Medinoid : computer-aided diagnosis and localization of glaucoma using deep learning

Glaucoma is a leading eye disease, causing vision loss by gradually affecting peripheral vision if left untreated. Current diagnosis of glaucoma is performed by ophthalmologists, human experts who typically need to analyze different types of medical images generated by different types of medical equipment: fundus, Retinal Nerve Fiber Layer (RNFL), Optical Coherence Tomography (OCT) disc, OCT macula, perimetry, and/or perimetry deviation. Capturing and analyzing these medical images is labor intensive and time consuming. In this paper, we present a novel approach for glaucoma diagnosis and localization, only relying on fundus images that are analyzed by making use of state-of-the-art deep learning techniques. Specifically, our approach towards glaucoma diagnosis and localization leverages Convolutional Neural Networks (CNNs) and Gradient-weighted Class Activation Mapping (Grad-CAM), respectively. We built and evaluated different predictive models using a large set of fundus images, collected and labeled by ophthalmologists at Samsung Medical Center (SMC). Our experimental results demonstrate that our most effective predictive model is able to achieve a high diagnosis accuracy of 96%, as well as a high sensitivity of 96% and a high specificity of 100% for Dataset-Optic Disc (OD), a set of center-cropped fundus images highlighting the optic disc. Furthermore, we present Medinoid, a publicly-available prototype web application for computer-aided diagnosis and localization of glaucoma, integrating our most effective predictive model in its back-end

Evaluation of machine learning classifiers in keratoconus detection from orbscan II examinations

PURPOSE: To evaluate the performance of support vector machine, multi-layer perceptron and radial basis function neural network as auxiliary tools to identify keratoconus from Orbscan II maps. METHODS: A total of 318 maps were selected and classified into four categories: normal (n = 172), astigmatism (n = 89), keratoconus (n = 46) and photorefractive keratectomy (n = 11). For each map, 11 attributes were obtained or calculated from data provided by the Orbscan II. Ten-fold cross-validation was used to train and test the classifiers. Besides accuracy, sensitivity and specificity, receiver operating characteristic (ROC) curves for each classifier were generated, and the areas under the curves were calculated. RESULTS: The three selected classifiers provided a good performance, and there were no differences between their performances. The area under the ROC curve of the support vector machine, multi-layer perceptron and radial basis function neural network were significantly larger than those for all individual Orbscan II attributes evaluated (p<0.05). CONCLUSION: Overall, the results suggest that using a support vector machine, multi-layer perceptron classifiers and radial basis function neural network, these classifiers, trained on Orbscan II data, could represent useful techniques for keratoconus detection

Visual screening for blinding diseases in the community using computer controlled video perimetry

Detecting early visual impairment in a community-based approach is difficult because of the variety of light contrast in which measurements have to be made. Finding ways which are functionally efficient, and yet cost-effective, could lead to important improvements to health and quality of life. To select an appropriate visual screening test for use in multicontrast situations, requires an understanding of the interface between clinical epidemiology, visual field technology and the environment in the community where the tests are to take place. Four issues have been taken into account in the study: basic multicontrast characteristics; aspects of clinical application of motion stimuli; discriminative ability, reliability and validity to detect early visual loss, and the acceptability of the test. The study included the development of a group of software programmes called collectively Computer Controlled Video Perimetry (CCVP). The Motion Sensitivity Tests (MSTs) were developed as a part of CCVP in collaboration with Dr Fitzke for early glaucoma detection. The Motion Sensitivity Screening Test (MSST) was finally developed by using a low cost and portable notebook computer to assess acceptability. The tests were carried out on 2632 individuals, from whom 5129 CCVP tests were recorded. Testing was undertaken in a wide variety of situations that included a glaucoma clinic in an eye hospital; an eye health survey in inner city community; a glaucoma survey in an Irish rural community; mass screening for optic nerve disease in region of meso-endemic for onchocerciasis in Nigeria and a self-testing programme set up during a clinical meeting in the USA. CCVP showed that it was possible to detect early visual function loss in a wide variety of situations, whether in clinic or in the community. The results from my study provide a framework for clinical application of using CCVP technology and motion testing to be made with respect to glaucoma and optic nerve disease screening

Machine Learning Approaches for Automated Glaucoma Detection using Clinical Data and Optical Coherence Tomography Images

Glaucoma is a multi-factorial, progressive blinding optic-neuropathy. A variety of factors, including genetics, vasculature, anatomy, and immune factors, are involved. Worldwide more than 80 million people are affected by glaucoma, and around 300,000 in Australia, where 50% remain undiagnosed. Untreated glaucoma can lead to blindness. Early detection by Artificial intelligence (AI) is crucial to accelerate the diagnosis process and can prevent further vision loss. Many proposed AI systems have shown promising performance for automated glaucoma detection using two-dimensional (2D) data. However, only a few studies had optimistic outcomes for glaucoma detection and staging. Moreover, the automated AI system still faces challenges in diagnosing at the clinicians’ level due to the lack of interpretability of the ML algorithms and integration of multiple clinical data. AI technology would be welcomed by doctors and patients if the "black box" notion is overcome by developing an explainable, transparent AI system with similar pathological markers used by clinicians as the sign of early detection and progression of glaucomatous damage. Therefore, the thesis aimed to develop a comprehensive AI model to detect and stage glaucoma by incorporating a variety of clinical data and utilising advanced data analysis and machine learning (ML) techniques. The research first focuses on optimising glaucoma diagnostic features by combining structural, functional, demographic, risk factor, and optical coherence tomography (OCT) features. The significant features were evaluated using statistical analysis and trained in ML algorithms to observe the detection performance. Three crucial structural ONH OCT features: cross-sectional 2D radial B-scan, 3D vascular angiography and temporal-superior-nasal-inferior-temporal (TSNIT) B-scan, were analysed and trained in explainable deep learning (DL) models for automated glaucoma prediction. The explanation behind the decision making of DL models were successfully demonstrated using the feature visualisation. The structural features or distinguished affected regions of TSNIT OCT scans were precisely localised for glaucoma patients. This is consistent with the concept of explainable DL, which refers to the idea of making the decision-making processes of DL models transparent and interpretable to humans. However, artifacts and speckle noise often result in misinterpretation of the TSNIT OCT scans. This research also developed an automated DL model to remove the artifacts and noise from the OCT scans, facilitating error-free retinal layers segmentation, accurate tissue thickness estimation and image interpretation. Moreover, to monitor and grade glaucoma severity, the visual field (VF) test is commonly followed by clinicians for treatment and management. Therefore, this research uses the functional features extracted from VF images to train ML algorithms for staging glaucoma from early to advanced/severe stages. Finally, the selected significant features were used to design and develop a comprehensive AI model to detect and grade glaucoma stages based on the data quantity and availability. In the first stage, a DL model was trained with TSNIT OCT scans, and its output was combined with significant structural and functional features and trained in ML models. The best-performed ML model achieved an area under the curve (AUC): 0.98, an accuracy of 97.2%, a sensitivity of 97.9%, and a specificity of 96.4% for detecting glaucoma. The model achieved an overall accuracy of 90.7% and an F1 score of 84.0% for classifying normal, early, moderate, and advanced-stage glaucoma. In conclusion, this thesis developed and proposed a comprehensive, evidence-based AI model that will solve the screening problem for large populations and relieve experts from manually analysing a slew of patient data and associated misinterpretation problems. Moreover, this thesis demonstrated three structural OCT features that could be added as excellent diagnostic markers for precise glaucoma diagnosis

Campimetry with Offset Stimulus and Dynamic Fixation

The dark-on-bright (negative contrast, light decremental, light offset) stimulus and dynamic fixation target are non-conventional and their usefulness in visual field examination has not been fully documented before. The utility of light offsets (i.e. offset stimuli) and dynamic fixation was investigated for kinetic and static perimetry on a tangent screen without or with automation and the results were compared to those from conventional bright-on-dark (positive contrast, light incremental, light onset) stimuli and static fixation. The disappearance eccentricities of offset and onset stimuli of equal size were determined in eight normal eyes, using dynamic fixation technique at two different levels of surrounding illumination. Kinetic' offset stimulus has a smaller "isoptre" than onset stimulus and, the variation of ambient illumination has less effect on the visibility of offset stimulus. The Oculokinetic Campimetry (OKC) with a constantly exposed offset stimulus was performed in 366 glaucomatous eyes and 217 normal eyes. When a 1.5 mm stimulus was used, a true positive OKC result was obtained in 45% of eyes with relative scotomas and 81% of eyes with small absolute scotomas. A false positive result was obtained in 9% of patients aged 60-70 yrs and 13% of patients older than 70 yrs. When a 3 mm stimulus was used in the glaucomatous patients above the age of 60 yrs, the OKC test was positive in 33% of eyes with relative scotomas and 56% of eyes with small absolute scotomas while none of the control subjects produced a positive result. In 63% of the eyes, abnormal OKC results reflected smaller scotomas than those to the conventional visual field tests, suggesting underestimation of the topographical extent of the scotomas. Inside the absolute scotomas, constantly exposed offset stimulus was still detectable with 19% - 67% frequency between

Deep learning-based improvement for the outcomes of glaucoma clinical trials

Glaucoma is the leading cause of irreversible blindness worldwide. It is a progressive optic neuropathy in which retinal ganglion cell (RGC) axon loss, probably as a consequence of damage at the optic disc, causes a loss of vision, predominantly affecting the mid-peripheral visual field (VF). Glaucoma results in a decrease in vision-related quality of life and, therefore, early detection and evaluation of disease progression rates is crucial in order to assess the risk of functional impairment and to establish sound treatment strategies. The aim of my research is to improve glaucoma diagnosis by enhancing state of the art analyses of glaucoma clinical trial outcomes using advanced analytical methods. This knowledge would also help better design and analyse clinical trials, providing evidence for re-evaluating existing medications, facilitating diagnosis and suggesting novel disease management. To facilitate my objective methodology, this thesis provides the following contributions: (i) I developed deep learning-based super-resolution (SR) techniques for optical coherence tomography (OCT) image enhancement and demonstrated that using super-resolved images improves the statistical power of clinical trials, (ii) I developed a deep learning algorithm for segmentation of retinal OCT images, showing that the methodology consistently produces more accurate segmentations than state-of-the-art networks, (iii) I developed a deep learning framework for refining the relationship between structural and functional measurements and demonstrated that the mapping is significantly improved over previous techniques, iv) I developed a probabilistic method and demonstrated that glaucomatous disc haemorrhages are influenced by a possible systemic factor that makes both eyes bleed simultaneously. v) I recalculated VF slopes, using the retinal never fiber layer thickness (RNFLT) from the super-resolved OCT as a Bayesian prior and demonstrated that use of VF rates with the Bayesian prior as the outcome measure leads to a reduction in the sample size required to distinguish treatment arms in a clinical trial

Machine Learning Techniques, Detection and Prediction of Glaucoma– A Systematic Review

Globally, glaucoma is the most common factor in both permanent blindness and impairment. However, the majority of patients are unaware they have the condition, and clinical practise continues to face difficulties in detecting glaucoma progression using current technology. An expert ophthalmologist examines the retinal portion of the eye to see how the glaucoma is progressing. This method is quite time-consuming, and doing it manually takes more time. Therefore, using deep learning and machine learning techniques, this problem can be resolved by automatically diagnosing glaucoma. This systematic review involved a comprehensive analysis of various automated glaucoma prediction and detection techniques. More than 100 articles on Machine learning (ML) techniques with understandable graph and tabular column are reviewed considering summery, method, objective, performance, advantages and disadvantages. In the ML techniques such as support vector machine (SVM), and K-means. Fuzzy c-means clustering algorithm are widely used in glaucoma detection and prediction. Through the systematic review, the most accurate technique to detect and predict glaucoma can be determined which can be utilized for future betterment