Are Macula or Optic Nerve Head Structures Better at Diagnosing Glaucoma? An Answer Using Artificial Intelligence and Wide-Field Optical Coherence Tomography.

Purpose: We wanted to develop a deep-learning algorithm to automatically segment optic nerve head (ONH) and macula structures in three-dimensional (3D) wide-field optical coherence tomography (OCT) scans and to assess whether 3D ONH or macula structures (or a combination of both) provide the best diagnostic power for glaucoma. Methods: A cross-sectional comparative study was performed using 319 OCT scans of glaucoma eyes and 298 scans of nonglaucoma eyes. Scans were compensated to improve deep-tissue visibility. We developed a deep-learning algorithm to automatically label major tissue structures, trained with 270 manually annotated B-scans. The performance was assessed using the Dice coefficient (DC). A glaucoma classification algorithm (3D-CNN) was then designed using 500 OCT volumes and corresponding automatically segmented labels. This algorithm was trained and tested on three datasets: cropped scans of macular tissues, those of ONH tissues, and wide-field scans. The classification performance for each dataset was reported using the area under the curve (AUC). Results: Our segmentation algorithm achieved a DC of 0.94 ± 0.003. The classification algorithm was best able to diagnose glaucoma using wide-field scans, followed by ONH scans, and finally macula scans, with AUCs of 0.99 ± 0.01, 0.93 ± 0.06 and 0.91 ± 0.11, respectively. Conclusions: This study showed that wide-field OCT may allow for significantly improved glaucoma diagnosis over typical OCTs of the ONH or macula. Translational Relevance: This could lead to mainstream clinical adoption of 3D wide-field OCT scan technology.

AI-based clinical assessment of optic nerve head robustness superseding biomechanical testing.

BACKGROUND/AIMS: 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 (ie, sensitivity of the ONH to changes in intraocular pressure (IOP)) from a single optical coherence tomography (OCT) volume scan of the ONH without the need for biomechanical testing and (3) identify what critical three-dimensional (3D) structural features dictate ONH robustness. METHODS: 316 subjects had their ONHs imaged with OCT before and after acute IOP elevation through ophthalmo-dynamometry. IOP-induced lamina cribrosa (LC) deformations were then mapped in 3D and used to classify ONHs. Those with an average effective LC strain superior to 4% were considered fragile, while those with a strain 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 convolutional neural network (DGCNN). The latter algorithm also allowed us to identify what critical 3D structural features make a given ONH robust. RESULTS: All three methods were able to predict ONH robustness from a single OCT volume scan alone and without the need to perform biomechanical testing. The DGCNN (area under the curve (AUC): 0.76±0.08) outperformed the autoencoder (AUC: 0.72±0.09) and the random forest classifier (AUC: 0.69±0.05). Interestingly, to assess ONH robustness, the DGCNN mainly used information from the scleral canal and the LC insertion sites. CONCLUSIONS: We propose an AI-driven approach that can assess the robustness of a given ONH solely from a single OCT volume 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. PRECIS: Using geometric deep learning, we can assess optic nerve head robustness (ie, sensitivity to a change in IOP) from a standard OCT scan that might help to identify fast visual field loss progressors.

Three-Dimensional Structural Phenotype of the Optic Nerve Head as a Function of Glaucoma Severity.

Importance: The 3-dimensional (3-D) structural phenotype of glaucoma as a function of severity was thoroughly described and analyzed, enhancing understanding of its intricate pathology beyond current clinical knowledge. Objective: To describe the 3-D structural differences in both connective and neural tissues of the optic nerve head (ONH) between different glaucoma stages using traditional and artificial intelligence-driven approaches. Design, Setting, and Participants: This cross-sectional, clinic-based study recruited 541 Chinese individuals receiving standard clinical care at Singapore National Eye Centre, Singapore, and 112 White participants of a prospective observational study at Vilnius University Hospital Santaros Klinikos, Vilnius, Lithuania. The study was conducted from May 2022 to January 2023. All participants had their ONH imaged using spectral-domain optical coherence tomography and had their visual field assessed by standard automated perimetry. Main Outcomes and Measures: (1) Clinician-defined 3-D structural parameters of the ONH and (2) 3-D structural landmarks identified by geometric deep learning that differentiated ONHs among 4 groups: no glaucoma, mild glaucoma (mean deviation [MD], ≥-6.00 dB), moderate glaucoma (MD, -6.01 to -12.00 dB), and advanced glaucoma (MD, <-12.00 dB). Results: Study participants included 213 individuals without glaucoma (mean age, 63.4 years; 95% CI, 62.5-64.3 years; 126 females [59.2%]; 213 Chinese [100%] and 0 White individuals), 204 with mild glaucoma (mean age, 66.9 years; 95% CI, 66.0-67.8 years; 91 females [44.6%]; 178 Chinese [87.3%] and 26 White [12.7%] individuals), 118 with moderate glaucoma (mean age, 68.1 years; 95% CI, 66.8-69.4 years; 49 females [41.5%]; 97 Chinese [82.2%] and 21 White [17.8%] individuals), and 118 with advanced glaucoma (mean age, 68.5 years; 95% CI, 67.1-69.9 years; 43 females [36.4%]; 53 Chinese [44.9%] and 65 White [55.1%] individuals). The majority of ONH structural differences occurred in the early glaucoma stage, followed by a plateau effect in the later stages. Using a deep neural network, 3-D ONH structural differences were found to be present in both neural and connective tissues. Specifically, a mean of 57.4% (95% CI, 54.9%-59.9%, for no to mild glaucoma), 38.7% (95% CI, 36.9%-40.5%, for mild to moderate glaucoma), and 53.1 (95% CI, 50.8%-55.4%, for moderate to advanced glaucoma) of ONH landmarks that showed major structural differences were located in neural tissues with the remaining located in connective tissues. Conclusions and Relevance: This study uncovered complex 3-D structural differences of the ONH in both neural and connective tissues as a function of glaucoma severity. Future longitudinal studies should seek to establish a connection between specific 3-D ONH structural changes and fast visual field deterioration and aim to improve the early detection of patients with rapid visual field loss in routine clinical care.

Medical Application of Geometric Deep Learning for the Diagnosis of Glaucoma.

Purpose: (1) To assess the performance of geometric deep learning in diagnosing glaucoma from a single optical coherence tomography (OCT) scan of the optic nerve head and (2) to compare its performance to that obtained with a three-dimensional (3D) convolutional neural network (CNN), and with a gold-standard parameter, namely, the retinal nerve fiber layer (RNFL) thickness. Methods: Scans of the optic nerve head were acquired with OCT for 477 glaucoma and 2296 nonglaucoma subjects. All volumes were automatically segmented using deep learning to identify seven major neural and connective tissues. Each optic nerve head was then represented as a 3D point cloud with approximately 1000 points. Geometric deep learning (PointNet) was then used to provide a glaucoma diagnosis from a single 3D point cloud. The performance of our approach (reported using the area under the curve [AUC]) was compared with that obtained with a 3D CNN, and with the RNFL thickness. Results: PointNet was able to provide a robust glaucoma diagnosis solely from a 3D point cloud (AUC = 0.95 ± 0.01).The performance of PointNet was superior to that obtained with a 3D CNN (AUC = 0.87 ± 0.02 [raw OCT images] and 0.91 ± 0.02 [segmented OCT images]) and with that obtained from RNFL thickness alone (AUC = 0.80 ± 0.03). Conclusions: We provide a proof of principle for the application of geometric deep learning in 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. Translational Relevance: Geometric deep learning may help us to improve and simplify diagnosis and prognosis applications in glaucoma.

A decision-support tool for funding health innovations at a tertiary academic medical center.

OBJECTIVES: To report the processes used to design and implement an assessment tool to inform funding decisions for competing health innovations in a tertiary hospital. METHODS: We designed an assessment tool for health innovation proposals with three components: "value to the institution," "novelty," and "potential for adoption and scaling." The "value to the institution" component consisted of twelve weighted value attributes identified from the host institution's annual report; weights were allocated based on a survey of the hospital's leaders. The second and third components consisted of open-ended questions on "novelty" and "barriers to implementation" to support further dialogue. Purposive literature review was performed independently by two researchers for each assessment. The assessment tool was piloted during an institutional health innovation funding cycle. RESULTS: We used 17 days to evaluate ten proposals. The completed assessments were shared with an independent group of panellists, who selected five projects for funding. Proposals with the lowest scores for "value to the institution" had less perceived impact on the patient-related value attributes of "access," "patient centeredness," "health outcomes," "prevention," and "safety." Similar innovations were reported in literature in seven proposals; potential barriers to implementation were identified in six proposals. We included a worked example to illustrate the assessment process. CONCLUSIONS: We developed an assessment tool that is aligned with local institutional priorities. Our tool can augment the decision-making process when funding health innovation projects. The tool can be adapted by others facing similar challenges of trying to choose the best health innovations to fund.

Geometric Deep Learning to Identify the Critical 3D Structural Features of the Optic Nerve Head for Glaucoma Diagnosis.

PURPOSE: To compare the performance of 2 relatively recent geometric deep learning techniques in diagnosing glaucoma from a single optical coherence tomographic (OCT) scan of the optic nerve head (ONH); and to identify the 3-dimensional (3D) structural features of the ONH that are critical for the diagnosis of glaucoma. DESIGN: Comparison and evaluation of deep learning diagnostic algorithms. METHODS: In this study, we included a total of 2247 nonglaucoma and 2259 glaucoma scans from 1725 participants. All participants 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 (area under the curve [AUC]: 0.97±0.01) and PointNet (AUC: 0.95±0.02) were able to accurately detect glaucoma from 3D ONH point clouds. The critical points (ie, critical structural features of the ONH) formed an hourglass pattern, with most of them located within the neuroretinal rim in the inferior and superior quadrant of the ONH. CONCLUSIONS: 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.

Discriminating Between Papilledema and Optic Disc Drusen Using 3D Structural Analysis of the Optic Nerve Head.

BACKGROUND AND OBJECTIVES: The distinction of papilledema from other optic nerve head (ONH) lesions mimicking papilledema, such as optic disc drusen (ODD), can be difficult in clinical practice. We aimed the following: (1) to develop a deep learning algorithm to automatically identify major structures of the ONH in 3-dimensional (3D) optical coherence tomography (OCT) scans and (2) to exploit such information to robustly differentiate among ODD, papilledema, and healthy ONHs. METHODS: This was a cross-sectional comparative study of patients from 3 sites (Singapore, Denmark, and Australia) with confirmed ODD, those with papilledema due to raised intracranial pressure, and healthy controls. Raster scans of the ONH were acquired using OCT imaging and then processed to improve deep-tissue visibility. First, a deep learning algorithm was developed to identify major ONH tissues and ODD regions. The performance of our algorithm was assessed using the Dice coefficient. Second, a classification algorithm (random forest) was designed to perform 3-class classifications (1: ODD, 2: papilledema, and 3: healthy ONHs) strictly from their drusen and prelamina swelling scores (calculated from the segmentations). To assess performance, we reported the area under the receiver operating characteristic curve for each class. RESULTS: A total of 241 patients (256 imaged ONHs, including 105 ODD, 51 papilledema, and 100 healthy ONHs) were retrospectively included in this study. Using OCT images of the ONH, our segmentation algorithm was able to isolate neural and connective tissues and ODD regions/conglomerates whenever present. This was confirmed by an averaged Dice coefficient of 0.93 ± 0.03 on the test set, corresponding to good segmentation performance. Classification was achieved with high AUCs, that is, 0.99 ± 0.001 for the detection of ODD, 0.99 ± 0.005 for the detection of papilledema, and 0.98 ± 0.01 for the detection of healthy ONHs. DISCUSSION: Our artificial intelligence approach can discriminate ODD from papilledema, strictly using a single OCT scan of the ONH. Our classification performance was very good in the studied population, with the caveat that validation in a much larger population is warranted. Our approach may have the potential to establish OCT imaging as one of the mainstays of diagnostic imaging for ONH disorders in neuro-ophthalmology, in addition to fundus photography.

The three-dimensional structural configuration of the central retinal vessel trunk and branches as a glaucoma biomarker.

PURPOSE: To assess whether the 3-dimensional (3D) structural configuration of the central retinal vessel trunk and its branches (CRVT&B) could be used as a diagnostic marker for glaucoma. DESIGN: Retrospective, deep-learning approach diagnosis study. METHODS: 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. Subsequently, 2 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 convolutional neural networks and the 3D structure of the CRVT&B. For the second approach, we projected the 3D structure of the CRVT&B orthographically onto sagittal, frontal, and transverse planes to obtain 3 two-dimensional (2D) images, and then a 2D convolutional neural network 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 (AUCs). The diagnostic performance of the CRVT&B was also compared with that of retinal nerve fiber layer (RNFL) thickness (calculated in the same cohorts). 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 ± 0.07. The 3D and 2D diagnostic networks were able to differentiate glaucoma from nonglaucoma subjects with accuracies of 82.7% and 83.3%, respectively. The corresponding AUCs for the CRVT&B were 0.89 and 0.90, higher than those obtained with RNFL thickness alone (AUCs ranging from 0.74 to 0.80). CONCLUSIONS: Our work demonstrated that the diagnostic power of the CRVT&B is superior to that of a gold-standard glaucoma parameter, that is, RNFL thickness. Our work also suggested that the major retinal blood vessels form a "skeleton"-the configuration of which may be representative of major optic nerve head structural changes as typically observed with the development and progression of glaucoma.

Describing the Structural Phenotype of the Glaucomatous Optic Nerve Head Using Artificial Intelligence.

PURPOSE: To develop a novel deep-learning approach that can describe the structural phenotype of the glaucomatous optic nerve head (ONH) and can be used as a robust glaucoma diagnosis tool. DESIGN: Retrospective, deep-learning approach diagnosis study. METHOD: We trained a deep-learning network to segment 3 neural-tissue and 4 connective-tissue layers of the ONH. The segmented optical coherence tomography images were then processed by a customized autoencoder network with an additional parallel branch for binary classification. The encoder part of the autoencoder reduced the segmented optical coherence tomography images into a low-dimensional latent space (LS), whereas the decoder and the classification branches reconstructed the images and classified them as glaucoma or nonglaucoma, respectively. We performed principal component analysis on the latent parameters and identified the principal components (PCs). Subsequently, the magnitude of each PC was altered in steps and reported how it impacted the morphology of the ONH. RESULTS: The image reconstruction quality and diagnostic accuracy increased with the size of the LS. With 54 parameters in the LS, the diagnostic accuracy was 92.0 ± 2.3% with a sensitivity of 90.0 ± 2.4% (at 95% specificity), and the corresponding Dice coefficient for the reconstructed images was 0.86 ± 0.04. By changing the magnitudes of PC in steps, we were able to reveal how the morphology of the ONH changes as one transitions from a "nonglaucoma" to a "glaucoma" condition. CONCLUSIONS: Our network was able to identify novel biomarkers of the ONH for glaucoma diagnosis. Specifically, the structural features identified by our algorithm were found to be related to clinical observations of glaucoma.

OCT-GAN: single step shadow and noise removal from optical coherence tomography images of the human optic nerve head.

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 ± 0.133 to 0.142 ± 0.102, 0.449 ± 0.116 to 0.0904 ± 0.0769, 0.381 ± 0.100 to 0.0590 ± 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.

Deep learning algorithms to isolate and quantify the structures of the anterior segment in optical coherence tomography images.

BACKGROUND/AIMS: 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. METHOD: In this study, we developed a deep convolutional neural network (DCNN) for the localisation of the scleral spur; moreover, we introduced an information-rich segmentation approach for this localisation problem. An ensemble of DCNNs for the segmentation of AS structures (iris, corneosclera shell adn anterior chamber) was developed. Based on the results of two previous processes, an algorithm to automatically quantify clinically important measurements were created. 200 images from 58 patients (100 eyes) were used for testing. RESULTS: With limited training data, the DCNN was able to detect the scleral spur on unseen anterior segment optical coherence tomography (ASOCT) images as accurately as an experienced ophthalmologist on the given test dataset and simultaneously isolated the AS structures with a Dice coefficient of 95.7%. We then automatically extracted eight clinically relevant ASOCT measurements and proposed an automated quality check process that asserts the reliability of these measurements. When combined with an OCT machine capable of imaging multiple radial sections, the algorithms can provide a more complete objective assessment. The total segmentation and measurement time for a single scan is less than 2 s. CONCLUSION: This is an essential step towards providing a robust automated framework for reliable quantification of ASOCT scans, for applications in the diagnosis and management of angle-closure glaucoma.

Towards label-free 3D segmentation of optical coherence tomography images of the optic nerve head using deep learning.

Recently proposed deep learning (DL) algorithms for the segmentation of optical coherence tomography (OCT) images to quantify the morphological changes to the optic nerve head (ONH) tissues during glaucoma have limited clinical adoption due to their device specific nature and the difficulty in preparing manual segmentations (training data). We propose a DL-based 3D segmentation framework that is easily translatable across OCT devices in a label-free manner (i.e. without the need to manually re-segment data for each device). Specifically, we developed 2 sets of DL networks: the 'enhancer' (enhance OCT image quality and harmonize image characteristics from 3 devices) and the 'ONH-Net' (3D segmentation of 6 ONH tissues). We found that only when the 'enhancer' was used to preprocess the OCT images, the 'ONH-Net' trained on any of the 3 devices successfully segmented ONH tissues from the other two unseen devices with high performance (Dice coefficients > 0.92). We demonstrate that is possible to automatically segment OCT images from new devices without ever needing manual segmentation data from them.

Glaucoma management in the era of artificial intelligence.

Glaucoma is a result of irreversible damage to the retinal ganglion cells. While an early intervention could minimise the risk of vision loss in glaucoma, its asymptomatic nature makes it difficult to diagnose until a late stage. The diagnosis of glaucoma is a complicated and expensive effort that is heavily dependent on the experience and expertise of a clinician. The application of artificial intelligence (AI) algorithms in ophthalmology has improved our understanding of many retinal, macular, choroidal and corneal pathologies. With the advent of deep learning, a number of tools for the classification, segmentation and enhancement of ocular images have been developed. Over the years, several AI techniques have been proposed to help detect glaucoma by analysis of functional and/or structural evaluations of the eye. Moreover, the use of AI has also been explored to improve the reliability of ascribing disease prognosis. This review summarises the role of AI in the diagnosis and prognosis of glaucoma, discusses the advantages and challenges of using AI systems in clinics and predicts likely areas of future progress.

A Deep Learning Approach to Denoise Optical Coherence Tomography Images of the Optic Nerve Head.

Optical coherence tomography (OCT) has become an established clinical routine for the in vivo imaging of the optic nerve head (ONH) tissues, that is crucial in the diagnosis and management of various ocular and neuro-ocular pathologies. However, the presence of speckle noise affects the quality of OCT images and its interpretation. Although recent frame-averaging techniques have shown to enhance OCT image quality, they require longer scanning durations, resulting in patient discomfort. Using a custom deep learning network trained with 2,328 'clean B-scans' (multi-frame B-scans; signal averaged), and their corresponding 'noisy B-scans' (clean B-scans + Gaussian noise), we were able to successfully denoise 1,552 unseen single-frame (without signal averaging) 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 signal to noise ratio (SNR) increased from 4.02 ± 0.68 dB (single-frame) to 8.14 ± 1.03 dB (denoised). For all the ONH tissues, the mean contrast to noise ratio (CNR) increased from 3.50 ± 0.56 (single-frame) to 7.63 ± 1.81 (denoised). The mean structural similarity index (MSSIM) increased from 0.13 ± 0.02 (single frame) to 0.65 ± 0.03 (denoised) when compared with the corresponding multi-frame B-scans. 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.

DRUNET: a dilated-residual U-Net deep learning network to segment optic nerve head tissues in optical coherence tomography images.

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 (custom U-NET) was designed and trained to segment 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 ± 0.05 when assessed against manual segmentations performed by an expert observer. Further, we automatically extracted six clinically relevant neural and connective tissue structural parameters from the segmented tissues. We offer here a robust segmentation framework that could also be extended to the 3D segmentation of the ONH tissues.

A Deep Learning Approach to Digitally Stain Optical Coherence Tomography Images of the Optic Nerve Head.

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 one eye of each of 100 subjects (40 healthy and 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) six tissue layers of the ONH. The accuracy of our algorithm was assessed (against manual segmentations) using the dice coefficient, sensitivity, specificity, intersection over union (IU), and accuracy. We studied the effect of compensation, number of training images, and performance comparison between glaucoma and healthy subjects. Results: For images it had not yet assessed, our algorithm was able to digitally stain the retinal nerve fiber layer + prelamina, the RPE, all other retinal layers, the choroid, and the peripapillary sclera and lamina cribrosa. For all tissues, the dice coefficient, sensitivity, specificity, IU, and accuracy (mean) were 0.84 ± 0.03, 0.92 ± 0.03, 0.99 ± 0.00, 0.89 ± 0.03, and 0.94 ± 0.02, respectively. Our algorithm performed significantly better when compensated images were used for training (P < 0.001). Besides offering a good reliability, digital staining also performed well on OCT images of both glaucoma and healthy individuals. Conclusions: Our deep learning algorithm can simultaneously stain the neural and connective tissues of the ONH, offering a framework to automatically measure multiple key structural parameters of the ONH that may be critical to improve glaucoma management.