Neurodegenerative diseases are increasingly recognized to involve detrimental interactions between the immune and nervous systems, yet whether failure of peripheral immune tolerance actively drives neuronal loss frequently remains unclear. Here, using primary open-angle glaucoma as a model of chronic neurodegeneration, we demonstrate that dysregulated adaptive immunity is sufficient to promote retinal ganglion cell degeneration. Peripheral blood mononuclear cells from glaucoma patients, but not healthy donors, induced retinal ganglion cell loss following transfer into humanized immunodeficient mice without changes to the intraocular pressure, demonstrating a causal role for immune responses in the patient derived material. Comprehensive immune profiling further revealed selective changes in the regulatory T-cell compartment, indicating reduced activation, an impaired suppressive phenotype, and altered differentiation and trafficking states despite preserved overall regulatory T cell abundance. We further demonstrate that transient expansion of regulatory T cells preserves visual function, reduced optic nerve axonal degeneration, and limited retinal ganglion cell loss in an experimental glaucoma model. Together, these findings identify failure of regulatory T cell mediated immune tolerance as a mechanism that permits neurodegeneration in glaucoma and demonstrate that restoring immune regulation can ameliorate neuronal injury. Our data indicate that immune tolerance is a modifiable determinant of chronic neurodegeneration and suggest that immunoregulatory therapies may complement conventional pressure-lowering treatments to preserve vision in glaucoma.

Primary open angle glaucoma (POAG) is a complex neurodegenerative disorder involving genetic susceptibility, environmental factors, and systemic abnormalities, whose pathogenesis has not been fully elucidated. Based on baseline intraocular pressure (IOP), POAG is classified into two subtypes: high-tension glaucoma (HTG) and normal-tension glaucoma (NTG). This review summarizes and integrates recent research advances, focusing on the roles of systemic disorders including cardiovascular, endocrine, neurodegenerative, and autoimmune diseases, as well as obstructive sleep apnea-hypopnea syndrome (OSAHS), in the onset and progression of POAG from an integrated eye-brain-body axis perspective. Current evidence suggests that optic nerve damage in POAG involves multiple interconnected pathological pathways, such as IOP-related mechanical stress, hemodynamic disturbances, impaired neurovascular coupling, microvascular dysfunction, oxidative stress, and chronic inflammation. Among them, dysfunctions of the eye-brain axis, gut-eye axis, and ocular lymphatic-glymphatic system serve as key regulatory networks that mediate and integrate the aforementioned pathological processes. The two subtypes display distinct pathogenic features: HTG is primarily driven by elevated IOP, whereas NTG relies more on IOP-independent mechanisms and is more susceptible to systemic influences. This integrative perspective deepens our understanding of POAG pathogenesis and provides a novel theoretical foundation for early diagnosis, multidimensional intervention, and precision therapy.

Background and Objectives: Glaucoma is a group of conditions of the eye that can damage the optic nerve, leading to optic neuropathy. Nevertheless, due to its chronic characteristics, it could also be the background for psychoneurotic disorders based on the psychological and emotional stress that it causes. The presented study aimed to examine the characteristics and the occurrence of obsessionality and hysteria, as well as Open-Angle Glaucoma (OAG) in glaucoma patients. Materials and Methods: A cross-sectional study was conducted in the Clinic for Eye Diseases at the Clinical Hospital Center Osijek on 200 patients with different stages of OAG progression from December 2023 to December 2024. A Crown-Crisp Experiential Index (CCEI) was used to observe the influence of different degrees of OAG damage on the severity of obsessionality and hysteria. Results: The obsessionality score was higher in women than in men (Mann-Whitney U test, p < 0.001). Multivariate logistic regression (stepwise method) indicated a significant model for predicting hysteria, consisting of one predictor: female sex (odds ratio = 2.9). According to CCEI, using bivariate and multivariate logistic regression to predict obsessionality, no significant predictors or models were observed. Conclusions: The psychological toll of coping with glaucoma could exacerbate glaucoma. Further investigations are necessary to help us understand OAG personality traits and establish a stable methodology for extending appropriate care to glaucoma patients.

This case illustrates that a pituitary tumor can be masked by coexisting glaucoma, and that early differential diagnosis using optical coherence tomography (OCT), Central 24-2 threshold visual field testing, and magnetic resonance imaging (MRI) to facilitate timely surgical intervention might avoid irreversible vision loss. A 73-year-old female was initially diagnosed with cataracts and glaucoma and monitored by retinal nerve fiber layer (RNFL) measurements using OCT, with readings of 97 μm in the right eye and 85 μm in the left eye in 2010. This case was followed continuously by the author for over 17 years. Although her intraocular pressure remained well controlled, her left eye RNFL progressively declined, dropping to 72 μm in 2022 and further to 62 μm in 2025. Visual field testing in 2016 revealed bitemporal defects, including a glaucomatous arcuate defect, which became increasingly pronounced by 2020 and, by 2025, demonstrated severe defects in the left eye, inconsistent with controlled glaucoma. MRI in 2025 confirmed a 2.2 cm adenoma compressing the optic chiasma with left optic nerve atrophy. In retrospect, review of the chart revealed early warning signs of a brain lesion, and the tumor was unfortunately identified only after significant vision loss had already occurred, underscoring that early diagnosis and timely surgery can prevent and sometimes reverse vision loss. Any atypical glaucoma presentation or inexplicable change in a patient with controlled glaucoma should therefore be carefully evaluated to exclude pituitary or other intracranial tumors, particularly through diligent visual field review and optic nerve examination. Glaucoma is fundamentally an optic nerve disease, and multidisciplinary cooperation is essential: neurologists managing pituitary tumor patients should refer them to ophthalmologists to rule out coexisting glaucoma, while ophthalmologists encountering unusual glaucoma cases should refer patients to primary care physicians or neurologists to exclude intracranial pathology. This report aims to remind clinicians of this rare but well-documented condition and highlight early diagnostic clues to prevent the pituitary tumor from being masked by a narrow specialty focus.

Lipopolysaccharide (LPS), a component of Gram-negative bacteria, is a potent activator of the innate immune system and has been implicated in the pathogenesis of eye diseases, including age-related macular degeneration (AMD), primary open-angle glaucoma (POAG), and diabetic retinopathy (DR). LPS enters systemic circulation through bacterial lysis or active secretion, leading to endotoxemia-either acute or chronic. Chronic endotoxemia, often resulting from gut dysbiosis, may link microbial imbalances to eye diseases. Indeed, chronic LPS exposure may contribute to both systemic and local inflammation. Within the retina, it activates resident immune and structural cells triggering pro-inflammatory cytokine production, oxidative stress, complement cascade activation, and inflammasome activation. These immune cascades compromise blood-retinal barrier integrity, increase vascular leakage, and impair neuronal viability. LPS exposure can stimulate the secretion of pro-angiogenic factors, promoting the development of neovascularization within the retina. Furthermore, the aging retina may be particularly vulnerable to LPS-mediated damage due to an increased exposure to LPS (linked to microbial dysbiosis and alterations of both intestinal and blood-retinal barriers) as well as a reduced capacity for repair. Although direct human evidence remains limited, emerging experimental data support a mechanistic role for LPS in AMD, glaucoma, and DR. This review emphasizes that addressing the impact of chronic endotoxemia represents a promising avenue for both understanding and treating eye diseases. Continued investigation into the multifaceted roles of LPS may yield innovative biomarkers and therapeutic targets to slow or prevent neurodegenerative, vascular, and inflammatory processes underlying conditions such as AMD, glaucoma, and DR.

PurposeTo report a rare case of bilateral conjunctival and epibulbar extranodal Rosai-Dorfman disease (RDD) without lymph node involvement, potentially associated with long-term use of benzalkonium chloride (BAK)-containing glaucoma medications.Case PresentationA 68-year-old male with a 10-year history of primary open-angle glaucoma, managed with multiple topical hypotensive agents, developed bilateral conjunctival and epibulbar nodules following chronic recurrent episodes of conjunctival inflammation over those 10 years. Histopathological examination and immunohistochemical staining confirmed the diagnosis of RDD, characterized by histiocytic proliferation with prominent emperipolesis. The patient underwent surgical excision of the lesions with homoconjunctival grafting. Postoperatively, his glaucoma regimen was modified to a preservative-free (BAK-free) topical therapy, and selective laser trabeculoplasty was performed to reduce the need for additional topical therapy. Comprehensive systemic evaluation revealed no lymphadenopathy or other extranodal organ involvement. At one-year follow-up, there was no evidence of recurrence, conjunctival inflammation had markedly subsided, and the glaucoma remained stable.ConclusionsThis case highlights a potential association between chronic conjunctival inflammation induced by BAK-containing glaucoma medications and the de novo emergence of epibulbar RDD. Although RDD remains a rare and poorly understood histiocytic disorder, our findings suggest that sustained ocular surface inflammation may act as a trigger in its pathogenesis. To our knowledge, this is the first reported case of ocular RDD potentially linked to long-term exposure to topical hypotensive therapy. Further studies are warranted to investigate the role of chronic inflammatory stimuli in the development of extranodal RDD, particularly within ocular tissues.

Primary open-angle glaucoma (POAG) is a leading cause of blindness, yet the biochemical mechanisms underlying disease progression remain poorly understood. This study characterized aqueous humor (AH) across early and advanced stages of POAG using large-scale proteomics. AH samples were collected from patients with mild POAG, advanced POAG, and non-glaucomatous controls in this prospective cross-sectional study. Profiling of 8000 proteins was performed using an antibody array. Hierarchical clustering, principal component analysis (PCA), Gene Ontology (GO), and pathway enrichment analyses were performed to identify differentially expressed proteins, biological processes, and molecular functions associated with disease stages. Top differential proteins were also correlated with key clinical parameters. Proteomic signatures demonstrated distinct clustering between control and glaucoma patients, with progressive shifts from mild to advanced stages. Comparisons between control and each glaucoma group revealed significant enrichment in pathways related to wound healing, extracellular matrix (ECM) remodeling, and immune responses. Notably, distinct proinflammatory and immune proteins and pathways were enriched when comparing mild to advanced POAG stages. Finally, the top differential AH proteins correlated with multiple clinical endpoints, including intraocular pressure and a variety of retinal outcomes. This signature revealed a tight network associated with disease stage, oriented on immune cell migration and function, and identifying soluble TRPC6 as a novel biomarker. To our knowledge this is the first study to compare large scale proteomic analysis of AH from patients with POAG across disease stages, suggesting new mechanisms underlying glaucoma progression.

This case report describes a rare mechanical etiology of postoperative refractive surprise - anterior displacement of an intraocular lens (IOL) secondary to localized posterior synechiae - in a patient with plateau iris syndrome (PIS) following combined clear lens extraction (CLE) and minimally invasive glaucoma surgery (MIGS). A 29-year-old man with PIS and medically refractory chronic angle-closure glaucoma underwent an uneventful left-eye CLE, goniosynechiolysis, implantation of a toric extended depth-of-focus (EDOF) IOL, and insertion of three iStent infinite® (Glaukos Corporation, Aliso Viejo, CA, USA) devices. Five weeks postoperatively, he presented with blurred vision, asthenopia, and binocular diplopia associated with a sudden -2.50 D myopic surprise. Dynamic slit-lamp examination revealed localized posterior synechiae extending from 1 to 5 o'clock. These adhesions exerted asymmetrical traction on the capsular bag, resulting in anterior displacement and temporal tilt of the IOL complex without pupillary block. The patient subsequently underwent targeted synechiolysis under local anesthesia. Postoperative biometry demonstrated an increase in anterior chamber depth (ACD) from 2.90 mm to 3.02 mm, confirming posterior repositioning of the IOL. Restoration of the effective lens position (ELP) reversed the myopic shift and resolved the patient's symptoms. This case highlights localized posterior synechiae as a rare but reversible cause of postoperative refractive surprise and underscores the importance of meticulous dynamic slit-lamp evaluation and ACD monitoring in patients with complex anterior segment conditions presenting with unexpected refractive outcomes. Timely synechiolysis may serve as a definitive and restorative intervention.

LIM domain kinase 1 (LIMK1) has been identified as a promising therapeutic target for a variety of conditions, such as chronic pain, open-angle glaucoma, various cancers, schizophrenia, and Fragile X syndrome. However, identifying inhibitors that selectively inhibit LIMK1 over LIM domain kinase 2 (LIMK2) has proven to be challenging. A viable strategy to overcome this difficulty is the development of covalent inhibitors, which can offer both potency and selectivity for LIMK1 due to a reactive cysteine, C349, near the active site absent in its paralog LIMK2. Here we identify an irreversible covalent inhibitor of LIMK1 (cLIMK1i), which is highly selective for LIMK1 over both LIMK2 and a panel of over 100 kinases. A crystal structure of LIMK1 soaked with cLIMK1i reveals it is a type I inhibitor occupying the ATP-binding site with its acrylamide moiety oriented toward the P-loop where C349 resides. Computational modeling supports that the P-loop of LIMK1 can adopt a conformation compatible with covalent bond formation. Biochemical and biophysical characterization of the interaction of cLIMK1i with LIMK1 demonstrates that the covalent bond with LIMK1-C349 is essential for its potent inhibition. These results support covalent inhibition of LIMK1 as a viable strategy for selectively inhibiting LIMK1 over LIMK2 and other kinases.