Glaucoma is the leading cause of irreversible blindness, and its pathophysiology includes neuroinflammatory changes. The present therapies for glaucoma target pressure-lowering mechanisms with limited success, making neuroinflammation a target for future interventions. This review summarizes the neuroinflammatory pathways seen in glaucoma and their interplay with stress. Glucocorticoids have been shown to activate proinflammatory glial cells, contributing to the neuroinflammation in glaucoma. Glucocorticoids have also been shown to increase the IOP directly. Stress-associated autonomic dysfunction can affect the vascular homeostasis in the retina and create oxidative stress. Diabetes, hyperglycemic-mediated endothelial damage, and vascular inflammation also play important roles in the neuroinflammation in glaucoma and diabetic retinopathy. Psychosocial stress has been implicated in an increased IOP and glaucoma outcomes. People who experience maladaptive chronic stress suffer from a condition known as allostatic load, which describes pathologic neuroendocrine dysregulation. The effects of allostatic load and chronic stress have been studied in patients affected by a lower socioeconomic status (SES) and marginalized racial identities. A lower SES is associated with higher rates of glaucoma and also affects the access to care and screening. Additionally, people of African ancestry are disproportionately affected by glaucoma for reasons that are multifactorial. In conclusion, this review explores neuroinflammation in glaucoma, highlighting opportunities for future investigation.

Background/Aims: Primary open-angle glaucoma (POAG) disproportionately affects individuals of African ancestry. In these patients’ eyes, a large cup-to-disc ratio (LCDR > 0.90) suggests greater retinal ganglion cell loss, though these patients often display varied visual ability. This study investigated the prevalence and risk factors associated with LCDR in African ancestry individuals with POAG and explored the differences between blind (>20/200) and not blind (≤20/200) LCDR eyes. Methods: A case–control methodology was used to investigate the demographic, optic disc, and genetic risk factors of subjects in the Primary Open-Angle African American Glaucoma Genetics Study. Risk factors were analyzed using univariable and multivariable logistic regression models with inter-eye correlation adjusted using generalized estimating equations. Results: Out of 5605 eyes with POAG, 1440 eyes (25.7%) had LCDR. In the multivariable analysis, LCDR was associated with previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.04), decreased mean deviation (OR = 1.08), increased pattern standard deviation (OR = 1.06), thinner retinal nerve fiber layer (OR = 1.05), nasalization of vessels (OR = 2.67), bayonetting of vessels (OR = 1.98), visible pores in the lamina cribrosa (OR = 1.68), and a bean-shaped cup (OR = 2.11). Of LCDR eyes, 30.1% were classified as blind (≤20/200). In the multivariable analysis, the statistically significant risk factors of blindness in LCDR eyes were previous glaucoma surgery (OR = 1.72), increased intraocular pressure (OR = 1.05), decreased mean deviation (OR = 1.04), and decreased pattern standard deviation (OR = 0.90). Conclusions: These findings underscore the importance of close monitoring of intraocular pressure and visual function in African ancestry POAG patients, particularly those with LCDR, to preserve visual function.

Glaucoma is a group of progressive optic neuropathies characterized by the degeneration of retinal ganglion cells (RGCs) and their axons, leading to irreversible vision loss or blindness if left untreated. Current glaucoma treatments primarily focus on lowering intraocular pressure (IOP), the only proven method to slow disease progression. However, these treatments do not effectively address RGC loss or promote optic nerve regeneration. Emerging research into both natural and synthetic bioactive compounds offers promising new avenues for glaucoma management. This review explores the multifaceted therapeutic potential of bioactive compounds in glaucoma treatment, focusing on their mechanisms of action in IOP reduction and neuroprotection, as well as antioxidant and anti-inflammatory effects. We further review ongoing clinical trials and discuss significant challenges to clinical translation, including the issues of bioavailability, standardization, long-term safety, and regulatory challenges. Furthermore, this paper highlights the potential of integrating precision medicine into bioactive treatments, emphasizing the value of personalized care based on genetic and phenotypic profiles. Finally, the review discusses the role of combination therapies, which leverage the complementary mechanisms of bioactive compounds and conventional treatments. As research progresses, the development of targeted, bioactive-based therapies could transform glaucoma management, offering more comprehensive and effective options for patients with this vision-threatening disease.