Glaucoma is a leading cause of irreversible blindness worldwide. Presently, elevated intraocular pressure (IOP) is the only approved modifiable risk factor. A consensus of the current literature suggests that both physiological and psychological stress may also impact the lifelong course of glaucoma. Specifically, stress is known to influence sympathetic nervous system activity. An increase in sympathetic nervous system activity may elevate a person’s blood pressure (BP) and IOP, and both are strongly associated with glaucomatous disease. Anxiety and depression have more conflicting evidence in relation to glaucoma. Socioeconomic and environmental stress may worsen adherence to therapy and disease outcomes due to a lack of financial resources and related access to healthcare. Neighborhood quality and environmental conditions, particularly urban environments, have been associated with glaucoma risk factors, higher glaucoma prevalence, and delayed surgical interventions. Racial differences have also been identified, with Black patients being more stressed and likely to present with increased glaucoma severity and faster disease progression than White patients. Mindfulness, meditation, and other forms of psychological relaxation have been shown to reduce IOP and stress biomarkers and result in improved quality of life (QOL). Larger studies in more diverse populations are needed to clarify risk and identify the best therapeutic approaches to reduce stress as a method to improve clinical outcomes and QOL for glaucoma patients.

Background and Objectives: Glaucoma is a major cause of irreversible blindness, with primary open-angle glaucoma (POAG) being the most prevalent form. While elevated intraocular pressure (IOP) is a well-known risk factor for POAG, emerging evidence suggests that the human gut microbiome may also play a role in the disease. This review synthesizes current findings on the relationship between gut microbiome and glaucoma, with a focus on mathematical modeling and artificial intelligence (AI) approaches to uncover key insights. Materials and Methods: A comprehensive literature search was conducted using PubMed and Google Scholar, covering studies from its inception to 1 August 2024. Selected studies included basic science, observational research, and those incorporating mathematical-related models. Results: Traditional statistical and machine learning approaches, such as random forest regression and Mendelian randomization, have identified associations between specific microbiota and POAG features. These findings highlight the potential of AI to explore complex, nonlinear interactions in the gut–eye axis. However, limitations include variability in study designs and a lack of integrative, mechanistic models. Conclusions: Preliminary evidence supports the existence of a gut–eye axis influencing POAG disease. Combining data-driven and mechanism-driven models with AI could identify therapeutic targets and novel biomarkers. Future research should prioritize longitudinal studies in diverse populations and integrate physiological data to improve model accuracy and clinical relevance. Furthermore, physics-based models could deepen our mechanistic understanding of the gut–eye axis in glaucoma, advancing beyond associative findings to actionable insights.

Purpose: We aimed to analyze the effects of age on human tear film (TF) using a novel nanometer resolution TF imaging device (Tear Film Imager, TFI, AdOM, Israel). Methods: 44 healthy adult subjects (≥18 years of age) without ocular or systemic diseases or prior eye treatments with ages spanning seven decades were enrolled in this prospective cross-sectional study. Subjects underwent a comprehensive ophthalmic examination and completed the Ocular Surface Disease Index questionnaire (OSDI). All study participants underwent TF imaging using the TFI, including assessment of muco-aqueous layer thickness (MALT), lipid-layer thickness (LLT), inter-blink interval, and lipid map uniformity. Associations between TFI parameters and age were tested using linear regression (accounting for multiple eyes). Results: A total of 80 eyes (44 subjects) were imaged: 19 eyes from 10 subjects in the 3rd decade of life (aged 20–29); 10 eyes from 5 subjects in the 4th decade of life (aged 30–39); 5 eyes from 3 subjects in the 5th decade of life (40–49); 12 eyes from 7 subjects in the 6th decade of life (50–59), 19 eyes from 11 subjects in the 7th decade of life (60–69); 11 eyes from 6 subjects in the 8th decade of life (70–79); and 4 eyes from 2 subjects in the 9th decade of life (80–89). With increasing age, MALT significantly decreased (p = 0.024), and LLT significantly increased (p = 0.001). No statistically significant linear age effects were found for the other TFI parameters (p > 0.05) or the OSDI scores of study participants of different ages (p = 0.786). Conclusions: Quantitative TF biomarkers varied significantly with advancing age in healthy individuals, highlighting the importance of accounting for age in TF assessments.

The ability of a cell to keep its volume constant irrespective of intra- and extracellular conditions is essential for cellular homeostasis and survival. The purpose of this study is to elaborate a theoretical model of cell volume homeostasis and to apply it to a simulation of human aqueous humor (AH) production. The model assumes a cell with a spherical shape and only radial deformation satisfying the property that the cell volume in rest conditions equals that of the cell couplets constituting the ciliary epithelium of the human eye. The cytoplasm is described as a homogeneous mixture containing fluid, ions, and neutral solutes whose evolution is determined by net production mechanisms occurring in the intracellular volume and by water and solute exchange across the membrane. Averaging the balance equations over the cell volume leads to a coupled system of nonlinear ordinary differential equations (ODEs) which are solved using the $\theta$-method and the Matlab function ode15s. Simulation tests are conducted to characterize the set of parameters corresponding to baseline conditions in AH production. The model is subsequently used to investigate the relative importance of (a) impermeant charged proteins; (b) sodium–potassium (Na+/K+) pumps; (c) carbonic anhydrase (CA) in the AH production process; and (d) intraocular pressure. Results suggest that (a) and (b) play a role; (c) lacks significant weight, at least for low carbon dioxide values; and (d) plays a role for the elevated values of intraocular pressure. Model results describe a higher impact from charged proteins and Na+/K+ ATPase than CA on AH production and cellular volume. The computational virtual laboratory provides a method to further test in vivo experiments and machine learning-based data analysis toward the prevention and cure of ocular diseases such as glaucoma.

Background and Objectives: Despite the growing amount of new research, the pathophysiology of glaucoma remains unclear. The aim of this study was to determine the relationship between intracranial pressure (ICP), ocular blood flow and structural optic nerve parameters. Materials and Methods: A prospective clinical study was conducted involving 24 patients with open-angle glaucoma and 25 healthy controls. Routine clinical examination was performed. Swept-source optical coherence tomography (SS-OCT) and OCT angiography (OCTA) images were taken (DRI-OCT Triton, Topcon). The vessel density (VD) values of the ONH were calculated around the optic nerve head (ONH). An orbital Doppler device (Vittamed 205, Kaunas, Lithuania) was used for non-invasive ICP measurements. Color Doppler imaging (CDI) (Mindray M7, Shenzhen, China) was used for retrobulbar blood flow measurements in the ophthalmic artery (OA), central retinal artery (CRA) and short posterior ciliary arteries (SPCAs). Results: ICP was 8.35 ± 2.8 mmHg in the glaucoma group and 8.45 ± 3.19 mmHg in the control group (p = 0.907). In the glaucoma group, the VD of the superficial vascular plexus in the inferior-nasal (NI) sector of the ONH showed a correlation with ICP (r = 0.451, p = 0.05). In contrast, the control group exhibited weaker correlations. CRA peak systolic velocity (PSV) demonstrated significant moderate correlations with VD in multiple retinal layers, including the avascular retina layer in the temporal (T) sector (r = 0.637, p = 0.001). Conclusions: Lower ICP was significantly associated with the lower VD of the superficial plexus layer in the inferior-nasal sector in the glaucoma group, with the control group exhibiting weaker correlations in all sectors. Further longitudinal studies with larger sample sizes are needed to establish associations between intracranial pressure, ocular blood flow and ONH parameters.

Mitochondrial dysfunction and oxidative stress have been suggested as potential contributors to the initiation and progression of primary open-angle glaucoma (POAG). Nicotinamide and pyruvate are important in the human body for maintaining metabolic function and preserving cytoskeletal structures. Both substances show an age-dependent decline in humans which may contribute to metabolic dysfunction and POAG vulnerability. Pilot works suggest their consumption may help prevent retinal ganglion cell deterioration under elevated intraocular pressure (IOP) and oxidative stress. Currently, there are no approved POAG treatments to mitigate risks from non-IOP drivers of disease, including oxidative stress. The purpose of this review is to summarize and critically evaluate interventional studies that have investigated nicotinamide and pyruvate supplementation in attempts to treat metabolic dysfunction in POAG patients. A review of the relevant literature from October 1979 to November 2025 was performed using related search terminologies through PubMed, ClinicalTrials.gov, and Google Scholar, and by reference cross-matching of all related articles. Current pilot data suggests that supplementation with nicotinamide and pyruvate demonstrates certain aspects of retinal neuroprotection and produces short-term improvements in visual function. However, much of the existing work has been conducted in animal models, and human study data are severely limited in scope and duration. Several clinical trials are registered as being in progress that aim to determine the chronic effects of nicotinamide and pyruvate in humans. Long-term longitudinal investigations with significantly larger and diverse sample sizes tied to functional and structural outcomes are needed for the safety and potential clinical utility of nicotinamide and pyruvate for POAG.