Search Results (2,469)

Oral squamous cell carcinoma (OSCC) is a highly aggressive malignancy with poor prognosis, mainly due to the presence of cancer stem cells (CSCs), a small subpopulation of cells that contribute to therapy resistance and tumor progression. The principal objective of this study was to investigate the role of miRNA-21 in the maintenance of cancer cell stemness and the possibility of altering it. The CD44 antigen was used as a marker for CSC isolation from oral cancer cell cultures. CD44+ and CD44− populations were sorted via magnetic separation. miRNA-21 inhibition was performed in CD44+ cells via transfection. CD44+ cells possessed a significantly higher migration and invasion potential compared to CD44− cells, higher levels of miRNA-21 (p = 0.004) and β-catenin (p = 0.005), and lower levels of BAX (p = 0.015). miRNA-21 inhibition in CD44+ cells reduced migration, invasion, and colony formation while increasing apoptosis. Stemness markers were significantly downregulated following miRNA-21 inhibition: OCT4 (p = 0.013), SOX2 (p = 0.008), and NANOG (p = 0.0001), as well as β-catenin gene (CTNNB1) (p < 0.05), an important member of WNT signaling pathway. Apoptotic activity was enhanced, with a significant downregulation of the antiapoptotic Bcl-2 (p = 0.008) gene. In conclusion, miRNA-21 plays a critical role in the regulation of oral cancer CD44+ cells properties. Targeting and inhibiting miRNA-21 in CD44+ cells could represent a promising novel strategy in OSCC treatment. Full article

Background: In this study, we evaluated the incidence of cystoid macular edema (CME) after pars plana vitrectomy (PPV) for different retinal pathologies and assessed the role of optical coherence tomography (OCT) biomarkers in guiding treatment decisions in post-surgical CME patients who were refractory to medical therapy over a follow-up period of 12 months. Methods: Medical records of consecutive pseudophakic patients, who underwent PPV for different retinal pathologies, were retrospectively evaluated in this single-center, uncontrolled study. The incidence of post-PPV CME was assessed. Eyes with post-PPV CME in the first 2 months after surgery, with available clinical and OCT data for 12 months after surgery, were included in the evaluation. The mean best-corrected visual acuity (BCVA; logMAR), mean central macular thickness (CMT; μm) change, and response to different treatments [medical therapy and intravitreal dexamethasone (DEX) implant] were evaluated 1, 3, 6, 9, and 12 months after PPV. The impact of OCT biomarkers on the exposure to DEX implants was assessed. Adverse events, potentially related to the treatment, were investigated as well. Results: Of the 346 pseudophakic patients (352 eyes) who participated in this study, 54 (54 eyes) developed CME within the first 2 months after PPV (incidence of 15.3%). Among them, 48 patients were deemed eligible for the 12-month analysis. Preoperative mean BCVA (1.44 ± 0.99 logMAR) significantly improved to 0.32 ± 0.37 logMAR after 12 months (p < 0.001). The mean baseline CMT of 347 (±123.5) μm significantly decreased to 290 μm (±80.4; p = 0.003) by the end of the follow-up. Twenty-five eyes (52%) required one or more DEX implants for CME, due to being refractory to topical therapy. Significant correlations were found between the mean CMT values at various time points. Additionally, patients who required DEX implants at months 3 and 9 were more likely to present intraretinal fluid (IRF), disorganization of inner retinal layers (DRIL), disorganization of outer retinal layers (DROL), and hyper-reflective foci (HRF) at 1-month OCT. Five patients experienced a slight increase in intraocular pressure (IOP), which was successfully managed with topical medication. Conclusions: Topical therapy alone can be a valuable option for post-PPV CME in approximately 50% of patients. Significant visual recovery and macular thickness reduction at 12 months demonstrated that DEX implants can be a safe and effective second-line treatment for pseudophakic patients with post-PPV CME and who are refractory to medical therapy. Early post-surgical OCT biomarkers may indicate a more severe CME that might benefit from the steroid implant. Full article

Background/Objectives: Treatment with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) has revolutionized disease management and has transformed CML from a life-threatening disease to a chronic condition for many patients. However, overcoming resistance, particularly related to leukemic stem cells (LSC) that can persist even when the bulk of the leukemic cells are eliminated, remains a significant challenge. Methods: K562 and KU812 cell lines were treated in vitro with the TKI Imatinib (IM). Gene expression, protein analysis, and metabolomic screening were conducted to investigate the ability of the drug to enhance stem cell (SC) features. Moreover, a gene ontology analysis was performed on different available datasets, to further consolidate our data. Results: 48 h of IM treatment can significantly increase the expression of genes related to SC self-renewal, particularly SOX2 and OCT 3/4. Interestingly, these modulations occur in cells that remain alive after drug treatment and that displayed features consistent with leukemia stem-like CML cells, suggesting that SC genes levels are crucial even in cell population survived upon TKI treatment. Moreover, after in silico analysis of available data, we observed an enrichment of SOX2/NANOG and OCT 3/4 signatures after TKI treatment, thus strengthening our results. Conclusions: Our results confirmed the relevance of LSC features after TKI treatment, highlighting the need for more effective and potentially curative strategies targeting LSCs to overcome resistance in CML. Full article

To date, therapeutic responses in plaque psoriasis are evaluated with clinical scores. No objective examination has been established. A recently developed non-invasive imaging tool, line-field confocal optical coherence tomography (LC-OCT), enables the in vivo live imaging of skin changes in psoriasis under therapy. The aim of this study was to measure therapeutic response clinically and with LC-OCT, comparing the subjectively scored epidermal changes with an AI-supported analysis. This prospective, observational study included 12 patients with psoriasis starting a systemic treatment with IL-17 inhibitors (secukinumab, ixekizumab, and bimekizumab). LC-OCT and clinical assessment with a local psoriasis and severity index of the study plaque and a control area were performed before the initiation of therapy as well as after 4 and 12 weeks of treatment. A manual and AI-supported measurement of the thickness of epidermis, stratum corneum, and undulation of the dermo-epidermal junction was carried out. Acanthosis and hyperkeratosis showed a significant reduction under treatment. AI-supported calculations were compared to subjective measurements showing good reliability with high correlation. AI-supported analysis of vascular changes may serve as a prognostic and therapeutic response marker in the future. Full article

Objectives: To evaluate the effects of subthreshold micropulse laser treatment (SMLT) on choroidal architecture in chronic central serous chorioretinopathy (CSC) and their correlations with functional outcomes. Methods: This retrospective study included 48 eyes with chronic CSC that were treated with 577 nm SMLT. The choroidal thickness (CT); Sattler’s layer and choriocapillaris complex thickness (SLCCT); Haller’s layer thickness (HLT); subretinal fluid (SRF); and best-corrected visual acuity (BCVA) were assessed at baseline and at 2 months post treatment. Results: At 2 months, the SLCCT increased from 185.92 ± 80.89 μm to 214.17 ± 83.36 μm (p = 0.023), and the total CT increased from 444.46 ± 80.43 μm to 484.33 ± 93.19 μm (p = 0.002). The SRF height decreased from 140.38 ± 95.89 μm to 57.58 ± 63.54 μm (p < 0.001), with complete resolution in 79.2% of cases. The BCVA improved from 0.41 ± 0.48 to 0.22 ± 0.30 logMAR (p < 0.001). Changes in the SLCCT correlated negatively with BCVA changes (r = −0.48, p = 0.025) and positively with total CT changes (r = 0.687, p < 0.001). Conclusions: SMLT induces significant choroidal remodeling in chronic CSC, particularly affecting the Sattler–Bruch layer complex. The increase in the SLCCT correlates with visual improvement, challenging the conventional understanding of choroidal thinning in CSC treatment. Full article

Objectives: This study aimed to assess the role of macular pigment optical density (MPOD) in patients with a full-thickness macular hole (FTMH) compared to healthy controls, evaluating postoperative changes in MPOD and exploring potential correlations with visual outcomes. Methods: This prospective, cross-sectional, comparative study included 16 eyes from FTMH patients who achieved anatomical hole closure following pars plana vitrectomy with the inverted ILM flap technique. Each eye underwent a comprehensive ophthalmologic examination, including BCVA and intraocular pressure measurements, anterior segment evaluation, fundus examination, and macular assessment with Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT, Spectralis, Heidelberg Engineering Inc., Heidelberg, Germany). Macular pigment optical density (MPOD) was measured using one-wavelength reflectometry (Visucam 200, Zeiss Meditec, Jena, Germany). These evaluations were conducted preoperatively and at 1, 3, and 6 months postoperatively to assess changes over time and correlate MPOD with visual outcomes. Results: Significant baseline differences were observed between FTMH patients and controls for BCVA, mean MPOD, maximum MPOD, and MPOD volume (p < 0.05). Postoperative BCVA improved significantly (p = 0.0011), with a notable increase in MPOD volume at 6 months (p = 0.01). A positive correlation was found between BCVA improvement and MPOD volume increase (r = 0.739; p = 0.002). Conclusions: In conclusion, MPOD measurement may serve as a valuable addition to the follow-up of FTMH surgery, providing insights into photoreceptor function and macular metabolic activity, potentially correlating with visual recovery. Further longitudinal studies are needed to clarify its relationship with clinical variables, such as metamorphopsia and OCT microstructural findings. Full article

Purpose: Augmented reality (AR) may allow vitreoretinal surgeons to leverage microscope-integrated digital imaging systems to analyze and highlight key retinal anatomic features in real time, possibly improving safety and precision during surgery. By employing convolutional neural networks (CNNs) for retina vessel segmentation, a retinal coordinate system can be created that allows pre-operative images of capillary non-perfusion or retinal breaks to be digitally aligned and overlayed upon the surgical field in real time. Such technology may be useful in assuring thorough laser treatment of capillary non-perfusion or in using pre-operative optical coherence tomography (OCT) to guide macular surgery when microscope-integrated OCT (MIOCT) is not available. Methods: This study is a retrospective analysis involving the development and testing of a novel image-registration algorithm for vitreoretinal surgery. Fifteen anonymized cases of pars plana vitrectomy with epiretinal membrane peeling, along with corresponding preoperative fundus photographs and optical coherence tomography (OCT) images, were retrospectively collected from the Mayo Clinic database. We developed a TPU (Tensor-Processing Unit)-accelerated CNN for semantic segmentation of retinal vessels from fundus photographs and subsequent real-time image registration in surgical video streams. An iterative patch-wise cross-correlation (IPCC) algorithm was developed for image registration, with a focus on optimizing processing speeds and maintaining high spatial accuracy. The primary outcomes measured were processing speed in frames per second (FPS) and the spatial accuracy of image registration, quantified by the Dice coefficient between registered and manually aligned images. Results: When deployed on an Edge TPU, the CNN model combined with our image-registration algorithm processed video streams at a rate of 14 FPS, which is superior to processing rates achieved on other standard hardware configurations. The IPCC algorithm efficiently aligned pre-operative and intraoperative images, showing high accuracy in comparison to manual registration. Conclusions: This study demonstrates the feasibility of using TPU-accelerated CNNs for enhanced AR in vitreoretinal surgery. Full article

Branch retinal vein occlusion (BRVO) is a common retinal vascular condition and a significant contributor to vision loss worldwide, particularly in middle-aged and elderly populations. This review synthesizes current knowledge on the epidemiology, pathogenesis, and clinical features of BRVO, alongside recent advancements in diagnostic and therapeutic strategies. BRVO is approximately four times more prevalent than central retinal vein occlusion (CRVO) and often leads to significant vision impairment. By focusing on BRVO, this review aims to address the specific challenges and advancements in its diagnosis and management. The pathophysiology of BRVO is complex, involving factors such as venous compression, inflammation, and increased levels of vascular endothelial growth factor (VEGF). Diagnostic approaches such as optical coherence tomography (OCT) and fluorescein angiography are highlighted for their roles in assessing disease severity and guiding treatment decisions. Therapeutic interventions, including laser photocoagulation, anti-VEGF therapy, and intravitreal corticosteroids, are critically evaluated, emphasizing emerging treatments such as gene therapy, peptide-based agents, and small-molecule inhibitors. Despite advancements in management strategies, the recurrence of macular edema and treatment resistance remain significant challenges. Continued research is essential to refine therapeutic protocols and improve long-term visual outcomes for patients with BRVO. Full article

Background and Objectives: Amblyopia is a condition where children undergo unilateral or bilateral vision loss due to a variety of disorders that impact the visual pathway. The assessment of retinal nerve fiber layer (RNFL) thickness in amblyopia has made optical coherence tomography (OCT) a useful technique for studying the pathophysiology of this condition. This study was conducted to assess OCT results for various forms of amblyopia, including macular thickness and peripapillary RNFL thickness. It is the first of its kind in Jordan. Materials and Methods: Sixty-one individuals, aged 14 to 67, who had been diagnosed with unilateral amblyopia participated in a prospective study. Both eyes underwent spectral-domain OCT imaging, and clinical and demographic information was gathered. Relationships between different types of amblyopia and OCT measurements were investigated. Results: Compared to the contralateral fellow eyes, the amblyopic eyes showed thicker fovea, and there were differences in foveal and macular thickness observed between the sexes. Individuals with anisometropic amblyopia exhibited a greater central macular thickness. While nasal optic nerve thickness was adversely correlated with age, inferior optic nerve thickness was considerably lower in amblyopia. Conclusions: This research indicates unique OCT traits in amblyopic eyes, which may have a role in amblyopia diagnosis and treatment. The prevention of long-term visual impairment depends heavily on early detection and care. More studies using larger cohorts and longitudinal designs are necessary to improve our knowledge of the pathogenesis of amblyopia and to provide the best possible clinical management approaches. Full article

Background/Objectives: Pseudomonas aeruginosa rapidly acquires antibiotic resistance and demonstrates increasing tolerance to antiseptics. This study evaluated the activity of eight antiseptics against P. aeruginosa, assessed its ability to develop adaptation to these antiseptics, and, for the first time, determined the Karpinski Adaptation Index (KAI) for this bacterium. Methods: The minimal inhibitory concentration (MIC), susceptibility to antibiotics, bactericidal time according to EN 1040:2005, adaptation potential, and KAI of P. aeruginosa strains were evaluated. Results: The most effective antiseptics against P. aeruginosa, based on MIC activity, were octenidine dihydrochloride (OCT; mean MIC 11.3 ± 4.5 µg/mL), polyhexamethylene biguanide (PHMB; MIC 22.6 ± 8.0 µg/mL), and chlorhexidine digluconate (CHX; MIC 26.6 ± 14.4 µg/mL). Sodium hypochlorite (NaOCl) and ethacridine lactate (ET) showed moderate activity, while boric acid (BA), povidone-iodine (PVI), and potassium permanganate (KMnO₄) exhibited the weakest MIC activity. MIC values for NaOCl (95 ± 15.4 µg/mL) and KMnO₄ (>10 mg/mL) were close to or exceeded the clinical concentrations used in commercial products. OCT, CHX, and PVI exhibited the fastest bactericidal effect within 1 min. Bactericidal times were up to 15 min for PHMB, up to 60 min for ET, and more than 60 min for BA, NaOCl, and KMnO₄. The lowest KAI values, indicating a low resistance risk, were observed for OCT (0.12), PHMB (0.19), and BA (0.19). Moderate resistance risk was noted for PVI (0.21), CHX (0.29), and ET (0.47). The highest KAI values, signifying a very high resistance risk, were found for NaOCl (1.0) and KMnO₄ (≥1.0). Conclusions: Antiseptics like OCT, CHX, and partially PVI can be critical in quick antibacterial action on infected wounds, while agents such as PHMB might be reserved for cases where prolonged contact times are possible. Given the rapid adaptation of P. aeruginosa to the clinical concentrations of NaOCl and KMnO₄ currently in use, reconsideration of their effectiveness in treating skin and mucous membrane infections is recommended. Full article

Background/Objective: The aim of this retrospective study was to compare corneal parameters and compliance using a Pentacam HR–Scheimpflug (Pentacam HR) and a swept-source OCT Casia (Casia) in keratoconus (KC) patients post penetrating keratoplasty (PKP) and KC patients without PKP, as well as a control group. Pachymetry measurements were also analyzed using a spectral domain OCT Solix (OCT Solix), Pentacam HR, and Casia. Methods: The study included 71 patients (136 keratoconic eyes; group A), 86 eyes with KC post-PKP (group B), 50 eyes with KC without PKP (group C), and 52 control participants (104 eyes). All participants were adults, Polish Caucasian, and met specific inclusion criteria. Patients with ophthalmological or systemic diseases, cognitive impairment, or pregnancy were excluded. Corneal parameters were measured using two devices (Casia and Pentacam HR), while pachymetry was assessed with three devices (Casia, Pentacam HR, and OCT Solix), with the inter-device agreement and group differences analyzed. Results: Significant differences (p < 0.05) were found across all groups. The post-PKP KC eyes showed significant differences in all front parameters and K2 and Astig. back, while the non-PKP KC eyes showed differences in the K1 back (p = 0.025). The controls displayed differences in all parameters except front astigmatism (p = 0.61). The Pentacam HR overestimated the thinnest corneal thickness (TCT) compared to the OCT Casia across groups. The inter-device agreement was excellent for the anterior parameters (ICC > 0.9) but good for the posterior parameters and TCT. Conclusions: This study highlights significant variability in corneal and pachymetry measurements across devices, with OCT Casia providing more consistent and clinically reliable results than Pentacam HR. Clinicians should exercise caution when using these devices interchangeably, particularly for posterior parameters and TCT. Full article

Purpose: Choroidal thickness (ChT) is an important measurement for evaluating eye and systemic disorders, but it is influenced by numerous elements, especially axial length (AL). It is known that the presence of a linear relationship between ChT and AL exists, but recently it has been shown that the AL measurement obtained with the current optical biometry is not very precise and needs to be corrected. This study aimed to verify if a similar correlation also persists with this corrected AL (ALc). Methods: All subjects underwent a complete eye examination, including spectral domain optical coherence tomography (OCT) with enhanced depth image (EDI) mode and AL measurement with IOLMaster. After a normality check of the data, the correlations between ChT with AL and ALc were investigated through the Pearson correlation coefficient. p values < 0.05 were considered statistically significant. Results: In total, 100 eyes of 50 healthy patients were evaluated. The mean AL was 24.36 ± 1.23 mm and mean ALc was 24.25 ± 1.22 mm. The mean nasal ChT, subfoveal ChT, and temporal ChT were, respectively, 250.57 ± 93.93 µm, 307.18 ± 101.66 µm, and 313.72 ± 88.86 µm. A significant negative linear correlation was found by comparing both AL and ALc to ChT (all r < −0.500, all p < 0.050). The negative linear correlation was stronger between nasal ChT and both AL and ALc (all r = −0.581). Conclusions: Through OCT and optical biometry, we confirmed that a statistically significant correlation persists between ALc and ChT, equal to the uncorrected AL. On these bases, in ChT studies or protocols, we recommend stratifying population according to ALc because linear correlation is still present; however, the cut-off values should be changed according to the systematic errors in optical biometry. In addition, both AL and ChT changes should be evaluated according to ALc. Full article

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. Full article

Background/Objectives: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Methods: The interactions of pinocembrin on drug transporters were determined in the Madin–Darby canine kidney (MDCK) cells overexpressing human (h)OAT1 or hOAT3 and in the Chinese hamster ovary (CHO-K1) cells overexpressing hOCT1, hOCT2, hMATE1, or hMATE2. The interactions of pinocembrin with BCRP and P-glycoprotein were determined in Caco-2 cells. The CYP450 enzyme inhibitory activity was assessed by a cell-free CYP450 screening assay. Results: Pinocembrin effectively inhibited the function of OAT1 and OAT3 with a half-inhibitory concentration (IC₅₀) and inhibitory constant (Ki) of ∼2 μM. In addition, it attenuated the toxicity of tenofovir, a substrate of hOAT1, in cells overexpressing hOAT1. Based on the kinetic study and molecular docking, pinocembrin inhibited OAT1 and OAT3 via a competitive inhibition. In contrast to hOAT1 and hOAT3, pinocembrin did not significantly inhibit the function of OCT1, OCT2, MATE1, MATE2, BCRP, and P-glycoprotein. In addition, pinocembrin potently inhibited the activity of CYP2C19, whereas it exhibited low inhibitory potency on CYP2B6 and CYP2C9. Conclusions: The present study reveals the potential drug interaction of pinocembrin on OAT1, OAT3, and CYP2C19. Co-administration with pinocembrin might affect OAT1-, OAT3-, and CYP2C19-mediated drug pharmacokinetic profiles. Full article

Background/Objectives: The interphotoreceptor matrix proteoglycans 1 and 2 (IMPG1 and IMPG2) are two interdependent proteoglycans of the interphotoreceptor matrix (IPM). Mutations in IMPG1 or IMPG2 are linked to retinal diseases such as retinitis pigmentosa (RP) and vitelliform macular dystrophy (VMD), yet the specific mutations responsible for each condition remain undefined. This study identifies mutations in IMPG1 and IMPG2 linked to either RP or VMD. It also provides an in-depth in silico analysis of these mutations’ structural and functional impact on protein domains, alongside a detailed examination of the corresponding disease phenotypes. Methods: From a cohort of 480 patients with inherited retinal diseases (IRDs), we identified seven patients with mutations in IMPG1 or IMPG2. Multimodal imaging was performed to assess the clinical phenotypes, including fundus photography, fundus autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography (SD-OCT). We provide structure modeling and analysis of each variant. Results: Our findings indicate a prevalence of 1.45% of IRD patients being affected by IMPG mutations; two were diagnosed with RP and five with VMD. One VMD patient carried a novel IMPG1 p.Asp423Glu mutation. Most patients exhibited heterozygous mutations, and one RP patient presented a compound heterozygous mutation in IMPG2. Conclusions: This work describes a novel mutation and expands our understanding of the specific IMPG protein domains implicated in RP and VMD. Furthermore, it establishes, for the first time, the prevalence of IMPG mutations in an IRD population. Full article