Impact of Optic Nerve Tortuosity, Globe Proptosis, and Size on Retinal Ganglion Cell Thickness Across General, Glaucoma, and Myopic Populations.

Purpose: The purpose of this study was to investigate the impact of optic nerve tortuosity (ONT), and the interaction of globe proptosis and size on retinal ganglion cell (RGC) thickness, using retinal nerve fiber layer (RNFL) thickness, across general, glaucoma, and myopic populations. Methods: This study analyzed 17,940 eyes from the UKBiobank cohort (ID 76442), including 72 glaucomatous and 2475 myopic eyes. Artificial intelligence models were developed to derive RNFL thickness corrected for ocular magnification from 3D optical coherence tomography scans and orbit features from 3D magnetic resonance images, including ONT, globe proptosis, axial length, and a novel feature: the interzygomatic line-to-posterior pole (ILPP) distance - a composite marker of globe proptosis and size. Generalized estimating equation (GEE) models evaluated associations between orbital and retinal features. Results: RNFL thickness was positively correlated with ONT and ILPP distance (r = 0.065, P < 0.001 and r = 0.206, P < 0.001, respectively) in the general population. The same was true for glaucoma (r = 0.040, P = 0.74 and r = 0.224, P = 0.059), and for myopia (r = 0.069, P < 0.001 and r = 0.100, P < 0.001). GEE models revealed that straighter optic nerves and shorter ILPP distance were predictive of thinner RNFL in all populations. Conclusions: Straighter optic nerves and decreased ILPP distance could cause RNFL thinning, possibly due to greater traction forces. ILPP distance emerged as a potential biomarker of axonal health. These findings underscore the importance of orbit structures in RGC axonal health and warrant further research into orbit biomechanics.