Felipe A. Medeiros

Samuel I. Berchuck, Felipe A. Medeiros, Sayan Mukherjee

As big spatial data becomes increasingly prevalent, classical spatiotemporal (ST) methods often do not scale well. While methods have been developed to account for high-dimensional spatial objects, the setting where there are exceedingly large samples of spatial observations has had less attention. The variational autoencoder (VAE), an unsupervised generative model based on deep learning and approximate Bayesian inference, fills this void using a latent variable specification that is inferred jointly across the large number of samples. In this manuscript, we compare the performance of the VAE with a more classical ST method when analyzing longitudinal visual fields from a large cohort of patients in a prospective glaucoma study. Through simulation and a case study, we demonstrate that the VAE is a scalable method for analyzing ST data, when the goal is to obtain accurate predictions. R code to implement the VAE can be found on GitHub: https://github.com/berchuck/vaeST.

Sayan Mandal, Alessandro A. Jammal, Felipe A. Medeiros

One of the leading causes of blindness is glaucoma, which is challenging to detect since it remains asymptomatic until the symptoms are severe. Thus, diagnosis is usually possible until the markers are easy to identify, i.e., the damage has already occurred. Early identification of glaucoma is generally made based on functional, structural, and clinical assessments. However, due to the nature of the disease, researchers still debate which markers qualify as a consistent glaucoma metric. Deep learning methods have partially solved this dilemma by bypassing the marker identification stage and analyzing high-level information directly to classify the data. Although favorable, these methods make expert analysis difficult as they provide no insight into the model discrimination process. In this paper, we overcome this using deep generative networks, a deep learning model that learns complicated, high-dimensional probability distributions. We train a Deep Feature consistent Variational Autoencoder (DFC-VAE) to reconstruct optic disc images. We show that a small-sized latent space obtained from the DFC-VAE can learn the high-dimensional glaucoma data distribution and provide discriminatory evidence between normal and glaucoma eyes. Latent representations of size as low as 128 from our model got a 0.885 area under the receiver operating characteristic curve when trained with Support Vector Classifier.

Shounak Datta, Eduardo B. Mariottoni, David Dov et al.

Glaucoma is the leading cause of irreversible blindness in the world, affecting over 70 million people. The cumbersome Standard Automated Perimetry (SAP) test is most frequently used to detect visual loss due to glaucoma. Due to the SAP test's innate difficulty and its high test-retest variability, we propose the RetiNerveNet, a deep convolutional recursive neural network for obtaining estimates of the SAP visual field. RetiNerveNet uses information from the more objective Spectral-Domain Optical Coherence Tomography (SDOCT). RetiNerveNet attempts to trace-back the arcuate convergence of the retinal nerve fibers, starting from the Retinal Nerve Fiber Layer (RNFL) thickness around the optic disc, to estimate individual age-corrected 24-2 SAP values. Recursive passes through the proposed network sequentially yield estimates of the visual locations progressively farther from the optic disc. While all the methods used for our experiments exhibit lower performance for the advanced disease group, the proposed network is observed to be more accurate than all the baselines for estimating the individual visual field values. We further augment RetiNerveNet to additionally predict the SAP Mean Deviation values and also create an ensemble of RetiNerveNets that further improves the performance, by increasingly weighting-up underrepresented parts of the training data.

Sonia Phene, R. Carter Dunn, Naama Hammel et al.

Glaucoma is the leading cause of preventable, irreversible blindness world-wide. The disease can remain asymptomatic until severe, and an estimated 50%-90% of people with glaucoma remain undiagnosed. Glaucoma screening is recommended for early detection and treatment. A cost-effective tool to detect glaucoma could expand screening access to a much larger patient population, but such a tool is currently unavailable. We trained a deep learning algorithm using a retrospective dataset of 86,618 images, assessed for glaucomatous optic nerve head features and referable glaucomatous optic neuropathy (GON). The algorithm was validated using 3 datasets. For referable GON, the algorithm had an AUC of 0.945 (95% CI, 0.929-0.960) in dataset A (1205 images, 1 image/patient; 18.1% referable), images adjudicated by panels of Glaucoma Specialists (GSs); 0.855 (95% CI, 0.841-0.870) in dataset B (9642 images, 1 image/patient; 9.2% referable), images from Atlanta Veterans Affairs Eye Clinic diabetic teleretinal screening program; and 0.881 (95% CI, 0.838-0.918) in dataset C (346 images, 1 image/patient; 81.7% referable), images from Dr. Shroff's Charity Eye Hospital's glaucoma clinic. The algorithm showed significantly higher sensitivity than 7 of 10 graders not involved in determining the reference standard, including 2 of 3 GSs, and showed higher specificity than 3 graders, while remaining comparable to others. For both GSs and the algorithm, the most crucial features related to referable GON were: presence of vertical cup-to-disc ratio of 0.7 or more, neuroretinal rim notching, retinal nerve fiber layer defect, and bared circumlinear vessels. An algorithm trained on fundus images alone can detect referable GON with higher sensitivity than and comparable specificity to eye care providers. The algorithm maintained good performance on an independent dataset with diagnoses based on a full glaucoma workup.

Felipe A. Medeiros, Alessandro A. Jammal, Atalie C. Thompson

Previous approaches using deep learning algorithms to classify glaucomatous damage on fundus photographs have been limited by the requirement for human labeling of a reference training set. We propose a new approach using spectral-domain optical coherence tomography (SDOCT) data to train a deep learning algorithm to quantify glaucomatous structural damage on optic disc photographs. The dataset included 32,820 pairs of optic disc photos and SDOCT retinal nerve fiber layer (RNFL) scans from 2,312 eyes of 1,198 subjects. A deep learning convolutional neural network was trained to assess optic disc photographs and predict SDOCT average RNFL thickness. The performance of the algorithm was evaluated in an independent test sample. The mean prediction of average RNFL thickness from all 6,292 optic disc photos in the test set was 83.3$\pm$14.5 $μ$m, whereas the mean average RNFL thickness from all corresponding SDOCT scans was 82.5$\pm$16.8 $μ$m (P = 0.164). There was a very strong correlation between predicted and observed RNFL thickness values (r = 0.832; P<0.001), with mean absolute error of the predictions of 7.39 $μ$m. The areas under the receiver operating characteristic curves for discriminating glaucoma from healthy eyes with the deep learning predictions and actual SDOCT measurements were 0.944 (95$\%$ CI: 0.912- 0.966) and 0.940 (95$\%$ CI: 0.902 - 0.966), respectively (P = 0.724). In conclusion, we introduced a novel deep learning approach to assess optic disc photographs and provide quantitative information about the amount of neural damage. This approach could potentially be used to diagnose and stage glaucomatous damage from optic disc photographs.