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

Current and future roles of artificial intelligence in retinopathy of prematurity

Retinopathy of prematurity (ROP) is a severe condition affecting premature infants, leading to abnormal retinal blood vessel growth, retinal detachment, and potential blindness. While semi-automated systems have been used in the past to diagnose ROP-related plus disease by quantifying retinal vessel features, traditional machine learning (ML) models face challenges like accuracy and overfitting. Recent advancements in deep learning (DL), especially convolutional neural networks (CNNs), have significantly improved ROP detection and classification. The i-ROP deep learning (i-ROP-DL) system also shows promise in detecting plus disease, offering reliable ROP diagnosis potential. This research comprehensively examines the contemporary progress and challenges associated with using retinal imaging and artificial intelligence (AI) to detect ROP, offering valuable insights that can guide further investigation in this domain. Based on 89 original studies in this field (out of 1487 studies that were comprehensively reviewed), we concluded that traditional methods for ROP diagnosis suffer from subjectivity and manual analysis, leading to inconsistent clinical decisions. AI holds great promise for improving ROP management. This review explores AI's potential in ROP detection, classification, diagnosis, and prognosis.Comment: 28 pages, 8 figures, 2 tables, 235 references, 1 supplementary tabl

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

Diabetic Reinopathy Classification using Deep Learning

With diabetes growing at an alarming rate, changes in the retina of diabetic patients causes a condition called diabetic retinopathy which eventually leads to blindness. Early detection of diabetic retinopathy is the best way to provide good timely treatment and thus prevent blindness. Many developed countries have put forward well-structured screening programs which screens every person diagnosed with diabetes at regular intervals. However, the cost of running these programs is increasing with ever increasing disease burden. These screening programs require well trained opticians or ophthalmologist which are expensive especially in developing countries. A global shortage of health care professionals is putting a pressing need to develop fast and efficient screening methods. Using artificial intelligent screening tools will help process and generate a plan for the patients thus skipping the health care provider needed to just classify the disease and will lower the burden on health care professional’s shortage significantly. A plethora of research exists to classify severity of diabetic retinopathy using traditional and end to end methods. In this thesis, we first trained and compared the performance of lightweight architecture MobileNetV2 with other classifiers like DenseNet121 and VGG16 using the Retinal fundus APTOS 2019 Kaggle dataset. We experimented with different image reprocessing techniques and employed various hyperparameter tuning techniques, and found the lightweight architecture MobileNetV2 to give better results in terms of AUC score which defines the ability of the classifier to separate between the classes. We then trained MobileNetV2 using handpicked custom dataset which was an amalgamation of 3 different publicly available datasets viz. the EyePacs Kaggle dataset, the APTOS 2019 Blindness detection dataset and the Messidor2 dataset. We enhanced the retinal features using bio-inspired retinal filters and tuned the hyper-parameters to achieve an accuracy of 91.68% and AUC score of 0.9 when tested on unseen data. The macro precision, recall, and f1-scores are 77.6%, 83.1%, and 80.1% respectively. Our results demonstrate that our computational efficient light weight model achieves promising results and can be deployed as a mobile application for clinical testing

Automatic Detection and Characterization of Pathological Fluid Regions in Optical Coherence Tomography Images

Programa Oficial de Doutoramento en Computación. 5009V01[Abstract] Intraretinal fluid accumulation is both the common symptom and culprit of the main causes of blindness in developed countries: Age-related Macular Degeneration and Diabetic Macular Edema. For its diagnosis, experts of the domain employ Optical Coherence Tomography images (OCT), providing non-invasive cross-sectional representations of the retinal structures. However, like any medical imaging modality, OCT is influenced by multiple factors that impact its quality and subsequent interpretation. Coupled with the subjectiveness of the human experts, these factors can significantly affect the diagnostic process, treatment and quality of life for the affected individuals (particularly in these pathologies where early detection is crucial). To address these challenges, Computer-Aided Diagnosis (CAD) methodologies are developed, offering a layer of abstraction of the information present in the images. Still, in the particular scenario of these pathological fluid accumulations, the development of these methodologies is specially difficult due to their diffuse nature without defined boundaries. In this thesis, we proposed different CAD methodologies with the objective of helping expert clinicians to better detect and understand these pathologies. Furthermore, we expand the developed methodologies to other medical imaging modalities and conditions, such as macular neovascularizations in OCT Angiographies and COVID-19 diagnosis through the analysis of lung chest radiographs.[Resumen] La acumulación de líquido intrarretiniano es tanto síntoma común como culpable de las principales causas de ceguera en los países desarrollados: la degeneración macular asociada a la edad y el edema macular diabético. Para su diagnóstico, los expertos en el campo emplean imágenes de Tomografía de Coherencia Óptica (OCT), que proporcionan representaciones transversales no invasivas de las estructuras retinianas. Sin embargo, al igual que cualquier modalidad de imagen médica, OCT se ve influenciado por múltiples factores que afectan a su calidad y posterior interpretación. Junto con la subjetividad de los expertos humanos, estos factores pueden afectar significativamente el proceso diagnóstico, tratamiento y calidad de vida de las personas afectadas (particularmente en estas patologías donde una detección temprana es crucial). Para abordar estos desafíos, se desarrollan metodologías de diagnóstico asistido por ordenador (CAD), que ofrecen una capa de abstracción de la información presente en las imágenes. Sin embargo, en el escenario particular de estas acumulaciones patológicas de fluido, el desarrollo de estas metodologías es especialmente difícil debido a su naturaleza difusa, sin bordes definidos. En esta tesis doctoral proponemos diferentes metodologías CAD con el objetivo de ayudar a las personas expertas del dominio a detectar y comprender mejor estas patologías. Además, expandimos las metodologías desarrolladas a otras modalidades de imagen médica y afecciones, como al análisis de neovascularizaciones maculares en Angiografía OCT y al diagnóstico de COVID-19 mediante radiografías torácicas.[Resumo] A acumulación de líquido intrarretiniano é tanto o síntoma común como culpable das principais causas de cegueira nos países desenvolvidos: a dexeneración macular asociada á idade e o edema macular diabético. Para o seu diagnóstico, os expertos no campo empregan imaxes de tomografía de coherencia óptica (OCT), que proporcionan representacións transversais non invasivas das estruturas retinianas. Non obstante, ao igual que calquera modalidade de imaxe médica, a OCT vese influenciada por múltiples factores que afectan a s´ua calidade e a súa posterior interpretación. Xunto coa subxectividade dos expertos humanos, estes factores poden afectar significativamente ao proceso diagn´ostico, ao tratamento e á calidade de vida das persoas afectadas (particularmente nestas patoloxías onde unha detección precoz é crucial). Para abordar estes desafíos, desenvólvense metodoloxías de diagnóstico asistido por ordenador (CAD), que ofrecen unha capa de abstracción da información presente nas imaxes. Non obstante, no escenario particular das acumulacións patolóxicas de líquido, o desenvolvemento destas metodoloxías é especialmente difícil debido a súa natureza difusa, sen bordes definidos. Nesta tese de doutoramento propoñemos diferentes metodoloxías de CAD co obxectivo de axudar ás persoas expertas do campo a detectar e comprender mellor estas patoloxías. Ademais, expandimos as metodoloxías desenvoltas a outras modalidades de imaxe médica e patoloxías, como a an´alise de neovascularizacións maculares en Anxiografía OCT e ao diagnóstico da COVID-19 mediante a análise de radiografías torácicas

Automatic analysis of retinal images to aid in the diagnosis and grading of diabetic retinopathy

Diabetic retinopathy (DR) is the most common complication of diabetes mellitus and one of the leading causes of preventable blindness in the adult working population. Visual loss can be prevented from the early stages of DR, when the treatments are effective. Therefore, early diagnosis is paramount. However, DR may be clinically asymptomatic until the advanced stage, when vision is already affected and treatment may become difficult. For this reason, diabetic patients should undergo regular eye examinations through screening programs. Traditionally, DR screening programs are run by trained specialists through visual inspection of the retinal images. However, this manual analysis is time consuming and expensive. With the increasing incidence of diabetes and the limited number of clinicians and sanitary resources, the early detection of DR becomes non-viable. For this reason, computed-aided diagnosis (CAD) systems are required to assist specialists for a fast, reliable diagnosis, allowing to reduce the workload and the associated costs. We hypothesize that the application of novel, automatic algorithms for fundus image analysis could contribute to the early diagnosis of DR. Consequently, the main objective of the present Doctoral Thesis is to study, design and develop novel methods based on the automatic analysis of fundus images to aid in the screening, diagnosis, and treatment of DR. In order to achieve the main goal, we built a private database and used five retinal public databases: DRIMDB, DIARETDB1, DRIVE, Messidor and Kaggle. The stages of fundus image processing covered in this Thesis are: retinal image quality assessment (RIQA), the location of the optic disc (OD) and the fovea, the segmentation of RLs and EXs, and the DR severity grading. RIQA was studied with two different approaches. The first approach was based on the combination of novel, global features. Results achieved 91.46% accuracy, 92.04% sensitivity, and 87.92% specificity using the private database. We developed a second approach aimed at RIQA based on deep learning. We achieved 95.29% accuracy with the private database and 99.48% accuracy with the DRIMDB database. The location of the OD and the fovea was performed using a combination of saliency maps. The proposed methods were evaluated over the private database and the public databases DRIVE, DIARETDB1 and Messidor. For the OD, we achieved 100% accuracy for all databases except Messidor (99.50%). As for the fovea location, we also reached 100% accuracy for all databases except Messidor (99.67%). The joint segmentation of RLs and EXs was accomplished by decomposing the fundus image into layers. Results were computed per pixel and per image. Using the private database, 88.34% per-image accuracy (ACCi) was reached for the RL detection and 95.41% ACCi for EX detection. An additional method was proposed for the segmentation of RLs based on superpixels. Evaluating this method with the private database, we obtained 84.45% ACCi. Results were validated using the DIARETDB1 database. Finally, we proposed a deep learning framework for the automatic DR severity grading. The method was based on a novel attention mechanism which performs a separate attention of the dark and the bright structures of the retina. The Kaggle DR detection dataset was used for development and validation. The International Clinical DR Scale was considered, which is made up of 5 DR severity levels. Classification results for all classes achieved 83.70% accuracy and a Quadratic Weighted Kappa of 0.78. The methods proposed in this Doctoral Thesis form a complete, automatic DR screening system, contributing to aid in the early detection of DR. In this way, diabetic patients could receive better attention for their ocular health avoiding vision loss. In addition, the workload of specialists could be relieved while healthcare costs are reduced.La retinopatía diabética (RD) es la complicación más común de la diabetes mellitus y una de las principales causas de ceguera prevenible en la población activa adulta. El diagnóstico precoz es primordial para prevenir la pérdida visual. Sin embargo, la RD es clínicamente asintomática hasta etapas avanzadas, cuando la visión ya está afectada. Por eso, los pacientes diabéticos deben someterse a exámenes oftalmológicos periódicos a través de programas de cribado. Tradicionalmente, estos programas están a cargo de especialistas y se basan de la inspección visual de retinografías. Sin embargo, este análisis manual requiere mucho tiempo y es costoso. Con la creciente incidencia de la diabetes y la escasez de recursos sanitarios, la detección precoz de la RD se hace inviable. Por esta razón, se necesitan sistemas de diagnóstico asistido por ordenador (CAD) que ayuden a los especialistas a realizar un diagnóstico rápido y fiable, que permita reducir la carga de trabajo y los costes asociados. El objetivo principal de la presente Tesis Doctoral es estudiar, diseñar y desarrollar nuevos métodos basados en el análisis automático de retinografías para ayudar en el cribado, diagnóstico y tratamiento de la RD. Las etapas estudiadas fueron: la evaluación de la calidad de la imagen retiniana (RIQA), la localización del disco óptico (OD) y la fóvea, la segmentación de RL y EX y la graduación de la severidad de la RD. RIQA se estudió con dos enfoques diferentes. El primer enfoque se basó en la combinación de características globales. Los resultados lograron una precisión del 91,46% utilizando la base de datos privada. El segundo enfoque se basó en aprendizaje profundo. Logramos un 95,29% de precisión con la base de datos privada y un 99,48% con la base de datos DRIMDB. La localización del OD y la fóvea se realizó mediante una combinación de mapas de saliencia. Los métodos propuestos fueron evaluados sobre la base de datos privada y las bases de datos públicas DRIVE, DIARETDB1 y Messidor. Para el OD, logramos una precisión del 100% para todas las bases de datos excepto Messidor (99,50%). En cuanto a la ubicación de la fóvea, también alcanzamos un 100% de precisión para todas las bases de datos excepto Messidor (99,67%). La segmentación conjunta de RL y EX se logró descomponiendo la imagen del fondo de ojo en capas. Utilizando la base de datos privada, se alcanzó un 88,34% de precisión por imagen (ACCi) para la detección de RL y un 95,41% de ACCi para la detección de EX. Se propuso un método adicional para la segmentación de RL basado en superpíxeles. Evaluando este método con la base de datos privada, obtuvimos 84.45% ACCi. Los resultados se validaron utilizando la base de datos DIARETDB1. Finalmente, propusimos un método de aprendizaje profundo para la graduación automática de la gravedad de la DR. El método se basó en un mecanismo de atención. Se utilizó la base de datos Kaggle y la Escala Clínica Internacional de RD (5 niveles de severidad). Los resultados de clasificación para todas las clases alcanzaron una precisión del 83,70% y un Kappa ponderado cuadrático de 0,78. Los métodos propuestos en esta Tesis Doctoral forman un sistema completo y automático de cribado de RD, contribuyendo a ayudar en la detección precoz de la RD. De esta forma, los pacientes diabéticos podrían recibir una mejor atención para su salud ocular evitando la pérdida de visión. Además, se podría aliviar la carga de trabajo de los especialistas al mismo tiempo que se reducen los costes sanitarios.Escuela de DoctoradoDoctorado en Tecnologías de la Información y las Telecomunicacione

Deep Feature Fusion Network for Computer-aided Diagnosis of Glaucoma using Optical Coherence Tomography

학위논문 (박사)-- 서울대학교 대학원 공과대학 협동과정 바이오엔지니어링전공, 2017. 8. 김희찬.Glaucoma has been able to be diagnosed noninvasively by analyzing the optic disc thickness with the development of optical coherence tomography. However, it is essential to maintain proper intraocular pressure through early diagnosis of glaucoma. Therefore, it is required to develop a computer-aided diagnosis system to accurately and objectively analyze glaucoma of early stage. In this paper, we propose deep feature fusion network for realizing computer-aided system which can accurately diagnose early glaucoma and verify the clinical efficacy through performance evaluation using patient images. Deep feature fusion network is analyzed by fusing features which are extracted by feature-based classification used in machine learning and by deep learning in deep neural network. Deep feature fusion network is deep neural network composed of heterogeneous features extracted through image processing and deep learning. The area and depth features of optic nerve defects related to glaucoma were extracted by using traditional image processing methods and the features related to distinction between glaucoma and normal subjects were extracted from the middle layer output of the deep neural network. Deep feature fusion network was developed by fusing extracted features. We analyzed features based on image processing using thickness map and deviation map of retinal nerve fiber layer and ganglion cell inner plexiform layer in order to extract features related to the area of the optic nerve defects. Optic nerve defects were segmented in each deviation map by three criteria and the area of the defects was calculated about 69 glaucoma patients and 79 normal subjects. The performance of the severity indices calculated by defects area was evaluated by the area under ROC curve (AUC). There were significant differences between glaucoma patients and normal subjects in all severity indices (p < 0.0001) and correctly distinguished between glaucoma patients and normal subjects (AUC = 0.91 to 0.95). This suggests that the area features of optic nerve defects can be used as an objective indicator of glaucoma diagnosis. We analyzed features based on another image processing using retinal nerve fiber layer thickness map and deviation map to extract the features related to the depth of the optic nerve defects. Depth related index was developed by using the ratio of the optic nerve thickness of the normal to the optic nerve thickness in the optic nerve defects analyzed by the deviation map. 108 early glaucoma patients, 96 moderate glaucoma patients, and 111 severe glaucoma patients were analyzed by using depth index and the performance was evaluated by AUC. There were significant differences between the groups in the index (p < 0.001) and the index discriminated between moderate glaucoma patients and severe glaucoma patients (AUC = 0.97) as well as early glaucoma patients and moderate glaucoma patients (AUC = 0.98). It was found that the depth index of the optic nerve defects were a significant feature to distinguish the degree of glaucoma. Two methods were used to apply thickness map to deep learning. One method is deep learning using randomly distributed weights in LeNet and the other method is deep learning using weights pre-trained by other large image data in VGGNet. We analyzed two methods for 316 normal subjects, 226 glaucoma patients of early stage, and 246 glaucoma patients of moderate and severe stage and evaluated performance through AUC for each groups. Deep neural networks learned with LeNet and VGGNet distinguished normal subjects not only from glaucoma patients (AUC = 0.94, 0.94), but also from glaucoma patients of early stage (AUC = 0.88, 0.89). It was found that two deep learning methods extract the features related to glaucoma. Finally, we developed deep feature fusion network by fusing the features extracted from image processing and the features extracted by deep learning and compared the performance with the previous studies though AUC. Deep feature fusion network fusing the features extracted in VGGNet correctly distinguished normal subjects not only from glaucoma patients (AUC = 0.96), but also from glaucoma patients of early stage (AUC = 0.92). This network is superior to the previous study (AUC = 0.91, 0.82). It showed excellent performance in distinguishing early glaucoma patients from normal subjects particularly. These results show that the proposed deep feature fusion network provides higher accuracy in diagnosis and early diagnosis of glaucoma than any other previous methods. It is expected that further accuracy of the features will be improved if additional features of demographic information and various glaucoma test results are added to deep feature fusion network. Deep feature fusion network proposed in this paper is expected to be applicable not only to early diagnosis of glaucoma but also to analyze progress of glaucoma.Chapter 1 : General Introduction 1 1.1. Glaucoma 2 1.2. Optical Coherence Tomography 5 1.3. Thesis Objectives 7 Chapter 2 : Feature Extraction for Glaucoma Diagnosis 1. Severity Index of Macular GCIPL and Peripapillary RNFL Deviation Maps 9 2.1. Introduction 10 2.2. Methods 12 2.2.1. Study subjects 12 2.2.2. Red-free RNFL photography 14 2.2.3. Cirrus OCT imaging 15 2.2.4. Deviation map analysis protocol 17 2.2.5. Statistical analysis 21 2.3. Results 23 2.4. Discussion 33 Chapter 3 : Feature Extraction for Glaucoma Diagnosis 2. RNFL Defect Depth Percentage Index of Thickness Deviation Maps 41 3.1. Introduction 42 3.2. Methods 44 3.2.1. Subjects 44 3.2.2. Red-free fundus photography imaging 46 3.2.3. Optical coherence tomography retinal nerve fiber layer imaging 51 3.2.4. Measuring depth of retinal nerve fiber layer defects on cirrus high-definition optical coherence tomography derived deviation map 52 3.2.5. Data analysis 57 3.3. Results 58 3.4. Discussion 69 Chapter 4 : Glaucoma Classification using Deep Feature Fusion Network 74 4.1. Introduction 75 4.2. Methods 77 4.2.1. Study subjects 77 4.2.2. OCT imaging 79 4.2.3. Deep Feature Fusion Network 81 4.2.4. Statistical analysis 88 4.3. Results 90 4.4. Discussion 105 Chapter 5 : Thesis Summary and Future Work 111 5.1 Thesis Summary and Contribution 112 5.2 Future Work 115 Bibliography 117 Abstract in Korean 125Docto

Development of Novel Diagnostic Tools for Dry Eye Disease using Infrared Meibography and In Vivo Confocal Microscopy

Dry eye disease (DED) is a multifactorial disease of the ocular surface where tear film instability, hyperosmolarity, neurosensory abnormalities, meibomian gland dysfunction, ocular surface inflammation and damage play a dedicated etiological role. Estimated 5 to 50% of the world population in different demographic locations, age and gender are currently affected by DED. The risk and occurrence of DED increases at a significant rate with age, which makes dry eye a major growing public health issue. DED not only impacts the patient’s quality of vision and life, but also creates a socio-economic burden of millions of euros per year. DED diagnosis and monitoring can be a challenging task in clinical practice due to the multifactorial nature and the poor correlation between signs and symptoms. Key clinical diagnostic tests and techniques for DED diagnosis include tearfilm break up time, tear secretion – Schirmer’s test, ocular surface staining, measurement of osmolarity, conjunctival impression cytology. However, these clinical diagnostic techniques are subjective, selective, require contact, and are unpleasant for the patient’s eye. Currently, new advances in different state-of-the-art imaging modalities provide non-invasive, non- or semi-contact, and objective parameters that enable objective evaluation of DED diagnosis. Among the different and constantly evolving imaging modalities, some techniques are developed to assess morphology and function of meibomian glands, and microanatomy and alteration of the different ocular surface tissues such as corneal nerves, immune cells, microneuromas, and conjunctival blood vessels. These clinical parameters cannot be measured by conventional clinical assessment alone. The combination of these imaging modalities with clinical feedback provides unparalleled quantification information of the dynamic properties and functional parameters of different ocular surface tissues. Moreover, image-based biomarkers provide objective, specific, and non / marginal contact diagnosis, which is faster and less unpleasant to the patient’s eye than the clinical assessment techniques. The aim of this PhD thesis was to introduced deep learning-based novel computational methods to segment and quantify meibomian glands (both upper and lower eyelids), corneal nerves, and dendritic cells. The developed methods used raw images, directly export from the clinical devices without any image pre-processing to generate segmentation masks. Afterward, it provides fully automatic morphometric quantification parameters for more reliable disease diagnosis. Noteworthily, the developed methods provide complete segmentation and quantification information for faster disease characterization. Thus, the developed methods are the first methods (especially for meibomian gland and dendritic cells) to provide complete morphometric analysis. Taken together, we have developed deep learning based automatic system to segment and quantify different ocular surface tissues related to DED namely, meibomian gland, corneal nerves, and dendritic cells to provide reliable and faster disease characterization. The developed system overcomes the current limitations of subjective image analysis and enables precise, accurate, reliable, and reproducible ocular surface tissue analysis. These systems have the potential to make an impact clinically and in the research environment by specifying faster disease diagnosis, facilitating new drug development, and standardizing clinical trials. Moreover, it will allow both researcher and clinicians to analyze meibomian glands, corneal nerves, and dendritic cells more reliably while reducing the time needed to analyze patient images significantly. Finally, the methods developed in this research significantly increase the efficiency of evaluating clinical images, thereby supporting and potentially improving diagnosis and treatment of ocular surface disease