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Purpose: To evaluate the outcomes of uveitic macular edema at 6 and 12 months in patients treated with methotrexate or mycophenolate mofetil., Design: Subanalysis of a block-randomized, observer-masked, multicenter clinical trial., Participants: Patients were enrolled in the First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial between August 2013 and August 2017., Methods: Patients were randomized to oral methotrexate 25 mg weekly or mycophenolate mofetil 1.5 g twice daily for 12 months, along with a corticosteroid taper. In addition to standardized clinical examination, all patients underwent spectral-domain OCT imaging at each visit. At the 6-month primary end point, patients who achieved treatment success continued the same treatment for a subsequent 6 months, and treatment failures switched to the other treatment group., Main Outcome Measures: Prespecified 6-month primary outcome and 12-month outcomes of central subfield thickness and visual acuity., Results: Of 216 patients in the FAST Trial, 42 eyes (30 patients) in the methotrexate group and 55 eyes (41 patients) in the mycophenolate group had uveitic macular edema. Baseline median central subfield thickness was 359 μm and 342 μm in the methotrexate and mycophenolate groups, respectively. At 12 months, for those who stayed on the same treatment, macular thickness decreased from baseline by 30.5 μm (interquartile range [IQR], -132.3 to 4.0) and 54 μm (IQR, -95.5 to -4.5) in the methotrexate and mycophenolate groups, respectively (P = 0.73). In patients who switched treatment at 6 months, macular thickness decreased from baseline by 12.5 μm (IQR, -32.3 to -0.5) and 50 μm (IQR, -181.0 to -10.0) in the methotrexate and mycophenolate groups, respectively (P = 0.34). At 12 months, 7 of 19 eyes (37%) on methotrexate had resolution of macular edema compared with 15 of 25 eyes (60%) on mycophenolate (P = 0.10). For those who switched treatments, 8 of 17 eyes (47%) on methotrexate and 6 of 11 eyes (55%) on mycophenolate had resolution of macular edema (P = 0.92)., Conclusions: Treatment with methotrexate or mycophenolate mofetil for uveitic macular edema results in similar improvements in macular thickness at 6 and 12 months. At 12 months, approximately half of eyes in each antimetabolite group still had persistent macular edema., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites., Design: Secondary analysis of a randomized controlled trial., Participants: Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico., Methods: From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests., Main Outcome Measures: Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months)., Results: Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively)., Conclusions: Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning., (Copyright © 2021 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

The solution properties of aqueous ethanol donor solutions were characterized for the particular case of an increased flux nitroglycerin transdermal system. Permeation through porous and nonporous polymer membranes was investigated and modelled. While the permeation of ethanol through the porous membranes is adequately described by theory, clogging of pores occurs in the presence of lactose. Permeation through ethylene vinyl acetate membranes reflects interactions of the solute and solvent with the polymer.

The self-association of insulin monomers into oligomers and macromolecular aggregates leads to complications in the administration of insulin, both in conventional administration and in the development of long-term insulin delivery systems. These problems are aggravated by the tendency of insulin to adsorb onto the surface of solution containers and infusion devices. Furthermore, with insulin infusion devices, shear rates can be generated which can accelerate the self-association and surface adsorption processes. The effects of urea on shear-induced insulin self-association and surface adsorption were investigated. It was found that the addition of a certain concentration range of urea to insulin solutions greatly reduces both insulin self-association and surface adsorption. Circular dichroic studies established that these concentrations of urea also preserve insulin conformation under high shear rates, where conformations are altered without urea. Higher urea concentrations lead to insulin denaturation and accelerated self-association.

An optimal concentration range of aqueous ethanol produces 5-10-fold increases in nitroglycerin flux across skin and ethanol skin permeation that are far greater than reported previously. For aqueous ethanol solutions saturated with nitroglycerin with an ethanol volume fraction less than or equal to 0.7, the flux of nitroglycerin across skin is linear with the ethanol flux and is traced to a linear solubility relationship and a constant diffusion coefficient.