BACKGROUND: Dry eye is a condition related to long-term topical eye therapy. We wish to evaluate the effectiveness and tolerability of preservative free prostaglandin drops versus benzalkonium chloride containing prostaglandin drops in the treatment of glaucoma.
METHODS: Patients undergoing prostaglandin monotherapy underwent a washout period of at least 1 month after which baseline measurements of dry eye severity were taken. Patients were randomised to receive either 0.0015% tafluprost drops or 0.005% latanoprost preserved with 0.02% benzalkonium chloride. Repeat measurements were taken after a 2-month interval.
RESULTS: Thirty-five patients completed randomised treatment. No significant difference between groups was found in objective and subjective measurements of dry eye severity. No significant difference was found in measurement of treatment effectiveness.
CONCLUSIONS: Preservative-free and benzalkonium chloride-containing drops were found to be equally effective in lowering IOP with no significant difference in either subjective or objective measurements of dry eye severity.

OBJECTIVE: To investigate whether Tafluprost could promote optic nerve regeneration in mice after optic nerve crush (ONC) and determine the underlying molecular mechanism.
METHODS: Tafluprost was injected into the vitreous body immediately after ONC. The level of Zn2+ in the inner plexiform layer (IPL) of the retina was stained using autometallography (AMG). The number of survival retinal ganglion cells (RGCs) was determined via dual staining with RGC markers Tuj1 and RBPMS. Individual axons that regenerated to 0.25, 0.5, 0.75 and 1 mm were manually counted in the whole-mount optic nerve labeled by cholera toxin B fragment (CTB). Immunofluorescence and Western blot were performed to detect protein expression levels. Pattern electroretinogram was used to evaluate RGCs function.
RESULTS: Tafluprost promoted RGC survival in a dose-dependent manner with an optimal concentration of 1 μM. Tafluprost significantly decreased ZnT-3 expression and Zn2+ accumulation in the IPL of retina. Tafluprost stimulated intense axonal regeneration and maintained RGCs function compared to control. Mechanistically, Tafluprost and Zn2+ elimination treatment (TPEN or ZnT-3 deletion) can activate the mTOR pathway with an improved percentage of pS6+ RGCs in the retina. However, rapamycin, a specific inhibitor of the mTOR1, inhibited the activation of the mTOR pathway and abolished the regenerative effect mediated by Tafluprost. Tafluprost also inhibited the upregulation of p62, LC3 and Beclin-1, attenuated the overactivation of microglia/macrophages and downregulated the expression of TNFα and IL-1β.
CONCLUSIONS: Our results suggest that Tafluprost promoted axon regeneration via regulation of the Zn2+-mTOR pathway, and provide novel research directions for glaucomatous optic nerve injury mechanisms.

Ocular hypertension is one of the most underdiagnosed ocular abnormalities among guinea pigs around the world.
The current study investigates the effect of 0.0015% preservative-free tafluprost ophthalmic solution (Zioptan) on the intraocular pressure of 16 healthy male guinea pigs (Cavia porcellus) under different light/darkness regimes.
All guinea pigs received a single drop of tafluprost at 5:30 in the right eye, whereas the contralateral eyes served as control to receive a placebo. Then, the animals were randomly divided into two groups; group A was exposed to light, whereas group B was placed in darkness from 5:30 to 18:00. Rebound tonometry (TonoVet) was instrumented to measure IOP values at 5:30 (baseline), 6:00, 7:00, 8:00, 9:00 and then every 3 h until 18:00.
The maximum IOP reduction associated with tafluprost was observed at 6:00 by -1.4 ± 1.1 mmHg (p-value = 0.026) and -2.5 ± 1.2 mmHg (p-value = 0.011) in group A and B, respectively (repeated measure ANOVA test). There was a significant difference between the mean right and left eye IOP values in both groups at 5:30, 6:00, 7:00 and 8:00 (p-value <0.05), which was greater in amount in group B compared to group A due to the effect of darkness on IOP reduction.
It is suggested that the variations of IOP in different light/dark conditions be taken into consideration when applying ocular hypotensive agents on guinea pigs\' eyes.

OBJECTIVE: To investigate the treatment pattern and safety of tafluprost for glaucoma and ocular hypertension (OH) in clinical practice in China.
METHODS: This post-marketing observational study included patients who received tafluprost to lower intraocular pressure (IOP) within 30d between September 2017 and March 2020 in 20 hospitals in China. Adverse drug reactions (ADRs) during tafluprost treatment and within 30d after the treatment were collected.
RESULTS: A total of 2544 patients were included in this study, of them 58.5% (1488/2544) had primary open angle glaucoma (POAG), 21.9% (556/2544) had OH and 19.7% (500/2544) used tafluprost for other reasons. Of 359 ADRs occurred in 10.1% (258/2544) patients, and no serious adverse event occurred. The most common ADR was conjunctival hyperemia (128 ADRs in 124 patients, 4.9%). Totally 1670 participants (65.6%) combined tafluprost with carbonic anhydrase inhibitors (CAIs; 37.1%, 620/1670), sympathomimetics (33.5%, 559/1670), β-blockers (33.2%, 555/1670), other prostaglandin analogs (PGAs; 15.6%, 260/1670) and other eye drops (15.1%, 253/1670). The highest incidence of conjunctival hyperemia was noted in patients who received tafluprost in combination with other PGAs (23 ADRs in 23 patients, 8.8%, 23/260) and the lowest was in combination with CAIs (16 ADRs in 16 patients, 2.6%, 16/620). Tafluprost was applied in primary angle-closure glaucoma (41.6%, 208/500), after glaucoma surgery (17.8%, 89/500) and after non-glaucoma surgery (15.8%, 79/500).
CONCLUSIONS: Tafluprost is safe for POAG and OH, and tolerable when combined with other eye drops and under various clinical circumstances.

To investigate whether prostaglandin analogue (PGA) eyedrops have a significant effect on central corneal thickness (CCT), we conducted a systematic search of literature published from 2000 to 2021. Among the studies conducted on topical PGA therapy in open-angle glaucoma or ocular hypertension patients over 18 years old, prospective studies with CCT change as an outcome were included. A single-arm meta-analysis was conducted to assess the overall effect on CCT, and subgroup analysis according to exposure time of PGA eyedrops was also performed. We counted the number of articles that reported on severe events (CCT reduction of 25 μm or more) and obtained their proportion. The methodological quality was assessed by the McHarm tool. Twenty-two reports of prospective studies were selected. The results of the single-arm meta-analysis showed very high heterogeneity. Still, in subgroup analysis, when PGA was used for more than 6 months, heterogeneity was low, and a significant decrease in CCT was observed. Severe events were reported in two reports and occurred in 3.8% to 14.8% of participants. PGA eyedrop use may cause a clinically significant CCT decrease, requiring CCT follow-up.

Increasing evidence indicates that improving ocular blood flow (OBF) can be a therapeutic direction for glaucoma therapy. Tafluprost, a prostaglandin analogue which lowers the intraocular pressure (IOP), has been shown to improve OBF in animals and humans. Several animal experiments showed that topical tafluprost significantly increased optic nerve head and retinal blood flow. Clinical trials also showed a beneficial effect of tafluprost on optic nerve head and macula blood flow, and a good ocular pulse amplitude-lowering effect. But, there are still a few conflicting results. Overall, tafluprost seems to have a beneficial effect on OBF, and the positive effect is probably independent from its IOP-lowering effect, which also is expected to improve OBF. Moreover, reducing the intracellular free Ca2+ concentration may be a possible mechanism of tafluprost\'s effect on OBF. More well-designed studies are required to reveal the truth.

UNASSIGNED: Preserved prostaglandin analogs (PGAs) have been linked to ocular surface disease (OSD). While the benefits of preservative-low (PL) or -free (PF) Tafluprost (Santen Inc., Japan) were reported in real-world studies in Western countries, this is the first study in Asia to assess the effectiveness and safety of switching from preserved PGA to PL or PF-Tafluprost.
UNASSIGNED: We conducted a meta-analysis on studies that included adults (>18 years of age) with a Corneal Fluorescein Staining Score (CFS) >1. These individuals had switched to PL or PF-tafluprost after using a preserved PGA therapy for at least 3 months for glaucoma and were identified from Santen\'s tafluprost study database. A total of six studies from South Korea, Philippines, Malaysia, Singapore, Thailand, Taiwan were pooled for analysis.
UNASSIGNED: An intraocular pressure (IOP) reduction of 5.9% (0.91 mmHg) was seen in 265 patients. However, this result was not statistically significant (95% CI: -3.64, 1.81; Figure 1). Among 132 patients, a 47.9% reduction in the CFS (95% CI: -3.65, -1.91) was seen. Tear film break-up (n=183) significantly increased by 1.06 seconds (95% CI: 0.65, 1.47). In 88 patients, the bulbar conjunctiva score decreased by -0.46 (95% CI: -0.81, -0.10) and palpebral conjunctiva score decreased by -0.42 (95% CI: -0.67-0.17). One or more new adverse reactions were reported in 3% of the individuals after switching.
UNASSIGNED: Tafluprost IOP reduction is comparable to other PGAs, with significant improvements in the ocular surface and minimal adverse reactions which were already previously reported.

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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%).
CONCLUSIONS: 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.

A new, simple and selective HPLC method was implemented for the simultaneous estimation of tafluprost (TFL) and timolol (TIM) in their new anti-glaucoma combination in the challengeable ratio of 3 and 1000 for TFL and TIM, respectively. Separation was achieved using a BDS Hypersil phenyl column and a mobile phase made up of acetonitrile: 0.015 M phosphate buffer (50:50 v/v, pH 3.5) delivered at 1 mL min-1 and the separation was completed in less than 6 min. UV detection was time programmed at 220 nm for the first 4.5 min and later at 254 nm. Mebeverine (MEB) was used as an internal standard (I.S.). The linearity was observed in the ranges of 0.6-45 and 50-2000 µg mL-1 with limits of detection (LOD) of 0.18, 16.48 µg mL-1 and limits of quantification (LOQ) of 0.55, 49.94 µg mL-1 for TFL and TIM, respectively. The method satisfied International Council for Harmonization (ICH) validation guidelines. The study was extended to the estimation of the studied drugs in their co-formulated eye drops as well as in their single dosage forms with acceptable percentage recoveries. Moreover, Green Analytical Procedure Index (GAPI) and analytical Eco-scale were investigated to confirm the greenness of the proposed HPLC method.

The identification of similar three-dimensional (3D) amino acid patterns among different proteins might be helpful to explain the polypharmacological profile of many currently used drugs. Also, it would be a reasonable first step for the design of novel multitarget compounds. Most of the current computational tools employed for this aim are limited to the comparisons among known binding sites, and do not consider several additional important 3D patterns such as allosteric sites or other conserved motifs. In the present work, we introduce Geomfinder2.0, which is a new and improved version of our previously described algorithm for the deep exploration and discovery of similar and druggable 3D patterns. As compared with the original version, substantial improvements that have been incorporated to our software allow: (i) to compare quaternary structures, (ii) to deal with a list of pairs of structures, (iii) to know how druggable is the zone where similar 3D patterns are detected and (iv) to significantly reduce the execution time. Thus, the new algorithm achieves up to 353x speedup as compared to the previous sequential version, allowing the exploration of a significant number of quaternary structures in a reasonable time. In order to illustrate the potential of the updated Geomfinder version, we show a case of use in which similar 3D patterns were detected in the cardiac ions channels NaV1.5 and TASK-1. These channels are quite different in terms of structure, sequence and function and both have been regarded as important targets for drugs aimed at treating atrial fibrillation. Finally, we describe the in vitro effects of tafluprost (a drug currently used to treat glaucoma, which was identified as a novel putative ligand of NaV1.5 and TASK-1) upon both ion channels\' activity and discuss its possible repositioning as a novel antiarrhythmic drug.