Search Results (182)

Background: Retinoblastoma (RB) is the most common pediatric ocular tumor that occurs due to the biallelic inactivation of the RB1 tumor suppressor gene. RB may be unilateral or bilateral and is hereditary in 50% of cases. An inactivation of the RB1 gene may occur due to gross rearrangements (20%) or due to small-length changes (80%): single nucleotide substitutions (SNVs) and insertions/deletions (INDELs). Objectives: Our objective was to study the frequency of the different RB1 variants present in patients with retinoblastoma and to correlate them with the functional domains of the pRb protein and with the clinical presentation. Methods: For this purpose, we analyzed all the clinically validated germline SNVs and INDELs annotated in the database. They were grouped into the pRb domains; contingency tables were made, and figures were constructed to compare the types of variants in the different domains between bilateral and unilateral patients. Results: The number of variants analyzed was 2103; 34% of them were nonsense, 34% INDELs, 22% splice-site and 10% missense. All these variants mainly gave rise to bilateral RB (88%); their frequency and distribution in relation to pRb domains varied between bilateral (Bi) and unilateral hereditary (Ug) RB. Nonsense variants occurred more frequently in Bi vs. Ug, whereas missense variants were more frequent in Ug vs. Bi. Indels and splice-site variants were not significantly different between Bi and Ug. The most frequent pRB location of variants was in the Pocket domain (the binding site of the E2F transcription factor). The slice-site of the consensus sequence most mutated was the first nucleotide of the donor, which is the driver of the splicing process. Conclusions: The highest percentage of variants in RB corresponded to nonsense substitutions and indels, mainly affecting the Pocket domain, which is the major functional site for the pRb regulatory process. These results indicate the predominance of the most pathogenic variants related to the bilateral presentation of retinoblastoma. Full article

Background/Objectives: Glaucoma is a multifactorial eye disease that can cause optic nerve damage and irreversible blindness. It is considered a significant public health problem worldwide. Topical intraocular pressure (IOP)-lowering eye preparations are used to prevent or slow further damage. Previously, we demonstrated that nimodipine (NMD), a calcium channel blocker, significantly reduced IOP after a single drop of NMD/HPMC suspension. The current study was designed to develop NMD chitosan nanoparticles (NMD-CS NPs) to improve the NMD IOP-lowering efficacy. Methods: NMD-CS NPs were prepared using the spontaneous-emulsification solvent diffusion method. Three different types of chitosan, carboxymethyl CS (CMCS), low molecular weight CS (LCS), and medium molecular weight CS (MCS), were used. Different concentrations of polymers, various stabilizers, and two pHs were used for formulation optimization. NMD-CS NPs were characterized regarding their particle size, polydispersity index (PDI), zeta potential, DSC, FTIR, and encapsulation efficiency. NMD-CS NPs were incorporated into eye drops and characterized in terms of their in vitro release, cytotoxicity, transcorneal permeability, and in vivo efficacy. Results: The optimized NMD-CS NPs demonstrate a small particle size with a narrow size distribution and acceptable zeta potential values. DSC and FTIR results confirmed the complete entrapment of NMD inside the NPs. NMD-CS NP eye drops successfully sustained NMD release without any burst effect. These NPs demonstrated a Higuchi non-Fickian diffusion mechanism and 79.41% improved corneal permeability. Cytotoxicity studies revealed that NMD formulations are nontoxic. After a single topical ocular application, NMD-MCS NP eye drops induced a significantly superior effect to Timolol maleate eye drops with regard to the %IOP reduction and duration of action. Conclusions: Evaluation results of NMD-CS NP eye drops show their positive effect in a preclinical animal model as a promising glaucoma therapy. Full article

Neurofibromatosis type 1 (NF1) is a prevalent neurocutaneous illness resulting from mutations in the NF1 gene, usually diagnosed according to clinical criteria set by the National Institutes of Health (NIH). These encompass café-au-lait macules, axillary freckling, Lisch nodules, ocular gliomas, osseous lesions, neurofibromas, and familial history. Atypical instances exhibiting partial or isolated characteristics, such as numerous cutaneous neurofibromas (cNFs) absent other classical manifestations, provide a diagnostic difficulty and may be little acknowledged in clinical environments. We describe a 47-year-old male with several soft, non-tender, pinkish-red papules and nodules dispersed throughout the face, torso, limbs, and back. A solitary café-au-lait macule measuring 3 x 2 cm was seen below the right breast, no axillary or inguinal freckling was observed, Lisch nodules were absent during ophthalmologic examination, and there was no pertinent family history. The histopathological examination of a skin lesion verified the diagnosis of cutaneous neurofibroma. According to the NIH guidelines, the patient did not satisfy the requirements for a conclusive diagnosis of NF1. This instance underscores the clinical intricacy of NF1 spectrum diseases and suggests the potential for mosaic NF1 or a minor phenotypic variation. The existence of several cNFs without systemic involvement undermines the adequacy of existing diagnostic paradigms, particularly in adults who exhibit no early-life signs. The psychosocial challenges linked to widespread cNF distribution highlight the necessity for a comprehensive assessment. Limitations encompass the lack of genetic testing, which would have facilitated the confirmation of the diagnosis and the assessment of probable mosaicism. Isolated cutaneous neurofibromas, devoid of other conventional NF1 characteristics, are an uncommon yet clinically pertinent manifestation. Clinicians must uphold a heightened level of suspicion for aberrant NF1 phenotypes and contemplate further examination, using molecular diagnostics where feasible. Reevaluating diagnostic criteria to include these polymorphisms is essential for prompt identification, effective care, and enhanced patient outcomes. Full article

Introduction: Dry Eye Syndrome (DES) is a multifactorial disorder of the ocular surface, characterized by complex interactions between environmental factors, immune dysregulation, and potential genetic predispositions. Vitamin D deficiency, known for its immunomodulatory properties, has increasingly been implicated in the pathogenesis of DES; however, the underlying mechanisms remain insufficiently elucidated. Of particular interest is the vitamin D receptor (VDR) gene, whose polymorphisms may influence the bioavailability and biological activity of vitamin D. Objective: The aim of this study was to investigate the association between serum 25-hydroxyvitamin D [25(OH)D₃] levels and selected polymorphisms in the VDR gene (Taq, Fok, Apa, and Bsm) in patients with DES and to analyze their potential clinical and genetic interactions. Methods: This prospective observational study included 60 patients with a confirmed diagnosis of DES. Serum 25(OH)D₃ levels were measured, and genotyping of four VDR single-nucleotide polymorphisms (SNPs) was performed using PCR followed by restriction fragment length polymorphism analysis. Genotype distributions were assessed in relation to vitamin D status using appropriate statistical tests and Hardy–Weinberg equilibrium analysis. Results: Over 85% of patients exhibited insufficient or deficient vitamin D levels. Among the analyzed SNPs, only the ApaI polymorphism (rs7975232) showed a statistically significant association with vitamin D status (p = 0.0384), with the homozygous AA genotype being more prevalent among patients with hypovitaminosis. The remaining polymorphisms (TaqI, FokI, BsmI) did not reach statistical significance; however, potential trends were observed that may warrant further investigation in larger cohorts. Conclusion: The findings suggest a potential role for VDR gene variability in the regulation of systemic vitamin D levels in patients with DES. Identification of specific genotypes may contribute to the development of personalized diagnostic and therapeutic strategies, particularly for patients with treatment-resistant forms of the disease. These results support the integration of genetic biomarkers and nutritional parameters into modern ophthalmologic practice. Full article

Background/Objectives: Ocular wavefront aberrations are clinically relevant for optimizing vision correction and predicting surgical outcomes. This study aimed to establish normative reference ranges for a Korean population by quantifying wavefront aberrations using a Hartmann–Shack wavefront sensor and Zernike coefficients, and to assess correlations with age, sex, and spherical equivalent (SE). Methods: Wavefront aberrations were measured in 98 Koreans (196 eyes) using a Hartmann–Shack aberrometer without cycloplegia. Five repeated measurements per eye at a 6 mm pupil size were averaged. Parameters included Zernike coefficients (Z3–Z20), higher-order aberration (HOA) root mean square (RMS, Z6–Z20), and total RMS (Z3–Z20). Associations with age, sex, and SE were assessed using univariable and multivariable linear mixed-effects models. Second-order polynomial regression assessed nonlinear relationships. Interocular symmetry was evaluated using mirror-symmetry-adjusted Spearman’s correlation and intraclass correlation coefficients (ICCs). Results: Vertical coma (Z7, 0.208 ± 0.174 μm) and spherical aberration (Z12, 0.200 ± 0.161 μm) were the largest contributors to HOA RMS. Mean HOA RMS and total RMS were 0.51 ± 0.21 μm and 3.03 ± 2.51 μm, respectively. HOA RMS increased with age (β = 0.003 μm/year, p = 0.010), whereas total RMS decreased with SE (β = −0.678 μm/D, p < 0.001). Most Zernike coefficients showed positive interocular correlations, with ICCs of 0.75 for total RMS and 0.64 for HOA RMS. Conclusions: In normal Korean eyes, HOAs increased with age and exhibited significant interocular symmetry. Vertical coma and spherical aberration were predominant components. While the pattern was similar to that in Western populations, the absolute values were greater. These normative values may aid future wavefront-guided refractive surgery and presbyopia correction procedures. Full article

Objective: IgG4-Related Orbital Disease (IgG4-ROD) is an incompletely understood differential of idiopathic orbital inflammatory syndrome (IOIS). Accurate separation guides therapy and prognosis. This retrospective study also profiles its clinical features, therapy needs, and compares them with IOIS. Methodology: Fifty-four patients were biopsied between January 2016 and December 2023, comprising 18 who were diagnosed with IgG4-ROD (4 definite, 14 probable) and 36 with IOIS. Mean follow-up was 21.7 ± 26.2 months for IgG4-ROD versus 7.5 ± 10.3 months for IOIS. Results: Patients with IgG4-ROD were older than those with IOIS (mean 61.8 vs. 49.9 years). Gender distribution was balanced. The lacrimal gland (66.7% vs. 61.6%; p = 0.690) and extra-ocular muscles (55.6% vs. 30.6%; p = 0.076) were frequently involved in both entities, whereas paranasal sinus infiltration was significantly associated with IgG4-ROD (p = 0.003). Common shared symptoms (p > 0.05) included eyelid swelling (83.3% vs. 86.1%), exophthalmos (50% vs. 36.1%), and motility restriction (22.2% vs. 25%). Relative afferent pupillary defect (p = 0.042), chemosis (p = 0.02), and systemic disease (p = 0.005) were more prevalent in IgG4-ROD. During ≥ 6-month follow-up (n = 7), only 28.6% of IgG4-ROD patients achieved sustained remission; Kaplan–Meier analysis yielded a mean time to first event of 926 days. Additional steroid-sparing therapy was required more often in IgG4-ROD than in IOIS (p = 0.002). Conclusion: IgG4-ROD and IOIS share clinical features but differ in key aspects such as associated diseases, therapy requirements, and disease control. Understanding these differences is crucial for targeted diagnostics and individualized treatment strategies. Full article

Background/Objectives: We report the development of a novel intraocular sustained-release implantable pharmaceutical formulation, designed to be placed in the anterior chamber of the eye after cataract surgery. The device is intended to reduce postoperative inflammation, and to prevent opportunistic bacterial infections that may lead to endophthalmitis. Methods: The implants were produced via hot-melt extrusion, using a twin-screw extruder to process a homogeneous mixture of polylactide-co-glycolic acid, moxifloxacin hydrochloride (MOX HCl) and dexamethasone (DEX). Quality control tests included drug content determination, release rate profile evaluation, and several instrumental characterization techniques (scanning electron microscopy (SEM), confocal Raman microscopy, differential scanning calorimetry, and X-ray diffraction). Long-term and accelerated stability tests were also performed, following ICH guidelines. Sterilization was achieved by exposing samples to gamma radiation. In vivo exploratory studies were carried out in healthy rabbits to evaluate the safety and overall performance of the implantable formulation. Results: In terms of quality control, drug content was found to be homogeneously distributed throughout the implants, and it also met the label claim. In vitro release rate was constant for MOX HCl, but non-linear for DEX, increasing over time. In vivo preliminary tests showed that the inserts completely biodegraded within approximately 20 days. No clinical signs of anterior segment toxic syndrome or statistically significant intraocular pressure differences were found between treatment and control groups. Conclusions: The implants developed in this study can act as sustained-release depots for the delivery of both DEX and MOX HCl, and are biocompatible with ocular structures. Full article

The ocular surface microbiome consists of microorganisms that play an important role in maintaining homeostasis and preventing disease from invading pathogens. Commensal microbes on the ocular surface interact with cells and molecules of the ocular surface immune system to promote immune tolerance to the normal flora of the ocular surface and facilitate immune protection against invading pathogenic microbes, which allows for a disease-free ocular surface. Various factors can impact the composition, distribution, and diversity of the ocular surface microbiome, including age, gender, disease state, antibiotic treatment, and contact lens use. In addition, there is no cohesive consensus on the species that make up the ocular surface microbes. There is, however, thorough research present on other similar mucosal membranes, such as the gut and oral mucosa, that share similarities with the ocular mucosa. Exploring the relationship of different mucosae allows us to explore treatment options for common ocular diseases such as dry eye syndrome. This review highlights studies that define the ocular surface microbiome, its diversity and composition, host–immune interactions at the ocular surface, factors that cause dysbiosis of the ocular surface microbiome, the impact of dysbiosis on the ocular surface microbiome, and microbiome-based therapy. Full article

Transcriptomic profiling is a powerful tool for dissecting the cellular and molecular complexity of ocular tissues, providing insights into retinal development, corneal disease, macular degeneration, and glaucoma. With the expansion of microarray, bulk RNA sequencing (RNA-seq), and single-cell RNA-seq technologies, artificial intelligence (AI) has emerged as a key strategy for analyzing high-dimensional gene expression data. This review synthesizes AI-enabled transcriptomic studies in ophthalmology from 2019 to 2025, highlighting how supervised and unsupervised machine learning (ML) methods have advanced biomarker discovery, cell type classification, and eye development and ocular disease modeling. Here, we discuss unsupervised techniques, such as principal component analysis (PCA), t-distributed stochastic neighbor embedding (t-SNE), uniform manifold approximation and projection (UMAP), and weighted gene co-expression network analysis (WGCNA), now the standard in single-cell workflows. Supervised approaches are also discussed, including the least absolute shrinkage and selection operator (LASSO), support vector machines (SVMs), and random forests (RFs), and their utility in identifying diagnostic and prognostic markers in age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma, keratoconus, thyroid eye disease, and posterior capsule opacification (PCO), as well as deep learning frameworks, such as variational autoencoders and neural networks that support multi-omics integration. Despite challenges in interpretability and standardization, explainable AI and multimodal approaches offer promising avenues for advancing precision ophthalmology. Full article

Transcorneal electrical stimulation (TES) is a promising treatment for several retinal degenerative diseases (RDDs). TES involves the application of a controlled electrical current to the anterior surface of the cornea, aimed at activating the retina and posterior ocular structures. Dawson–Trick–Litzkow (DTL) and ERG-JET electrodes are among the most widely used for TES. However, their continuous metallic surface design limits spatial resolution and the ability to perform selective ES. In this work, we present the development of a transcorneal electrical stimulation (TES) electrode that, unlike conventional electrodes, enables spatially selective TES. The proposed electrode design consists of an array of 20 independent microelectrodes distributed across the central and paracentral regions of the cornea. The fabrication process combines surface micromachining and flexible electronics technologies, employing only three structural materials: aluminum (Al), titanium (Ti), and polyimide (PI). This material selection is critical for achieving a simplified, reproducible, and low-cost fabrication process. The fabricated electrode was validated through electrical and electrochemical testing. The results show a relatively high electrical conductivity of Al/Ti structures, low electrochemical impedance values—ranging from 791 kΩ to 1.75 MΩ for the clinically relevant frequency range (11 to 30 Hz)—and a high charge storage capacity of 1437 mC/cm². The electrode capacity for electrical signal transmission was demonstrated through in vitro testing. Finally, the applicability of the TES electrode for electroretinogram (ERG) recording was evaluated by measuring its optical transmittance across the visible wavelength range. Full article

Ocular disease (OD) represents a complex medical condition affecting humans. OD diagnosis is a challenging process in the current medical system, and blindness may occur if the disease is not detected at its initial phase. Recent studies showed significant outcomes in the identification of OD using deep learning (DL) models. Thus, this work aims to develop a multi-classification DL-based model for the classification of seven ODs, including normal (NOR), age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma (GLU), maculopathy (MAC), non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR), using color fundus images (CFIs). This work proposes a custom model named the ocular disease detection model (ODDM) based on a CNN. The proposed ODDM is trained and tested on a publicly available ocular disease dataset (ODD). Additionally, the SMOTE Tomek (SM-TOM) approach is also used to handle the imbalanced distribution of the OD images in the ODD. The performance of the ODDM is compared with seven baseline models, including DenseNet-201 (R₁), EfficientNet-B0 (R₂), Inception-V3 (R₃), MobileNet (R₄), Vgg-16 (R₅), Vgg-19 (R₆), and ResNet-50 (R₇). The proposed ODDM obtained a 98.94% AUC, along with 97.19% accuracy, a recall of 88.74%, a precision of 95.23%, and an F1-score of 88.31% in classifying the seven different types of OD. Furthermore, ANOVA and Tukey HSD (Honestly Significant Difference) post hoc tests are also applied to represent the statistical significance of the proposed ODDM. Thus, this study concludes that the results of the proposed ODDM are superior to those of baseline models and state-of-the-art models. Full article

Background: Postoperative ocular inflammation is a frequent complication of eye surgeries commonly managed using corticosteroids or nonsteroidal anti-inflammatory drug (NSAIDs) eye drops. However, poor ocular bioavailability and patient non-adherence due to frequent dosing limit the therapeutic efficacy of conventional eye drops. This study aimed to develop a sustained-release ocular insert containing bromfenac sodium (BS)-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles (MPs) with an initial 3% (w/w) free BS fraction incorporated into a poly(vinyl alcohol) (PVA) matrix designed to achieve a dual-phase release profile for improved postoperative therapy. Methods: PLGA-based MPs were fabricated using a double emulsion solvent evaporation technique and incorporated into PVA films to produce ocular inserts with varying MP content. Formulations were characterized for morphology, particle size, zeta potential, drug loading, entrapment efficiency, mucoadhesion, drug distribution, and in vitro release. Data were analyzed by an ANOVA and t-tests with p < 0.05 as significance. Results: MPs were smooth, spherical, and well-dispersed in the PVA inserts. Particle sizes ranged from 3.7 to 5.6 µm, with drug loading 7–8% and entrapment efficiencies 47–52%. Multiphoton imaging confirmed uniform drug distribution. In vitro release showed a dual-phase profile with an initial burst followed by sustained release for up to 4 days, with only negligible further release through Day 6 in one formulation (M1-7525). Conclusions: The developed BS-loaded PLGA MP/PVA insert demonstrated a dual-phase release profile relevant to postoperative ocular inflammation. Its biodegradable, single-application design holds promise for enhancing compliance and therapeutic outcomes in ophthalmic care. Full article

Topical drug administration is a common method of delivering medications to the eye to treat various ocular conditions, including glaucoma, dry eye, and inflammation. Drug efficacy following topical administration, including the drug’s distribution within the eye, absorption and elimination rates, and physiological responses can be predicted using physiologically based pharmacokinetic (PBPK) modeling. High-resolution computational models of the eye are desirable to improve simulations of drug delivery; however, these approaches can have long run times. In this study, a fast-running computational quasi-3D (Q3D) model of the human tear film was developed to account for absorption, blinking, drainage, and evaporation. Visualization of blinking mechanics and flow distributions throughout the tear film were enabled using this Q3D approach. Average drug absorption throughout the tear film subregions was quantified using a high-resolution compartment model based on a system of ordinary differential equations (ODEs). Simulations were validated by comparing them with experimental data from topical administration of 0.1% dexamethasone suspension in the tear film (R² = 0.76, RMSE = 8.7, AARD = 28.8%). Overall, the Q3D tear film model accounts for critical mechanistic factors (e.g., blinking and drainage) not previously included in fast-running models. Further, this work demonstrated methods toward improved computational efficiency, where central processing unit (CPU) time was decreased while maintaining accuracy. Building upon this work, this Q3D approach applied to the tear film will allow for more seamless integration into full-body models, which will be an extremely valuable tool in the development of treatments for ocular conditions. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), is known to affect multiple organ systems, including the respiratory tract and nervous and ocular systems. This retrospective study aimed to characterize the spatiotemporal distribution of viral antigen and associated pathological changes in the nose, lungs, brain, and eyes of K18-hACE2 mice intranasally infected with SARS-CoV-2. Using histology and immunohistochemistry, tissues were examined at 3, 6, and 7/8 days post-infection (dpi). In addition, lung and brain tissues were analyzed by means of RT-qPCR to determine viral RNA titers. Viral antigen was most pronounced in the nose, brain, and lung at 3, 6, and 7/8 dpi, respectively, whereas viral antigen was detected at 6 and 7/8 dpi in the retina. Quantitative PCR confirmed increasing viral RNA levels in both lung and brain, peaking at 7/8 dpi. Nasal and lung inflammation mirrored viral antigen distribution and localization. In the brain, the predominantly basal viral spread correlated with lymphohistiocytic meningoencephalitis, neuronal vacuolation, and altered neurofilament immunoreactivity. Retinal ganglion cells showed viral antigen expression without associated lesions. Microglial activation was evident in both the optic chiasm and the brain. These findings highlight the K18-hACE2 model’s utility for studying extrapulmonary SARS-CoV-2 pathogenesis. Understanding the temporal and spatial dynamics of viral spread enhances insights into SARS-CoV-2 neurotropism and its clinical manifestations. Full article

Pollinating fig wasps (Agaonidae) engage in an obligate mutualism with Ficus species, which is mediated by host-specific chemical cues. However, the role of visual perception in host recognition remains poorly understood, particularly because of a lack of structural studies of their compound eyes. We investigated the ocular morphology of female Ceratosolen gravelyi (exclusive pollinator of F. semicordata) using scanning/transmission electron microscopy. The oval apposition eyes contain 228–263 ommatidia, which are asymmetrically distributed between the left and right eyes. Each ommatidium comprises a biconvex corneal lens overlying a tetrapartite eucone crystalline cone; proximal cone cells reveal an interlaced labyrinth. Pigment cells encapsulate each ommatidium, and numerous pigment granules and mitochondria are present in both pigment and retinular cells. Nine retinular cells comprise a unit, with eight photoreceptors (R1–R8) forming the rhabdom from the cone base to the basal matrix; a ninth cell replaces R8 in the apical third of the rhabdom. Optical metrics, including F-number (1.1°), acceptance angle (10.0°), and ommatidial sensitivity (0.26 µm²/sr), indicate diurnal activity in bright environments. These adaptations suggest that their eyes are critical for processing visual cues during host interactions, which advances our understanding of multimodal sensory integration in fig–wasp mutualism. Full article