The progressive degeneration of retinal ganglion cells (RGCs) is the primary pathological characteristic of glaucoma. The role of the NEAT1/miR-93-5p axis, a crucial part of the ceRNA network, in the plasma-aqueous dual-fluid of glaucoma and its regulatory mechanism for RGC degeneration remain unclear. Patients with glaucoma and those with simple cataracts had their plasma and aqueous humor (AH) samples taken. The expressions of NEAT1 and miR-93-5p were detected by qRT-PCR. The Pearson correlation analysis method was used to examine the expression correlation in the plasma-aqueous dual-fluid. Logistic regression analysis was used to identify independent factors associated with the disease state. To investigate the regulatory effects of the NEAT1/miR-93-5p axis on cell viability, inflammatory response, and oxidative stress, a NaIO₃-induced cell damage model was built. In comparison to the control group, glaucoma patients had significantly higher levels of NEAT1 in their plasma and AH, significantly lower levels of miR-93-5p, and a negative correlation between NEAT1 and miR-93-5p. NEAT1 and miR-93-5p are independent factors related to the pathological state of glaucoma. According to cell experiments, high NEAT1 expression would inhibit cell viability, promotes the release of inflammatory factors. Silencing NEAT1 can reverse this damage, and this regulatory effect may be mediated by miR-93-5p. The NEAT1/miR-93-5p axis in plasma may potentially serve as a biomarker for the diagnosis of glaucoma.

The visual impairment in diabetic retinopathy (DR) has been associated with the pathophysiological changes of the entire visual pathway. However, only a few studies have specifically examined dynamic metabolic changes in the visual cortex of DR. The purpose of the study was to longitudinally characterize dynamic metabolic alterations in the visual cortex of DR rats using 11.7 T proton magnetic resonance spectroscopy (1H-MRS), with histopathological validation. 3-month-old male DR rats and matched healthy rats were randomly selected into the study (n = 7/group), with metabolic assessments in the visual cortex conducted at 2, 4, 6, and 8 weeks. Immunohistochemical analyses were performed at 8 weeks to evaluate visual cortex alterations. The metabolite concentration ratios were compared between DR rats and controls at different time points using repeated measures analysis of variance followed by Bonferroni post hoc tests. The comparison of immunohistochemical indicators between DR rats and controls was evaluated using independent samples t test. p < 0.05 was considered statistically significant. Compared to controls, DR rats exhibited significantly higher Ins/tCr and Cho/tCr ratios in the visual cortex at 2, 4, 6, and 8 weeks, while NAA/tCr, Glu/tCr, GABA/tCr, and Tau/tCr ratios were significantly lower, respectively (all p < 0.05). Notably, Ins/tCr and Cho/tCr progressively increased with the progression of DR, whereas NAA/tCr, Glu/tCr, GABA/tCr, and Tau/tCr gradually decreased correspondingly (all p < 0.05). At 8 weeks, DR rats showed a reduction in NeuN-, Tau-, NR2B-, and GABAA-positive cells, along with an increased expression of GFAP-positive cells, compared to controls (all p < 0.0001). In conclusion, with the progression of DR, the dynamic metabolic alterations in the visual cortex indicated ongoing cortical degeneration, impaired neurotransmitter metabolism, dysregulated cellular homeostasis and glial cell proliferation, highlighting the underlying neurobiological mechanisms of visual impairment in DR.

Glaucoma is no longer viewed solely as a pressure-mediated optic neuropathy but as a chronic neurodegenerative disease with a strong immune component. Across experimental models and patient samples, convergent inflammatory circuitry complement activation, NLRP3 inflammasome signaling, and microglial reactivity emerge as a central driver of retinal ganglion cell (RGC) dysfunction and death. Local complement upregulation (C1q, C3, C5) in the retina and optic nerve head (ONH) promotes aberrant synaptic tagging, phagoptosis, and membrane attack complex stress. In parallel, biomechanical strain, ischemia, mitochondrial damage, and danger-associated molecular patterns prime and activate the NLRP3 inflammasome in microglia, astrocytes, and ONH cells, leading to caspase-1 activation, IL-1β/IL-18 maturation, and pyroptotic or apoptotic injury. Microglia integrate these cues, shifting from early protective surveillance to chronic maladaptive states that amplify complement and inflammasome outputs. This review synthesizes mechanistic links within the complement NLRP3 microglia axis, considers systemic and adaptive immune contributions, and proposes a translational framework for immune-based clinical stratification. The literature for this review was identified through searches of PubMed, Web of Science, and Scopus using combinations of the terms ‘glaucoma’, ‘complement’, ‘inflammasome’, ‘NLRP3’, ‘microglia’, and ‘neuroinflammation’. Priority was given to recent experimental, translational, and clinical studies. We then evaluate emerging immunomodulatory therapies, complement inhibitors, inflammasome blockers, microglial state reprogrammers, cytokine biologics, and cell-derived immunoregulatory approaches, highlighting biomarkers and trial design needs. An immune systems view of glaucoma enables precision neuroprotection for patients who progress despite controlled intraocular pressure.

BACKGROUND:Glaucoma is one of the leading causes of irreversible blindness due to the ongoing loss of retinal ganglion cells (RGCs) and degeneration of the axons that form a major part of the retino-cortical pathway. Although there are some therapies available that primarily ameliorate the intraocular pressure, loss of sight often continues, and thus illustrates the need for therapies that address the degeneration of the nervous system. SUMMARY:Stem cell interventions have the unique potential to assist with the preservation and restoration of dysfunctional RGCs via direct cellular replacement, differential neuroprotection, and stimulation of endogenous repair mechanisms. The focus of this review is on the most contemporary innovations which utilize stem cells to preserve and regenerate RGCs, which are vitally important for sight. The review addresses some of the newer cell source and cell prep technologies, particularly those using disorganized retinal microenvironment cell preps. Retinal microenvironment cell preps have resulted in some novel microenvironment cells designed to sequester stem cell grafts, to improve stem cell microenvironment cell preps, and to augment microenvironment cell preps. Some of the major challenges are reconstructing and integrating the lost retino-tectal and retino-collateral synapses in the visual pathway and the axonal outgrowth to and targeting appropriate central visual synaptic areas. KEY MESSAGES:Some major challenges are safety, RGC immunochemistry and cell type diversity, and scalable cell prep technologies. This review encapsulates how stem cell biology, along with other technologies like gene editing and tissue engineering, is forming the basis for developing first-of-its-kind regenerative therapies to restore vision in glaucoma patients, based on recent preclinical studies and ongoing early-phase clinical trials.

Glaucoma is a leading cause of blindness in the world. It is painless and irreversible. Prevention and control of the progression depend on early diagnosis. Early symptoms include loss and thinning of optical nerve fiber, and accurate and quantitative measurement of the thickness of the optical nerve fiber layer provides an objective tool for early diagnosis. Due to the periodic structure of the optic nerve fiber, it possesses the property of form birefringence. Therefore, the thickness of the optic nerve fiber layer can be measured by the phase retardation when a polarized light is incident on to the eye and travels back from the eye. The confounding factor is that the cornea is also birefringent, and each individual has different phase retardation in the cornea. We have developed a method to measure the phase retardation of the cornea by using the intrinsic polarimeter in the Henle nerve fiber layer and then use an adaptive optical phase retarder to compensate for the retardance of the cornea. We further developed an algorithm to significantly improve the system measurement accuracy of the optical nerve fiber layer by more than an order of magnitude.

INTRODUCTION:Glaucoma is a main cause of irreversible blindness, which is mainly characterized by increased intraocular pressure (IOP) and degeneration of retinal ganglion cells. Current therapies primarily act by reducing aqueous humor production or enhancing its outflow to lower IOP. However, because glaucoma is a chronic disease requiring lifelong management, many patients experience reduced efficacy or develop tolerance to available medications over time. Consequently, there is an urgent need for novel pharmacological strategies that provide sustained IOP control. Dysfunction in human trabecular meshwork cells (HTMCs), which are crucial for the drainage of aqueous humor, significantly contributes to rising IOP. Phosphatidylcholine (PC) species have been recognized as potential therapeutic agents, but their causal relevance and mechanisms in glaucoma remain unclear. METHODS:We initially applied bidirectional Mendelian randomization (MR) analysis based on genome-wide associations of 648,214 individuals from European and East Asian ancestry to investigate the causal associations between 179 lipid species and glaucoma. We then explored the causal effects of PC(18:2/20:4) using HTMCs under hydrostatic pressure. The RNA sequencing, western blotting, immunofluorescence, proteomics, and flow cytometry were applied to explore the molecular mechanisms. RESULTS:MR results revealed that PC(18:2/20:4) functions as a protective factor for glaucoma (odds ratio = 0.89; 95% confidence interval = 0.82-0.96; P = 0.004) and no evidence for reverse causation was observed. In HTMCs, PC(18:2/20:4) could reduce the ROS production, inhibit apoptosis and fibrosis (Bax, Caspase-3, TGF-β2/3, MYOC), and recover the mitochondrial membrane potential. Transcriptomic and proteomic level data both demonstrated the activation of AMPK pathway and autophagy-related genes. Mechanistically, PC(18:2/20:4) activated AMPK via TGFBR3-dependent mechanism and inhibited mTOR. Meanwhile, blocking TGFBR3 reversed the beneficial effects. CONCLUSION:This integrative study demonstrated that PC(18:2/20:4) is a causal and relevant lipid modulator in pathogenesis of glaucoma. PC(18:2/20:4) protects HTMCs from pressure-induced oxidative stress, fibrosis, and apoptosis by activating the TGFBR3-AMPK/mTOR pathway. Our findings provide experimental basis for further development of lipid-based therapy to preserve HTMCs in glaucoma.

Purpose:To evaluate associations between ambient temperature and surgical failure after incisional glaucoma surgery. Methods:Individual-level clinical data were obtained from electronic medical records. Ambient temperature was estimated via spatiotemporal bilinear interpolation. Multivariable random-effects Cox proportional hazards models, incorporating restricted cubic splines and segmented regression, assessed the temperature-outcome relationship. Stratified analyses identified potentially susceptible populations. Likelihood ratio tests examined interactive effects between air pollution and ambient temperature on both multiplicative and additive scales. Results:Although conventional linear analyses did not show a significant association between ambient temperature and surgical failure risk, a spline-based nonlinear models suggested a U-shaped, asymmetric nonlinear association between ambient temperature and surgical failure risk within prolonged exposure windows (P_nonlinearity < 0.0001). Under these nonlinear specifications, exposure to temperature extremes relative to the mid-range was associated with an increased estimated risk of surgical failure. These nonlinear patterns appeared more evident in older patients and those with primary open-angle glaucoma. Air pollutants showed statistically significant effect modification in interaction analyses of the temperature-outcome association 180 days after surgery. With the exception of O₃, common air pollutants demonstrated negative interaction terms with temperature, suggesting that the modeled association between lower temperatures and surgical failure risk was stronger at higher pollutant concentrations. Conclusions:Nonlinear modeling suggested potential heterogeneity in risk across temperature ranges, with the estimated associations varying by PM₂.₅ exposure strata and other air pollutant levels. These findings are model-dependent and warrant confirmation in independent cohorts and prospective studies. Translational Relevance:Under spline-based nonlinear modeling, postoperative ambient temperature showed a U-shaped association with glaucoma surgical failure risk, with the estimated relationship differing across levels of concurrent air pollutant exposure. These findings are hypothesis-generating and suggest that environmental conditions may warrant consideration in postoperative risk assessment.

The aim of this study was to compare long-term effect of phacoemulsification combined with goniosynechialysis (Phaco-GSL) in patients with acute primary angle-closure glaucoma (APACG) and those with chronic primary angle-closure glaucoma (CPACG), and to evaluate the influencing factors of the surgical prognosis. In this prospective cohort study, patients with APACG or CPACG who underwent Phaco-GSL at the glaucoma clinics of Eye and ear, nose, and throat (ENT) Hospital were recruited consecutively from January 2019 to December 2022. Standardized 2-year follow-ups assessed baseline characteristics and surgical outcomes. The cumulative success rates and influencing factors of surgical prognosis were analyzed. A total of 213 patients were enrolled, including 116 patients (116 eyes) with APACG and 97 patients (97 eyes) with CPACG. The average age was 64.5 ± 7.2 years and 153 (71.8

Real-time in vivo imaging of retinal ganglion cell (RGC) degeneration is critical for glaucoma research but remains challenging due to limitations of conventional neural tracers in deep-tissue penetration and spatiotemporal resolution. Here, through covalent conjunction of FDA-approved indocyanine green (ICG) and cholera toxin subunit B (CTB), a novel fluorescent neural tracing probe (ICG-CTB) in the second near-infrared region (NIR-II) was developed for anterograde labeling of RGCs via intravitreal injection. ICG-CTB achieved effective, real-time visualization of RGC somas and axons with high biosafety and signal persistence sufficient for longitudinal monitoring. Using this probe, we successfully tracked dynamic axonal degeneration in multiple glaucoma-related models. This proposed novel ICG-CTB probe could facilitate high-fidelity in vivo mapping of pathological axonal alterations, providing a critical tool for evaluating therapeutic interventions targeting optic neuropathies.

The Ahmed Glaucoma Valve (AGV) is a drainage device commonly used in the treatment of refractory glaucoma. Implant exposure is a major cause of surgical failure. This study aimed to identify factors associated with AGV exposure. This retrospective cohort study included all inpatients who underwent primary AGV implantation at the Eye ENT Hospital of Fudan University between January 2015 and December 2024. Baseline demographic and surgical data were collected. Factors associated with AGV exposure were evaluated using univariate and multivariate logistic regression. In this comprehensive cohort study, involving a total of 2,905 eyes, with participants having a mean age of 49.2 ± 18.0 years and 64

PRÉCIS:In patients with untreated primary open-angle glaucoma, the higher the corneal deformability, the lower the changes of 24-hour intraocular pressure variation. PURPOSE:To investigate the relationship between corneal biomechanics and 24-hour intraocular pressure (IOP) variation in patients with untreated primary open-angle glaucoma (POAG). METHODS:Two hundred forty-five (245) eyes of 124 patients with POAG were included in this cross-sectional study. Each patient underwent measurement of corneal biomechanics with Corvis ST. IOP measurements were taken every 2 hours during a 24-hour period by a noncontact tonometer. RESULTS:The study included 70 men and 54 women. The mean age was 51.41±14.42 years. In the multivariate regression analyses, lower SP-A1 was associated with smaller values of 24-hour IOP fluctuation (difference between peak and trough IOP of 24-hour recordings), mean amplitude of intraocular pressure excursion (MAPE) and average, peak and trough IOPs of the 24-hour, diurnal and nocturnal time periods. Integrated radius was negatively correlated with average, peak and trough IOPs of both the 24-hour and diurnal time course, as well as with the trough nocturnal IOP. CONCLUSIONS:Corneal deformability reflected by biomechanical properties measured by Corvis ST is associated with 24-hour IOP variation in untreated POAG patients. Increased corneal deformability is associated with lower 24-hour IOP changes.

BACKGROUND:Dry eye disease (DED) commonly impairs quality of life. This phase 3, randomized, double-masked, multicenter, vehicle-controlled trial evaluated the efficacy of 5.0% lifitegrast ophthalmic solution (KH732) in improving signs and symptoms of DED. METHODS:Adults with moderate-to-severe DED and corneal staining score ≥2.0 in any corneal region were randomized 1:1 to lifitegrast (KH732) or vehicle twice daily for 84 days after a 3-7-day vehicle washout. The primary endpoint was change from baseline in inferior corneal staining score (ICSS) at Day 84. Secondary endpoints included changes in total corneal staining score, Eye Dryness Score (EDS), Ocular Surface Disease Index (OSDI), 7-item visual analogue scale, and Ocular Discomfort Score. RESULTS:At Day 84, lifitegrast (n = 309) significantly reduced ICSS versus vehicle (n = 306) (P = 0.027). In a post hoc analysis, the effect was more pronounced in participants with the highest baseline staining in the inferior region (P = 0.046). Lifitegrast also significantly improved EDS (adjusted P = 0.006), ocular discomfort (adjusted P = 0.010), photophobia (adjusted P = 0.004), and OSDI (adjusted P = 0.014) versus vehicle. Post hoc analyses showed significant between-group differences in EDS, photophobia, and OSDI as early as Day 14. No serious ocular adverse events were reported. CONCLUSIONS:Lifitegrast (KH732) improved both signs and symptoms of DED and was generally well tolerated, with potentially greater benefit in patients with prominent inferior corneal staining.

Background: To investigate the cause of ocular hypotension following retinal vein occlusion (RVO) and to elucidate the effect of vascular endothelial growth factor (VEGF) on intraocular pressure (IOP) reduction.Methods: A retrospective analysis was performed in 109 treatment-naïve unilateral central retinal vein occlusion (CRVO) patients to compare IOP between affected and fellow eyes. A subsequent prospective, cross-sectional study included 14 CRVO patients (before anti-VEGF therapy) and 27 cataract controls, from whom aqueous humor samples were acquired for VEGF measurement by ELISA. In animal experiments, rats received intravitreal VEGF injection in the right eye and vehicle in the left eye. IOP was measured at multiple time points post-injection. Trabecular meshwork tissues were collected at 4 hours for Western blot, PCR, and immunofluorescence analysis of Akt and eNOS expression.Findings: IOP was significantly lower in CRVO-affected eyes than in fellow eyes. The magnitude of IOP reduction correlated with aqueous VEGF levels. Additionally, eyes with presumed ischemic CRVO exhibited a significantly greater reduction in IOP and elevated aqueous VEGF levels compared with their non-ischemic counterparts. Subsequent animal experiments revealed that intravitreal injections of VEGF in rats significantly lowered IOP, an effect mediated by upregulation of the Akt/eNOS signaling pathway in the trabecular meshwork.Interpretation: VEGF reduces IOP via activation of the Akt/eNOS cascade in the conventional outflow pathway, contributing to RVO-associated ocular hypotension. Our findings suggest that the extent of IOP reduction may serve as a biomarker for RVO severity, and components of this pathway offer potential targets for novel glaucoma treatments.

Purpose: This study investigated the clinical characteristics, management strategies, and visual outcomes of perforating ocular injuries associated with intraorbital foreign bodies (IOrFBs). Methods: We retrospectively reviewed 54 patients with perforating ocular injuries and IOrFBs admitted to the Eye & ENT Hospital of Fudan University from January 1, 2007, to December 31, 2024. This study was reviewed and approved by the Ethics Committee of the Eye & ENT Hospital of Fudan University (Approval No. 2024146). Data collected included demographics, injury circumstances, foreign body composition, size and location (measured on preoperative computed tomography [CT] images), surgical approaches, and visual outcomes. Statistical analyses were performed using R, with significance set at p < 0.05. Results: Of the 54 patients, 87.0% (47) were male, and 92.6% (50) sustained occupational injuries (both p < 0.001). Ferromagnetic metallic fragments were the predominant cause (77.8%, 42). Anatomically, 40.7% (22) of foreign bodies were confined to the orbit, while 18.5% (10) involved the inferior globe wall and 16.7% (9) extended to the posterior pole. Larger IOrFB diameters were significantly associated with poorer preoperative and postoperative visual acuity (p < 0.05). Surgical interventions were performed as either single-stage or staged procedures, depending on the severity of the injury. The surgical strategies included pars plana vitrectomy (PPV) alone without foreign body removal; PPV combined with IOrFB extraction; PPV followed by subsequent orbital surgery for foreign body removal; orbital surgery for foreign body extraction followed by subsequent PPV; and IOrFB extraction alone without PPV. The most common surgical approach was combined PPV with orbital surgery (35.2%, 19). Notably, surgical approach was not an independent predictor of final visual outcomes. Conclusion: IOrFBs primarily affect working-age men and are typically caused by occupational metallic trauma. Larger foreign bodies predict worse baseline and final vision, whereas foreign body location and surgical approach do not independently influence visual prognosis. These findings highlight the need for early detection, occupational safety measures, and individualized management to optimize outcomes.

Abstract Purpose To identify the ocular biometric parameters associated with refractive outcomes in Chinese Primary angle closure glaucoma (PACG) patients receiving phacoemulsification and intraocular lens (IOL) implantation (PEI) surgery. Methods 165 Chinese PACG patients receiving PEI and goniosynechialysis (GSL) and 53 cataract patients as controls only receiving PEI surgery were recruited. The prediction accuracy of IOL power calculation was assessed by the prediction error (PE), mean absolute error (MAE), median absolute error (MedAE), and proportions of eyes with a PE within ± 0.25 diopters (D), ± 0.50 D, ± 0.75 D, and ± 1.00 D. The association of different ocular biometric parameters with the PE of IOL calculation were evaluated. Results The PACG patients had significantly higher absolute of PE as compared to the control subjects, especially the acute PACG patients. The axial length (AL), changes in aqueous depth pre- and post-surgery (△AD), and the ratio of △AD/AL were significantly associated with the PE in acute PACG patients. The association of △AD with the PE of IOL power calculation was found in PACG patients with AL ≥ 22 mm. Conclusions This study revealed the association of AL and △AD with the PE of IOL calculation in Chinese PACG patients. Precisely predict the △AD is necessary for acute PACG patients, especially for those with AL ≥ 22 mm, to improve the refractive outcomes.

Mechanical strain-induced myofibroblast differentiation is a pivotal mechanism underlying scleral extracellular matrix (ECM) remodeling in glaucoma. However, the conversion of mechanical strain into biochemical signals within scleral fibroblasts remains inadequately elucidated. This study sought to investigate the role of Piezo1 in cellular proliferation and differentiation, in the context of mechanical strain-induced myofibroblast differentiation during scleral ECM remodeling. The study design combines in vivo expression observations from a one‑week rat ocular hypertension model with in vitro mechanistic assays using cyclic mechanical stretch (10% at 0.5 Hz for up to 24 h) and pharmacological modulation of Piezo1 (agonist Yoda1, inhibitor GsMTx4, and siRNA knockdown) in primary human scleral fibroblasts (HSF cells). Our findings demonstrate that Piezo1 is expressed in scleral tissue and HSF cells. In the in vivo arm, a significant increase in Piezo1 protein levels was observed in the sclera of ocular hypertensive rats after one week, which coincided with elevated expression of type I collagen (COL1) and α‑smooth muscle actin (α‑SMA). In the in vitro experiments, mechanical stretch (8-24 h) upregulated Piezo1 expression in HSF cells. Moreover, activation of Piezo1 with Yoda1 (24 h) facilitated HSF cell proliferation and enhanced the expression of α‑SMA and COL1. Conversely, knockdown or inhibition of Piezo1 suppressed COL1 expression and hindered myofibroblast differentiation under mechanical strain. Additionally, Piezo1 activation led to an upregulation of Yes‑associated protein (YAP) expression, whereas mechanical strain‑induced YAP expression was diminished upon Piezo1 knockdown or inhibition. In summary, our findings suggest that Piezo1 plays a role in mechanical strain‑induced expression of key ECM components in the sclera in the context of glaucoma and may represent a potential therapeutic target requiring further in vivo validation.

Glaucoma-induced optic nerve damage is known to be a leading cause of blindness worldwide, yet current therapies mainly focus on reducing intraocular pressure without paying significant attention to the oxidative stress and inflammation in ocular tissues. Here, we address this issue by developing a self-adaptive two-dimensional nanosheet that enables sustained hydrogen release in the ocular microenvironment. The nanoagent (termed HyNDs) is constructed by modifying the surface of hydrogenated silicene (SiH), a biocompatible nanosheet that self-decomposes to generate hydrogen under physiological conditions, with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) polymer. HyNDs exhibit excellent dispersity, making them suitable for ocular delivery, while the TPGS coating ensures prolonged hydrogen release through its shielding effect. We demonstrate that HyNDs can efficiently scavenge oxidative radicals and downregulate the expression of oxidative stress-associated biomarkers in both cellular and animal models, contributing to significantly reduced intraocular pressure. Additionally, the nanoagent exhibits negligible cytotoxicity and adverse effects on ocular tissues. This hydrogen-based therapeutic approach features a dual mechanism of intraocular pressure reduction and oxidative stress mitigation, thereby exhibiting attractive promise for advancing the clinical management of glaucoma.

We describe a case of a 4-year-old Chinese girl who presented with elevated intraocular pressure (IOP), and foveal retinoschisis (FRS) in both eyes, which was later diagnosed as CRB1-associated retinopathy. Ultrasound biomicroscopy demonstrated shallow anterior chamber, angle closure, anterior insertion of iris and anteriorly positioned ciliary body. The patient received laser peripheral iridotomy and topical medications for ocular hypertension and macular oedema. Longitudinal follow-up over 2 years revealed improved visual acuity, and effective IOP control. However, the FRS continued to progress. Genetic screening confirmed a novel copy number loss and a pseudo-homozygous c.4207G > C (p.Glu1403Gln) variant of the CRB1 gene. This case underscores the importance of comprehensive ophthalmologic examination and genetic testing in young patients with primary angle closure. In addition, the patient's hemizygous state for the CRB1 gene provides a unique opportunity to establish a genotype–phenotype association between the c.4207G > C (p.Glu1403Gln) variant and maculopathy as well as elevated IOP.

Meibomian glands (MGs) are holocrine glands that secrete lipids to maintain the homeostasis of the ocular surface, and their dysfunction leads to dry eye disease. Herein, we established long-term 3D organoid culture for murine and human MGs, which retained the cell lineages and lipid-producing ability. The organoids mimicked the drug treatment responses and generated functional MGs after orthotopic transplantation. Inspired by organoid cultures, we found FGF10 eye drops could rescue all-trans retinoic acid-induced MG dysfunction in mice. Besides, nicotinamide uniquely hampered the human MG organoid expansion by inhibiting FGF10 signaling. Single-cell atlas and lipidome not only aligned the delineated cell types and featured lipids between human MGs and organoids, but also highlighted MAPK signaling inhibition enhanced acinar cell differentiation and functional maturation of MG organoids. In summary, this study established an organoid platform to explore epithelial homeostasis and dysfunction of MGs, facilitating drug development and regenerative medicine for dry eye disease.

Glaucoma is the leading cause of irreversible blindness. Primary open-angle glaucoma (POAG) is the most common form globally and has been linked to mitochondrial dysfunction and energy deficiency. Plasma was used to investigate the energy metabolomic profiles of patients with POAG and controls, and to determine the metabolite flux within the core interconnected energy pathways. Targeted liquid chromatography-mass spectrometry (LC-MS) was used to analyze plasma energy metabolism in POAG patients and controls. Differential metabolite expression analysis, correlation analysis, and pathway flux analysis were then conducted to elucidate the metabolic alterations and the mechanisms underlying POAG. Our findings reveal elevated levels of D-Glucose-6-phosphate(G6P), 6-Phosphogluconic acid(6PGA), Adenosine diphosphate(ADP), Adenosine monophosphate(AMP), Adenosine triphosphate(ATP), Guanosine diphosphate(GDP), Inosine monophosphate(IMP), Phosphoenolpyruvic acid(PEP), Phosphorylethanolamine(pEtN), and uridine diphosphate N-acetylglucosamine(UDP-GlcNAc) in POAG patients. Conversely, POAG patients showed reduced ratios of ATP/ADP, Glycerol-3-phosphate(G3P)/ Dihydroxyacetone phosphate(DHAP), 1,3-Bisphosphoglyceric acid(BPG)/DHAP, PYR/PEP, Fumarate/Succinate, Arginine/ASA, and Citrulline/Ornithine. These findings collectively suggest disrupted flux in glycolysis, the TCA cycle, urea cycle, and tyrosine metabolism, offering new insights into POAG mechanisms and potential therapeutic strategies targeting energy metabolic pathways.