Association of Deep Optic Nerve Head Structural Remodeling with Choroidal Microvasculature Dropout in Glaucoma with and without Myopia

Introduction

Glaucoma remains a leading cause of irreversible blindness worldwide, characterized by progressive optic nerve damage. Recent research highlights the crucial role of vascular factors in its pathogenesis, particularly choroidal microvasculature dropout (MvD) – areas of capillary nonperfusion around the optic nerve head. This study investigates how structural alterations in deep optic nerve head (ONH) architecture relate to MvD development in glaucomatous eyes across varying myopia severities. Understanding these relationships could unlock new diagnostic and therapeutic approaches for this complex neurodegenerative disease.

Study Design and Methodology

This cross-sectional analysis involved 394 eyes from 262 patients with primary open-angle glaucoma or glaucoma suspect status. Participants underwent comprehensive ophthalmic evaluations including Spectralis OCT imaging aligned to the Foveal-Bruch’s Membrane Opening (FoBMO) axis. Eyes were stratified by axial length into three groups: non-myopic (AL<24mm, n=144), mild myopia (24mm≤AL<26mm, n=174), and high myopia (AL≥26mm, n=76). Researchers manually segmented Bruch's Membrane Opening (BMO) and anterior scleral canal opening (ASCO) landmarks to quantify: BMO/ASCO offset magnitude, neural canal obliqueness, and neural canal minimum cross-sectional area (NCMCA). MvD parameters (presence, area, angular circumference) were assessed using OCT-angiography en face choroidal images and B-scans.

Key Structural and Vascular Findings

Highly myopic eyes demonstrated significantly larger MvD areas (0.38 mm²) compared to mild myopia (0.33 mm²) and non-myopia (0.21 mm²). Angular circumference measurements followed similar patterns. Remarkably, high myopia eyes exhibited substantially different ONH architecture: enlarged BMO area, increased NCMCA ovality index, greater BMO/ASCO offset, elevated neural canal obliqueness, and reduced NCMCA. Multivariable analysis confirmed independent associations between deep ONH structural parameters and MvD metrics. Specifically: NCMCA dimensions, ovality index, BMO/ASCO offset magnitude, and neural canal obliqueness correlated significantly with both MvD presence and affected area. Additionally, NCMCA ovality and neural canal obliqueness independently predicted MvD angular circumference extension.

Clinical Implications and Pathophysiological Insights

Findings suggest mechanical forces in myopic eyes induce profound ONH structural reorganization, particularly elongation and tilting of the neural canal. This remodeling appears to trigger localized vascular compromise through multiple pathways: compression of posterior ciliary artery branches, altered choroidal perfusion pressure gradients, and biomechanical stress on microvasculature. The geometry of the neural canal (quantified through NCMCA ovality and obliqueness) emerged as a strong predictor of MvD configuration, potentially explaining why myopic glaucoma exhibits distinct patterns of visual field loss. These structural-vascular relationships persisted after adjusting for intraocular pressure, supporting microvascular dysfunction as an independent disease mechanism beyond pressure-induced damage.

Research Significance and Future Directions

This study provides novel evidence linking deep ONH architecture with choriocapillaris perfusion integrity. The simultaneous evaluation of structural and vascular parameters offers a comprehensive framework for understanding glaucoma pathogenesis in myopic eyes. Clinically, OCT-based assessment of neural canal geometry might help identify high-risk patients before irreversible visual field loss occurs. Future longitudinal studies should explore whether these structural parameters predict glaucoma progression rates. Additionally, investigations into whether reducing mechanical stress through targeted therapies could mitigate MvD development might offer new neuroprotective avenues for myopic glaucoma patients.

Conclusion

Deep ONH structural alterations, particularly neural canal geometry and orientation, significantly associate with choroidal microvascular dropout in glaucomatous eyes, with strongest manifestations in high myopia. These findings highlight the importance of integrated structural-vascular assessment in glaucoma management. Evaluating both domains may enhance early detection, risk stratification, and personalized treatment approaches, especially for myopic individuals facing elevated glaucoma risks. Future research should validate these associations longitudinally and explore therapeutic interventions targeting this newly identified structural-vascular axis.