An objective structural and functional reference standard in glaucoma.

The current lack of consensus for diagnosing glaucoma makes it difficult to develop diagnostic tests derived from deep learning (DL) algorithms. In the present study, we propose an objective definition of glaucomatous optic neuropathy (GON) using clearly defined parameters from optical coherence tomography and standard automated perimetry. We then use the proposed objective definition as reference standard to develop a DL algorithm to detect GON on fundus photos. A DL algorithm was trained to detect GON on fundus photos, using the proposed objective definition as reference standard. The performance was evaluated on an independent test sample with sensitivity, specificity, area under the receiver operating characteristic curve (AUC), and likelihood ratios (LR). The test sample had 2118 fundus photos from 585 eyes of 405 individuals. The AUC to discriminate between GON and normal was 0.92 with sensitivity of 77% at 95% specificity. LRs indicated that the DL algorithm provided large changes in the post-test probability of disease for the majority of eyes. A DL algorithm to evaluate fundus photos had high performance to discriminate GON from normal. The newly proposed objective definition of GON used as reference standard may increase the comparability of diagnostic studies of glaucoma across devices and populations.