Impact of Optic Nerve Tortuosity, Globe Proptosis, and Size on Retinal Ganglion Cell Thickness Across General, Glaucoma, and Myopic Populations: Insights from the UK Biobank

TL;DR

This study investigates how optic nerve tortuosity, globe proptosis, and size influence retinal ganglion cell thickness across different populations using advanced imaging and AI, revealing biomechanical factors affecting retinal health.

Contribution

It introduces a novel ILPP metric combining globe size and position, and demonstrates the impact of orbital structures on retinal nerve fiber layer thickness across populations.

Findings

RNFL thickness correlates with ONT and ILPP distance.

Straighter optic nerves predict thinner RNFL.

ILPP metric shows potential as a biomarker for axonal health.

Abstract

Purpose: To investigate the impact of optic nerve tortuosity (ONT), and the interaction of globe proptosis and globe size on retinal ganglion cell (RGC) thickness, using Retinal Nerve Fiber Layer (RNFL) thickness, across general, glaucoma, and myopic populations. Methods: We analyzed 17,940 eyes from the UKBiobank cohort (ID 76442), including 72 glaucoma and 2475 myopic eyes. AI models segmented structures from 3D optical coherence tomography (OCT) scans and magnetic resonance images (MRI). RNFL thickness was derived from OCT scans and corrected for ocular magnification, was derived from OCT. From MRIs, we extracted: ONT, globe proptosis, axial length, and a novel interzygomatic line-to-posterior pole (ILPP) distance, a composite marker of globe proptosis and size. GEE models assessed associations between orbital and retinal features across all populations. Results: Segmentation models achieved Dice coefficients over 0.94 for both MRI and OCT. RNFL thickness was positively correlated with both ONT and ILPP distance (r = 0.065, p < 0.001, and r = 0.206, p < 0.001 respectively). 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 < 0.0001). GEE models revealed straighter optic nerves and shorter ILPP distance as predictive of thinner RNFL in all populations. Conclusions: This study emphasizes the impact of ONT, globe size, and proptosis on retinal health, suggesting RNFL thinning may arise from biomechanical stress due to straighter optic nerves or reduced ILPP distance, particularly in glaucoma or myopia. The novel ILPP metric, integrating globe size and position, shows potential as a biomarker for axonal health. These findings highlight the role of orbit structures in RGC axonal health and warrant further exploration of the biomechanical relationship between the orbit and optic nerve.