Neurodegenerative disorders are characterized by typical neuronal degeneration and axonal loss in the central nervous system (CNS). Demyelination occurs when myelin or oligodendrocytes experience damage. Pathological changes in demyelination contribute to neurodegenerative diseases and worsen clinical symptoms during disease progression. Glaucoma is a neurodegenerative disease characterized by progressive degeneration of retinal ganglion cells (RGCs) and the optic nerve. Since it is not yet well understood, we hypothesized that demyelination could play a significant role in glaucoma. Therefore, this study started with the morphological and functional manifestations of demyelination in the CNS. Then, we discussed the main mechanisms of demyelination in terms of oxidative stress, mitochondrial damage, and immuno-inflammatory responses. Finally, we summarized the existing research on the relationship between optic nerve demyelination and glaucoma, aiming to inspire effective treatment plans for glaucoma in the future.

Purpose: Circumpapillary retinal nerve fiber layer thickness (RNFLT) measurement aids in the clinical diagnosis of glaucoma. Spectral domain optical coherence tomography (SD-OCT) machines measure RNFLT and provide normative color-coded plots. In this retrospective study, we investigate whether normative percentiles of RNFLT (pRNFLT) from Spectralis SD-OCT improve prediction of glaucomatous visual field loss over raw RNFLT. Methods: A longitudinal database containing OCT scans and visual fields from Massachusetts Eye & Ear glaucoma clinic patients was generated. Reliable OCT-visual field pairs were selected. Spectralis OCT normative distributions were extracted from machine printouts. Supervised machine learning models compared predictive performance between pRNFLT and raw RNFLT inputs. Regional structure-function associations were assessed with univariate regression to predict mean deviation (MD). Multivariable classification predicted MD, pattern standard deviation, MD change per year, and glaucoma hemifield test. Results: There were 3016 OCT-visual field pairs that met the reliability criteria. Spectralis norms were found to be independent of age, sex, and ocular magnification. Regional analysis showed significant decrease in R² from pRNFLT models compared to raw RNFLT models in inferotemporal sectors, across multiple regressors. In multivariable classification, there were no significant improvements in area under the curve of receiver operating characteristic curve (ROC-AUC) score with pRNFLT models compared to raw RNFLT models. Conclusions: Our results challenge the assumption that normative percentiles from OCT machines improve prediction of glaucomatous visual field loss. Raw RNFLT alone shows strong prediction, with no models presenting improvement by the manufacturer norms. This may result from insufficient patient stratification in tested norms. Translational Relevance: Understanding correlation of normative databases to visual function may improve clinical interpretation of OCT data.

Background: This case–control study evaluated the concentrations of zinc (Zn), iron (Fe), and copper (Cu) in the aqueous humor (AH) of patients with primary glaucoma, and their relationships with clinical factors. Methods: This study enrolled 100 patients with primary glaucoma and categorized them into subtypes: acute angle-closure crisis (AACC), primary angle-closure glaucoma (PACG), and primary open-angle glaucoma (POAG). A total of 67 patients with senile cataract were enrolled as controls. Their AH samples and clinical information were obtained. Results: In primary glaucoma, Zn, Fe, and Cu concentrations increased, especially in AACC group; Zn, Fe, and Cu were positively correlated mutually; and decreased Zn/Fe and increased Fe/Cu were observed. The number of quadrants with closed anterior chamber angle on gonioscopy was positively associated with Fe and Cu levels in AACC and with Zn and Cu levels in PACG. In POAG, we found negative associations between Zn and the number of quadrants with retinal nerve fiber layer thinning on optical coherence tomography, Fe and age, and Cu and the cup-to-disc ratio. Trace metals showed high efficiency in discriminating primary glaucoma from controls. Conclusions: Zn, Fe, and Cu concentrations in patients with primary glaucoma increased and were associated with clinical factors, acting as potential biomarkers.