Structural and Functional Measures of Efficacy in Response to Bevacizumab Monotherapy in Diabetic Macular Oedema: Exploratory Analyses of the BOLT Study (Report 4)

Background To describe structural and functional changes associated with diabetic macular oedema (DMO) treated with intravitreal bevacizumab over 24 months. Methods A post-hoc analysis of the data of 34 patients that completed 24 months follow-up in the intravitreal bevacizumab arm of a prospective, randomized controlled trial (BOLT study) was performed. The outcome measures previously used in clinical trials of intravitreal ranibizumab in DMO were employed to describe the visual acuity and macular thickness changes at 12 and 24 months. Results The standard outcomes of mean change in best corrected visual acuity (BCVA) and central macular thickness (CMT) in participants treated with bevacizumab were comparable to those reported in association with ranibizumab. However, exploratory analyses showed that thick maculae at baseline defined as CMT of ≥400 µm, remained significantly thicker than those <400 µm with intensive bevacizumab therapy, despite a comparable gain in visual acuity at both 12 and 24 months. The proportion of subjects that attained a dry macula doubled in both CMT groups between the 12 and 24-month time-points. Conclusions These findings provide valuable information both for clinical practice and trials. Further studies are required to investigate the impact of intravitreal bevacizumab on retinal thickness profiles in DMO

Further Step in the Transition from Conventional Plasticizers to Versatile Bioplasticizers Obtained by the Valorization of Levulinic Acid and Glycerol

Valorization of glycerol and levulinicacid by a solvent-freeand mild-condition reaction to obtain a high-efficiency bioplasticizersuitable for different polymers.In the last two decades,the use of phthalates has beenrestrictedworldwide due to their well-known toxicity. Nonetheless, phthalatesare still widely used for their versatility, high plasticization effect,low cost, and lack of valuable alternatives. This study presents thefully bio-based and versatile glycerol trilevulinate plasticizer (GT)that was obtained by the valorization of glycerol and levulinic acid.The mild-conditions and solvent-free esterification used to synthesizeGT was optimized by investigating the product by Fourier transforminfrared and NMR spectroscopy. An increasing content of GT, from 10to 40 parts by weight per hundred parts of resin (phr), was testedwith poly(vinyl chloride), poly(3-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate), poly(lactic acid), and poly(caprolactone),which typically present complicatedprocessability and/or mechanical properties. GT produced a significantplasticization effect on both amorphous and semicrystalline polymers,reducing their glass-transition temperature and stiffness, as observedby differential scanning calorimetry measurements and tensile tests.Remarkably, GT also decreased both the melting temperature and crystallinitydegree of semicrystalline polymers. Furthermore, GT underwent enzyme-mediatedhydrolysis to its initial constituents, envisioning a promising prospectivefor environmental safety and upcycling. Furthermore, 50% inhibitoryconcentration (IC50) tests, using mouse embryo fibroblasts,proved that GT is an unharmful alternative plasticizer, which makesit potentially applicable in the biomedical field

Levulinic acid-based bioplasticizers: a facile approach to enhance the thermal and mechanical properties of polyhydroxyalkanoates

PHB has been engineered by incorporating different levulinic acid-based bioplasticizers, which enhance flexibility and thermal processability of the neat biopolymer, while retaining excellent biocompatibility and biodegradability

Randomized Phase IIb Study of Brimonidine Drug Delivery System Generation 2 for Geographic Atrophy in Age-Related Macular Degeneration

Purpose: To evaluate the safety and efficacy of repeat injections of Brimonidine Drug Delivery System (Brimo DDS) Generation 2 (Gen 2) containing 400-μg brimonidine in patients with geographic atrophy (GA) secondary to age-related macular degeneration (AMD). Design: A phase IIb, randomized, multicenter, double-masked, sham-controlled, 30-month study (BEACON). Participants: Patients diagnosed with GA secondary to AMD and multifocal lesions with total area of &gt; 1.25 mm2 and ≤ 18 mm2 in the study eye. Methods: Enrolled patients were randomized to treatment with intravitreal injections of 400-μg Brimo DDS (n = 154) or sham procedure (n = 156) in the study eye every 3 months from day 1 to month 21. Main Outcome Measures: The primary efficacy endpoint was GA lesion area change from baseline in the study eye, assessed with fundus autofluorescence imaging, at month 24. Results: The study was terminated early, at the time of the planned interim analysis, because of a slow GA progression rate (∼ 1.6 mm2/year) in the enrolled population. Least squares mean (standard error) GA area change from baseline at month 24 (primary endpoint) was 3.24 (0.13) mm2 with Brimo DDS (n = 84) versus 3.48 (0.13) mm2 with sham (n = 91), a reduction of 0.25 mm2 (7%) with Brimo DDS compared with sham (P = 0.150). At month 30, GA area change from baseline was 4.09 (0.15) mm2 with Brimo DDS (n = 49) versus 4.52 (0.15) mm2 with sham (n = 46), a reduction of 0.43 mm2 (10%) with Brimo DDS compared with sham (P = 0.033). Exploratory analysis showed numerically smaller loss over time in retinal sensitivity assessed with scotopic microperimetry with Brimo DDS than with sham (P = 0.053 at month 24). Treatment-related adverse events were usually related to the injection procedure. No implant accumulation was observed. Conclusions: Multiple intravitreal administrations of Brimo DDS (Gen 2) were well tolerated. The primary efficacy endpoint at 24 months was not met, but there was a numeric trend for reduction in GA progression at 24 months compared with sham treatment. The study was terminated early because of the lower-than-expected GA progression rate in the sham/control group. Financial Disclosure(s): Proprietary or commercial disclosures may be found after the references

Preparation, characterization, and antibacterial activity of photocured thymol-doped acrylic resins

This article describes the preparation of thymol-doped acrylic resins by photopolymerization of solutions of thymol in tripropylenglycoldiacrylic monomer. This provides an easy, energy-saving, and environmental friendly process to prepare antibacterial plastics (fulfilling most of the "green chemistry" requirements). The results demonstrate that thymol can be included in the resin even at high concentration (up to 28.6%) without affecting the photocuring reaction and losing transparency. The glass transition temperature of the doped resin decreases when the thymol content increases, as it behaves like a plasticizer with respect to the acrylic resin. As indicated by HPLC analysis, thymol can be released in liquid media at a rate that depends on the chemical nature of the liquid. Evaluation by agar diffusion assays showed an antibacterial activity on both Gram-negative and Gram-positive bacteria (Staphylococcus aureus, Listeria monocytogenes, and Escherichia coli). The antibacterial activity can occur just on the plastic surface when the thymol-doped resins is applied as thin coating, while it is evident also in the surrounding agar medium for doped plastic discs, 1.2 mm thick with a concentration of thymol in the resin higher than 16.7%

Attività anti-listeria di Enterococcus casseliflavus 416K1batteriocino-produttore intrappolato in forma vivente incoating applicati a film di PET da impiegarsi nel campodell’active food packaging

OBIETTIVI Il consumo di alimenti “ready-to-eat” e di prodotti refrigerati ha provocato un incremento di listeriosi e, poiché la refrigerazione è uno dei mezzi più efficaci di conservazione, la riconosciuta psicotrofia del patogeno ne rende il controllo estremamente difficoltoso. Una innovativa metodologia di “active food packaging” è stata da noi messa a punto incorporando nel materiale di confezionamento agenti microbici in grado di rallentare o inibire la proliferazione di L. monocytogenes. MATERIALI E METODI E’ stata valutata l’attività antilisteria di film polimerici (coating) contenenti una batteriocina purificata (Enterocina 416K1) e quella di film preparati inglobando lo stesso microrganismo produttore Enterococcus casseliflavus 416K1 in forma vitale. Tale attività è stata determinata qualitativamente “in vitro” e quantitativamente su campioni (formaggio e wurstel) artificialmente contaminati con L. monocytogenes NCTC10888. RISULTATIEntrambe le valutazioni hanno messo in evidenza l’attività antibatterica dei due tipi di coating nei confronti di L. monocytogenes NCTC10888. E’ stato possibile anche osservare nei coating allestiti con batteri vivi, la crescita di minicolonie di E. casseliflavus che in corrispondenza del loro sviluppo evidenziano attività antibatterica. CONCLUSIONI I risultati ottenuti dimostrano una buona attività antilisteria sia della batteriocina che del microrganismo stesso inglobato in forma vitale e che l’intrappolamento nei coating ibridi è sia compatibile col mantenimento della forma attiva della batteriocina che con la vitalità dei microrganismi. Il lavoro presentato è, a nostro avviso, una novità nel campo dell’active food packaging e in prospettiva potrà trovare un’utile applicazione nel campo della bioconservazione

Prospective exploratory study to assess the safety and efficacy of aflibercept in cystoid macular oedema associated with retinitis pigmentosa

AIMS: To report the safety and efficacy of intravitreal aflibercept (Eylea) (ivA) for retinitis pigmentosa-associated cystoid macular oedema (RP-CMO) at 12 months via mean central macular thickness (CMT) and reported adverse events. METHODS: A prospective, exploratory, phase II, non-randomised, single-centre, open-label, 1-arm clinical trial involving 30 eyes of 30 patients. Serial ivA was given via loading dose (three injections) followed by treat and extend protocol over 12 months. RESULTS: Twenty-nine out of 30 (96.7%) patients completed 12 months of follow-up. A total of four to 11 injections per patient were given over the 12 month study. No statistically significant reduction of CMT or visual acuity (VA) improvement was demonstrated in the group overall. Eleven out of 29 (37.9%) participants were considered as 'responders', demonstrating at least an 11% reduction of CMT at 12 months on spectral domain optical coherence tomography compared with baseline. A reduction of CMT by mean (SD) 28.1% (12.9 %) was observed in responders at 12 months, however, no statistically significant corresponding improvement in best corrected VA was seen. Baseline characteristics were similar between responder and non-responder groups. No clinically significant adverse events were deemed secondary to ivA. CONCLUSION: This first prospective exploratory study demonstrates both the safety and acceptability of serial ivA in patients with RP-CMO, effective at reducing CMT in 37.9% of patients. All patients demonstrating anatomical response did so after their first injection. Longer duration of CMO did not negatively affect response to anti-VEGF. Further study in a larger cohort of patients with shorter CMO duration would be valuable to better establish the utility of VEGF blockade in RP-CMO. TRIAL REGISTRATION NUMBERS: EudraCT (2015-003723-65); ClinicalTrials.gov (NCT02661711)