Corneal endothelium assessment in specular microscopy images with Fuchs’ dystrophy via deep regression of signed distance maps

Specular microscopy assessment of the human corneal endothelium (CE) in Fuchs’ dystrophy is challenging due to the presence of dark image regions called guttae. This paper proposes a UNet-based segmentation approach that requires minimal post-processing and achieves reliable CE morphometric assessment and guttae identification across all degrees of Fuchs’ dystrophy. We cast the segmentation problem as a regression task of the cell and gutta signed distance maps instead of a pixel-level classification task as typically done with UNets. Compared to the conventional UNet classification approach, the distance-map regression approach converges faster in clinically relevant parameters. It also produces morphometric parameters that agree with the manually-segmented ground-truth data, namely the average cell density difference of -41.9 cells/mm2 (95% confidence interval (CI) [-306.2, 222.5]) and the average difference of mean cell area of 14.8 µm 2 (95% CI [-41.9, 71.5]). These results suggest a promising alternative for CE assessment.This work has been partly funded by Ministerio de Ciencia, Tecnología e Innovación, Colombia, Project 124489786239 (Contract 763-2021), Universidad Tecnológica de Bolívar (UTB) Project CI2021P02, and Agencia Estatal de Investigación del Gobierno de España (PID2020-114582RB-I00/ AEI / 10.13039/501100011033). J. Sierra thanks UTB for a post-graduate scholarship.Peer ReviewedPostprint (published version

Artificial Intelligence Algorithms for Eye Banking

Eye banking plays a critical role in modern medicine by providing cornea tissues for transplantation to restore vision for millions of people worldwide. The evaluation of corneal endothelium is done by measuring the corneal endothelial cell density (ECD). Unfortunately, the current system to measure ECD is manual, time-consuming, and error prone. Furthermore, the impact of social behaviors and biological conditions on corneal endothelium and corneal transplant success is largely unexplored. To overcome these challenges, this dissertation aims to develop tools for corneal endothelial image and data analysis that enhance the efficiency and quality of the cornea transplants. In the first study, an image processing algorithm is developed to analyze corneal endothelial images captured by a Konan CellChek specular microscope. The algorithm successfully identifies the region of interest, filters the image, and employs stochastic watershed segmentation to determine cell boundaries and evaluate endothelial cell density (ECD). The proposed algorithm achieves a high correlation with manual counts (R2 = 0.98) and has an average analysis time of 2.5 seconds. In the second study, a deep learning-based cell segmentation algorithm called Mobile-CellNet is proposed to estimate ECD. This technique addresses the limitations of classical algorithms and creates a more robust and highly efficient algorithm. The approach achieves a mean absolute error of 4.06% for ECD on the test set, similar to U-Net but with significantly fewer floating-point operations and parameters. The third study explores the correlation between alcohol abuse and corneal endothelial morphology in a donor pool of 5,624 individuals. Multivariable regression analysis shows that alcohol abuse is associated with a reduction in endothelial cell density, an increase in the coefficient of variation, and a decrease in percent hexagonality. These studies highlight the potential of big data and artificial algorithms in accurately and efficiently analyzing corneal images and donor medical data to improve the efficiency of eye banking and patient outcomes. By automating the analysis of corneal images and exploring the impact of social behaviors and biological conditions on corneal endothelial morphology, we can enhance the quality and availability of cornea transplants and ultimately improve the lives of millions of people worldwide

Elongated Physiological Structure Segmentation via Spatial and Scale Uncertainty-aware Network

Robust and accurate segmentation for elongated physiological structures is challenging, especially in the ambiguous region, such as the corneal endothelium microscope image with uneven illumination or the fundus image with disease interference. In this paper, we present a spatial and scale uncertainty-aware network (SSU-Net) that fully uses both spatial and scale uncertainty to highlight ambiguous regions and integrate hierarchical structure contexts. First, we estimate epistemic and aleatoric spatial uncertainty maps using Monte Carlo dropout to approximate Bayesian networks. Based on these spatial uncertainty maps, we propose the gated soft uncertainty-aware (GSUA) module to guide the model to focus on ambiguous regions. Second, we extract the uncertainty under different scales and propose the multi-scale uncertainty-aware (MSUA) fusion module to integrate structure contexts from hierarchical predictions, strengthening the final prediction. Finally, we visualize the uncertainty map of final prediction, providing interpretability for segmentation results. Experiment results show that the SSU-Net performs best on cornea endothelial cell and retinal vessel segmentation tasks. Moreover, compared with counterpart uncertainty-based methods, SSU-Net is more accurate and robust

Evaluation of a computer-aided diagnostic model for corneal diseases by analyzing in vivo confocal microscopy images

ObjectiveIn order to automatically and rapidly recognize the layers of corneal images using in vivo confocal microscopy (IVCM) and classify them into normal and abnormal images, a computer-aided diagnostic model was developed and tested based on deep learning to reduce physicians’ workload.MethodsA total of 19,612 corneal images were retrospectively collected from 423 patients who underwent IVCM between January 2021 and August 2022 from Renmin Hospital of Wuhan University (Wuhan, China) and Zhongnan Hospital of Wuhan University (Wuhan, China). Images were then reviewed and categorized by three corneal specialists before training and testing the models, including the layer recognition model (epithelium, bowman’s membrane, stroma, and endothelium) and diagnostic model, to identify the layers of corneal images and distinguish normal images from abnormal images. Totally, 580 database-independent IVCM images were used in a human-machine competition to assess the speed and accuracy of image recognition by 4 ophthalmologists and artificial intelligence (AI). To evaluate the efficacy of the model, 8 trainees were employed to recognize these 580 images both with and without model assistance, and the results of the two evaluations were analyzed to explore the effects of model assistance.ResultsThe accuracy of the model reached 0.914, 0.957, 0.967, and 0.950 for the recognition of 4 layers of epithelium, bowman’s membrane, stroma, and endothelium in the internal test dataset, respectively, and it was 0.961, 0.932, 0.945, and 0.959 for the recognition of normal/abnormal images at each layer, respectively. In the external test dataset, the accuracy of the recognition of corneal layers was 0.960, 0.965, 0.966, and 0.964, respectively, and the accuracy of normal/abnormal image recognition was 0.983, 0.972, 0.940, and 0.982, respectively. In the human-machine competition, the model achieved an accuracy of 0.929, which was similar to that of specialists and higher than that of senior physicians, and the recognition speed was 237 times faster than that of specialists. With model assistance, the accuracy of trainees increased from 0.712 to 0.886.ConclusionA computer-aided diagnostic model was developed for IVCM images based on deep learning, which rapidly recognized the layers of corneal images and classified them as normal and abnormal. This model can increase the efficacy of clinical diagnosis and assist physicians in training and learning for clinical purposes

Novel medical imaging technologies for processing epithelium and endothelium layers in corneal confocal images. Developing automated segmentation and quantification algorithms for processing sub-basal epithelium nerves and endothelial cells for early diagnosis of diabetic neuropathy in corneal confocal microscope images

Diabetic Peripheral Neuropathy (DPN) is one of the most common types of diabetes that can affect the cornea. An accurate analysis of the corneal epithelium nerve structures and the corneal endothelial cell can assist early diagnosis of this disease and other corneal diseases, which can lead to visual impairment and then to blindness. In this thesis, fully-automated segmentation and quantification algorithms for processing and analysing sub-basal epithelium nerves and endothelial cells are proposed for early diagnosis of diabetic neuropathy in Corneal Confocal Microscopy (CCM) images. Firstly, a fully automatic nerve segmentation system for corneal confocal microscope images is proposed. The performance of the proposed system is evaluated against manually traced images with an execution time of the prototype is 13 seconds. Secondly, an automatic corneal nerve registration system is proposed. The main aim of this system is to produce a new informative corneal image that contains structural and functional information. Thirdly, an automated real-time system, termed the Corneal Endothelium Analysis System (CEAS) is developed and applied for the segmentation of endothelial cells in images of human cornea obtained by In Vivo CCM. The performance of the proposed CEAS system was tested against manually traced images with an execution time of only 6 seconds per image. Finally, the results obtained from all the proposed approaches have been evaluated and validated by an expert advisory board from two institutes, they are the Division of Medicine, Weill Cornell Medicine-Qatar, Doha, Qatar and the Manchester Royal Eye Hospital, Centre for Endocrinology and Diabetes, UK

A review of artificial intelligence applications in anterior segment ocular diseases

Background: Artificial intelligence (AI) has great potential for interpreting and analyzing images and processing large amounts of data. There is a growing interest in investigating the applications of AI in anterior segment ocular diseases. This narrative review aims to assess the use of different AI-based algorithms for diagnosing and managing anterior segment entities. Methods: We reviewed the applications of different AI-based algorithms in the diagnosis and management of anterior segment entities, including keratoconus, corneal dystrophy, corneal grafts, corneal transplantation, refractive surgery, pterygium, infectious keratitis, cataracts, and disorders of the corneal nerves, conjunctiva, tear film, anterior chamber angle, and iris. The English-language databases PubMed/MEDLINE, Scopus, and Google Scholar were searched using the following keywords: artificial intelligence, deep learning, machine learning, neural network, anterior eye segment diseases, corneal disease, keratoconus, dry eye, refractive surgery, pterygium, infectious keratitis, anterior chamber, and cataract. Relevant articles were compared based on the use of AI models in the diagnosis and treatment of anterior segment diseases. Furthermore, we prepared a summary of the diagnostic performance of the AI-based methods for anterior segment ocular entities. Results: Various AI methods based on deep and machine learning can analyze data obtained from corneal imaging modalities with acceptable diagnostic performance. Currently, complicated and time-consuming manual methods are available for diagnosing and treating eye diseases. However, AI methods could save time and prevent vision impairment in eyes with anterior segment diseases. Because many anterior segment diseases can cause irreversible complications and even vision loss, sufficient confidence in the results obtained from the designed model is crucial for decision-making by experts. Conclusions: AI-based models could be used as surrogates for analyzing manual data with improveddiagnostic performance. These methods could be reliable tools for diagnosing and managing anterior segmentocular diseases in the near future in remote areas. It is expected that future studies can design algorithms thatuse less data in a multitasking manner for the detection and management of anterior segment diseases

Corneal Pachymetry by AS-OCT after Descemet's Membrane Endothelial Keratoplasty

Corneal thickness (pachymetry) maps can be used to monitor restoration of corneal endothelial function, for example after Descemet's membrane endothelial keratoplasty (DMEK). Automated delineation of the corneal interfaces in anterior segment optical coherence tomography (AS-OCT) can be challenging for corneas that are irregularly shaped due to pathology, or as a consequence of surgery, leading to incorrect thickness measurements. In this research, deep learning is used to automatically delineate the corneal interfaces and measure corneal thickness with high accuracy in post-DMEK AS-OCT B-scans. Three different deep learning strategies were developed based on 960 B-scans from 50 patients. On an independent test set of 320 B-scans, corneal thickness could be measured with an error of 13.98 to 15.50 micrometer for the central 9 mm range, which is less than 3% of the average corneal thickness. The accurate thickness measurements were used to construct detailed pachymetry maps. Moreover, follow-up scans could be registered based on anatomical landmarks to obtain differential pachymetry maps. These maps may enable a more comprehensive understanding of the restoration of the endothelial function after DMEK, where thickness often varies throughout different regions of the cornea, and subsequently contribute to a standardized postoperative regime.Comment: Fixed typo in abstract: The development set consists of 960 B-scans from 50 patients (instead of 68). The B-scans from the other 18 patients were used for testing onl