Efficacy of preserved Tafluprost 0.0015% in lowering intraocular pressure.

OBJECTIVE: To investigate the intraocular pressure (IOP) lowering effect of topical preserved tafluprost 0.0015% in a tertiary hospital setting in India. METHODS: This is a retrospective chart review of patients with primary open-angle glaucoma (POAG) or ocular hypertension (OHT) attending regular outpatient visits in December 2019 and January 2021, and treated with topical preserved tafluprost 0.0015%. Based on their medication history, patients were divided into two groups, the "treatment naïve" group and the "switched" group, which included patients switched to tafluprost monotherapy after treatment with at least one prior drug. RESULTS: The mean IOP of the study population reduced significantly from baseline level by 20.6% and 25.5% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with only OHT reduced significantly from baseline level by 21% and 26% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The mean IOP in patients with POAG reduced significantly from baseline level by 19% and 24% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG treatment naïve patients was 25.3 ± 0.3 mmHg, which reduced significantly by 24% and 28% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). The baseline IOP ± SD in POAG switched patients was 24.3 ± 0.1 mmHg, which reduced significantly by 18% and 22% at 1 month and 3 months after preserved tafluprost 0.0015% treatment (P < 0.001 for both). In the POAG switch group, the percent reduction in IOP at 3 months after preserved tafluprost 0.0015% treatment was 23% with timolol as first line, 22% with bimatoprost as first line, 20% with latanoprost as first line, and 19% with travoprost as first line (P < 0.001 for all). CONCLUSIONS: We show significant IOP reduction with preserved tafluprost 0.0015% in a real-world setting. As first-line monotherapy in patients with OHT and in POAG-naïve patients, preserved tafluprost 0.0015% significantly reduced IOP at 3 months. Even as second-line therapy in nonresponders (POAG-Switched) to various drugs (same class [PGAs] versus different class), treatment with preserved tafluprost 0.0015% resulted in significant IOP reduction at 3 months.

Screening and quantification of undeclared PGF2α analogs in eyelash-enhancing cosmetic serums using LC-MS/MS.

In recent years, cosmetics deemed equivalent to pharmaceutical products containing prostaglandin F2α (PGF2α) analogs have been distributed overseas in the form of eyelash serums that can be purchased via the internet. The purpose of this study was to investigate the presence or absence of PGF2α analogs in eyelash serums procured in Japan via the internet to elucidate the actual composition. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement system was developed for the determination of 14 PGF2α analogs in cosmetic serums. In total, 64 eyelash serum samples were purchased from 34 websites. After pretreatment, eyelash serum samples were screened for PGF2α analogs using the LC-MS/MS system. Products containing PGF2α analogs were subjected to quantification of these compounds. Of the 64 products, four were found to contain bimatoprost, among which, three did not indicate their contents on their package labels. In contrast, no samples were found to contain latanoprost, travoprost, or tafluprost, which are prescribed for glaucoma treatment. Additionally, eight products contained other PGF2α analogs, which have not been used as pharmaceuticals. The ease of access to cosmetic serums containing PGF2α analogs via online purchases presents a risk of serious side effects, particularly when consumers are not informed of their contents on the packages. This issue requires serious consideration to avoid the incorporation of pharmaceutical substances into cosmetic products.

Proposal of a simple grading system integrating cosmetic and tonometric aspects of prostaglandin-associated periorbitopathy.

ABSTRACT: 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 ±â€Šstandard deviation, 69.9 ±â€Š14.5 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 ±â€Š5.4 mm Hg) than grades 0 (15.0 ±â€Š5.1 mm Hg, P = .032) and 1 (14.5 ±â€Š4.2 mm Hg, P = .008), and the IOPGAT-RBT was significantly higher in grade 3 (5.8 ±â€Š3.2 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 ±â€Š0.8) and bimatoprost (2.0 ±â€Š0.7) than latanoprost (1.0 ±â€Š0.8, P < .001 for both comparisons) and tafluprost (1.0 ±â€Š0.7, P < .001 for both comparisons), but significantly lower associated with omidenepag (0.0 ±â€Š0.0, P < .001 for all comparisons) than the other 4 prostaglandins. Multivariate analyses showed older age (standard ß = 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.

Treatment of Open-Angle Glaucoma and Ocular Hypertension with Preservative-Free Tafluprost/Timolol Fixed-Dose Combination Therapy: The VISIONARY Study.

INTRODUCTION: A non-interventional, multicenter, European, prospective evaluation of the effectiveness, tolerability, and safety of a topical preservative-free tafluprost (0.0015%) and timolol (0.5%) fixed-dose combination (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) demonstrating insufficient response to topical beta-receptor blockers or prostaglandin analogue (PGA) monotherapy. METHODS: Mean intraocular pressure (IOP) change from baseline was measured at study visits following a switch to PF tafluprost/timolol FC. Primary endpoint was absolute mean IOP change at month 6. Change from baseline concerning ocular signs and symptoms was also explored. RESULTS: Analyses included 577 patients (59.6% female). Mean age (SD) was 67.8 (11.67) years. Mean (SD) IOP reduction from baseline was significant at all study visits; 5.4 (3.76) mmHg (23.7%) at week 4, 5.9 (3.90) mmHg (25.6%) at week 12, and 5.7 (4.11) mmHg (24.9%) at month 6 (p < 0.0001 for all visits). At month 6, 69.2%, 53.6%, 40.0%, and 25.8% were responders based on ≥ 20%, ≥ 25%, ≥ 30%, and ≥ 35% cutoff values for mean IOP, respectively. Significant reductions were observed concerning corneal fluorescein staining (p < 0.0001), dry eye symptoms, irritation, itching, and foreign body sensation (p < 0.001 for each parameter). Conjunctival hyperemia was significantly reduced at all study visits (p < 0.0001 at each visit). Overall, 69 treatment-related adverse events (AEs) were reported, one of which was serious (status asthmaticus). Most AEs were mild to moderate in severity, and the majority had resolved or were resolving at the end of the study period. CONCLUSION: In clinical practice, PF tafluprost/timolol FC provided statistically and clinically significant IOP reductions in patients with OAG and OHT insufficiently controlled on or intolerant to PGA or beta-receptor blocker monotherapy. The full IOP reduction appeared at week 4 and was maintained over the 6-month study period. Key symptoms of ocular surface health improved. TRIAL REGISTRATION: European Union electronic Register of Post-Authorisation Studies (EU PAS) register number, EUPAS22204.

Efficacy and safety of the fixed combinations of tafluprost/timolol and latanoprost/carteolol.

In this study, we made a comparative efficacy and safety assessment of two different fixed combinations of drugs, viz., tafluprost/timolol (TAF/TIM) and latanoprost/carteolol (LAT/CAR), by determining their effects on intraocular pressure (IOP) in ocular normotensive monkeys and examining their toxic effects on ocular surface using human corneal epithelial cells. TAF/TIM was found to be more effective in lowering IOP for a longer duration compared to LAT/CAR. We found that the difference in the intensity of IOP-lowering effect was because of the differences in the strength of timolol compared with that of carteolol as a beta-adrenergic antagonist and strength of tafluprost compared with that of latanoprost as a prostaglandin analogue. In addition, TAF/TIM showed much less cytotoxic effects compared to LAT/CAR on the human corneal epithelial cells. Our findings showed that TAF/TIM is better than LAT/CAR with regard to the IOP-lowering effect in monkeys and toxicity on ocular surface.

Changes in ocular signs and symptoms in patients switching from bimatoprost-timolol to tafluprost-timolol eye drops: an open-label phase IV study.

OBJECTIVES: 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. DESIGN: This was a 12-week, open-label, phase IV study. SETTING: Sixteen centres in Finland, Germany, Italy and the UK. PARTICIPANTS: 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. INTERVENTIONS: Patients were switched to PF tafluprost-timolol once daily in the treated eye(s). PRIMARY AND SECONDARY OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION NUMBER: EudraCT2014-005273-37; Results.

Patient stratification in clinical glaucoma trials using the individual tear proteome.

Glaucoma patients are prone to concomitant ocular surface diseases; however, switching from preserved to preservative-free medication can often alleviate these symptoms. The objective of this study was to examine how the adverse effects and tear proteome change for glaucoma patients (n = 28) during a 12-month drug switch from preserved latanoprost (Xalatan) to preservative-free tafluprost (Taflotan). We hypothesized that patient stratification could help identify novel recovery patterns in both tear proteomics and clinical data. In order to accomplish patient stratification, we implemented sequential window acquisition of all theoretical mass spectrometry (SWATH-MS) as a tool for quantitative analysis of individual tear protein profiles. During each visit (baseline and four follow-up visits), the patients' tears were sampled and the state of their ocular surface was evaluated clinically. Altogether 785 proteins were quantified from each tear sample using SWATH strategy and as these protein expression levels were compared between baseline and 12-month follow-up, three distinct patient groups were identified. We evaluated how these patient groups differed in their protein expression levels at baseline and discovered that the patients with increased levels of pro-inflammatory proteins and decreased levels of protective proteins benefitted most from the medication switch.

Prospective Observational Post-Marketing Study of Tafluprost for Glaucoma and Ocular Hypertension: Effectiveness and Treatment Persistence.

INTRODUCTION: The aim of this study was to investigate the long-term intraocular pressure (IOP)-lowering effect and safety of tafluprost, a prostaglandin analogue, in actual clinical practice and to determine persistency of tafluprost as an indicator of its benefit-risk balance. METHODS: This was a large-scale, post-marketing, multicenter, non-interventional, open-label, long-term study. Patients with glaucoma or ocular hypertension who initiated tafluprost treatment were registered and prospectively observed over a 2-year period in the real-world setting in Japan. Long-term IOP and safety data were collected. RESULTS: Of the 4502 patients registered from 553 medical institutions, 4265 patients were analyzed. The majority of patients had normal-tension glaucoma (44.4%) and primary open-angle glaucoma (37.8%), and patients with ocular hypertension constituted 7.0%. Treatment patterns with tafluprost during the study period were as follows: naïve monotherapy (48.1%), switching monotherapy (18.4%), and concomitant therapy (33.5%). In all patients analyzed, mean IOP was significantly reduced from 18.6 ± 5.9 mmHg (month 0) to 15 mmHg or below throughout the 2-year observation period after initiation of tafluprost. Significant IOP-lowering effects were shown in various treatment patterns and disease types. Adverse reactions were observed in 795 patients (18.64%). Major adverse reactions included eyelid pigmentation, ocular hyperemia, eyelash changes, eyelid hypertrichosis, and iris hyperpigmentation. Kaplan-Meier curves showed that 84.6% and 76.1% of patients were persistent on tafluprost for 1 and 2 years, respectively, when discontinuation due to insufficient efficacy or adverse events was defined as a treatment failure event. Furthermore, among treatment-naïve patients (n = 2304), the persistency rates on tafluprost monotherapy were 77.0% for 1 year and 67.0% for 2 years. CONCLUSION: Tafluprost showed significant long-term IOP-lowering effects regardless of treatment patterns or diagnosis, with minimum safety concerns in the actual clinical practice. The observed treatment persistence suggests that tafluprost can be used long term owing to its benefit-risk profile. FUNDING: Santen Pharmaceutical Co., Ltd., Osaka, Japan.

24-Hour Efficacy and Ocular Surface Health with Preservative-Free Tafluprost Alone and in Conjunction with Preservative-Free Dorzolamide/Timolol Fixed Combination in Open-Angle Glaucoma Patients Insufficiently Controlled with Preserved Latanoprost Monotherapy.

INTRODUCTION: The aim of the present study was to evaluate the 24-h efficacy, tolerability, and ocular surface health with preservative-free (PF) tafluprost and a PF triple drug regimen comprising tafluprost and dorzolamide/timolol fixed combination (DTFC) in open-angle glaucoma patients who were insufficiently controlled with preserved branded or generic latanoprost monotherapy and who exhibited signs or symptoms of ocular surface disease (OSD). METHODS: Prospective, observer-masked, crossover, comparison. Eligible consecutive open-angle glaucoma patients were randomized to either PF tafluprost or the triple PF regimen for 3 months. They were then crossed over to the opposite therapy for another 3 months. At the end of the latanoprost run-in period and after each PF treatment period, patients underwent habitual 24-h intraocular pressure (IOP) monitoring with Goldmann tonometry in the sitting position (at 10:00, 14:00, 18:00, and 22:00) and Perkins tonometry in the supine position (at 02:00 and 06:00). Tolerability and selected ocular surface parameters were evaluated at baseline and the end of each treatment period. RESULTS: Forty-three open-angle glaucoma patients completed the trial. Mean 24-h IOP on preserved latanoprost was 22.2 ± 3.9 mmHg. Compared with latanoprost monotherapy, PF tafluprost obtained a greater reduction in mean, peak, and fluctuation of 24-h IOP including the 02:00 and 06:00 time points (P < 0.05). With the exception of 24-h fluctuation, the triple PF regimen provided significantly lower IOP parameters than latanoprost or PF tafluprost (P < 0.001). Finally, PF tafluprost therapy displayed significantly improved tear film break-up times (6.7 vs 6.0 s), corneal staining (1.3 vs 2.2), and Schirmer I test results (9.1 vs 8.2 mm) compared with the preserved latanoprost baseline (all P < 0.01). The triple PF regimen demonstrated similar tear film break-up times (6.1 vs 6.0 s) and Schirmer I test results (8.2 vs 8.2 mm) to latanoprost, but revealed a significant improvement in the corneal stain test (1.7 vs 2.2; P < 0.001). CONCLUSIONS: In this trial PF tafluprost therapy provided statistically greater 24-h efficacy and improved tolerability compared with preserved latanoprost. The combination of PF tafluprost and PF dorzolamide/timolol fixed combination was statistically and clinically more efficacious than both monotherapies and demonstrated similar ocular surface characteristics to preserved latanoprost monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02802137). FUNDING: Santen.

Preservative-free tafluprost in the treatment of open-angle glaucoma or ocular hypertension in India: a phase III clinical trial.

AIM: The aim of this study was to evaluate the efficacy and safety of preservative-free (PF) tafluprost compared with PF timolol in Indian subjects with open-angle glaucoma (OAG) or ocular hypertension. METHODS: This was a randomised, multicentre, double-masked, phase III trial. Subjects aged 18-80 years, following washout of current medication, with intraocular pressure (IOP) ≥ 24 and ≤ 36 mmHg in at least one eye were randomised in a 1:1 ratio to 0.0015% PF tafluprost or 0.5% PF timolol for 4 weeks. IOP was measured at 08:00, 10:00 and 16:00 hours at baseline and at weeks 2 and 4. The primary efficacy end-point was the mean diurnal IOP change from baseline at week 4, and PF tafluprost was considered non-inferior to PF timolol if the upper bound of the 95% confidence interval (CI) for between-treatment differences was ≤ 1.5 mmHg. The secondary end-point was the proportion of subjects with ≥ 25% reduction in IOP from baseline at week 4. RESULTS: In total, 190 subjects were randomised, 95 each, to PF tafluprost and PF timolol treatment. PF tafluprost was non-inferior to PF timolol with respect to diurnal IOP changes from baseline over 4 weeks. The mean PF tafluprost-PF timolol difference in the diurnal IOP change was -1.7 (95% CI -2.6 to -0.7), suggestive of superiority for PF tafluprost. The secondary end-point was achieved in a higher proportion of PF tafluprost group subjects. Both PF tafluprost and PF timolol were well-tolerated with similar incidences of adverse events. CONCLUSIONS: PF tafluprost was safe and efficacious in reducing IOP in Indian subjects.

Preservative-free tafluprost/timolol fixed combination: a new opportunity in the treatment of glaucoma.

INTRODUCTION: Medical therapy of glaucoma aims to maintain the patient's visual function and quality of life. This generally commences with monotherapy, but it is often difficult to reach the predetermined target pressure with this approach. Fixed combinations (FCs) are therefore selected as the next step of the medical therapy algorithm. By employing a prostaglandin/timolol fixed combination (PTFC) the desired target 24-hour intraocular pressure can be reached in many glaucoma patients with the convenience of once-a-day administration and the associated high rate of adherence. AREAS COVERED: The current role and value of FCs in the medical therapy of glaucoma is critically appraised. Special attention is paid to the PTFCs and the emerging role of preservative-free PTFCs. This review summarizes existing information on the efficacy and tolerability of the new preservative-free tafluprost/timolol FC (Taptiqom®). EXPERT OPINION: The preservative-free tafluprost/timolol FC represents a promising stepwise treatment option for those patients whose intraocular pressure is insufficiently controlled with available monotherapy options. This novel FC has the potential to substantially improve glaucoma management and through evolution of the current glaucoma treatment paradigm, to become a core therapeutic option in the future. Nonetheless, future research is needed to better delineate the therapeutic role of current and future preservative-free FCs in glaucoma therapy.

Pharmacokinetics, Efficacy, and Safety of the Preservative-free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% in Healthy Volunteers: A Phase I Comparison vs. the Corresponding Preservative-free Monotherapies.

PURPOSE: Plasma concentrations of tafluprost acid and timolol were compared after single (Day 1) and repeated (Day 8) instillations of once-daily tafluprost 0.0015%-timolol 0.5% preservative-free (PF) fixed-dose combination (FDC), once-daily PF tafluprost 0.0015%, and twice-daily PF timolol 0.5%. PATIENTS AND METHODS: Fifteen healthy volunteers were randomized to this double-masked, single-center, three-period cross-over study. A wash-out interval of at least 4 weeks separated each three 8-day dosing period. Blood samples were drawn on the first and last day of each dosing period, prior to the morning dose, as well as 5, 10, 15, 30, and 45 min, and 1, 1.5, 2, 4, 8, and 12 h post-dosing. Sample plasma concentrations of tafluprost acid and/or timolol were determined and maximum concentration (C max), area under the concentration-over-time curve from time zero to the last time point with a quantifiable measurement (AUC0-last), and time to maximum concentration were calculated. Intraocular pressure (IOP), adverse events, and ocular/systemic safety variables were also evaluated. RESULTS: Plasma concentrations of tafluprost acid were low, with similar levels measured subsequent to either single or repeated dosing of PF FDC and PF tafluprost. On both sampling days, concentrations peaked at 10 min after the dose, and were cleared from the blood circulation by 30 min; average C max ranged from 17 to 24 pg/mL, and AUC0-last from 3 to 5 pg*h/mL. Plasma concentrations of timolol were comparable after the first dose of PF FDC or PF timolol. Concentrations peaked at 15 min post-dose and diminished in a similar manner after 2 h; average C max was 800 pg/mL and AUC0-last 3900 pg*h/mL. As expected, PF timolol produced a higher Day 8 pre-dose timolol concentration than PF FDC (235 vs. 37 pg/mL; p < 0.001, respectively). The Day 8 post-dose changes in timolol concentrations were relative to this pre-dose difference. All study treatments were well tolerated and safe. PF FDC seemed to provide the best IOP reduction. CONCLUSIONS: PF FDC demonstrated good IOP-lowering efficacy and displayed similar pharmacokinetic characteristics to the monotherapy agents. Exposure to timolol was reduced via the halved dosing.

Safety and tolerability of the tafluprost/timolol fixed combination for the treatment of glaucoma.

INTRODUCTION: The preservative-free (PF) fixed combination (FC) of tafluprost 0.0015%/timolol 0.5% is the newest member of the prostaglandin analogue/timolol FC class. AREAS COVERED: In this review, we summarize data on safety and tolerability of this FC. EXPERT OPINION: The intraocular pressure-lowering effect of the tafluprost/timolol FC is approximately 30 - 35%, which is similar to that of the other members of the class. However, in contrast to most similar eye drops the tafluprost/timolol FC is manufactured in a PF, unit-dose pipette formulation. The PF nature eliminates preservative-related ocular surface changes, and improves tolerability. In clinical studies, the tafluprost/timolol FC was well tolerated. The side effects represented the typical side effects of the topical prostaglandin analogue class. The most common side effect, conjunctival hyperemia was mild, and occurred in only 6.4 - 8% of patients during 6 months of treatment. The figures for ocular irritation were also low (7.0 - 12.7%). The other side effects occurred only in very few patients. The frequency and severity of conjunctival hyperemia was lower than those published for most prostaglandin/timolol FCs. Thus, the main clinical advantage of this PF FC is improved tolerability, which may support treatment adherence of glaucoma patients.

Comparison of the toxicity profile of benzalkonium chloride-preserved tafluprost and SofZia-preserved travoprost applied to the ocular surface.

PURPOSE: To evaluate some clinically important features of benzalkonium chloride (BAK) toxicity by comparing tafluprost with 0.001% BAK and travoprost preserved with SofZia applied to the ocular surface of the eyes with glaucoma. METHODS: This was a prospective, randomized, observer unmasked, multicenter crossover trial. A total of 195 patients were randomized and 174 patients completed the study at 19 clinics between November 2011 and August 2012. Topical BAK-preserved tafluprost or SofZia-preserved travoprost was newly administered or continued. Superficial punctate keratopathy (SPK), tear break-up time (BUT), the conjunctival hyperemia score, and intraocular pressure (IOP) were compared at the baseline visit, 4, and 12 weeks after the start of therapy. The eye drops were switched to another eye drop after 12 weeks of observation. RESULTS: The total SPK and conjunctival hyperemia scores were significantly lower in the tafluprost compared with those in the travoprost phase (both P=0.038). There were no significant differences in the SPK scores of the superior area (P=0.679), central area (P=0.089), inferior area (P=0.090), and tear BUT (P=0.271). The IOP-lowering effects were similar (P=0.155). CONCLUSIONS: SPK, hyperemia score, and tear BUT while using tafluprost with 0.001% BAK were not inferior compared with those caused by travoprost with SofZia.

Safety and Efficacy of Benzalkonium Chloride-optimized Tafluprost in Japanese Glaucoma Patients With Existing Superficial Punctate Keratitis.

PURPOSE: To evaluate the safety and efficacy of benzalkonium chloride (BAK)-optimized tafluprost (with a BAK concentration reduced from 0.01% to 0.001%) in glaucoma patients with existing superficial punctate keratitis (SPK). PATIENTS AND METHODS: A prospective, multicenter, open-label study was designed to compare BAK-optimized tafluprost administered over 12 weeks relative to other preserved prostaglandin analogs previously administered in Japanese glaucoma patients. Thirty patients with SPK graded at <6 points by area density (AD) scoring in 1 eye were recruited. The primary outcome measure was change in AD score at 12 weeks after the switch in treatment compared with that at baseline. Secondary outcome measures included changes in tear film breakup time (TBUT), hyperemia score, and intraocular pressure (IOP). Four patients were excluded from analysis because of treatment discontinuation. RESULTS: Mean AD score±SD decreased significantly from 3.4±0.9 to 1.8±1.8 after the switch (P<0.0001). Mean TBUT increased significantly from 6.3±3.3 to 8.0±4.2 seconds (P<0.01). Mean hyperemia score remained unchanged, whereas mean IOP decreased significantly from 15.6±2.6 to 14.4±2.0 mm Hg (P<0.01). For patients previously treated with BAK-preserved latanoprost (n=17) or bimatoprost (n=2), mean AD score decreased significantly from 3.4±0.9 to 1.8±1.8 (P<0.01) and mean TBUT increased significantly from 6.4±3.6 to 8.2±4.3 seconds (P<0.01); no such changes were apparent for patients previously treated with sofZia-preserved travoprost (n=7). CONCLUSIONS: BAK-optimized tafluprost is a treatment option to improve the condition of the ocular surface and to maintain IOP control in glaucoma patients with existing SPK who have been previously treated with other BAK-preserved prostaglandin analogs.

A 6-month study comparing efficacy, safety, and tolerability of the preservative-free fixed combination of tafluprost 0.0015% and timolol 0.5% versus each of its individual preservative-free components.

INTRODUCTION: The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015% and timolol 0.5% (once daily) were compared to those of the individual components (PF tafluprost 0.0015% once daily and PF timolol 0.5% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6 months. METHODS: A stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n = 95) or timolol 0.5% (TIM; n = 94). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n = 188) or tafluprost 0.0015% (TAF; n = 187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of ≥22 mmHg when on timolol (TIM) or of ≥20 mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6 weeks, 3 and 6 months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m. RESULTS: In the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was -8.55 mmHg (32%) for FC and -7.35 mmHg (28%) for TIM. The model-based treatment difference (FC-TIM) was -0.885 mmHg [95% confidence interval (CI) -1.745 to -0.024; p = 0.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was -8.61 mmHg (33%) for FC and -7.23 mmHg (28%) for TAF. The model-based treatment difference (FC-TAF) was -1.516 mmHg (95% CI -2.044 to -0.988; p < 0.001) demonstrating the superiority of FC over TAF. In the TS, related ocular adverse events (AEs) were more frequent for patients treated with FC compared to TIM (16.8% versus 6.4%), whereas related non-ocular AEs were more frequent with TIM compared to FC (2.1% versus 0.0%). In the PS, AEs were similarly distributed between FC and TAF. The frequency of conjunctival hyperemia of FC was low (6.4%). CONCLUSION: The preservative-free fixed combination of tafluprost and timolol provided a substantial and significant IOP reduction in both strata. The IOP reduction was superior to both tafluprost 0.0015% and timolol 0.5% when given as monotherapies. Overall, the study treatments were safe and well tolerated. FUNDING: Santen Oy, Tampere, Finland.

Fixed-dose combination of tafluprost and timolol in the treatment of open-angle glaucoma and ocular hypertension: comparison with other fixed-combination products.

A new preservative-free fixed-dose combination of 0.0015% tafluprost, a prostaglandin F2α analog, and 0.5% timolol (TAF/TIM; Santen Oy, Tampere, Finland), a beta-adrenergic antagonist has recently been developed. The intraocular pressure (IOP) reduction with TAF/TIM in open-angle glaucoma and ocular hypertension is similar to that of other prostaglandin-timolol fixed-combination products. Patients with high IOP responded well to TAF/TIM with reductions of up to 40% (>13 mmHg) and beyond. Compared to previous controlled and double-masked clinical trials with DuoTrav(®) (Alcon, Fort Worth, USA) and Ganfort(®) (Allergan, Irvine, USA), TAF/TIM caused less superficial ocular side effects and less conjunctival hyperemia. Plausible explanations for the differences in side effects between the fixed-combination products are discussed.

Comparative efficacy and tolerability of topical prostaglandin analogues for primary open-angle glaucoma and ocular hypertension.

OBJECTIVE: 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. DATA SOURCES: 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. STUDY SELECTION AND DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSIONS: 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.

Efficacy and safety of tafluprost 0.0015% and timolol maleate 0.5% fixed combination in patients with ocular hypertension or open-angle glaucoma.

INTRODUCTION: Lowering intraocular pressure (IOP) is at present the only therapeutic approach to the treatment of glaucoma proven to be successful. The choice of therapy must take into account efficacy, tolerability, safety, quality of life, adherence and cost. Monotherapy fails to achieve a satisfactory IOP reduction in 40 - 75% of glaucoma patients after > 2 years of therapy. So far, three prostaglandin/timolol maleate 0.5% fixed combinations (FCs) are available. AREAS COVERED: This review provides a background on the tafluprost-timolol FC (TTFC, Santen Oy) and its individual compounds. It summarizes the data on efficacy and safety, including comparative data with prostaglandin/timolol FCs already available. EXPERT OPINION: Tafluprost is a preservative-free prostaglandin analog with a similar IOP efficacy when compared with other prostaglandin analogs. However, its improved adverse effect profile seems to be beneficial in patients sensitive to preservatives. The preservative-free TTFC has no market authorization yet. Only one Phase III trial was published so far, but results are promising in terms of efficacy, tolerability and safety. It is likely that the TTFC will play a role in the treatment of open-angle glaucoma and ocular hypertension.

Efficacy, safety, and tolerability of preservative-free fixed combination of tafluprost 0.0015%/timolol 0.5% versus concomitant use of the ingredients.

PURPOSE: To compare efficacy, safety, and tolerability of the preservative-free fixed combination (FC) and non-fixed combination (NFC) of tafluprost 0.0015% and timolol 0.5% in patients with open-angle glaucoma or ocular hypertension. METHODS: This 6-month, prospective, randomized, double-masked, active-controlled, parallel group, multicenter phase III study was performed in patients with ocular hypertension and open-angle glaucoma with untreated intraocular pressure (IOP) ≥23 and ≤36 mmHg at baseline. RESULTS: Four hundred patients washed out from IOP-lowering medication were randomized, 201 received the FC, and 199 received the NFC. Mean time-wise IOP decreases from baseline ranged from -7.3 to -9.1 mmHg (29.6%-34.6%) in the FC and from -7.5 to -9.4 mmHg (30.7%-36.0%) in the NFC arm [per-protocol (PP) dataset, P<0.0001 compared with baseline for both groups]. At month 6, the estimated overall treatment difference (FC-NFC) was 0.308 mmHg (PP dataset, 95% confidence interval from -0.194 to 0.810 mmHg). An IOP decrease ≥30% was achieved in 58.3% and 66.9% of the patients in the FC and NFC groups, respectively (PP dataset; P=0.105); an IOP decrease ≥35% was achieved in 36.6% and 43.1% of patients in the FC and NFC groups, respectively (PP dataset; P=0.297). Patients with ocular adverse events were evenly distributed in both groups. The most common side effect, conjunctival/ocular hyperemia was found in 8% and 5% of patients in the FC and NFC arms, respectively. CONCLUSIONS: All measures of IOP reduction for FC of preservative-free tafluprost/timolol were statistically and clinically significant and non-inferior to those of the NFC, throughout the 6-month study period.