Naoki Takahashi

Précis: Plasma BDNF differed across glaucoma severity stages and was cross-sectionally associated with visual and structural parameters; in exploratory age-stratified analyses, the fitted csGCCT–BCVA relationship differed between younger and older patients. Purpose: To compare the plasma level of brain-derived neurotrophic factor (BDNF) in open-angle glaucoma (OAG) patients across disease stages and to examine its associations with visual and structural parameters. Patients and Methods: This cross-sectional study included 167 control (cataract) patients and 800 patients with OAG. Plasma BDNF level was measured using a bead-based immunoassay (Luminex). Clinical variables included best-corrected visual acuity (BCVA), Humphrey Field Analyzer 24-2 indices, and swept-source optical coherence tomography measurements of superior, central, and inferior papillomacular central-strip ganglion cell complex thickness (csGCCT). Glaucoma severity was classified with the Anderson-Patella criteria. Exploratory generalized additive models characterized the central csGCCT–BCVA relationship by age group and by lowest versus highest quartile. Results: Plasma BDNF was lower in early and moderate glaucoma patients than in controls ( P =0.006, 0.001) but higher in advanced than in early or moderate glaucoma patients ( P =0.040, 0.006). The highest-BDNF-quartile glaucoma patients had worse BCVA and mean deviation (MD) than the lowest-quartile patients, with significantly lower central csGCCT. Among patients aged <60 years, the fitted central csGCCT–BCVA relationship differed between the highest and lowest BDNF quartiles, with higher fitted logMAR in the highest-quartile group at lower csGCCT values. Conclusions: Plasma BDNF level differed across OAG disease stages and was associated with visual and structural parameters. Among younger patients, plasma BDNF quartile was associated with the fitted csGCCT–BCVA relationship. These cross-sectional findings do not establish temporal or causal relationships.

The global prevalence of myopia is increasing, and the combination of myopia and glaucoma is widely expected to become an important clinical and public health issue. Myopic eyes undergo axial elongation and posterior pole remodeling, leading to optic disc tilt, peripapillary deformation, choroidal thinning, and altered spatial relationships between the optic nerve head and its vascular supply. Glaucomatous optic neuropathy is associated with retinal ganglion cell damage, lamina cribrosa deformation, and ocular blood flow impairment. Recent advances in optical coherence tomography angiography and laser speckle flowgraphy have enabled noninvasive assessment of retinal, peripapillary, choroidal, and optic nerve head circulation. These modalities have revealed reduced radial peripapillary capillary density, choroidal microvasculature dropout, and reduced optic nerve head tissue blood-flow signal in glaucomatous eyes. In eyes with myopia and glaucoma, myopia-related structural deformation and glaucoma-associated perfusion abnormalities may coexist and show sectoral correspondence with neural damage, particularly in regions related to the central visual field. This review summarizes the anatomical background of ocular blood flow, myopia-induced structural and vascular changes, glaucoma-associated blood flow impairment, and their interaction in eyes with myopia and glaucoma. Potential therapeutic approaches targeting ocular blood flow are also discussed, although evidence beyond intraocular pressure reduction remains limited.

Glaucoma is the leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) loss and optic nerve degeneration. While elevated intraocular pressure (IOP) remains the primary modifiable risk factor, a certain proportion of patients continue to deteriorate despite adequate IOP control, pointing to IOP-independent mechanisms of neurodegeneration. Oxidative stress—defined as an imbalance between the production of reactive oxygen species and the capacity of endogenous antioxidant defenses—has emerged as a central, multi-tiered contributor to glaucoma pathogenesis. In the anterior segment, chronic oxidative damage to the trabecular meshwork impairs aqueous humor outflow and drives IOP elevation. In addition, oxidative stress may impair ocular biomechanical integrity, including corneal hysteresis and lamina cribrosa, resulting in heightened susceptibility to IOP fluctuations. In the posterior segment, oxidative stress directly contributes to mitochondrial damage and vascular endothelial injury, leading to RGC apoptosis. The nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway coordinates the principal endogenous antioxidant response, while nicotinamide adenine dinucleotide (NAD⁺) depletion links redox imbalance to metabolic vulnerability of RGCs. This narrative review synthesizes evidence published up to March 2026 on the molecular mechanisms of oxidative stress in glaucoma, the role of biomarkers in aqueous humor and systemic circulation, and the translational landscape of antioxidant-based neuroprotection—including nicotinamide, coenzyme Q10, alpha-lipoic acid, and Nrf2-activating compounds. We highlight gaps between preclinical promise and clinical evidence, and outline priorities for future randomized controlled trials.

Objectives: Glaucoma is an age-related neurodegenerative disease, characterized by retinal ganglion cell loss and progressive visual field deterioration. Beyond intraocular pressure (IOP), vascular and metabolic dysregulation contributes to optic nerve head (ONH) ischemia and neuronal vulnerability. Nutritional factors with antioxidative and vasodilatory properties may help preserve ocular perfusion. This study investigated the acute and subacute effects of a single dose of a dietary supplement containing red ginger extract (Zingiber officinale var. rubra), lutein, and vitamin B6 on ONH blood flow in patients with open-angle glaucoma (OAG). Methods: A retrospective self-controlled study was conducted at Tohoku University Hospital between August 2023 and March 2025. ONH blood flow was quantified using a laser speckle flowgraphy (LSFG) baseline one hour after and one month after continuous oral supplementation in patients with OAG. Systemic parameters, ocular biometry, and concomitant glaucoma medications were recorded in medical charts. Relative mean blur rate (MBR) changes were analyzed using a linear mixed-effects model, accounting for repeated measures and inter-eye correlations. Results: Nineteen glaucoma patients (38 eyes) were included in the acute phase and 13 patients (26 eyes) completed the one-month follow-up. After adjusting for age and sex, a single oral dose of red ginger extract significantly increased the relative MBR at 1 h (106.9 ± 3.1%; p < 0.05), and this enhancement increased after 1 month of continuous intake (115.4 ± 6.7%; p < 0.05). Greater ONH perfusion was particularly prominent in eyes with shorter axial length. Conclusions: Oral supplementation was associated with acute and short-term increases in ONH blood flow in glaucomatous eyes. Although this study was a retrospective study without a placebo-controlled comparison group, our findings offer hypothesis-generating evidence that nutritional interventions may support ocular perfusion alongside conventional glaucoma management. Future prospective randomized controlled trials are required to confirm these associations.

Glaucoma is a major ocular neurodegenerative disease and a leading cause of irreversible blindness worldwide, with prevalence projected to exceed 110 million by 2040. Although lowering intraocular pressure (IOP) remains the only proven treatment, glaucoma arises from a complex interplay of genetic, local, and systemic factors—including oxidative stress, vascular dysregulation, mitochondrial dysfunction, and neuroinflammation. Emerging evidence suggests that modifiable lifestyle factors may influence these pathogenic pathways. In this review, higher dietary nitrate from leafy greens is consistently associated with lower primary open-angle glaucoma risk, aligning with nitric-oxide-mediated endothelial support and more stable ocular perfusion pressure. Flavonoids (anthocyanins and flavanols), carotenoids (lutein/zeaxanthin), and B vitamins have strong biological rationale for glaucoma prevention but have limited support from long-term, large population-based studies. The effect of polyunsaturated fats on glaucoma remains inconsistent and warrants source-(plant vs. animal) and substitution-based analyses. Consistent protective effects of aerobic exercise and high-quality sleep may be associated with favorable metabolic profiles and ocular perfusion, potentially mitigating retinal ganglion cell loss. Conversely, smoking and alcohol use are frequently coupled with poorer diet quality (e.g., lower vegetable intake) and heightened oxidative stress, which may exacerbate glaucomatous neurodegeneration. However, much of the current literature is constrained by cross-sectional designs, reliance on self-reported food frequency questionnaires, and insufficient use of structural endpoints such as retinal nerve fiber layer imaging. This review focuses on the potential of lifestyle modification and future directions in prevention and treatment strategies for glaucoma, highlighting the need for large-scale, multi-ethnic, genotype-stratified longitudinal studies and randomized controlled trials to establish causality and define optimal intervention strategies.

Glaucoma, a leading cause of blindness, requires accurate early detection. We present an AI-based Glaucoma Screening (AI-GS) network comprising six lightweight deep learning models (total size: 110 MB) that analyze fundus images to identify early structural signs such as optic disc cupping, hemorrhages, and nerve fiber layer defects. The segmentation of the optic cup and disc closely matches that of expert ophthalmologists. AI-GS achieved a sensitivity of 0.9352 (95% CI 0.9277–0.9435) at 95% specificity. In real-world testing, sensitivity dropped to 0.5652 (95% CI 0.5218–0.6058) at ~0.9376 specificity (95% CI 0.9174–0.9562) for the standalone binary glaucoma classification model, whereas the full AI-GS network maintained higher sensitivity (0.8053, 95% CI 0.7704–0.8382) with good specificity (0.9112, 95% CI 0.8887–0.9356). The sub-models in AI-GS, with enhanced capabilities in detecting early glaucoma-related structural changes, drive these improvements. With low computational demands and tunable detection parameters, AI-GS promises widespread glaucoma screening, portable device integration, and improved understanding of disease progression.

Purpose: This study aimed to investigate differences in microvasculature dropout (MvD) between the superior and inferior hemispheres in glaucoma patients. Study design: Retrospective and cross-sectional. Methods: Fifty-eight eyes of 58 open-angle glaucoma patients (age 61.12 ± 10.19 years, mean deviation − 7.32 ± 6.36 dB) were included. MvD was detected with en face images from swept-source optical coherence tomography angiography. Blood flow at the optic nerve head was measured with laser speckle flowgraphy, represented as the mean blur rate in tissue (MBRT). Logistic and linear regression models adjusted for age, intraocular pressure, axial length, and circumpapillary retinal nerve fiber layer thickness were used to investigate the relationship between various factors and MvD angle in each hemisphere. Results: The presence of inferior MvD was related to peripapillary atrophy-β area (odds ratio = 14.10 [2.49–234.00], P = 0.019). Superior MvD angle was significantly related to MBRT in the superior quadrant (β = −0.31 [− 0.60 – −0.02], P = 0.037). Inferior MvD angle was significantly related to peripapillary atrophy-β area (β = 0.49 [0.21–0.77], P = 0.001). Conclusions: Only superior MvD demonstrated a significant relationship with reduced ocular blood flow. In contrast, inferior MvD was associated with mechanical stress. These findings may suggest a potential difference in pathophysiology between superior and inferior MvD.