Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial.

BACKGROUND: Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. METHODS: In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. FINDINGS: We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. INTERPRETATION: This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. FUNDING: Pfizer, UK National Institute for Health Research Biomedical Research Centre.

Glaucoma and fitness to drive: using binocular visual fields to predict a milestone to blindness.

PURPOSE: To use binocular integrated visual field (IVF) measures to predict which patients will lose visual function to a level below the legal standard for driving. METHODS: Data from patients attending a glaucoma clinic were collected longitudinally. The time from baseline until failure to meet the criteria of the driver's license test was modeled with Cox regression. Visual field status at baseline and visual field deterioration rate at 2 years from baseline for various monocular and binocular VF indices were investigated as predictor variables. The model that provided the best fit to the data was validated using bootstrap resampling. RESULTS: Of the patients, 20% (60/299; 95% confidence interval, 16%-25%) failed to meet the visual field criteria to prevent driver's license loss during an average follow-up of 7 years. The median age of patients was 64 years. The binocular IVF measurements gave a better fit to the observed data than the monocular measurements. Initial average visual field sensitivity and rate of visual field loss of sensitivity were significant predictors of failure to meet driver's license test criteria. CONCLUSIONS: The IVF provides a method by which binocular visual fields can be incorporated into patient management and allows, for example, a prediction of future driver's license loss. The rate of binocular IVF sensitivity loss at 2 years of follow-up may help identify patients who could benefit from intensified intervention.

Preparation of Ibuprofen Microparticles by Antisolvent Precipitation Crystallization Technique: Characterization, Formulation, and In Vitro Performance.

This study demonstrates the preparation and characterization of ibuprofen (IBP) microparticles with some excipients by a controlled crystallization technique with improved dissolution performance. Using the optimum concentrations pluronic F127, hydroxypropyl methyl cellulose, D-mannitol, and l-leucine in aqueous ethanol, the IBP microparticles were prepared. The dissolution tests were performed in phosphate buffer saline using a United States Pharmacopoeia dissolution tester at 37°C. The Raman spectroscopy was used to investigate the interactions and distribution of the IBP with the additives in the microcrystals. The prepared IBP microparticles showed higher dissolution compared to that of the smaller sized original IBP particles. The Raman data revealed that the excipients with a large number of hydroxyl groups distributed around the IBP particle in the crystal enhanced the dissolution of the drug by increasing the drug-solvent interaction presumably through hydrogen bonding. The Raman mapping technique gave an insight into the enhanced dissolution behavior of the prepared IBP microparticles, and such information will be useful for developing pharmaceutical formulations of hydrophobic drugs. The controlled crystallization was a useful technique to prepare complex crystals of IBP microparticles along with other additives to achieve the enhanced dissolution profile.

Dissolution behavior of soy proteins and effect of initial concentration.

The solution concentration profiles of soy protein and its components, glycinin and beta-conglycinin, as a function of pH and initial concentration have been measured. The concentration profiles generally followed a U-shaped trend with pH, with a minimum at around pH 4-5. Dissolution concentration unexpectedly increased with the initial concentration of the solution, with the increase being approximately proportional to the increase in initial concentration. The reasons for this are not clear. For the initial concentrations studied, beta-conglycinin is undersaturated between pH 5 and 7 and remains in solution, while glycinin becomes supersaturated in the same pH range and precipitates. Therefore separation of the two proteins can be achieved.

Osmotic second virial cross-coefficient measurements for binary combination of lysozyme, ovalbumin, and α-amylase in salt solutions.

Interactions measurement is a valuable tool to predict equilibrium phase separation of a desired protein in the presence of unwanted macromolecules. In this study, cross-interactions were measured as the osmotic second virial cross-coefficients (B23 ) for the three binary protein systems involving lysozyme, ovalbumin, and α-amylase in salt solutions (sodium chloride and ammonium sulfate). They were correlated with solubility for the binary protein mixtures. The cross-interaction behavior at different salt concentrations was interpreted by either electrostatic or hydrophobic interaction forces. At low salt concentrations, the protein surface charge dominates cross-interaction behavior as a function of pH. With added ovalbumin, the lysozyme solubility decreased linearly at low salt concentration in sodium chloride and increased at high salt concentration in ammonium sulfate. The B23 value was found to be proportional to the slope of the lysozyme solubility against ovalbumin concentration and the correlation was explained by preferential interaction theory.

Comparison of neuroretinal rim area measurements made by the Heidelberg Retina Tomograph I and the Heidelberg Retina Tomograph II.

PURPOSE: To investigate the agreement between neuroretinal rim area (RA) measurements using the Heidelberg Retina Tomograph I (HRT Classic) and Heidelberg Retina Tomograph II (HRT II). To compare apparent RA changes in follow-up series of HRT II topographies when using either an HRT Classic or HRT II mean topography as baseline. DESIGN: Cross-sectional study and "no-change," short time series study. PARTICIPANTS: Forty-three ocular hypertensive and 31 primary open angle glaucoma subjects. METHODS: Five HRT Classic and 5 HRT II examinations were acquired from 1 eye of each subject, across 2 visits within 6 weeks. For the cross-sectional study, follow-up RA measurements from HRT Classic and HRT II were compared, using the same HRT Classic mean topography as the baseline. The linear rates of RA change were compared in 2 short time series with either an HRT Classic or an HRT II mean topography as baseline, and 4 follow-up HRT II mean topographies. Intervals between topographies were arbitrarily set at 1 year for meaningful comparisons of rates. Rates of RA change over time were calculated by linear regression. Separate analyses were performed using 3 available reference planes (RP). MAIN OUTCOME MEASURES: Global and sectoral RA measurements in HRT Classic and HRT II mean topographies; linear rates of RA change. RESULTS: HRT Classic minus HRT II mean differences (95% limits of agreement) were 0.09 (-0.17, 0.35) mm, 0.09 (-0.13, 0.32) mm, and 0.11 (-0.24, 0.46) mm for the Moorfields, 320 µm, and standard RPs, respectively (P<0.001 for all RPs, Wilcoxon rank sum test). In the time series, the mean differences (95% limits of agreement) of RA rates of change (HRT Classic baseline minus HRT II baseline) were -0.01 (-0.06, 0.03) mm/y, -0.01 (-0.06, 0.04) mm/y, and -0.0 (-0.09, 0.05) mm/y using the Moorfields, 320 µm, and standard RPs, respectively. CONCLUSION: Although HRT software is backward-compatible, follow-up RA measurements made in the same eye using HRT Classic and HRT II devices display statistically and clinically meaningful systematic differences when HRT Classic topographies are used as a baseline.

Correlation of second virial coefficient with solubility for proteins in salt solutions.

In this work, osmotic second virial coefficients (B(22)) were determined and correlated with the measured solubilities for the proteins, α-amylase, ovalbumin, and lysozyme. The B(22) values and solubilities were determined in similar solution conditions using two salts, sodium chloride and ammonium sulfate in an acidic pH range. An overall decrease in the solubility of the proteins (salting out) was observed at high concentrations of ammonium sulfate and sodium chloride solutions. However, for α-amylase, salting-in behavior was also observed in low concentration sodium chloride solutions. In ammonium sulfate solutions, the B(22) are small and close to zero below 2.4 M. As the ammonium sulfate concentrations were further increased, B(22) values decreased for all systems studied. The effect of sodium chloride on B(22) varies with concentration, solution pH, and the type of protein studied. Theoretical models show a reasonable fit to the experimental derived data of B(22) and solubility. B(22) is also directly proportional to the logarithm of the solubility values for individual proteins in salt solutions, so the log-linear empirical models developed in this work can also be used to rapidly predict solubility and B(22) values for given protein-salt systems.