Basel Obied

We evaluated gadolinium biodistribution, clearance, and long-term brain retention following high-dose gadolinium-based contrast agent (GBCA) exposure in 90 mice. Macrocyclic and linear agents were assessed using particle-induced X-ray emission (PIXE) alongside complementary elemental, imaging, and histological methods. Following intravenous administration, gadolinium was detected in blood and multiple tissues during the acute phase, with declining blood levels and detectable urinary excretion. No brain Gd signal was detected by PIXE at the long-term endpoints following single exposure. Repeated-exposure findings were descriptive because the individual subgroups contained only 1–3 animals. Endpoint MRI showed no apparent persistent signal changes, and H&E examination showed preserved tissue morphology. Metallothionein staining varied qualitatively, whereas Iba1 staining showed no apparent increase in microglial activation. Intraperitoneal administration produced no detectable blood gadolinium at the 1-h sampling timepoint. These findings characterize high-dose experimental exposure and support the feasibility of multimodal assessment of gadolinium biodistribution. Negative findings do not exclude residual Gd below the detection capabilities of the methods used.

Ocular tilt reaction (OTR) and trochlear nerve palsy (TNP) can induce cyclotorsion. We aimed to assess the utility of fundus photography in distinguishing between these disorders. The database of a neuro-ophthalmology hospital-based clinic was retrospectively searched for patients referred for new-onset vertical diplopia between 2020 and 2023. Medical data were collected, and the angle between the optic disc and fovea was measured using ImageJ software to quantify torsion. Distinct torsional patterns were identified between the groups. OTR was characterized by variable, often conjugate torsion, whereas TNP demonstrated consistent disconjugate extorsion. Analysis of interocular torsional relationships, rather than magnitude alone, provided useful diagnostic discrimination. Fundus photography may be useful for differentiating OTR from TNP in complicated neurological cases, particularly in patients who are difficult to examine. This study emphasizes the practical clinical value of fundus photography as a simple, accessible, and objective tool for differentiating OTR from TNP, by contributing the torsional component of OTR triad, particularly in emergency or diagnostically challenging settings where standard examination may be limited.

Glaucoma is a leading cause of irreversible blindness, and animal models are essential for studying its pathophysiology and testing therapeutic strategies. In this study, a novel hydrogel-based approach was developed and evaluated to induce experimental glaucoma in mice, using composites of hyaluronic acid (HA) and the self-assembling peptide fluorenylmethoxycarbonyl-diphenylalanine (FmocFF). Two formulations with different HA-to-FmocFF ratios were injected either intracamerally or intravitreally in C57BL/6 mice. Intraocular pressure (IOP) was monitored over 21 days, and retinal tissues were analyzed histologically and immunohistochemically. Significant IOP elevation was observed in one hydrogel formulation (Mixture B), yet without detectable retinal ganglion cell loss. A significant reduction in retinal ganglion cell (RGC) density, independent of IOP changes or injection site, was observed in Mixture A. Histological staining confirmed successful delivery and localization of the hydrogel in the anterior chamber, and no evidence of gliosis, microglial activation, or increased apoptosis was revealed by immunostaining. Collectively, these data position the HA-FmocFF hydrogel as a proof-of-concept that advances glaucoma model development, although it does not yet recapitulate the full disease. This model may facilitate future studies of neuroprotection and disease-modifying therapies in glaucoma without confounding inflammatory responses.

Background/Objectives: To evaluate the concentrations of trace elements in tear fluid among athletes using particle-induced X-ray emission (PIXE), and to assess the associations with gender, sports intensity, and nutritional supplement intake. Methods: In this cohort study, 84 athletes engaged in high- or low-intensity sports completed a demographic and supplement-use questionnaire. Tear samples were collected using Schirmer strips and analyzed for elemental composition with PIXE, a high-sensitivity technique suited for small biological samples. Multivariate and nonparametric statistical analyses were used to compare groups. Results: There were 46 males and 38 females, aged 17–63 years (mean 30.21 years). Tear phosphorus, potassium, and sulfur concentrations were higher in women than men and higher in women participating in low-intensity compared to high-intensity sports. Tear concentrations of magnesium were higher in men participating in high-intensity sports compared to low-intensity sports. They were higher in men than women regardless of supplement intake. Iron concentrations were higher in men than women only when neither group was taking supplements. Smoking had a slight inverse relationship to iron values. Iron levels were particularly high in men participating in intense sports and low in smokers. Magnesium supplements were associated with raised magnesium levels in tears. Conclusions: This study demonstrates an association between trace element levels in human tears and gender, sports intensity, and food supplement intake. PIXE enables the evaluation of trace element concentration in tears, which may serve as potential biomarkers for the clinical assessment of athletes’ health.

Background/Objectives: Uncontrolled or long-standing diabetes can lead to proliferative diabetic retinopathy (PDR), a condition that significantly impairs vision. A subset of patients does not respond adequately to conventional therapies, such as intravitreal injections of anti-vascular endothelial growth factor (VEGF) or laser treatment. This study aims to identify potential biomarkers for alternative treatment pathways in the vitreous and blood of patients with severe PDR. Methods: Vitreous samples were collected from PDR patients (n = 3) undergoing vitrectomy for vitreous hemorrhage and from control patients (n = 9) undergoing ocular surgery for epiretinal membrane or macular holes. Blood samples were collected from a separate group of PDR patients (n = 13) and non-diabetic control patients without retinopathy (n = 13). Medical histories were obtained. Two-stage real-time quantitative polymerase chain reaction (qPCR) was used to evaluate mRNA expression levels of genes potentially implicated in PDR, including HIF2A, PAI-1, TIE1, TIE2, ANGPT2, and VEGFA. Molecular and statistical analyses were performed to compare PDR and control vitreous and blood samples. Results: The PDR vitrectomy group included two females and one male, aged 71–77 years (mean 74 years). All participants had undergone pan-retinal photocoagulation and two had received anti-VEGF injections before vitrectomy. These participants had elevated HbA1c levels. Targeted vitreous gene analysis revealed varying levels of increased expression of all genes examined as compared to the control group. A trend for increased median expression was demonstrated for all examined genes: HIF2A by 1.44-fold (PDR = 2.50, control = 1.74, p = 0.21), PAI-1 by 1.56-fold (PDR = 3.00, control = 1.93, p = 0.37), TIE1 by 1.36-fold (PDR = 2.33, control = 1.72, p = 0.66), TIE2 by 2.06-fold (PDR = 2.81, control = 1.36, p = 0.51), ANGPT2 by 2.93-fold (PDR = 6.32, control = 2.16, p = 0.1), and VEGFA by 3.53-fold (PDR = 3.51, control = 0.99, p = 0.08). PDR blood sample analysis as compared to controls showed a trend for increased expression of VEGFA by 1.2-fold (PDR = 0.88, control = 0.74, p = 0.57), whereas the other examined genes showed a trend of reduced expression; HIF2A decreased by 0.50-fold (PDR = 0.38, control = 0.75, p = 0.07), PAI by 0.51-fold (PDR = 0.35, control = 0.69, p = 0.09), TIE-1 by 0.79-fold (PDR = 0.79, control = 1.00, p = 0.54), TIE-2 by 0.70-fold (PDR = 0.58, control = 0.82, p = 0.34), and ANGPT2 by 0.45-fold (PDR = 0.51, control = 1.15, p = 0.11). Conclusions: Vitreous sample analysis revealed a trend of increased mRNA expression of ANGPT2 and VEGFA in patients with PDR. Blood sample analysis did not show a significant increase of VEGFA mRNA expression but a decreased trend of HIF2A, PAI-1, and ANGPT2 mRNA expression. These trends warrant validation in a larger cohort to explore alternative pathways for targeted treatment.

Background/Objectives: To simplify diagnosing congenital and acquired nystagmus using fundus photographs. Methods: A retrospective study included patients with congenital or childhood-acquired nystagmus examined at a hospital-based ophthalmology clinic (September 2020–September 2023) with fundus photos taken. Exclusions were for incomplete data or low-quality images. Demographics, aetiology, orthoptic measurements, and ophthalmologic and neurological exams were reviewed. Two independent physicians graded fundus photos based on amplitude (distance between “ghost” images), the number of images visible, and the direction of nystagmus. Severity was rated on a 0–3 scale using qualitative and quantitative methods. Photographic findings were compared to clinical data, and statistical analysis used Mann-Whitney tests. Results: A total of 53 eyes from 29 patients (16 females, 13 males; mean age 12.5 years, range 3–65) were studied: 25 with binocular nystagmus and 3 with monocular nystagmus. Diagnoses included congenital (n = 15), latent-manifest (n = 3), neurologically associated (n = 2), and idiopathic (n = 9). Types observed were vertical (n = 5), horizontal (n = 23), rotatory (n = 10), and multidirectional (n = 15). Visual acuity ranged from 20/20 to no light perception. Fundus photos correlated with clinical diagnoses, aiding qualitative assessment of direction and amplitude and mitigating eye movement effects for clearer retinal detail visualization. Conclusions: Fundus photography effectively captures nystagmus characteristics and retinal details, even in young children, despite continuous eye movements. Integrating fundus cameras into routine practice may enhance nystagmus diagnosis and management, improving patient outcomes.

Cobalt is a trace element, crucial for red blood cell formation and neurological function. Cobalt toxicity is often only diagnosed after severe manifestations, including visual impairment. We aimed to investigate whether optical coherence tomography (OCT) and magnetic resonance imaging (MRI) can effectively detect cobalt-induced ocular toxicity in a murine model. Five wild-type mice (WT, C57Bl6) received daily intraperitoneal cobalt chloride injections for 28 days with a dosage of 12.5 mg/kg. Another 5 WT mice served as controls. After 28 days, all mice underwent manganese contrast-enhanced MRI and OCT examinations. Macroscopic and histological analysis of the enucleated eyes were performed. MRI revealed an increased signal in the optic nerves of injected mice. Anterion OCT provided in vivo visualization of the entire eye, demonstrating incipient cataract formation in the cobalt-injected mice. Both Spectralis domain OCT and Anterion, followed by histological analyses, confirmed preserved retinal structure with decreased thickness in the cobalt-injected group, with only minor neuronal damage and cell loss. Optic nerve analysis demonstrated myelin loss and increased inflammation with high levels of reactive gliosis. This study demonstrates optic neuropathy induced by cobalt toxicity, as shown by increased optic nerve signal on MRI without significant retinopathy. Anterion OCT showed incipient cataracts in the anterior segment.

Cobalt toxicity is difficult to detect and therefore often underdiagnosed. The aim of this study was to explore the pathophysiology of cobalt-induced oxidative stress in the brain and its impact on structure and function. Thirty-five wild-type C57B16 mice received intraperitoneal cobalt chloride injections: a single high dose with evaluations at 24, 48, and 72 h (n = 5, each) or daily low doses for 28 (n = 5) or 56 days (n = 15). A part of the 56-day group also received minocycline (n = 5), while 10 mice served as controls. Behavioral changes were evaluated, and cobalt levels in tissues were measured with particle-induced X-ray emission. Brain sections underwent magnetic resonance imaging (MRI), electron microscopy, and histological, immunohistochemical, and molecular analyses. High-dose cobalt caused transient illness, whereas chronic daily low-dose administration led to long-term elevations in cobalt levels accompanied by brain inflammation. Significant neurodegeneration was evidenced by demyelination, increased blood–brain barrier permeability, and mitochondrial dysfunction. Treated mice exhibited extended latency periods in the Morris water maze test and heightened anxiety in the open field test. Minocycline partially mitigated brain injury. The observed signs of neurodegeneration were dose- and time-dependent. The neurotoxicity after acute exposure was reversible, but the neurological and functional changes following chronic cobalt administration were not.

Purpose: To report the rate of ocular torsion in children with horizontal strabismus or orthophoria. Methods: A retrospective study design was used. Nineteen children were included in the study, including seven girls, aged 4–16 years. All patients were examined for strabismus and 12 were scheduled for surgical intervention. All participants had digital fundus photos (DRSplus, Padova, Italy) of both eyes at presentation, and 5 of 12 also had fundus photos following the strabismus operation. Patient files were reviewed for age, demographic data, type of strabismus, clinical symptoms and signs, orthoptic exams, subjective and objective reports of torsion, inferior oblique overaction, and V pattern. Fundus photos were analyzed for torsion by ImageJ software [ImageJ 1.54f, National Institute of Health, USA]. The disc-foveal angle was calculated for ocular torsion. Disc-foveal angle was defined as the angle formed between a line passing through the center of the optic disc to the fovea and another horizontal line passing through the center of the optic disc, using fundus photographs. Results: Of the 19 children, 18 had horizontal strabismus: 9 with exotropia and 9 with esotropia. One child was orthophoric with torsional strabismus. Inferior oblique overaction was detected in all but 3 children, while V pattern was documented in 10. Visual acuity was reduced (under 6/12) in four eyes of four children. None were symptomatic for ocular torsion. Although extorsion was documented clinically in 3 of 19 children, it was measurable on fundus photos in all patients before surgery with a mean of 8.7 ± 8.5 degrees and 8.5 ± 9.7 degrees in the right and left eyes, respectively. The mean extorsion in both eyes was 19.7 ± 10.1 degrees and improved to a mean of 15.3 ± 7.9 degrees in the children who were operated on and had documented postoperative fundus photographs. Conclusions: Extorsion was detected on fundus photos at a significantly higher rate than in clinical examination. Notably, inferior oblique overaction was mainly associated with torsion. This study demonstrated that torsion is underdiagnosed in clinical examinations, as the children are often asymptomatic, but fundus photos which are easily obtained can improve its detection.