Search Results (245)

Depression is often associated with functional disturbances in the visual system. However, the fundamental features underlying these visual system aberrations in depression remain to be fully elucidated. In particular, in the first stage of visual processing, how different retinal output neuron types change their intrinsic properties and output features in response to specific light stimulation remains unclear. Here, by adopting a mouse model of depression induced by chronic unpredictable stress (CUS), we found that depression is associated with reduced blood perfusion in the retinal inner plexiform layer (IPL). The hypoperfusion in the IPL is paralleled by a remarkable reduction of retinal ganglion cell (RGC) density, with more cell loss in ipRGCs than in the general RGCs. The surviving RGCs—particularly, ipRGCs—changed their intrinsic electrical properties, exhibiting decreased membrane input resistance, more depolarized resting membrane potential, and altered spiking properties. Additionally, these cells showed stimulus-size-dependent increases in light-evoked responses. Together, our findings demonstrate that depression is associated with the retinal IPL hypoperfusion and RGC impairments (particularly ipRGCs) and suggest retinal layer- and RGC-type-specific susceptibilities, furthering our understanding of retinal pathophysiology in depression. Full article

Background/Objectives: Retinal imaging has considerable potential for monitoring Alzheimer’s disease (AD) neurodegeneration, as retinal ganglion cell dendritic atrophy within the inner plexiform layer (IPL) is an early event. We tested whether quantitative optical coherence tomography (OCT) speckle texture analysis combined with supervised machine learning could discriminate AD-related IPL alterations without exogenous contrast agents in a mouse model. Methods: Retinal explants from triple-transgenic AD mice (n = 7, aged 12 months) and C57BL/6 controls (n = 3, aged 15 months) were imaged ex vivo using a custom 1040 nm spectral-domain OCT system. Five grey-level co-occurrence matrix (GLCM) features were extracted from IPL volumes of interest (VOIs) and classified using a linear support vector machine (SVM). Results: AD and control IPL textures formed two completely separable clusters in a two-dimensional feature space defined by contrast and entropy (0°), achieving 100% VOI-level classification accuracy (95% CI: 96.4–100%). However, given the small sample size, VOI-level rather than animal-level validation, lack of histological confirmation, non-interleaved image acquisition, and differences in age/strain between groups, these results represent exploratory dataset separability rather than a validated diagnostic test. Conclusions: These findings demonstrate the feasibility of the ligand-free, texture-based OCT discrimination of IPL alterations, indicating a strong underlying optical signal. Adequately powered, in vivo longitudinal studies with matched controls, interleaved acquisition, animal-level cross-validation, and histological validation are required before any clinical translation. Full article

Intraluminal unicystic ameloblastoma is characterized by tumor proliferation confined to the cystic lumen, without invasion of the supporting connective tissue, a feature that has led some authors to regard it as particularly suited to conservative surgical treatment. Objective: This study aims to describe the conservative two-stage management of a mandibular unicystic ameloblastoma with an intraluminal pattern, treated by decompression followed by enucleation with the aim of avoiding mandibular resection. Case Report: A 24-year-old female patient presented with a slight swelling in the right mandibular angle that had evolved over two years without prior treatment. Panoramic radiography revealed a well-defined radiolucent lesion extending from the mesial surface of the right mandibular second molar through the mandibular ramus to the ipsilateral coronoid process. Cone-beam computed tomography (CBCT) confirmed the lesion as a hypodense area measuring approximately 6 × 3.4 × 2.9 cm. A two-stage surgical approach was performed: the first stage consisted of an incisional biopsy and the placement of a decompression tube for six months; the second stage consisted of enucleation of the lesion. The definitive histopathological diagnosis was intraluminal unicystic ameloblastoma with a plexiform growth pattern. The surgical procedures were completed without preoperative, intraoperative, or postoperative complications. Follow-up evaluations were performed at 3 and 6 months and at 1 and 2 years after the initial surgical stage. Conclusions: At 24 months from the initiation of treatment, the outcome was favorable, with evidence of mandibular bone apposition and no signs of lesion recurrence. Full article

Background: Neurofibromatosis type 1 (NF1) is a multisystem genetic disorder characterized by marked phenotypic heterogeneity. This study aimed to describe the clinical spectrum and multisystem burden of NF1 in a regional retrospective cohort. Methods: We retrospectively analyzed 77 unique patients with NF1 after removal of duplicate records. Demographic characteristics, cutaneous manifestations, extracutaneous involvement, therapeutic interventions, and disease evolution were evaluated. An exploratory multisystem burden score was calculated using six extracutaneous clinical domains. Results: Café-au-lait macules were present in all patients, axillary/inguinal freckling in 93.5%, cutaneous neurofibromas in 63.6%, and plexiform tumors in 28.6%. Psychiatric/behavioral (67.5%), skeletal (57.1%), ophthalmological (51.9%), and neurological (45.5%) involvement were common. More than half of the cohort had involvement of at least three extracutaneous domains. Plexiform tumors were more common in patients with progressive or unfavorable disease compared to those with stationary disease. Progressive or unfavorable evolution was associated with a higher frequency of plexiform tumors. Therapeutic interventions were reported descriptively. Conclusions: NF1 showed substantial multisystem involvement beyond its characteristic cutaneous manifestations. Plexiform tumors were associated with a more complex clinical course. The proposed exploratory multisystem burden score may facilitate descriptive assessment of disease breadth but requires prospective validation. Full article

Background/Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder caused by pathogenic variants in the NF1 gene, characterized by high phenotypic variability. Methods: We present clinical and molecular data from a Romanian cohort of 54 patients initially diagnosed clinically. Results: Phenotypic evaluation (n = 54) revealed a high prevalence of café-au-lait macules (100%), Lisch nodules (64.8%), axillary/inguinal freckling (61.1%), and cutaneous neurofibromas (42.6%). Due to financial constraints (genetic testing not covered by the national health system), molecular confirmation by next-generation sequencing (NGS) was possible in only 12 patients (mostly sporadic cases and young children). Genetic testing identified a diverse spectrum of variants, including frameshift (41.7%, n = 5), nonsense (33.3%, n = 4), missense (16.7%, n = 2), and one splicing deletion (8.3%, n = 1). A novel complex NF1 frameshift variant, c.7504_7508delinsC (p.Ser2502Argfs*24) in exon 54, was identified in a patient exhibiting an aggressive phenotype characterized by plexiform neurofibromas, a malignant peripheral nerve sheath tumor (MPNST), and severe skeletal abnormalities. Additionally, a recurrent nonsense variant, NF1 c.910C>T (p.Arg304*), was detected in two unrelated individuals. Conclusions: The high proportion of sporadic cases (58.3%) in the molecularly tested subgroup underscores the critical role of early genetic screening. By integrating clinical data from 54 patients with the first molecular characterization of NF1 in Romania, this study expands the mutational spectrum and provides preliminary, descriptive insights into genotype–phenotype correlations. It also proposes a cost-effective diagnostic algorithm adapted for resource limited settings and lays the groundwork for future multicenter initiatives. Given the exploratory nature of the molecular subgroup (n = 12), all genotype–phenotype observations require validation in larger independent cohorts. Full article

Background: The latest revision of the McDonald criteria for diagnosis of multiple sclerosis (MS) establishes that the optic nerve can serve as a fifth anatomical location within the central nervous system for diagnosis. Optical coherence tomography (OCT) images can serve as evidence for this purpose. Objective: To assess the accuracy of automated artificial-intelligence-based classification of MS patients using OCT data obtained from two different centers. Methods: OCT data were collected from two centers using standardized APOSTEL-based protocols and similar equipment. Retinal layer thicknesses—mean and standard deviation (STD) values—were analyzed in four layers and in six regions per layer per eye. A support vector machine classifier with recursive feature elimination and Shapley additive explanations value analysis was applied to identify the most relevant features and maximize classification accuracy between control subject and MS patient eyes. Results: The database drawn from two hospitals comprised 112 eyes with MS without prior history of optic neuritis and 193 eyes of control subjects. The classifier achieved maximum accuracy (0.8459) using 20 input features. The mean and STD metrics had similar importance, with the most influential layers being the ganglion cell layer, inner plexiform layer, and the inner retinal layer complex. Key regions included the papillomacular bundle and the superior temporal perimacular area. Conclusions: OCT data facilitates highly accurate MS diagnosis across different centers. Artificial intelligence assessment could facilitate automated classification. These findings provide evidence of the important role of the optic nerve in MS diagnosis. Full article

Background/Objectives: This study investigates the correlation between substantia nigra (SN) hyperechogenicity, detected via transcranial sonography (TCS), and retinal thinning in patients with Parkinson’s disease (PD). Methods: In this cross-sectional study, 86 PD patients (172 eyes) underwent clinical assessment (UPDRS, Hoehn–Yahr), TCS for SN area measurement, and optical coherence tomography (OCT) for retinal nerve fiber layer (RNFL), ganglion cell-inner plexiform layer (GCIPL), and macular thickness analysis. Results: PD patients exhibited significant thinning of the GCIPL, average RNFL, and central macular thickness compared to healthy controls (p < 0.001 in all instances). Pathological SN hyperechogenicity (>0.19 cm²) was detected in 85.9% of patients with a preserved temporal bone window (71 out of 86). A significant negative correlation was found specifically between the SN echogenic area and central macular thickness (r = −0.248, p = 0.003). Patients with pathological SN findings had a significantly thinner central macula (p = 0.006) compared to those with a normal SN, while no significant correlations were observed between the SN area and RNFL or GCIPL. Conclusions: These findings demonstrate a specific correlation between SN hyperechogenicity and central macular thinning. While RNFL and GCIPL effectively differentiate PD from controls, the central macula might serve as a promising biomarker candidate reflecting SN changes. Further longitudinal studies are required to evaluate the role of these combined markers in the PD diagnostic algorithm. Full article

Background/Objectives: To evaluate long-term neuroretinal changes in patients with persistent COVID-19 (PC) versus asymptomatic controls, using optical coherence tomography (OCT) over a two-year follow-up. Methods: This prospective longitudinal study enrolled 133 participants: 94 PC patients and 39 control subjects. Participants underwent comprehensive ophthalmological assessment at baseline, at 1 year (voluntary), and at 2 years. Structural retinal changes were analysed using spectral-domain OCT with the Bruch’s Membrane Opening–Minimum Rim Width and Posterior Pole protocols. Longitudinal analyses focused on within-subject change from baseline to 2 years and on between-group comparisons of these change scores, with Bonferroni correction applied within predefined families of comparisons. Results: The most robust corrected between-group longitudinal finding was a greater decrease in the central macular sector (C0) of the inner plexiform layer (IPL) in PC patients than in control subjects. Conclusions: Although these findings suggest possible subtle inner retinal involvement in PC patients, particularly in the central IPL, the results should be interpreted cautiously because of the modest control sample, control-group heterogeneity, and the exploratory nature of the sectoral OCT analyses. OCT may be useful in research settings as a complementary tool for exploring subtle neuroretinal changes in PC patients; however, its clinical utility and role as a validated biomarker remain unproven. Full article

Progression independent of relapse activity (PIRA) and smouldering multiple sclerosis (MS) represent major unmet challenges in contemporary MS care. Disability may accumulate independently of clinical relapses, driven in part by chronic compartmentalised inflammation behind a relatively intact blood–brain barrier and incompletely captured by conventional monitoring tools. This narrative review synthesises evidence across four complementary biomarker domains for detecting smouldering MS and PIRA: advanced MRI (paramagnetic rim lesions [PRLs], slowly expanding lesions, deep grey matter atrophy, quantitative susceptibility mapping); fluid biomarkers (serum glial fibrillary acidic protein [sGFAP], serum neurofilament light chain [sNfL]); retinal optical coherence tomography (ganglion cell–inner plexiform layer thinning); and digital health metrics (wearable accelerometry, digital Symbol Digit Modalities Test). In a single prospective cohort, combined elevation of sGFAP and sNfL conferred a 4.71-fold increased hazard for PIRA (HR 4.71; 95% CI 2.05–9.77); independent data suggest sGFAP may carry selectivity for progression beyond sNfL, although this remains to be confirmed. No single domain sufficiently characterises smouldering pathology. We therefore propose a hypothesis-generating Multimodal PIRA Score (MPS) as a conceptual validation scaffold intended to structure—rather than inform—prospective multicentre evaluation against a long-horizon disability endpoint. Harmonisation of acquisition protocols, reference ranges, and digital phenotyping algorithms remains a prerequisite. Full article

Background: Chronic kidney disease (CKD) is associated with systemic microvascular dysfunction, yet the relationship between retinal changes and mineral metabolism disturbances across CKD treatment modalities remains incompletely characterized. Methods: We performed a baseline cross-sectional analysis of 77 participants (29 hemodialysis [HD] patients, and 48 kidney transplant recipients [KTR]) who underwent 7 × 7 mm structural optical coherence tomography (OCT) and 6 × 6 mm OCT angiography (OCTA) imaging. Structural parameters included central macular thickness (CMT), ganglion cell layer plus inner plexiform layer (GCL+), ganglion cell complex (GCL++), and subfoveal choroidal thickness (SCT). Microvascular parameters included superficial and deep capillary plexus vessel density (SVPD, DVPD), choriocapillaris density (CCD), and foveal avascular zone (FAZ) area. Serum mineral metabolism markers were correlated with retinal findings. Eyes were analyzed separately as the primary approach, while generalized estimating equation (GEE) models adjusted for age, sex, body mass index, diabetes, and hypertension (HTN) were used for confirmation. Results: FAZ area, SVPD, DVPD, CCD, GCL+, GCL++, and CMT did not differ significantly between cohorts in either per-eye analyses or adjusted GEE models. SCT was lower in HD patients than in KTR in the right eye (p = 0.019) and remained significantly higher in KTR in the adjusted GEE models (p = 0.016), a difference that persisted after excluding participants with diabetes and after adjustment for HTN grade. HTN grade was associated with FAZ area in HD and SCT in KTR. Serum magnesium was inversely associated with FAZ area in HD (B = −95.27, p = 0.034) and positively associated with GCL+ in KTR (B = 10.55, p = 0.048). Conclusions: Retinal microvascular and inner-retinal structural parameters were largely comparable between HD patients and KTR, with SCT the only parameter showing a consistent between-cohort difference (higher in KTR). Serum magnesium and HTN grade were the metabolic and clinical variables most consistently associated with retinal measures. Full article

Neurofibromatosis type 1 (NF1) is a genetic tumor predisposition syndrome characterized by a substantial risk of developing peripheral nerve sheath tumors, including malignant peripheral nerve sheath tumors (MPNSTs), which occur in 8–13% of patients. Approximately 50% arise from plexiform neurofibromas (PNs) and 40% develop de novo, making them a major cause of premature mortality. Current clinical management is limited by the intrinsic shortcomings of standard imaging modalities: magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT), and tissue biopsy in distinguishing benign PNs from early malignant transformation, which remains a major clinical challenge. This progression follows a stepwise molecular continuum marked by cumulative genetic alterations and widespread epigenetic dysregulation. In this setting, liquid biopsy has emerged as a promising non-invasive approach to help fill these diagnostic gaps by enabling real-time molecular monitoring through the analysis of circulating tumor DNA (ctDNA) and other blood-based biomarkers. This review examines the current evidence supporting liquid biopsy applications in NF1 management, including early detection of MPNST, discrimination between benign and malignant lesions, mutational profiling for therapeutic targeting, and disease monitoring before and during treatment. We also discuss the current evidence on fragmentomics, methylomics and driver mutation profiling as tools to distinguish PNs from MPNSTs. Recent evidence suggests that liquid biopsy may help detect molecular changes associated with malignant transformation before clear clinical signs emerge, potentially opening an important window for intervention and supporting a shift towards a more molecularly informed surveillance model. Finally, this review considers the possible extension of liquid biopsy to other tumor types, including NF1-deficient breast cancer, and outlines a future management framework aimed at improving early diagnosis and personalized therapeutic intervention in this high-risk population. Full article

Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy caused by SCN1A haploinsufficiency. While brain pathology has been extensively studied, the retina remains underexplored. This study investigated retinal structural, functional, vascular, and cellular changes in a Scn1a^+/− rat model of DS. Anatomical quantification revealed thinning of the retinal nerve fiber layer and thickening of the outer plexiform layer. Electroretinography (ERG) showed selectively reduced oscillatory potential amplitudes, suggesting dysfunction of neurovascular coupling. Consistent with these findings, immunohistochemistry demonstrated aberrant vascular morphology, including increased vessel curvature and reduced branching density. In addition, we observed robust microglial activation in the outer and inner plexiform layers; however, astrocyte morphology remained largely unchanged. Fenfluramine, an approved anti-seizure drug for DS, attenuated microglial activation but failed to rescue retinal structural or vascular deficits, indicating a dissociation between its anti-inflammatory and disease-modifying effects. Our findings suggest that multimodal retinal assessment could serve as a noninvasive biomarker platform for monitoring disease progression and therapeutic response in DS. Full article

Background/Objectives: Retinal optical coherence tomography (OCT) has emerged as a sensitive biomarker of neurodegeneration in multiple sclerosis (MS), yet eyes without overt optic neuritis (ON) are routinely pooled as “clinically unaffected” despite their heterogeneous histories. We evaluated whether never-ON eyes and fellow eyes after unilateral ON differ structurally and microvascularly using swept-source OCT (SS-OCT) and OCT angiography (OCTA). Methods: In this cross-sectional, single-center study, 126 clinically unaffected MS eyes—96 never-ON eyes and 30 fellow eyes after unilateral ON—were compared with 118 healthy control eyes. SS-OCT quantified ganglion cell–inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and macular RNFL (mRNFL) thickness, while OCTA measured superficial vascular plexus (SVP) vessel density. Between-group differences were assessed using generalized estimating equations with participant-level clustering, empirical (sandwich) standard errors, adjustment for age and sex, and false discovery rate correction. Results: Despite preserved visual acuity, both never-ON and fellow eyes showed structural retinal thinning relative to controls. GCIPL thickness followed a stepwise gradient—66.14 ± 4.31, 62.08 ± 7.03, and 58.03 ± 7.71 µm in controls, never-ON eyes, and fellow eyes, respectively (FDR-adjusted q = 0.020 for fellow vs. never-ON eyes)—and pRNFL and mRNFL showed a similar overall pattern. After false discovery rate correction, OCTA parameters did not differ significantly between groups. Conclusions: Clinically unaffected eyes in MS are not structurally normal, and fellow eyes after unilateral ON carry a greater burden of silent retinal damage than never-ON eyes. These two phenotypes should be analyzed separately in MS imaging research. Structural OCT measures, particularly GCIPL thickness, appear more sensitive than microvascular indices for detecting subclinical retinal involvement. Full article

This study investigated retinal interspecific differences between two sympatric lizards from the Turpan Basin of Xinjiang that occupy distinct microhabitats. Eremias roborowskii inhabits shrublands, while Phrynocephalus axillaris lives in open sandy areas. We adopted retinal whole-mounting, paraffin sectioning, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) to compare retinal structure, oil droplet traits, photoreceptor arrangement, and ultrastructural characteristics between the two species. Both species exhibited five types of colored oil droplets, a temporal fovea, and a highly vascularized conus papillaris, confirming cone-dominant retinas. P. axillaris had larger oil droplets with an average diameter of 3.719 ± 1.100 μm. In contrast, E. roborowskii showed a higher oil droplet density of 1473 ± 1203 ind/mm². The inner plexiform layer (IPL) was significantly thicker in E. roborowskii (56.01 ± 14.76 μm) relative to P. axillaris (50.76 ± 15.25 μm). The two species also differed markedly in photoreceptor ultrastructure. E. roborowskii contained mitochondria-rich ellipsoids, while P. axillaris possessed glycogen-enriched paraboloids. These structural variations reflect compatibility with local ambient light conditions. E. roborowskii is predisposed to suit diffuse shrubland light through high droplet density and mitochondrial-dominant ellipsoids, whereas P. axillaris tends to accommodate intense open-field sunlight via larger oil droplets and well-developed paraboloids. This study provides key morphological evidence to reveal how microhabitat divergence drives retinal specialization among desert reptiles. Full article

Objective: We aimed to assess whether modified OCT acquisition parameters improve GCIPL measurement reliability. Methods: Participants with multiple sclerosis (PwMS) and age- and sex-matched healthy controls (HC) underwent OCT (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany) at baseline and after two and four weeks. At each visit, five macular scan protocols were acquired: standard (49 lines, high-speed [HS], automated real-time tracking [ART]: 9), high-ART (49 lines, HS, ART: 50), high-lines (97 lines, HS, ART: 9), high-resolution (49 lines, high-resolution [HR], ART: 9), and maximum (97 lines, HR, ART: 50). Reliability was assessed using intraclass correlation coefficients (ICC). Absolute test–retest reproducibility was quantified using the mean absolute difference (MAD). Results: Thirty-eight eyes from nine PwMS (mean age 34.1 ± 8.0 years, 44.4% female) and ten HC (31.7 ± 11.1 years, 50.0% female) were included. At baseline, mean GCIPL thickness ranged from 70.8 µm to 71.5 µm across protocols, demonstrating excellent inter-protocol agreement (ICC 0.99; 95% confidence interval [CI]: 0.98–0.99; p < 0.001) and only marginally higher values with increased ART. Test–retest reliability was excellent for all protocols, demonstrating marginally lower absolute measurement variability of high-ART and high-lines protocols (MAD 0.26–0.27; 95% CI: 0.21–0.32), while temporal agreement remained excellent and comparable across acquisition settings. Mean acquisition time ranged from 10.6 ± 1.6 s for the standard protocol to 231.9 ± 36.4 s for the maximum protocol. Conclusions: All OCT acquisition protocols demonstrated excellent inter-protocol and test–retest reliability for GCIPL measurements. The high-lines protocol provides the most favourable balance between measurement reliability and acquisition time, supporting its potential utility for longitudinal GCIPL monitoring. Full article