The paper introduces Professor JI Laixi's academic thought and clinical experience in treatment of primary open angle glaucoma with "nape-eight-needle" acupotomy. Professor JI Laixi believes that the key pathogenesis lies in "occlusion of xuanfu (subtle orifices) within the eyes and obstruction of meridian pathways". Using the unblocking principle of treatment, taking meridian theory of traditional acupuncture as the core and based on the anatomical principles of structural acupuncture, Professor JI has proposed his academic thought, "treating eye diseases from the nape". In treatment, "nape-eight-needle" acupotomy is adopted, combined with filiform needle acupuncture. It is the advantageous compound therapeutic method, aiming to open xuanfu, restore brain-eye meridian connectivity, harmonize body, qi and mind through systemic regulation, address both the causative factors and symptoms and prevent from blindness. This therapeutic approach provides a new idea for clinical treatment of primary open angle glaucoma.
Humans ; Acupuncture Therapy/history* ; Glaucoma, Open-Angle/therapy* ; Male ; Meridians ; Female ; Acupuncture Points ; Middle Aged ; Aged

BACKGROUND: Retinal ganglion cell (RGC) death caused by acute ocular hypertension is an important characteristic of acute glaucoma. Receptor-interacting protein kinase 3 (RIPK3) that mediates necroptosis is a potential therapeutic target for RGC death. However, the current understanding of the targeting agents and mechanisms of RIPK3 in the treatment of glaucoma remains limited. Notably, artificial intelligence (AI) technologies have significantly advanced drug discovery. This study aimed to discover RIPK3 inhibitor with AI assistance. METHODS: An acute ocular hypertension model was used to simulate pathological ocular hypertension in vivo . We employed a series of AI methods, including large language and graph neural network models, to identify the target compounds of RIPK3. Subsequently, these target candidates were validated using molecular simulations (molecular docking, absorption, distribution, metabolism, excretion, and toxicity [ADMET] prediction, and molecular dynamics simulations) and biological experiments (Western blotting and fluorescence staining) in vitro and in vivo . RESULTS: AI-driven drug screening techniques have the potential to greatly accelerate drug development. A compound called HG9-91-01, identified using AI methods, exerted neuroprotective effects in acute glaucoma. Our research indicates that all five candidates recommended by AI were able to protect the morphological integrity of RGC cells when exposed to hypoxia and glucose deficiency, and HG9-91-01 showed a higher cell survival rate compared to the other candidates. Furthermore, HG9-91-01 was found to protect the retinal structure and reduce the loss of retinal layers in an acute glaucoma model. It was also observed that the neuroprotective effects of HG9-91-01 were highly correlated with the inhibition of PANoptosis (apoptosis, pyroptosis, and necroptosis). Finally, we found that HG9-91-01 can regulate key proteins related to PANoptosis, indicating that this compound exerts neuroprotective effects in the retina by inhibiting the expression of proteins related to apoptosis, pyroptosis, and necroptosis. CONCLUSION AI-enabled drug discovery revealed that HG9-91-01 could serve as a potential treatment for acute glaucoma.
Animals ; Glaucoma/metabolism* ; Neuroprotective Agents/pharmacology* ; Mice ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Artificial Intelligence ; Retinal Ganglion Cells/metabolism* ; Disease Models, Animal ; Molecular Docking Simulation ; Mice, Inbred C57BL ; Male

Glaucoma is the leading cause of irreversible blindness worldwide, with its primary risk factor arising from elevated intraocular pressure (IOP) due to an imbalance between aqueous humor production and outflow. This study aims to establish quantitative correlations among IOP, iris mechanical properties, channel microstructures, and aqueous humor dynamics through three-dimensional modeling and finite element analysis, overcoming the limitations of conventional experimental techniques in studying aqueous flow within the trabecular meshwork (TM) outflow pathway. A three-dimensional fluid-structure interaction (FSI) model incorporating the layered TM structure, Schlemm's canal (SC), iris, and other anterior segment tissues was developed based on human ocular anatomy. FSI simulations were performed to quantify the effects of IOP variations and iris Young's modulus on tissue morphology and aqueous humor dynamics parameters. The computational results demonstrated that axial iris deformation showed significant correlations with IOP and iris Young's modulus. Although elevated IOP exhibited minimal effects on hydrodynamic parameters in the anterior and posterior chambers, it markedly suppressed aqueous flow velocity in the TM region. Additionally, wall shear stress in SC and collector channels displayed high sensitivity to IOP variations. These findings reveal that the tissue mechanics-FSI mechanism modulates outflow resistance by regulating aqueous humor dynamics, offering valuable references for developing clinical therapies targeting IOP reduction in glaucoma management.
Humans ; Trabecular Meshwork/anatomy & histology* ; Finite Element Analysis ; Aqueous Humor/metabolism* ; Intraocular Pressure/physiology* ; Glaucoma/physiopathology* ; Iris/anatomy & histology* ; Computer Simulation ; Models, Biological

Neuronal injury in glaucoma persists despite effective intraocular pressure (IOP) control, necessitating neuroprotective strategies for retinal ganglion cells (RGCs). In this study, we investigated the neuroprotective role of the γ-hydroxybutyrate analog HOCPCA in a glaucoma model, focusing on its effects on CaMKII signaling, oxidative stress, and neuroinflammatory responses. Retinal tissue from high IOP animal models was analyzed via proteomics. In vitro mouse retinal explants were subjected to elevated pressure and oxidative stress, followed by HOCPCA treatment. HOCPCA significantly mitigated the RGC loss induced by oxidative stress and elevated pressure, preserving neuronal function. It restored CaMKIIα and β levels, preserving RGC integrity, while also modulating oxidative stress and neuroinflammatory responses. These findings suggest that HOCPCA, through its interaction with CaMKII, holds promise as a neuroprotective therapy for glaucoma.
Animals ; Retinal Ganglion Cells/metabolism* ; Glaucoma/pathology* ; Oxidative Stress/drug effects* ; Neuroprotective Agents/pharmacology* ; Mice ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism* ; Mice, Inbred C57BL ; Disease Models, Animal ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotection/drug effects* ; Male ; Intraocular Pressure/drug effects*

Animals ; Macaca mulatta ; Optic Disk ; Glaucoma ; Craniocerebral Trauma ; Intraocular Pressure ; Low Tension Glaucoma

OBJECTIVE: To observe the clinical effect of acupuncture for glaucoma-induced optic atrophy. METHODS: A total of 70 patients (89 affected eyes) with glaucoma-induced optic atrophy were randomized into an observation group and a control group, 35 cases in each group. The control group was given basic western medicine treatment. In the observation group, on the basis of the treatment in the control group, acupuncture was applied at main acupoints i.e. Baihui (GV 20), Shangjingming (Extra), Chengqi (ST 1), Fengchi (GB 20), Zusanli (ST 36), combined with supplementary acupoints based on syndrome differentiation, once every three days, twice a week. The treatment for 3 months was required in both groups. Before treatment, after treatment and in follow-up of 6 months after treatment, the best corrected visual acuity (BCVA), intraocular pressure (IOP), indexes of visual field (visual field index [VFI], mean deviation [MD], pattern standard deviation [PSD]) and mean thickness of retinal nerve fiber layer (RNFL) were observed in the two groups. RESULTS: Compared before treatment, BCVA was decreased after treatment and in follow-up in the control group (P<0.05); in the follow-up, BCVA in the observation group was higher than that in the control group (P<0.05). On each time point before and after treatment, there was no significant difference within or between the two groups (P>0.05). After treatment and in the follow-up, the mean thickness of RNFL was larger than the control group (P<0.05). CONCLUSION On the basis of the basic western medicine treatment, acupuncture can delay the decline of vision and the thinning of retinal nerve fiber layer in patients with glaucoma-induced optic atrophy.
Humans ; Retinal Ganglion Cells ; Glaucoma/therapy* ; Optic Atrophy/therapy* ; Intraocular Pressure ; Acupuncture Therapy

Humans ; Pharmacogenetics ; Precision Medicine ; Glaucoma/genetics*

Glaucoma is one of blind causing diseases. The cup-to-disc ratio is the main basis for glaucoma screening. Therefore, it is of great significance to precisely segment the optic cup and disc. In this article, an optic cup and disc segmentation model based on the linear attention and dual attention is proposed. Firstly, the region of interest is located and cropped according to the characteristics of the optic disc. Secondly, linear attention residual network-34 (ResNet-34) is introduced as a feature extraction network. Finally, channel and spatial dual attention weights are generated by the linear attention output features, which are used to calibrate feature map in the decoder to obtain the optic cup and disc segmentation image. Experimental results show that the intersection over union of the optic disc and cup in Retinal Image Dataset for Optic Nerve Head Segmentation (DRISHTI-GS) dataset are 0.962 3 and 0.856 4, respectively, and the intersection over union of the optic disc and cup in retinal image database for optic nerve evaluation (RIM-ONE-V3) are 0.956 3 and 0.784 4, respectively. The proposed model is better than the comparison algorithm and has certain medical value in the early screening of glaucoma. In addition, this article uses knowledge distillation technology to generate two smaller models, which is beneficial to apply the models to embedded device.
Humans ; Optic Disk/diagnostic imaging* ; Glaucoma/diagnosis* ; Algorithms ; Diagnostic Techniques, Ophthalmological ; Databases, Factual

Glaucoma is one of the most common optic neuropathies, featuring progressive retinal ganglion cell damage and visual field loss (Tham et al., 2014; Xu et al., 2020). Currently, the only effective treatment for this condition is the reduction of intraocular pressure (IOP) (Palmberg, 2001; Heijl et al., 2002). Canaloplasty is a proven bleb-independent surgery with good efficacy and safety profiles in primary open-angle glaucoma (POAG) (Gołaszewska et al., 2021). However, early transient postoperative IOP elevation has been reported in up to 30% of cases (Riva et al., 2019), similar to that commonly observed in other internal drainage glaucoma surgeries such as implantation using iStent (0%-21.0%), CyPass (10.8%), and Hydrus (4.8%-6.5%) (Lavia et al., 2017). This complication may be a predictor of poor reserve in the outflow system and is potentially associated with surgical failure. Nonetheless, the exact pathophysiology of glaucoma remains unknown, and studies clarifying the risk factors for postoperative IOP elevation have been scarce.
Humans ; Intraocular Pressure ; Glaucoma, Open-Angle/surgery* ; Incidence ; Treatment Outcome ; Risk Factors

Objective: This study compared the economic viability of initial medical therapy with topical prostaglandin analogues (PGAs) versus selective laser trabeculoplasty (SLT) in the treatment of primary open-angle glaucoma (POAG). Method: This was an economic analysis using actual, current treatment costs of PGA therapy versus SLT applied to theoretical, literature-derived clinical efficacy data projected for a period of 19 years. A socioeconomic and demographic survey conducted among POAG patients at the Department of Health Eye Center of the East Avenue Medical Center from March-April 2022 provided the economic context and setting for the analysis. The treatment regimens were compared in terms of total cost, clinical efficacy, cost-effectiveness and cost-utility in the setting of a tertiary government hospital. Results: Thirty-one (31) patients were included in the study. The total annual cost of topical PGAs was Philippine Pesos (Php) 13,532 versus Php 6,195 for SLT. Cost-effectiveness was Php 1,933 for PGAs/mmHg reduction in intraocular pressure (IOP) versus Php 983 for SLT. Cost-utility was Php 59,793/Quality Adjusted Life Years (QALY) gained for PGAs versus Php 27,373/QALY gained for SLT projected for 19 years. With government insurance coverage, cost-utility ratio was Php 47,831/QALY gained for topical PGAs versus 16,327/QALY gained for SLT. Conclusion In POAG patients, SLT was more cost-effective versus PGAs with a lower cost per mmHg IOP reduction, and lower cost-utility ratio for every QALY gained. SLT can be recommended as initial therapy for POAG especially for patients being treated at tertiary government hospitals.
Economic analysis ; cost-utility ; glaucoma ; prostaglandin analogues ; quality adjusted life years ; Philippines