Macular Pigment Distribution as Prognostic Marker for Disease Progression in Macular Telangiectasia Type 2

PURPOSE To evaluate macular pigment distribution pattern as a prognostic marker for disease progression in patients with macular telangiectasia type 2 (MacTel). DESIGN Retrospective cohort study. METHODS In this single-center study, 90 eyes of 47 patients were analyzed. Macular pigment optical density (MPOD) was measured with dual-wavelength fundus autofluorescence. Eyes were graded into MPOD distribution classes 1 to 3 with increasing loss of macular pigment and grading was performed masked by 2 independent graders. Best-corrected visual acuity, reading acuity, total scotoma size in fundus-controlled perimetry (microperimetry), and break of the ellipsoid zone (EZ) in optical coherence tomography (en face measurement) were defined as functional and morphologic outcome parameters and evaluated at baseline and after 60 months. RESULTS After a mean review period of 59.6 months (±standard deviation 5.2 months), no change between MPOD classes was observed compared to baseline. Morphologic and functional deficits were limited to the area of MPOD loss. At last follow-up, a significant mean decrease of visual acuity and reading acuity as well as a significant mean increase of scotoma size and EZ break were observed in eyes assigned to MPOD classes 2 and 3, while outcome parameters remained stable in eyes of class 1. CONCLUSIONS The results indicate that MPOD and its distribution may serve as a prognostic marker for disease progression and functional impairment in patients with MacTel

State of the art spatial visualization of the response of neovascularisation to anti-vascular endothelial growth factor therapy

PURPOSE: To visualize the mode of action of anti-vascular endothelial growth factor (anti-VEGFs) therapy on retinal neovascularization (RNV) in a patient with macular telangiectasia (MacTel) type 2 using a detailed three-dimensional data environment. OBSERVATION: A 60-year-old man presented with visual acuity loss and was diagnosed with MacTel type 2. Fluorescein angiography was not possible for safety reasons because of a history of severe reaction to fluorescein dye at his referring hospital. Optical coherence tomography angiography (OCTA) imaging revealed new retinal neovascular membranes (RNV) in the macula of both eyes. A marked reduction in the size of the RNV in both eyes was evident on volume-rendered three-dimensional OCTA retinal imaging after the first anti-VEGF injection. CONCLUSION AND IMPORTANCE: The ability to directly observe the effect of anti-VEGF injections on a RNV using three-dimensional OCTA was successfully demonstrated. This can be useful in patients with previous allergic and potentially lethal complications to fluorescein. In addition, enhanced three-dimensional spatial display of RNV leads to a greater understanding of the perfusion profile and the anatomical changes that occur in ocular neovascularization relative to surrounding tissue. This has the potential to provide insight into the pathobiology of angiogenesis

Quantification of Retinal and Choriocapillaris Perfusion in Different Stages of Macular Telangiectasia Type 2

Purpose: To quantify the retinal and choriocapillaris perfusion in different disease stages of macular telangiectasia type 2 (MacTel) using optical coherence tomography-angiography (OCT-A). / Methods: We examined 76 eyes of 76 patients and 24 eyes of 24 age-related controls. Participants underwent multimodal imaging, including OCT and OCT-A. Patients' eyes were divided into three groups considering predefined criteria from funduscopy, OCT, and fluorescein angiography, thus reflecting the disease severity (“early,” “advanced,” and “neovascular”). Quantitative analyses of vessel density (VD), skeleton density (SD), and fractal dimension (FD) were conducted in the superficial and deep retinal plexus and in the avascular layer. The choriocapillaris was analyzed for mean signal intensity and percentage of nondetectable perfused choriocapillaris-area (PNPA). / Results: The deep retinal plexus showed a progressive decrease of mean VD, SD, and FD in the temporal parafovea in all disease stages. In the superficial layer, VD, SD, and FD were significantly decreased in the temporal parafovea of advanced and neovascular stages, while these parameters did not differ from controls in early stages. In MacTel, signals of blood flow were also detectable at the level of the avascular layer and showed a significant increase with disease progression. The choriocapillaris in MacTel showed a significant increase of mean PNPA and a decrease of mean signal intensity in comparison to controls. These findings were consistent in all disease stages. / Conclusions: Quantitative OCT-A data show a progressive rarefication of the retinal microvasculature in MacTel. We propose an altered choriocapillaris perfusion as a possibly early alteration of the disease

Stereoscopic Vision in Macular Telangiectasia Type 2

PURPOSE: To investigate stereoscopic vision in patients with macular telangiectasia type 2 and correlate a paracentral sensitivity loss to reduced stereoscopic function. METHODS: In a prospective single-center study, 50 patients with macular telangiectasia type 2 and 25 age-matched controls were investigated. Stereoscopic function was evaluated with Lang I, Titmus and TNO-test. Sensitivity of the central 16° was tested using fundus-controlled perimetry (microperimetry). Functional loss was quantified as depth, size and localization of scotomata. RESULTS: Both Titmus and TNO-test revealed significantly reduced stereoscopic vision in patients compared to controls (both, p<0.0001). This applied even to patients with only relative or monocular paracentral scotomata. A strong correlation was observed for reduced stereoscopic vision with horizontal scotoma size and with the distance of scotomata from the foveal center. CONCLUSIONS: The results indicate that stereoscopic vision is impaired early in patients with MacTel type 2. A paracentral sensitivity loss, even if mild and limited to one eye, may considerably interfere with stereoscopic function despite normal visual acuity. Projection of paracentral scotomata within the patient`s central visual field plays an important role in stereoscopic vision and should be considered when interpreting stereoscopic test results

Low Density Lipoprotein Receptor-Related Protein 1 Dependent Endosomal Trapping and Recycling of Apolipoprotein E

BACKGROUND: Lipoprotein receptors from the low density lipoprotein (LDL) receptor family are multifunctional membrane proteins which can efficiently mediate endocytosis and thereby facilitate lipoprotein clearance from the plasma. The biggest member of this family, the LDL receptor-related protein 1 (LRP1), facilitates the hepatic uptake of triglyceride-rich lipoproteins (TRL) via interaction with apolipoprotein E (apoE). In contrast to the classical LDL degradation pathway, TRL disintegrate in peripheral endosomes, and core lipids and apoB are targeted along the endocytic pathway for lysosomal degradation. Notably, TRL-derived apoE remains within recycling endosomes and is then mobilized by high density lipoproteins (HDL) for re-secretion. The aim of this study is to investigate the involvement of LRP1 in the regulation of apoE recycling. PRINCIPAL FINDINGS: Immunofluorescence studies indicate the LRP1-dependent trapping of apoE in EEA1-positive endosomes in human hepatoma cells. This processing is distinct from other LRP1 ligands such as RAP which is efficiently targeted to lysosomal compartments. Upon stimulation of HDL-induced recycling, apoE is released from LRP1-positive endosomes but is targeted to another, distinct population of early endosomes that contain HDL, but not LRP1. For subsequent analysis of the recycling capacity, we expressed the full-length human LRP1 and used an RNA interference approach to manipulate the expression levels of LRP1. In support of LRP1 determining the intracellular fate of apoE, overexpression of LRP1 significantly stimulated HDL-induced apoE recycling. Vice versa LRP1 knockdown in HEK293 cells and primary hepatocytes strongly reduced the efficiency of HDL to stimulate apoE secretion. CONCLUSION: We conclude that LRP1 enables apoE to accumulate in an early endosomal recycling compartment that serves as a pool for the intracellular formation and subsequent re-secretion of apoE-enriched HDL particles

Tradeoffs in Model Performance and Effort for Long-Term Phosphorus Leaching Based on In Situ Field Data

Phosphorus and N are critical nutrients for agriculture but are also responsible for surface water enrichment that leads to toxic algal growth. Although P loading to surface waters has traditionally been thought to occur primarily in surface runoff, contributions from subsurface transport can also be significant. The primary objectives of this research were to evaluate several methods of representing macropore flow and transport in a finite element model using plot-scale infiltration and leaching data and to compare several models of various levels of complexity to simulate long-term P leaching. To determine flow and transport parameters, single- and dual-porosity models in HYDRUS-2D were calibrated with infiltration, Cl−, and P data from a 22-h plot-scale leaching experiment on a silt loam mantle with gravel subsoil. Both homogeneous and heterogeneous gravel profiles were simulated. The dual-porosity model with heterogeneous hydraulic conductivity best matched experimental data, with physical nonequilibrium (dual porosity) being more important than two-dimensional (2D) heterogeneity. Long-term (9 yr) P leaching to the water table (3 m below the soil surface) at the field site was simulated with both one-dimensional (1D) and 2D models using the calibrated parameters. There was little difference between analogous 1D and 2D models, suggesting that HYDRUS-1D may be sufficient to model long-term P leaching. Overall, the most important elements for accurately simulating P leaching in this silt loam and gravel soil profile were found to be (i) field-measured hydraulic conductivity of the limiting soil layer, (ii) calibrated dispersivity, and (iii) dual-porosity, in some circumstances

Providing care for older adults in the Emergency Department: expert clinical recommendations from the European Task Force on Geriatric Emergency Medicine

Cures agudes; Medicina d'urgències; GeriatriaCuidados agudos; Medicina de urgencias; GeriatríaAcute care; Emergency medicine; GeriatricsPurpose: Despite the rapidly expanding knowledge in the field of Geriatric Emergency Medicine in Europe, widespread implementation of change is still lacking. Many opportunities in everyday clinical care are missed to improve care for this susceptible and growing patient group. The aim was to develop expert clinical recommendations on Geriatric Emergency Medicine to be disseminated across Europe. Methods: A group of multi-disciplinary experts in the field of Geriatric Emergency Medicine in Europe was assembled. Using a modified Delphi procedure, a prioritized list of topics related to Geriatric Emergency Medicine was created. Next, a multi-disciplinary group of nurses, geriatricians and emergency physicians performed a review of recent guidelines and literature to create recommendations. These recommendations were voted upon by a group of experts and placed on visually attractive posters. The expert group identified the following eight subject areas to develop expert recommendations on: Comprehensive Geriatric Assessment in the Emergency Department (ED), age/frailty adjusted risk stratification, delirium and cognitive impairment, medication reviews in the ED for older adults, family involvement, ED environment, silver trauma, end of life care in the acute setting. Results: Eight posters with expert clinical recommendations on the most important topics in Geriatric Emergency Medicine are now available through https://posters.geriemeurope.eu/ . Conclusion: Expert clinical recommendations for Geriatric Emergency Medicine may help to improve care for older patients in the Emergency Department and are ready for dissemination across Europe

Integration of hydrogeophysical datasets and empirical orthogonal functions for improved irrigation water management

Precision agriculture offers the technologies to manage for infield variability and incorporate variability into irrigation management decisions. The major limitation of this technology often lies in the reconciliation of disparate data sources and the generation of irrigation prescription maps. Here the authors explore the utility of the cosmic-ray neutron probe (CRNP) which measures volumetric soil water content (SWC) in the top ~ 30 cm of the soil profile. The key advantages of CRNP is that the sensor is passive, non-invasive, mobile and soil temperature-invariant, making data collection more compatible with existing farm operations and extending the mapping period. The objectives of this study were to: (1) improve the delineation of irrigation management zones within a field and (2) estimate spatial soil hydraulic properties to make effective irrigation prescriptions. Ten CRNP SWC surveys were collected in a 53-ha field in Nebraska. The SWC surveys were analyzed using Empirical Orthogonal Functions (EOFs) to isolate the underlying spatial structure. A statistical bootstrapping analysis confirmed the CRNP + EOF provided superior soil hydraulic property estimates, compared to other hydrogeophysical datasets, when linearly correlated to laboratory measured soil hydraulic properties (field capacity estimates reduced 20–25% in root mean square error). The authors propose a soil sampling strategy for better quantifying soil hydraulic properties using CRNP + EOF methods. Here, five CRNP surveys and 6–8 sample locations for laboratory analysis were sufficient to describe the spatial distribution of soil hydraulic properties within this field. While the proposed strategy may increase overall effort, rising scrutiny for agricultural water-use could make this technology cost-effective

Altered endocannabinoid signalling after a high-fat diet in Apoe −/− mice: relevance to adipose tissue inflammation, hepatic steatosis and insulin resistance

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Right-angled vessels in macular telangiectasia type 2

PURPOSE: To evaluate the role of right-angled vessels (RAVs) during disease progression in macular telangiectasia type 2 (MacTel). METHODS: In this study, 100 eyes of 52 patients and 52 eyes of 26 age-related controls were examined using fundus photography, spectral-domain optical coherence tomography (SD-OCT), OCT angiography (OCT-A) and fundus fluorescein angiography (FFA). Two masked readers graded fundus photographs of patients' eyes into five disease stages according to Gass and Blodi, and evaluated all eyes for the presence of RAVs. If RAVs were present, their course and origin (arterial vs venous) was evaluated with OCT-A and FFA, respectively. Additionally, we looked for morphological correlates of these vessels on SD-OCT scans. Neovascular eyes were analysed for the presence of RAVs and for morphological changes on formation of neovascularisations (NVs). RESULTS: In OCT-A, RAVs were already detectable in eyes with early stages (1 to 2), could be tracked from superficial to outer retinal layers and were shown to form anastomoses in the outer retina with disease progression. These vessels were of both arterial and venous origin as shown by early phase FFA. Dilated capillaries and RAVs in OCT-A corresponded to hyper-reflective alterations of the outer retina on SD-OCT scans. In 19/19 eyes, NVs were associated with the presence of RAVs, and RAVs were shown to directly connect to neovascular complexes and to undergo morphological changes upon NV formation. CONCLUSIONS: The results emphasise the role of RAVs during disease progression from an early stage on and demonstrate their involvement in the development of secondary NVs in MacTel