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

Automatic extraction of retinal features from colour retinal images for glaucoma diagnosis: a review

Glaucoma is a group of eye diseases that have common traits such as, high eye pressure, damage to the Optic Nerve Head and gradual vision loss. It affects peripheral vision and eventually leads to blindness if left untreated. The current common methods of pre-diagnosis of Glaucoma include measurement of Intra-Ocular Pressure (IOP) using Tonometer, Pachymetry, Gonioscopy; which are performed manually by the clinicians. These tests are usually followed by Optic Nerve Head (ONH) Appearance examination for the confirmed diagnosis of Glaucoma. The diagnoses require regular monitoring, which is costly and time consuming. The accuracy and reliability of diagnosis is limited by the domain knowledge of different ophthalmologists. Therefore automatic diagnosis of Glaucoma attracts a lot of attention.This paper surveys the state-of-the-art of automatic extraction of anatomical features from retinal images to assist early diagnosis of the Glaucoma. We have conducted critical evaluation of the existing automatic extraction methods based on features including Optic Cup to Disc Ratio (CDR), Retinal Nerve Fibre Layer (RNFL), Peripapillary Atrophy (PPA), Neuroretinal Rim Notching, Vasculature Shift, etc., which adds value on efficient feature extraction related to Glaucoma diagnosis. © 2013 Elsevier Ltd

Analysis of Retinal Image Data to Support Glaucoma Diagnosis

Fundus kamera je široce dostupné zobrazovací zařízení, které umožňuje relativně rychlé a nenákladné vyšetření zadního segmentu oka – sítnice. Z těchto důvodů se mnoho výzkumných pracovišť zaměřuje právě na vývoj automatických metod diagnostiky nemocí sítnice s využitím fundus fotografií. Tato dizertační práce analyzuje současný stav vědeckého poznání v oblasti diagnostiky glaukomu s využitím fundus kamery a navrhuje novou metodiku hodnocení vrstvy nervových vláken (VNV) na sítnici pomocí texturní analýzy. Spolu s touto metodikou je navržena metoda segmentace cévního řečiště sítnice, jakožto další hodnotný příspěvek k současnému stavu řešené problematiky. Segmentace cévního řečiště rovněž slouží jako nezbytný krok předcházející analýzu VNV. Vedle toho práce publikuje novou volně dostupnou databázi snímků sítnice se zlatými standardy pro účely hodnocení automatických metod segmentace cévního řečiště.Fundus camera is widely available imaging device enabling fast and cheap examination of the human retina. Hence, many researchers focus on development of automatic methods towards assessment of various retinal diseases via fundus images. This dissertation summarizes recent state-of-the-art in the field of glaucoma diagnosis using fundus camera and proposes a novel methodology for assessment of the retinal nerve fiber layer (RNFL) via texture analysis. Along with it, a method for the retinal blood vessel segmentation is introduced as an additional valuable contribution to the recent state-of-the-art in the field of retinal image processing. Segmentation of the blood vessels also serves as a necessary step preceding evaluation of the RNFL via the proposed methodology. In addition, a new publicly available high-resolution retinal image database with gold standard data is introduced as a novel opportunity for other researches to evaluate their segmentation algorithms.

Retinal Fundus Image Analysis for Diagnosis of Glaucoma: A Comprehensive Survey

© 2016 IEEE. The rapid development of digital imaging and computer vision has increased the potential of using the image processing technologies in ophthalmology. Image processing systems are used in standard clinical practices with the development of medical diagnostic systems. The retinal images provide vital information about the health of the sensory part of the visual system. Retinal diseases, such as glaucoma, diabetic retinopathy, age-related macular degeneration, Stargardt's disease, and retinopathy of prematurity, can lead to blindness manifest as artifacts in the retinal image. An automated system can be used for offering standardized large-scale screening at a lower cost, which may reduce human errors, provide services to remote areas, as well as free from observer bias and fatigue. Treatment for retinal diseases is available; the challenge lies in finding a cost-effective approach with high sensitivity and specificity that can be applied to large populations in a timely manner to identify those who are at risk at the early stages of the disease. The progress of the glaucoma disease is very often quiet in the early stages. The number of people affected has been increasing and patients are seldom aware of the disease, which can cause delay in the treatment. A review of how computer-aided approaches may be applied in the diagnosis and staging of glaucoma is discussed here. The current status of the computer technology is reviewed, covering localization and segmentation of the optic nerve head, pixel level glaucomatic changes, diagonosis using 3-D data sets, and artificial neural networks for detecting the progression of the glaucoma disease

Extraction of Features from Fundus Images for Glaucoma Assessment

Master'sMASTER OF ENGINEERIN

Deep learning in ophthalmology: The technical and clinical considerations

The advent of computer graphic processing units, improvement in mathematical models and availability of big data has allowed artificial intelligence (AI) using machine learning (ML) and deep learning (DL) techniques to achieve robust performance for broad applications in social-media, the internet of things, the automotive industry and healthcare. DL systems in particular provide improved capability in image, speech and motion recognition as well as in natural language processing. In medicine, significant progress of AI and DL systems has been demonstrated in image-centric specialties such as radiology, dermatology, pathology and ophthalmology. New studies, including pre-registered prospective clinical trials, have shown DL systems are accurate and effective in detecting diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD), retinopathy of prematurity, refractive error and in identifying cardiovascular risk factors and diseases, from digital fundus photographs. There is also increasing attention on the use of AI and DL systems in identifying disease features, progression and treatment response for retinal diseases such as neovascular AMD and diabetic macular edema using optical coherence tomography (OCT). Additionally, the application of ML to visual fields may be useful in detecting glaucoma progression. There are limited studies that incorporate clinical data including electronic health records, in AL and DL algorithms, and no prospective studies to demonstrate that AI and DL algorithms can predict the development of clinical eye disease. This article describes global eye disease burden, unmet needs and common conditions of public health importance for which AI and DL systems may be applicable. Technical and clinical aspects to build a DL system to address those needs, and the potential challenges for clinical adoption are discussed. AI, ML and DL will likely play a crucial role in clinical ophthalmology practice, with implications for screening, diagnosis and follow up of the major causes of vision impairment in the setting of ageing populations globally

Aspects of structural and functional assessment in open angle glaucoma

Early detection of glaucoma is a prerequisite for effective management of the disease. The study was concerned with aspects of structural and functional assessment in open angle glaucoma. The major part of the study was concerned with the utilization of digital stereoscopic imaging of the optic nerve head in the detection of open angle glaucoma (OAG). Specifically, it addressed possible sources of variability that confound the diagnosis of glaucoma and are associated with the monoscopic, as opposed to stereoscopic, observation of the optic nerve head (ONH) the limited diagnostic value of the features of the peripapillary retina accompanying glaucomatous damage and the between-observer variation in the subjective evaluation of the ONH. The study utilised a dataset of magnification corrected digital images from 51 normal individuals and from 113 patients with OAG. Misdiagnosis of glaucoma was associated with discrepancies in the evaluation of the rim area due to the monoscopic presentation of the ONH masking the presence of focal rim loss, otherwise evident with stereoscopic observation. The frequency and patterns of distribution of the alpha and beta peripapillary atrophy (PPA) were confirmed among normal and glaucomatous eyes but meaningful conclusions on the diagnostic value of PPA were hindered by the clinically broad criteria of this feature. Regression analysis of the global and sectorial rim areas for the discrimination of glaucomatous damage compared favourably with the subjective glaucoma diagnosis by expert observers. The remaining part of the study was concerned with the evaluation of the Total and Pattern Deviation probability analysis in short-wavelength perimetry (SWAP). The material comprised the Humphrey Field Analyzer single field print-outs from standard automated perimetry (SAP) and from SWAP of 53 normal individuals 18 patients with cataract, 22 with OHT and 55 with OAG. Focal visual field loss derived by SWAP was markedly less compared to SWAP indicating wider limits of normality for SWAP. Considerable caution should be exercised before the use of SWAP

Automatic extraction of retinal features to assist diagnosis of glaucoma disease

Glaucoma is a group of eye diseases that have common traits such as high eye pressure, damage to the Optic Nerve Head (ONH) and gradual vision loss. It affects the peripheral vision and eventually leads to blindness if left untreated. The current common methods of diagnosis of glaucoma are performed manually by the clinicians. Clinicians perform manual image operations such as change of contrast, zooming in zooming out etc to observe glaucoma related clinical indications. This type of diagnostic process is time consuming and subjective. With the advancement of image and vision computing, by automating steps in the diagnostic process, more patients can be screened and early treatment can be provided to prevent any or further loss of vision. The aim of this work is to develop a system called Glaucoma Detection Framework (GDF), which can automatically determine changes in retinal structures and imagebased pattern associated with glaucoma so as to assist the eye clinicians for glaucoma diagnosis in a timely and effective manner. In this work, several major contributions have been made towards the development of the automatic GDF consisting of the stages of preprocessing, optic disc and cup segmentation and regional image feature methods for classification between glaucoma and normal images. Firstly, in the preprocessing step, a retinal area detector based on superpixel classification model has been developed in order to automatically determine true retinal area from a Scanning Laser Ophthalmoscope (SLO) image. The retinal area detector can automatically extract artefacts out from the SLO image while preserving the computational effciency and avoiding over-segmentation of the artefacts. Localization of the ONH is one of the important steps towards the glaucoma analysis. A new weighted feature map approach has been proposed, which can enhance the region of ONH for accurate localization. For determining vasculature shift, which is one of glaucoma indications, we proposed the ONH cropped image based vasculature classification model to segment out the vasculature from the ONH cropped image. The ONH cropped image based vasculature classification model is developed in order to avoid misidentification of optic disc boundary and Peripapillary Atrophy (PPA) around the ONH of being a part of the vasculature area. Secondly, for automatic determination of optic disc and optic cup boundaries, a Point Edge Model (PEM), a Weighted Point Edge Model (WPEM) and a Region Classification Model (RCM) have been proposed. The RCM initially determines the optic disc region using the set of feature maps most suitable for the region classification whereas the PEM updates the contour using the force field of the feature maps with strong edge profile. The combination of PEM and RCM entitled Point Edge and Region Classification Model (PERCM) has significantly increased the accuracy of optic disc segmentation with respect to clinical annotations around optic disc. On the other hand, the WPEM determines the force field using the weighted feature maps calculated by the RCM for optic cup in order to enhance the optic cup region compared to rim area in the ONH. The combination of WPEM and RCM entitled Weighted Point Edge and Region Classification Model (WPERCM) can significantly enhance the accuracy of optic cup segmentation. Thirdly, this work proposes a Regional Image Features Model (RIFM) which can automatically perform classification between normal and glaucoma images on the basis of regional information. Different from the existing methods focusing on global features information only, our approach after optic disc localization and segmentation can automatically divide an image into five regions (i.e. optic disc or Optic Nerve Head (ONH) area, inferior (I), superior(S), nasal(N) and temporal(T)). These regions are usually used for diagnosis of glaucoma by clinicians through visual observation only. It then extracts image-based information such as textural, spatial and frequency based information so as to distinguish between normal and glaucoma images. The method provides a new way to identify glaucoma symptoms without determining any geometrical measurement associated with clinical indications glaucoma. Finally, we have accommodated clinical indications of glaucoma including the CDR, vasculature shift and neuroretinal rim loss with the RIFM classification and performed automatic classification between normal and glaucoma images. Since based on the clinical literature, no geometrical measurement is the guaranteed sign of glaucoma, the accommodation of the RIFM classification results with clinical indications of glaucoma can lead to more accurate classification between normal and glaucoma images. The proposed methods in this work have been tested against retinal image databases of 208 fundus images and 102 Scanning Laser Ophthalmoscope (SLO) images. These databases have been annotated by the clinicians around different anatomical structures associated with glaucoma as well as annotated with healthy or glaucomatous images. In fundus images, ONH cropped images have resolution varying from 300 to 900 whereas in SLO images, the resolution is 341 x 341. The accuracy of classification between normal and glaucoma images on fundus images and the SLO images is 94.93% and 98.03% respectively