Defining Dry Eye from a Clinical Perspective

Over the past decades, the number of patients with dry eye disease (DED) has increased dramatically. The incidence of DED is higher in Asia than in Europe and North America, suggesting the involvement of cultural or racial factors in DED etiology. Although many definitions of DED have been used, discrepancies exist between the various definitions of dry eye disease (DED) used across the globe. This article presents a clinical consensus on the definition of DED, as formulated in four meetings with global DED experts. The proposed new definition is as follows: “Dry eye is a multifactorial disease characterized by a persistently unstable and/or deficient tear film (TF) causing discomfort and/or visual impairment, accompanied by variable degrees of ocular surface epitheliopathy, inflammation and neurosensory abnormalities.” The key criteria for the diagnosis of DED are unstable TF, inflammation, ocular discomfort and visual impairment. This definition also recommends the assessment of ocular surface epitheliopathy and neurosensory abnormalities in each patient with suspected DED. It is easily applicable in clinical practice and should help practitioners diagnose DED consistently. This consensus definition of DED should also help to guide research and clinical trials that, to date, have been hampered by the lack of an established surrogate endpoint.     

The effects of glycol methacrylate as a dehydrating agent on the dimensional changes of liver tissue

The dimensional changes of liver sections during the course of processing with glycol methacrylate (GMA) or with ethanol are described. Tissue processing with ethanol served as a control. During prolonged processing steps (24 h each), linear shrinkage of tissue specimens dehydrated with GMA at room temperature was 13.2%. Subsequent infiltration with GMA resulted in trivial swelling, and polymerization in slight shrinkage (2.3%). In comparison, processing with cold GMA resulted in shrinkage during dehydration (about 10.8%), a slight swelling in pure GMA, followed by shrinkage during polymerization (2.2%). Short routine processing schedules resulted in similar shrinkage/swelling patterns, although precise values differed slightly. In all experiments, ethanolic dehydration resulted in smaller dimensional tissue changes than did GMA dehydration. The dimensional changes of tissue sections during stretching on water, mounting and drying compensated for the major part of the shrinkage manifested during processing.     

A method for quantifying cell size from differential interference contrast images: validation and application to osmotically stressed chondrocytes

An automatic image analysis method was developed to determine the shape and size of spheroidal cells from a time series of differential interference contrast (DIC) images. The program incorporates an edge detection algorithm and dynamic programming for edge linking. To assess the accuracy and working range of the method, results from DIC images of different focal planes and resolutions were compared to confocal images in which the cell membrane was fluorescently labelled. The results indicate that a 1‐µm focal drift from the in‐focus plane can lead to an overestimation of cell volume up to 14.1%, mostly due to shadowing effects of DIC microscopy. DIC images allow for accurate measurements when the focal plane lies in a zone slightly above the centre of a spherical cell. In this range the method performs with 1.9% overall volume error without taking into account the error introduced by the representation of the cell as a sphere. As a test case, the method was applied to quantify volume changes due to acute changes of osmotic stress.     

Unsupervised tissue classification of brain MR images for voxel‐based morphometry analysis

In this article, a fully unsupervised method for brain tissue segmentation of T1‐weighted MRI 3D volumes is proposed. The method uses the Fuzzy C‐Means (FCM) clustering algorithm and a Fully Connected Cascade Neural Network (FCCNN) classifier. Traditional manual segmentation methods require neuro‐radiological expertise and significant time while semiautomatic methods depend on parameter's setup and trial‐and‐error methodologies that may lead to high intraoperator/interoperator variability. The proposed method selects the most useful MRI data according to FCM fuzziness values and trains the FCCNN to learn to classify brain’ tissues into White Matter, Gray Matter, and Cerebro‐Spinal Fluid in an unsupervised way. The method has been tested on the IBSR dataset, on the BrainWeb Phantom, on the BrainWeb SBD dataset, and on the real dataset “University of Palermo Policlinico Hospital” (UPPH), Italy. Sensitivity, Specificity, Dice and F‐Factor scores have been calculated on the IBSR and BrainWeb datasets segmented using the proposed method, the FCM algorithm, and two state‐of‐the‐art brain segmentation software packages (FSL and SPM) to prove the effectiveness of the proposed approach. A qualitative evaluation involving a group of five expert radiologists has been performed segmenting the real dataset using the proposed approach and the comparison algorithms. Finally, a usability analysis on the proposed method and reference methods has been carried out from the same group of expert radiologists. The achieved results show that the segmentations of the proposed method are comparable or better than the reference methods with a better usability and degree of acceptance.     

Morphometric and some immunohistochemical characteristics of human choroids plexus stroma and psammoma bodies

Psammoma bodies (PBs) are one of many choroids plexus aging changes. The aim of our research was to perform the quantification of PBs' presence in human choroids plexus stroma, as well as to evaluate the characteristics of choroids plexus stroma in cases in which PBs were present. Afterwards, the observations of the histochemical analysis would be confirmed by immunohistochemical analysis. Choroid plexuses of 30 cadavers were used for the histochemical and, choroids plexuses of 15 cadavers in which PBs' presence was confirmed during the histochemical analysis, were used as material for the immunohistochemical analysis. Light microscopy, histochemical, immunohistochemical, and morphometric method were applied during the study. Classification of the cases was performed by cluster analysis. We observed increase of choroids plexus PBs' presence during the aging process. But this increase is not linear. Their presence is the largest in the second cluster that is younger than the third and older than the first. Nuclear morphometric parameters of the stroma in these cases showed that the cellular composition in this cluster is different than in other two and, that contain larger number of lymphoid cells. Immunohistochemical analysis showed PBs' positive reaction on vimentin, CD45R0, and LCA markers, while in their vicinity, as well as inside them, numerous T-cells were observed. So, the presence of CD45R0 and LCA-positive T cells, PBs' positive reaction on the same markers, indirectly connect these cells with PBs' formation process.     

Bathymetric study of Lake Hayq,Ethiopia

The generation of scientific information for improved understating of the physical dynamics of a lake is fundamental for guiding lake stakeholders and managers at the local level to implement best management practices and help design effective management strategies and policies at higher levels. Multitemporal bathymetric information on lakes is very important in hydrology and sediment studies to more clearly indicate environmental changes and to understand the effects of land processes on the hydrology of lakes. Accordingly, the purpose of this study was to map bathymetric charts of Lake Hayq ¹ in Ethiopia and to derive morphometric parameters, including depth, volume, area, width and length, and to plot curves illustrating the relationships between these parameters. The bathymetric survey was carried out using a combination of a SonarLite Portable Echo Sounder and Global Positioning System (GPS) to generate three‐dimensional (XYZ) hydrographic data. Surfer 8.01 and ArcGIS 9.3 software program were used for surface, gridding and morphometric analyses. Comparison of the results of this study with a previous study conducted in 1941 indicated the lake has experienced changes in depth and surface area. To reduce the negative impacts of human‐induced activities on the ecohydrology of the lake, and to maintain its ecological integrity, appropriate and integrated lake management practices must be adopted. This will necessitate policy formulation, active lake basin stakeholder involvement and implementation of basin‐wide lake management to ensure sustainable use of the lake and its basin resources.     

A new computer-assisted three-dimensional reconstruction method provides accurate measurement of glomerular mesangial volume

Many glomerulopathies are characterized by progressive mesangial (interstitial) expansion which can be quantitated by morphometric analysis. The purpose of this study was to analyze mesangial and glomerular volumes using a new computer-assisted reconstruction (CAR) method. CAR was compared to two standard planar methods, point-counting and linear integration, for accuracy and time efficiency. In Phase I of the study, a computer-based model of the mesangial space was created by placing spherical and ellipsoidal objects of known volume into an enclosing volume mimicking the glomerulus. The simulated mesangium occupied approximately 10 percent of the glomerular volume. The model glomerulus was sectioned serially into ten sections of equal thickness and the three morphometric methods applied to determine the mesangial/glomerular volume. The complexity of the mesangial model was varied by increasing the number of mesangial regions from one to ten to 100. The CAR method estimated the model mesangial volume more accurately (1–9 percent error) through each level of complexity compared to point-counting (3–17 percent error) and linear integration (3–18 percent error). The point-counting method consistently overestimated (P < 0.05) the fractional mesangial volume for the ten- and 100-region mesangium models. In Phase II of the study, a normal rat glomerulus was sectioned serially (215 sections) and a transmission electron micrograph (TEM) of every fifth section (n = 43) was obtained. Each TEM image (2% of glomerular surface) was digitized for analysis by CAR. Point-counting and linear integration were also performed on the whole glomerular TEMs (n = 10, randomly chosen). The estimated relative mesangial/glomerular volume was 6.6 ± 0.1 percent by CAR (x? ± SD), 9.7 ± 1.5 by linear integration, and 14.9 ± 3.4 by point-counting. The point-counting method was most efficient, requiring 40 ± 8 sec/section, followed by CAR at 85 ± 24 sec/section. Linear integration was least efficient (93 ± 23 sec/section). We conclude that CAR is the most accurate morphometric method of the three compared for estimating mesangial and glomerular methods, although it is more time consuming than the point-counting method and requires more complex instrumentation. CAR is the only method that will analyze the shape and three-dimensional complexity of glomerular structures using TEMs.     

Human SMILE-Derived Stromal Lenticule Scaffold for Regenerative Therapy: Review and Perspectives

A transparent cornea is paramount for vision. Corneal opacity is one of the leading causes of blindness. Although conventional corneal transplantation has been successful in recovering patients’ vision, the outcomes are challenged by a global lack of donor tissue availability. Bioengineered corneal tissues are gaining momentum as a new source for corneal wound healing and scar management. Extracellular matrix (ECM)-scaffold-based engineering offers a new perspective on corneal regenerative medicine. Ultrathin stromal laminar tissues obtained from lenticule-based refractive correction procedures, such as SMall Incision Lenticule Extraction (SMILE), are an accessible and novel source of collagen-rich ECM scaffolds with high mechanical strength, biocompatibility, and transparency. After customization (including decellularization), these lenticules can serve as an acellular scaffold niche to repopulate cells, including stromal keratocytes and stem cells, with functional phenotypes. The intrastromal transplantation of these cell/tissue composites can regenerate native-like corneal stromal tissue and restore corneal transparency. This review highlights the current status of ECM-scaffold-based engineering with cells, along with the development of drug and growth factor delivery systems, and elucidates the potential uses of stromal lenticule scaffolds in regenerative therapeutics.     

基于MLP神经网络的圆锥角膜辅助诊断北大核心CSCD

圆锥角膜在病变过程中会导致角膜中央部位向前凸出,使角膜呈现出圆锥形,而且会导致高度不规则近视和散光,对视力造成不同程度损害。疾病一般发生于青少年时期,为了能及时治疗避免病变严重,筛查区分圆锥角膜具有十分重要的意义。而且临床上对于圆锥角膜诊断通常是采用角膜地形图的方法,可以得到角膜形态学的改变,但是有一定的误诊率。目前研究发现,角膜力学特性改变先于形态学,所以本文从角膜生物力学角度出发,提出一种基于多层感知机(multi-layer perceptron,MLP)神经网络区分圆锥角膜的模型。首先,利用可视化生物力学分析仪(corneal visualization scheimpflug technology,Corvis-ST)测得角膜的生物力学视频,进行处理计算得到角膜生物力学参数作为数据集,其中包含正常角膜和圆锥角膜2种类别;然后,针对角膜生物力学参数数据集构建MLP神经网络模型,将70%数据集作为训练集,30%数据集作为测试集。在数据集上训练及测试的结果表明,该模型区分圆锥角膜的准确率为97.6%。