Toru Nakazawa

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.

Purpose: To identify risk factors for relapse in patients with myelin oligodendrocyte glycoprotein antibody–associated optic neuritis (MOG-ON) during the onset event. Study design: Retrospective cohort study. Methods: We included 44 eyes of 44 Japanese patients with MOG-ON (median age 40.0 years [interquartile range 23.5–54.0]; male to female ratio 16:28) who visited Tohoku University Hospital between August 2013 and December 2024. We compared patient background characteristics; ophthalmic findings, including optical coherence tomography parameters; laboratory findings, including hematological, biochemical, and immunological parameters; anti-MOG antibody titers; and contrast-enhanced orbital MRI findings at baseline in relapse and non-relapse groups. Relapse risk was evaluated using a Kaplan–Meier survival analysis and a Cox proportional hazards regression. Results: Nine of 44 (20.5%) patients relapsed during follow-up. The Kaplan–Meier analysis showed lower relapse-free survival in patients without eye-movement pain, those with a lower serum IgG level, and those with a thinner macular retinal nerve fiber layer (mRNFL; log-rank P=0.013, 0.049, and 0.040, respectively). In the age- and sex-adjusted Cox proportional hazards analysis, relapse risk was significantly associated with absence of eye-movement pain (hazard ratio [HR] 5.58, 95% confidence interval [CI] 1.35–23.04; P=0.018), a lower serum IgG level (HR 0.55, 95% CI 0.30–1.00; P=0.048), and a higher anti-MOG antibody titer (HR 1.98, 95% CI 1.05–3.71; P=0.034). Conclusion: Baseline absence of eye-movement pain, lower serum IgG level, and higher anti-MOG antibody titer were associated with relapse risk in patients with MOG-ON. A thinner mRNFL may represent a potential marker of relapse-related outcomes.

Many nanoscale materials, ranging from environmental particulates to carrier‐free nanomedicine platforms, enter the human body, yet their metabolic fates remain poorly understood. This process involves complex physical changes and molecular transformations within lysosomes; however, the particle‐to‐molecule transition–defined here as “nanometabolism”–has remained difficult to quantify due to intrinsic limitations of nanoscale bioimaging. To circumvent the fluorescence quenching of conventional fluorophores and the challenges of observing nanoscale dynamics, peak‐shifted, dual‐state emissive nanoprobes composed entirely of donor–acceptor bithiophene dyes are introduced here. This approach establishes a highly adaptable design strategy for constructing heterogeneous organic nanoparticles templated by these molecular metrics. These molecular probes generate bright, ratiometric spectral shifts that directly encode nanoparticle disassembly, enabling robust optical monitoring of intracellular nanometabolism with cell‐type‐ and particle‐size‐resolution. Time‐resolved imaging identifies protonation‐induced lysosomal membrane destabilization as the primary driver of nanoparticle breakdown within 6–12 h. Supported by cryogenic correlative imaging and tissue‐level tracking, this platform provides a promising optical framework for monitoring nanometabolism in living systems. It serves as a pivotal breakthrough in elucidating the mechanistic design rules required for the future development of carrier‐free nanomedicines with predictable intracellular behavior.

Purpose: Glaucoma is a leading cause of visual impairment in Japan. Because it is often asymptomatic in its early stages, many individuals with glaucoma remain unaware of their condition. To address this, we are promoting eye-care culture ( memigaki bunka ). As part of this initiative, we conducted a study to assess glaucoma awareness in Japan. Study design: Cross sectional, online panel survey. Methods: An online survey was conducted in Japan among men and women aged 30–69 years. Participants were stratified into four 10-year age groups (30–39, 40–49, 50–59, and 60–69 years) and by sex, with 100 men and 100 women recruited for each age group in each of the two study regions: (1) the cities of Sendai and Tomiya in Miyagi, and (2) all other 46 Japanese prefectures combined (excluding the 47th prefecture, Miyagi). The total sample comprised 1,600 participants, including 800 residents of Sendai/Tomiya and 800 residents of the remaining 46 prefectures. All participants answered the question: what do you know about glaucoma? using a 5-point Likert scale. Results: Residents of Sendai and Tomiya demonstrated significantly higher glaucoma awareness than those from other regions (p = 0.01). Women showed higher awareness than men (p = 0.03). In a sex-stratified analysis, regional differences were observed among women (p = 0.03) but not among men (p = 0.18). Path analysis revealed that willingness to undergo paid eye examinations was associated with being female, being a driver, having a sense of fear of glaucoma, and understanding glaucoma (p < 0.05). Conclusions: Glaucoma awareness was relatively higher among participants from Sendai and Tomiya than among participants from the other 46 prefectures. Women demonstrated higher levels of awareness than men. Future public health efforts should focus on improving awareness among men to promote early detection and treatment of glaucoma.

Glaucoma remains one of the leading causes of acquired irreversible blindness worldwide, with normal-tension glaucoma representing the dominant subtype in Japan and several East Asian populations. The insidious, asymptomatic progression of this condition, combined with the demonstrated inadequacy of intraocular pressure alone as a screening criterion, creates a critical gap between disease burden and case detection. Population-based epidemiological studies consistently reveal that the majority of individuals with glaucoma are undiagnosed. Two responses have been suggested: incorporation of retinal imaging into annual health checkups, which warrants formal prospective evaluation, and characterization of individuals at higher risk — integrating genomic risk, oxidative stress biomarkers, systemic lifestyle factors, and ocular blood flow dynamics — which may help identify those in whom damage is most likely to occur. The principal contribution of this Perspective is therefore the implementation model rather than the individual screening components. We introduce the Living Lab (‘neighborhood health lab’), a community co-creation platform established under the Japan Science and Technology Agency COI-NEXT ‘Vision to Connect’ hub at Tohoku University, as a scalable model for operationalizing this framework. Embedded within commercial retail environments, the Living Lab integrates non-invasive screening, longitudinal health data collection, and evidence-based health product development—exemplified by the Ronbun Recipe ® concept—within a stakeholder-aligned ecosystem encompassing citizens, researchers, industry, and municipal authorities. Conceived as a platform for well-being rather than as a disease-specific screening service, it engages individuals who are asymptomatic, undiagnosed, and outside existing screening pathways, and who would not otherwise be assessed at all.

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.

Purpose: To develop and validate a machine-learning model using systemic and ophthalmic parameters that predicts sleep-disordered breathing (SDB) in patients with open-angle glaucoma (OAG). Study design: Retrospective cross-sectional study Methods: We analyzed 513 patients with OAG (955 eyes) treated at Seiryo Eye Clinic. All the participants underwent comprehensive ophthalmic examinations, including Humphrey visual field (HVF) testing, and home sleep apnea testing (HSAT) to obtain the 4% oxygen desaturation index (ODI). SDB was operationally defined as ODI-SAS, ie, sleep apnea syndrome (SAS) defined by HSAT-derived 4% ODI ≥15 events per hour. Sixteen algorithms were trained to predict ODI-SAS; model performance was assessed by the area under the receiver operating characteristic curve (ROC–AUC), precision, recall, the F1 score, and the Matthews correlation coefficient (MCC). Results: One hundred fifty-eight patients (30.80%) met the ODI-SAS criterion. ODI-SAS status was associated with a history of hypertension, higher body mass index, family-reported apnea, shorter axial length, fewer antiglaucoma medications, and worse inferocentral total deviation on HVF (all P < 0.05), but not with self-awareness of snoring or previous SAS diagnosis. A gradient-boosted decision-tree model (CatBoost) achieved the best performance (ROC–AUC 0.86), with precision 0.692, recall 0.711, F1 score 0.701, and MCC 0.543. Conclusion: Machine-learning models can predict ODI-SAS in glaucoma using systemic risk factors together with ophthalmic features, including inferocentral visual-field defects. Such models may help identify OAG patients who warrant formal sleep evaluation.