The increasing prevalence of retinal diseases poses a significant challenge to the healthcare system, as the demand for ophthalmologists surpasses the available workforce. This imbalance creates a bottleneck in diagnosis and treatment, potentially delaying critical care. Traditional methods of generating medical reports from retinal images rely on manual interpretation, which is time-consuming and prone to errors, further straining ophthalmologists' limited resources. This thesis investigates the potential of Artificial Intelligence (AI) to automate medical report generation for retinal images. AI can quickly analyze large volumes of image data, identifying subtle patterns essential for accurate diagnosis. By automating this process, AI systems can greatly enhance the efficiency of retinal disease diagnosis, reducing doctors' workloads and enabling them to focus on more complex cases. The proposed AI-based methods address key challenges in automated report generation: (1) A multi-modal deep learning approach captures interactions between textual keywords and retinal images, resulting in more comprehensive medical reports; (2) Improved methods for medical keyword representation enhance the system's ability to capture nuances in medical terminology; (3) Strategies to overcome RNN-based models' limitations, particularly in capturing long-range dependencies within medical descriptions; (4) Techniques to enhance the interpretability of the AI-based report generation system, fostering trust and acceptance in clinical practice. These methods are rigorously evaluated using various metrics and achieve state-of-the-art performance. This thesis demonstrates AI's potential to revolutionize retinal disease diagnosis by automating medical report generation, ultimately improving clinical efficiency, diagnostic accuracy, and patient care.

Retinal diseases such as Diabetic Retinopathy (DR) and Macular Hole (MH) significantly impact vision and affect millions worldwide. Early detection is crucial, as DR, a complication of diabetes, damages retinal blood vessels, potentially leading to blindness, while MH disrupts central vision, affecting tasks like reading and facial recognition. This paper employed two lightweight and efficient Convolution Neural Network architectures, MobileNet and NASNetMobile, for the classification of Normal, DR, and MH retinal images. The models were trained on the RFMiD dataset, consisting of 3,200 fundus images, after undergoing preprocessing steps such as resizing, normalization, and augmentation. To address data scarcity, this study leveraged transfer learning and data augmentation techniques, enhancing model generalization and performance. The experimental results demonstrate that MobileNetV2 achieved the highest accuracy of 90.8%, outperforming NASNetMobile, which achieved 89.5% accuracy. These findings highlight the effectiveness of CNNs in retinal disease classification, providing a foundation for AI-assisted ophthalmic diagnosis and early intervention.

Our research is motivated by the urgent global issue of a large population affected by retinal diseases, which are evenly distributed but underserved by specialized medical expertise, particularly in non-urban areas. Our primary objective is to bridge this healthcare gap by developing a comprehensive diagnostic system capable of accurately predicting retinal diseases solely from fundus images. However, we faced significant challenges due to limited, diverse datasets and imbalanced class distributions. To overcome these issues, we have devised innovative strategies. Our research introduces novel approaches, utilizing hybrid models combining deeper Convolutional Neural Networks (CNNs), Transformer encoders, and ensemble architectures sequentially and in parallel to classify retinal fundus images into 20 disease labels. Our overarching goal is to assess these advanced models' potential in practical applications, with a strong focus on enhancing retinal disease diagnosis accuracy across a broader spectrum of conditions. Importantly, our efforts have surpassed baseline model results, with the C-Tran ensemble model emerging as the leader, achieving a remarkable model score of 0.9166, surpassing the baseline score of 0.9. Additionally, experiments with the IEViT model showcased equally promising outcomes with improved computational efficiency. We've also demonstrated the effectiveness of dynamic patch extraction and the integration of domain knowledge in computer vision tasks. In summary, our research strives to contribute significantly to retinal disease diagnosis, addressing the critical need for accessible healthcare solutions in underserved regions while aiming for comprehensive and accurate disease prediction.

Recent advancements in deep learning have shown significant potential for classifying retinal diseases using color fundus images. However, existing works predominantly rely exclusively on image data, lack interpretability in their diagnostic decisions, and treat medical professionals primarily as annotators for ground truth labeling. To fill this gap, we implement two key strategies: extracting interpretable concepts of retinal diseases using the knowledge base of GPT models and incorporating these concepts as a language component in prompt-learning to train vision-language (VL) models with both fundus images and their associated concepts. Our method not only improves retinal disease classification but also enriches few-shot and zero-shot detection (novel disease detection), while offering the added benefit of concept-based model interpretability. Our extensive evaluation across two diverse retinal fundus image datasets illustrates substantial performance gains in VL-model based few-shot methodologies through our concept integration approach, demonstrating an average improvement of approximately 5.8\% and 2.7\% mean average precision for 16-shot learning and zero-shot (novel class) detection respectively. Our method marks a pivotal step towards interpretable and efficient retinal disease recognition for real-world clinical applications.

Optical Coherence Tomography (OCT) is a non-invasive imaging modality essential for diagnosing various eye diseases. Despite its clinical significance, developing OCT-based diagnostic tools faces challenges, such as limited public datasets, sparse annotations, and privacy concerns. Although deep learning has made progress in automating OCT analysis, these challenges remain unresolved. To address these limitations, we introduce the Vision Transformer-based Dual-Stream Self-Supervised Pretraining Network (ViT-2SPN), a novel framework designed to enhance feature extraction and improve diagnostic accuracy. ViT-2SPN employs a three-stage workflow: Supervised Pretraining, Self-Supervised Pretraining (SSP), and Supervised Fine-Tuning. The pretraining phase leverages the OCTMNIST dataset (97,477 unlabeled images across four disease classes) with data augmentation to create dual-augmented views. A Vision Transformer (ViT-Base) backbone extracts features, while a negative cosine similarity loss aligns feature representations. Pretraining is conducted over 50 epochs with a learning rate of 0.0001 and momentum of 0.999. Fine-tuning is performed on a stratified 5.129% subset of OCTMNIST using 10-fold cross-validation. ViT-2SPN achieves a mean AUC of 0.93, accuracy of 0.77, precision of 0.81, recall of 0.75, and an F1 score of 0.76, outperforming existing SSP-based methods.

Inherited retinal diseases (IRDs) are a diverse group of genetic disorders that lead to progressive vision loss and are a major cause of blindness in working-age adults. The complexity and heterogeneity of IRDs pose significant challenges in diagnosis, prognosis, and management. Recent advancements in artificial intelligence (AI) offer promising solutions to these challenges. However, the rapid development of AI techniques and their varied applications have led to fragmented knowledge in this field. This review consolidates existing studies, identifies gaps, and provides an overview of AI's potential in diagnosing and managing IRDs. It aims to structure pathways for advancing clinical applications by exploring AI techniques like machine learning and deep learning, particularly in disease detection, progression prediction, and personalized treatment planning. Special focus is placed on the effectiveness of convolutional neural networks in these areas. Additionally, the integration of explainable AI is discussed, emphasizing its importance in clinical settings to improve transparency and trust in AI-based systems. The review addresses the need to bridge existing gaps in focused studies on AI's role in IRDs, offering a structured analysis of current AI techniques and outlining future research directions. It concludes with an overview of the challenges and opportunities in deploying AI for IRDs, highlighting the need for interdisciplinary collaboration and the continuous development of robust, interpretable AI models to advance clinical applications.

Optical coherence tomography (OCT) has become critical for diagnosing retinal diseases as it enables 3D images of the retina and optic nerve. OCT acquisition is fast, non-invasive, affordable, and scalable. Due to its broad applicability, massive numbers of OCT images have been accumulated in routine exams, making it possible to train large-scale foundation models that can generalize to various diagnostic tasks using OCT images. Nevertheless, existing foundation models for OCT only consider 2D image slices, overlooking the rich 3D structure. Here, we present OCTCube, a 3D foundation model pre-trained on 26,605 3D OCT volumes encompassing 1.62 million 2D OCT images. OCTCube is developed based on 3D masked autoencoders and exploits FlashAttention to reduce the larger GPU memory usage caused by modeling 3D volumes. OCTCube outperforms 2D models when predicting 8 retinal diseases in both inductive and cross-dataset settings, indicating that utilizing the 3D structure in the model instead of 2D data results in significant improvement. OCTCube further shows superior performance on cross-device prediction and when predicting systemic diseases, such as diabetes and hypertension, further demonstrating its strong generalizability. Finally, we propose a contrastive-self-supervised-learning-based OCT-IR pre-training framework (COIP) for cross-modality analysis on OCT and infrared retinal (IR) images, where the OCT volumes are embedded using OCTCube. We demonstrate that COIP enables accurate alignment between OCT and IR en face images. Collectively, OCTCube, a 3D OCT foundation model, demonstrates significantly better performance against 2D models on 27 out of 29 tasks and comparable performance on the other two tasks, paving the way for AI-based retinal disease diagnosis.

Inability to express the confidence level and detect unseen classes has limited the clinical implementation of artificial intelligence in the real-world. We developed a foundation model with uncertainty estimation (FMUE) to detect 11 retinal conditions on optical coherence tomography (OCT). In the internal test set, FMUE achieved a higher F1 score of 96.76% than two state-of-the-art algorithms, RETFound and UIOS, and got further improvement with thresholding strategy to 98.44%. In the external test sets obtained from other OCT devices, FMUE achieved an accuracy of 88.75% and 92.73% before and after thresholding. Our model is superior to two ophthalmologists with a higher F1 score (95.17% vs. 61.93% &71.72%). Besides, our model correctly predicts high uncertainty scores for samples with ambiguous features, of non-target-category diseases, or with low-quality to prompt manual checks and prevent misdiagnosis. FMUE provides a trustworthy method for automatic retinal anomalies detection in the real-world clinical open set environment.

Retinal optical coherence tomography (OCT) images provide crucial insights into the health of the posterior ocular segment. Therefore, the advancement of automated image analysis methods is imperative to equip clinicians and researchers with quantitative data, thereby facilitating informed decision-making. The application of deep learning (DL)-based approaches has gained extensive traction for executing these analysis tasks, demonstrating remarkable performance compared to labor-intensive manual analyses. However, the acquisition of Retinal OCT images often presents challenges stemming from privacy concerns and the resource-intensive labeling procedures, which contradicts the prevailing notion that DL models necessitate substantial data volumes for achieving superior performance. Moreover, limitations in available computational resources constrain the progress of high-performance medical artificial intelligence, particularly in less developed regions and countries. This paper introduces a novel ensemble learning mechanism designed for recognizing retinal diseases under limited resources (e.g., data, computation). The mechanism leverages insights from multiple pre-trained models, facilitating the transfer and adaptation of their knowledge to Retinal OCT images. This approach establishes a robust model even when confronted with limited labeled data, eliminating the need for an extensive array of parameters, as required in learning from scratch. Comprehensive experimentation on real-world datasets demonstrates that the proposed approach can achieve superior performance in recognizing Retinal OCT images, even when dealing with exceedingly restricted labeled datasets. Furthermore, this method obviates the necessity of learning extensive-scale parameters, making it well-suited for deployment in low-resource scenarios.

Failure to recognize samples from the classes unseen during training is a major limitation of artificial intelligence in the real-world implementation for recognition and classification of retinal anomalies. We established an uncertainty-inspired open-set (UIOS) model, which was trained with fundus images of 9 retinal conditions. Besides assessing the probability of each category, UIOS also calculated an uncertainty score to express its confidence. Our UIOS model with thresholding strategy achieved an F1 score of 99.55%, 97.01% and 91.91% for the internal testing set, external target categories (TC)-JSIEC dataset and TC-unseen testing set, respectively, compared to the F1 score of 92.20%, 80.69% and 64.74% by the standard AI model. Furthermore, UIOS correctly predicted high uncertainty scores, which would prompt the need for a manual check in the datasets of non-target categories retinal diseases, low-quality fundus images, and non-fundus images. UIOS provides a robust method for real-world screening of retinal anomalies.