Topical nepafenac in the treatment of diabetic macular edema

David Callanan, Patrick WilliamsTexas Retina Associates, Arlington, TX, USAPurpose: To determine the safety and efficacy of topical nepafenac 0.1% in the treatment of diabetic macular edema.Methods: A consecutive case series was performed of patients treated with nepafenac monotherapy twice daily for diabetic macular edema. Visual acuities (VA) at baseline and final visit were recorded. Foveal thickness, based on optical coherence tomography, was also recorded.Results: Six eyes of 5 patients were included in this study. Median initial Snellen vision was 20/100 (range, 20/40–20/400). After a mean of 210 days (range, 182–259), median final VA was 20/75 (range, 20/40–20/400). Four eyes gained vision and two eyes maintained vision. Mean pre-treatment vision was 0.78 logMAR and final VA was 0.67 logMAR, for a statistically significant improvement (p < 0.05). Mean initial foveal thickness was 417 microns (range, 286–599). After a mean of 178 days (range, 91–259), mean foveal thickness was 267 microns (range, 158–423), showing a statistically significant improvement (p < 0.05). Each eye had an improvement in foveal thickness.Conclusion: The results from these 6 eyes suggest that nepafenac 0.1% may have activity against diabetic macular edema and warrants further investigation.Keywords: diabetes, diabetic macular edema, inflammation, macular edema, nepafenac, NSAID

The role of difluprednate ophthalmic emulsion in clinical practice

The mainstay in the treatment of ocular inflammation, either post-surgical or endogenous, is the use of steroids. While these agents effectively address inflammation, they are not without their risks, including ocular hypertension and acceleration of cataract formation. The most notorious culprits are the strong steroids, such as prednisolone acetate and betamethasone. This review aims to cover the biochemistry and drug development of difluprednate, a novel synthetic strong steroid emulsion. In vivo pharmacokinetics as well as ocular distribution and metabolism are discussed, followed by a comprehensive summary of phase I, II, and III clinical trials evaluating safety and efficacy in patients suffering from postoperative inflammation or anterior uveitis. The objective is to provide an increased familiarity with this newly approved medication as a welcome addition to the ophthalmologist’s armamentarium

A Real Option Approach for the Valuation of Switching Output Flexibility in Residential Property Investment

Uncertainties in residential property investment performance require that real estate assets are designed flexible in order to respond to impacts of market dynamics. Though estimating the cost of flexibility is straightforward, assessing the economic value of flexibility is not. The purpose of this study is to explore the potential practical application of real option analysis to determine the economic value of a switching output flexibility embedded in a residential property investment in Australia. The study involves the exploration of an optimal strategy for investment in a residential development through real option analysis and valuation of a mixed use investment. The real option valuation model developed by McDonald and Siegel (1986) is adopted for the evaluation because the switching output flexibility is likened to a perpetual American call option with dividend payouts. Through real option analysis, the economic value of switching output flexibility of the mixed use building was determined to be higher than the initial upfront costs. Moreover, a payoff of about $4million was determined to be the value of the switching output flexibility, therefore justifying upfront investments in flexibility as an uncertainty and risk management tool. This application is an important demonstration of the practical use of options pricing techniques (real options analysis) and delivers further evidence needed to support the adoption of real option tools in practice. Flexibility can also enhance risks and uncertainty management in residential property investment better than the adjustment of discount rates. There is limited evidence on the use of real options techniques for the valuation of switching output flexibility in practice and this comes as an original application; both the case study and data are all initial applications of switching flexibility in the Australian property market

Staging Option Application to Residential Development: Real Options Approach

Purpose: Real option valuation is capable of accounting for uncertainties in residential development projects but still lacks practical adoption due to limited evidence to support application of the theory in practice. The purpose of this paper is to use option valuation to value staging option embedded in residential projects and compare with results from DCF to determine which of the two methods delivers superior results. Design/methodology/approach: The fuzzy payoff method (FPOM), a real options model that uses scenario planning approach to generate a range of figures, from which a single-numerical value is computed for decision-making. Findings: The results showed that the use of a range of figures was able to represent uncertainties to a higher degree of accuracy than the static DCF. As a result, the FPOM was able to capture about 3 per cent of the value of the project that was missed by the DCF. The staging option offers an opportunity to abandon unprofitable phases of a project, thereby limiting downside losses. Thus, real option models are practically applicable to cases in property sector. Practical implications: Residential property developers must consider flexibility in financial feasibility evaluation of development because of the embedded value in uncertain property projects. It is important to account for optionality in financial evaluation of property projects for value maximisation. Originality/value: The FPOM has been used for the first time to evaluate a horizontal phasing of a residential development project

Blended electrospinning with human liver extracellular matrix for engineering new hepatic microenvironments

Abstract Tissue engineering of a transplantable liver could provide an alternative to donor livers for transplant, solving the problem of escalating donor shortages. One of the challenges for tissue engineers is the extracellular matrix (ECM); a finely controlled in vivo niche which supports hepatocytes. Polymers and decellularized tissue scaffolds each provide some of the necessary biological cues for hepatocytes, however, neither alone has proved sufficient. Enhancing microenvironments using bioactive molecules allows researchers to create more appropriate niches for hepatocytes. We combined decellularized human liver tissue with electrospun polymers to produce a niche for hepatocytes and compared the human liver ECM to its individual components; Collagen I, Laminin-521 and Fibronectin. The resulting scaffolds were validated using THLE-3 hepatocytes. Immunohistochemistry confirmed retention of proteins in the scaffolds. Mechanical testing demonstrated significant increases in the Young’s Modulus of the decellularized ECM scaffold; providing significantly stiffer environments for hepatocytes. Each scaffold maintained hepatocyte growth, albumin production and influenced expression of key hepatic genes, with the decellularized ECM scaffolds exerting an influence which is not recapitulated by individual ECM components. Blended protein:polymer scaffolds provide a viable, translatable niche for hepatocytes and offers a solution to current obstacles in disease modelling and liver tissue engineering

Erratum to: ‘Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis’

ErratumErratum to: ‘Integrated analysis of the local and systemic changes preceding the development of post-partum cytological endometritis’ -http://hdl.handle.net/11019/90

Treatment of steroid-induced elevated intraocular pressure with anecortave acetate: a randomized clinical trial.

PURPOSE: The present study is the first randomized clinical trial designed to evaluate the intraocular pressure (IOP)-lowering effect of anecortave acetate (AA) administered at 3 doses (3, 15, or 30 mg) as an anterior juxtascleral depot (AJD) in patients experiencing elevated IOP due to corticosteroid therapy. METHODS: This was a double-masked, randomized, placebo-controlled, multicenter, parallel group trial. Eligible patients had an IOP of at least 24 mmHg and an IOP increase of at least 10 mmHg relative to their IOP before treatment with steroids. A target IOP was established for each patient at baseline. Patients were randomized to 1 of the 4 treatment groups: vehicle, 3 mg AA, 15 mg AA, or 30 mg AA. All patients then received a 0.5 mL AJD of the assigned treatment. Patients returned for scheduled examination visits at weeks 1, 2, 4, 6, months 3, 4, 5, and 6. IOP was measured at each visit as well as best corrected visual acuity (logMAR), ocular motility, eyelid responsiveness, slit lamp examination, and assessment of any adverse events. In addition, at baseline and at exit, a dilated fundus examination was carried out and the lens was examined using LOCS II criteria. RESULTS: Seventy patients were randomized to treatment. At week 4, eyes in the vehicle group showed a 3.4 mmHg (9.1%) decrease from baseline. Reductions for the 3 mg AA (3.1 mmHg, 10.7%) and the 30 mg AA groups (5.4 mmHg, 16.6%) were not significantly different than for vehicle control. However, IOP for the 15 mg AA group at week 4 was reduced 11.5 mmHg (31.3%) from baseline, which was statistically significant (P=0.0487). The mean time to treatment failure was 32.2, 38.9, 56.3, and 32.6 days for the vehicle, 3 mg AA, 15 mg AA, and 30 mg AA groups, respectively. Adverse events were assessed at each post-treatment visit. There were no serious adverse events that were determined to be related to the test article or its administration. CONCLUSIONS: AA can be of benefit to some patients requiring treatment with corticosteroids, but suffering from the side effect of elevated IOP

3D human liver tissue from pluripotent stem cells displays stable phenotype in vitro and supports compromised liver function in vivo.

Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue lacking certain functions and long-term stability. Efforts to overcome these limiting factors have led to the building of three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application is limited due to their reliance on variable biological components. Our studies focused on the development of 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype for over 1 year in culture, providing an attractive resource for long-term in vitro studies. Moreover, 3D derived tissue provided critical liver support in two animal models, including immunocompetent recipients. Therefore, we believe that our study provides stable human tissue to better model liver biology 'in the dish', and in the future may permit the support of compromised liver function in humans

Preliminary Assessment of Celecoxib and Microdiode Pulse Laser Treatment of Diabetic Macular Edema

Purpose: Inflammation may play an important role in the pathogenesis of diabetic macular edema, a major cause of vision loss in persons with diabetes. The purpose of this study was to evaluate combined antiinflammatory therapy and laser approaches for treating patients with diabetic macular edema. Methods: In this prospective, factorial, randomized, multicenter trial, we compared cyclo-oxygenase-2 inhibitor (celecoxib) with placebo and diode grid laser with standard Early Treatment Diabetic Retinopathy Study focal laser treatment in 86 participants with diabetic macular edema. The primary outcome is change in visual acuity of ≥15 letters from baseline, and the secondary outcomes include a 50% reduction in the retinal thickening of diabetic macular edema measured by optical coherence tomography and a 50% reduction in leakage severity on fluorescein angiography. Results: Visual acuity and retinal thickening data from >2 years of follow-up did not show evidence of differences between the medical and laser treatments. However, participants assigned to the celecoxib group were more likely to have a reduction in fluorescein leakage when compared with the placebo group (odds ratio = 3.6; P < 0.01). Conclusion: This short-term study did not find large visual function benefits of treatment with celecoxib or diode laser compared with those of standard laser treatment. A suggestive effect of celecoxib in reducing fluorescein leakage was observed