Artificial Intelligence Algorithms for Eye Banking

Eye banking plays a critical role in modern medicine by providing cornea tissues for transplantation to restore vision for millions of people worldwide. The evaluation of corneal endothelium is done by measuring the corneal endothelial cell density (ECD). Unfortunately, the current system to measure ECD is manual, time-consuming, and error prone. Furthermore, the impact of social behaviors and biological conditions on corneal endothelium and corneal transplant success is largely unexplored. To overcome these challenges, this dissertation aims to develop tools for corneal endothelial image and data analysis that enhance the efficiency and quality of the cornea transplants. In the first study, an image processing algorithm is developed to analyze corneal endothelial images captured by a Konan CellChek specular microscope. The algorithm successfully identifies the region of interest, filters the image, and employs stochastic watershed segmentation to determine cell boundaries and evaluate endothelial cell density (ECD). The proposed algorithm achieves a high correlation with manual counts (R2 = 0.98) and has an average analysis time of 2.5 seconds. In the second study, a deep learning-based cell segmentation algorithm called Mobile-CellNet is proposed to estimate ECD. This technique addresses the limitations of classical algorithms and creates a more robust and highly efficient algorithm. The approach achieves a mean absolute error of 4.06% for ECD on the test set, similar to U-Net but with significantly fewer floating-point operations and parameters. The third study explores the correlation between alcohol abuse and corneal endothelial morphology in a donor pool of 5,624 individuals. Multivariable regression analysis shows that alcohol abuse is associated with a reduction in endothelial cell density, an increase in the coefficient of variation, and a decrease in percent hexagonality. These studies highlight the potential of big data and artificial algorithms in accurately and efficiently analyzing corneal images and donor medical data to improve the efficiency of eye banking and patient outcomes. By automating the analysis of corneal images and exploring the impact of social behaviors and biological conditions on corneal endothelial morphology, we can enhance the quality and availability of cornea transplants and ultimately improve the lives of millions of people worldwide

A fully automated cell segmentation and morphometric parameter system for quantifying corneal endothelial cell morphology

YesBackground and Objective Corneal endothelial cell abnormalities may be associated with a number of corneal and systemic diseases. Damage to the endothelial cells can significantly affect corneal transparency by altering hydration of the corneal stroma, which can lead to irreversible endothelial cell pathology requiring corneal transplantation. To date, quantitative analysis of endothelial cell abnormalities has been manually performed by ophthalmologists using time consuming and highly subjective semi-automatic tools, which require an operator interaction. We developed and applied a fully-automated and real-time system, termed the Corneal Endothelium Analysis System (CEAS) for the segmentation and computation of endothelial cells in images of the human cornea obtained by in vivo corneal confocal microscopy. Methods First, a Fast Fourier Transform (FFT) Band-pass filter is applied to reduce noise and enhance the image quality to make the cells more visible. Secondly, endothelial cell boundaries are detected using watershed transformations and Voronoi tessellations to accurately quantify the morphological parameters of the human corneal endothelial cells. The performance of the automated segmentation system was tested against manually traced ground-truth images based on a database consisting of 40 corneal confocal endothelial cell images in terms of segmentation accuracy and obtained clinical features. In addition, the robustness and efficiency of the proposed CEAS system were compared with manually obtained cell densities using a separate database of 40 images from controls (n = 11), obese subjects (n = 16) and patients with diabetes (n = 13). Results The Pearson correlation coefficient between automated and manual endothelial cell densities is 0.9 (p < 0.0001) and a Bland–Altman plot shows that 95% of the data are between the 2SD agreement lines. Conclusions We demonstrate the effectiveness and robustness of the CEAS system, and the possibility of utilizing it in a real world clinical setting to enable rapid diagnosis and for patient follow-up, with an execution time of only 6 seconds per image

A new method for detecting the outer corneal contour in images from an ultra‑fast Scheimpflug camera

BACKGROUND: The Corvis® ST tonometer is an innovative device which, by combining a classic non-contact tonometer with an ultra-fast Scheimpflug camera, provides a number of parameters allowing for the assessment of corneal biomechanics. The acquired biomechanical parameters improve medical diagnosis of selected eye diseases. One of the key elements in biomechanical measurements is the correct corneal contour detection, which is the basis for further calculations. The presented study deals with the problem of outer corneal edge detection based on a series of images from the afore-mentioned device. Corneal contour detection is the first and extremely important stage in the acquisition and analysis of corneal dynamic parameters. RESULT: A total of 15,400 images from the Corvis® ST tonometer acquired from 110 patients undergoing routine ophthalmologic examinations were analysed. A method of outer corneal edge detection on the basis of a series of images from the Corvis® ST was proposed. The method was compared with known and commonly used edge detectors: Sobel, Roberts, and Canny operators, as well as others, known from the literature. The analysis was carried out in MATLAB® version 9.0.0.341360 (R2016a) with the Image Processing Toolbox (version 9.4) and the Neural Network Toolbox (version 9.0). The method presented in this paper provided the smallest values of the mean error (0.16%), stability (standard deviation 0.19%) and resistance to noise, characteristic for Corvis® ST tonometry tests, compared to the methods known from the literature. The errors were 5.78 ± 9.19%, 3.43 ± 6.21%, and 1.26 ± 3.11% for the Roberts, Sobel, and Canny methods, respectively. CONCLUSIONS: The proposed new method for detecting the outer corneal contour increases the accuracy of intraocular pressure measurements. It can be used to analyse dynamic parameters of the cornea

Novel medical imaging technologies for processing epithelium and endothelium layers in corneal confocal images. Developing automated segmentation and quantification algorithms for processing sub-basal epithelium nerves and endothelial cells for early diagnosis of diabetic neuropathy in corneal confocal microscope images

Diabetic Peripheral Neuropathy (DPN) is one of the most common types of diabetes that can affect the cornea. An accurate analysis of the corneal epithelium nerve structures and the corneal endothelial cell can assist early diagnosis of this disease and other corneal diseases, which can lead to visual impairment and then to blindness. In this thesis, fully-automated segmentation and quantification algorithms for processing and analysing sub-basal epithelium nerves and endothelial cells are proposed for early diagnosis of diabetic neuropathy in Corneal Confocal Microscopy (CCM) images. Firstly, a fully automatic nerve segmentation system for corneal confocal microscope images is proposed. The performance of the proposed system is evaluated against manually traced images with an execution time of the prototype is 13 seconds. Secondly, an automatic corneal nerve registration system is proposed. The main aim of this system is to produce a new informative corneal image that contains structural and functional information. Thirdly, an automated real-time system, termed the Corneal Endothelium Analysis System (CEAS) is developed and applied for the segmentation of endothelial cells in images of human cornea obtained by In Vivo CCM. The performance of the proposed CEAS system was tested against manually traced images with an execution time of only 6 seconds per image. Finally, the results obtained from all the proposed approaches have been evaluated and validated by an expert advisory board from two institutes, they are the Division of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and the Manchester Royal Eye Hospital, Centre for Endocrinology and Diabetes, UK

Methods for Analysing Endothelial Cell Shape and Behaviour in Relation to the Focal Nature of Atherosclerosis

The aim of this thesis is to develop automated methods for the analysis of the spatial patterns, and the functional behaviour of endothelial cells, viewed under microscopy, with applications to the understanding of atherosclerosis. Initially, a radial search approach to segmentation was attempted in order to trace the cell and nuclei boundaries using a maximum likelihood algorithm; it was found inadequate to detect the weak cell boundaries present in the available data. A parametric cell shape model was then introduced to fit an equivalent ellipse to the cell boundary by matching phase-invariant orientation fields of the image and a candidate cell shape. This approach succeeded on good quality images, but failed on images with weak cell boundaries. Finally, a support vector machines based method, relying on a rich set of visual features, and a small but high quality training dataset, was found to work well on large numbers of cells even in the presence of strong intensity variations and imaging noise. Using the segmentation results, several standard shear-stress dependent parameters of cell morphology were studied, and evidence for similar behaviour in some cell shape parameters was obtained in in-vivo cells and their nuclei. Nuclear and cell orientations around immature and mature aortas were broadly similar, suggesting that the pattern of flow direction near the wall stayed approximately constant with age. The relation was less strong for the cell and nuclear length-to-width ratios. Two novel shape analysis approaches were attempted to find other properties of cell shape which could be used to annotate or characterise patterns, since a wide variability in cell and nuclear shapes was observed which did not appear to fit the standard parameterisations. Although no firm conclusions can yet be drawn, the work lays the foundation for future studies of cell morphology. To draw inferences about patterns in the functional response of cells to flow, which may play a role in the progression of disease, single-cell analysis was performed using calcium sensitive florescence probes. Calcium transient rates were found to change with flow, but more importantly, local patterns of synchronisation in multi-cellular groups were discernable and appear to change with flow. The patterns suggest a new functional mechanism in flow-mediation of cell-cell calcium signalling

Computer Vision Based Early Intraocular Pressure Assessment From Frontal Eye Images

Intraocular Pressure (IOP) in general, refers to the pressure in the eyes. Gradual increase of IOP and high IOP are conditions or symptoms that may lead to certain diseases such as glaucoma, and therefore, must be closely monitored. While the pressure in the eye increases, different parts of the eye may become affected until the eye parts are damaged. An effective way to prevent rise in eye pressure is by early detection. Exiting IOP monitoring tools include eye tests at clinical facilities and computer-aided techniques from fundus and optic nerves images. In this work, a new computer vision-based smart healthcare framework is presented to evaluate the intraocular pressure risk from frontal eye images early-on. The framework determines the status of IOP by analyzing frontal eye images using image processing and machine learning techniques. A database of images from the Princess Basma Hospital was used in this work. The database contains 400 eye images; 200 images with normal IOP and 200 high eye pressure case images. This study proposes novel features for IOP determination from two experiments. The first experiment extracts the sclera using circular hough transform, after which four features are extracted from the whole sclera. These features are mean redness level, red area percentage, contour area and contour height. The pupil/iris diameter ratio feature is also extracted from the frontal eye image after a series of pre-processing techniques. The second experiment extracts the sclera and iris segment using a fully conventional neural network technique, after which six features are extracted from only part of the segmented sclera and iris. The features include mean redness level, red area percentage, contour area, contour distance and contour angle along with the pupil/iris diameter ratio. Once the features are extracted, classification techniques are applied in order to train and test the images and features to obtain the status of the patients in terms of eye pressure. For the first experiment, neural network and support vector machine algorithms were adopted in order to detect the status of intraocular pressure. The second experiment adopted support vector machine and decision tree algorithms to detect the status of intraocular pressure. For both experiments, the framework detects the status of IOP (normal or high IOP) with high accuracies. This computer vison-based approach produces evidence of the relationship between the extracted frontal eye image features and IOP, which has not been previously investigated through automated image processing and machine learning techniques from frontal eye images

Investigating Mechanical Interactions of Cells with Their Environment

Recent studies have shown that cells not only respond to chemical signals such as growth factors or chemoattractants, but they are also capable of detecting mechanical stimuli and responding to them. The process during which these mechanical stimuli are detected and transferred to chemical signals, that cells can process, is called mechanotransduction. The mechanical stimuli that can affect cells can be either an external stimulus applied to cells, such as shear flow or cyclic compression and tension, or they can be linked to the mechanical properties of their substrates. One of the mechanical properties of a substrate that can affect cellular behavior is known to be stiffness, mostly measured by elastic modulus. Stiffness influences a wide variety of cellular behaviour such as cell shape, adhesion to substrate, proliferation, and differentiation. Anchorage dependent cells are in direct contact with their environment, which then leads to complicated interactions. These interactions can be both biological and mechanical. In the current research, the mechanical interactions are often called the “mechanical responses” of cells. For anchorage-dependent migrating cells, mechanical responses can be the substrate deformations induced by the forces generated by cells also called cell traction forces. These mechanical responses can be studied in three levels of complexity. The first level is when cells are cultured on a 2D matrix and responses are also studied in 2D. The second level of complexity is when cells are cultured on a 2D matrix and the biological behaviour of cells, such as growth or migration, is studied in 2D, however, the mechanical responses of cells are studied in 3D, meaning that not only in plane deformation and forces are studied, but out of plane ones are also assessed. The third level of complexity is when cells are cultured inside a 3D matrix and both biological responses and mechanical responses are studied in 3D. In the current research, the second level of complexity is chosen. After testing different types of materials, polyacrylamide (PAAm) was chosen as the model biomaterial. Following mechanical characterization of PAAm samples, substrates were prepared with three different elastic moduli. Both biological responses and mechanical responses of human corneal epithelial cells (HCECs) were studied. For biological responses, cell viability, activation, adhesion molecules, apoptosis and migration behaviour were studied. For mechanical responses, confocal microscopy in junction with image processing technique, digital volume correlation (DVC), was used to measure cell induced deformations. It was found that elastic modulus, as a mechanical stimulus, affects not only biological behaviour of cells, but also their mechanical behaviour. Decreasing elastic modulus led to significantly lower migration speed of HCECs, slightly higher number of apoptotic cells as well as significantly higher number of necrotic cells. Furthermore, while no significant changes in adhesion molecules occurred, dramatic changes in cytoskeleton structure was seen on cells cultured on compliant matrices. Also, the DVC code was capable of detecting both in plane and out of plane deformations from confocal images. It was found that substrate elastic modulus can change the pattern of displacements on compliant substrate compared to stiff ones. Results of the present study suggest that the deformation pattern and magnitude does not change over the body of cells and that they are rather similar in the leading edge and trailing edge. Deformation under the nucleus was also assessed and for compliant and stiff substrates were present while no deformation was found under the cells cultured on medium stiffness substrates. It was also speculated that mechanical interaction of HCECs with their substrates can be more complicated than currently known and cells seem to be able to exert moments on their substrate as well as forces. Results presented in this thesis demonstrate that HCECs are sensitive to substrate stiffness and elastic modulus can affect their behaviour. Furthermore, considering the complexity of HCECs mechanical interaction with their substrates, it is critical to study both biology and mechanics for full comprehension of cellular interaction with the ocular environment

Glaucoma

This book addresses the basic and clinical science of glaucomas, a group of diseases that affect the optic nerve and visual fields and is usually accompanied by increased intraocular pressure. The book incorporates the latest development as well as future perspectives in glaucoma, since it has expedited publication. It is aimed for specialists in glaucoma, researchers, general ophthalmologists and trainees to increase knowledge and encourage further progress in understanding and managing these complicated diseases