereas BAK-free solutions showed little to no evidence of toxicity.

Topics: Amides; Antihypertensive Agents; Benzalkonium Compounds; Bimatoprost; Cell Survival; Cells, Cultured; Cloprostenol; Epithelial Cells; Epithelium, Corneal; Humans; Latanoprost; Polymers; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic; Travoprost

This study compared the toxicity profiles of three antiglaucoma prostaglandin F2alpha analogs, latanoprost, travoprost, and bimatoprost which contain benzalkonium chloride (BAK), with tafluprost, a new preservative-free prostaglandin analog.. IOBA-NHC cells were exposed to BAK-containing prostanoid solutions, their respective BAK concentrations, and preservative-free tafluprost solution for 30 min. Membrane integrity, apoptosis, oxidative stress, and cells morphology were evaluated.. Preservative-free tafluprost resulted in significantly higher membrane integrity and lower pro-apoptotic and pro-oxidative effects than preservative-containing prostaglandin analog preparations.. These results suggest that tafluprost, a new preservative-free prostaglandin analog, has very low or no pro-apoptotic, pro-necrotic, or pro-oxidative effects in vitro compared to preservative-containing formulations.

Topics: Amides; Apoptosis; Benzalkonium Compounds; Bimatoprost; Cell Line; Cell Membrane; Cell Survival; Cloprostenol; Conjunctiva; Dinoprost; DNA; Drug Combinations; Epithelial Cells; Glaucoma; Humans; Latanoprost; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Receptors, Purinergic P2; Receptors, Purinergic P2X7; Superoxides; Travoprost