Search Results (449)

Optic neuropathy represents a leading cause of irreversible vision loss, in which oxidative stress, chronic inflammation, dysregulated lipid metabolism, and mitochondrial dysfunction contribute to the progressive degeneration of retinal ganglion cells (RGCs). In recent years, a number of nutraceuticals have been investigated as potential neuroprotective agents; however, the molecular mechanisms through which they exert their effects remain incompletely understood and are often considered in isolation. In the present in silico study, an integrative network-based approach was applied for a systematic analysis of the predicted molecular targets of selected nutraceuticals with antioxidant and anti-inflammatory potential. By combining target prediction, protein–protein interaction analysis, and functional enrichment, their functional convergence was assessed in the context of optic nerve pathophysiology. The results indicate that, despite their chemical and functional heterogeneity, the investigated nutraceuticals do not act through fully independent mechanisms but instead converge on interconnected regulatory axes. In particular, lipid–inflammatory signaling, epigenetic and stress-adaptive mechanisms, as well as nuclear-receptor mediated transcriptional regulation emerged as key pathways. These pathways form integrated molecular models potentially determining cellular susceptibility to injury and the adaptive capacity of RGCs. In conclusion, the present analysis provides a systems-level framework for understanding the neuroprotective potential of nutraceuticals, highlighting the importance of network convergence and multi-target activity. The obtained results support the conceptual shift from isolated antioxidant strategies towards integrative, network-oriented approaches in the study of optic neuropathy. Full article

Cytomegalovirus (CMV) infection of the anterior segment is increasingly recognized as an important cause of corneal endotheliitis and secondary glaucoma, even in immunocompetent individuals. CMV corneal endotheliitis typically presents with coin-shaped or linear keratic precipitates (KPs), corneal edema, mild anterior chamber inflammation, and recurrent intraocular pressure (IOP) elevation; persistent or episodic ocular hypertension may progress to glaucomatous optic neuropathy if inadequately treated. Definitive diagnosis relies on aqueous humor polymerase chain reaction (PCR) testing for CMV DNA, supported by adjunctive imaging including specular microscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). Management requires a comprehensive strategy integrating antiviral therapy, anti-inflammatory treatment, and appropriate IOP control. Topical or systemic ganciclovir remains the cornerstone, while refractory disease may necessitate surgical intervention. Older age and male sex, host immune status, prolonged or recurrent CMV infection, and pre-existing ocular conditions are major risk factors for progression and poor outcomes. The pathogenesis of secondary glaucoma is thought to involve both direct viral cytopathic effects and inflammation-mediated damage to the trabecular meshwork (TM), resulting in impaired aqueous outflow. Therefore, early recognition, accurate diagnosis, and effective treatment are essential to prevent corneal decompensation and permanent vision loss. Full article

High myopia is increasingly prevalent and complicates glaucoma diagnosis. Axial elongation remodels the optic nerve head (ONH) and parapapillary tissues, producing structural and functional changes that mimic glaucoma—termed myopic optic neuropathy (MON). We reviewed current concepts on the MON–glaucomatous optic neuropathy (GON) spectrum and practical implications for diagnosis, monitoring, and management. A focused PubMed search targeted high/pathologic myopia, glaucoma, ONH and parapapillary anatomy, optical coherence tomography (OCT)/OCT angiography, visual fields, and progression. Major reviews, population-based studies, and longitudinal investigations were prioritized and integrated into a clinician-oriented framework. Greater myopia severity is associated with higher glaucoma risk and, in some cohorts, greater treatment burden, including surgery. Disc tilt, torsion, parapapillary atrophy, and staphyloma-related curvature complicate structural assessment and reduce reliability of single-visit OCT due to magnification and segmentation artifacts. Visual fields may be atypical, and central defects are under-sampled by standard 24-2 testing. Progression-centered strategies—combining event- and trend-based analyses and confirmation rules—distinguish MON-predominant changes from true GON or overlap and guide follow-up. In highly myopic eyes, multimodal structure–function assessment anchored on reproducible progression enhances diagnostic confidence and guides individualized intraocular pressure–lowering therapy. Standardized reporting of myopia definitions and progression criteria is recommended. Full article

Background/Objectives: The OPA1 gene encodes a dynamin-related GTPase essential for mitochondrial fusion. Variants in OPA1 are a major cause of autosomal dominant optic atrophy (DOA). A subset of DOA patients exhibits hearing loss, often manifesting as auditory neuropathy spectrum disorder (ANSD). In this study, we aimed to describe the frequency of OPA1-related hearing loss in a large cohort of patients with hearing loss and to explore the genotype–phenotype correlations and appropriate interventions. Methods: A total of 18,475 Japanese patients with hearing loss were recruited. Targeted massively parallel sequencing of 158 deafness-related genes was performed, and individuals with OPA1 variants were identified. Clinical data, including age of onset, audiological findings, and systemic features, were retrospectively reviewed. Results: Ten individuals from eight independent families carrying OPA1 variants were identified. Three variants were classified as pathogenic or likely pathogenic, while five were variants of uncertain significance. Hearing loss was typically post-lingual in onset and progressive, with predominantly mild-to-moderate severity. Missense variants tended to be associated with DOA-plus phenotypes and ANSD. Five patients obtained only limited benefit from hearing aids, whereas one patient who received a cochlear implant achieved good speech perception. Conclusions: OPA1 is a rare causative gene for hearing loss and is frequently associated with the ANSD phenotype. Affected individuals exhibited phenotypic heterogeneity, which may reflect incomplete penetrance or the influence of mitochondrial DNA-related factors. Full article

Glaucoma is a multifaceted optic neuropathy, characterized by the progressive loss of retinal ganglion cells. This damage frequently continues even after intraocular pressure (IOP) has been effectively lowered. This resistance to conventional IOP-lowering therapy underscores the critical role of interacting IOP-independent mechanisms; specifically metabolic failure and systemic mitochondrial dysfunction have emerged as key parallel drivers. This review analyzes the paradigm shift from a pressure-centric model to a bioenergetic one, focusing on mitochondrial function, peripheral blood mononuclear cell (PBMC) biomarkers, and oxygen consumption dynamics. We synthesize evidence demonstrating that glaucoma patients exhibit a metabolic vulnerability, characterized by lower PBMC oxygen consumption rates and depleted systemic nicotinamide adenine dinucleotide levels relative to healthy individuals. Furthermore, compromised systemic respiratory performance correlates with more rapid worsening of visual fields and structural thinning, independent of IOP status. Moreover, we delineate the role of Complex I defects, SARM1-mediated axonal degeneration, and proteomic alterations, which indicate defective mitophagy. These findings establish systemic metabolic profiling as a valuable supplementary tool for assessing patient risk and support the clinical translation of neuroprotective therapies targeting mitochondrial bioenergetics, specifically nicotinamide, pyruvate, coenzyme Q₁₀, and metformin. Full article

Mitochondrial reactive oxygen species (mtROS) play a dual role in retinal physiology, acting as essential redox signalling mediators under homeostatic conditions but driving oxidative damage and neurodegeneration once regulatory thresholds are exceeded. Owing to the exceptionally high energetic demands of retinal neurons and supporting cells, even subtle perturbations in mitochondrial redox balance can precipitate progressive retinal dysfunction. Increasing evidence indicates that retinal neurodegenerative diseases, including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), and inherited optic neuropathies, are characterised not by uniform oxidative stress, but by disease- and stage-specific mtROS signatures shaped by mitochondrial quality control capacity. This review synthesises current insights into the sources, regulation, and signalling functions of mtROS in the retina, with particular emphasis on threshold-dependent redox transitions, reverse electron transport, and the progressive failure of mitochondrial quality control mechanisms, including mitophagy, mitochondrial dynamics, and redox-responsive transcriptional networks. The limitations of non-selective antioxidant strategies are critically examined, highlighting why indiscriminate ROS suppression has yielded limited clinical benefit. In contrast, emerging therapeutic approaches aimed at recalibrating mitochondrial redox homeostasis, rather than abolishing physiological signalling, are discussed in the context of disease stage, metabolic state, and mitochondrial competence. By integrating redox biology with mitochondrial quality control and precision medicine concepts, this review proposes a unifying framework in which retinal neurodegeneration is governed by regulated mtROS signalling and the progressive exhaustion of mitochondrial resilience. This model defines critical therapeutic windows for mitochondria-targeted intervention and provides a framework for biomarker-guided patient stratification. Full article

Non-arteritic ischemic optic neuropathy (NAION) results from vascular insufficiency within the optic nerve head. The precise pathogenesis of NAION remains unclear; however, insufficient blood supply from the short posterior ciliary arteries and the choroidal circulation has been associated with its development. Although major risk factors include diabetes, hypertension, and hyperlipidemia, coronavirus disease 2019 (COVID-19) may also contribute to the development of NAION. This literature review presents our case of NAION associated with COVID-19 infection and summarizes previously reported cases of NAION following COVID-19 infection published in the English-language literature worldwide. Because direct infection of ocular tissues, including ocular vessels, via the angiotensin-converting enzyme 2 receptor is thought to contribute to the development of NAION, cases of NAION associated with COVID-19 vaccination were excluded from this review. Furthermore, we discuss the possible molecular mechanisms underlying the development of NAION after COVID-19 infection and highlight the potential risks of COVID-19 for clinical ophthalmologists. Full article

Background: The aim of this study was to evaluate the influence of demographic, clinical and physical factors on the occurrence of ocular complications after ruthenium-106 (Ru-106) brachytherapy, iodine-125 (I-125) brachytherapy and proton therapy of uveal melanoma. Methods: A retrospective analysis of 300 patients’ electronic and paper medical records treated for uveal melanoma at the Department of Ophthalmology and Ocular Oncology, University Hospital in Krakow, Poland, from May 2014 to December 2016 was performed. The created database, which includes numerous parameters characterizing patients, tumors, applied treatments and their effects, with particular emphasis on the occurrence of ocular complications, was subjected to detailed analysis. The influence of selected factors on the occurrence of identified complications was checked by performing a univariable Cox proportional hazards regression analysis, and then the factors that were statistically significant were included in a multivariable Cox proportional hazards regression analysis which gave the final results. Results: Of the 300 patients, 125 (41.67%) were treated with Ru-106 brachytherapy (87 (29%) with CCB plaque and 38 (12.67%) with COB plaque), 102 (34%) with I-125 brachytherapy and 73 (24.33%) with proton therapy. Mean follow-up was 88.63 months (median 89, range: 20–127). The occurrence of cataract was associated with the older age of patients. Maculopathy was associated with female sex, younger age, use of I-125 brachytherapy, tumor location involving the macula and/or optic disc and moderate tumor pigmentation. Diagnosis of systemic hypertension was associated with a lower risk of maculopathy. Retinopathy was associated with younger age, tumor location involving the macula and/or optic disc and the use of I-125 brachytherapy. Optic neuropathy was associated with younger age, greater tumor largest base diameter, tumor location involving the macula and/or optic disc and the use of I-125 brachytherapy. Secondary glaucoma was associated with baseline best corrected visual acuity (BCVA) weaker than 0.5, greater tumor thickness, involvement of the left eye and the use of I-125 brachytherapy. Vitreous hemorrhage was associated with greater tumor thickness, tumor location including the macula and/or optic disc and mushroom-shaped tumor. Conclusions: Our study demonstrated an association between demographic, clinical, and physical factors and the occurrence of ocular complications after radiotherapy for uveal melanoma. Full article

Background: Fibrotic remodelling of the lamina cribrosa (LC) is a defining pathological feature of glaucomatous optic neuropathy and contributes to progressive optic nerve head deformation and axonal vulnerability. LC cells from glaucomatous donors exhibit a myofibroblast-like phenotype characterised by excessive extracellular matrix (ECM) production, a process associated with chronic cellular stress. cAMP responsive element-binding protein 3-like 1 (CREB3L1) is an endoplasmic reticulum–resident transcription factor implicated in stress-responsive regulation of collagen synthesis and matrix homeostasis. The role of CREB3L1 in glaucomatous LC cells, however, remains poorly defined. Methods: Primary human LC cells derived from donors with confirmed glaucoma (GLC; n = 3) and age-matched non-glaucomatous controls (NLC; n = 3) were examined. CREB3L1 expression was assessed at the mRNA and protein levels using quantitative RT-PCR and Western immunoblotting. The functional effects of CREB3L1 suppression were evaluated using siRNA-mediated knockdown in GLC cells, followed by analysis of ECM gene transcription (α-smooth muscle actin, collagen type I alpha 1, fibronectin) and cellular metabolic activity using an MTS assay. Results: CREB3L1 mRNA and protein expression were significantly elevated in GLC cells compared with NLC cells. siRNA-mediated knockdown of CREB3L1 effectively reduced its expression in GLC cells and was associated with significant suppression of profibrotic ECM gene transcription. In addition, CREB3L1 knockdown resulted in a marked reduction in cellular metabolic activity in glaucomatous LC cells. Conclusions: These findings identify CREB3L1 as a regulator of ECM-associated gene expression and cellular behaviour in glaucomatous lamina cribrosa cells. While preliminary, the data suggest that CREB3L1 may contribute to pathological fibrotic remodelling at the optic nerve head. Further mechanistic and in vivo studies will be required to determine whether modulation of CREB3L1-mediated pathways represents a viable therapeutic strategy in glaucoma. Full article

Background/Objectives: The aim of this study was to investigate the longitudinal visual field (VF) and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) changes in open-angle glaucomatous (OAG) participants with unilateral peripapillary intrachoroidal cavitation (PICC) and to identify factors associated with VF progression. Methods: Sixty eyes of 30 OAG patients with unilateral PICC were included in this retrospective longitudinal observational study. Humphrey 24–2 VF testing and optical coherence tomography scanning were performed in all eyes over a period exceeding 5 years. VF progression was assessed using mean deviation (MD) and superior and inferior total deviation (TD) slopes. Structural progression was evaluated using global, superior, and inferior cpRNFLT thinning rates. Longitudinal changes were compared between PICC eyes and their contralateral non-PICC eyes. Factors associated with superior or inferior TD slopes were analyzed using linear mixed-effects models. The following variables were included as explanatory variables: age, sex, intraocular pressure, axial length, Bruch’s membrane opening (BMO) and scleral flange opening (SFO) area, SFO/BMO offset magnitude, disk tilt, disk rotation, baseline superior or inferior TD, baseline corresponding cpRNFLT, and the presence of PICC. Results: MD slope was −0.24 ± 0.35 dB/year in PICC eyes and −0.35 ± 0.53 dB/year in contralateral eyes. There was no significant difference in MD slope, superior and inferior TD slope, or the rate of cpRNFLT thinning (all p > 0.05). In multivariable analysis, the presence of PICC was associated with slower progression in the corresponding superior VF (p = 0.037), whereas greater SFO/BMO offset magnitude was associated with faster progression (p = 0.047). Conclusions: OAG eyes with PICC exhibited modest functional and structural progression over 5 years, comparable to that of contralateral non-PICC eyes. The presence of PICC was associated with slower corresponding superior VF progression, whereas greater myopia-associated structural change was related to faster progression. Our findings characterize the clinical course of eyes with pronounced myopic ONH deformation, highlighting the importance of detailed ONH structural assessment in the management of myopic glaucoma. Full article

Multiple sclerosis (MS) is a chronic immune-mediated demyelinating disorder of the central nervous system, traditionally considered distinct from neuromuscular diseases, which primarily affect the peripheral nervous system, neuromuscular junction, or skeletal muscle. Growing clinical and experimental evidence, however, indicates that certain neuromuscular disorders may coexist with MS or shared overlapping pathophysiological, immunological, and metabolic mechanisms. This narrative review summarizes reported associations between MS and neuromuscular diseases, with particular focus on well-characterized overlaps such as Leber hereditary optic neuropathy (LHON)-associated MS (Harding’s disease), combined central and peripheral demyelination (CCPD), and myasthenia gravis (MG) co-occurring with MS. Additional associations with Charcot–Marie–Tooth disease, mitochondrial disorders with MS-like phenotypes, inherited and autoimmune myopathies, and rare syndromes such as Guillain–Barré syndrome are also discussed. This review highlights proposed mechanisms potentially linking these conditions, including immune dysregulation, T- and B-cell-mediated autoimmunity, antibody-driven demyelination, mitochondrial dysfunction, impaired neuromuscular transmission, and molecular mimicry. Limitations of the current literature are acknowledged, particularly the predominance of case reports for rare associations and the frequent lack of systematic screening for coexisting disorders. By integrating evidence from case series, cohort studies, and mechanistic research, this review provides a comprehensive overview of the biological and clinical intersections between MS and neuromuscular diseases. Enhanced understanding of these overlaps may improve diagnostic accuracy, guide individualized management strategies, and inform future research on shared neuroimmunological and neurodegenerative pathways. Full article

With the global population predicted to reach 10 billion by 2050, pesticides are essential for agricultural production. However, they can introduce chemical stressors into aquatic ecosystems. Chlorpyrifos (CPF) is a widely used organophosphate insecticide that can enter aquatic environments and poses potential risks to early-life-stage fish. Because the retina is an extension of the central nervous system and vision-guided behaviors are highly sensitive to neural dysfunction, we hypothesized that CPF exposure disrupts neurobehavioral and visual function via oxidative stress and PPARα-related signaling. Zebrafish larvae were exposed to CPF (0.01, 0.1, 1, 10, and 100 μg/L) with a vehicle control (VC). During the photomotor response assay, exposure to 100 μg/L CPF reduced overall swimming activity by 48.90% and dark-period activity by 57.71%, whereas 1 μg/L CPF modestly increased total distance by 6.96% (p = 0.003) and dark-period distance by 5.40% (p = 0.011). Transcriptomic profiling highlighted nervous- and vision-related functional categories, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment implicated pathways including gonadotropin-releasing hormone (GnRH), mitogen-activated protein kinase (MAPK), and peroxisome proliferator-activated receptor (PPAR) signaling. Targeted neurotransmitter metabolomics showed significant increases in dopamine, γ-aminobutyric acid (GABA), and acetylcholine across treatment groups, indicating broad neurotransmitter dysregulation. Consistent with these findings, neuronal fluorescence in Tg (elavl3: EGFP) larvae decreased by 12.1% and 32.5% in the 1 and 100 μg/L groups, respectively (p < 0.001), and glial fibrillary acidic protein (GFAP) immunofluorescence increased in the eye/brain/olfactory bulb at 1 μg/L (p = 0.037) and 100 μg/L (p = 0.002). Histology further showed retinal injury, with a 14.3% reduction in photoreceptor layer thickness at 100 μg/L (p = 0.034). Mechanistically, coexposure to a PPARα antagonist (GW6471) alleviated CPF-induced behavioral deficits (1.80-fold increase in dark locomotion) and reduced elevated GABA and dopamine levels by 36.8% and 47.3%, respectively. Together, these results indicate that CPF can impair neuro-visual development and that oxidative stress and PPARα-related signaling are closely associated with these effects. Full article

Background: UBE has gained popularity as a minimally invasive alternative to open spinal procedures. However, it raises concerns about potential ocular complications. Despite these concerns, there is a lack of studies evaluating UBE’s impact on retinal microvasculature using objective imaging tools such as OCTA. This study aims to evaluate the effects of UBE on the microvascular structures of the retina and optic nerve using OCTA, and to determine whether UBE poses a risk for perioperative vision loss. Methods: This study included 32 patients who underwent UBE for lumbar stenosis and received ophthalmologic examinations preoperatively, and at postoperative weeks 1 and 4. Patients with systemic or ocular vascular comorbidities were excluded. OCTA parameters including vascular density (VD), foveal avascular zone (FAZ), retinal nerve fiber layer (RNFL), central macular thickness (CMT), and subfoveal choroidal thickness (SFCT) were evaluated using swept-source OCT. Results: No patients experienced clinical vision loss. A statistically significant change was observed over time in FAZ (p = 0.043), VDd superior (p = 0.018), VDd temporal (p = 0.032), and RNFLts (p = 0.032). However, only VDd superior showed a statistically significant decrease at postoperative week 4 compared to baseline (p = 0.050). All other parameters either returned to baseline or showed no significant change. No clinically relevant visual changes were detected. Conclusions: In this study, UBE spinal surgery was not associated with clinically evident visual loss or sustained OCTA-detected microvascular alterations during short-term follow-up. These findings should be interpreted as reflecting the absence of detectable short-term changes rather than definitive evidence of ocular safety. Full article

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. Full article

Background: Bilateral optic neuritis is a rare condition generally associated with inflammatory, demyelinating, or toxic causes. Its association with glyphosate exposure has rarely been documented. Case Presentation: A 66-year-old man with hypertension, hypercholesterolemia, and hypothyroidism developed rapid bilateral vision loss within hours after acute inhalational exposure to glyphosate during agricultural work. MRI showed bilateral optic nerve hyperintensity consistent with optic neuritis. Cerebrospinal fluid and serum anti-NMO antibody tests were negative, while visual evoked potentials demonstrated increased latencies. High-dose corticosteroid therapy led to progressive clinical improvement. At follow-up, MRI revealed no new lesions and the patient experienced near-complete visual recovery. Conclusion: This case suggests a possible link between acute glyphosate exposure and reversible bilateral optic neuritis. Early recognition and corticosteroid therapy may support full functional recovery even in severe presentations. Full article