Search Results (124)

Background: Glaucoma is a group of eye conditions that damage the optic nerve, and it can be interconnected with psychoneurotic disorders due to the psychological and emotional stress that comes with such a chronic condition. The aim of this study was to examine the characteristics of the occurrence of anxiety, depression and open-angle glaucoma (OAG) in glaucoma patients from December 2023 to December 2024. Methods: This cross-sectional study was conducted on 200 patients with three different stages of OAG. Multiple questionnaires were used to determine the influence of different OAG stages on the severity of anxiety and depression. Results: While predicting the anxiety expression, in a multivariate logistic regression (stepwise method), there was a significant model in predicting the expression of anxiety: female gender (Odds ratio (OR) = 3.03), age of 66 and over (OR = 3.4) and the feeling of being under stress (OR = 7.07). In the prediction of a higher severity of depression, predictors are age 66 and older (OR = 2.03) and feeling stressed (OR = 9.47). Conclusions: While glaucoma and psychoneurotic disorders affect different systems in the body, the psychological toll of living with glaucoma can lead to exacerbation of glaucoma. Full article

SEC31A-related neurodevelopmental disorder (Halperin–Birk syndrome) was recently identified in two siblings who shared the phenotype of profound developmental delay, structural brain defects, spastic quadriplegia with multiple contractures, seizures, dysmorphism, and optic nerve atrophy. Both patients died during childhood. In this study, we identified an additional patient who suffers from global developmental delay and seizures. Genetic analysis inclusive of whole exome and genome sequencing identified a homoallelic variant in the SEC31A (p.Cys453Trp). Various in silico classifiers predicted a deleterious effect of the replacement of cystein with tryptophan at the 453rd position. Protein–protein interaction (PPI) network analysis of SEC31A revealed high-confidence interactions with SEC13, SEC23A, and SEC23B, suggesting potential regulatory roles in these processes. Structural analysis of the SEC31A–SEC13 interaction and the Cys453Trp mutant in SEC31A predicted that the stability of coat protein complex II would be compromised. Our findings support the clinical correlation of SEC31A variants with neurodevelopmental disorder. Full article

Objectives: This review explores the role of swept-source optical coherence tomography (OCT) in diagnosing and monitoring optic nerve neuropathy in Wernicke’s encephalopathy (WE) due to hyperemesis gravidarum, including a case of neuropathy from intractable vomiting in pregnancy. Methods: A literature search was conducted in the PubMed database to select high-quality reviews and original articles on the use of swept-source OCT for assessing optic nerve involvement in WE due to hyperemesis gravidarum. Results: WE is a potentially fatal neuropsychiatric syndrome caused by thiamine deficiency due to various causes, like alcoholism, malnutrition, and prolonged parenteral nutrition. This condition can cause neurological disorders such as imbalance, altered mental status, nystagmus, and ophthalmoplegia. Sometimes, there is also a deterioration of visual acuity with swelling of the optic disc. OCT is a non-invasive imaging tool that can detect optic nerve involvement in WE by assessing peripapillary retinal nerve fiber layer (pRNFL) thickness. In the acute phase, optic disc edema and increased pRNFL thickness may be observed, while chronic-phase changes include optic nerve atrophy and pRNFL thinning. WE may occur in the course of hyperemesis gravidarum in pregnant women. We present a case of a 23-year-old woman at 14 weeks of gestation with WE due to severe hyperemesis gravidarum, manifesting as visual impairment and neurological deficits. MRI confirmed the diagnosis, while OCT revealed transient pRNFL thickening followed by optic nerve atrophy. Conclusions: Early diagnosis and thiamine supplementation are crucial to preventing severe complications. OCT is a valuable tool for detecting and tracking optic nerve changes in WE. Full article

Artificial intelligence (AI) is reshaping precision medicine by revealing diagnostic links between ocular biomarkers and systemic musculoskeletal disorders. This review synthesizes clinical evidence on the associations between optical coherence tomography (OCT)-derived parameters, such as retinal nerve fiber layer (RNFL) thinning and choroidal thickness, and conditions including osteoporosis, cervical spine instability, and inflammatory arthritis. The findings, based on an analysis of studies that integrate AI with ocular and musculoskeletal imaging, highlight consistent correlations between ocular microstructural changes and systemic degenerative pathologies. These results suggest that the eye may serve as a non-invasive window into biomechanical dysfunction. This review also discusses the emerging role of AI-assisted surgical systems informed by ocular metrics. Overall, AI-driven ocular analysis offers a promising avenue for early detection and management of musculoskeletal disease, supporting its clinical relevance and interdisciplinary potential. Full article

Pontocerebellar hypoplasia is a rare neurodegenerative syndrome characterized by severe hypoplasia or atrophy of pons and cerebellum that may be associated with other brain malformations, microcephaly, optic nerve atrophy, dystonia, ataxia and neuromuscular disorders. At this time, there are 17 variants of PCH distinguished by clinical presentation and distinctive radiological and biochemical features in addition to pontine and cerebellar hypoplasia. PCH1 is defined as PCH variant associated with anterior horn degeneration in the spinal cord with muscle weakness and hypotonia, and is associated with recessive variants in genes VRK1, EXOSC3, EXOSC8, EXOSC9 and SLC25A46. Neuromuscular manifestations may clinically present as amyotrophic lateral sclerosis (ALS), motor neuropathy (HMN) or neuronopathy (non-5q spinal muscular atrophy; SMA) or sensorimotor polyneuropathy (HMSN). Physiologic functions of PCH1-associated genes include regulation of RNA metabolism, mitochondrial fission and neuronal migration. Overall, complex phenotypes associated with PCH1 gene variants ranging from PCH and related neurodevelopmental disorders combined with neuromuscular disorders to isolated neuromuscular disorders have variable outcomes with isolated neuromuscular disorders typically having later onset with better outcomes. Improved understanding of pathogenesis of pontocerebellar hypoplasia and its association with motor neuronopathies and peripheral neuropathies may provide us with valuable insights and lead to potential new therapeutic targets for neurodegenerative disorders. Full article

Nonsyndromic and syndromic hereditary optic neuropathies (HONs) encompass a variety of genetic illnesses that cause progressive optic nerve damage, resulting in considerable vision impairment. These disorders result from pathogenic variants in mitochondrial or nuclear DNA, impacting essential cellular processes like oxidative phosphorylation, mitochondrial dynamics, and neuroprotection. Advances in next-generation sequencing (NGS) have significantly improved the identification of genetic variations, enabling precise diagnoses and genotype–phenotype correlations. This review consolidates current knowledge regarding the classification, molecular pathogenesis, clinical manifestations, diagnostic methodologies, and emerging therapeutic strategies for HONs. The critical role of mitochondrial dysfunction in optic nerve degeneration highlights the necessity for multimodal therapeutic approaches. Recent clinical trials evaluating gene therapy for Leber hereditary optic neuropathy (LHON) and neuroprotective strategies in dominant optic atrophy (DOA) are discussed. Additionally, individualized therapeutic interventions, as demonstrated by recent case studies involving tailored gene therapies, are evaluated. The integration of molecular and imaging biomarkers in future personalized treatment strategies aims to enhance prognosis and therapeutic outcomes. Full article

Background and Objectives: Pathogenic variants in the PAX2 gene have been associated with a spectrum of eye and kidney disorders, ranging from papillorenal syndrome (known as renal coloboma syndrome) to isolated nephrosis without kidney morphological anomalies (focal segmental glomerulosclerosis), inherited in an autosomal dominant manner. However, due to the growing number of reports of pathogenic variants in the PAX2 gene, it is observed that genotype–phenotype correlation is not always consistent. We present patients from two unrelated families with PAX2 pathogenic variants c.685C>T and c.250G>A, highlighting the diverse phenotypic expression of PAX2-related disorders. Materials and Methods: We analyzed clinical and genetic data from two families who were tested for genomic abnormalities using targeted next-generation sequencing and Sanger sequencing for segregation analysis. Results: In Family A, a 27-year-old male presented with chronic kidney disease stage 3, proteinuria, and multicystic kidney dysplasia diagnosed at 11 years old. An ophthalmologic examination revealed bilateral optic nerve dysplasia. In Family B, a 6-year-old female and her 4-year-old sister were clinically diagnosed with renal hypoplasia, while their 36-year-old father presented with chronic kidney disease stage 3, focal segmental glomerulosclerosis, and optic disc pits. Genetic analysis identified a heterozygous PAX2 pathogenic variant c.685C>T, p.(Arg229*), in Family A and a heterozygous PAX2 pathogenic variant c.250G>A, p.(Gly84Ser) in Family B. Conclusions: The literature and our data further support that the same PAX2 variants may cause diverse kidney and ocular phenotypes among unrelated families and within the same family. Due to variable expressivity, a wide range of clinical manifestations of rare hereditary kidney diseases are still underdiagnosed, and a multidisciplinary approach is required to detect extrarenal signs of PAX2-related disorder. Full article

Background: Multiple sclerosis (MS) is a chronic, immune-mediated disorder of the central nervous system (CNS), characterized by inflammation, demyelination, and neurodegeneration, resulting in the disruption of axonal signal conduction. Optic neuritis (ON) occurs in over 70% of MS cases, highlighting the involvement of the optic nerve in the progression of the disease. Optic nerve atrophy secondary to the inflammatory episode can be observed during fundoscopy as pallor in the temporal quadrant or of the entire optic disc. Our study aims to evaluate the diagnostic capacity of fundus ophthalmoscopy when compared with the temporal thickness of the pRNFL (peripapillary retinal nerve fiber layer) measured using optical coherence tomography (OCT). Methods: We analyzed 88 eyes from 44 relapsing remitting MS patients using fundus photography (FP) and OCT optic disc measurements, correlating the temporal pallor of the optic disc seen in fundus photographs (FPs) with structural parameters obtained using OCT. Results: Our analysis revealed the significant capacity of optic disc pallor grading using FPs in MS patients in order to discriminate between normal and quadrants with pallor (p = 0.006) or strong pallor (p = 0.003) and between ones with light pallor and moderate pallor (p = 0.002) or strong pallor (p = 0.001), while being unable to clearly differentiate between normal quadrants and ones with light pallor (p = 0.608) or between pallor and strong pallor (p = 0.33). Conclusions: Fundoscopy and FP are useful screening tools in evaluating optic nerve atrophy in MS patients that could be used to assess neurodegeneration because of their universal availability. With the proposed inclusion of the optic disc as the fifth part of the CNS, the optic nerve will benefit from multiple exploratory techniques in order to increase the understanding of disease progression and patient quality of life. Full article

Thyroid-associated ophthalmopathy (TAO), or Graves’ orbitopathy (GO), is a complex autoimmune disorder affecting orbital tissues, often leading to vision-threatening complications such as dysthyroid optic neuropathy (DON). In this systematic review, conducted following PRISMA guidelines, 22 studies were evaluated to investigate the role of optical coherence tomography (OCT) in assessing retinal and choroidal changes in TAO. Parameters such as the retinal nerve fiber layer (RNFL), ganglion cell complex (GCC), ganglion cell layer (GCL), and choroidal thickness were analyzed. RNFL changes varied by disease severity, with significant thinning in DON due to nerve fiber loss and thickening in early DON due to optic disk edema. Subfoveal choroidal thickness (SFCT) was consistently higher in active TAO, correlating positively with the clinical activity score (CAS) and proptosis, suggesting its role as a marker of disease activity. Subgroup analysis revealed that spectral-domain OCT (SD-OCT) was the most sensitive for detecting retinal changes. The findings highlight the effectiveness of OCT in detecting minor retinal and choroidal alterations in TAO. However, the variability of study designs, as well as the lack of longitudinal data, limits the ability to draw broad conclusions. Further standardized, long-term investigations are required to properly understand OCT’s diagnostic and prognostic value in TAO. Full article

Eye diseases can significantly affect the quality of life of patients due to decreased visual acuity. Although modern ophthalmological diagnostic methods exist, some diseases of the visual system are asymptomatic in the early stages. Most patients seek advice from an ophthalmologist as a result of rapidly progressive manifestation of symptoms. A number of inherited and acquired eye diseases have only supportive treatment without eliminating the etiologic factor. A promising solution to this problem may be gene therapy, which has proven efficacy and safety shown in a number of clinical studies. By directly altering or replacing defective genes, this therapeutic approach will stop as well as reverse the progression of eye diseases. This review examines the concept of gene therapy and its application in the field of ocular pathologies, emphasizing the most recent scientific advances and their potential impacts on visual function status. Full article

Post-acute sequelae of COVID-19 (PASC) syndrome is considered an emergent and diffuse multidisciplinary problem. Compelling evidence suggests that COVID-19 increases symptoms of pre-existent small fiber neuropathy (SFN) and might trigger de novo onset of SFN. In this systematic review, for the first time, we provide a comprehensive overview of the clinical and diagnostic features of PASC-SFN, including the accompanying disorders, disease evolution, and possible treatments, described in the recent literature. Following infection, many patients reported a wide range of symptoms and complications, not self-limiting and independent from previous infection severity. SFN begins more frequently with distal limb burning pain and numbness, which accompany other dysautonomia, cognitive, visual, and osteoarticular disorders involving multiple organ systems. In an initial diagnostic suspicion, some tests might be useful as complementary examinations, such as nerve quantitative sensory testing, electromyography, and optic nerve tomography. Otherwise, definite diagnosis is reached with skin biopsy as the gold standard, along with corneal in vivo microscopy when ocular discomfort is present. Being a long-term condition, multiple and dissimilar symptomatic and disease-modifying drugs were employed for the treatment of this condition with the achievement of partial results, including steroids, pregabalin, gabapentin, duloxetine, vitamins, homotaurine and phosphatidylserine, alpha lipoic acid, immunosuppressants, and intravenous immunoglobulin therapy. PASC-SFN is a complex emerging disease and extremely challenging for physicians. At present, the only feasible management of PASC-SFN is represented by a multidisciplinary tailored approach, with future definitive protocols for diagnosis and treatment deemed essential. Full article

Childhood glaucoma encompasses a group of rare but severe ocular disorders characterized by increased intraocular pressure (IOP), posing significant risks to vision and quality of life. Primary congenital glaucoma has a prevalence of one in 10,000–68,000 people in Western countries. More worryingly, it is responsible for 5–18% of all childhood blindness cases. According to the Childhood Glaucoma Research Network (CGRN), this spectrum of disease is classified into primary glaucoma (primary congenital glaucoma and juvenile open-angle glaucoma) and secondary glaucomas (associated with non-acquired ocular anomalies, non-acquired systemic disease, acquired conditions, and glaucoma after cataract surgery). They present very specific ocular characteristics, such as buphthalmos or progressive myopic shift, corneal modifications such as Haab striae, corneal edema or increased corneal diameter, and also glaucoma findings including high intraocular pressure, specific visual fields abnormalities, and optic nerve damage such as increased cup-disc ratio, cup-disc ratio asymmetry of at least 0.2 and focal rim thinning. Surgical intervention remains the cornerstone of treatment, and initial surgical options include angle surgeries such as goniotomy and trabeculotomy, aimed at improving aqueous outflow. For refractory cases, trabeculectomy and glaucoma drainage devices (GDDs) serve as second-line therapies. Advanced cases may require cyclodestructive procedures, including transscleral cyclophotocoagulation, reserved for eyes with limited visual potential. All in all, with appropriate management, the prognosis of PCG may be quite favorable: stationary disease has been reported in 90.3% of cases after one year, with a median visual acuity in the better eye of 20/30. Immediate recognition of the specific signs and symptoms by caregivers, primary care providers, and ophthalmologists, followed by prompt diagnosis, comprehensive surgical planning, and involving the caregivers in the follow-up schedule remain critical for optimizing outcomes in childhood glaucoma management. Full article

Background/Objectives: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-related neurological disease that primarily affects the optic nerve and spinal cord. According to current international consensus guidelines for NMOSD, confirming the presence of aquaporin-4 immunoglobulin G antibody (AQP4-IgG) is one of the most important diagnostic criteria because AQP4-IgG is a significant diagnostic biomarker of NMOSD. Several assays are currently available for detecting AQP4-IgG, including cell-based assays (CBAs) and enzyme-linked immunosorbent assays (ELISAs). However, each assay has certain disadvantages, including insufficient sensitivity and specificity, the need for sophisticated techniques, and semi-quantitative results. Methods: We developed a fully automated chemiluminescent enzyme immunoassay (CLEIA) to detect AQP4-IgG (AQP4-CLEIA). This assay utilizes the recombinant antigen purified from the newly generated AQP4-M23 stably expressing Chinese hamster ovary cell line and an anti-AQP4 monoclonal antibody as a calibrator. Results: In analytical performance studies, the assay demonstrates good precision and linearity over the entire measurement range. Moreover, this assay showed no high-dose hook effect and interference from endogenous substances. In clinical validation studies, patients with AQP4-IgG positive NMOSD, multiple sclerosis, or myelin oligodendrocyte glycoprotein antibody-associated disorder and healthy individuals were tested. A cutoff value of 10.0 U/mL was determined by receiver operating characteristic curves based on the results of a microscopic live CBA. The sensitivity and specificity for AQP4-IgG-positive NMOSD were 97.0% and 100.0%, respectively, at the cutoff value. Conclusions: The results suggest that AQP4-CLEIA is a convenient automated method for measuring AQP4-IgG titers in hospitals and clinical laboratories, offering an effective alternative to the gold-standard CBA. Full article

Visual electrophysiology is a valuable tool for evaluating the visual system in various systemic syndromes. This review highlights its clinical application in a selection of syndromes associated with hearing loss, mitochondrial dysfunction, obesity, and other multisystem disorders. Techniques such as full-field electroretinography (ffERG), multifocal electroretinography (mfERG), pattern electroretinography (PERG), visual evoked potentials (VEP), and electrooculography (EOG) offer insights into retinal and optic nerve function, often detecting abnormalities before clinical symptoms manifest. In hearing loss syndromes like Refsum disease, Usher syndrome (USH), and Wolfram syndrome (WS), electrophysiology facilitates the detection of early retinal changes that precede the onset of visual symptoms. For mitochondrial disorders such as maternally-inherited diabetes and deafness (MIDD), Kearns–Sayre syndrome (KSS), and neuropathy, ataxia, and retinitis pigmentosa (NARP) syndrome, these tests can be useful in characterizing retinal degeneration and optic neuropathy. In obesity syndromes, including Bardet-Biedl syndrome (BBS), Alström syndrome, and Cohen syndrome, progressive retinal degeneration is a hallmark feature. Electrophysiological techniques aid in pinpointing retinal dysfunction and tracking disease progression. Other syndromes, such as Alagille syndrome (AGS), abetalipoproteinemia (ABL), Cockayne syndrome (CS), Joubert syndrome (JS), mucopolysaccharidosis (MPS), Neuronal ceroid lipofuscinoses (NCLs), and Senior–Løken syndrome (SLS), exhibit significant ocular involvement that can be evaluated using these methods. This review underscores the role of visual electrophysiology in diagnosing and monitoring visual system abnormalities across a range of syndromes, potentially offering valuable insights for early diagnosis, monitoring of progression, and management. Full article

Multiple sclerosis (MS) is a highly disabling chronic neurological condition affecting young adults. Inflammation, demyelination, and axonal damage are key pathological features of MS and its animal model, experimental autoimmune encephalomyelitis (EAE). Our previous work demonstrated that inhibiting spermine oxidase (SMOX) with MDL72527, a selective irreversible pharmacological inhibitor, significantly reduced clinical symptoms, retinal ganglion cell (RGC) loss, and optic nerve inflammation in EAE mice. The present study explored the broader therapeutic potential of SMOX inhibition, focusing on myelin preservation, axonal integrity, and visual function in the EAE model. Electron microscopy of optic nerve cross-sections showed significant preservation of myelin thickness and axonal integrity due to SMOX inhibition. The quantitative assessment showed that g-ratio and axon count metrics were significantly improved in MDL72527-treated EAE mice compared to their vehicle-treated counterparts. Immunofluorescence studies confirmed these findings, showing increased preservation of myelin and axonal proteins in MDL72527-treated EAE mice compared to the vehicle-treated group. Functional assessment studies (Electroretinography) demonstrated significant improvement in RGC function and axonal conduction in EAE mice treated with MDL72527. Furthermore, SMOX inhibition downregulated the expression of galectin3 (Gal3), a mediator of neuroinflammation, indicating Gal3’s role in SMOX-mediated neuroprotection. This study provides compelling evidence for the potential of SMOX inhibition as a therapeutic strategy in multiple sclerosis and other demyelinating disorders. Full article