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

CAD system for early diagnosis of diabetic retinopathy based on 3D extracted imaging markers.

This dissertation makes significant contributions to the field of ophthalmology, addressing the segmentation of retinal layers and the diagnosis of diabetic retinopathy (DR). The first contribution is a novel 3D segmentation approach that leverages the patientspecific anatomy of retinal layers. This approach demonstrates superior accuracy in segmenting all retinal layers from a 3D retinal image compared to current state-of-the-art methods. It also offers enhanced speed, enabling potential clinical applications. The proposed segmentation approach holds great potential for supporting surgical planning and guidance in retinal procedures such as retinal detachment repair or macular hole closure. Surgeons can benefit from the accurate delineation of retinal layers, enabling better understanding of the anatomical structure and more effective surgical interventions. Moreover, real-time guidance systems can be developed to assist surgeons during procedures, improving overall patient outcomes. The second contribution of this dissertation is the introduction of a novel computeraided diagnosis (CAD) system for precise identification of diabetic retinopathy. The CAD system utilizes 3D-OCT imaging and employs an innovative approach that extracts two distinct features: first-order reflectivity and 3D thickness. These features are then fused and used to train and test a neural network classifier. The proposed CAD system exhibits promising results, surpassing other machine learning and deep learning algorithms commonly employed in DR detection. This demonstrates the effectiveness of the comprehensive analysis approach employed by the CAD system, which considers both low-level and high-level data from the 3D retinal layers. The CAD system presents a groundbreaking contribution to the field, as it goes beyond conventional methods, optimizing backpropagated neural networks to integrate multiple levels of information effectively. By achieving superior performance, the proposed CAD system showcases its potential in accurately diagnosing DR and aiding in the prevention of vision loss. In conclusion, this dissertation presents novel approaches for the segmentation of retinal layers and the diagnosis of diabetic retinopathy. The proposed methods exhibit significant improvements in accuracy, speed, and performance compared to existing techniques, opening new avenues for clinical applications and advancements in the field of ophthalmology. By addressing future research directions, such as testing on larger datasets, exploring alternative algorithms, and incorporating user feedback, the proposed methods can be further refined and developed into robust, accurate, and clinically valuable tools for diagnosing and monitoring retinal diseases

Multimodal Assessment of Structure and Function in Inherited Retinal Degenerations

Inherited retinal degenerations (IRDs) affect approximately 1:4,000 people worldwide and are currently the leading cause of vision loss of people between the ages of 15-45. The mechanisms of degeneration in many IRDs remain unclear. It is vital to establish relationships between retinal structural and functional measures in order to better understand the relationship between the genetic mutations and the phenotypes they cause in these diseases. For example, retinitis pigmentosa (RP), the most prevalent IRD, and choroideremia (CHM), an X-linked degeneration that affects choroidal, RPE and photoreceptor cells, both progress over time due to rod, then cone, photoreceptor loss. Greater understanding of disease progression may clarify the underlying mechanisms of retinal degenerations. Furthermore, the development of novel outcome measures could accelerate clinical trials of treatments designed to treat these relentless, sight-threatening diseases. The experiments and research described in this document use multimodal state-of-the-art, novel, high-resolution techniques in addition to standard technologies used in the clinical setting to study the relationship between structure and function of the retina including rod and cone photoreceptors, retinal pigment epithelium, choriocapillaris and other retinal layers affected in the eyes of patients with retinal degeneration

NON-INVASIVE IMAGE ENHANCEMENT OF COLOUR RETINAL FUNDUS IMAGES FOR A COMPUTERISED DIABETIC RETINOPATHY MONITORING AND GRADING SYSTEM

Diabetic Retinopathy (DR) is a sight threatening complication due to diabetes mellitus affecting the retina. The pathologies of DR can be monitored by analysing colour fundus images. However, the low and varied contrast between retinal vessels and the background in colour fundus images remains an impediment to visual analysis in particular in analysing tiny retinal vessels and capillary networks. To circumvent this problem, fundus fluorescein angiography (FF A) that improves the image contrast is used. Unfortunately, it is an invasive procedure (injection of contrast dyes) that leads to other physiological problems and in the worst case may cause death. The objective of this research is to develop a non-invasive digital Image enhancement scheme that can overcome the problem of the varied and low contrast colour fundus images in order that the contrast produced is comparable to the invasive fluorescein method, and without introducing noise or artefacts. The developed image enhancement algorithm (called RETICA) is incorporated into a newly developed computerised DR system (called RETINO) that is capable to monitor and grade DR severity using colour fundus images. RETINO grades DR severity into five stages, namely No DR, Mild Non Proliferative DR (NPDR), Moderate NPDR, Severe NPDR and Proliferative DR (PDR) by enhancing the quality of digital colour fundus image using RETICA in the macular region and analysing the enlargement of the foveal avascular zone (F AZ), a region devoid of retinal vessels in the macular region. The importance of this research is to improve image quality in order to increase the accuracy, sensitivity and specificity of DR diagnosis, and to enable DR grading through either direct observation or computer assisted diagnosis system

Recent Developments in Detection of Central Serous Retinopathy through Imaging and Artificial Intelligence Techniques – A Review

Central Serous Retinopathy (CSR) or Central Serous Chorioretinopathy (CSC) is a significant disease that causes blindness and vision loss among millions of people worldwide. It transpires as a result of accumulation of watery fluids behind the retina. Therefore, detection of CSR at early stages allows preventive measures to avert any impairment to the human eye. Traditionally, several manual methods for detecting CSR have been developed in the past; however, they have shown to be imprecise and unreliable. Consequently, Artificial Intelligence (AI) services in the medical field, including automated CSR detection, are now possible to detect and cure this disease. This review assessed a variety of innovative technologies and researches that contribute to the automatic detection of CSR. In this review, various CSR disease detection techniques, broadly classified into two categories: a) CSR detection based on classical imaging technologies, and b) CSR detection based on Machine/Deep Learning methods, have been reviewed after an elaborated evaluation of 29 different relevant articles. Additionally, it also goes over the advantages, drawbacks and limitations of a variety of traditional imaging techniques, such as Optical Coherence Tomography Angiography (OCTA), Fundus Imaging and more recent approaches that utilize Artificial Intelligence techniques. Finally, it is concluded that the most recent Deep Learning (DL) classifiers deliver accurate, fast, and reliable CSR detection. However, more research needs to be conducted on publicly available datasets to improve computation complexity for the reliable detection and diagnosis of CSR disease

Caracterización del Edema Macular Diabético mediante análisis automático de Tomografías de Coherencia Óptica

Programa Oficial de Doctorado en Computación. 5009V01[Abstract] Diabetic Macular Edema (DME) is one of the most important complications of diabetes and a leading cause of preventable blindness in the developed countries. Among the di erent image modalities, Optical Coherence Tomography (OCT) is a non-invasive, cross-sectional and high-resolution imaging technique that is commonly used for the analysis and interpretation of many retinal structures and ocular disorders. In this way, the development of Computer-Aided Diagnosis (CAD) systems has become relevant over the recent years, facilitating and simplifying the work of the clinical specialists in many relevant diagnostic processes, replacing manual procedures that are tedious and highly time-consuming. This thesis proposes a complete methodology for the identi cation and characterization of DMEs using OCT images. To do so, the system combines and exploits di erent clinical knowledge with image processing and machine learning strategies. This automatic system is able to identify and characterize the main retinal structures and several pathological conditions that are associated with the DME disease, following the clinical classi cation of reference in the ophthalmological eld. Despite the complexity and heterogeneity of this relevant ocular pathology, the proposed system achieved satisfactory results, proving to be robust enough to be used in the daily clinical practice, helping the clinicians to produce a more accurate diagnosis and indicate adequate treatments[Resumen] El Edema Macular Diabético (EMD) es una de las complicaciones más importantes de la diabetes y una de las principales causas de ceguera prevenible en los países desarrollados. Entre las diferentes modalidades de imagen, la Tomografía de Coherencia Óptica (TCO) es una técnica de imagen no invasiva, transversal y de alta resolución que se usa comúnmente para el análisis e interpretación de múltiples estructuras retinianas y trastornos oculares. De esta manera, el desarrollo de los sistemas de Diagnóstico Asistido por Ordenador (DAO) se ha vuelto relevante en los últimos años, facilitando y simplificando el trabajo de los especialistas clínicos en muchos procesos diagnósticos relevantes, reemplazando procedimientos manuales que son tediosos y requieren mucho tiempo. Esta tesis propone una metodología completa para la identificación y caracterización de EMDs utilizando imágenes TCO. Para ello, el sistema desarrollado combina y explota diferentes conocimientos clínicos con estrategias de procesamiento de imágenes y aprendizaje automático. Este sistema automático es capaz de identificar y caracterizar las principales estructuras retinianas y diferentes afecciones patológicas asociadas con el EMD, siguiendo la clasificación clínica de referencia en el campo oftalmológico. A pesar de la complejidad de esta relevante patología ocular, el sistema propuesto logró resultados satisfactorios, demostrando ser lo sufi cientemente robusto como para ser usado en la práctica clínica diaria, ayudando a los médicos a producir diagnósticos más precisos y tratamientos más adecuados.[Resumo] O Edema Macular Diabético ( EMD) é unha das complicacións máis importantes da diabetes e unha das principais causas de cegueira prevenible nos países desenvoltos. Entre as diferentes modalidades de imaxe, a Tomografía de Coherencia Óptica ( TCO) é unha técnica de imaxe non invasiva, transversal e de alta resolución que se usa comunmente para a análise e interpretación de múltiples estruturas retinianas e trastornos oculares. Desta maneira, o desenvolvemento dos sistemas de Diagnóstico Asistido por Computador ( DAO) volveuse relevante nos últimos anos, facilitando e simplificando o traballo dos especialistas clínicos en moitos procesos diagnósticos relevantes, substituíndo procedementos manuais que son tediosos e requiren moito tempo. Esta tese propón unha metodoloxía completa para a identificación e caracterización de EMDs utilizando imaxes TCO. Para iso, o sistema desenvolto combina e explota diferentes coñecementos clínicos con estratexias de procesamento de imaxes e aprendizaxe automático. Este sistema automático é capaz de identificar e caracterizar as principais estruturas retinianas e diferentes afeccións patolóxicas asociadas co EMD, seguindo a clasificación clínica de referencia no campo oftalmolóxico. A pesar da complexidade desta relevante patoloxía ocular, o sistema proposto logrou resultados satisfactorios, demostrando ser o sufi cientemente robusto como para ser usado na práctica clínica diaria, axudando aos médicos para producir diagnósticos máis precisos e tratamentos máis adecuados

Scattering angle resolved optical coherence tomography for early retinal detection of Alzheimer’s disease in a murine model

Alzheimer’s disease (AD), a debilitating neurodegenerative disease, is becoming more prevalent with an aging population. Early detection of AD is critical to extending healthy lives, but current techniques for AD detection are invasive and cost-prohibitive. The retina is embryonically derived from the forebrain and, with recent mounting evidence that it may reveal markers of brain injury, is considered a “window to the brain.” Early neurodegenerative changes in the brain are likely to be observed in the retina—synaptic failure and shifts in mitochondrial dynamics. Optical imaging techniques could hold the key to non-invasive early detection of AD in the retina since these disruptions may be observed with light. In particular, optical coherence tomography (OCT) retinal imaging offers 3D images of retinal neurons, but the resolution of clinical OCT systems is not fine enough to observe disruptions in the sub-cellular space. Scattering angle resolved (SAR-) OCT, a new method introduced in this work, aims to access sub-resolution scattering properties which could expose fundamental changes in the neurons associated with AD. In this dissertation, a custom SAR-OCT system and new image processing protocols are designed and constructed for murine retinal imaging. Then, three in-vivo studies are conducted using the imaging system to demonstrate its potential use in disease detection. In the first study, which establishes fundamental measures provided by SAR OCT, the imaging system discerns native scattering differences between retinal layers and regions in healthy mice. In the second study, significant scattering angle shifts are observed in ischemic retinas. Finally, a cross-sectional study compares a transgenic murine model of AD (3xTg-AD) with age-matched wild type controls. By examining the distribution of scattering angles detected by the SAR-OCT system, significant differences are observed in the earliest ages of the diseased mice compared the control mice. In the final chapter, limitations of these studies as well as the imaging and image processing protocols are examined, and recommendations are made for future studies to leverage SAR-OCT for early detection of AD or other neurodegenerative diseasesBiomedical Engineerin

Evaluation of the potentials for optical coherence tomography (OCT) to detect early signs of retinal neurodegeneration

Among neuroretinal degenerations, glaucoma and age-related macular degeneration (AMD) have become the most frequent reasons for irreversible blindness globally. Among the causes of the elderly and senile dementia, Alzheimer’s disease (AD) has the leading position, the early ocular symptoms of which can potentially be a prognostic factor. The aim of this thesis was the early in vivo ligand-free detection of degenerative changes in the inner and outer retinal layers, which was possible using high-resolution optical coherence tomography (OCT) with the machine learning (ML) algorithms: support vector machine (SVM) and principal component analysis (PCA). Prior to the application of SVM and PCA for the classification of human OCT images, evaluation of the classifiers was performed in the classification of optical phantoms, the accuracy of which was in the range of 82-100%. This was the first attempt to measure the textural properties of various polystyrene and silica beads optical phantoms. To identify optical changes that characterise early apoptosis, OCT imaging of axotomised retinal ganglion cells (RGCs) in ex vivo retinal murine explants was performed. Substantial optical alterations in RGC dendrites in the early stages of apoptosis (up to 2 hours) were detected. ML algorithms correctly classified the retinal texture of the inner plexiform layer (IPL) of transgenic AD mice in all cases, indicating the potential for further investigation in in vivo animal and human studies. Not only the optical signature but also the transparency of the dissected murine retinal explants was investigated. Moreover, ML classification of 3xTg mice IPL layer was studied in terms of optical changes due to the RGD dendritic atrophy. ML classifiers’ accuracy in the detection of early and neovascular AMD was 93-100% for the texture of retinal pigment epithelium, 69-67% for the outer nuclear layer, 70% for the inner segment and 60-90% for the outer segment of photoreceptors. Classification of AMD stages and comparison with the age-matched healthy controls was carried out in the outer retina and RPE. Grey-level co-occurrence, run-length matrices, local binary patterns features were extracted from the IPL of the macula to classify glaucoma OCT images. The accuracy of linear and non-linear SVMs, linear and quadratic discriminant analyses, decision tree and logistic regression was between 55-70%. Based on the classifiers’ precision, recall and F1-score, Gaussian SVM outperformed other ML techniques. In this study, the observation of early glaucomatous subtle optical changes of human IPL was conducted. Also, the significance of various supervised ML algorithms was investigated. Understanding the optical signature of cumulative inherent speckle of OCT scans arising from apoptotic retinal ganglion cells and photoreceptors may provide vital information for the prevention of retinal neurodegeneration