Search

The interest of polymer-surfactant systems has undergone a spectacular development in the last thirty years due to their complex behavior and their importance in different industrial sectors. The importance can be mainly associated with the rich phase behavior of these mixtures that confers a wide range of physico-chemical properties to the complexes formed by polymers and surfactants, both in bulk and at the interfaces. This latter aspect is especially relevant because of the use of their mixture for the stabilization of dispersed systems such as foams and emulsions, with an increasing interest in several fields such as cosmetic, food science or fabrication of controlled drug delivery structures. This review presents a comprehensive analysis of different aspects related to the phase behavior of these mixtures and their intriguing behavior after adsorption at the liquid/air interface. A discussion of some physical properties of the bulk is also included. The discussion clearly points out that much more work is needed for obtaining the necessary insights for designing polymer-surfactant mixtures for specific applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

This work addresses the formation and the internal morphology of polyelectrolyte layers obtained by the layer-by-layer method. A multimodal characterization showed the absence of stratification of the films formed by the alternate deposition of poly(diallyldimethylammonium chloride) and poly(sodium 4-styrenesulfonate). Indeed the final organization might be regarded as three-dimensional solid-supported inter-polyelectrolyte films. The growth mechanism of the multilayers, followed using a quartz crystal microbalance, evidences two different growth trends, which show a dependency on the ionic strength due to its influence onto the polymer conformation. The hydration state does not modify the multilayer growth, but it contributes to the total adsorbed mass of the film. The water associated with the polyelectrolyte films leads to their swelling and plastification. The use of X-ray photoelectron spectroscopy has allowed for deeper insights on the internal structure and composition of the polyelectrolyte multilayers.

Systematic study of the mechanisms underlying pathological ocular neovascularization has yielded a wealth of knowledge about pro- and anti-angiogenic factors that modulate diseases such as neovascular age-related macular degeneration. The evidence implicating vascular endothelial growth factor (VEGF) in particular has led to the development of a number of approved anti-VEGF therapies. Additional proangiogenic targets that have emerged as potential mediators of ocular neovascularization include hypoxia-inducible factor-1, angiopoietin-2, platelet-derived growth factor-B and components of the alternative complement pathway. As for VEGF, knowledge of these factors has led to a product pipeline of many more novel agents that are in various stages of clinical development in the setting of ocular neovascularization. These agents are represented by a range of drug classes and, in addition to novel small- and large-molecule VEGF inhibitors, include gene therapies, small interfering RNA agents and tyrosine kinase inhibitors. In addition, combination therapy is beginning to emerge as a strategy to improve the efficacy of individual therapies. Thus, a variety of agents, whether administered alone or as adjunctive therapy with agents targeting VEGF, offer the promise of expanding the range of treatments for ocular neovascular diseases., (© 2016 S. Karger AG, Basel.)

The use of polymer and polymer - surfactant mixtures for designing and developing textile and personal care cosmetic formulations is associated with various physico-chemical aspects, e.g. detergency and conditioning in the case of hair or wool, that determine their correct performances in preserving and improving the appearance and properties of the surface where they are applied. In this work, special attention is paid to the systems combining polycations and negatively charged surfactants. The paper introduces the hair surface and presents a comprehensive review of the adsorption properties of these systems at solid-water interfaces mimicking the negative charge and surface energy of hair. These model surfaces include mixtures of thiols that confer various charge densities to the surface. The kinetics and factors that govern the adsorption are discussed from the angle of those used in shampoos and conditioners developed by the cosmetic industry. Finally, systems able to adsorb onto negatively charged surfaces regardless of the anionic character are presented, opening new ways of depositing conditioning polymers onto keratin substrates such as hair., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The magnetic needle interfacial shear rheometer is a valuable tool for the study of the mechanical properties of thin fluid films or monolayers. However, it is difficult to differentiate the interfacial and subphase contributions to the drag on the needle. In principle, the problem can be addressed by decreasing the needle diameter, which decreases the bulk contribution while the interfacial contribution remains essentially the same. Here we show the results obtained when using a new type of needle, that of magnetic microwires with diameter approximately 10 times thinner than for commercial needles. We show that the lower inertia of the microwires calls for a new calibration procedure. We propose such a new calibration procedure based on the flow field solution around the needle introduced in refs 1 and 2. By measuring thin silicone oil films with well-controlled interfacial viscosities as well as eicosanol (C20) and pentadecanoic acid (PDA, C15) Langmuir monolayers, we show that the new calibration method works well for standard needles as well as for the microwire probes. Moreover, we show that the analysis of the force terms contributing to the force on the needle helps to ascertain whether the measurements obtained are reliable for given surface shear viscosity values. We also show that the microwire probes have at least a 10-fold-lower resolution limit, allowing one to measure interfacial viscosities as low as 10(-7) N·m/s.

Objective: To evaluate the 24-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly or as needed (pro re nata [PRN]) in patients with neovascular age-related macular degeneration (wet AMD)., Design: Twenty-four-month, multicenter, randomized, double-masked, active treatment-controlled phase 3 trial., Participants: Patients (n = 1098) ≥ 50 years of age with treatment-naïve subfoveal wet AMD., Methods: Patients were randomized to receive intravitreal injections of ranibizumab 0.5 mg or 2.0 mg monthly or PRN after 3 monthly loading doses., Main Outcome Measures: The primary efficacy end point was the mean change in best-corrected visual acuity (BCVA) from baseline at month 12. Key secondary end points included mean change in BCVA from baseline at month 24, proportion of patients who gained ≥ 15 letters in BCVA, mean number of ranibizumab injections, and mean change in central foveal thickness from baseline over time by spectral-domain optical coherence tomography. Ocular and systemic safety events also were evaluated through month 24., Results: At month 24, the mean change from baseline in BCVA was (letters) +9.1 (0.5 mg monthly), +7.9 (0.5 mg PRN), +8.0 (2.0 mg monthly), and +7.6 (2.0 mg PRN). The change in mean BCVA from month 12 to 24 was (letters) -1.0, -0.3, -1.2, and -1.0, respectively. The proportion of patients who gained ≥ 15 letters from baseline in BCVA at month 24 was 34.5%, 33.1%, 37.6%, and 34.8%, respectively. The mean number of ranibizumab injections through month 24 was 21.4, 13.3, 21.6, and 11.2, respectively; 5.6 and 4.3 mean injections were required in year 2 in the 0.5 mg and 2.0 mg PRN groups, respectively. The average treatment interval in the 0.5 mg PRN group was 9.9 weeks after 3 monthly loading doses, and 93% of these patients did not require monthly dosing. Ocular and systemic safety profiles over 2 years were similar among all 4 treatment groups and were consistent with previous ranibizumab trials in AMD., Conclusions: At month 24, mean BCVA improvements were clinically meaningful and similar among all 4 ranibizumab treatment groups. The 0.5 mg PRN group achieved a mean gain of 7.9 letters at month 24 with an average of 13.3 injections (5.6 injections in year 2). No new safety events were identified over 24 months., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the incidence of collateral vessel formation and to determine their impact on best-corrected visual acuity and central foveal thickness in patients with branch or central retinal vein occlusion (BRVO, CRVO) receiving 0.3 mg or 0.5 mg of ranibizumab, or sham., Methods: This retrospective analysis was performed in patients with macular edema secondary to retinal vein occlusion who received 6 monthly intravitreal injections of ranibizumab (0.3 mg or 0.5 mg), or sham, followed by 6 months of as-needed treatment. Collateral vessel presence, change from baseline best-corrected visual acuity, and change from baseline central foveal thickness were assessed at baseline and months 3, 6, 9, and 12., Results: At month 12, 19.6% of BRVO patients receiving sham/0.5 mg and 16.7% receiving ranibizumab (0.3 mg and 0.5 mg pooled) manifested collaterals at the disk, whereas 48.2% and 47.2% displayed collaterals within the retina, respectively. In CRVO patients, 57.9% and 59.2% of all groups manifested collaterals on the disk, respectively, whereas 12.1% and 15.1% displayed collaterals within the retina. Mean best-corrected visual acuity gain in ranibizumab-treated BRVO and CRVO patients was similar, irrespective of collaterals within the retina (, Brvo: P > 0.05; CRVO: P > 0.05)., Conclusion: The location of collaterals differed between retinal vein occlusion subtypes and ranibizumab treatment did not affect collateral vessel incidence. The presence of collaterals did not seem to impact best-corrected visual acuity gains at month 12 in both BRVO and CRVO patients receiving ranibizumab, whereas generally greater central foveal thickness reductions were observed with presence of collaterals in BRVO patients.

Objective: To describe the systemic pharmacokinetics of ranibizumab after intravitreal administration in patients with retinal vein occlusion (RVO) or diabetic macular edema (DME)., Design: A population approach of nonlinear mixed-effect pharmacokinetics modeling based on serum concentrations of ranibizumab measured at various times after intravitreal administration., Participants: Patients with RVO (n = 441) and DME (n = 435) from 4 large, randomized, phase 3 clinical trials of monthly ranibizumab intravitreal administration., Methods: A 1-compartment pharmacokinetics model with first-order absorption and elimination rate constants previously developed in patients with age-related macular degeneration (AMD) was fitted separately to RVO and DME data. Population pharmacokinetic parameters and interindividual variability were estimated for each model. Baseline covariates were evaluated for potential effects on systemic pharmacokinetics. Model performance was validated using general diagnostic plots and a visual predictive check., Main Outcome Measures: Ranibizumab disposition was determined in RVO and DME patients and compared with that previously seen in AMD patients., Results: The AMD pharmacokinetics model correctly predicted the measured serum ranibizumab concentration data for RVO and DME patients. Most observed data points were within the simulated 90% confidence interval, indicating that systemic ranibizumab concentrations were comparable among AMD, RVO, and DME patients. No disease-related covariates were identified by the population pharmacokinetics analysis., Conclusions: The systemic pharmacokinetics of ranibizumab were similar among patients with AMD, RVO, or DME. Disease-related differences and patient demographics, measured in this study, did not lead to variability in ocular elimination or in systemic exposure of ranibizumab after intravitreal administration. In all disease processes tested, ranibizumab exits the eye slowly and then is eliminated rapidly from the circulation, thus minimizing systemic exposure., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the effect of suppression of vascular endothelial growth factor (VEGF) by monthly injection of ranibizumab on posterior retinal nonperfusion (RNP) in patients with diabetic macular edema (DME)., Design: Unplanned retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials., Participants: Six hundred sixty-six patients with DME., Methods: An independent reading center measured the area of RNP on fluorescein angiograms obtained in the phase 3 RISE and RIDE trials., Main Outcome Measures: The percentage of patients with no posterior RNP., Results: The percentage of patients with no posterior RNP decreased in the sham group between baseline and month 24, but remained relatively stable in the 2 ranibizumab groups. After month 24, the sham group crossed over to receive monthly injections of ranibizumab 0.5 mg, and the differences between the sham and ranibizumab groups were reduced. The percentage of patients who showed an increase in posterior RNP from baseline increased over time in all 3 groups, but at a faster rate in the sham group, resulting in statistically significant differences at every time point between months 3 (9.6% vs. 18.5%; P = 0.016) and 24 (16.1% vs. 37.6%; P<0.0001) for ranibizumab 0.5 mg versus sham and from months 6 (12.3% vs. 23.0%; P = 0.013) through 24 (15.0% vs. 37.6%; P<0.0001) for ranibizumab 0.3 mg. Initiation of ranibizumab in the sham group at month 24 was followed by reduction in the percentage of patients with an increase in posterior RNP from baseline at months 30 and 36, whereas the 2 ranibizumab groups continued their gradual rise., Conclusions: Just as high VEGF levels contribute to progression of retinal nonperfusion in retinal vein occlusion, the same is true in patients with DME, suggesting that regardless of the underlying disease process, high levels of VEGF can cause closure of retinal vessels. However, our data also suggest that VEGF-induced worsening of retinal perfusion in DME is superimposed on another cause of more gradually worsening perfusion, possibly glucotoxicity. Thus, monthly injections of ranibizumab can slow, but not completely prevent, retinal capillary closure in patients with DME., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To characterize preinjection intraocular pressure (IOP) in eyes receiving monthly ranibizumab versus sham or verteporfin photodynamic therapy (PDT) for age-related macular degeneration (AMD)., Design: Post hoc analysis of IOP data from 2 phase 3 clinical trials, the Minimally Classic/Occult Trial of the Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) and the Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trial., Participants: All safety-evaluable patients who received 1 or more injections of sham or PDT or of ranibizumab and had 1 or more postbaseline IOP measurements recorded for the study eye., Methods: Preinjection IOP measurements for study eyes (n = 1125) and fellow eyes in MARINA and ANCHOR at baseline and at each monthly visit through month 24 were analyzed., Main Outcome Measures: End points evaluated were maximum preinjection IOP during the 24-month treatment period; any occurrence of absolute preinjection IOP of 21 mmHg or more, 25 mmHg or more, or 30 mmHg or more; any occurrence of IOP increase of 6 mmHg or more, 8 mmHg or more, or 10 mmHg or more from baseline; any combination of IOP increase of 6 mmHg or more or 8 mmHg or more from baseline with concurrent absolute preinjection IOP of 21 mmHg or more or 25 mmHg or more; glaucoma-related adverse events; new glaucoma medications used for 45 days or more; and glaucoma filtration or laser surgeries., Results: Across treatment groups, 60.1% to 70.9% of study eyes had a maximum preinjection IOP of less than 21 mmHg. Comparing ranibizumab 0.5 mg versus sham or PTD treatment, respectively: 39.9% versus 29.1% and 10.9% versus 5.1% had maximum preinjection IOPs of 21 mmHg or more or 25 mmHg or more, respectively; 44.1% versus 29.9% and 24.2% versus 13.6% had IOP increases from baseline of 6 mmHg or more or 8 mmHg or more, respectively; 26.1% versus 13.6% and 16.8% versus 9.0% had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 21 mmHg or more; 9.6% versus 3.7% and 7.5% versus 2.4% had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, respectively, with a concurrent IOP of 25 mmHg or more. No differences were observed in fellow eyes., Conclusions: Most ranibizumab-treated eyes did not experience sustained preinjection IOP of 21 mmHg or more (>2 consecutive visits) over 24 months. When evaluating the combined IOP end point, more ranibizumab-treated eyes had 1 or more IOP increase from baseline of 6 mmHg or more or 8 mmHg or more, with concurrent highest IOPs of 21 mmHg or more and 25 mmHg or more versus sham or PDT. Intraocular pressure should be monitored in eyes receiving ranibizumab., (Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

We review the dynamics of particle laden interfaces, both particle monolayers and particle+surfactant monolayers. We also discuss the use of the Brownian motion of microparticles trapped at fluid interfaces for measuring the shear rheology of surfactant and polymer monolayers. We describe the basic concepts of interfacial rheology and the different experimental methods for measuring both dilational and shear surface complex moduli over a broad range of frequencies, with emphasis in the micro-rheology methods. In the case of particles trapped at interfaces the calculation of the diffusion coefficient from the Brownian trajectories of the particles is calculated as a function of particle surface concentration. We describe in detail the calculation in the case of subdiffusive particle dynamics. A comprehensive review of dilational and shear rheology of particle monolayers and particle+surfactant monolayers is presented. Finally the advantages and current open problems of the use of the Brownian motion of microparticles for calculating the shear complex modulus of monolayers are described in detail., (© 2013.)

The recent progress in theoretical and experimental studies of simultaneous spreading and evaporation of liquid droplets on solid substrates is discussed for pure liquids including nanodroplets, nanosuspensions of inorganic particles (nanofluids) and surfactant solutions. Evaporation of both complete wetting and partial wetting liquids into a nonsaturated vapour atmosphere are considered. However, the main attention is paid to the case of partial wetting when the hysteresis of static contact angle takes place. In the case of complete wetting the spreading/evaporation process proceeds in two stages. A theory was suggested for this case and a good agreement with available experimental data was achieved. In the case of partial wetting the spreading/evaporation of a sessile droplet of pure liquid goes through four subsequent stages: (i) the initial stage, spreading, is relatively short (1-2 min) and therefore evaporation can be neglected during this stage; during the initial stage the contact angle reaches the value of advancing contact angle and the radius of the droplet base reaches its maximum value, (ii) the first stage of evaporation is characterised by the constant value of the radius of the droplet base; the value of the contact angle during the first stage decreases from static advancing to static receding contact angle; (iii) during the second stage of evaporation the contact angle remains constant and equal to its receding value, while the radius of the droplet base decreases; and (iv) at the third stage of evaporation both the contact angle and the radius of the droplet base decrease until the drop completely disappears. It has been shown theoretically and confirmed experimentally that during the first and second stages of evaporation the volume of droplet to power 2/3 decreases linearly with time. The universal dependence of the contact angle during the first stage and of the radius of the droplet base during the second stage on the reduced time has been derived theoretically and confirmed experimentally. The theory developed for pure liquids is applicable also to nanofluids, where a good agreement with the available experimental data has been found. However, in the case of evaporation of surfactant solutions the process deviates from the theoretical predictions for pure liquids at concentration below critical wetting concentration and is in agreement with the theoretical predictions at concentrations above it., (Crown Copyright © 2013. All rights reserved.)

Phase transitions in two-dimensional (2D) systems are of considerable fundamental and practical importance. However, the kinetics of these processes are difficult to predict and understand, even in simple systems for which equilibrium states are properly described, owing to the difficulty of studying crystallites with single-particle resolution and free of defects. Here we introduce an alternative method for the sublimation of 2D colloidal crystallites by a sudden induction of repulsive forces between the particles. The sublimation kinetics, studied in real space by microscopy and by computer simulations, shows a scaling behavior that suggests a universal mechanism fundamentally different from the one usually accepted for thermal sublimation. The universal behavior found for the early stages of the process may be useful for understanding the dynamic features of particle systems at liquid interfaces and for designing technological applications without the need of performing extensive experimental studies.

Purpose: To report 36-month outcomes of RIDE (NCT00473382) and RISE (NCT00473330), trials of ranibizumab in diabetic macular edema (DME)., Design: Phase III, randomized, multicenter, double-masked, 3-year trials, sham injection-controlled for 2 years., Participants: Adults with DME (n=759), baseline best-corrected visual acuity (BCVA) 20/40 to 20/320 Snellen equivalent, and central foveal thickness (CFT) ≥ 275 μm on optical coherence tomography., Methods: Patients were randomized equally (1 eye per patient) to monthly 0.5 mg or 0.3 mg ranibizumab or sham injection. In the third year, sham patients, while still masked, were eligible to cross over to monthly 0.5 mg ranibizumab. Macular laser was available to all patients starting at month 3; panretinal laser was available as necessary., Main Outcome Measures: The proportion of patients gaining ≥15 Early Treatment Diabetic Retinopathy Study letters in BCVA from baseline at month 24., Results: Visual acuity (VA) outcomes seen at month 24 in ranibizumab groups were consistent through month 36; the proportions of patients who gained ≥15 letters from baseline at month 36 in the sham/0.5 mg, 0.3 mg, and 0.5 mg ranibizumab groups were 19.2%, 36.8%, and 40.2%, respectively, in RIDE and 22.0%, 51.2%, and 41.6%, respectively, in RISE. In the ranibizumab arms, reductions in CFT seen at 24 months were, on average, sustained through month 36. After crossover to 1 year of treatment with ranibizumab, average VA gains in the sham/0.5 mg group were lower compared with gains seen in the ranibizumab patients after 1 year of treatment (2.8 vs. 10.6 and 11.1 letters). Per-injection rates of endophthalmitis remained low over time (∼0.06% per injection). The incidence of serious adverse events potentially related to systemic vascular endothelial growth factor inhibition was 19.7% in patients who received 0.5 mg ranibizumab compared with 16.8% in the 0.3 mg group., Conclusions: The strong VA gains and improvement in retinal anatomy achieved with ranibizumab at month 24 were sustained through month 36. Delayed treatment in patients receiving sham treatment did not seem to result in the same extent of VA improvement observed in patients originally randomized to ranibizumab. Ocular and systemic safety was generally consistent with the results seen at month 24., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The simultaneous spreading and evaporation of droplets of aqueous trisiloxane (superspreader) solutions onto a hydrophobic substrate has been studied both experimentally, using a video-microscopy technique, and theoretically. The experiments have been carried out over a wide range of surfactant concentration, temperature, and relative humidity. Similar to pure liquids, four different stages have been observed: the initial one corresponds to spreading until the contact angle, θ, reaches the value of the static advancing contact angle, θad. Duration of this stage is rather short, and the evaporation during this stage can be neglected. The evaporation is essential during the next three stages. The next stage after the spreading, which is referred to herein as the first stage, takes place at constant perimeter and ends when θ reaches the static receding contact angle, θr. During the next, second stage, the perimeter decreases at constant contact angle θ = θr for surfactant concentration above the critical wetting concentration (CWC). The static receding contact angle decreases during the second stage for concentrations below CWC because the concentration increases due to the evaporation. During the final stage both the perimeter and the contact angle decrease. In what follows, we consider only the longest stages I and II. The developed theory predicts universal curves for the contact angle dependency on time during the first stage, and for the droplet perimeter on time during the second stage. A very good agreement between theory and experimental data has been found for the first stage of evaporation, and for the second stage for concentrations above CWC; however, some deviations were found for concentrations below CWC.

Evaporation kinetics of sessile droplets of aqueous suspension of inorganic nanoparticles on solid substrates of various wettabilities is investigated from both experimental and theoretical points of view. Experimental results on evaporation of various kinds of inorganic nanosuspensions on solid surfaces of different hydrophobicities/hydrophilicities are compared with our theoretical predictions of diffusion limited evaporation of sessile droplets in the presence of contact angle hysteresis. The theory describes two main stages of evaporation process: (I) evaporation with a constant radius of the droplet base when the contact angle decreases from static advancing contact angle down to static receding contact angle and (II) evaporation with constant contact angle equal to the static receding contact angle when the radius of the droplet base decreases. Theoretically predicted universal dependences for both evaporation stages are compared with experimental data, and a very good agreement is found., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Importance: Treatment of macular edema secondary to retinal vein occlusion with ranibizumab has been shown to improve visual acuity compared with macular laser or observation. It is important to determine whether these visual acuity improvements translate into measurable improvements in visual function., Objective: To examine the benefit of ranibizumab (Lucentis) on measured reading speed, a direct performance assessment, through 6 months in eyes of patients with macular edema after retinal vein occlusion (RVO). DESIGN Two multicenter, double-masked, phase 3 trials in which participants with macular edema after branch RVO or central RVO were randomized 1:1:1 to monthly sham, ranibizumab, 0.3 mg, or ranibizumab, 0.5 mg, for 6 months., Setting: Community- and academic-based ophthalmology practices specializing in retinal diseases., Participants: Seven hundred eighty-nine eyes of 789 participants who were at least aged 18 years with macular edema secondary to retinal vein occlusion in the branch vein occlusion (BRAVO) and central vein occlusion (CRUISE) trials., Interventions: Eyes were randomized 1:1:1 to 1 of 3 groups for monthly injections for 6 months: sham (132 in BRAVO and 130 in CRUISE), intravitreal ranibizumab, 0.3 mg (134 in BRAVO and 132 in CRUISE), and intravitreal ranibizumab, 0.5 mg (131 in BRAVO and 130 in CRUISE). Patients were able to receive macular laser after 3 months if they met prespecified criteria., Main Outcomes and Measures: Reading speed in the study eye was measured with enlarged text (letter size equivalent to approximately 20/1500 at the test distance) at baseline and 1, 3, and 6 months. The number of correctly read words per minute (wpm) was reported. The reading speed test requires a sixth-grade reading level and does not account for literacy or cognitive state. RESULTS In patients with branch RVO, the mean gain for the 0.5-mg group was 31.3 wpm compared with 15.0 wpm in sham-treated eyes (difference, 16.3 wpm; P = .007) at 6 months. In patients with central RVO, the mean gain for the 0.5-mg group was 20.5 wpm compared with 8.1 wpm in sham-treated eyes (difference, 12.4 wpm; P = .01) at 6 months. A gain of 15 or more letters of best-corrected visual acuity letter score corresponded to an increase in reading speed of 12.3 wpm and 15.8 wpm in patients with branch and central RVO, respectively., Conclusions and Relevance: These results suggest that patients with macular edema after RVO treated monthly with ranibizumab are more likely to have improvements in reading speed of the affected eyes through 6 months compared with sham treatment. These results demonstrate the relevance of the treatment benefit to functional visual gain., Trial Registration: clinicaltrials.gov Identifier: NCT00486018 and NCT00485836.

Lithium cations are known to form complexes with the oxygen atoms of poly(oxyethylene) chains. The effect of Li(+) on the surface properties of three block-copolymers containing poly(oxyethylene) (PEO) have been studied. Two types of copolymers have been studied, a water soluble one of the pluronic family, PEO-b-PPO-b-PEO, PPO being poly(propyleneoxyde), and two water insoluble ones: PEO-b-PS and PEO-b-PS-b-PEO, PS being polystyrene. In the case of the pluronic the adsorption kinetics, the equilibrium surface tension isotherm and the aqueous/air surface rheology have been measured, while for the two insoluble copolymers only the surface pressure and the surface rheology have been studied. In all the cases two different Li(+) concentrations have been used. As in the absence of lithium ions, the adsorption kinetics of pluronic solutions shows two processes, and becomes faster as [Li(+)] increases. The kinetics is not diffusion controlled. For a given pluronic concentration the equilibrium surface pressure increases with [Li(+)], and the isotherms show two surface phase transitions, though less marked than for [Li(+)]=0. A similar behavior was found for the equilibrium isotherms of PEO-b-PS and PEO-b-PS-b-PEO. The surface elasticity of these two copolymers was found to increase with [Li(+)] over the whole surface concentration and frequency ranges studied. A smaller effect was found in the case of the pluronic solutions. The results of the pluronic solutions were modeled using a recent theory that takes into account that the molecules can be adsorbed at the surface in two different states. The theory gives a good fit for the adsorption kinetics and a reasonably good prediction of the equilibrium isotherms for low and intermediate concentrations of pluronic. However, the theory is not able to reproduce the isotherm for [Li(+)]=0. Only a semi-quantitative prediction of the surface elasticity is obtained for [pluronic]≤1×10(-3) mM., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To evaluate the 12-month efficacy and safety of intravitreal ranibizumab 0.5 mg and 2.0 mg administered monthly and on an as-needed (PRN) basis in treatment-naïve patients with subfoveal neovascular age-related macular degeneration (wet AMD)., Design: A 24-month, phase III, randomized, multicenter, double-masked, dose-response study., Participants: Patients aged ≥ 50 years with subfoveal wet AMD., Methods: Patients (n = 1098) were randomized to receive ranibizumab 0.5 mg or 2.0 mg intravitreal injections administered monthly or on a PRN basis after 3 monthly loading doses., Main Outcome Measures: The primary efficacy end point was the mean change from baseline in best-corrected visual acuity (BCVA) at month 12. Key secondary end points included the mean number of ranibizumab injections, the mean change from baseline in central foveal thickness (CFT) over time, and the proportion of patients who gained ≥ 15 letters of BCVA. Unless otherwise specified, end point analyses were performed using the last-observation-carried-forward method to impute missing data., Results: At month 12, the mean change from baseline in BCVA for the 4 groups was +10.1 letters (0.5 mg monthly), +8.2 letters (0.5 mg PRN), +9.2 letters (2.0 mg monthly), and +8.6 letters (2.0 mg PRN). The proportion of patients who gained ≥ 15 letters from baseline at month 12 in the 4 groups was 34.5%, 30.2%, 36.1%, and 33.0%, respectively. The mean change from baseline in CFT at month 12 in the 4 groups was -172.0 μm, -161.2 μm, -163.3 μm, and -172.4 μm, respectively. The mean number of injections was 7.7 and 6.9 for the 0.5-mg PRN and 2.0-mg PRN groups, respectively. Ocular and systemic safety profiles were consistent with previous ranibizumab trials in AMD and comparable between groups., Conclusions: At month 12, the ranibizumab 2.0 mg monthly group did not meet the prespecified superiority comparison and the ranibizumab 0.5 mg and 2.0 mg PRN groups did not meet the prespecified noninferiority (NI) comparison. However, all treatment groups demonstrated clinically meaningful visual improvement (+8.2 to +10.1 letters) and improved anatomic outcomes, with the PRN groups requiring approximately 4 fewer injections (6.9-7.7) than the monthly groups (11.2-11.3). No new safety events were observed despite a 4-fold dose escalation in the study. The pHase III, double-masked, multicenter, randomized, Active treatment-controlled study of the efficacy and safety of 0.5 mg and 2.0 mg Ranibizumab administered monthly or on an as-needed Basis (PRN) in patients with subfoveal neOvasculaR age-related macular degeneration (HARBOR) study confirmed that ranibizumab 0.5 mg dosed monthly provides optimum results in patients with wet AMD., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine if optical coherence tomography (OCT) at baseline or month 3 in the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Treatment of Macular Edema following Central Retinal Vein Occlusion: Evaluation of Efficacy and Safety (CRUISE) studies provides information that predicts visual outcome., Design: Post hoc analysis from 2 prospective, randomized, controlled clinical trials., Participants: Three hundred ninety-seven patients from the BRAVO study and 392 patients from the CRUISE study., Methods: Time-domain OCT imaging data were analyzed., Main Outcome Measures: Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6 and month 12., Results: Among ranibizumab-treated patients, 71.2% (0.3 mg) and 78.5% (0.5 mg) in the CRUISE study and 79.1% (0.3 mg) and 84.7% (0.5 mg) in the BRAVO study had central foveal thickness (CFT) of 250 μm or less at month 3 and therefore were categorized as early ranibizumab responders. Early ranibizumab responders had excellent visual outcomes regardless of ranibizumab dose; mean improvement in BCVA letter score at 6 and 12 months was 15.0 to 16.5 (central retinal vein occlusion [CRVO]) and 17.4 to 19.1 (branch retinal vein occlusion [BRVO]). Late or incomplete ranibizumab responders with CRVO (CFT >250 μm at month 3) did not fare as well as early responders if they were treated with 0.3 mg ranibizumab (month 6, P = 0.012). At month 6, compared with ranibizumab-treated CRVO patients with resolved cystoid macular edema (CME) at month 3, those with persistent CME did worse, on average, and significantly so for 0.5 mg (13.1 vs. 18.6; P = 0.027). At baseline, subretinal fluid (SRF) was present in 57% of patients with CRVO and in 45% of patients with BRVO; its presence did not portend a poor outcome in patients treated with ranibizumab for whom SRF was eliminated in almost all by month 3., Conclusions: At month 3 of ranibizumab treatment, OCT images provide predictive information for patients with CRVO, but not for those with BRVO. Visual outcome at months 6 and 12 was reduced in 0.5 mg ranibizumab-treated patients with CRVO who had persistent CME at month 3. It also was reduced in CRVO for those with CFT of more than 250 μm at month 3 who were treated with 0.3 mg ranibizumab. The findings suggest that late or incomplete responders may need careful follow-up., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: Central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO) causes hypoperfusion, high levels of vascular endothelial growth factor (VEGF), macular edema, and loss of vision. Many patients also show areas of complete closure of retinal vessels (retinal nonperfusion [RNP]) that increase over time. The objective was to assess the effect of blocking VEGF on progression of RNP., Design: Retrospective analysis of prospectively collected data from 2 randomized, sham injection-controlled, double-masked, multicenter clinical trials., Participants: A total of 392 and 397 patients with macular edema due to CRVO or BRVO., Methods: An independent reading center measured the area of RNP on fluorescein angiograms (FAs) in 2 phase III trials investigating the effect of ranibizumab (RBZ; Lucentis; Genentech, Inc, South San Francisco, CA) in patients with CRVO or BRVO., Main Outcome Measures: The percentage of patients with no posterior RNP at months 0, 3, 6, 9, and 12., Results: There was no difference among treatment groups at baseline, but at the month 6 primary end point the percentage of patients with CRVO and no RNP was significantly greater in the RBZ groups (0.3 mg, 82.0%, P = 0.0092; 0.5 mg, 84.0%, P = 0.0067) versus the sham group (67.0%). Reperfusion of nonperfused retina was rare (1%) in sham-treated patients with CRVO, but occurred in 6% to 8% of patients with CRVO treated with RBZ (30% of those who had RNP and could improve). Results in patients with BRVO mirrored those in patients with CRVO. Crossover to 0.5 mg RBZ from sham at month 6 halted the progression of RNP and resulted in improvement in both CRVO and BRVO., Conclusions: Treatment with RBZ did not worsen RNP in patients with RVO, but rather reduced its occurrence compared with sham. These data provide an important new insight regarding the pathogenesis of RVO; the initial vein occlusion is a precipitating event that causes baseline ischemia and release of VEGF, which then contributes to progression of RNP and thus worsening of ischemia. Timely, aggressive blockade of VEGF prevents the worsening of RNP, promotes reperfusion, and eliminates a positive feedback loop., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

In this work, we study how structures develop on 2D dense binary colloidal monolayers as a function of the relative concentration of small/large particles. Translational and orientational distribution functions have been used to monitor the continuous phase transition through a detailed characterization of the global and local order. We have observed how a gradual enhancement in the number of particles of different sizes leads to a continuous vitrification process and how homogeneous binary glasses form in equimolar mixtures. Also, we have performed a simple calculation that relates the structures found to the pair dipolar potential, allowing the forecast of local structures in other arbitrary binary mixtures. Finally, we have corroborated the goodness of the binary systems as a glass-forming model by comparing the established scenario with the structural features found in partially aggregated monolayers.

The aim of the current work is to present results of computer simulations, which show the influence of kinetic effects on evaporation of pinned sessile water droplets of submicrometer size placed on a heat conductive substrate. The computer simulation model also takes into account the following phenomena: influence of curvature of the droplet's surface on saturated vapor pressure above the surface (Kelvin's equation), the effect of latent heat of vaporization, thermal Marangoni convection, and Stefan flow inside an air domain above the droplet. The suggested model combines both diffusive and kinetic models of evaporation. The obtained results allow the characteristic droplet sizes to be estimated, where each of the mentioned above phenomena becomes important or can be neglected.

Purpose: To analyze cerebrovascular accidents (CVAs) pooled from large, randomized, controlled clinical trials of ranibizumab treatment for neovascular age-related macular degeneration., Methods: Events in five trials (FOCUS, MARINA, ANCHOR, PIER, and SAILOR) were analyzed using a standard safety monitoring process. Exact methods, stratified by study, were used to test for treatment differences based on odds ratios. A stepwise logistic regression model was fit to classify subjects' risk for CVA based on medical history. Treatment differences in CVA rates at 1 year or 2 years were evaluated within risk groups using stratified exact methods., Results: Pooled 2-year CVA rates were <3%; odds ratios (95% confidence intervals) for CVA risk were 1.2 (0.4-4.4) for ranibizumab 0.3-mg versus control, 2.2 (0.8-7.1) for 0.5 mg versus control, and 1.5 (0.8-3.0) for 0.5-mg versus 0.3-mg ranibizumab. No substantial increased risk of CVA for 0.5 mg versus 0.3 mg was identified in pooled analyses or any of the individual trials. In pooled analyses, the difference between 0.5-mg ranibizumab and control was larger (7.7 [1.2-177]) among high-risk CVA patients., Conclusion: This analysis provided some evidence, although not definitive, of a potential increased risk of CVA with ranibizumab versus control or with 0.5-mg versus 0.3-mg ranibizumab. Continued monitoring for CVA within clinical trials seems warrented.

Purpose: To examine the impact of intravitreal ranibizumab on patient-reported visual function using the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) through 6 months in patients with macular edema (ME) secondary to branch or central retinal vein occlusion (RVO)., Design: Two multicenter, double-masked trials, which enrolled participants with ME secondary to branch or central RVO: the RanibizumaB for the Treatment of Macular Edema following BRAnch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) trial or the Central Retinal Vein OcclUsIon Study: Evaluation of Efficacy and Safety (CRUISE) trial., Participants: Three hundred ninety-seven BRAVO and 392 CRUISE patients., Methods: Patients were randomized 1:1:1 to monthly sham, 0.3-mg, or 0.5-mg injections of ranibizumab for 6 months., Main Outcome Measures: Although visual acuity was the main outcome measure for the trials, mean change from baseline in NEI VFQ-25 scores at month 6 was a secondary outcome measure., Results: In BRAVO, among the 132, 134, and 131 patients randomized, respectively, to sham, 0.3 mg ranibizumab, or 0.5 mg ranibizumab, the study eye was the worse-seeing eye in 121 (91.7%), 118 (88.1%), and 125 (95.4%) patients and 123 (93.2%), 128 (95.5%), and 125 (95.4%), respectively, had a 6-month follow-up visit. In CRUISE, among the 130, 132, and 130 patients randomized, respectively, to sham, 0.3 mg ranibizumab, and 0.5 mg ranibizumab, the study eye was the worse-seeing eye in 117 (90.0%), 123 (93.2%), and 120 (92.3%) patients and 115 (88.5%), 129 (97.7%), and 119 (91.5%), respectively, had a 6-month follow-up visit. In both trials, patients treated with ranibizumab reported greater mean improvements in visual function, with substantial differences observed as early as month 1, including the NEI VFQ-25 composite score and near and distance activities subscales, compared with sham patients. P values for comparisons with sham for the composite score and these 2 subscales were <0.05., Conclusions: These results from the BRAVO and CRUISE trials indicate that patients with ME from RVOs treated with monthly ranibizumab report greater improvements in vision-related function compared with sham-treated patients through 6 months, even when a majority of patients present with RVOs in the worse-seeing eye., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Liquid crystalline polymers (LCPs) are complex systems that include features of both orientationally ordered mesophases and amorphous polymers. Frequently, the isotropic amorphous state cannot be studied due to the rapid mesophase formation. Here, a new main chain LCP, poly(triethyleneglycol methyl p,p'-bibenzoate), PTEMeB, has been synthesized. It shows a rather slow mesophase formation making possible to study independently both the amorphous and the liquid crystalline states. The structure and phase transitions of PTEMeB have been investigated by calorimetry, variable-temperature MAXS/WAXS employing synchrotron radiation, and X-ray diffraction in oriented fibers. These experiments have pointed out the presence of two glass transitions, related to the amorphous or to the liquid crystal phases. Additionally, the mesophase seems to be a coexistence of orthogonal and tilted smectic phases. A dielectric relaxation study of PTEMeB over broad ranges of temperature and pressure has been performed. The dynamic glass transition turns out to be slower for the amorphous state than for the liquid crystal. Monitoring of the α relaxation has allowed us to follow the isothermal mesophase formation at atmospheric pressure. Additionally, the dynamical behavior at high pressures has pointed out the fast formation of the mesophase induced by sudden pressure changes.

This work presents a detailed study of the dilational viscoelastic moduli of the adsorption layers of the milk protein β-casein (BCS) and a surfactant at the liquid/air interface, over a broad frequency range. Two complementary techniques have been used: a drop profile tensiometry technique and an excited capillary wave method, ECW. Two different surfactants were studied: the nonionic dodecyldimethylphosphine oxide (C12DMPO) and the cationic dodecyltrimethylammonium bromide (DoTAB). The interfacial dilational elasticity and viscosity are very sensitive to the composition of protein-surfactant mixed adsorption layers at the air/water interface. Two different dynamic processes have been observed for the two systems studied, whose characteristic frequencies are close to 0.01 and 100 Hz. In both systems, the surface elasticity was found to show a maximum when plotted versus the surfactant concentration. However, at frequencies above 50 Hz the surface elasticity of BCS + C12DMPO is higher than the one of the aqueous BCS solution over most of the surfactant concentration range, whereas for the BCS + DoTAB it is smaller for high surfactant concentrations and higher at low concentrations. The BCS-surfactant interaction modifies the BCS random coil structure via electrostatic and/or hydrophobic interactions, leading to a competitive adsorption of the BCS-surfactant complexes with the free, unbound surfactant molecules. Increasing the surfactant concentration decreases the adsorbed proteins. However, the BCS molecules are rather strongly bound to the interface due to their large adsorption energy. The results have been fitted to the model proposed by C. Kotsmar et al. ( J. Phys. Chem. B 2009 , 113 , 103 ). Even though the model describes well the concentration dependence of the limiting elasticity, it does not properly describe its frequency dependence.

Purpose: To assess long-term safety and efficacy of intraocular ranibizumab injections in patients with macular edema after retinal vein occlusion (RVO)., Design: Open-label extension trial of the 12-month Ranibizumab for the Treatment of Macular Edema following Branch Retinal Vein Occlusion: Evaluation of Efficacy and Safety (BRAVO) and Central Retinal Vein Occlusion Study: Evaluation of Efficacy and Safety (CRUISE) trials., Participants: We included 304 patients who completed BRAVO and 304 patients who completed CRUISE., Methods: Patients were seen at least every 3 months and given an intraocular injection of 0.5 mg ranibizumab if they met prespecified retreatment criteria., Main Outcome Measures: Primary outcomes were incidence and severity of ocular and nonocular adverse events (AEs). Key efficacy outcomes included mean change from baseline best-corrected visual acuity (BCVA) letter score by Early Treatment Diabetic Retinopathy Study protocol and central foveal thickness., Results: In patients who completed month 12, the mean number of injections (excluding month 12 injection) in the sham/0.5-, 0.3/0.5-, and 0.5-mg groups was 2.0, 2.4, and 2.1 (branch RVO) and 2.9, 3.8, and 3.5 (central RVO), respectively. The incidence of study eye ocular serious AEs (SAEs) and SAEs potentially related to systemic vascular endothelial growth factor inhibition across treatment arms was 2% to 9% and 1% to 6%, respectively. The mean change from baseline BCVA letter score at month 12 in branch RVO patients was 0.9 (sham/0.5 mg), -2.3 (0.3/0.5 mg), and -0.7 (0.5 mg), respectively. The mean change from baseline BCVA at month 12 in central RVO patients was -4.2 (sham/0.5 mg), -5.2 (0.3/0.5 mg), and -4.1 (0.5 mg), respectively., Conclusions: No new safety events were identified with long-term use of ranibizumab; rates of SAEs potentially related to treatment were consistent with prior ranibizumab trials. Reduced follow-up and fewer ranibizumab injections in the second year of treatment were associated with a decline in vision in central RVO patients, but vision in branch RVO patients remained stable. Results suggest that during the second year of ranibizumab treatment of RVO patients, follow-up and injections should be individualized and, on average, central RVO patients may require more frequent follow-up than every 3 months., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the efficacy and safety of intravitreal ranibizumab in diabetic macular edema (DME) patients., Design: Two parallel, methodologically identical, phase III, multicenter, double-masked, sham injection-controlled, randomized studies., Participants: Adults with vision loss from DME (best-corrected visual acuity [BCVA], 20/40-20/320 Snellen equivalent) and central subfield thickness ≥275 μm on time-domain optical coherence tomography (OCT)., Intervention: Monthly intravitreal ranibizumab (0.5 or 0.3 mg) or sham injections. Macular laser was available per-protocol-specified criteria., Main Outcome Measures: Proportion of patients gaining ≥15 letters in BCVA from baseline at 24 months., Results: In RISE (NCT00473330), 377 patients were randomized (127 to sham, 125 to 0.3 mg, 125 to 0.5 mg). At 24 months, 18.1% of sham patients gained ≥15 letters versus 44.8% of 0.3-mg (P<0.0001; difference vs sham adjusted for randomization stratification factors, 24.3%; 95% confidence interval [CI], 13.8-34.8) and 39.2% of 0.5-mg ranibizumab patients (P<0.001; adjusted difference, 20.9%; 95% CI, 10.7-31.1). In RIDE (NCT00473382), 382 patients were randomized (130 to sham, 125 to 0.3 mg, 127 to 0.5 mg). Significantly more ranibizumab-treated patients gained ≥15 letters: 12.3% of sham patients versus 33.6% of 0.3-mg patients (P<0.0001; adjusted difference, 20.8%; 95% CI, 11.4-30.2) and 45.7% of 0.5-mg ranibizumab patients (P<0.0001; adjusted difference, 33.3%; 95% CI, 23.8-42.8). Significant improvements in macular edema were noted on OCT, and retinopathy was less likely to worsen and more likely to improve in ranibizumab-treated patients. Ranibizumab-treated patients underwent significantly fewer macular laser procedures (mean of 1.8 and 1.6 laser procedures over 24 months in the sham groups vs 0.3-0.8 in ranibizumab groups). Ocular safety was consistent with prior ranibizumab studies; endophthalmitis occurred in 4 ranibizumab patients. The total incidence of deaths from vascular or unknown causes, nonfatal myocardial infarctions, and nonfatal cerebrovascular accidents, which are possible effects from systemic vascular endothelial growth factor inhibition, was 4.9% to 5.5% of sham patients and 2.4% to 8.8% of ranibizumab patients., Conclusions: Ranibizumab rapidly and sustainably improved vision, reduced the risk of further vision loss, and improved macular edema in patients with DME, with low rates of ocular and nonocular harm., (Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The effect of the structure of copolymers (random, alternate or diblock) on their dynamics has been studied by dielectric spectroscopy. Six copolymers of styrene and methyl methacrylate (three diblocks, one alternate and two random) have been studied. The results show that the sub- T (g) transitions of the diblock samples can be described by one asymmetric Havriliak-Negami (HN) function, while two are necessary for the rest of the copolymers (β and γ relaxations). The characteristic times of the sub- T (g) relaxations show an Arrhenius temperature dependence and there is a strong coupling of the α and β relaxations at high temperatures. The deconvolution of the merging relaxations has been made in the framework of the Williams Ansatz set out in terms of Havriliak-Negami distributions. Because the 2D (2)H-NMR results excluded any significant contribution from the rotation of the methoxy group of the methacrylate group around the C-OCH(3) bond, the γ relaxation may be assigned to the rotation of the methyl methacrylate group in a styrene-rich environment. The Molecular Dynamics simulations of a poly(methyl methacrylate) homopolymer and of the alternate copolymer are in qualitative agreement with the experimental results, although they predict smaller values for the activation energy of the sub- T (g) relaxations.

The Layer-by-Layer (LbL) self-assembly of polyelectrolyte multilayers (PEMs) formed by poly(acrylic acid) (PAA) and chitosan (CHI) of two different percentages of acetylation (AC) has been studied by dissipative quartz crystal microbalance (D-QCM) and ellipsometry. The results point out that the non-linear growth (exponential growth) of the films is not modified by the percentage of acetylation of the CHI (AC). The comparison of the thickness obtained by D-QCM and by ellipsometry has allowed us to calculate the water content of the films showing that the multilayers are highly hydrated. This agrees with the values of the complex shear modulus obtained from the analysis of D-QCM data that are in the MPa range, and show a transition from a viscous to mainly elastic behavior depending on the charge density of the CHI chains. The monomer surface density in each layer (obtained from the combination of ellipsometry and differential refractive index measurements) indicated that the mechanism of charge compensation depends on the percentage of acetylation of the CHI. It was found that the adsorption kinetics is a bimodal process with characteristic times that depend on the number and nature of each layer. The load capacity of the multilayers for a β-blocker, propranolol, was found to be higher for the lowest acetylation degree., (This journal is © the Owner Societies 2011)

Purpose: Assess the 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO)., Design: Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial., Participants: We included 392 patients with macular edema after CRVO., Methods: Eligible patients were randomized 1:1:1 to receive 6 monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections. After 6 months, all patients with BCVA ≤20/40 or central subfield thickness ≥250 μm could receive ranibizumab., Main Outcome Measures: Mean change from baseline best-corrected visual acuity (BCVA) letter score at month 12, additional parameters of visual function, central foveal thickness (CFT), and other anatomic changes were assessed., Results: Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 13.9 (11.2-16.5) and 13.9 (11.5-16.4) in the 0.3 mg and 0.5 mg groups, respectively, and 7.3 (4.5-10.0) in the sham/0.5 mg group (P<0.001 for each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 47.0% and 50.8% in the 0.3 mg and 0.5 mg groups, respectively, and 33.1% in the sham/0.5 mg group. On average, there was a marked reduction in CFT after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group to the level of the ranibizumab groups, which was sustained through month 12. No new ocular or nonocular safety events were identified., Conclusions: On average, treatment with ranibizumab as needed during months 6 through 11 maintained the visual and anatomic benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after CRVO, with low rates of ocular and nonocular safety events. After sham injections for 6 months, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT in the sham/0.5 mg group to a level similar to that in the 2 ranibizumab treatment groups and an improvement in BCVA, but not to the same level as that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after CRVO., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The processes of adsorption of grafted copolymers onto negatively charged surfaces were studied using a dissipative quartz crystal microbalance (D-QCM) and ellipsometry. The control parameters in the study of the adsorption are the existence or absence on the molecular architecture of grafted polyethyleneglycol (PEG) chains with different lengths and the chemical nature of the main chain, poly(allylamine) (PAH) or poly(L-lysine) (PLL). It was found out that the adsorption kinetics of the polymers showed a complex behavior. The total adsorbed amount depends on the architecture of the polymer chains (length of the PEG chains), on the polymer concentration and on the chemical nature of the main chain. The comparison of the thicknesses of the adsorbed layers obtained from D-QCM and from ellipsometry allowed calculation of the water content of the layers that is intimately related to the grafting length. The analysis of D-QCM results also provides information about the shear modulus of the layers, whose values have been found to be typical of a rubber-like polymer system. It is shown that the adsorption of polymers with a charged backbone is not driven exclusively by the electrostatic interactions, but the entropic contributions as a result of the trapping of water in the layer structure are of fundamental importance.

Purpose: Assess 12-month efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after branch retinal vein occlusion (BRVO)., Design: Prospective, randomized, sham injection-controlled, double-masked, multicenter trial., Participants: A total of 397 patients with macular edema after BRVO., Methods: Eligible patients were randomized 1:1:1 to 6 monthly injections of 0.3 mg or 0.5 mg ranibizumab or sham injections. After 6 months, all patients with study eye best-corrected visual acuity (BCVA) ≤20/40 or central subfield thickness ≥250 μm were to receive ranibizumab. Patients could receive rescue laser treatment once during the treatment period and once during the observation period if criteria were met., Main Outcome Measures: The main efficacy outcome reported is mean change from baseline BCVA letter score at month 12. Additional visual and anatomic parameters were assessed., Results: Mean (95% confidence interval) change from baseline BCVA letter score at month 12 was 16.4 (14.5-18.4) and 18.3 (15.8-20.9) in the 0.3 mg and 0.5 mg groups, respectively, and 12.1 (9.6-14.6) in the sham/0.5 mg group (P<0.01, each ranibizumab group vs. sham/0.5 mg). The percentage of patients who gained ≥15 letters from baseline BCVA at month 12 was 56.0% and 60.3% in the 0.3 mg and 0.5 mg groups, respectively, and 43.9% in the sham/0.5 mg group. On average, there was a marked reduction in central foveal thickness (CFT) after the first as-needed injection of 0.5 mg ranibizumab in the sham/0.5 mg group, which was sustained through month 12. No new ocular or nonocular safety events were identified., Conclusions: At month 12, treatment with ranibizumab as needed during months 6-11 maintained, on average, the benefits achieved by 6 monthly ranibizumab injections in patients with macular edema after BRVO, with low rates of ocular and nonocular safety events. In the sham/0.5 mg group, treatment with ranibizumab as needed for 6 months resulted in rapid reduction in CFT to a similar level as that in the 0.3 mg ranibizumab treatment group and an improvement in BCVA, but not to the extent of that in the 2 ranibizumab groups. Intraocular injections of ranibizumab provide an effective treatment for macular edema after BRVO., Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The adsorption processes of polymers that belong to two different families (neutral hydrophilic polymers and cationic polysaccharide polymers) onto solid surfaces with different charge density have been studied using dissipative quartz crystal microbalance (D-QCM) and ellipsometry. The polymers studied are very frequently used in the cosmetic industry as conditioning agents. The adsorption kinetics of the polymers involves at least two steps. The total adsorbed amount depends on the charge density of the surface for both types of polymers. The comparison of the adsorbed mass on each layer obtained from D-QCM and from ellipsometry has allowed calculating the water content of the layers that reaches high values for the polymers studied. The analysis of D-QCM results also provided information about the shear modulus of the layers, whose values have been found to be typical of a rubber-like polymer system. The main driving force of the adsorption was found to be the energy of the interactions between chains and surface.

Multilayers of poly(acrylic acid), PAA, and chitosan, CHI, have been built by the layer-by-layer (LbL) method from aqueous solutions at different pH values and analyzed by the dissipative quartz crystal microbalance (D-QCM) and ellipsometry. The results showed that under all of the assembly conditions considered the growth of the films is nonlinear. The thickness of the PAA layers increases as the pH of the assembling solutions decreases, whereas the adsorption of CHI is almost unaffected by the pH conditions. The comparison of the thickness obtained by D-QCM and by ellipsometry has allowed us to calculate the water content of the films, showing that the multilayers are highly hydrated, with an average water content higher than 20%. The analysis of D-QCM data has provided high-frequency values of the complex shear modulus that are in the megapascal range and shows a transition from mainly viscous to mainly elastic behavior for the added PAA layers, depending on the pH. The monomer surface density in each layer (obtained from the combination of ellipsometry and differential refractive index measurements) indicated that the monomer density depends on the assembly conditions. It was found that the adsorption kinetics is a bimodal process, with characteristic times that depend on the number and nature of the layers. Finally, the possibility of using of these multilayers as a drug storage and delivery system has been evaluated.

We report an experimental study that points out the existence of a fluid to soft-glass transition in Langmuir polymer monolayers of poly(methyl methacrylate) (PMMA), for which the water/air interface behaves as a poor-solvent. The temperature dependence of surface pressure vs. surface area equilibrium isotherms shows a glass-like transition temperature at T(g,2D)≈ 298 K, significantly lower than the value for bulk PMMA (T(g,bulk)≈ 378 K). The plot of the film thickness h vs. temperature shows a sharp change of slope at about the same temperature, 298 K, which is a typical hallmark of a glass transition in thin polymer films [J. L. Keddie, R. A. L. Jones, R. A. Cory, Europhys. Lett., 1996, 27, 59-64]. Furthermore, slightly above T(g,2D), the temperature dependence of the dilational viscosity does not follow an Arrhenius law, but instead can be described by a Vogel-Fulcher-Tamman equation with parameters that are typical of a fragile glass. Not only the qualitative behavior of three distinct equilibrium and dynamic properties, but also the quantitative agreement of the values of T(g) obtained, are a strong evidence of the existence of a fluid to soft-glass transition in this quasi-2D system., (This journal is © the Owner Societies 2011)

The structure and the interaction potential of monolayers of charged polystyrene microparticles at fluid interfaces have been studied by optical microscopy. Microparticles of different sizes have been studied over a broad range of surface particle densities. The structural characterization is based on the analysis of images obtained by digital optical microscopy. From the experimental images, radial distribution functions, hexagonal bond order correlation functions, and temporal orientational correlation functions have been calculated for different monolayer states at both the air/water and oil/water interfaces. The interaction potential has been calculated from the structure factor using integral equations within the hypernetted chain closure relationship. For particles trapped at the oil-water interface, it was found that, upon increasing the surface coverage, a freezing transition occurs, that leads to the formation of a 2D crystalline structure. We have studied the freezing densities of particle monolayers at the oil/water interface and compared them with Monte Carlo simulation results reported by H. Löwen. In contrast, at the air-water interface, freezing is inhibited due to the formation of particle aggregates.

An experimental study of the equilibrium properties and of the surface rheology of Langmuir monolayers of poly(methyl methacrylate) (PMMA) at the air/water interface has been carried out as a function of polymer concentration (Γ) and molecular weight (M(w)). Dilational and shear complex elasticity moduli covering a frequency range from 10(-3) to 0.2 Hz have been discussed. It was found that the air∕water interface behaves as a poor solvent for PMMA monolayers, thus suggesting that the polymer coils take collapsed soft-disks (pancakes) shape at the interface. The equilibrium and dynamic results suggest a fluid-to-soft-glass transition as the polymer concentration increases above a critical packing fraction at constant temperature. This two-dimensional transition is in agreement with results previously discussed for the dilational rheology of poly(4-hydroxystyrene) [F. Monroy, F. Ortega, R. G. Rubio, H. Ritacco, and D. Langevin, J. Chem. Phys. 95, 056103 (2005)]. Furthermore, the Γ-dependence of the relaxation dynamics of the monolayers suggests that the gel state may be considered as a fragile soft glass.

Objective: To compare the incidence rates of myocardial infarction (MI) and cerebrovascular accident (CVA) in hospitalized patients with and without branch or central retinal vein occlusion (RVO)., Methods: In this retrospective cohort study, a US population-based health care claims database was used to identify patients with RVO and control patients, matched for age and sex. Events of MI, CVA, and covariates were identified for patients with and without RVO. Incidences of MI or CVA events prompting hospitalization and adjusted rate ratios (RRs) were calculated; RRs were adjusted for covariates consistent with risk factors for outcomes., Results: Of 4500 patients with RVO and 13,500 controls, the event rates for MI were 0.87 per 100 person-years and 0.67 per 100 person-years, respectively. The adjusted RR for MI was 1.03 (95% confidence interval [CI], 0.75-1.42; P = .85 for RVO vs controls). Event rates for CVA were 1.16 and 0.52 per 100 person-years for RVO and controls, respectively. The adjusted RR for CVA was 1.72 (95% CI, 1.27-2.34; P = .001) for RVO vs controls., Conclusions: This study provides quantitative data on the incidence of cardiovascular and cerebrovascular outcomes in patients with RVO in a large US population-based health care claims database. Event rates for MI were similar in patients with RVO and controls; however, the event rate for CVA in patients with RVO was almost 2-fold that observed in controls.

Spreading of aqueous surfactant solution droplets over hydrophobic substrates proceeds in one slow stage at concentration of surfactants below some critical value and in two stages if the surfactant concentration is above the critical value: the fast and relatively short first stage is followed by a slower second stage. It is shown that the kinetics of a slow spreading at concentrations below the critical value and the second stage at concentrations above the critical value are determined by a transfer of surfactant molecules on a bare hydrophobic substrate in front of the moving three-phase contact line (autophilic phenomenon). The latter process results in an increase of the solid-vapour interfacial tension of the hydrophobic solid surface in front of the moving three-phase contact line and spreading as a result. It is proven that the adsorption of surfactant molecules in front of the moving three-phase contact line results in a decrease of the total free energy of the droplet. Hence, the adsorption of surfactants molecules on a bare hydrophobic substrate in front of the moving three-phase contact line is a spontaneous process in spite of an increase of the local solid-vapour interfacial tension. The duration of the first stage of spreading in the case of the surfactant concentration above the critical value correlates well with the duration of adsorption of surfactant molecules onto a liquid-vapour interface. The latter allows assuming that the adsorption on the liquid-vapour interface is the driving mechanism of spreading during the first fast stage of spreading at surfactant concentrations above the critical value. It is discussed why the first stage of spreading does not take place in the case of surfactant concentrations below the critical concentration in spite of the longer duration of adsorption on liquid-vapour interface in this case., (Copyright © 2010 Elsevier B.V. All rights reserved.)

We address a systematic study of the three-phase contact angle, θ, of microparticles at flat fluid-liquid interfaces by using different experimental methods. We measured the dependence of θ not only on the particle chemical composition and size, but also on the solvent used to spread the microparticles onto the fluid interface. We found a non-expected and non-regular dependence of θ with size, chemical nature and spreading solvent used for the different particles studied. We propose that these dependences are due to porosity/roughness of the particles that allows the adsorption of the spreading solvent onto the solid particle surface. This conclusion is supported by the values of the line tensions estimated for the different systems.

Multilayers formed by the sodium salt of poly(4-styrenesulfonate), PSS, and triblock copolymers of the form PDMAEMA-PCL-PDMAEMA (PDMAEMA corresponding to poly[2-(N,N-dimethylamino)ethyl methacrylate), and PCL to poly(epsilon-caprolactone) have been built by layer-by-layer self-assembly from the aqueous polyelectrolyte solutions. Two types of block copolymers have been used which differ on the type of the amino groups, either hydrochloride or quaternized. This leads to changes in the charge density of the chains for the same content of amino groups. The growth of the multilayers has been followed using dissipative quartz crystal microbalance and ellipsometry techniques. The results show that, independently of the conditions used in the assembling, the film thickness grows linearly with the number of layers. The comparison of the thickness values obtained from D-QCM and ellipsometry has allowed us to calculate the water content of the polymer film. The analysis of the D-QCM data also provides the shear modulus, whose values are typical of a rubber-like polymer system. The analysis of the mass adsorbed calculated by the ellipsometric measurements indicated that the nature of the charge compensation mechanism is extrinsic for all the studied systems, although the degree of extrinsic compensation is strongly dependent on the copolymer used and the concentration in solution. Finally, it was found that the adsorption kinetic of the layers is bimodal for all the films built. Even though the characteristic adsorption times depend on the specific copolymer used, no dependence on the number of layers has been found for a given multilayer.

Purpose: To assess the efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema after central retinal vein occlusion (CRVO)., Design: Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial., Participants: A total of 392 patients with macular edema after CRVO., Methods: Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 or 0.5 mg of ranibizumab or sham injections., Main Outcome Measures: The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT)., Results: Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 12.7 (9.9-15.4) and 14.9 (12.6-17.2) in the 0.3 mg and 0.5 mg ranibizumab groups, respectively, and 0.8 (-2.0 to 3.6) in the sham group (P<0.0001 for each ranibizumab group vs. sham). The percentage of patients who gained > or =15 letters in BCVA at month 6 was 46.2% (0.3 mg) and 47.7% (0.5 mg) in the ranibizumab groups and 16.9% in the sham group (P<0.0001 for each ranibizumab group vs. sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg = 43.9%; 0.5 mg = 46.9%) had BCVA of > or = 20/40 compared with sham patients (20.8%; P<0.0001 for each ranibizumab group vs. sham), and CFT had decreased by a mean of 434 microm (0.3 mg) and 452 microm (0.5 mg) in the ranibizumab groups and 168 microm in the sham group (P<0.0001 for each ranibizumab group vs. sham). The median percent reduction in excess foveal thickness at month 6 was 94.0% and 97.3% in the 0.3 mg and 0.5 mg groups, respectively, and 23.9% in the sham group. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with CRVO., Conclusions: Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid improvement in 6-month visual acuity and macular edema following CRVO, with low rates of ocular and nonocular safety events., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess efficacy and safety of intraocular injections of 0.3 mg or 0.5 mg ranibizumab in patients with macular edema following branch retinal vein occlusion (BRVO)., Design: Prospective, randomized, sham injection-controlled, double-masked, multicenter clinical trial., Participants: A total of 397 patients with macular edema following BRVO., Methods: Eligible patients were randomized 1:1:1 to receive monthly intraocular injections of 0.3 mg or 0.5 mg of ranibizumab or sham injections., Main Outcome Measures: The primary efficacy outcome measure was mean change from baseline best-corrected visual acuity (BCVA) letter score at month 6. Secondary outcomes included other parameters of visual function and central foveal thickness (CFT)., Results: Mean (95% confidence interval [CI]) change from baseline BCVA letter score at month 6 was 16.6 (14.7-18.5) and 18.3 (16.0-20.6) in the 0.3 mg and 0.5 mg ranibizumab groups and 7.3 (5.1-9.5) in the sham group (P<0.0001 for each ranibizumab group vs sham). The percentage of patients who gained > or =15 letters in BCVA at month 6 was 55.2% (0.3 mg) and 61.1% (0.5 mg) in the ranibizumab groups and 28.8% in the sham group (P<0.0001 for each ranibizumab group vs sham). At month 6, significantly more ranibizumab-treated patients (0.3 mg, 67.9%; 0.5 mg, 64.9%) had BCVA of > or =20/40 compared with sham patients (41.7%; P<0.0001 for each ranibizumab group vs sham); and CFT had decreased by a mean of 337 microm (0.3 mg) and 345 microm (0.5 mg) in the ranibizumab groups and 158 microm in the sham group (P<0.0001 for each ranibizumab group vs sham). The median percent reduction in excess foveal thickness at month 6 was 97.0% and 97.6% in 0.3 mg and 0.5 mg groups and 27.9% in the sham group. More patients in the sham group (54.5%) received rescue grid laser compared with the 0.3 mg (18.7%) and 0.5 mg (19.8%) ranibizumab groups. The safety profile was consistent with previous phase III ranibizumab trials, and no new safety events were identified in patients with BRVO., Conclusions: Intraocular injections of 0.3 mg or 0.5 mg ranibizumab provided rapid, effective treatment for macular edema following BRVO with low rates of ocular and nonocular safety events., (Copyright 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

We have studied monolayers of poly(n-tetradecyl 4-vinylpyridinium-co-4-vinylpyridine) bromide with different degrees of quaternization at the air-water interface. The isotherms (surface pressure vs area) present several phase transitions: at low monolayer coverage, there is a phase transition over a characteristic area that increases on increasing the quaternization degree. This behavior can be rationalized in terms of a mean-field theory of 2D semiflexible polymeric chains and could be an indication of a disorder-order transition from a 2D isotropic liquid (IL) at low surface concentration to a 2D nematic phase (N) at higher concentrations. Low-frequency oscillatory strain experiments show that at low surface coverage the monolayers exhibit highly nonlinear behavior, even for low strain amplitude, whereas at higher surface coverage the response is linear for strains higher than 20%. In addition, stress relaxation experiments show a minimum in the characteristic times that coincide with the transition area. These unexpected results at low surface coverage might be characteristic of the system or related to the fact that the oscillatory experiments do not strictly correspond to constant surface-coverage conditions. However, they are in agreement with high-frequency viscoelasticity, obtained by surface quasielastic light scattering, that shows that the dilational viscosity is higher at low surface concentration than for concentrations beyond the surface phase transition. At higher coverage, there is a second phase transition, after which the isotherms present hysteresis, which is not observed below. Ellipsometry indicates that, after this transition, the monolayer thicken, which may be related to 3D growth into a multilayer.