tafluprost and Glaucoma

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

Childhood glaucoma is a major therapeutic challenge for pediatric ophthalmologists and glaucoma specialists worldwide. Management depends on the etiology and age at presentation. A variety of drugs are available for the control of intraocular pressure in children; however, none of these drugs have been licensed by the regulatory agencies for use in children. Furthermore, evidence gained from randomized controlled trials in the pediatric population is sparse, and little is known regarding the use of newer anti-glaucoma preparations. This evidence-based review aims to discuss the available pharmacotherapeutic options for glaucoma in children. Topical adrenoceptor blockers, topical and systemic carbonic anhydrase inhibitors, prostaglandin (PG) analogs, adrenoceptor agonists, parasympathomimetics, and combined preparations are available for use in children, but usually as an off-label indication. Therefore, it is important to recognize that serious side effects have been reported, even with topical drops, and measures to reduce systemic absorption should be taken. Most drugs have been shown to have comparable ocular hypotensive effects, with the lowest occurrence of systemic side effects with PG analogs. Whereas a newly introduced prostaglandin analog, tafluprost, and some other preservative-free preparations have shown promising results in adult glaucoma patients, no pediatric reports are available as yet. Future studies may describe their role in treating pediatric glaucoma. This review also shares some suggested treatment pathways for primary congenital glaucoma (PCG), juvenile open angle glaucoma (JOAG), developmental glaucoma, aphakic/pseudophakic glaucoma, and uveitic glaucoma.

Topics: Carbonic Anhydrase Inhibitors; Child; Glaucoma; Humans; Intraocular Pressure; Prostaglandins F; Randomized Controlled Trials as Topic

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.. 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®).. 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.

Topics: Antihypertensive Agents; Disease Management; Drug Combinations; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Quality of Life; Timolol

Tafluprost ophthalmic solution 0.0015 % preserved with benzalkonium chloride (BAK) 0.001 % is available in several Asian countries, including Japan. In pivotal trials, BAK-preserved tafluprost ophthalmic solution 0.0015 % lowered intraocular pressure (IOP) more effectively than placebo in Asian patients with normal-tension glaucoma and was at least as effective as latanoprost ophthalmic solution 0.005 % in Asian patients with primary open-angle glaucoma or ocular hypertension. In other prospective studies in Asian patients with glaucoma or ocular hypertension, tafluprost ophthalmic solution 0.0015 % was at least as effective as latanoprost ophthalmic solution 0.005 % or travoprost ophthalmic solution 0.004 % in terms of IOP lowering, and was considered easier to use and/or store. The efficacy of tafluprost ophthalmic solution 0.0015 % was maintained in the longer term. Tafluprost ophthalmic solution 0.0015 % was generally well tolerated. In conclusion, BAK-preserved tafluprost ophthalmic solution 0.0015 % remains a useful option for the treatment of Asian patients with glaucoma and ocular hypertension.

Topics: Antihypertensive Agents; Asia; Asian People; Glaucoma; Humans; Intraocular Pressure; Ocular Hypertension; Ophthalmic Solutions; Prostaglandins F; Randomized Controlled Trials as Topic

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.. In this review, we summarize data on safety and tolerability of this FC.. 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.

Topics: Antihypertensive Agents; Conjunctival Diseases; Drug Combinations; Glaucoma; Humans; Hyperemia; Intraocular Pressure; Medication Adherence; Prostaglandins F; Timolol

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.. 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.. 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.

Topics: Antihypertensive Agents; Drug Combinations; Drug Evaluation; Drug-Related Side Effects and Adverse Reactions; Glaucoma; Glaucoma, Open-Angle; Humans; Ocular Hypertension; Prostaglandins F; Timolol

Lowering intraocular pressure (IOP) is, at present, the only therapeutic approach to the treatment of glaucoma. Good compliance is essential in every chronic therapy; therefore, the development of IOP-lowering eye drops that are well tolerated and have an easy administration schedule is essential for the treatment of glaucoma. Prostaglandins are a first-choice drug class for the treatment of glaucoma.. This review provides a background on tafluprost, a newly synthesized prostaglandin analogue, and summarizes the existing data on its efficacy and safety, including comparative data with the other prostaglandin derivatives now available on the market. A review of the literature was performed.. Current research focuses not only on the efficacy of the drugs but also on their tolerability. The importance of obtaining good compliance by the patient is increasingly relevant; therefore, new formulations are studied to provide fewer side effects and an easier schedule. Tafluprost is a new prostaglandin analogue that has been marketed in some European countries and in Japan for more than 2 years and was recently (July 2009) approved in 21 countries. Besides a well-demonstrated IOP-lowering effect, tafluprost is the first topical prostaglandin available as a preservative-free formulation.

Topics: Administration, Ophthalmic; Glaucoma; Humans; Hypersensitivity; Intraocular Pressure; Prostaglandins F

Glaucoma affects an increasing number of people worldwide and is the second leading cause of blindness. The aim of antiglaucoma therapy is to maintain a patient's visual function and quality of life. Prostaglandin analogues are first-line topical antiglaucoma therapy. They are effective at lowering intraocular pressure (IOP) and are generally well tolerated, with fewer systemic adverse events compared with the other classes. However, the use of prostaglandin analogues can be associated with ocular adverse effects, such as stinging/burning sensation, dry eyes, iris and periocular hyperpigmentation, and eye lash growth, which can affect patient compliance. Preservatives used in antiglaucoma preparations can have dose-dependent toxic effects, which contribute to adverse effects. The development of preservative-free preparations may reduce such adverse effects and therefore improve patient compliance. Tafluprost is a prostaglandin analogue in a preservative-free formulation that was recently approved for the reduction of elevated IOP in open-angle glaucoma and ocular hypertension.

Topics: Blindness; Glaucoma; Glaucoma, Open-Angle; Humans; Hypersensitivity; Latanoprost; Ocular Hypertension; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Prostaglandins, Synthetic

Topics: Antihypertensive Agents; Cloprostenol; Drug Therapy, Combination; Glaucoma; Humans; Intraocular Pressure; Lasers; Ophthalmic Solutions; Prostaglandins F; Trabeculectomy; Travoprost

Prostaglandin analogs (PGAs) are the first-line treatment for primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study aimed to confirm the effectiveness and safety of Tapros® (0.0015% tafluprost eye drops) in Chinese patients with POAG and OH.. This phase IV, multicenter, non-comparative, prospective study enrolled patients with POAG and OH in China between 12/27/2017 and 04/15/2020. Patients who were treatment-naïve or untreated within one month (group A) or with unreached intraocular pressure (IOP) target after previous monotherapy of other PGAs (group B) or non-PGA IOP-lowering drugs (group C) were treated with 0.0015% tafluprost for three months. The IOP reduction, response rate, and safety were observed.. There were 165, 89, and 31 patients in groups A, B, and C, with baseline IOPs of 22.4 ± 4.7, 21.0 ± 3.5, and 22.5 ± 3.2 mmHg, respectively. The least-square means and percentages of IOP reduction at 3 months for groups A, B, and C were 4.7 (19.8%), 1.6 (6.1%), and 4.6 mmHg (20.3%), respectively. A significant reduction in IOP was observed at each visit compared with baseline (all P < 0.05). At the final visit, 57.0% of the participants in group A achieved an IOP reduction of ≥ 20%, while 40.4% and 77.4% in groups B and C achieved an IOP reduction of ≥ 10%. Fifty-eight treatment-related adverse events occurred in 46 participants (15.7%), of which the most common one was conjunctival hyperemia (34/293, 11.6%).. Tafluprost showed a sustained and significant effect with tolerable adverse events in Chinese patients with POAG and OH who were treatment-naïve or untreated within one month or received prior treatments with unsatisfying outcomes.

Topics: Antihypertensive Agents; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Marketing; Ocular Hypertension; Ocular Hypotension; Prospective Studies; Prostaglandins F; Prostaglandins, Synthetic; Treatment Outcome

To compare the efficacies of latanoprost 0.005%, travoprost 0.004%, and tafluprost 0.0015% in reducing diurnal intraocular pressure (IOP) fluctuations in patients with newly diagnosed primary open-angle glaucoma (POAG).. In this prospective randomized clinical trial, 60 patients who were newly diagnosed with POAG were divided into three equal groups. Patients were examined at presentation and at second and sixth weeks. Diurnal phasing of IOP was conducted using a calibrated Goldmann applanation tonometer. IOP measurements were recorded from 8:00 am to 9:00 am, from 3:00 pm to 4:00 pm, and from 7:00 pm to 8:00 pm.. The study groups were distributed similarly in terms of age and gender (. Latanoprost, travoprost, and tafluprost show a similar effectiveness in reducing the mean IOP and the diurnal IOP fluctuation in POAG. Importantly, the three drugs have comparable tolerability with insignificant differences regarding the pattern of their side effects.

Topics: Adult; Aged; Antihypertensive Agents; Cloprostenol; Double-Blind Method; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost; Treatment Outcome

The aim of this work is to evaluate efficacy and tolerability of preservative containing 0.0015% tafluprost and preservative-free 0.0015% tafluprost using a prospective crossover study.. Primary open angle glaucoma (POAG) and normotensive glaucoma (NTG) patients were randomized enrolled. Group 1 ("NPT to PT") patients used preservative-free 0.0015% tafluprost (NPT) for 6 months and then changed to preservative containing 0.0015% tafluprost(PT) for 6 months. Group 2 ("PT to NPT") patients used preservative containing 0.0015% tafluprost for 6 months and changed to preservative-free 0.0015% tafluprost for 6 months. At 1, 3, 6, 7, 9, and 12 months, we measured intraocular pressure for efficacy and graded corneal erosion, tear break-up time (TBUT), and subjective discomfort.. A total of 20 patients and 20 eyes were enrolled. In Group 1 and 2, intraocular pressure was well controlled to approximately 14 mmHg (9.38-18.46% decrease). Generally, subjective satisfaction was improved after changing from PT to NPT (p = 0.03) and TBUT using PT was numerically inferior to that using NPT (p = 0.06) but not when changing from NPT to PT.. Both preservative containing and preservative-free 0.0015% tafluprost reduced intraocular pressure significantly. In addition, changing medication from PT to NPT might improve subjective satisfaction and tear break up time.. The trial registration number is NCT 03104621 (Apr/1/2017). Retrospectively registered.

Topics: Cross-Over Studies; Dose-Response Relationship, Drug; Drug Tolerance; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ophthalmic Solutions; Prospective Studies; Prostaglandins F; Tonometry, Ocular; Treatment Outcome

The aim of the present study was to compare the confocal and clinical features of newly diagnosed glaucoma patients receiving unpreserved prostaglandins (tafluprost) versus preserved prostaglandins (latanoprost).. 40 patients were randomized to tafluprost 0.0015% (20 patients; 32 eyes) or latanoprost 0.005% + benzalkonium chloride 0.02% (20 patients; 35 eyes) once daily for 1 year. Inclusion criteria were new glaucoma diagnosis, and no ocular treatments for 6 months before the study. Patients were evaluated at baseline and every 3 months with a complete ophthalmologic evaluation, Schirmer's test, break-up time test, confocal microscopy of the central cornea, and measurement of intraocular pressure (IOP). Investigators were masked to treatment. Both eyes were analyzed if they fulfilled inclusion criteria. Treatments and changes between follow-up and baseline were compared by analysis of variance (ANOVA), t test and Chi-square test.. At baseline, the two groups had similar age, ocular surface and confocal findings; keratocyte activation was present in 40%, branching pattern in 85%, and beading in 75%, with no inter-group differences. At follow-up, no significant clinical changes were detected, apart from a drop of IOP by 3.6-4.2 mmHg in the two groups (p < 0.001, with no difference between treatments). Despite inter-treatment ANOVA for confocal microscopy being negative, subtle changes were present. During follow-up, all eyes without nerve branching pattern at baseline progressively developed it when treated with latanoprost, whereas no change occurred using tafluprost treatment (p = 0.05). None of the eyes without beading at baseline developed it at the end of the study in the tafluprost group, whereas beading did occur in 75% of patients treated with latanoprost (p = 0.05). Both treatments were associated with increased keratocyte activation at follow-up; the change from baseline was statistically significant after month 3 with latanoprost (p = 0.02) and after month 6 with tafluprost (p = 0.04).. The two study treatments had similar clinical effects, but tafluprost had a more favorable profile for some confocal parameters of the cornea.. Merck Sharp & Dohme International.

Topics: Administration, Ophthalmic; Aged; Aged, 80 and over; Antihypertensive Agents; Cornea; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Male; Middle Aged; Prospective Studies; Prostaglandins F; Prostaglandins F, Synthetic

To evaluate the density of conjunctival goblet cells (GCs) in glaucomatous patients treated with preservative-free (PF) tafluprost, using laser scanning confocal microscopy (LSCM) and impression cytology (IC).. Thirty glaucomatous patients (30 eyes) naive for therapy and thirty healthy subjects (30 eyes) were enrolled. Conjunctiva was examined by means of Heidelberg Retina Tomography/Rostock cornea module. Afterwards, the specimens for IC were obtained. Patients were randomized to PF-tafluprost (Group 1) or preserved latanoprost (Group 2) and controls to the vehicle of latanoprost (Group 3) or physiological buffered saline solution (Group 4). Both LSCM and IC were performed at baseline, and after the 1st and 6th months of therapy, GC density (GCD) (cells/mm(2) ) was the main outcome measurement..   Baseline. Mean GCD was 240.69 ± 25.43 and 232.65 ± 23.52, for LSCM, and 162.10 ± 23.44 and 164.71 ± 21.03 for IC in Group 1 and 2, respectively. GC density values were not significantly different in Group 3 and 4 (p > 0.05%). Month one. Mean GCD increased to 284.16 ± 43.88 and 230.62 ± 48.32 in Group 1 (p < 0.001) and to 297.86 ± 26.87 and 221.78 ± 43.02 in Group 2 (p < 0.05), measured with LSCM and IC, respectively. In Group 3, GCD decreased to 205.88 ± 25.04 and 139.54 ± 17.37 measured with LSCM and IC, respectively (p < 0.05). Month six. Mean GCD did not change in Group 1 (p > 0.05) whereas it decreased in Group 2 (p < 0.05), compared to month 1. In Group 3, GCD further decreased to 166.32 ± 22.31 and 120.76 ± 11.66, measured with LSCM and IC, respectively (p < 0.05); in Group 4, mean GCD did not change during the study period (p > 0.05).. Treatment with PF tafluprost was associated with an increase in conjunctival GCD in glaucomatous eyes naïve for therapy. Further studies are mandatory to verify this finding because its validation may have important consequences in the medical management of glaucoma.

Topics: Cell Count; Conjunctiva; Cytological Techniques; Dose-Response Relationship, Drug; Follow-Up Studies; Glaucoma; Goblet Cells; Humans; Microscopy, Confocal; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins F; Single-Blind Method; Treatment Outcome

The objective of this study was to evaluate efficacy, local tolerability, and safety of this first-in-class preservative-free prostaglandin preparation in patients with ocular hypertension and glaucoma.. Patients with glaucoma or ocular hypertension who required a change of medication or were naïve to treatment were included in this noninterventional and observational study. Noninterventional means that no influence was made upon the decision of the physicians to include specific patients and upon the treatment algorithm used. German law for observational studies does not allow any influence on the choice of drugs used, patient selection, masking, and comparator treatment regimens. The main aim of this observational study was to collect "real-life data" on the efficacy and safety of a new medical treatment after approval in a large patient population. Participating ophthalmologists were asked to provide anonymous patient data collected during regular visits by filling a simple data entry form. Intraocular pressure (IOP) readings were recorded at baseline (previous therapy or untreated) and 6-12 weeks after changing medical treatment to or initiating treatment with preservative-free tafluprost once daily. Changes in the IOP were evaluated over the study period for all patients as well as for specific pretreatment subgroups. Local comfort was determined using a five-point scale (very good, good, satisfactory, less satisfactory, not acceptable) before and after the change of medical treatment. All adverse events were recorded.. Data from 2123 patients with glaucoma or ocular hypertension were considered for the final evaluation. Medication was changed in 41.1% of patients due to tolerability issues and in 25.6% of patients due to insufficient efficacy with prior medication. In all patients preservative-free tafluprost 0.0015% lowered IOP from 19.5 ± 4.4 mmHg (baseline) to 16.4 ± 2.9 mmHg after 6-12 weeks. Preservativefree tafluprost also significantly lowered the IOP in all monotherapy subgroups: treatment-naïve patients (n=440): 22.6 ± 3.9 mmHg (baseline) to 16.7 ± 2.7 mmHg (week 6-12); beta blockers (n=307): 20.3 ± 3.5 mmHg (baseline) to 16.7 ± 2.6 mmHg (week 6-12); carbonic anhydrase inhibitors (n=158): 19.0 ± 3.6 mmHg (baseline) to 16.0 ± 2.6 mmHg (week 6-12); prostaglandin analogs (PGAs; n=447): 16.8 ± 2.9 mmHg (baseline) to 15.8 ± 2.6 mmHg (week 6-12). Local comfort was rated as "very good" or "good" by 85.6% of patients at the final visit (P<0.001). Only few adverse events occurred during the treatment period: 18 patients (0.8%) discontinued medical treatment with preservative-free tafluprost due to local intolerance; six patients (0.3%) due to efficacy issues; four patients complained about systemic side effects (0.2%); and two patients preferred to use a multidose treatment regimen (0.2%).. Although this study was limited by its observational design the results demonstrate that preservative-free tafluprost 0.0015% was effective, generally well tolerated, and safe in a broad and heterogeneous patient population.

Topics: Adolescent; Adult; Aged; Female; Germany; Glaucoma; Humans; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F; Treatment Outcome; Young Adult

Tafluprost is a novel prostaglandin F(2alpha)-receptor agonist shown to lower intraocular pressure (IOP) in healthy humans and patients with elevated IOP. We investigated the efficacy, safety, and tolerability of tafluprost 0.0015% compared with latanoprost 0.005% in patients with primary open-angle glaucoma, exfoliation glaucoma, or ocular hypertension.. This was a randomized, double-masked, active-controlled, parallel-group, multinational, and multicenter phase II study. Patients received either tafluprost 0.0015% (n = 19) or latanoprost 0.005% (n = 19), both once daily. The extent and duration of action of the IOP-lowering effects at Day 42 and Day 43 were the primary efficacy endpoints. Efficacy and safety parameters were analyzed throughout.. Maximum IOP reduction was achieved by Day 7 and was sustained until Day 42 in both groups (mean [standard deviation] change from baseline -9.7 [3.3] mm Hg for tafluprost and -8.8 [4.3] mm Hg for latanoprost). The overall treatment group difference was 0.17 mm Hg (95% confidence interval -1.27 to 1.61; P = 0.811). The IOP-lowering effect was maintained for >or=24 h after the last dose in both groups. Most adverse events were ocular and were similar in frequency and severity between groups. There were 3 severe adverse events, all ocular, and all in the tafluprost group (3/19 = 16%).. Tafluprost and latanoprost have comparable effects on the extent, duration, and stability of IOP reduction, and are well tolerated in patients.

Topics: Double-Blind Method; Exfoliation Syndrome; Eye; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Latanoprost; Male; Ocular Hypertension; Prostaglandins F; Prostaglandins F, Synthetic; Time Factors; Treatment Outcome; Young Adult

Tafluprost, the first preservative-free prostaglandin analogue for topical ophthalmic use to lower IOP, was introduced in Germany in 2008. After the approval for ophthalmic use, an open-label, multicentre, observational study was conducted between October 2008 and April 2009. Major objectives of this study were to evaluate the real world efficacy, local tolerability and safety of this first in class preservative-free prostaglandin preparation in patients with ocular hypertension and glaucoma.. A total of 544 patients were treated with the preservative-free formulation of tafluprost 0.0015%. The majority of these patients had poor IOP control and/or poor local tolerance of their medication prior change of medication. The decision to change the previous therapy or to initiate treatment was made solely by the participating ophthalmologists. IOP readings were recorded at baseline before changing medication or initiating treatment in newly diagnosed patients, 4-6 weeks and 12 weeks after change of medication or initiation of treatment with preservative-free tafluprost. In addition, patient demographics, subjective symptoms (i.e. burning, foreign body sensation, itching and stinging) and objective clinical signs such as conjunctival hyperaemia were collected. Subjective symptoms were evaluated using a 4 point scale ranging from 'no symptoms', 'mild symptoms', 'moderate symptoms' to 'severe symptoms'. As a clinical sign severity of conjunctival hyperaemia was evaluated. All adverse events were collected.. Three hundred and sixty patients were switched from monotherapy, 45 patients were naïve to treatment. A total of 139 patients were treated with fixed or non-fixed combinations prior to changing medication. In these patients preservative-free tafluprost was used either as a substitution for the fixed or non-fixed combination, as an add-on to the existing combination therapy or as one agent in a newly initiated treatment regimen. Preservative-free tafluprost provided an IOP decrease in most pre-treatment subgroups, with an overall reduction of IOP in all patients (N = 544) from 19.4 +/- 5.0 mmHg at baseline to 15.7 +/- 4.1 mmHg after 4 to 6 weeks and to 15.3 +/- 3.5 mmHg after 12 weeks. Both values were significantly lower than treated baseline IOP (p < 0.001). An IOP of

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Patient Dropouts; Preservatives, Pharmaceutical; Prostaglandins F; Treatment Outcome; Young Adult

Prostaglandin receptor analogs lower intraocular pressure (IOP) and are used for the treatment of glaucoma. This study aimed to compare the safety, tolerability and pharmacodynamics of four doses of the new, selective-prostanoid receptor agonist, tafluprost (AFP-168) in a Phase I placebo-controlled study.. Healthy volunteers (n = 16) received sequentially ascending doses of tafluprost (0.0001%, 0.0005%, 0.0025% and 0.005%) in one eye, and placebo in the other. Each treatment period consisted of 2 days of treatment, with 5 days between the treatment periods. Safety and tolerability assessments, as well as IOP measurements, were performed at defined intervals.. Tafluprost was generally well tolerated and no volunteer discontinued due to adverse events (AEs). The most common ocular AE was ocular hyperemia, which was mild-to-moderate, and highly concentration-dependent. All doses of tafluprost decreased IOP, with the maximum effect occurring 12 hours after treatment. The decrease in IOP relative to placebo was significantly more effective with tafluprost 0.0025% and 0.005%, compared with tafluprost 0.0001% (p pound 0.005).. Tafluprost was well tolerated and effective in lowering IOP. These data support further testing of tafluprost 0.0025% and 0.005%.

Topics: Administration, Topical; Adult; Antihypertensive Agents; Dose-Response Relationship, Drug; Glaucoma; Humans; Hyperemia; Intraocular Pressure; Male; Middle Aged; Prostaglandins F; Receptors, Prostaglandin; Time Factors

To investigate the intraocular pressure (IOP) lowering effect of topical preserved tafluprost 0.0015% in a tertiary hospital setting in India.. 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.. 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).. 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.

Topics: Antihypertensive Agents; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Prostaglandins F; Retrospective Studies; Timolol; 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

Analysis and comparison of country-level data from the VISIONARY study, examining treatment outcomes with the topical fixed-dose combination of preservative-free tafluprost (0.0015%) and timolol (0.5%) (PF tafluprost/timolol FC) in adults with open-angle glaucoma (OAG) and ocular hypertension (OHT) who were insufficiently treated with or unable to tolerate either beta-blocker or prostaglandin analogue (PGA) topical monotherapy.. A European, prospective, observational study was conducted in 11 countries. Adults with OAG/OHT were switched to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Statistical analysis examined changes in mean standard deviation (SD) intraocular pressure (IOP) from baseline at Week 4, Week 12 and Month 6. Data were documented for each eye separately at baseline and during follow up visits, with the eye reported to have the higher IOP (mmHg), as measured using Goldmann applanation tonometry, being selected for analysis (study eye). Country-level subanalysis examined outcomes by prior monotherapy, diagnosis and timing of dosing for those countries recruiting ≥20 patients (Country-level Subanalysis Population). Two-sided paired. Subanalysis of VISIONARY study data revealed significant IOP reductions following a switch to the PF tafluprost/timolol FC from either PGA or beta-blocker topical monotherapy. Cross-country variation was likely due to baseline IOP differences. Within country, outcomes were consistent regardless of diagnosis, dosing or prior monotherapy. Treatment was generally well tolerated.

Topics: Adrenergic beta-Antagonists; Adult; Antihypertensive Agents; Drug Combinations; Female; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins A; Prostaglandins F; Timolol; Treatment Outcome

Elevated intraocular pressure (IOP) is the most important modifiable risk factor for irreversible sight loss in open-angle glaucoma (OAG). The topical fixed-dose combination (FC) of preservative-free (PF) tafluprost (0.0015%) and timolol (0.5%) (tafluprost/timolol) is among the second-line IOP-lowering options for OAG and ocular hypertension (OHT).. PubMed searches identified publications reporting key evidence from randomized controlled trials (RCTs) and real-world studies examining the safety, tolerability, and IOP-lowering efficacy of PF tafluprost/timolol FC therapy in OAG/OHT management.. Glaucoma patients are more likely to have ocular surface disease, and treatment should be individualized so that target response may be achieved while considering tolerability and quality of life, according to European Glaucoma Society guidelines. PF FC therapies, such as PF tafluprost/timolol FC, avoid ocular surface exposure to toxic preservative agents and reduce the required number of treatment administrations. These properties may enhance treatment tolerability and adherence, resulting in improved IOP-lowering efficacy and disease control. Treatment outcomes from RCTs and real-world studies examining PF tafluprost/timolol FC therapy support this hypothesis, with significant IOP reductions and/or improvements in tolerability parameters demonstrated, regardless of the prior topical therapy used and even when switched directly to PF tafluprost/timolol FC treatment (without washout).

Topics: Antihypertensive Agents; Drug Combinations; Glaucoma; Glaucoma, Open-Angle; Humans; Intraocular Pressure; Ocular Hypertension; Preservatives, Pharmaceutical; Timolol

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

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 investigate the usefulness of meibomian gland (MG) dropout rate in the evaluation of MG morphological change associated with the use of prostaglandin for glaucoma treatment through the association between MG and the ocular surface parameters and medication duration and presence of preservative.. This cross-sectional study was conducted on 88 eyes of 88 patients who were diagnosed with glaucoma and used only Tafluprost as treatment. The patients were divided into four "user" groups: 1) 23 patients used preservative-free (PF) Tafluprost for 6 months; 2) 21 patients used preservative-containing (PC) Tafluprost for 6 months; 3) 23 patients used PF-Tafluprost for 24 months; 4) 21 patients used PC-Tafluprost for 24 months. Ocular surface parameters and the MG condition, including MG dropout rate and meiboscale, were evaluated. Multiple regression was used to identify associations.. There were significant differences in age (p = 0.003), tear breakup time (p = 0.016), lid margin abnormality (p = 0.016), expressibility (p = 0.039), meiboscale (p<0.001), and MG dropout rate (p<0.001) among the 4 groups. MG dropout rate and meiboscale showed significant differences in all post hoc analyses, except for the comparison between the PF-Tafluprost and PC-Tafluprost 6-month user groups. Medication duration, preservative status, and meiboscale were significantly correlated with MG dropout rate (p<0.001, p = 0.024, p<0.001, respectively). In the 6-month user group, preservative status significantly correlated with MG dropout rate (p = 0.015). However, in the 24-month user group, meiboscale was the only parameter significantly associated with MG dropout rate (p<0.001).. MG dropout rate in patients using Tafluprost showed a significant correlation with medication duration and preservative status. This result indicates MG dropout rate reflects MG morphologic change associated with prostaglandin.

Topics: Adult; Age Factors; Aged; Cross-Sectional Studies; Female; Glaucoma; Humans; Male; Meibomian Glands; Middle Aged; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins, Synthetic; Regression Analysis; Time Factors; Treatment Outcome

Topics: Administration, Topical; Benzalkonium Compounds; Cross-Sectional Studies; Dinoprost; Glaucoma; Humans; Latanoprost; Oxidative Stress; Poland; Prostaglandins F; Tears

Long-term glaucoma therapy with preservative-containing eye drops may impact ocular surface health. This study was performed to investigate whether a switch from preserved topical prostaglandin therapy to preservative-free tafluprost therapy improves precorneal tear film thickness in patients with glaucoma or ocular hypertension.. A total of 30 patients who were under topical preservative-containing prostaglandin monotherapy for at least 6 months were included. Patients were then switched from preserved prostaglandin therapy to unpreserved tafluprost drops once daily. Tear film thickness was measured at baseline and 4 and 12 weeks after therapy change with an ultrahigh-resolution optical coherence tomography system. Furthermore, clinical measures of ocular surface disease were determined and symptoms were assessed using the Dry Eye-Related Quality-of-Life Score.. After switching to unpreserved tafluprost, tear film thickness significantly increased from 4.7 ± 0.5 to 5.0 ± 0.6 µm 4 weeks after therapy change and still tended to be increased after 12 weeks (4.8 ± 0.7 µm). Breakup time significantly increased from 5.1 ± 2.3 to 7.2 ± 3.4 s and to 10.1 ± 3.6 s after therapy change. In addition, a significant decrease in corneal staining score from 1.8 ± 0.7 to 1.4 ± 0.8 after 4 weeks and to 0.7 ± 0.7 after 12 weeks treatment was observed. Switching to preservative-free drops reduced Dry Eye-Related Quality-of-Life Score from 11.4 ± 11.0 to 5.7 ± 6.4 and to 4.7 ± 7.5.. Our data show that switching to preservative-free tafluprost leads to an increase in tear film thickness, breakup time, and an improvement of Dry Eye-Related Quality-of-Life Score. Our results therefore indicate that a switch to unpreserved tafluprost is beneficial for ocular surface health in patients under long-term preserved prostaglandin eye drops.

Topics: Aged; Dry Eye Syndromes; Female; Glaucoma; Humans; Male; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins, Synthetic; Tears

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.

Topics: Aged; Antihypertensive Agents; Benzalkonium Compounds; Female; Glaucoma; Humans; Latanoprost; Male; Middle Aged; Preservatives, Pharmaceutical; Prostaglandins F; Proteome; Tears

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

There is no consensus on the diagnosis or treatment policy for Preperimetric Glaucoma (PPG) because the pathogenesis of PPG is not clear at this time. Preperimetric Glaucoma Prospective Observational Study (PPGPS) is a first multicenter, prospective, observational study to clarify the pathogenesis of PPG. This article indicates study design, patient baseline characteristics, and analysis focused on optic nerve head (ONH) blood flow in PPG, as well as the intraocular pressure (IOP) -lowering effect and ONH blood flow-improving effects of Tafluprost.. In this study, 122 eyes from 122 subjects (mean age: 53.1 ± 14.3) newly diagnosed as PPG were enrolled. The circumpapillary retinal nerve fiber layer thickness (cpRNFLT) was evaluated with optical coherence tomography (OCT). The ONH blood flow was measured with laser speckle flowgraphy. The therapeutic effect of Tafluprost was evaluated at Month 0 (ONH blood flow-improving effect) and Month 4 (IOP-lowering effect).. The untreated IOP, cpRNFLT, and baseline Mean deviation (MD) value was 16.4 ± 2.5 mmHg, 80.4 ± 8.2 μm, and -0.48 ± 1.29 dB, respectively. In the site-specific visual field evaluation using the sector map, there was no appreciable site-specific visual field defect in the eye with PPG. The inferior region of cpRNFLT in 4-quadrant OCT sector analysis and 6 o'clock region in 12-o'clock OCT sector analysis was the highest rate of abnormality in PPG eyes. Topical administration of Tafluprost significantly reduced IOP from 16.4 ± 2.5 mmHg at baseline to 14.5 ± 2.3 mmHg at Month 4 (P < 0.001, paired t-test). In the linear regression analysis, there was a significant relationship between the increase of ONH blood flow and baseline value.. PPGPS is a first prospective study focusing on the pathology of PPG. This study is expected to elucidate the pathology of PPG, with evidence useful for determining a treatment strategy for PPG.

Topics: Adult; Aged; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Optic Disk; Prospective Studies; Prostaglandins F; Tomography, Optical Coherence; Visual Field Tests

Tafluprost (AFP-168, 5) is a unique 15-deoxy-15,15-difluoro-16-phenoxy prostaglandin F2α (PGF2α) analog used as an efficacious ocular hypotensive agent in the treatment of glaucoma and ocular hypertension, as monotherapy, or as adjunctive therapy to β-blockers. A novel convergent synthesis of 5 was developed employing Julia-Lythgoe olefination of the structurally advanced prostaglandin phenylsulfone 16, also successfully applied for manufacturing of pharmaceutical grade latanoprost (2), travoprost (3) and bimatoprost (4), with an aldehyde ω-chain synthon 17. The use of the same prostaglandin phenylsulfone 16, as a starting material in parallel syntheses of all commercially available antiglaucoma PGF2α analogs 2-5, significantly reduces manufacturing costs resulting from its synthesis on an industrial scale and development of technological documentation. Another key aspect of the route developed is deoxydifluorination of a trans-13,14-en-15-one 30 with Deoxo-Fluor. Subsequent hydrolysis of protecting groups and final esterification of acid 6 yielded tafluprost (5). The main advantages are the preparation of high purity tafluprost (5) and the application of comparatively cheap reagents. The preparation and identification of two other tafluprost acid derivatives, tafluprost methyl ester (32) and tafluprost ethyl amide (33), are also described.

Topics: Antihypertensive Agents; Chemistry Techniques, Synthetic; Dinoprost; Glaucoma; Molecular Structure; Ocular Hypertension; Prostaglandins F

To evaluate the impact of antiglaucoma drugs on the corneal healing process and corneal toxicity.. Four eye drops to treat glaucoma--Xalatan (latanoprost 50 μg/mL; Pfizer), Monoprost (latanoprost 50 μg/mL; Théa Pharma), Taflotan Sine (tafluprost 15 μg/mL; Santen Pharmaceutical Co.), Travatan (travoprost 40 μg/mL; Alcon), and 0.02% benzalkonium chloride (BAC) solution and HyloComod (1 mg/mL sodium hyaluronate; Ursapharm) as positive and negative control were tested regarding corneal irritability and effect on corneal healing. Formulas were tested over 3 days and administered 6 times daily on rabbit corneas cultured on an artificial anterior chamber (the Ex Vivo Eye Irritation Test system). Initially, 4 corneal abrasions (2.5 to 5.7 mm2) were applied. All defects were monitored during drug application by fluorescein stains and photographs. Glucose/lactate concentrations were monitored for corneal metabolic activity evaluation.. For Xalatan and BAC, the corneal erosion size increased from 14.65 to 66.57 mm2 and 14.80 to 87.26 mm2. Travatan and Taflotan Sine did not interfere with corneal healing. Monoprost delayed corneal healing. For Xalatan and BAC, histology showed severe alteration of the superficial cornea. An increase in anterior chamber lactate concentration indicates corneal toxicity for Xalatan, BAC, and Monoprost.. Corneal toxicity of Xalatan is most probably caused by BAC. Monoprost delays corneal healing, which is not well understood. The Monoprost effects could be caused by its additive, macrogolglycerolhydroxystearate 40. This excipient is a known skin irritant, and its concentration is relatively elevated in Monoprost, 50 mg/mL, compared with its active ingredient, latanoprost (0.05 mg/mL).

Topics: Administration, Topical; Animals; Antihypertensive Agents; Benzalkonium Compounds; Cornea; Corneal Injuries; Glaucoma; Intraocular Pressure; Latanoprost; Ophthalmic Solutions; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Rabbits; Travoprost; Wound Healing

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

To compare the safety and efficacy of fixed-dose tafluprost/timolol combination (Taf/T-FDC) with those of fixed-dose latanoprost/timolol combination (Lat/T-FDC) by measuring the intraocular pressure (IOP)-lowering effect, ocular pharmacokinetics, and ocular surface toxicity.. The IOP-lowering effect of Taf/T-FDC and Lat/T-FDC in ocular normotensive monkeys was evaluated at 4 and 8 h after instillation in study A, at 12, 14, 16, and 18 h after instillation in study B, and at 24, 26, 28, and 30 h after instillation in study C. Drug penetration into the eye was evaluated by measuring the concentrations of timolol, tafluprost acid (active metabolic form of tafluprost), and latanoprost acid (active metabolic form of latanoprost) using liquid chromatography coupled with tandem mass spectrometry after single instillation of Taf/T-FDC or Lat/T-FDC to Sprague Dawley rats. Cytotoxicity following 1-30 min exposure of SV40-transformed human corneal epithelial cells to Taf/T-FDC or Lat/T-FDC was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assays. Undiluted and 10-fold diluted solutions of each FDC were evaluated.. The IOP-lowering effect of Taf/T-FDC was almost equivalent to that of Lat/T-FDC at 4-8 h after instillation. The peak IOP reduction of Taf/T-FDC and Lat/T-FDC was observed at 8 h after instillation, and there is no difference between the two. The difference between them was observed at 24-30 h after instillation, and Taf/T-FDC demonstrated a significantly greater IOP-lowering effect than Lat/T-FDC at 24-30 h after instillation. The IOP-lowering effect of Taf/T-FDC was sustained up to 30 h after instillation, while that of Lat/T-FDC had almost disappeared at 28 h after instillation. Timolol concentrations in aqueous humor after Taf/T-FDC instillation were higher than those after Lat/T-FDC instillation (Cmax, 3870 ng/mL vs 1330 ng/mL; AUCinf, 3970 ng·h/mL vs 1250 ng·h/mL). The concentrations of tafluprost acid and latanoprost acid in aqueous humor after instillation of Taf/T-FDC and Lat/T-FDC, respectively, were similar to those after instillation of mono-preparations of tafluprost and latanoprost, respectively. The cytotoxic effect of Taf/T-FDC to the human corneal epithelial cells was significantly lower than that of Lat/T-FDC at all evaluated time points in both undiluted and 10-fold diluted FDCs.. Taf/T-FDC provides increased IOP-lowering effect duration and lower potential ocular surface toxicity than Lat/T-FDC.

Topics: Animals; Antihypertensive Agents; Area Under Curve; Cell Line; Chromatography, Liquid; Disease Models, Animal; Drug Combinations; Female; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Macaca fascicularis; Male; Metabolic Clearance Rate; Ocular Hypertension; Prostaglandins F; Prostaglandins F, Synthetic; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Time Factors; Timolol; Treatment Outcome

To investigate the association between patterns of eye drop prescription and medication usage in patients with glaucoma.. Sixty-seven Japanese patients with glaucoma who were prescribed topical antiglaucoma medications including a prostaglandin analogue bilaterally for >6 months at Nayoro City General Hospital, Nayoro, Japan, were included in the study. A self-administered, 5-item patient questionnaire was administered to determine how patients routinely use medications, including the method of eye drop administration, number of eye drops per instillation, accuracy of eye drop placement, weekly frequency of eye drop application, and their awareness of local side effects. The number of prostaglandin analogue bottles prescribed monthly was compared in each factor.. The mean patient age was 74.4±10.0 years (range, 52 to 95 y; 39 women, 28 men). The mean duration of glaucoma treatment was 4.2±3.2 years (range, 0.7 to 10.6 y). Patients who placed the eye drops outside the eye were prescribed significantly more bottles monthly (P=0.008). The other factors had no significant effect on the number of bottles prescribed monthly.. Patients with glaucoma who used eye drops incorrectly were routinely prescribed additional bottles of eye drops. Ophthalmologists should determine whether patients who request an unusual number of eye drops are using the eye drops correctly.

Topics: Administration, Topical; Aged; Aged, 80 and over; Antihypertensive Agents; Cloprostenol; Drug Prescriptions; Female; Glaucoma; Humans; Intraocular Pressure; Japan; Latanoprost; Male; Medication Adherence; Middle Aged; Ophthalmic Solutions; Prostaglandins F; Prostaglandins F, Synthetic; Surveys and Questionnaires; Travoprost

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).. 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.. 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).. 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.

Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Asian People; Benzalkonium Compounds; Female; Glaucoma; Humans; Intraocular Pressure; Keratitis; Male; Middle Aged; Ocular Hypertension; Preservatives, Pharmaceutical; Prospective Studies; Prostaglandins F; Tonometry, Ocular

To assess the usefulness of 0.0015% tafluprost and 0.5% timolol fixed-dose combination (TT-FDC) for glaucoma, the ocular hypotensive effect of TT-FDC and concentration of tafluprost and timolol in the aqueous humor were compared with those of the concomitant administration of 0.0015% tafluprost and 0.5% timolol with or without an appropriate administration interval.. The ocular hypotensive effect was assessed by intraocular pressure (IOP) measurement in cynomolgus monkeys. Drug penetration into the aqueous humor was estimated by the concentrations of tafluprost acid (active metabolic form of tafluprost) and timolol, which were measured using liquid chromatography-tandem mass spectrometry after administration of tafluprost and timolol to Sprague Dawley rats.. The ocular hypotensive effect of TT-FDC was equivalent to that of the concomitant administration of timolol and tafluprost at a more than 5-min interval in monkeys. However, the ocular hypotensive effect of the concomitant administration of timolol and tafluprost without an interval (-2.8 ± 0.2 mmHg at peak IOP reduction) was significantly weaker compared with TT-FDC (-4.3 ± 0.5 mmHg at peak IOP reduction, P = 0.008 vs. concomitant administration of timolol and tafluprost) in monkeys. The aqueous humor concentration of the second administered drug (tafluprost) was not affected by the dosing conditions, whereas the concentration of the first instilled drug (timolol) without the interval was lower than that with a 5-min interval (1,200 ng · h/mL vs. 1,890 ng · h/mL in AUC0-4) in rats.. TT-FDC demonstrates a clear benefit by preventing efficacy loss without an appropriate interval in experimental animal models.

Topics: Administration, Ophthalmic; Animals; Antihypertensive Agents; Aqueous Humor; Chromatography, Liquid; Disease Models, Animal; Drug Combinations; Female; Glaucoma; Intraocular Pressure; Macaca fascicularis; Male; Ocular Hypertension; Prostaglandins F; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Timolol

This study investigated the intraocular pressure (IOP)-lowering effects and safety of tafluprost ophthalmic solution 0.0015% in actual clinical practice.. We started a mandatory prospective 2-year observational study, which collected IOP, conjunctival hyperemia score, corneal staining score, and adverse event data from glaucoma and ocular hypertension (OH) patients not previously treated with tafluprost at 2, 12, and 24 months. This report analyzes the 2-month findings.. Of the 4,180 patients from 553 medical institutions in Japan, most patients had primary open-angle glaucoma (POAG, 38.1%) or normal-tension glaucoma (NTG, 44.2%). After 2 months of tafluprost administration, IOP was significantly reduced by 4.3 ± 5.2 mmHg in POAG, 2.4 ± 2.5 mmHg in NTG, 3.6 ± 5.3 mmHg in primary angle-closure glaucoma, 5.6 ± 7.1 mmHg in other types of glaucoma, and 5.3 ± 4.8 mmHg in OH. IOP was significantly reduced by 4.3 ± 4.0 mmHg in the naïve monotherapy group, 1.9 ± 3.5 mmHg in switching from prior treatment, and 3.7 ± 4.1 mmHg in the add-on therapy group. Among patients switched, the prostaglandin analog (PGA) latanoprost was the previous predominant drug (57.4%), followed by travoprost (13.8%). Significant IOP reductions were observed by 1.5 ± 3.4 mmHg in switching from latanoprost and 1.3 ± 3.7 mmHg in switching from travoprost. The conjunctival hyperemia score peaked at 1 month in the naïve monotherapy and add-on therapy groups, whereas it was significantly decreased in patients switched from another PGA. The corneal staining score showed no particular changes. Incidence of adverse drug reaction (ADR) was 7.70 % (322/4,180 patients), and all major ADRs involved the eyes or skin around the eyes.. Tafluprost showed significant IOP-lowering effects without any safety concerns in patients with various types of glaucoma and OH in daily clinical practice and tafluprost is highly effective in any therapeutic patterns.

Topics: Aged; Conjunctival Diseases; Female; Glaucoma; Humans; Intraocular Pressure; Japan; Male; Middle Aged; Ocular Hypertension; Ophthalmic Solutions; Product Surveillance, Postmarketing; Prospective Studies; Prostaglandins F; Tonometry, Ocular; Treatment Outcome

Five new drugs that are used for medical problems often experienced by the elderly have been selected for consideration in this review. The uses and most important properties of these agents are considered, and a rating for each new drug is determined. The rating is based on a comparison of the new drug with related drugs already marketed. Advantages, disadvantages, and other important information regarding the new drug are identified and used as the basis for determining the rating.

Topics: Acetanilides; Aged; Bronchodilator Agents; Constipation; Drug Approval; Glaucoma; Humans; Peptides; Prostaglandins F; Thiazoles; United States; Urinary Bladder, Overactive

Topics: Administration, Ophthalmic; Glaucoma; Humans; Prostaglandins F

The aim of this study was to evaluate the safety of preservative-free tafluprost in newly diagnosed patients and to confirm its efficacy in lowering intraocular pressure (IOP).. Naïve patients were submitted to an ophthalmic examination, including ocular surface status and quality of life evaluation. All examinations were performed at baseline and after 1 and 6 months.. 28 patients were enrolled and treated with tafluprost, once a day, in the evening. TF-BUT changed from 9 (interquartile range (IQR) 6 - 11) s at baseline to 10 (IQR 7 - 10) s at 1 month (p = 0.106) and 9 (IQR 6 - 12) s at 6 months (p = 0.003). No eye developed corneal staining. Quality of life was (median (IQR)) 91.6 (79.2 - 95.8) at baseline and 95.8 (66.7 - 100) at 6 months (p = 0.62). Only a few adverse events occurred during the follow-up period (three patients experienced ocular burning and one developed redness). The mean IOP reduction was 5.5 mm Hg (95% CI 3.8 - 7.2). The median (IQR) baseline IOP was 18.7 (15 - 23.7) mm Hg; 14 (13 - 16) mm Hg and 16 (14 - 16) mm Hg (p < 0.0001) after 1 and 6 months, respectively.. No patient developed ocular surface disease and quality of life perception was preserved. Preservative-free tafluprost is therefore an effective drug that is safe for the ocular surface after 6 months of daily therapy.

Topics: Aged; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prostaglandins F; Quality of Life; Single-Blind Method

The aim of the study was to evaluate the efficacy, safety and local tolerability of preservative-free tafluprost 0.0015% (Taflotan®) in patients with glaucoma and ocular hypertension.. Multicentric, prospective observation study was performed in the Czech Republic from October 2010 to April 2011. A total of 78 centers participated and 754 patients were included. After the doctors decision to start the treatment with Taflotan®, the patients demographic data, previous treatment, intraocular pressure and the reason for switching the medication were recorded. At the follow-up visit after 6-12 weeks, the intraocular pressure, local tolerability (a 5-level scale), the patients and doctors satisfaction (a 4-level scale), and the patients preference were recorded.. Altogether, data of 496 patients were evaluated. The majority of them were women (64.9 %). The patients mean age was 58.5 years. The most common diagnosis was primary open angle glaucoma (79.2 %), followed by ocular hypertension (7.3 %), normal tension glaucoma (4.2 %), and pseudoexfoliation glaucoma (3.6 %). In 140 patients, tafluprost 0.0015% was the first antiglaucomatous medication started, 261 patients switched from another monotherapy, and 95 patients were treated with fixed- or nonfixed combinations before starting tafluprost 0.0015%. The most common reason for switching to Taflotan® was local intolerability to the current antiglaucomatous therapy (most often irritation of the eye and hyperemia). The intraocular pressure decreased significantly from 19.9 ± 4.5 mm Hg to 16.3 ± 3.0 mm Hg (p < 0.001). The subjective tolerability of the antiglaucomatous therapy improved rapidly, with 57.4 % of patients rating the tolerability of Taflotan® as "very good" and 34.5 % as "good". In addition, 94.4 % of patients and 96.0 % of ophthalmologists were "very satisfied" or "satisfied" with the treatment. At the final visit, 79.8 % of patients preferred Taflotan® to the previous treatment.. Taflotan® significantly decreased the intraocular pressure. It was well tolerated even in patients with previous intolerability to another antiglaucomatous therapy, including prostaglandins. The patients and ophthalmologists satisfaction with Taflotan® was high.

Topics: Adolescent; Adult; Aged; Child; Female; Glaucoma; Humans; Intraocular Pressure; Male; Middle Aged; Ocular Hypertension; Prostaglandins F; Prostaglandins, Synthetic; Young Adult

To investigate the metabolism of a new antiglaucoma difluoroprostaglandin, tafluprost, in ocular tissues and evaluate the distribution of the parent drug and its metabolites in ocular and systemic tissues after a single ocular administration to cynomolgus monkeys (Macaca fascicularis).. A single dose of an ophthalmic solution containing 0.0005%, 0.005%, or 0.05% [(3)H]tafluprost was topically instilled (20 μL/eye) to male and/or female cynomolgus monkeys to study tissue distribution and metabolism. Blood, ocular/systemic tissues, or excreta were collected until 24 h after dosing. The radioactivity of each sample was measured by liquid scintillation counting, and metabolites were characterized by liquid chromatography-mass spectrometry. The major metabolites found in ocular tissues were intracameraly administered to monkeys to confirm their effect on intraocular pressure (IOP).. Soon after dosing, high concentrations of drug-related radioactivity were observed in the cornea and bulbar/palpebral conjunctiva, followed by the iris, sclera, choroid with retinal pigmented epithelium, and aqueous humor. The highest concentration of radioactivity concentrations occurred in the anterior and posterior ocular tissues within 2 h after dosing. The radioactivity measured in the plasma and ocular tissues was proportional to the dose administered. The major metabolites of tafluprost identified in the ocular tissues were tafluprost acid and 1,2-dinor- and 1,2,3,4-tetaranor-tafluprost acid. The estimated concentration of tafluprost acid in the aqueous humor and ciliary body was enough to stimulate prostanoid FP-receptors. After hydrolysis to the acid form, the primary metabolic pathway of tafluprost was via β-oxidation and, subsequently, oxidation. No metabolic reactions to the 15-carbon position were observed. Tafluprost acid was shown to significantly lower the IOP, whereas 1,2-dinor- and 1,2,3,4-tetaranor-tafluprost acid did not.. Topically administered [(3)H]tafluprost was well absorbed into the ocular and systemic tissues of the primary nonclinical species, monkey. The amount of the pharmacologically active form, that is, tafluprost acid, was high enough to occupy the target FP receptors at the site of action. The pharmacokinetic and metabolic properties of this difluorinated prostaglandin in primates are believed to result in clinical benefits of a long-term IOP-lowering effect.

Topics: Absorption; Acetylation; Animals; Biotransformation; Dose-Response Relationship, Drug; Eye; Feces; Female; Glaucoma; Half-Life; Hydrolysis; Injections, Intraocular; Intraocular Pressure; Macaca fascicularis; Male; Ophthalmic Solutions; Prostaglandins F; Radioactive Tracers; Tissue Distribution; Urine

To compare the effects of a topical alpha agonist (vasoconstrictor) and a prostaglandin receptor (FP) agonist (vasodilator) on circulation in the optic nerve head (ONH) in experimental glaucomatous and normal eyes of monkeys.. Tissue blood velocity in the ONH (NB(ONH)) was determined using the laser speckle method in both eyes of eight normal cynomolgus monkeys under systemic anesthesia for 180 minutes after bilateral instillation of 5% phenylephrine. The effect of 0.0015% tafluprost, a potent FP agonist, was also studied after single and once-daily 7-day instillations. Measurements were repeated in both eyes of the eight monkeys after establishment of unilateral laser-induced glaucoma.. NB(ONH) decreased significantly in both eyes of normal monkeys 30 to 120 minutes after phenylephrine instillation by a maximum of 9% to 11% (P < 0.05) without significant change in intraocular pressure (IOP). A similar decrease in NB(ONH) was found in non-laser-treated eyes in glaucomatous monkeys despite the absence of significant changes in contralateral experimental glaucomatous eyes. NB(ONH) increased by 16% (P < 0.05) 60 minutes after a single instillation and also after 7-day repeated instillations of tafluprost in both eyes of normal monkeys. A similar increase in NB(ONH) occurred in both eyes after the establishment of unilateral glaucoma but was completely abolished by 5 mg/kg indomethacin injected intravenously 15 minutes after tafluprost instillation. Tafluprost significantly reduced IOP only in experimental glaucomatous eyes by 34%.. The ONH vasculature in glaucomatous and normal eyes reacts differently to an exogenous alpha agonist, whereas it reacts similarly to an FP agonist.

Topics: Administration, Topical; Adrenergic alpha-Agonists; Animals; Blood Flow Velocity; Disease Models, Animal; Female; Glaucoma; Intraocular Pressure; Laser-Doppler Flowmetry; Macaca fascicularis; Optic Disk; Phenylephrine; Prostaglandins F; Receptors, Prostaglandin; Regional Blood Flow; Tonometry, Ocular

INTRODUCTION|: To investigate potentially adverse effects of different topical glaucoma medications and preservatives on cultured ocular epithelial cells. METHODS|: Confluent cultures of human corneal (10.014 pRSV-T) and conjunctival cells (1-5c-4) were assayed with 100 μL of different glaucoma medications for 25 minutes at 37°C and 5% CO₂. We also tested the preservative sofZia® (Alcon Laboratories, Fort Worth, TX, USA), as well as a range of concentrations of the preservative benzalkonium chloride (BAK; 0.001% to 0.050%). Balanced salt solution was used as the "live" control and a solution containing 70% methanol and 0.2% saponin was used as a "dead" control. The LIVE/DEAD viability/cytotoxicity kit (Invitrogen, Carlsbad, CA, USA) was used to determine the percentage of dead and live cells via ethidium homodimer and calcein fluorescence, respectively. RESULTS|: The toxicity of the prostaglandin analogs latanoprost, tafluprost and travoprost preserved with BAK was similar to the toxicity observed in their respective BAK concentrations. The prostaglandin analog travoprost (0.004%) preserved with the oxidizing preservative sofZia had much greater corneal and conjunctival cell survival than travoprost preserved with BAK. Travoprost (0.004%) containing polyquad also performed statistically better than its BAK-preserved formulation. CONCLUSION|: Ocular surface side effects have previously been demonstrated with chronic, long-term exposure to intraocular pressure-lowering medications containing the common preservative BAK. BAK alone has significant in-vitro cytotoxicity to cultured ocular epithelial cells. Substitution of BAK with polyquad or sofZia resulted in significantly higher percentages of live conjunctival and corneal cells. Further studies are needed to understand the- clinical implications of these findings.

Topics: Administration, Topical; Antihypertensive Agents; Benzalkonium Compounds; Cell Survival; Cells, Cultured; Cloprostenol; Conjunctiva; Dose-Response Relationship, Drug; Epithelium, Corneal; Glaucoma; Humans; Latanoprost; Ophthalmic Solutions; Polymers; Preservatives, Pharmaceutical; Prostaglandins F; Prostaglandins F, Synthetic; Travoprost

The disposition and metabolism of tafluprost, an ester prodrug of the 15,15-difluoro-prostaglandin F(2alpha) antiglaucoma agent, have been studied in rats after ocular administration. Radioactivity was absorbed very rapidly into the eye and systemic circulation after a single ocular dose of 0.005% [(3)H]tafluprost ophthalmic solution, with maximum levels in plasma and most eye tissues occurring within 15 min. The absorption ratio of radioactivity was approximately 75%, suggesting the high availability of ocular administration of tafluprost. Approximately 10% of the dose was present in cornea at this time, and radioactivity concentrations in this tissue exceeded those in aqueous humor and iris/ciliary body throughout the 24-h study period. After repeated daily ocular doses, radioactivity levels remained greatest in cornea, followed by iris/ciliary body that replaced aqueous humor as the eye tissue containing the second highest radioactivity concentration. In female rats, radioactivity was excreted equally between urine and feces after a single ocular dose, whereas in male rats more was excreted in feces, reflecting the greater biliary excretion in males rats (50% dose) compared with females rats (33% dose). Tafluprost was extensively metabolized in the rat, such that intact prodrug was not detected in plasma, tissues, or excreta by radio-high-performance liquid chromatography. On the other hand, the active moiety, tafluprost acid, was the only noteworthy radioactive component in cornea, aqueous humor, and iris/ciliary body for at least 8 h after the ocular dose, and it was also a major plasma metabolite in early time points. The gender differences in conjugation reactions resulted in the differences in the excretion.

Topics: Administration, Topical; Animals; Biological Availability; Biotransformation; Chromatography, Liquid; Dogs; Eye; Feces; Female; Glaucoma; Glucuronides; Hepatocytes; Humans; Hydrolysis; Injections, Intravenous; Lactation; Macaca fascicularis; Male; Metabolomics; Milk; Ophthalmic Solutions; Placenta; Pregnancy; Prodrugs; Prostaglandins F; Rats; Rats, Sprague-Dawley; Sex Factors; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Tissue Distribution; Tritium

Topics: Antihypertensive Agents; Glaucoma; Humans; Intraocular Pressure; Prostaglandins F

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

To evaluate the pharmacological characteristics of AFP-168 (tafluprost), a new prostaglandin (PG) F(2alpha) derivative, we examined its receptor-binding affinities, intraocular pressure (IOP)-lowering effect, effects on aqueous humor dynamics, and stimulating effect on melanogenesis. The receptor-binding profile for AFP-172, a carboxylic acid of AFP-168, was determined by measuring muscle contractions in an organ bath, inhibition of platelet aggregation, and competitive binding of a radio-labelled ligand. For the IOP-measurement study, ocular normotensive and laser-induced ocular hypertensive cynomolgus monkeys were used, and IOP was measured using a pneumatonograph. For the studies of aqueous humor dynamics, IOP (Goldmann applanation tonometry), fluorophotometry, two-level constant pressure perfusion, and isotope dilution and accumulation techniques were used in ocular normotensive monkeys. The melanin contents in the medium and in the cell bodies of cultured B16-F0 melanoma cells were measured. The affinity for the FP receptor shown by AFP-172 (Ki : 0.4 nm) was 12 times that of PhXA85 ( Ki : 4.7 nm), a carboxylic acid of latanoprost. A single application of AFP-168 at 0.0025% significantly lowered IOP in both ocular normotensive and hypertensive monkeys (3.1 and 11.8 mmHg, respectively, p < 0.01) and latanoprost at 0.005% significantly lowered IOP (2.1 mmHg, p < 0.01 and 9.5 mmHg, p = 0.059 respectively). Once daily instillation of AFP-168 at 0.001, 0.0025, or 0.005% for 5 days in normotensive monkeys significantly reduced IOP not only for a few hours, but also at the drug-trough time 24hr after application. Latanoprost at 0.005% also reduced IOP, but not at the drug-trough time. AFP-168 decreased IOP mainly by increasing uveoscleral outflow by 65% (p < 0.05) and, as sometimes seen with other prostanoids, also increased total outflow facility (33% increase, p < 0.05). In cultured B16-F0 melanoma cells, AFP-172 (100 microM) did not stimulate melanogenesis, but PhXA85 (100 microM) did. These findings indicate that AFP-168 has a high affinity for the prostanoid FP receptor, has potent IOP-lowering effects in both ocular normotensive and hypertensive monkeys that exceed those of latanoprost, and has less stimulating effect on melanogenesis in melanoma cells.

Topics: Animals; Antihypertensive Agents; Aqueous Humor; Binding, Competitive; Cell Line, Tumor; Eye Color; Glaucoma; Guinea Pigs; Intraocular Pressure; Latanoprost; Macaca fascicularis; Male; Melanosis; Prostaglandins F; Prostaglandins F, Synthetic; Protein Binding; Receptors, Prostaglandin