A 6-Month Study Comparing Efficacy, Safety, and Tolerability of the Preservative-free Fixed Combination of Tafluprost 0.0015% and Timolol 0.5% versus Each of Its Individual Preservative-Free Components

The efficacy, safety and tolerability of the preservative-free (PF) fixed combination (FC) of tafluprost 0.0015\% and timolol 0.5\% (once daily) were compared to those of the individual components (PF tafluprost 0.0015\% once daily and PF timolol 0.5\% twice daily) in patients with open-angle glaucoma or ocular hypertension inadequately controlled on prior timolol or prostaglandin monotherapy for 6\ua0months.A stratified, double-masked, randomized, multicenter phase III study was conducted. A total of 189 prior timolol users were randomized within the timolol stratum (TS) to receive either FC (n\ua0=\ua095) or timolol 0.5\% (TIM; n\ua0=\ua094). Furthermore, a total of 375 prior prostaglandin analog (PGA) users were randomized within the prostaglandin stratum (PS) to receive either FC (n\ua0=\ua0188) or tafluprost 0.0015\% (TAF; n\ua0=\ua0187). To be eligible for participation in the study, the patients were required to have an intraocular pressure (IOP) of\ua0 6522\ua0mmHg when on timolol (TIM) or of\ua0 6520\ua0mmHg when on PGA in either treated eye at the screening and end-of-run-in visits. In addition to these, the study included visits at baseline, 2 and 6\ua0weeks, 3 and 6\ua0months and at a post-study visit. IOP was measured at 8 a.m., 10 a.m., 4 p.m., and 8 p.m.In the TS, a significant reduction from baseline IOP was seen with FC and TIM throughout the study. Average diurnal IOP change from baseline at month 3 was -8.55\ua0mmHg (32\%) for FC and -7.35\ua0mmHg (28\%) for TIM. The model-based treatment difference (FC-TIM) was -0.885\ua0mmHg [95\% confidence interval (CI) -1.745 to -0.024; p\ua0=\ua00.044] demonstrating the superiority of FC over TIM. In the PS, a significant reduction in IOP was seen with both FC and TAF throughout the study. The average diurnal IOP change from baseline at month 3 was -8.61\ua0mmHg (33\%) for FC and -7.23\ua0mmHg (28\%) for TAF. The model-based treatment difference (FC-TAF) was -1.516\ua0mmHg (95\% CI -2.044 to -0.988; p\ua0<\ua00.001) demonstrating the superiority of FC over TAF. In the TS, related ocular adverse events (AEs) were more frequent for patients treated with FC compared to TIM (16.8\% versus 6.4\%), whereas related non-ocular AEs were more frequent with TIM compared to FC (2.1\% versus 0.0\%). In the PS, AEs were similarly distributed between FC and TAF. The frequency of conjunctival hyperemia of FC was low (6.4\%).The preservative-free fixed combination of tafluprost and timolol provided a substantial and significant IOP reduction in both strata. The IOP reduction was superior to both tafluprost 0.0015\% and timolol 0.5\% when given as monotherapies. Overall, the study treatments were safe and well tolerated.Santen Oy, Tampere, Finland

Assessing the in vivo toxicity of titanium dioxide nanoparticles in Schmidtea mediterranea:uptake pathways and (neuro)developmental outcomes

Titanium dioxide nanoparticles (TiO 2-NPs) in aquatic environments, originating from urban run-off, product use and post-consumer degradation, interact with aquatic organisms through water and sediments. Thorough toxicity assessment requires comprehensive data across all ecosystem compartments especially the benthic zone, which is currently lacking. Moreover, a proper physicochemical characterization of the particles is needed before and during toxicity assessment. In the present work, we used the planarian Schmidtea mediterranea to investigate the effects of TiO 2-NPs (5 mg/L and 50 mg/L). Planarians are benthic organisms that play an important role in the food chain as predators. Our study integrated particle characterization with toxicokinetic and toxicodynamic parameters and showed that the uptake of TiO 2-NPs of 21 nm occurred through the epidermis and intestine. Epidermal irritation and mucus production occurred immediately after exposure, and TiO 2-NPs induced stronger effects in regenerating organisms. More specifically, TiO 2-NPs interfered with neuroregeneration, inducing behavioral effects. A delay in the formation of the anterior commissure between the two brain lobes after seven and nine days of exposure to 50 mg/L was observed, probably as a result of a decrease in stem cell proliferation. Our findings underscore the need to incorporate multiple exposure routes in toxicity screenings. Additionally, we highlight the vulnerability of developing organisms and recommend their inclusion in future risk assessment strategies. </p