Exploring the Relationship between Glaucoma and Macular Ellipsoid Zone

Abstract

<strong>Purpose:</strong> This study aims to investigate whether the mitochondria-rich ellipsoid zone (EZ) in the outer retina is affected in glaucoma. <br/> <strong>Methods:</strong> We recruited two different types of glaucoma: primary open-angle glaucoma (POAG) and normal-tension glaucoma (NTG). According to the severity of visual field (VF) defects, patients were divided into the significantly affected group, early glaucoma group, and pre-perimetric glaucoma group for global comparison analysis. According to the characteristics of hemispheric visual field defects, patients were further divided into isolated superior hemisphere, isolated inferior hemisphere, both hemispheres defect groups for hemispheric comparison analysis. The primary outcome was relative EZ/ELM reflectivity (rEZR), defined as the ratio of the peak reflectivity of the EZ to that of the external limiting membrane (ELM). We used spectral-domain optical coherence tomography (SD-OCT). Each retinal imaging was performed using posterior pole asymmetry analysis, which consists of 241 B-scans. All scans were acquired with the automatic real-time (ART) function set to 15 frames to improve image quality. The scan covered a pattern size of 25° × 30°. We examined all automatically generated B-scan lines in each retinal image to determine whether there were segmentation errors. If segmentation errors were found, they were corrected manually. <br/> <strong>Results:</strong> In the global comparison analysis, glaucoma, including POAG and NTG, tended to show lower rEZR compared with controls. Even in glaucoma with visual field damage, which represents functional impairment, including both POAG and NTG, lower rEZR was also observed; however, no statistically significant associations between glaucoma and rEZR were found. In the hemispheric comparison analysis, we first compared the retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) between affected and non-affected hemispheres. Both RNFL and GCL showed statistically significant differences between affected and non-affected hemispheres. However, the associations between rEZR and affected hemispheres were not significant. <br/> <strong>Conclusions:</strong> This study found no significant reduction in EZ reflectivity on SD-OCT in either POAG or NTG patients, even in retinal regions with marked thinning of the RNFL and GCL. These findings suggest that photoreceptor mitochondria may remain structurally intact despite glaucomatous damage to inner retinal layers. It is possible that glaucoma exerts minimal influence on photoreceptor mitochondria, or that current imaging techniques lack the sensitivity to detect subtle mitochondrial alterations over the course of disease progression. This work establishes an imaging-based framework for future studies of mitochondrial biomarkers in glaucoma.