DMENet: Diabetic Macular Edema diagnosis using Hierarchical Ensemble of CNNs.

Diabetic Macular Edema (DME) is an advanced stage of Diabetic Retinopathy (DR) and can lead to permanent vision loss. Currently, it affects 26.7 million people globally and on account of such a huge number of DME cases and the limited number of ophthalmologists, it is desirable to automate the diagnosis process. Computer-assisted, deep learning based diagnosis could help in early detection, following which precision medication can help to mitigate the vision loss. METHOD:In order to automate the screening of DME, we propose a novel DMENet Algorithm which is built on the pillars of Convolutional Neural Networks (CNNs). DMENet analyses the preprocessed color fundus images and passes it through a two-stage pipeline. The first stage detects the presence or absence of DME whereas the second stage takes only the positive cases and grades the images based on severity. In both the stages, we use a novel Hierarchical Ensemble of CNNs (HE-CNN). This paper uses two of the popular publicly available datasets IDRiD and MESSIDOR for classification. Preprocessing on the images is performed using morphological opening and gaussian kernel. The dataset is augmented to solve the class imbalance problem for better performance of the proposed model. RESULTS:The proposed methodology achieved an average Accuracy of 96.12%, Sensitivity of 96.32%, Specificity of 95.84%, and F-1 score of 0.9609 on MESSIDOR and IDRiD datasets. CONCLUSION:These excellent results establish the validity of the proposed methodology for use in DME screening and solidifies the applicability of the HE-CNN classification technique in the domain of biomedical imaging

Mycophenolic Acid for Topical Immunosuppression in Vascularized Composite Allotransplantation: Optimizing Formulation and Preliminary Evaluation of Bioavailability and Pharmacokinetics

Mycophenolic acid (MPA), is the active form of the ester prodrug mycophenolate mofetil (MMF). MMF is an FDA approved immunosuppressive drug that has been successfully used in systemic therapy in combination with other agents for the prevention of acute rejection (AR) following solid organ transplantation (SOT) as well as in vascularized composite allotransplantation (VCA). Systemic use of MMF is associated with gastrointestinal adverse effects. Topical delivery of the prodrug could thus provide graft-targeted immunosuppression while minimizing systemic drug exposure. Our goal was to develop a topical formulation of MPA with optimal in vitro/in vivo characteristics such as release, permeation, and tissue bioavailability to enable safety and efficacy evaluation in clinical VCA.Permeation studies were performed with a solution of MPA (10 mg/ml). In vitro release and permeation studies were performed for different semisolid formulations (Aladerm, Lipoderm, emollient, and VersaBase) of MPA (1% w/w) using a Franz Diffusion Cell System (FDCS). In vivo pharmacokinetic characterization of MPA release from Lipoderm was performed in rats.MPA in solution exhibited a steady state flux (3.8 ± 0.1 µg/cm2/h) and permeability (1.1 × 10−7 ± 3.2 × 10−9 cm/s). MPA in Lipoderm exhibited a steady state flux of 1.12 ± 0.24 µg/cm2/h, and permeability of 6.2 × 10−09 ± 1.3 × 10−9 cm/s across the biomimetic membrane. The cumulative release of MPA from Lipoderm, showed a linear single-phase profile with a R2 of 0.969. In vivo studies with MPA in Lipoderm showed markedly higher local tissue MPA levels and lower systemic MPA exposure as compared to values obtained after intravenous delivery of the same dose of drug (p < 0.05).We successfully developed for the first time, a topical formulation of MPA in Lipoderm with optimal in vitro/in vivo permeability characteristics and no undesirable local or systemic adverse effects in vivo. Our study provides key preliminary groundwork for translational efficacy studies of topical MPA in pre-clinical large animal VCA models and for effectiveness evaluation in patients receiving VCA

Mycophenolic Acid for Topical Immunosuppression in Vascularized Composite Allotransplantation: Optimizing Formulation and Preliminary Evaluation of Bioavailability and Pharmacokinetics

Mycophenolic acid (MPA), is the active form of the ester prodrug mycophenolate mofetil (MMF). MMF is an FDA approved immunosuppressive drug that has been successfully used in systemic therapy in combination with other agents for the prevention of acute rejection (AR) following solid organ transplantation (SOT) as well as in vascularized composite allotransplantation (VCA). Systemic use of MMF is associated with gastrointestinal adverse effects. Topical delivery of the prodrug could thus provide graft-targeted immunosuppression while minimizing systemic drug exposure. Our goal was to develop a topical formulation of MPA with optimal /in vivo characteristics such as release, permeation, and tissue bioavailability to enable safety and efficacy evaluation in clinical VCA. Permeation studies were performed with a solution of MPA (10 mg/ml). release and permeation studies were performed for different semisolid formulations (Aladerm, Lipoderm, emollient, and VersaBase) of MPA (1% w/w) using a Franz Diffusion Cell System (FDCS). pharmacokinetic characterization of MPA release from Lipoderm was performed in rats. MPA in solution exhibited a steady state flux (3.8 ± 0.1 µg/cm/h) and permeability (1.1 × 10 ± 3.2 × 10 cm/s). MPA in Lipoderm exhibited a steady state flux of 1.12 ± 0.24 µg/cm/h, and permeability of 6.2 × 10 ± 1.3 × 10 cm/s across the biomimetic membrane. The cumulative release of MPA from Lipoderm, showed a linear single-phase profile with a R of 0.969. studies with MPA in Lipoderm showed markedly higher local tissue MPA levels and lower systemic MPA exposure as compared to values obtained after intravenous delivery of the same dose of drug ( < 0.05). We successfully developed for the first time, a topical formulation of MPA in Lipoderm with optimal / permeability characteristics and no undesirable local or systemic adverse effects . Our study provides key preliminary groundwork for translational efficacy studies of topical MPA in pre-clinical large animal VCA models and for effectiveness evaluation in patients receiving VCA