3D Structural Phenotype of the Optic Nerve Head at the Intersection of Glaucoma and Myopia - A Key to Improving Glaucoma Diagnosis in Myopic Populations

Purpose: To characterize the 3D structural phenotypes of the optic nerve head (ONH) in patients with glaucoma, high myopia, and concurrent high myopia and glaucoma, and to evaluate their variations across these conditions. Participants: A total of 685 optical coherence tomography (OCT) scans from 754 subjects of Singapore-Chinese ethnicity, including 256 healthy (H), 94 highly myopic (HM), 227 glaucomatous (G), and 108 highly myopic with glaucoma (HMG) cases. Methods: We segmented the retinal and connective tissues from OCT volumes and their boundary edges were converted into 3D point clouds. To classify the 3D point clouds into four ONH conditions, i.e., H, HM, G, and HMG, a specialized ensemble network was developed, consisting of an encoder to transform high-dimensional input data into a compressed latent vector, a decoder to reconstruct point clouds from the latent vector, and a classifier to categorize the point clouds into the four ONH conditions. Results: The classification network achieved high accuracy, distinguishing H, HM, G, and HMG classes with a micro-average AUC of 0.92 $\pm$ 0.03 on an independent test set. The decoder effectively reconstructed point clouds, achieving a Chamfer loss of 0.013 $\pm$ 0.002. Dimensionality reduction clustered ONHs into four distinct groups, revealing structural variations such as changes in retinal and connective tissue thickness, tilting and stretching of the disc and scleral canal opening, and alterations in optic cup morphology, including shallow or deep excavation, across the four conditions. Conclusions: This study demonstrated that ONHs exhibit distinct structural signatures across H, HM, G, and HMG conditions. The findings further indicate that ONH morphology provides sufficient information for classification into distinct clusters, with principal components capturing unique structural patterns within each group.

The 3D Structural Phenotype of the Glaucomatous Optic Nerve Head and its Relationship with The Severity of Visual Field Damage

$\bf{Purpose}$: 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.