Alexandre H. Thiery, Fabian Braeu, Tin A. Tun et al.
Purpose: (1) To assess the performance of geometric deep learning (PointNet) in diagnosing glaucoma from a single optical coherence tomography (OCT) 3D scan of the optic nerve head (ONH); (2) To compare its performance to that obtained with a standard 3D convolutional neural network (CNN), and with a gold-standard glaucoma parameter, i.e. retinal nerve fiber layer (RNFL) thickness. Methods: 3D raster scans of the ONH were acquired with Spectralis OCT for 477 glaucoma and 2,296 non-glaucoma subjects at the Singapore National Eye Centre. All volumes were automatically segmented using deep learning to identify 7 major neural and connective tissues including the RNFL, the prelamina, and the lamina cribrosa (LC). Each ONH was then represented as a 3D point cloud with 1,000 points chosen randomly from all tissue boundaries. To simplify the problem, all ONH point clouds were aligned with respect to the plane and center of Bruch's membrane opening. Geometric deep learning (PointNet) was then used to provide a glaucoma diagnosis from a single OCT point cloud. The performance of our approach was compared to that obtained with a 3D CNN, and with RNFL thickness. Results: PointNet was able to provide a robust glaucoma diagnosis solely from the ONH represented as a 3D point cloud (AUC=95%). The performance of PointNet was superior to that obtained with a standard 3D CNN (AUC=87%) and with that obtained from RNFL thickness alone (AUC=80%). Discussion: We provide a proof-of-principle for the application of geometric deep learning in the field of glaucoma. Our technique requires significantly less information as input to perform better than a 3D CNN, and with an AUC superior to that obtained from RNFL thickness alone. Geometric deep learning may have wide applicability in the field of Ophthalmology.
Fabian A. Braeu, Alexandre H. Thiéry, Tin A. Tun et al.
Purpose: The optic nerve head (ONH) undergoes complex and deep 3D morphological changes during the development and progression of glaucoma. Optical coherence tomography (OCT) is the current gold standard to visualize and quantify these changes, however the resulting 3D deep-tissue information has not yet been fully exploited for the diagnosis and prognosis of glaucoma. To this end, we aimed: (1) To compare the performance of two relatively recent geometric deep learning techniques in diagnosing glaucoma from a single OCT scan of the ONH; and (2) To identify the 3D structural features of the ONH that are critical for the diagnosis of glaucoma. Methods: In this study, we included a total of 2,247 non-glaucoma and 2,259 glaucoma scans from 1,725 subjects. All subjects had their ONHs imaged in 3D with Spectralis OCT. All OCT scans were automatically segmented using deep learning to identify major neural and connective tissues. Each ONH was then represented as a 3D point cloud. We used PointNet and dynamic graph convolutional neural network (DGCNN) to diagnose glaucoma from such 3D ONH point clouds and to identify the critical 3D structural features of the ONH for glaucoma diagnosis. Results: Both the DGCNN (AUC: 0.97$\pm$0.01) and PointNet (AUC: 0.95$\pm$0.02) were able to accurately detect glaucoma from 3D ONH point clouds. The critical points formed an hourglass pattern with most of them located in the inferior and superior quadrant of the ONH. Discussion: The diagnostic accuracy of both geometric deep learning approaches was excellent. Moreover, we were able to identify the critical 3D structural features of the ONH for glaucoma diagnosis that tremendously improved the transparency and interpretability of our method. Consequently, our approach may have strong potential to be used in clinical applications for the diagnosis and prognosis of a wide range of ophthalmic disorders.
Fabian A. Braeu, Thanadet Chuangsuwanich, Tin A. Tun et al.
$\mathbf{Purpose}$: To use artificial intelligence (AI) to: (1) exploit biomechanical knowledge of the optic nerve head (ONH) from a relatively large population; (2) assess ONH robustness from a single optical coherence tomography (OCT) scan of the ONH; (3) identify what critical three-dimensional (3D) structural features make a given ONH robust. $\mathbf{Design}$: Retrospective cross-sectional study. $\mathbf{Methods}$: 316 subjects had their ONHs imaged with OCT before and after acute intraocular pressure (IOP) elevation through ophthalmo-dynamometry. IOP-induced lamina-cribrosa deformations were then mapped in 3D and used to classify ONHs. Those with LC deformations superior to 4% were considered fragile, while those with deformations inferior to 4% robust. Learning from these data, we compared three AI algorithms to predict ONH robustness strictly from a baseline (undeformed) OCT volume: (1) a random forest classifier; (2) an autoencoder; and (3) a dynamic graph CNN (DGCNN). The latter algorithm also allowed us to identify what critical 3D structural features make a given ONH robust. $\mathbf{Results}$: All 3 methods were able to predict ONH robustness from 3D structural information alone and without the need to perform biomechanical testing. The DGCNN (area under the receiver operating curve [AUC]: 0.76 $\pm$ 0.08) outperformed the autoencoder (AUC: 0.70 $\pm$ 0.07) and the random forest classifier (AUC: 0.69 $\pm$ 0.05). Interestingly, to assess ONH robustness, the DGCNN mainly used information from the scleral canal and the LC insertion sites. $\mathbf{Conclusions}$: We propose an AI-driven approach that can assess the robustness of a given ONH solely from a single OCT scan of the ONH, and without the need to perform biomechanical testing. Longitudinal studies should establish whether ONH robustness could help us identify fast visual field loss progressors.
Fabian A. Braeu, Thanadet Chuangsuwanich, Tin A. Tun et al.
$\bf{Purpose}$: To describe the 3D structural changes in both connective and neural tissues of the optic nerve head (ONH) that occur concurrently at different stages of glaucoma using traditional and AI-driven approaches. $\bf{Methods}$: We included 213 normal, 204 mild glaucoma (mean deviation [MD] $\ge$ -6.00 dB), 118 moderate glaucoma (MD of -6.01 to -12.00 dB), and 118 advanced glaucoma patients (MD < -12.00 dB). All subjects had their ONHs imaged in 3D with Spectralis optical coherence tomography. To describe the 3D structural phenotype of glaucoma as a function of severity, we used two different approaches: (1) We extracted human-defined 3D structural parameters of the ONH including retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) shape and depth at different stages of glaucoma; (2) we also employed a geometric deep learning method (i.e. PointNet) to identify the most important 3D structural features that differentiate ONHs from different glaucoma severity groups without any human input. $\bf{Results}$: We observed that the majority of ONH structural changes occurred in the early glaucoma stage, followed by a plateau effect in the later stages. Using PointNet, we also found that 3D ONH structural changes were present in both neural and connective tissues. In both approaches, we observed that structural changes were more prominent in the superior and inferior quadrant of the ONH, particularly in the RNFL, the prelamina, and the LC. As the severity of glaucoma increased, these changes became more diffuse (i.e. widespread), particularly in the LC. $\bf{Conclusions}$: In this study, we were able to uncover complex 3D structural changes of the ONH in both neural and connective tissues as a function of glaucoma severity. We hope to provide new insights into the complex pathophysiology of glaucoma that might help clinicians in their daily clinical care.
Se-In Jang, Michael J. A. Girard, Alexandre H. Thiery
In this paper, we propose an explainable and interpretable diabetic retinopathy (ExplainDR) classification model based on neural-symbolic learning. To gain explainability, a highlevel symbolic representation should be considered in decision making. Specifically, we introduce a human-readable symbolic representation, which follows a taxonomy style of diabetic retinopathy characteristics related to eye health conditions to achieve explainability. We then include humanreadable features obtained from the symbolic representation in the disease prediction. Experimental results on a diabetic retinopathy classification dataset show that our proposed ExplainDR method exhibits promising performance when compared to that from state-of-the-art methods applied to the IDRiD dataset, while also providing interpretability and explainability.
Charis Y. N. Chiang, Fabian Braeu, Thanadet Chuangsuwanich et al.
Purpose: (1) To develop a deep learning algorithm to automatically segment structures of the optic nerve head (ONH) and macula in 3D wide-field optical coherence tomography (OCT) scans; (2) To assess whether 3D macula or ONH structures (or the combination of both) provide the best diagnostic power for glaucoma. Methods: A cross-sectional comparative study was performed which included wide-field swept-source OCT scans from 319 glaucoma subjects and 298 non-glaucoma subjects. All scans were compensated to improve deep-tissue visibility. We developed a deep learning algorithm to automatically label all major ONH tissue structures by using 270 manually annotated B-scans for training. The performance of our algorithm was assessed using the Dice coefficient (DC). A glaucoma classification algorithm (3D CNN) was then designed using a combination of 500 OCT volumes and their corresponding automatically segmented masks. This algorithm was trained and tested on 3 datasets: OCT scans cropped to contain the macular tissues only, those to contain the ONH tissues only, and the full wide-field OCT scans. The classification performance for each dataset was reported using the AUC. Results: Our segmentation algorithm was able to segment ONH and macular tissues with a DC of 0.94 $\pm$ 0.003. The classification algorithm was best able to diagnose glaucoma using wide-field 3D-OCT volumes with an AUC of 0.99 $\pm$ 0.01, followed by ONH volumes with an AUC of 0.93 $\pm$ 0.06, and finally macular volumes with an AUC of 0.91 $\pm$ 0.11. Conclusions: this study showed that using wide-field OCT as compared to the typical OCT images containing just the ONH or macular may allow for a significantly improved glaucoma diagnosis. This may encourage the mainstream adoption of 3D wide-field OCT scans. For clinical AI studies that use traditional machines, we would recommend the use of ONH scans as opposed to macula scans.
Thanadet Chuangsuwanich, Monisha E. Nongpiur, Fabian A. Braeu et al.
Objective. (1) To assess whether neural tissue structure and biomechanics could predict functional loss in glaucoma; (2) To evaluate the importance of biomechanics in making such predictions. Design, Setting and Participants. We recruited 238 glaucoma subjects. For one eye of each subject, we imaged the optic nerve head (ONH) using spectral-domain OCT under the following conditions: (1) primary gaze and (2) primary gaze with acute IOP elevation. Main Outcomes: We utilized automatic segmentation of optic nerve head (ONH) tissues and digital volume correlation (DVC) analysis to compute intraocular pressure (IOP)-induced neural tissue strains. A robust geometric deep learning approach, known as Point-Net, was employed to predict the full Humphrey 24-2 pattern standard deviation (PSD) maps from ONH structural and biomechanical information. For each point in each PSD map, we predicted whether it exhibited no defect or a PSD value of less than 5%. Predictive performance was evaluated using 5-fold cross-validation and the F1-score. We compared the model's performance with and without the inclusion of IOP-induced strains to assess the impact of biomechanics on prediction accuracy. Results: Integrating biomechanical (IOP-induced neural tissue strains) and structural (tissue morphology and neural tissues thickness) information yielded a significantly better predictive model (F1-score: 0.76+-0.02) across validation subjects, as opposed to relying only on structural information, which resulted in a significantly lower F1-score of 0.71+-0.02 (p < 0.05). Conclusion: Our study has shown that the integration of biomechanical data can significantly improve the accuracy of visual field loss predictions. This highlights the importance of the biomechanics-function relationship in glaucoma, and suggests that biomechanics may serve as a crucial indicator for the development and progression of glaucoma.
Michaël J. A. Girard, Satish K. Panda, Tin Aung Tun et al.
Purpose: (1) To develop a deep learning algorithm to identify major tissue structures of the optic nerve head (ONH) in 3D optical coherence tomography (OCT) scans; (2) to exploit such information to robustly differentiate among healthy, optic disc drusen (ODD), and papilledema ONHs. It was a cross-sectional comparative study with confirmed ODD (105 eyes), papilledema due to high intracranial pressure (51 eyes), and healthy controls (100 eyes). 3D scans of the ONHs were acquired using OCT, then processed to improve deep-tissue visibility. At first, a deep learning algorithm was developed using 984 B-scans (from 130 eyes) in order to identify: major neural/connective tissues, and ODD regions. The performance of our algorithm was assessed using the Dice coefficient (DC). In a 2nd step, a classification algorithm (random forest) was designed using 150 OCT volumes to perform 3-class classifications (1: ODD, 2: papilledema, 3: healthy) strictly from their drusen and prelamina swelling scores (derived from the segmentations). To assess performance, we reported the area under the receiver operating characteristic curves (AUCs) for each class. Our segmentation algorithm was able to isolate neural and connective tissues, and ODD regions whenever present. This was confirmed by an average DC of 0.93$\pm$0.03 on the test set, corresponding to good performance. Classification was achieved with high AUCs, i.e. 0.99$\pm$0.01 for the detection of ODD, 0.99 $\pm$ 0.01 for the detection of papilledema, and 0.98$\pm$0.02 for the detection of healthy ONHs. Our AI approach accurately discriminated ODD from papilledema, using a single OCT scan. Our classification performance was excellent, with the caveat that validation in a much larger population is warranted. Our approach may have the potential to establish OCT as the mainstay of diagnostic imaging in neuro-ophthalmology.
Purpose: To assess whether the three-dimensional (3D) structural configuration of the central retinal vessel trunk and its branches (CRVT&B) could be used as a diagnostic marker for glaucoma. Method: We trained a deep learning network to automatically segment the CRVT&B from the B-scans of the optical coherence tomography (OCT) volume of the optic nerve head (ONH). Subsequently, two different approaches were used for glaucoma diagnosis using the structural configuration of the CRVT&B as extracted from the OCT volumes. In the first approach, we aimed to provide a diagnosis using only 3D CNN and the 3D structure of the CRVT&B. For the second approach, we projected the 3D structure of the CRVT&B orthographically onto three planes to obtain 2D images, and then a 2D CNN was used for diagnosis. The segmentation accuracy was evaluated using the Dice coefficient, whereas the diagnostic accuracy was assessed using the area under the receiver operating characteristic curves (AUC). The diagnostic performance of the CRVT&B was also compared with that of retinal nerve fiber layer (RNFL) thickness. Results: Our segmentation network was able to efficiently segment retinal blood vessels from OCT scans. On a test set, we achieved a Dice coefficient of 0.81\pm0.07. The 3D and 2D diagnostic networks were able to differentiate glaucoma from non-glaucoma subjects with accuracies of 82.7% and 83.3%, respectively. The corresponding AUCs for CRVT&B were 0.89 and 0.90, higher than those obtained with RNFL thickness alone. Conclusions: Our work demonstrated that the diagnostic power of the CRVT&B is superior to that of a gold-standard glaucoma parameter, i.e., RNFL thickness. Our work also suggested that the major retinal blood vessels form a skeleton -- the configuration of which may be representative of major ONH structural changes as typically observed with the development and progression of glaucoma.
Gihan Panapitiya, Michael Girard, Aaron Hollas et al.
Determining the aqueous solubility of molecules is a vital step in many pharmaceutical, environmental, and energy storage applications. Despite efforts made over decades, there are still challenges associated with developing a solubility prediction model with satisfactory accuracy for many of these applications. The goal of this study is to develop a general model capable of predicting the solubility of a broad range of organic molecules. Using the largest currently available solubility dataset, we implement deep learning-based models to predict solubility from molecular structure and explore several different molecular representations including molecular descriptors, simplified molecular-input line-entry system (SMILES) strings, molecular graphs, and three-dimensional (3D) atomic coordinates using four different neural network architectures - fully connected neural networks (FCNNs), recurrent neural networks (RNNs), graph neural networks (GNNs), and SchNet. We find that models using molecular descriptors achieve the best performance, with GNN models also achieving good performance. We perform extensive error analysis to understand the molecular properties that influence model performance, perform feature analysis to understand which information about molecular structure is most valuable for prediction, and perform a transfer learning and data size study to understand the impact of data availability on model performance.
The optic nerve head (ONH) typically experiences complex neural- and connective-tissue structural changes with the development and progression of glaucoma, and monitoring these changes could be critical for improved diagnosis and prognosis in the glaucoma clinic. The gold-standard technique to assess structural changes of the ONH clinically is optical coherence tomography (OCT). However, OCT is limited to the measurement of a few hand-engineered parameters, such as the thickness of the retinal nerve fiber layer (RNFL), and has not yet been qualified as a stand-alone device for glaucoma diagnosis and prognosis applications. We argue this is because the vast amount of information available in a 3D OCT scan of the ONH has not been fully exploited. In this study we propose a deep learning approach that can: \textbf{(1)} fully exploit information from an OCT scan of the ONH; \textbf{(2)} describe the structural phenotype of the glaucomatous ONH; and that can \textbf{(3)} be used as a robust glaucoma diagnosis tool. Specifically, the structural features identified by our algorithm were found to be related to clinical observations of glaucoma. The diagnostic accuracy from these structural features was $92.0 \pm 2.3 \%$ with a sensitivity of $90.0 \pm 2.4 \% $ (at $95 \%$ specificity). By changing their magnitudes in steps, we were able to reveal how the morphology of the ONH changes as one transitions from a `non-glaucoma' to a `glaucoma' condition. We believe our work may have strong clinical implication for our understanding of glaucoma pathogenesis, and could be improved in the future to also predict future loss of vision.
Haris Cheong, Sripad Krishna Devalla, Thanadet Chuangsuwanich et al.
Speckle noise and retinal shadows within OCT B-scans occlude important edges, fine textures and deep tissues, preventing accurate and robust diagnosis by algorithms and clinicians. We developed a single process that successfully removed both noise and retinal shadows from unseen single-frame B-scans within 10.4ms. Mean average gradient magnitude (AGM) for the proposed algorithm was 57.2% higher than current state-of-the-art, while mean peak signal to noise ratio (PSNR), contrast to noise ratio (CNR), and structural similarity index metric (SSIM) increased by 11.1%, 154% and 187% respectively compared to single-frame B-scans. Mean intralayer contrast (ILC) improvement for the retinal nerve fiber layer (RNFL), photoreceptor layer (PR) and retinal pigment epithelium (RPE) layers decreased from 0.362 \pm 0.133 to 0.142 \pm 0.102, 0.449 \pm 0.116 to 0.0904 \pm 0.0769, 0.381 \pm 0.100 to 0.0590 \pm 0.0451 respectively. The proposed algorithm reduces the necessity for long image acquisition times, minimizes expensive hardware requirements and reduces motion artifacts in OCT images.
Haris Cheong, Sripad Krishna Devalla, Tan Hung Pham et al.
Purpose: To remove retinal shadows from optical coherence tomography (OCT) images of the optic nerve head(ONH). Methods:2328 OCT images acquired through the center of the ONH using a Spectralis OCT machine for both eyes of 13 subjects were used to train a generative adversarial network (GAN) using a custom loss function. Image quality was assessed qualitatively (for artifacts) and quantitatively using the intralayer contrast: a measure of shadow visibility ranging from 0 (shadow-free) to 1 (strong shadow) and compared to compensated images. This was computed in the Retinal Nerve Fiber Layer (RNFL), the Inner Plexiform Layer (IPL), the Photoreceptor layer (PR) and the Retinal Pigment Epithelium (RPE) layers. Results: Output images had improved intralayer contrast in all ONH tissue layers. On average the intralayer contrast decreased by 33.7$\pm$6.81%, 28.8$\pm$10.4%, 35.9$\pm$13.0%, and43.0$\pm$19.5%for the RNFL, IPL, PR, and RPE layers respectively, indicating successful shadow removal across all depths. This compared to 70.3$\pm$22.7%, 33.9$\pm$11.5%, 47.0$\pm$11.2%, 26.7$\pm$19.0%for compensation. Output images were also free from artifacts commonly observed with compensation. Conclusions: DeshadowGAN significantly corrected blood vessel shadows in OCT images of the ONH. Our algorithm may be considered as a pre-processing step to improve the performance of a wide range of algorithms including those currently being used for OCT image segmentation, denoising, and classification. Translational Relevance: DeshadowGAN could be integrated to existing OCT devices to improve the diagnosis and prognosis of ocular pathologies.
Tan Hung Pham, Sripad Krishna Devalla, Aloysius Ang et al.
Accurate isolation and quantification of intraocular dimensions in the anterior segment (AS) of the eye using optical coherence tomography (OCT) images is important in the diagnosis and treatment of many eye diseases, especially angle closure glaucoma. In this study, we developed a deep convolutional neural network (DCNN) for the localization of the scleral spur, and the segmentation of anterior segment structures (iris, corneo-sclera shell, anterior chamber). With limited training data, the DCNN was able to detect the scleral spur on unseen ASOCT images as accurately as an experienced ophthalmologist; and simultaneously isolated the anterior segment structures with a Dice coefficient of 95.7%. We then automatically extracted eight clinically relevant ASOCT parameters and proposed an automated quality check process that asserts the reliability of these parameters. When combined with an OCT machine capable of imaging multiple radial sections, the algorithms can provide a more complete objective assessment. This is an essential step toward providing a robust automated framework for reliable quantification of ASOCT scans, for applications in the diagnosis and management of angle closure glaucoma.
Sripad Krishna Devalla, Giridhar Subramanian, Tan Hung Pham et al.
Purpose: To develop a deep learning approach to de-noise optical coherence tomography (OCT) B-scans of the optic nerve head (ONH). Methods: Volume scans consisting of 97 horizontal B-scans were acquired through the center of the ONH using a commercial OCT device (Spectralis) for both eyes of 20 subjects. For each eye, single-frame (without signal averaging), and multi-frame (75x signal averaging) volume scans were obtained. A custom deep learning network was then designed and trained with 2,328 "clean B-scans" (multi-frame B-scans), and their corresponding "noisy B-scans" (clean B-scans + gaussian noise) to de-noise the single-frame B-scans. The performance of the de-noising algorithm was assessed qualitatively, and quantitatively on 1,552 B-scans using the signal to noise ratio (SNR), contrast to noise ratio (CNR), and mean structural similarity index metrics (MSSIM). Results: The proposed algorithm successfully denoised unseen single-frame OCT B-scans. The denoised B-scans were qualitatively similar to their corresponding multi-frame B-scans, with enhanced visibility of the ONH tissues. The mean SNR increased from $4.02 \pm 0.68$ dB (single-frame) to $8.14 \pm 1.03$ dB (denoised). For all the ONH tissues, the mean CNR increased from $3.50 \pm 0.56$ (single-frame) to $7.63 \pm 1.81$ (denoised). The MSSIM increased from $0.13 \pm 0.02$ (single frame) to $0.65 \pm 0.03$ (denoised) when compared with the corresponding multi-frame B-scans. Conclusions: Our deep learning algorithm can denoise a single-frame OCT B-scan of the ONH in under 20 ms, thus offering a framework to obtain superior quality OCT B-scans with reduced scanning times and minimal patient discomfort.
Sripad Krishna Devalla, Prajwal K. Renukanand, Bharathwaj K. Sreedhar et al.
Given that the neural and connective tissues of the optic nerve head (ONH) exhibit complex morphological changes with the development and progression of glaucoma, their simultaneous isolation from optical coherence tomography (OCT) images may be of great interest for the clinical diagnosis and management of this pathology. A deep learning algorithm was designed and trained to digitally stain (i.e. highlight) 6 ONH tissue layers by capturing both the local (tissue texture) and contextual information (spatial arrangement of tissues). The overall dice coefficient (mean of all tissues) was $0.91 \pm 0.05$ when assessed against manual segmentations performed by an expert observer. We offer here a robust segmentation framework that could be extended for the automated parametric study of the ONH tissues.
Sripad Krishna Devalla, Jean-Martial Mari, Tin A. Tun et al.
Purpose: To develop a deep learning approach to digitally-stain optical coherence tomography (OCT) images of the optic nerve head (ONH). Methods: A horizontal B-scan was acquired through the center of the ONH using OCT (Spectralis) for 1 eye of each of 100 subjects (40 normal & 60 glaucoma). All images were enhanced using adaptive compensation. A custom deep learning network was then designed and trained with the compensated images to digitally stain (i.e. highlight) 6 tissue layers of the ONH. The accuracy of our algorithm was assessed (against manual segmentations) using the Dice coefficient, sensitivity, and specificity. We further studied how compensation and the number of training images affected the performance of our algorithm. Results: For images it had not yet assessed, our algorithm was able to digitally stain the retinal nerve fiber layer + prelamina, the retinal pigment epithelium, all other retinal layers, the choroid, and the peripapillary sclera and lamina cribrosa. For all tissues, the mean dice coefficient was $0.84 \pm 0.03$, the mean sensitivity $0.92 \pm 0.03$, and the mean specificity $0.99 \pm 0.00$. Our algorithm performed significantly better when compensated images were used for training. Increasing the number of images (from 10 to 40) to train our algorithm did not significantly improve performance, except for the RPE. Conclusion. Our deep learning algorithm can simultaneously stain neural and connective tissues in ONH images. Our approach offers a framework to automatically measure multiple key structural parameters of the ONH that may be critical to improve glaucoma management.