Pharmacokinetic aspects of retinal drug delivery

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.Peer reviewe

withdrawn 2017 hrs ehra ecas aphrs solaece expert consensus statement on catheter and surgical ablation of atrial fibrillation

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Functionally Assembled Terrestrial Ecosystem Simulator (FATES) for Hurricane Disturbance and Recovery

Abstract Tropical cyclones are an important cause of forest disturbance, and major storms caused severe structural damage and elevated tree mortality in coastal tropical forests. Model capabilities that can be used to understand post‐hurricane forest recovery are still limited. We use a vegetation demography model, the Functionally Assembled Terrestrial Ecosystem Simulator, coupled with the Energy Exascale Earth System Model Land Model (ELM‐FATES) to study the processes and the key factors regulating post‐hurricane forest recovery. We implemented hurricane‐induced forest damage, including defoliation, structural biomass reduction, and tree mortality, performed ensemble model simulations, and used random forest feature importance. For the simulation in the Luquillo Experimental Forest, Puerto Rico, we identified factors controlling the post‐hurricane forest recovery, and quantified the sensitivity of key model parameters to the post‐hurricane forest recovery. The results indicate a tendency for the Bisley forests to shift toward the light demanding plant functional type (PFT) when the pre‐hurricane biomass between the light demanding and shade tolerant PFTs is nearly equal and forests experience hurricane disturbance with mortality >60% for both the two PFTs. Under more realistic conditions where the shade tolerant PFT is initially dominant, mortality >80% is required for a shift toward dominance of the light demanding PFT at Bisley. Hurricane mortality and background mortality are the two major factors regulating post‐hurricane forest recovery in simulations. This research improves understanding of the ELM‐FATES model behavior associated with hurricane disturbance and provides guidance for dynamic vegetation model development in representing hurricane induced forest damage with varied intensities