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An interpretable multiple-instance approach for the detection of referable diabetic retinopathy in fundus images.

ABSTRACT: Diabetic retinopathy (DR) is one of the leading causes of vision loss across the world. Yet despite its wide prevalence, the majority of affected people lack access to the specialized ophthalmologists and equipment required for monitoring their condition. This can lead to delays in the start of treatment, thereby lowering their chances for a successful outcome. Machine learning systems that automatically detect the disease in eye fundus images have been proposed as a means of facilitating access to retinopathy severity estimates for patients in remote regions or even for complementing the human expert's diagnosis. Here we propose a machine learning system for the detection of referable diabetic retinopathy in fundus images, which is based on the paradigm of multiple-instance learning. Our method extracts local information independently from multiple rectangular image patches and combines it efficiently through an attention mechanism that focuses on the abnormal regions of the eye (i.e. those that contain DR-induced lesions), thus resulting in a final image representation that is suitable for classification. Furthermore, by leveraging the attention mechanism our algorithm can seamlessly produce informative heatmaps that highlight the regions where the lesions are located. We evaluate our approach on the publicly available Kaggle, Messidor-2 and IDRiD retinal image datasets, in which it exhibits near state-of-the-art classification performance (AUC of 0.961 in Kaggle and 0.976 in Messidor-2), while also producing valid lesion heatmaps (AUPRC of 0.869 in the 81 images of IDRiD that contain pixel-level lesion annotations). Our results suggest that the proposed approach provides an efficient and interpretable solution against the problem of automated diabetic retinopathy grading.

SUBMITTER: Papadopoulos A

PROVIDER: S-EPMC8275626 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Purpose: To assess the accuracy and efficacy of a semi-automated deep learning algorithm (DLA) assisted approach to detect vision-threatening diabetic retinopathy (DR). Methods: We developed a two-step semi-automated DLA-assisted approach to grade fundus photographs for vision-threatening referable DR. Study images were obtained from the Lingtou Cohort Study, and captured at participant enrollment in 2009-2010 ("baseline images") and annual follow-up between 2011 and 2017. To begin, a validated DLA automatically graded baseline images for referable DR and classified them as positive, negative, or ungradable. Following, each positive image, all other available images from patients who had a positive image, and a 5% random sample of all negative images were selected and regraded by trained human graders. A reference standard diagnosis was assigned once all graders achieved consistent grading outcomes or with a senior ophthalmologist's final diagnosis. The semi-automated DLA assisted approach combined initial DLA screening and subsequent human grading for images identified as high-risk. This approach was further validated within the follow-up image datasets and its time and economic costs evaluated against fully human grading. Results: For evaluation of baseline images, a total of 33,115 images were included and automatically graded by the DLA. 2,604 images (480 positive results, 624 available other images from participants with a positive result, and 1500 random negative samples) were selected and regraded by graders. The DLA achieved an area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and accuracy of 0.953, 0.970, 0.879, and 88.6%, respectively. In further validation within the follow-up image datasets, a total of 88,363 images were graded using this semi-automated approach and human grading was performed on 8975 selected images. The DLA achieved an AUC, sensitivity, and specificity of 0.914, 0.852, 0.853, respectively. Compared against fully human grading, the semi-automated DLA-assisted approach achieved an estimated 75.6% time and 90.1% economic cost saving. Conclusions: The DLA described in this study was able to achieve high accuracy, sensitivity, and specificity in grading fundus images for referable DR. Validated against long-term follow-up datasets, a semi-automated DLA-assisted approach was able to accurately identify suspect cases, and minimize misdiagnosis whilst balancing safety, time, and economic cost.

Project description:Importance:Convolutional neural networks have recently been applied to ophthalmic diseases; however, the rationale for the outputs generated by these systems is inscrutable to clinicians. A visualization tool is needed that would enable clinicians to understand important exposure variables in real time. Objective:To systematically visualize the convolutional neural networks of 2 validated deep learning models for the detection of referable diabetic retinopathy (DR) and glaucomatous optic neuropathy (GON). Design, Setting, and Participants:The GON and referable DR algorithms were previously developed and validated (holdout method) using 48 116 and 66 790 retinal photographs, respectively, derived from a third-party database (LabelMe) of deidentified photographs from various clinical settings in China. In the present cross-sectional study, a random sample of 100 true-positive photographs and all false-positive cases from each of the GON and DR validation data sets were selected. All data were collected from March to June 2017. The original color fundus images were processed using an adaptive kernel visualization technique. The images were preprocessed by applying a sliding window with a size of 28 × 28 pixels and a stride of 3 pixels to crop images into smaller subimages to produce a feature map. Threshold scales were adjusted to optimal levels for each model to generate heat maps highlighting localized landmarks on the input image. A single optometrist allocated each image to predefined categories based on the generated heat map. Main Outcomes and Measures:Visualization regions of the fundus. Results:In the GON data set, 90 of 100 true-positive cases (90%; 95% CI, 82%-95%) and 15 of 22 false-positive cases (68%; 95% CI, 45%-86%) displayed heat map visualization within regions of the optic nerve head only. Lesions typically seen in cases of referable DR (exudate, hemorrhage, or vessel abnormality) were identified as the most important prognostic regions in 96 of 100 true-positive DR cases (96%; 95% CI, 90%-99%). In 39 of 46 false-positive DR cases (85%; 95% CI, 71%-94%), the heat map displayed visualization of nontraditional fundus regions with or without retinal venules. Conclusions and Relevance:These findings suggest that this visualization method can highlight traditional regions in disease diagnosis, substantiating the validity of the deep learning models investigated. This visualization technique may promote the clinical adoption of these models.

Project description:Retinal blood vessels are considered valuable biomarkers for the detection of diabetic retinopathy, hypertensive retinopathy, and other retinal disorders. Ophthalmologists analyze retinal vasculature by manual segmentation, which is a tedious task. Numerous studies have focused on automatic retinal vasculature segmentation using different methods for ophthalmic disease analysis. However, most of these methods are computationally expensive and lack robustness. This paper proposes two new shallow deep learning architectures: dual-stream fusion network (DSF-Net) and dual-stream aggregation network (DSA-Net) to accurately detect retinal vasculature. The proposed method uses semantic segmentation in raw color fundus images for the screening of diabetic and hypertensive retinopathies. The proposed method's performance is assessed using three publicly available fundus image datasets: Digital Retinal Images for Vessel Extraction (DRIVE), Structured Analysis of Retina (STARE), and Children Heart Health Study in England Database (CHASE-DB1). The experimental results revealed that the proposed method provided superior segmentation performance with accuracy (Acc), sensitivity (SE), specificity (SP), and area under the curve (AUC) of 96.93%, 82.68%, 98.30%, and 98.42% for DRIVE, 97.25%, 82.22%, 98.38%, and 98.15% for CHASE-DB1, and 97.00%, 86.07%, 98.00%, and 98.65% for STARE datasets, respectively. The experimental results also show that the proposed DSA-Net provides higher SE compared to the existing approaches. It means that the proposed method detected the minor vessels and provided the least false negatives, which is extremely important for diagnosis. The proposed method provides an automatic and accurate segmentation mask that can be used to highlight the vessel pixels. This detected vasculature can be utilized to compute the ratio between the vessel and the non-vessel pixels and distinguish between diabetic and hypertensive retinopathies, and morphology can be analyzed for related retinal disorders.

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An interpretable multiple-instance approach for the detection of referable diabetic retinopathy in fundus images.

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