Clinical Applications of Artificial Intelligence in Glaucoma

Ophthalmology is one of the major imaging-intensive fields of medicine and thus has potential for extensive applications of artificial intelligence (AI) to advance diagnosis, drug efficacy, and other treatment-related aspects of ocular disease. AI has made impressive progress in ophthalmology within the past few years and two autonomous AIenabled systems have received US regulatory approvals for autonomously screening for mid-level or advanced diabetic retinopathy and macular edema. While no autonomous AI-enabled system for glaucoma screening has yet received US regulatory approval, numerous assistive AI-enabled software tools are already employed in commercialized instruments for quantifying retinal images and visual fields to augment glaucoma research and clinical practice. In this literature review (non-systematic), we provide an overview of AI applications in glaucoma, and highlight some limitations and considerations for AI integration and adoption into clinical practice

Image analysis algorithms for feature extraction in eye fundus images

Retinal images are widely used for diagnostic purposes by ophthalmolo- gists. Therefore, these images are suitable for digital image analysis for their visual enhancement and pathological risk or damage detection. Here, we implement a lu- minosity and contrast enhancement technique based on domain knowledge. We also review and analyze a previous approach in optic nerve head segmentation to extend its applicability to non circular shaped contours. We introduce a di erent strategy based on the use of active contours

The Impact of Artificial Intelligence and Deep Learning in Eye Diseases: A Review

Artificial intelligence (AI) is a subset of computer science dealing with the development and training of algorithms that try to replicate human intelligence. We report a clinical overview of the basic principles of AI that are fundamental to appreciating its application to ophthalmology practice. Here, we review the most common eye diseases, focusing on some of the potential challenges and limitations emerging with the development and application of this new technology into ophthalmology

Computational models for stuctural analysis of retinal images

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University LondonThe evaluation of retina structures has been of great interest because it could be used as a non-intrusive diagnosis in modern ophthalmology to detect many important eye diseases as well as cardiovascular disorders. A variety of retinal image analysis tools have been developed to assist ophthalmologists and eye diseases experts by reducing the time required in eye screening, optimising the costs as well as providing efficient disease treatment and management systems. A key component in these tools is the segmentation and quantification of retina structures. However, the imaging artefacts such as noise, intensity homogeneity and the overlapping tissue of retina structures can cause significant degradations to the performance of these automated image analysis tools. This thesis aims to provide robust and reliable automated retinal image analysis technique to allow for early detection of various retinal and other diseases. In particular, four innovative segmentation methods have been proposed, including two for retinal vessel network segmentation, two for optic disc segmentation and one for retina nerve fibre layers detection. First, three pre-processing operations are combined in the segmentation method to remove noise and enhance the appearance of the blood vessel in the image, and a Mixture of Gaussians is used to extract the blood vessel tree. Second, a graph cut segmentation approach is introduced, which incorporates the mechanism of vectors flux into the graph formulation to allow for the segmentation of very narrow blood vessels. Third, the optic disc segmentation is performed using two alternative methods: the Markov random field image reconstruction approach detects the optic disc by removing the blood vessels from the optic disc area, and the graph cut with compensation factor method achieves that using prior information of the blood vessels. Fourth, the boundaries of the retinal nerve fibre layer (RNFL) are detected by adapting a graph cut segmentation technique that includes a kernel-induced space and a continuous multiplier based max-flow algorithm. The strong experimental results of our retinal blood vessel segmentation methods including Mixture of Gaussian, Graph Cut achieved an average accuracy of 94:33%, 94:27% respectively. Our optic disc segmentation methods including Markov Random Field and Compensation Factor also achieved an average sensitivity of 92:85% and 85:70% respectively. These results obtained on several public datasets and compared with existing methods have shown that our proposed methods are robust and efficient in the segmenting retinal structures such the blood vessels and the optic disc.Brunel University Londonhttp://bura.brunel.ac.uk/bitstream/2438/10387/1/FulltextThesis.pd

REFUGE Challenge: A unified framework for evaluating automated methods for glaucoma assessment from fundus photographs

[EN] Glaucoma is one of the leading causes of irreversible but preventable blindness in working age populations. Color fundus photography (CFP) is the most cost-effective imaging modality to screen for retinal disorders. However, its application to glaucoma has been limited to the computation of a few related biomarkers such as the vertical cup-to-disc ratio. Deep learning approaches, although widely applied for medical image analysis, have not been extensively used for glaucoma assessment due to the limited size of the available data sets. Furthermore, the lack of a standardize benchmark strategy makes difficult to compare existing methods in a uniform way. In order to overcome these issues we set up the Retinal Fundus Glaucoma Challenge, REFUGE (https://refuge.grand-challenge.org), held in conjunction with MIC-CAI 2018. The challenge consisted of two primary tasks, namely optic disc/cup segmentation and glaucoma classification. As part of REFUGE, we have publicly released a data set of 1200 fundus images with ground truth segmentations and clinical glaucoma labels, currently the largest existing one. We have also built an evaluation framework to ease and ensure fairness in the comparison of different models, encouraging the development of novel techniques in the field. 12 teams qualified and participated in the online challenge. This paper summarizes their methods and analyzes their corresponding results. In particular, we observed that two of the top-ranked teams outperformed two human experts in the glaucoma classification task. Furthermore, the segmentation results were in general consistent with the ground truth annotations, with complementary outcomes that can be further exploited by ensembling the results.This work was supported by the Christian Doppler Research Association, the Austrian Federal Ministry for Digital and Economic Affairs and the National Foundation for Research, Technology and Development, J.I.O is supported by WWTF (Medical University of Vienna: AugUniWien/FA7464A0249, University of Vienna: VRG12- 009). Team Masker is supported by Natural Science Foundation of Guangdong Province of China (Grant 2017A030310647). Team BUCT is partially supported by the National Natural Science Foundation of China (Grant 11571031). The authors would also like to thank REFUGE study group for collaborating with this challenge.Orlando, JI.; Fu, H.; Breda, JB.; Van Keer, K.; Bathula, DR.; Diaz-Pinto, A.; Fang, R.... (2020). 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Dual Machine-Learning system to aid Glaucoma Diagnosis using disc and cup feature extraction.

Glaucoma is a degenerative disease that affects vision, causing damage to the optic nerve that ends in vision loss. The classic techniques to detect it have undergone a great change since the intrusion of machine learning techniques into the processing of eye fundus images. Several works focus on training a convolutional neural network (CNN) by brute force, while others use segmentation and feature extraction techniques to detect glaucoma. In this work, a diagnostic aid tool to detect glaucoma using eye fundus images is developed, trained and tested. It consists of two subsystems that are independently trained and tested, combining their results to improve glaucoma detection. The first subsystem applies machine learning and segmentation techniques to detect optic disc and cup independently, combine them and extract their physical and positional features. The second one applies transfer learning techniques to a pre-trained CNN to detect glaucoma through the analysis of the complete eye fundus images. The results of both systems are combined to discriminate positive cases of glaucoma and improve final detection. The results show that this system achieves a higher classification rate than previous works. The system also provides information on the basis for the proposed diagnosis suggestion that can help the ophthalmologist to accept or modify it

딥러닝을 이용한 녹내장 진단 보조 시스템

학위논문 (박사) -- 서울대학교 대학원 : 공과대학 협동과정 바이오엔지니어링전공, 2021. 2. 김희찬.본 논문에서는 딥 러닝 기반의 진단 보조 시스템을 제안하였다. 새로운 방법이 녹내장 데이터에 적용되었고 결과를 평가하였다. 첫번째 연구에서는 스펙트럼영역 빛간섭단층촬영기(SD-OCT)를 딥 러닝 분류 기를 이용해 분석하였다. 스펙트럼영역 빛간섭단층촬영기는 녹내장으로 인한 구조적 손상을 평가하기 위해 사용하는 장비이다. 분류 알고리즘은 합성 곱 신경망을 이용해 개발 되었으며, 스펙트럼영역 빛간섭단층촬영기의 망막신경섬유층(RNFL)과 황반부 신경절세포내망상층 (GCIPL) 사진을 이용해 학습했다. 제안한 방법은 두개의 이미지를 입력으로 받는 이중입력합성곱신경망(DICNN)이며, 딥 러닝 분류에서 효과적인 것으로 알려져 있다. 이중입력합성곱신경망은 망막신경섬유층 과 신경절세포층 의 두께 지도를 이용하여 학습 됐으며, 학습된 네트워크는 녹내장과 정상 군을 구분한다. 이중입력합성곱신경망은 정확도와 수신기동작특성곡선하면적 (AUC)으로 평가 되었다. 망막신경섬유층과 신경절세포층 두께 지도로 학습된 설계한 딥 러닝 모델을 조기 녹내장과 정상 군을 분류하는 성능을 평가하고 비교하였다. 성능평가 결과 이중입력합성곱신경망은 조기 녹내장을 분류하는데 0.869의 수신기동작특성곡선의넓이와 0.921의 민감도, 0.756의 특이도를 보였다. 두번째 연구에서는 딥 러닝을 이용해 시신경유두사진의 해상도와 대비, 색감, 밝기를 보정하는 방법을 제안하였다. 시신경유두사진은 녹내장을 진단하는데 있어 효과적인 것으로 알려져 있다. 하지만, 녹내장의 진단에서 환자의 나, 작은 동공, 매체 불투명성 등으로 인해 평가가 어려운 경우가 있다. 초 해상도와 보정 알고리즘은 초 해상도 적대적생성신경망을 통해 개발되었다. 원본 고해상도의 시신경 유두 사진은 저해상도 사진으로 축소되고, 보정된 고해상도 시신경유두사진으로 보정 되며, 보정된 사진은 시신경여백의 가시성과 근처 혈관을 잘 보이도록 후처리 알고리즘을 이용한다. 저해상도이미지를 보정된 고해상도이미지로 복원하는 과정을 초해상도적대적신경망을 통해 학습한다. 설계한 네트워크는 신호 대 잡음 비(PSNR)과 구조적유사성(SSIM), 평균평가점(MOS)를 이용해 평가 되었다. 현재의 연구는 딥 러닝이 안과 이미지를 4배 해상도와 구조적인 세부 항목이 잘 보이도록 개선할 수 있다는 것을 보여주었다. 향상된 시신경유두 사진은 시신경의 병리학적인 특성의 진단 정확도를 명확히 향상시킨다. 성능평가결과 평균 PSNR은 25.01 SSIM은 0.75 MOS는 4.33으로 나타났다. 세번째 연구에서는 환자 정보와 안과 영상(시신경유두 사진과 붉은색이 없는 망막신경섬유층 사진)을 이용해 녹내장 의심 환자를 분별하고 녹내장 의심 환자의 발병 연수를 예측하는 딥 러닝 모델을 개발하였다. 임상 데이터들은 녹내장을 진단하거나 예측하는데 유용한 정보들을 가지고 있다. 하지만, 어떻게 다양한 유형의 임상정보들을 조합하는 것이 각각의 환자들에 대해 잠재적인 녹내장을 예측하는데 어떤 영향을 주는지에 대한 연구가 진행 된 적이 없다. 녹내장 의 심자 분류와 발병 년 수 예측은 합성 곱 자동 인코더(CAE)를 비 지도적 특성 추출 기로 사용하고, 기계학습 분류 기와 회귀기를 통해 진행하였다. 설계한 모델은 정확도와 평균제곱오차(MSE)를 통해 평가 되었으며, 이미지 특징과 환자 특징은 조합했을 때 녹내장 의심 환자 분류와 발병 년 수 예측의 성능이 이미지 특징과 환자 특징을 각각 썼을 때보다 성능이 좋았다. 정답과의 MSE는 2.613으로 나타났다. 본 연구에서는 딥 러닝을 이용해 녹내장 관련 임상 데이터 중 망막신경섬유층, 신경절세포층 사진을 녹내장 진단에 이용되었고, 시신경유두 사진은 시신경의 병리학적인 진단 정확도를 높였고, 환자 정보는 보다 정확한 녹내장 의심 환자 분류와 발병 년 수 예측에 이용되었다. 향상된 녹내장 진단 성능은 기술적이고 임상적인 지표들을 통해 검증되었다.This paper presents deep learning-based methods for improving glaucoma diagnosis support systems. Novel methods were applied to glaucoma clinical cases and the results were evaluated. In the first study, a deep learning classifier for glaucoma diagnosis based on spectral-domain optical coherence tomography (SD-OCT) images was proposed and evaluated. Spectral-domain optical coherence tomography (SD-OCT) is commonly employed as an imaging modality for the evaluation of glaucomatous structural damage. The classification model was developed using convolutional neural network (CNN) as a base, and was trained with SD-OCT retinal nerve fiber layer (RNFL) and macular ganglion cell-inner plexiform layer (GCIPL) images. The proposed network architecture, termed Dual-Input Convolutional Neural Network (DICNN), showed great potential as an effective classification algorithm based on two input images. DICNN was trained with both RNFL and GCIPL thickness maps that enabled it to discriminate between normal and glaucomatous eyes. The performance of the proposed DICNN was evaluated with accuracy and area under the receiver operating characteristic curve (AUC), and was compared to other methods using these metrics. Compared to other methods, the proposed DICNN model demonstrated high diagnostic ability for the discrimination of early-stage glaucoma patients in normal subjects. AUC, sensitivity and specificity was 0.869, 0.921, 0.756 respectively. In the second study, a deep-learning method for increasing the resolution and improving the legibility of Optic-disc Photography(ODP) was proposed. ODP has been proven to be useful for optic nerve evaluation in glaucoma. But in clinical practice, limited patient cooperation, small pupil or media opacities can limit the performance of ODP. A model to enhance the resolution of ODP images, termed super-resolution, was developed using Super Resolution Generative Adversarial Network(SR-GAN). To train this model, high-resolution original ODP images were transformed into two counterparts: (1) down-scaled low-resolution ODPs, and (2) compensated high-resolution ODPs with enhanced visibility of the optic disc margin and surrounding retinal vessels which were produced using a customized image post-processing algorithm. The SR-GAN was trained to learn and recognize the differences between these two counterparts. The performance of the network was evaluated using Peak Signal to Noise Ratio (PSNR), Structural Similarity (SSIM), and Mean Opinion Score (MOS). The proposed study demonstrated that deep learning can be applied to create a generative model that is capable of producing enhanced ophthalmic images with 4x resolution and with improved structural details. The proposed method can be used to enhance ODPs and thereby significantly increase the detection accuracy of optic disc pathology. The average PSNR, SSIM and MOS was 25.01, 0.75, 4.33 respectively In the third study, a deep-learning model was used to classify suspected glaucoma and to predict subsequent glaucoma onset-year in glaucoma suspects using clinical data and retinal images (ODP & Red-free Fundus RNFL Photo). Clinical data contains useful information about glaucoma diagnosis and prediction. However, no study has been undertaken to investigate how combining different types of clinical information would be helpful for predicting the subsequent course of glaucoma in an individual patient. For this study, image features extracted using Convolutional Auto Encoder (CAE) along with clinical features were used for glaucoma suspect classification and onset-year prediction. The performance of the proposed model was evaluated using accuracy and Mean Squared Error (MSE). Combing the CAE extracted image features and clinical features improved glaucoma suspect classification and on-set year prediction performance as compared to using the image features and patient features separately. The average MSE between onset-year and predicted onset year was 2.613 In this study, deep learning methodology was applied to clinical images related to glaucoma. DICNN with RNFL and GCIPL images were used for classification of glaucoma, SR-GAN with ODP images were used to increase detection accuracy of optic disc pathology, and CAE & machine learning algorithm with clinical data and retinal images was used for glaucoma suspect classification and onset-year predication. The improved glaucoma diagnosis performance was validated using both technical and clinical parameters. The proposed methods as a whole can significantly improve outcomes of glaucoma patients by early detection, prediction and enhancing detection accuracy.Contents Abstract i Contents iv List of Tables vii List of Figures viii Chapter 1 General Introduction 1 1.1 Glaucoma 1 1.2 Deep Learning for Glaucoma Diagnosis 3 1.4 Thesis Objectives 3 Chapter 2 Dual-Input Convolutional Neural Network for Glaucoma Diagnosis using Spectral-Domain Optical Coherence Tomography 6 2.1 Introduction 6 2.1.1 Background 6 2.1.2 Related Work 7 2.2 Methods 8 2.2.1 Study Design 8 2.2.2 Dataset 9 2.2.3 Dual-Input Convolutional Neural Network (DICNN) 15 2.2.4 Training Environment 18 2.2.5 Statistical Analysis 19 2.3 Results 20 2.3.1 DICNN Performance 20 2.3.1 Grad-CAM for DICNN 34 2.4 Discussion 37 2.4.1 Research Significance 37 2.4.2 Limitations 40 2.5 Conclusion 42 Chapter 3 Deep-learning-based enhanced optic-disc photography 43 3.1 Introduction 43 3.1.1 Background 43 3.1.2 Needs 44 3.1.3 Related Work 45 3.2 Methods 46 3.2.1 Study Design 46 3.2.2 Dataset 46 3.2.2.1 Details on Customized Image Post-Processing Algorithm 47 3.2.3 SR-GAN Network 50 3.2.3.1 Design of Generative Adversarial Network 50 3.2.3.2 Loss Functions 55 3.2.4 Assessment of Clinical Implications of Enhanced ODPs 58 3.2.5 Statistical Analysis 60 3.2.6 Hardware Specifications & Software Specifications 60 3.3 Results 62 3.3.1 Training Loss of Modified SR-GAN 62 3.3.2 Performance of Final Network 66 3.3.3 Clinical Validation of Enhanced ODP by MOS comparison 77 3.3.4 Comparison of DH-Detection Accuracy 79 3.4 Discussion 80 3.4.1 Research Significance 80 3.4.2 Limitations 85 3.5 Conclusion 88 Chapter 4 Deep Learning Based Prediction of Glaucoma Onset Using Retinal Image and Patient Data 89 4.1 Introduction 89 4.1.1 Background 89 4.1.2 Related Work 90 4.2 Methods 90 4.2.1 Study Design 90 4.2.2 Dataset 91 4.2.3 Design of Overall System 94 4.2.4 Design of Convolutional Auto Encoder 95 4.2.5 Glaucoma Suspect Classification 97 4.2.6 Glaucoma Onset-Year Prediction 97 4.3 Result 99 4.3.1 Performance of Designed CAE 99 4.3.2 Performance of Designed Glaucoma Suspect Classification 101 4.3.3 Performance of Designed Glaucoma Onset-Year Prediction 105 4.4 Discussion 110 4.4.1 Research Significance 110 4.4.2 Limitations 110 4.5 Conclusion 111 Chapter 5 Summary and Future Works 112 5.1 Thesis Summary 112 5.2 Limitations and Future Works 113 Bibliography 115 Abstract in Korean 127 Acknowledgement 130Docto