Search Results (205)

Personalized, point-of-care testing of human tears is essential for ocular disease diagnosis, yet it is hampered by picomolar biomarker levels and microliter sample volumes. In this work, we developed an integrated, portable electrochemiluminescence (ECL)-based device for rapid and quantitative detection of tumor necrosis factor alpha (TNF-α), a pivotal inflammatory marker in ocular surface disease, with particular relevance to dry eye syndrome (DES). The device integrates a miniaturized electrochemical cell for ECL reactions and a compact silica photomultiplier for signal measurement. A vertical silica mesochannel (VSM)-coated ITO electrode is also integrated and further functionalized with TNF-α-specific aptamers. The VSM enables the enrichment of ECL luminophores, thus enabling further amplification of ECL signals and enhancing sensitivity. A wide linear range from 0.1 to 200 pg/mL was achieved using 10-fold dilution of 3 μL tear samples. Overall, this study provides a portable, highly sensitive platform for personalized analysis of TNF-α in tear fluid, enabling rapid point-of-care assessment of DES. Full article

Uveal melanoma is the most common primary intraocular malignancy in adults, most frequently arising from the choroid, followed by the ciliary body and iris. Its diagnosis and management require precise characterization of tumor morphology, localization, and associated complications to optimize visual and systemic outcomes. Recent advances in optical coherence tomography (OCT), anterior segment OCT (AS-OCT), and OCT angiography (OCTA) have expanded the ophthalmologist’s ability to non-invasively visualize structural and vascular changes associated with this disease. In fact, enhanced depth imaging (EDI) and swept-source (SS) OCT can provide detailed views of deep ocular structures, enabling early detection of hallmark features such as subretinal fluid, retinal pigment epithelium disruption, and dome- or mushroom-shaped choroidal elevations; AS-OCT improves evaluation of lesions of the anterior segment, revealing iris architecture distortion and angle involvement; OCTA facilitates the visualization of abnormal tumor vasculature and detection of radiation-induced microvascular changes, including capillary dropout and foveal avascular zone enlargement. Moreover, these imaging modalities have demonstrated utility in differentiating uveal melanoma from pseudomelanomas, such as choroidal nevi, hemangiomas, and metastases. The present review aims at objectively assessing the use of OCT and OCTA in the diagnosis, treatment, and follow up of ocular melanoma, emphasizing their crucial role in identifying pathologic biomarkers of this potentially fatal ocular disease. Full article

Background/Objectives: Neoadjuvant systemic therapy may enhance ocular and visual preservation, also prolonging life in patients with choroidal melanoma. We investigated how many choroidal melanomas would be eligible for such treatment to enable Ruthenium-106 brachytherapy. Methods: The cohort comprised 5859 patients treated for choroidal melanoma at the Liverpool Ocular Oncology Centre between 1993 and 2023. Results: If the objective is ocular conservation, then, after excluding tumors > 16 mm in diameter, involving disc and/or more than two clock hours of angle or iris, and/or extending extraocularly, approximately 60.5%, 65.1%, and 67.6% of patients would remain eligible for neoadjuvant systemic therapy, according to whether the maximum allowable tumor thickness is 8 mm, 10 mm or 12 mm, respectively. If the objective is preservation of 20/80 vision, and if exclusion criteria also include vision worse than 20/80 and tumor extension to within 3 mm of optic disc and/or fovea, then 31.0%, 33.2% and 34.1% of tumors would remain in the three tumor-thickness groups, respectively. Chromosome 3 loss would be found in approximately 33%, 52% and 56% of tumors measuring 11–12 mm, 13–14 mm and >14 mm, respectively. Conclusions: Based on the provided data and with effective neoadjuvant treatment, approximately two thirds of subjects with choroidal melanoma requiring enucleation could potentially become candidates for ruthenium-106 brachytherapy and as many as one third could also have the potential for preservation of useful vision. Full article

Retinoblastoma is a rare but malignant pediatric retinal tumor, affecting 1 in 15,000–20,000 live births annually. It arises from biallelic mutations in the RB1 tumor suppressor gene (chromosome 13q14.2), leading to uncontrolled cell cycle progression. Clinically, it presents as unilateral (60%) or bilateral (40%) disease, with leukocoria and strabismus as hallmark signs. Untreated, retinoblastoma is fatal due to metastatic spread. The disease follows Knudson’s two-hit model: heritable forms (30–40% of cases) involve a germline RB1 mutation (M1) and a somatic second hit (M2), predisposing to bilateral/multifocal tumors and secondary cancers. Non-heritable cases (60–70%) result from somatic RB1 mutations or, rarely, MYCN amplification (2%). Genetic testing is critical to classify risk (H0, H1, and HX categories), guide surveillance, and inform family counseling. Bilateral cases almost always harbor germline mutations, while 15% of unilateral cases may carry germline/mosaic RB1 defects. Advanced techniques (Sanger/NGS sequencing for mutation detection, NGS for copy number alterations, and methylation assays) detect RB1 mutations, CNVs, and epigenetic silencing. Tumor DNA analysis resolves ambiguous cases. H1 patients require intensive ocular and brain MRI surveillance, while H0 cases need no follow-up. Prenatal/preimplantation genetic diagnosis (PGD) can prevent transmission in high-risk families. Emerging research explores additional genes (BCOR, CREBBP) and MYCN-amplified subtypes. Genetic counseling addresses recurrence risks, reproductive options, and long-term cancer monitoring. Integrating genetic insights into clinical practice enhances precision medicine, reducing morbidity and healthcare costs. Future directions include whole-genome sequencing and functional studies to refine therapeutic strategies. Full article

Background and Clinical Significance: Carcinoid tumors are rare, slow-growing neuroendocrine cell neoplasms that typically affect the gastrointestinal tract. While metastasis may occur, it most commonly occurs in the liver, and orbital metastasis is extremely rare, especially while on systemic somatostatin suppression. Case Presentation: A 57-year-old man with a history of gastrointestinal carcinoid tumor treated with lanreotide for 5 years presented with a left proptotic, red eye and double vision for several months. Clinical examination revealed left proptosis, supraduction deficit, lower lid retraction, and dilated episcleral vessels inferiorly. Magnetic resonance imaging demonstrated a 1.8 cm enhancing lesion centered within the left inferior rectus muscle. Left orbitotomy and biopsy were performed, which confirmed metastatic carcinoid tumor. He will undergo localized orbital radiation and substitution of lanreotide with systemic chemotherapy. Conclusions: Orbital metastasis of carcinoid tumor is extremely uncommon. Given its rarity, diagnosis may be challenging. In patients presenting with ocular complaints including chronic red eye, double vision, proptosis, and mass effect with a prior history of neuroendocrine cancer, a high index of suspicion for orbital metastasis is necessary with timely workup and treatment even if the disease has been otherwise well-controlled with somatostatin analogs. Full article

Background and Clinical Significance: Intralabyrinthine schwannoma (ILS) is a rare benign tumor of the inner ear, often presenting with nonspecific symptoms such as hearing loss, tinnitus and vertigo. Vestibular function in ILS patients remains underexplored. This study aims to evaluate vestibulo-ocular reflex (VOR) function and inner ear magnetic resonance imaging (MRI) signal changes in ILS, and to provide insights into potential mechanisms underlying vestibular dysfunction. Case Presentation: We report four cases of MRI confirmed ILS, including two intravestibular and two intravestibulocochlear schwannomas. All patients exhibited unilateral canal paresis on caloric testing, and two of three showed abnormal video head impulse test (vHIT) with decreased VOR gain and corrective saccades. Decreased signal intensity was observed in the semicircular canals in three cases, in the vestibule in one case, and in the cochlea in one case. A systematic literature review including 10 studies (n = 171) showed a 73.3% rate of abnormal caloric responses. Five studies conducted vHIT, reporting reduced mean VOR gain and corrective saccades, though quantitative analysis was limited. Cervical and ocular vestibular evoked myogenic potential abnormalities were found in 68.4% and 65.7% of reported cases, respectively. Conclusions: Impaired VOR function in patients with ILS may result not only from anatomical disruption but also from underlying biochemical or metabolic alterations within the inner ear. Full article

The eye, a complex organ essential for visual perception, is composed of diverse cell populations with specialized functions; however, the complex interplay between these cellular components and their underlying molecular mechanisms remains largely elusive. Traditional biotechnologies, such as bulk RNA sequencing and in vitro models, are limited in capturing cellular heterogeneity or accurately mimicking the complexity of human ophthalmic diseases. The advent of single-cell RNA sequencing (scRNA-seq) has revolutionized ocular research by enabling high-resolution analysis at the single-cell level, uncovering cellular heterogeneity, and identifying disease-specific gene profiles. In this review, we provide a review of scRNA-seq application advancement in ocular physiology and pathology, highlighting its role in elucidating the molecular mechanisms of various ocular diseases, including myopia, ocular surface and corneal diseases, glaucoma, uveitis, retinal diseases, and ocular tumors. By providing novel insights into cellular diversity, gene expression dynamics, and cell–cell interactions, scRNA-seq has facilitated the identification of novel biomarkers and therapeutic targets, and the further integration of scRNA-seq with other omics technologies holds promise for deepening our understanding of ocular health and diseases. Full article

Radiation-induced keratoconjunctivitis sicca (KCS) is a significant late complication in dogs receiving radiation therapy for intranasal tumors, particularly with hypofractionated intensity-modulated radiation therapy (IMRT). This retrospective case-control study was performed to identify anatomical and dosimetric risk factors for KCS in 15 canine patients treated with IMRT delivered in 4–6 weekly fractions of 8 Gy. Orbital structures were retrospectively contoured, and dose–volume metrics (D50) were calculated. Receiver operating characteristic (ROC) curve analysis and odds ratios were used to evaluate the associations between radiation dose and KCS development. Six dogs (33%) developed KCS within three months post-treatment. Statistically significant dose differences were observed between affected and unaffected eyes for the eyeball, cornea, and retina. ROC analyses identified dose thresholds predictive of KCS: 13.8 Gy (eyeball), 14.9 Gy (cornea), and 17.0 Gy (retina), with the retina showing the highest odds ratio (28.33). To ensure clinical relevance, KCS was diagnosed based on decreased tear production combined with corneal damage to ensure clinical relevance. This study proposes dose thresholds for ocular structures that may guide treatment planning and reduce the risk of KCS in canine patients undergoing IMRT. Further prospective studies are warranted to validate these thresholds and explore mitigation strategies for high-risk cases. Full article

Chronic kidney disease (CKD)-associated anemia is a global health concern and is linked to vascular and ocular complications. Hypoxia-inducible factor (HIF) stabilizers, or HIF prolyl hydroxylase inhibitors (PHIs), are promising candidates for the treatment of CKD-associated anemia. Since hypoxia and angiogenesis are involved in eye diseases, this study examined the effects of HIF-PHIs on metabolism and gene expression in retinal pigment epithelium (RPE) cells. Results revealed that PHIs differentially induced angiogenic (VEGFA, ANG) and glycolytic (PDK1, GLUT1) gene expression, with Roxadustat causing the strongest transcriptional changes. However, Roxadustat-induced angiogenic signals did not promote endothelial tube formation. Moreover, it did not induce oxidative stress, inflammation, or significant antioxidant gene responses in ARPE-19 cells. Roxadustat also reduced the inflammatory cytokine response to tumor necrosis factor-α, including IL-6, IL-8, and MCP-1, and did not exacerbate VEGF expression under high-glucose conditions. Overall, Roxadustat triggered complex gene expression changes without promoting inflammation or oxidative stress in RPE cells. Despite these findings, ophthalmologic monitoring is advised during PHI treatment in CKD patients receiving HIF-PHIs. Full article

The 90 kDa heat shock proteins (Hsp90) are molecular chaperones that regulate the stability and maturation of numerous client proteins implicated in the regulation of cancer hallmarks. Despite the potential of pan-Hsp90 inhibitors as anticancer therapeutics, their clinical development has been hindered by on-target toxicities, particularly ocular and cardiotoxic effects, as well as the induction of pro-survival, compensatory heat shock responses. Together, these and other complications have prompted the development of isoform-selective Hsp90 inhibitors. In this review, we discuss the molecular bases for Hsp90 function and inhibition and emphasize recent advances in isoform-selective targeting. Importantly, we highlight how Hsp90 inhibition can sensitize tumors to cancer immunotherapy by enhancing antigen presentation, reducing immune checkpoint expression, remodeling the tumor microenvironment, and promoting innate immune activation. Special focus is given to Hsp90β-selective inhibitors, which modulate immunoregulatory pathways without eliciting the deleterious effects observed with pan-inhibition. Preclinical and early clinical data support the integration of Hsp90 inhibitors with immune checkpoint blockade and other immunotherapeutic modalities to overcome resistance mechanisms in immunologically cold tumors. Therefore, the continued development of isoform-selective Hsp90 inhibitors offers a promising avenue to potentiate cancer immunotherapy with improved efficacy. Full article

The covalent conjugation of pharmaceutical compounds to polymeric carriers represents an effective strategy for enhancing drug properties, including improved bioavailability, targeted delivery, and sustained release, while reducing systemic toxicity and adverse effects. By exploiting the physicochemical characteristics of biopolymers—particularly molecular charge and weight—we engineered a polymeric platform for glucocorticoid delivery with precisely controlled parameters including particle size, surface charge, targeting capability, and release kinetics. This study reports a linker-free synthesis of hyaluronic acid-dexamethasone (HA-DEX) conjugates through Steglich esterification, catalyzed by 4-dimethylaminopyridine (DMAP), which facilitates the acylation of sterically hindered alcohols. The reaction specifically couples carboxyl groups of hyaluronic acid with the C21 hydroxyl group of dexamethasone. Incorporation of hydrophobic dexamethasone moieties induced self-assembly into nanoparticles featuring a hydrophobic core and negatively charged hydrophilic shell (−20 to −25 mV ζ-potential). In vitro characterization revealed pH-dependent release profiles, with 80–90% dexamethasone liberated in mildly acidic phosphate buffer (pH 5.2) versus 50–60% in phosphate-buffered saline (pH 7.4) over 35 days, demonstrating both sustained release and inflammation-responsive behavior. The conjugates exhibited potent anti-inflammatory activity in a human tumor necrosis factor-α (TNFα)-induced inflammation model. These findings position HA-DEX conjugates as promising candidates for targeted glucocorticoid delivery to specific anatomical sites including ocular, articular, and tympanic tissues, where their combination of CD44-targeting capability, enhanced permeability and retention effects, and stimulus-responsive release can optimize therapeutic outcomes while minimizing off-target effects. Full article

Purpose: The objective of this study was to evaluate the implementation of a Multidisciplinary Tumor Board (MDTB) strategy in the treatment of patients with uveal melanoma. Methods: A retrospective analysis was conducted on the implementation of MDTB meetings over a 24-month period. During this time, 72 intraocular tumors were discussed, including 59 confirmed cases of uveal melanoma. The MDTB involved a core group of specialists (e.g., ophthalmologists, oncologists, and radiologists), with other experts included when clinically appropriate. To assess patient satisfaction with the MDTB approach, a structured questionnaire was administered, including items on clarity of communication, perceived quality of care, and overall satisfaction, which were ranked on a 5-point scale. Results: A total of 319 patients with ocular, periocular, or orbital tumors were discussed during the study period, of which, 72 had intraocular tumors. A total of 13 (18%) were diagnosed to have choroidal metastases, whereas 59 (82%) had uveal melanomas. The average time between patient care and MDTB discussion was 15.9 days (IQR: 7.5–16.5). The mean time between the case discussion and the implementation of recommendations (diagnostic, therapeutic, or referral decisions) was 14.8 days (IQR: 6.0–23.75). Overall, 4 (7%) patients were classified as Stage I, 16 (27%) as Stage IIa, 18 (31%) as Stage IIb, 7 (12%) as Stage IIIa, 2 (3%) as Stage IIIb, and 12 (20%) as Stage IV. Regarding the satisfaction questionnaire, all patients (100%) agreed to have the clinical case discussed at the TB even though this could result in a delay in diagnostic/therapeutic implementation. However, only 60% of patients perceived they had been directly involved in the decision-making process. Conclusions: In selected cases of uveal melanoma and other types of cancer, MDTBs should be recognized as a gold standard in cancer care, allowing for comprehensive decision-making that draws on a wide range of highly specialized expertise. Full article

Background/Objectives: To determine if the results of cytogenetic analyses of choroidal melanoma biopsies after ruthenium-106 plaque brachytherapy (RPB) are affected by this procedure. Methods: A retrospective study was conducted on 368 patients with choroidal melanoma treated with RPB who underwent cytogenetic testing at the Liverpool Ocular Oncology Centre (LOOC) between May 2012 and November 2024. Data on demographics, tumor characteristics, treatment date, biopsy timing (pre- or post-RPB), and cytogenetic results were extracted from the LOOC database. Statistical analysis included descriptive statistics, binary, and multinomial logistic regression to assess associations between biopsy timing and biopsy success rates. Results: Biopsies were performed before RPB in 58.7% (216/368) cases, and post-PBR in 41.3%. Cytomorphological identification and molecular genetic testing were successful in 96.4% and 85.1% cases, respectively. Timing of biopsy, patient demographics, and tumor characteristics did not significantly influence cytogenetic test outcomes. Molecular testing could not be performed on 6.8% (25/368) cases as the DNA was insufficient in these samples. Genetic testing success slightly declined beyond three months post-RPB, though a few cases had delayed biopsy (n = 8). Pre-RPB biopsies more frequently demonstrated monosomy 3, whereas post-RPB biopsies had higher rates of disomy 3 (χ², p < 0.05). Conclusions: Prognostic biopsies post-RPB provide reliable cytomorphological and molecular genetic results using MLPA or MSA. Test failure is not significantly influenced by biopsy timing, patient or tumor characteristics, biopsy modality, or genetic technique. Insufficient DNA yield remains a key limitation, emphasizing the importance of obtaining adequate tissue samples. Biopsies within three months are preferable to optimize success in molecular testing. Full article

Background: Intra-arterial chemotherapy (IAC) is increasingly useful for treating intraocular retinoblastoma (Rb). It offers targeted delivery of chemotherapy with reduced systemic exposure. In this study, we evaluate management outcomes and identify predictive factors for globe salvage following IAC in children with Rb. Methods: This retrospective study included 20 eyes of 20 melphalan-based IAC-treated patients (67 sessions) between 2015 and 2023 in a tertiary cancer center (King Hussein Cancer Center) in Jordan. Data collection included patients’ demographics, tumor staging, eye salvage, complications, and survival, followed by statistical comparisons between eye salvage rates and clinical factors. Results: The median age of IAC initiation was 38 months (range: 6–78 months). IAC was used as a primary treatment in 35% (7/20) of eyes and as a secondary treatment following systemic chemotherapy in 65% (13/20) of eyes. Nineteen (95%) eyes showed initial tumor regression, 15 (75%) eyes showed short term tumor control, and long-term eye salvage was achieved in 11 (55%) eyes. Poor prognostic factors for eye salvage included advanced tumor stage (Group D/E: 43% salvage rate vs. Group C: 83%; p = 0.047), vitreous seeding at the time of IAC (38% with seeding vs. 75% without; p = 0.046), use of IAC as a secondary rather than a primary treatment (46% vs. 71%; p = 0.047), and the need for >3 IAC cycles (20% success with >3 cycles vs. 67% with ≤3 cycles; p = 0.034). Complications were notable: systemic adverse effects were seen in five (25%) patients, including neutropenia (20%) and bronchospasm (6%). Procedure-related complications were seen with 22% of injections, including failure of the procedure (7%), ophthalmic artery spasm (6%), and intra-procedural stroke (3%). Five (25%) eyes developed ocular complications, including vitreous hemorrhage (15%), retinal detachment (10%), optic atrophy (10%), and retinal or choroidal ischemia (10%). Notably, all infants under 12 months of age (4/4) developed complications, including the two events of stroke. At a median follow-up of 60 months, eye salvage was achieved in 11 (55%) eyes, and none of the 9 (45%) enucleated eyes showed high-risk pathological features. There was no orbital recurrence, and one (5%) child developed CNS metastasis and passed away. Conclusion: IAC achieves long-term globe salvage in 55% of Rb cases; however, outcomes are poorer with Group D/E tumors, vitreous seeds, prior IVC failure, or requiring >3 IAC cycles. While reducing systemic chemotherapy toxicity, IAC carries significant risks of vision- and life-threatening complications. Infants and single-eyed patients require particularly cautious consideration. Though IAC remains crucial for globe preservation, optimal implementation demands improved patient selection criteria, multicenter collaboration, and long-term outcome studies to maximize safety and efficacy. Full article

Dry eye disease (DED) is a common, multifactorial disorder of the ocular surface. Although DED can affect individuals at any age, its prevalence, clinical manifestations, underlying mechanisms, and optimal management strategies differ considerably across the lifespan. In children, symptoms are frequently associated with atopy and allergic disorders and environmental factors, whereas in young adults, digital device usage and contact lens wear are the predominant contributors. In older adults, systemic diseases and polypharmacy significantly elevate the risk of DED. Across all age groups, tear film instability, decreased tear production, and chronic inflammation are central pathogenic features. Key tear biomarkers, such as pro-inflammatory cytokines, have been widely linked to disease development. Cathepsin S and tumor necrosis factor-alpha have recently been implicated in age-related DED. A nuanced understanding of these age-related differences is crucial for improving diagnostic accuracy and tailoring interventions to specific patient populations. This review synthesizes current evidence on DED across age groups, focusing on prevalence, risk factors, pathophysiology, molecular mechanisms, coexisting conditions, biomarkers, and treatment options. Finally, it highlights critical unmet clinical needs in the management of age-related DED. Full article