Classifying visual field loss in glaucoma through baseline matching of stable reference sequences

Glaucoma is a common disease of the eye that often results in partial blindness. The main symptom of glaucoma is progressive loss of sight in the visual field over time. The clinical management of glaucoma involves monitoring the progress of the disease using a sequence of regular visual field tests. However, there is currently no universally accepted standard method for classifying changes in the visual field test data. Sequence matching techniques typically rely on similarity measures. However, visual field measurements are very noisy, particularly in people with glaucoma. It is therefore difficult to establish a reference data set including both stable and progressive visual fields. This paper proposes a method that uses a "baseline" computed from a query sequence, to match stable sequences in a database of visual field measurements collected from volunteers. The purpose of the new method is to classify a given query sequence as being stable or progressive. The results suggest that the new method gives a significant improvement in accuracy for identifying progressive sequences, though there is a small penalty for stable sequences

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

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

Eye-Movement-Based Assessment of the Perceptual Consequences of Glaucomatous and Neuro-Ophthalmological Visual Field Defects

Purpose: Assessing the presence of visual field defects (VFD) through procedures such as perimetry is an essential aspect of the management and diagnosis of ocular disorders. However, even the latest perimetric methods have shortcomings & mdash;a high cognitive demand and requiring prolonged stable fixation and feedback through a button response. Consequently, an approach using eye movements (EM)& mdash;as a natural response & mdash;has been proposed as an alternate way to evaluate the presence of VFD. This approach has given good results for computer-simulated VFD. However, its use in patients is not well documented yet. Here we use this new approach to quantify the spatiotemporal properties (STP) of EM of various patients suffering from glaucoma and neuro-ophthalmological VFD and controls. Methods: In total, 15 glaucoma patients, 37 patients with a neuro-ophthalmological disorder, and 21 controls performed a visual tracking task while their EM were being recorded. Subsequently, the STP of EM were quantified using a cross-correlogram analysis. Decision trees were used to identify the relevant STP and classify the populations. Results: We achieved a classification accuracy of 94.5% (TPR/sensitivity = 96%, TNR/specificity = 90%) between patients and controls. Individually, the algorithm achieved an accuracy of 86.3% (TPR for neuro-ophthalmology [97%], glaucoma [60%], and controls [86%]). The STP of EM were highly similar across two different control cohorts. Conclusions: In an ocular tracking task, patients with VFD due to different underlying pathology make EM with distinctive STP. These properties are interpretable based on different clinical characteristics of patients and can be used for patient classification. Translational Relevance: Our EM-based screening tool may complement existing perimetric techniques in clinical practice. Superscript/Subscript Available ABSTRACT Purpose: Assessing the presence of visual field defects (VFD) through procedures such as perimetry is an essential aspect of the management and diagnosis of ocular disorders. However, even the latest perimetric methods have shortcomings?a high cognitive demand and requiring prolonged stable fixation and feedback through a button response. Consequently, an approach using eye movements (EM)?as a natural response?has been proposed as an alternate way to evaluate the presence of VFD. This approach has given good results for computer-simulated VFD. However, its use in patients is not well documented yet. Here we use this new approach to quantify the spatiotemporal properties (STP) of EM of various patients suffering from glaucoma and neuro-ophthalmological VFD and controls. Methods: In total, 15 glaucoma patients, 37 patients with a neuro-ophthalmological disorder, and 21 controls performed a visual tracking task while their EM were being recorded. Subsequently, the STP of EM were quantified using a cross-correlogram analysis. Decision trees were used to identify the relevant STP and classify the populations. Results: We achieved a classification accuracy of 94.5% (TPR/sensitivity = 96%, TNR/specificity = 90%) between patients and controls. Individually, the algorithm achieved an accuracy of 86.3% (TPR for neuro-ophthalmology [97%], glaucoma [60%], and controls [86%]). The STP of EM were highly similar across two different control cohorts

OCTA multilayer and multisector peripapillary microvascular modeling for diagnosing and staging of glaucoma

Purpose: To develop and assess an automatic procedure for classifying and staging glaucomatous vascular damage based on optical coherence tomography angiography (OCTA) imaging. Methods: OCTA scans (Zeiss Cirrus 5000 HD-OCT) from a random eye of 39 healthy subjects and 82 glaucoma patients were used to develop a new classification algorithm based on multilayer and multisector information. The averaged circumpapillary retinal nerve fiber layer (RNFL) thickness was also collected. Three models, support vector machine (SVM), random forest (RF), and gradient boosting (xGB), were developed and optimized for classifying between healthy and glaucoma patients, primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG), and glaucoma severity groups. Results: All the models, the SVM (area under the receiver operating characteristic [AUROC] 0.89 ± 0.06), the RF (AUROC 0.86 ± 0.06), and the xGB (AUROC 0.85 ± 0.07), with 26, 22, and 29 vascular features obtained after feature selection, respectively, presented a similar performance to the RNFL thickness (AUROC 0.85± 0.06) in classifying healthy and glaucoma patients. The superficial vascular plexus was the most informative layer with the infero temporal sector as the most discriminative region of interest. No significant differentiation was obtained in discriminating the POAG from the NTG group. The xGB model, after feature selection, presented the best performance in classifying the severity groups (AUROC 0.76± 0.06), outperforming the RNFL (AUROC 0.67± 0.06). Conclusions: OCTA multilayer and multisector information has similar performance to RNFL for glaucoma diagnosis, but it has an added value for glaucoma severity classification, showing promising results for staging glaucoma progression. Translational Relevance: OCTA, in its current stage, has the potential to be used in clinical practice as a complementary imaging technique in glaucoma management

Predicting Progressive Glaucomatous Optic Neuropathy Using Baseline Standard Automated Perimetry Data

PURPOSE. To test the hypothesis that specific locations and patterns of threshold findings within the visual field have predictive value for progressive glaucomatous optic neuropathy (pGON). METHODS. Age-adjusted standard automated perimetry thresholds, along with other clinical variables gathered at the initial examination of 168 individuals with high-risk ocular hypertension or early glaucoma, were used as predictors in a classification tree model. The classification variable was a determination of pGON, based on longitudinally gathered stereo optic nerve head photographs. Only data for the worse eye of each individual were included. Data from 100 normal subjects were used to test the specificity of the models. RESULTS. Classification tree models suggest that patterns of baseline visual field findings are predictive of pGON with sensitivity 65% and specificity 87% on average. Average specificity when data from normal subjects were run on the models was 69%. CONCLUSIONS. Classification trees can be used to determine which visual field locations are most predictive of poorer prognosis for pGON. Spatial patterns within the visual field convey useable predictive information, in most cases when thresholds are still well within the classically defined normal range. (Invest Ophthalmol Vis Sci. 2009;50:674 -680

Detecting abnormality in optic nerve head images using a feature extraction analysis

Imaging and evaluation of the optic nerve head (ONH) plays an essential part in the detection and clinical management of glaucoma. The morphological characteristics of ONHs vary greatly from person to person and this variability means it is difficult to quantify them in a standardized way. We developed and evaluated a feature extraction approach using shiftinvariant wavelet packet and kernel principal component analysis to quantify the shape features in ONH images acquired by scanning laser ophthalmoscopy (Heidelberg Retina Tomograph [HRT]). The methods were developed and tested on 1996 eyes from three different clinical centers. A shape abnormality score (SAS) was developed from extracted features using a Gaussian process to identify glaucomatous abnormality. SAS can be used as a diagnostic index to quantify the overall likelihood of ONH abnormality. Maps showing areas of likely abnormality within the ONH were also derived. Diagnostic performance of the technique, as estimated by ROC analysis, was significantly better than the classification tools currently used in the HRT software – the technique offers the additional advantage of working with all images and is fully automated

Analysis of the asymmetry between both eyes in early diagnosis of glaucoma combining features extracted from retinal images and OCTs into classification models

This study aims to analyze the asymmetry between both eyes of the same patient for the early diagnosis of glaucoma. Two imaging modalities, retinal fundus images and optical coherence tomographies (OCTs), have been considered in order to compare their different capabilities for glaucoma detection. From retinal fundus images, the difference between cup/disc ratio and the width of the optic rim has been extracted. Analogously, the thickness of the retinal nerve fiber layer has been measured in spectral-domain optical coherence tomographies. These measurements have been considered as asymmetry characteristics between eyes in the modeling of decision trees and support vector machines for the classification of healthy and glaucoma patients. The main contribution of this work is indeed the use of different classification models with both imaging modalities to jointly exploit the strengths of each of these modalities for the same diagnostic purpose based on the asymmetry characteristics between the eyes of the patient. The results show that the optimized classification models provide better performance with OCT asymmetry features between both eyes (sensitivity 80.9%, specificity 88.2%, precision 66.7%, accuracy 86.5%) than with those extracted from retinographies, although a linear relationship has been found between certain asymmetry features extracted from both imaging modalities. Therefore, the resulting performance of the models based on asymmetry features proves their ability to differentiate healthy from glaucoma patients using those metrics. Models trained from fundus characteristics are a useful option as a glaucoma screening method in the healthy population, although with lower performance than those trained from the thickness of the peripapillary retinal nerve fiber layer. In both imaging modalities, the asymmetry of morphological characteristics can be used as a glaucoma indicator, as detailed in this work.This work has been partially supported by Spanish National projects AES2017–PI17/00771, AES2017–PI17/00821 (Instituto de Salud Carlos III), and Regional project 20901/PI/18 (Fundación Séneca)

Comparative study of pattern recognition methods for predicting glaucoma diagnosis

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd 2020. Glaucoma is the second leading cause of blindness globally; it is characterised by degeneration of the optic nerve with particular patterns of corresponding defects in the visual field. Aiding doctors in early diagnosis and detection of progression is crucial, as glaucoma is asymptomatic in nature. Furthermore there are good therapeutic results in early cases before irreversible visual loss occurs. Thus it is of great importance to find automated methods to discriminate glaucomatous diseases giving insight to doctors. In order to develop a Computer-Aided Diagnosis system (CAD), we realised an extensive competitive study of pattern recognition methods should be undertaken. A range of methods has been evaluated including the use of Deep Neural Networks (DNN), Support Vector Machines (SVM), Decision Trees (DT), and K-Nearest Neighbours (KNN) for diagnosing glaucoma. Using a range of classification techniques, this paper aims to diagnose glaucomatous diseases. Results have been produced with data comprising of Visual Field and OCT Disc readings from anonymous patients with and without glaucoma. Multiple systems are proposed that can predict diagnosis for ocular hypertension, primary open-angle glaucoma, normal tension glaucoma, and healthy patients with a reasonable confidence. Best performance has been obtained from voting classier comprised of SVM and KNN at 0.87 (AUC) and DNN at 0.87 (AUC) which possibly could be used as an automatic diagnosis aid in order to streamline the diagnosis of glaucoma for complex cases or flagging of urgent cases