Age-related macular degeneration (AMD) and diabetic macular edema (DME) are leading causes of vision loss, and optical coherence tomography (OCT) is the standard modality for detecting and monitoring the subtle lesions that drive treatment decisions. Most deep-learning segmentation work for OCT is validated only in-domain, leaving generalization to clinical data collected under different acquisition protocols largely untested. This work develops and systematically ablates four lesion-segmentation pipelines -- 2D and 3D variants for AMD and DME -- reaching Dice scores of 0.76 to 0.82 with strong volumetric and surface calibration (r vol, r surf greater than or equal to 0.97 across all four pipelines) on an in-domain validation set. The ablation process establishes a full-volume, calibration-aware adoption standard that catches mechanisms an ordinary slice-level evaluation would keep, and identifies ensemble composition as the most consistent driver of improvement. To test generalization, the models are evaluated on OLIVES, an external clinical cohort with no lesion-level ground truth, using a proxy-metric framework built around biomarker AUROC, central subfield thickness (CST) correlation, and longitudinal concordance. Predictions track clinical biomarkers outside the training distribution, though less strongly than in-domain -- evidence for, not validation of, automated lesion-burden tracking as a clinical tool.
Retinal diseases are a leading cause of irreversible vision impairment, making early and accurate diagnosis essential for effective treatment. Optical Coherence Tomography (OCT) serves as a critical imaging modality for this purpose, yet its automated analysis is hindered by inherent speckle noise, varying lesion scales, and subtle inter-class similarities. To address these challenges, we propose a novel framework, RetiWave-Mamba, which integrates spatial-frequency domain learning with state-of-the-art state space models. The framework utilizes Discrete Wavelet Transform (DWT) to decompose OCT images into low- and high-frequency streams, enabling decoupled processing of structural context and fine-grained details. For the low-frequency branch, we design a Multi-scale Contextual Localization Module (MCLM), which synergizes multi-scale dilation with spatial attention to expand the global receptive field and precisely localize lesion regions. For the high-frequency branch, we introduce an Attention-Guided High-Resolution Network (AG-HRNet) equipped with an intelligent gating mechanism to suppress noise propagation during multi-scale interactions. Furthermore, a Frequency-Adaptive Mamba Projector (FAMP) is incorporated to capture long-range dependencies within disjoint high-frequency textural features. Extensive experiments on the OCT-C8 dataset demonstrate that our approach achieves a state-of-the-art (SOTA) classification accuracy of 98.25%, surpassing existing methods. These results highlight the efficacy of RetiWave-Mamba in robustly identifying retinal pathologies under noisy conditions, offering a promising tool for clinical diagnosis.
Yihan Wang, Ruilin You, Shaobai Li +4physics.optics cs.CV physics.med-ph
Peripheral nerves buried beneath intact tissue are difficult to visualize during surgery and remain inaccessible to white light wide-field imaging and other surface optical imaging methods. Existing OCT nerve studies have largely relied on exposed nerves or polarization contrast with limited depth penetration, restricting their value for subsurface intraoperative guidance. Here, we introduce, to our knowledge, the first label-free framework for detecting peripheral nerves beneath unopened tissue and resolving their depth using intensity-based OCT structural signatures alone. The framework combines a handheld multimodal probe, integrating swept-source OCT with co-registered white light and autofluorescence imaging, with a ``confirm-then-capture'' workflow designed for practical surgical use. To enable efficient analysis of sparsely sampled OCT volumes, we develop NerveDetNet, a lightweight 2.5D segmentation network that recovers weak and spatially displaced nerve signals by incorporating spatial context, frame-order information, and shift-tolerant correlations across frames through a dedicated nerve feature correlation module. In ex vivo tissue experiments, NerveDetNet consistently outperformed six representative 2D baselines across all frame spacings, achieving a Dice score of 0.725 under the sparsest sampling condition while using approximately half the model parameters. End-to-end validation demonstrated localization of nerves invisible at the surface and depth-resolved detection up to 1.3--1.4~mm below the tissue surface, with OCT derived depth maps overlaid directly onto the surgical view. Together, these results establish a practical label-free approach for subsurface nerve visualization that supports intraoperative compatibility, enables efficient sparse-volume analysis, and provides depth-resolved guidance without tissue opening, contrast agents, or nerve exposure.
Fernando García-Torres, Rocío del Amor, Sandra Morales +4cs.CV cs.AI
Background and Objective: Generating realistic medical images with anatomically accurate segmentation masks helps address the shortage of annotated data in medical imaging, particularly in optical coherence tomography (OCT) of mouse eyes, where manual retinal layer delineation is labour-intensive due to tiny structures and required expertise, resulting in scarce datasets. While diffusion models perform well in medical image synthesis, joint image-mask generation has relied mainly on U-Net-based denoisers, leaving diffusion transformers largely unexplored. Methods: We propose a conditional dual-output Diffusion Transformer (DualDiT) for joint synthesis of OCT B-scans and segmentation masks of the upper retinal cell layers in ex vivo mouse retina. DualDiT encodes both modalities into a shared latent space via a pretrained VAE, concatenates their latent representations, and performs conditional diffusion over the joint tensor. We compared DualDiT against two adapted diffusion baselines: DDPM and LDM. Generative quality was assessed via Fréchet Inception Distance (FID) and spatial FID (sFID); practical utility via synthetic data augmentation for downstream U-Net segmentation; and perceptual realism via evaluation by three domain experts. Results: DualDiT achieved the best generative quality (FID 56.14, sFID 114.35), outperforming DDPM and LDM. Expert panels misclassified 46% of synthetic samples as real and 42% of real samples as synthetic. Adding DualDiT-generated images and masks improved Dice and IoU scores on a held-out segmentation test set. Conclusions: DualDiT shows that transformer-based diffusion models can effectively learn the joint distribution of OCT images and segmentation masks, surpassing DDPM- and LDM-based baselines in generative fidelity, downstream utility, and perceptual realism, highlighting its potential for data augmentation in annotation-scarce medical imaging.
Optical coherence tomography (OCT) imaging is essential for the diagnosis and treatment of retinal diseases. Although multimodal large language models (MLLMs) have demonstrated considerable potential in medical image analysis, existing benchmarks largely reduce OCT understanding to coarse-grained disease classification or isolated visual question answering, leaving the complete cognitive process from visual perception to clinical reasoning insufficiently evaluated. To address this limitation, we introduce OCT-Bench, a comprehensive benchmark dedicated to OCT image understanding. OCT-Bench comprises 10,076 high-quality multiple-choice questions constructed from 4,137 OCT images across seven public datasets. Following the real-world clinical interpretation workflow, we establish a hierarchical capability taxonomy consisting of 20 fine-grained tasks across three dimensions: Perception, Cognition, and Reasoning. These tasks cover a broad range of capabilities, including imaging attributes, retinal anatomy, lesion characteristics, spatial relationships, disease assessment, therapeutic decision-making, and prognostic management. We systematically evaluate 20 representative MLLMs, including proprietary models, open-source general-purpose models, and medical-domain models. Experimental results demonstrate that current models remain substantially short of reliable OCT understanding. Moreover, neither medical-domain adaptation nor increased model scale consistently improves performance across capability levels. OCT-Bench enables comprehensive and fine-grained evaluation of MLLMs, providing a foundation for identifying capability bottlenecks and advancing clinically grounded OCT understanding.
Retinal layer segmentation in Optical Coherence Tomography (OCT) is a fundamental step for extracting quantitative biomarkers of retinal structure. Indeed, there is a growing interest in the analysis of OCTs in the context of neurodegenerative diseases. However, segmentation remains challenging due to speckle noise, shadowing artifacts, low contrast between adjacent layers, anatomical variability across subjects, and domain shifts arising from different acquisition protocols and clinical populations. While deep learning methods have achieved remarkable performance, their robustness and generalization across heterogeneous datasets remain limited. In this work, we investigate the role of spatial normalization as a preprocessing strategy to mitigate geometric domain shifts and improve the consistency of retinal layer segmentation. Inspired by standard practices in neuroimaging, we introduce a fovea-centered normalization framework that aligns OCT volumes into a common anatomical reference. We perform a comprehensive evaluation of state-of-the-art deep learning architectures. To provide a comprehensive assessment of segmentation quality, we combine conventional overlap-based metrics at B-scan level with topology-aware metrics at A-scan level and thickness-based measures at the en-face level. In cases where a ground truth is not available, we propose topology violation quantitative metrics that do not require ground truth annotations and a thickness-based qualitative assessment that captures structural consistency and clinically relevant patterns at the en-face level. The results demonstrate the importance of spatial normalization in OCT segmentation pipelines toward the development of robust and clinically meaningful retinal analysis tools, enabling reliable biomarker extraction and downstream computational analysis in neurodegenerative research.
Rashadul Hasan Badhon, Atalie Carina Thompson, Jennifer I. Lim +2eess.IV cs.CV cs.LG
Diabetic retinopathy (DR) is a leading cause of vision impairment worldwide, highlighting the need for accurate and accessible screening tools. Optical Coherence Tomography (OCT) provides high-resolution structural information of the retina, whereas OCT angiography (OCTA) offers complementary vascular information that is highly relevant for DR diagnosis. In this study, we propose a cross-modal fusion of OCT B-scans with single-channel en face OCTA using a bidirectional cross-modal attention network for automated DR classification. Two independent datasets, OCT500 and UIC, comprising 730 subjects in total, were utilized to evaluate performance under within-dataset, combined-dataset, and cross-dataset generalization settings. A ConvNeXt V2 model trained solely on OCT images served as the unimodal baseline. In addition to ground-truth (GT) OCTA, we explored the use of translated (TR) OCTA generated from OCT scans, eliminating the requirement for dedicated OCTA hardware. Experimental results demonstrate that cross-modal fusion consistently outperforms unimodal OCT classification across all evaluation scenarios. Fusion with GT OCTA improved classification accuracy and discriminative performance, while TR OCTA achieved comparable or superior results in most settings. Furthermore, TR OCTA improved sensitivity and cross-dataset generalization, indicating enhanced robustness to domain shifts. These findings demonstrate that attention-based OCT-OCTA en face fusion provides clinically meaningful improvements for DR detection and suggest that computationally generated OCTA can serve as a practical, low-cost alternative to hardware-acquired OCTA, enabling broader deployment of high-performance retinal screening systems in resource-limited clinical environments.
Wolf-Dieter Vogl, Hlynur Skulason, Oliver Leingang +3cs.CV
Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) requires precise monitoring of relevant structural biomarkers to assess disease stage, progression, and treatment response. This paper presents a fully automated, deep learning-based framework for the high-precision, pixel-wise segmentation of key biomarkers in optical coherence tomography (OCT) imaging: retinal pigment epithelium (RPE) loss, ellipsoid zone (EZ) loss, and EZ thinning. The proposed pipeline uses three specialized semantic segmentation models to delineate RPE loss, EZ boundaries (including interruptions), and Bruch's membrane. To ensure robustness and generalizability, the models were developed on a diverse dataset of 298 SD-OCT volumes representing the full phenotypic spectrum of AMD (GA:222, intermediate AMD: 40, neovascular AMD: 17, healthy: 19) and validated on an independent external dataset (n=43). The comprehensive evaluation was further strengthened using additional datasets to assess repeatability, inter-reader reliability, the impact of B-scan density on measurement accuracy, and subgroup performance stratified by lesion size. Results demonstrated high segmentation accuracy (Dice RPE loss: 0.88, Dice EZ loss: 0.87, Pearson's r > 0.99). Total EZ thickness measurements exhibited a sub-pixel average deviation of 2.15 $μm$, and segmentation reliability was confirmed by a strong reproducibility score (ICC > 0.98). By accurately and consistently quantifying outer photoreceptor degeneration and RPE loss, this fully automated framework provides a highly reliable tool for GA assessment in both clinical trials and routine real-world ophthalmic care.
To develop and evaluate deep learning models for automated grading of age-related macular degeneration (AMD) severity using optical coherence tomography (OCT) and OCT angiography (OCTA) data. Two hundred seventy-one participants aged >= 50 years with varying AMD severities. Central macular 6 x 6 mm OCT/OCTA volumes were acquired using a swept-source OCTA system (SOLIX; Visionix/Optovue Inc., CA). AMD severity was graded into four stages (No AMD, Early AMD, Intermediate AMD, and Advanced AMD) according to the AREDS simplified severity scale. Three deep learning models were developed using different input modalities: (1) biomarker maps derived from segmented pathological features, including retinal fluid, drusen, geographic atrophy (GA), and macular neovascularization (MNV); (2) two-dimensional (2D) en face OCT and OCTA projections; and (3) three-dimensional (3D) OCT/OCTA volumes. EfficientNet-based architectures were trained using normalized inputs, data augmentation, and five-fold cross-validation. A total of 2,030 OCT/OCTA volumes from 351 eyes of 271 participants were analyzed. All models demonstrated strong AMD staging performance with substantial agreement with the reference standard (QWK >= 0.83). The biomarker-based model achieved the highest overall performance (QWK = 0.85 +/- 0.03, mean +/- standard deviation) and the best detection of early AMD (F1-score = 0.59 +/- 0.14). The 3D model achieved performance comparable to the 2D OCT/OCTA model (QWK = 0.83 +/- 0.04 vs. 0.83 +/- 0.09), while the 2D OCT/OCTA model showed the highest precision (0.79 +/- 0.06) and most accurately identified eyes without AMD. Deep learning models using OCT/OCTA data can accurately and automatically grade AMD severity. Among the evaluated approaches, the biomarker-based model provided the most balanced performance and showed particular value for early AMD detection.
Optical coherence tomography (OCT), a commonly used retinal imaging modality, plays a central role in retinal disease diagnosis by providing high-resolution visualization of retinal layers. While deep learning (DL) has achieved expert-level accuracy in OCT-based retinal disease detection, its "black box" nature poses challenges for clinical adoption, where explainability is essential for clinical trust and regulatory approval. Existing post-hoc explainable AI (XAI) methods often struggle to delineate fine-grained lesion structures, respect anatomical boundaries, or suppress noise, limiting the trustworthiness of their explanations. To bridge these gaps, we propose a Structure-Aware Interpretable Learning (SAIL) framework that integrates retinal anatomical priors at the representation level and couples them with semantic features via a fusion design. Without modifying standard post-hoc explainability methods, this representation yields sharper and more anatomically aligned attribution maps. Comprehensive experiments on diverse OCT datasets demonstrate that our structure-aware method consistently enhances interpretability, producing clinically meaningful and anatomy-aware explanations. Ablation studies further show that strong interpretability requires both structural priors and semantic features, and that properly fusing the two is critical to achieve the best explanation quality. Together, these results highlight structure-aware representations as a key step toward reliable explainability in OCT.
Optical Coherence Tomography (OCT) has become one of the most used imaging modality in ophthalmology. It provides high-resolution, non-invasive visualization of retinal microarchitecture. The automated analysis of OCT images through representation learning has emerged as a central research frontier. This has mainly been driven by the clinical need to process large acquisition volumes. The objective is to reduce the reliance on expert annotation, and improve diagnostic consistency across devices and populations. This survey provides a comprehensive and structured review of representation learning methods for retinal OCT image analysis. It covers the period from early deep learning approaches to the most recent developments in foundation models and vision-language systems. We organize the literature along a principled taxonomy of learning paradigms, encompassing supervised learning with CNN-based and transformer-based architectures, self-supervised and semi-supervised methods, generative approaches, as well as 3D volumetric modeling, multimodal representation learning, and large-scale pretrained foundation models. For each paradigm, we analyze the core methodological contributions, identify persistent limitations, and trace the connections between successive approaches. We further provide a structured overview of publicly available OCT datasets, discuss evaluation protocol considerations, and present a unified problem formulation that situates each learning paradigm within a common mathematical framework. Building on this analysis, we identify and discuss the most pressing open research directions emerging in the literature. This includes volumetric foundation model pretraining, uncertainty-aware representation learning, federated and privacy-preserving training, fairness and bias mitigation, concept-based interpretability,...