The robust segmentation of different targets in multiple modality images is challenging due to factors such as low contrast, variations in target size and shape, and interference from diseases, which may lead to segmentation ambiguity. In addition, the assessment of the reliability of artificial intelligence is crucial for its clinical application. This paper proposes the Online Bayesian approximation based Uncertainty-aware Network (OBU-Net) for robust ophthalmic image segmentation. Our approach introduces an efficient online Bayesian method to update a spatial uncertainty map during training continuously. Then, the Spatial Uncertainty Aware Block (SUA-B) leverages the uncertainty map to localize and prioritize attention to ambiguous regions. Additionally, we extract pixel-wise confidence from multi-scale predictions to integrate hierarchical predictions. We compare OBU-Net with state-of-the-art (SOTA) methods on six datasets. The experimental results demonstrate that our method achieves the best overall performance across different modalities and segmentation tasks, highlighting the robustness of our approach. Additionally, metamorphic testing experiments were conducted, exploring the algorithm's stability against random perturbations. Lastly, we propose an image-level uncertainty score and demonstrate its effectiveness for evaluating the model's segmentation reliability.

Efficient convolutional neural network (CNN) architecture design has attracted growing research interests. However, they typically apply single receptive field (RF), small asymmetric RFs, or pyramid RFs to learn different feature representations, still encountering two significant challenges in medical image classification tasks: i) They have limitations in capturing diverse lesion characteristics efficiently, e.g., tiny, coordination, small and salient, which have unique roles on the classification results, especially imbalanced medical image classification. ii) The predictions generated by those CNNs are often unfair/biased, bringing a high risk when employing them to real-world medical diagnosis conditions. To tackle these issues, we develop a new concept, Expert-Like Reparameterization of Heterogeneous Pyramid Receptive Fields (ERoHPRF), to simultaneously boost medical image classification performance and fairness. This concept aims to mimic the multi-expert consultation mode by applying the well-designed heterogeneous pyramid RF bag to capture lesion characteristics with varying significances effectively via convolution operations with multiple heterogeneous kernel sizes. Additionally, ERoHPRF introduces an expert-like structural reparameterization technique to merge its parameters with the two-stage strategy, ensuring competitive computation cost and inference speed through comparisons to a single RF. To manifest the effectiveness and generalization ability of ERoHPRF, we incorporate it into mainstream efficient CNN architectures. The extensive experiments show that our proposed ERoHPRF maintains a better trade-off than state-of-the-art methods in terms of medical image classification, fairness, and computation overhead. The code of this paper is available at https://github.com/XiaoLing12138/Expert-Like-Reparameterization-of-Heterogeneous-Pyramid-Receptive-Fields.

Iris motion tracking is critical for discriminating the iris stiffness and developmental stage of primary angle-closure disease (PACD). Anterior segment optical coherence tomography (AS-OCT) video is a highly efficient approach to observe the morphological determinant in iris motion. However, the iris exhibits inconsistent elastic changes during movement, accompanied by changes in local features after long-term frames. Currently, iris tracking methods have not yet been studied in AS-OCT videos. In this paper, we propose a Temporal Constraint-based Tracking Morph (TCTMorph) for estimating iris trajectory in long-term AS-OCT videos. We first estimate the deformation fields between three interrelated frames by a multi-frame diffeomorphic registration network. Then, we estimate iris trajectory from these results in long-term AS-OCT video sequences by leveraging temporal constraints among the consecutive flows. Our experiments on multi-center AS-OCT glaucoma datasets demonstrate that our method outperforms conventional motion tracking methods for long-term iris trajectory tracking.

Anterior segment optical coherence tomography (AS-OCT) is a popular imaging technique that can directly visualize the anterior segment structures while inherent speckle noise severely impairs visual readability and subsequent clinical analysis. Though unpaired OCT image denoising algorithms have been developed to improve visual quality considering the limited supervised clinical data, preserving the edge structures while denoising remains challenging, especially in AS-OCT images with little hierarchy and low contrast. This work proposes an edge enhancement generative adversarial network ($E^{2}GAN$) based contrast-aware, particularly for unpaired AS-OCT image denoising. Specifically, to improve edge-structure consistency, we design a contrast attention mechanism for exploiting diverse hierarchical knowledge from multiple contrast images and adopt particular gradient-guided speckle filtering modules with an edge preservation loss for stabilizing the network. Additionally, considering that bi-directional GANs often focus on global appearance rather than essential features,$E^{2}GAN$adds a perceptual quality constraint into the cycle consistency. Extensive experiments validate the superiority of$E^{2}GAN$for AS-OCT image denoising and the benefits for downstream clinical analysis. Further experiments on the synthetic retinal OCT images prove the generalization of$E^{2}GAN$.

Optical coherence tomography (OCT) is a widely used non-invasive imaging modality for ophthalmic diagnosis. However, the inherent speckle noise becomes the leading cause of OCT image quality, and efficient speckle removal algorithms can improve image readability and benefit automated clinical analysis. As an ill-posed inverse problem, it is of utmost importance for speckle removal to learn suitable priors. In this work, we develop a score prior guided iterative solver (SPIS) with logarithmic space to remove speckles in OCT images. Specifically, we model the posterior distribution of raw OCT images as a data consistency term and transform the speckle removal from a nonlinear into a linear inverse problem in the logarithmic domain. Subsequently, the learned prior distribution through the score function from the diffusion model is utilized as a constraint for the data consistency term into the linear inverse optimization, resulting in an iterative speckle removal procedure that alternates between the score prior predictor and the subsequent non-expansive data consistency corrector. Experimental results on the private and public OCT datasets demonstrate that the proposed SPIS has an excellent performance in speckle removal and out-of-distribution (OOD) generalization. Further downstream automatic analysis on the OCT images verifies that the proposed SPIS can benefit clinical applications.

The segmentation of blurred cell boundaries in cornea endothelium microscope images is challenging, which affects the clinical parameter estimation accuracy. Existing deep learning methods only consider pixel-wise classification accuracy and lack of utilization of cell structure knowledge. Therefore, the segmentation of the blurred cell boundary is discontinuous. This paper proposes a structural prior guided network (SPG-Net) for corneal endothelium cell segmentation. We first employ a hybrid transformer convolution backbone to capture more global context. Then, we use Feature Enhancement (FE) module to improve the representation ability of features and Local Affinity-based Feature Fusion (LAFF) module to propagate structural information among hierarchical features. Finally, we introduce the joint loss based on cross entropy and structure similarity index measure (SSIM) to supervise the training process under pixel and structure levels. We compare the SPG-Net with various state-of-the-art methods on four corneal endothelial datasets. The experiment results suggest that the SPG-Net can alleviate the problem of discontinuous cell boundary segmentation and balance the pixel-wise accuracy and structure preservation. We also evaluate the agreement of parameter estimation between ground truth and the prediction of SPG-Net. The statistical analysis results show a good agreement and correlation.

Optical coherence tomography (OCT) imaging technique has been widely used for ocular disease diagnosis. However, speckles occur in OCT images due to the property of coherent imaging, inevitably affecting the visual quality and clinical analysis. To alleviate this problem, we propose a novel gradient-guided speckle image filtering method (GGSF) with structure enhancement for directly removing speckles in OCT images. Specifically, the multiplicative characteristic of speckle noise is incorporated into the guided filtering processing for modeling raw OCT images. To avoid getting trapped in image distortions, we further employ gradient regularization to integrate the structure prior information into the guided speckle image filtering procedure. Additionally, we introduce the statistical property of speckle noise obeying a gamma distribution into the least square method solver for the resulting non-convex GGSF model. Experimental results on the AS-OCT dataset demonstrate the effectiveness of GGSF for OCT image despeckling compared with competitive methods. Furthermore, we validate the benefits of GGSF for subsequent clinical analysis with the CM-OCT dataset.

Cataracts are the leading cause of visual impairment and blindness globally attracting abroad attention from society. Over the years researchers have developed many state-of-the-art convolutional neural networks (CNNs) to recognize cataract severity levels based on different ophthalmic images. However most current works focus on improving cataract recognition performance by designing complex CNNs often ignoring resource-constrained medical device limitations. To this problem this paper proposes a novel dual-mixed channel-independent convolution (DMIConv) method which takes advantage of the multiscale convolution kernels by combining a depthwise convolution with a depthwise dilated convolution sequentially. Moreover we build a lightweight dual-mixed channel-independent network (DMINet) to recognize cataracts. To verify the effectiveness and efficiency of DMINet we conduct extensive experiments on a clinical anterior segment optical coherence tomography (AS-OCT) dataset of nuclear cataract (NC) and a publicly available OCT dataset. The results show that our proposed DMINet keeps a better tradeoff between the model complexity and the classification performance than efficient CNNs e.g DMINet outperforms MixNet by 3.34% of accuracy by using 4.58 % fewer parameters

Corneal endothelial cell segmentation plays an important role in quantifying clinical indicators for the cornea health state evaluation. Although Convolution Neural Networks (CNNs) are widely used for medical image segmentation, their receptive fields are limited. Recently, Transformer outperforms convolution in modeling long-range dependencies but lacks local inductive bias so the pure transformer network is difficult to train on small medical image datasets. Moreover, Transformer networks cannot be effectively adopted for secular microscopes as they are parameter-heavy and computationally complex. To this end, we find that appropriately limiting attention spans and modeling information at different granularity can introduce local constraints and enhance attention representations. This paper explores a hierarchy full self-attention lightweight network for medical image segmentation, using Local and Global (LoGo) transformers to separately model attention representation at low-level and high-level layers. Specifically, the local efficient transformer (LoTr) layer is employed to decompose features into finer-grained elements to model local attention representation, while the global axial transformer (GoTr) is utilized to build long-range dependencies across the entire feature space. With this hierarchy structure, we gradually aggregate the semantic features from different levels efficiently. Experiment results on segmentation tasks of the corneal endothelial cell, the ciliary body, and the liver prove the accuracy, effectiveness, and robustness of our method. Compared with the convolution neural networks (CNNs) and the hybrid CNN-Transformer state-of-the-art (SOTA) methods, the LoGo transformer obtains the best result.

Ciliary muscle segmentation in Anterior Segment Optical Coherence Tomography (AS-OCT) images is critical significance, yet challenging due to ambiguous boundaries. In this paper, we propose a hierarchical attention multi-task network, HA-Net, based on U-Net for ciliary muscle segmentation using AS-OCT images. The network comprises a primary task for ciliary muscle segmentation and two auxiliary tasks for signed distance map regression and key point localization. The signed distance map is employed to incorporate shape priors into the model and delineate the ciliary muscle boundary, while key point localization guides the model to focus on ambiguous regions. Notably, in contrast to the widely-used multi-task model that generates results in parallel, we introduce a hierarchical attention module to exploit the affiliation prior of three tasks for generating outputs serially. Experimental results on CM544 dataset demonstrate that HA-Net outperforms state-of-the-art methods in ciliary muscle segmentation, with 0.9178 Dice score and 7.11 pixels HD95. Additionally, as a by-product of the multi-task model, key point localization facilitates the measurement of ciliary muscle thickness in clinical analysis.

Nuclear cataract (NC) is a prior age-related disease for blindness and vision impairment globally. Anterior segment optical coherence tomography (AS-OCT) image is a new ophthalmology image, which can capture the lens nucleus region clearly compared with other ophthalmic images, e.g., slit lamp images. Clinical research has suggested that features e.g., mean from AS-OCT images have varying correlations with NC severity levels. However, existing convolutional neural network (CNN) based NC classification works have not incorporated the clinical features into the network design to improve the performance. To this end, we propose a novel channel-wise and spatial feature recalibration network (CSFR-Net) to predict NC severity levels automatically, which is built on a stack of channel-wise and spatial feature recalibration (CSFR) modules. In each CSFR module, we construct a channel-wise feature recalibration block and a spatial feature recalibration block to recalibrate intermediate feature maps dynamically. This feature recalibration strategy enables CSFR-Net to highlight feature representations and suppress unnecessary ones in a global-and-local manner. We conduct extensive experiments on a clinical AS-OCT image dataset and CIFAR benchmarks. The results show that our CSFR-Net achieves better performance than state-of-the-art methods with less model complexity.

Nuclear cataract (NC) is a leading eye disease for blindness and vision impairment globally. Accurate and objective NC grading/classification is essential for clinically early intervention and cataract surgery planning. Anterior segment optical coherence tomography (AS-OCT) images are capable of capturing the nucleus region clearly and measuring the opacity of NC quantitatively. Recently, clinical research has suggested that the opacity correlation and repeatability between NC severity levels and the average nucleus density on AS-OCT images is high with the interclass and intraclass analysis. Moreover, clinical research has suggested that opacity distribution is uneven on the nucleus region, indicating that the opacities from different nucleus regions may play different roles in NC diagnosis. Motivated by the clinical priors, this paper proposes a simple yet effective region-based integration-and-recalibration attention (RIR), which integrates multiple feature map region representations and recalibrates the weights of each region via softmax attention adaptively. This region recalibration strategy enables the network to focus on high contribution region representations and suppress less useful ones. We combine the RIR block with the residual block to form a Residual-RIR module, and then a sequence of Residual-RIR modules are stacked to a deep network named region-based integration-and-recalibration network (RIR-Net), to predict NC severity levels automatically. The experiments on a clinical AS-OCT image dataset and two OCT datasets demonstrate that our method outperforms strong baselines and previous state-of-the-art methods. Furthermore, attention weight visualization analysis and ablation studies verify the capability of our RIR-Net for adjusting the relative importance of different regions in feature maps dynamically, agreeing with the clinical research.

Automatic angle-closure assessment in Anterior Segment OCT (AS-OCT) images is an important task for the screening and diagnosis of glaucoma, and the most recent computer-aided models focus on a binary classification of anterior chamber angles (ACA) in AS-OCT, i.e., open-angle and angle-closure. In order to assist clinicians who seek better to understand the development of the spectrum of glaucoma types, a more discriminating three-class classification scheme was suggested, i.e., the classification of ACA was expended to include open-, appositional- and synechial angles. However, appositional and synechial angles display similar appearances in an AS-OCT image, which makes classification models struggle to differentiate angle-closure subtypes based on static AS-OCT images. In order to tackle this issue, we propose a 2D-3D Hybrid Variation-aware Network (HV-Net) for open-appositional-synechial ACA classification from AS-OCT imagery. Specifically, taking into account clinical priors, we first reconstruct the 3D iris surface from an AS-OCT sequence, and obtain the geometrical characteristics necessary to provide global shape information. 2D AS-OCT slices and 3D iris representations are then fed into our HV-Net to extract cross-sectional appearance features and iris morphological features, respectively. To achieve similar results to those of dynamic gonioscopy examination, which is the current gold standard for diagnostic angle assessment, the paired AS-OCT images acquired in dark and light illumination conditions are used to obtain an accurate characterization of configurational changes in ACAs and iris shapes, using a Variation-aware Block. In addition, an annealing loss function was introduced to optimize our model, so as to encourage the sub-networks to map the inputs into the more conducive spaces to extract dark-to-light variation representations, while retaining the discriminative power of the learned features. The proposed model is evaluated across 1584 paired AS-OCT samples, and it has demonstrated its superiority in classifying open-, appositional- and synechial angles.

Nuclear cataract is one of the most common types of cataract. In the recent, ophthalmologists are increasingly using anterior segment optical coherence tomography (AS-OCT) images to diagnose many ocular diseases including cataract. The relationship between cataract and the lens opacity based on AS-OCT images has been being studied in clinical pioneer research. However, using AS-OCT images to classify cataract automatically based on computer-aided diagnosis (CAD) technique has not been seriously studied. This paper proposes a novel Convolutional Neural Network (CNN) model named GraNet for nuclear cataract classification based on AS-OCT images. In the GraNet, we introduce a grading block to learn high-level feature representations based on the pointwise convolution method. To further improve the classification performance, we propose a simple and efficient cross-training method is comprised of focal loss and cross-entropy loss. Extensive experiments are conducted on the AS-OCT image dataset, the results demonstrate that the proposed methods achieve better nuclear cataract classification results than baselines.