Progression or Aging? A Deep Learning Approach for Distinguishing Glaucoma Progression from Age-Related Changes in OCT scans

Purpose To develop deep learning (DL) algorithm to detect glaucoma progression using optical coherence tomography (OCT) images, in the absence of a reference standard. Design Retrospective cohort study. Methods Glaucomatous and healthy eyes with ≥5 reliable peripapillary OCT (Spectralis, Heidelberg Engineering) circle scans were included. A weakly supervised time-series learning model, called Noise Positive-Unlabeled (Noise-PU) DL was developed to classify whether sequences of OCT B-scans showed glaucoma progression. The model used two learning schemes, one to identify age-related changes by differentiating test sequences from glaucoma vs. healthy eyes, and the other to identify test-retest variability based on scrambled OCTs of glaucoma eyes. Both models' bases were convolutional neural networks (CNN) and long short-term memory (LSTM) networks which were combined to form a CNN-LSTM model. Model features were combined and jointly trained to identify glaucoma progression, accounting for age-related loss. The DL model's outcomes were compared with ordinary least squares (OLS) regression of retinal nerve fiber layer (RNFL) thickness over time, matched for specificity. The hit ratio was used as a proxy for sensitivity. Results 8,785 follow-up sequences of 5 consecutive OCT tests from 3253 eyes (1859 subjects) were included in the study. Mean follow-up time was 3.5±1.6 years. In the test sample, the hit ratios of the DL and OLS methods were 0.498 (95%CI:0.470—0.526) and 0.284 (95%CI:0.258—0.309) respectively (P<0.001) when the specificities were equalized to 95%. Conclusion A DL model was able to identify longitudinal glaucomatous structural changes in OCT B-scans using a surrogate reference standard for progression.