This study aimed to evaluate the feasibility of visualizing and quantitatively analyzing the corneal endothelium of sheep using a specular microscope designed for a human eye bank. Twenty-four healthy corneas from 12 one-year-old male sheep (Ovis aries) were examined. Four central endothelial images per cornea were analyzed using a semi-automated method. Endothelial parameters were automatically calculated by the proprietary software integrated into the specular microscope, including endothelial cell density (ECD), average cell area (AVE), coefficient of variation (CV) in cell size, and percentage of hexagonal cells (HEX). Data normality was assessed using the Kolmogorov-Smirnov test, and paired comparisons between right and left eyes were performed using Student's t-test. High-quality endothelial images were successfully obtained from all corneas. The mean ECD was 3198.3 ± 428.3 cells/mm2, AVE was 318.7 ± 42.3 μm2, CV in cell size was 38.0% ± 7.9%, and HEX was 57.7%. No statistically significant differences were observed between right and left eyes for any parameter (p > 0.05). A human eye bank specular microscope allows reliable visualization and quantitative assessment of the ovine corneal endothelium, demonstrating its applicability in experimental and translational veterinary ophthalmology.

Baseline dynamics in human visual behaviour.

To describe the radial outer retina reflectivity (RORR) sign in patients carrying pathogenic variants in the X-linked lysosome-associated membrane protein-2 (LAMP2) gene and to review the histologic characteristics of LAMP2 expression in the human retina. International multicentre observational case series and experimental laboratory study of patients with LAMP2 deficiency. Baseline demographics and multimodal retinal imaging including colour and fundus autofluorescence (FAF), optical coherence tomography (OCT) with en face reconstruction and fluorescein angiography were obtained. Sections through the retina of a human donor eye were processed for immunofluorescence combining antibodies against LAMP2 with markers for Müller glia, rod and cone photoreceptors. Sections were imaged using high-resolution multichannel confocal microscopy. Assessment of en face OCT reflectivity profiles at 5-50 μm internal to the plane of external limiting membrane (ELM) was performed as well as histologic localisation of LAMP2. We recruited 11 cases with pathogenic variants in LAMP2 across five countries. Six cases demonstrated peripheral radial streaks of hyper- and hypopigmentation with UWF imaging. The RORR sign was best visualised 10-25 μm internal to ELM in 9 cases. We hypothesise the radial pattern to be secondary to X-chromosome inactivation. LAMP2 immunoreactivity was observed internal and external to the ELM. Our findings expand the phenotypic spectrum of LAMP2-associated retinopathy by demonstrating the RORR sign using en face OCT. Histologic sections revealed LAMP2 expression in the neuroretina.

Human eyes are hypothesized to play a critical role in social cognition, but this hypothesis has yet to be tested concretely in naturalistic settings. This study investigated how direct gaze (i.e., looking someone in their eyes) during live interactions contributes to impression formation and subsequent social cognition processes. Participants were invited to interact with confederates acting as impression targets (e.g., four different people, one at a time), rated each target's personality after the interaction, and then completed a gaze-cuing procedure as a measure of joint attention. Our research questions were (1) whether direct gaze occurrence varies as a function of eyes' visibility, (2) whether such variations meaningfully relate to impression accuracy, and (3) whether they additionally modulate subsequent joint attention. Results show that participants mainly looked at the targets' eyes during the interaction, particularly when their eyes were visible. Additionally, direct gaze showed limited abilities to predict impression accuracy but preliminary links with joint attention. Integrating theories and methods from both social cognitive psychology and personality psychology, this research shows the concrete importance of the social information conveyed by eyes in our everyday lives.

This study evaluated a combined ex vivo fundus imaging-histology protocol to improve accuracy of diagnosis in human donor eyes with limited medical history. Fifty-one formalin-fixed eyes from 32 donors underwent a standardised workflow comprising ex vivo fundus photography, selective spectral-domain optical coherence tomography (SD-OCT), and comprehensive histological examination. Medical/surgical retinal ophthalmologists independently reviewed imaging, while ophthalmic pathologists performed masked histological assessment. Diagnostic metrics were calculated using histology as the reference standard. Ex vivo imaging identified definitive pathology in 10 of 51 eyes (19.6%) and possible abnormalities in 4 eyes (7.8%). Histological analysis, however, revealed definitive pathology in 20 eyes (39.2%), detecting a broader range of diseases, including early age-related macular degeneration, hypertensive vasculopathy, and a rare choroidal tumour. Concordance was observed in 27 eyes (52.9%), mainly where no pathology was present. Significant discordance occurred in 24 eyes (47.1%), comprising 13 false negatives and 11 false positives (including misclassified pathology). Consequently, the sensitivity and specificity of ex vivo imaging for detecting pathology were 18.8% and 68.6%, respectively. While ex vivo imaging is a practical screening tool, imaging alone may miss or misclassify pathology due to postmortem artefacts and a lack of validated interpretive criteria. A combined imaging-histology approach validates the limited tissue available from eye-bank programs and maximises research value.

Artificial intelligence-driven image analysis has enabled significant advances in digital pathology. However, most approaches have focused on cell or organ structures. This manuscript presents a reproducible deep learning methodology for pixel-level analysis of amorphic patterns in haematoxylin and eosin-stained whole-slide histological images. This study analysed the pixel patterns in the extracellular matrix (ECM) part of connective tissue to identify differences in airway wall ECM compartments and their heterogeneity, which are microscopically similar and difficult to discern with the human eye. Through a targeted preprocessing pipeline, the deep learning model is guided to emphasise learning from pixel-level patterns in non-cellular tissue components while reducing the influence of cellular structures and artefacts. Combined with transfer learning, the model accurately distinguishes the characteristics of the airway submucosa and adventitia, achieving a test area under the curve of 0.84. Using visualisation techniques and statistical analysis, we demonstrate that random pixel imputation successfully reduces the effects of cellular structures on model learning. The framework is applied in a proof-of-principle study of lung tissue from patients with chronic obstructive pulmonary disease, illustrating how this quantitative approach can study population heterogeneity and inform novel research directions. Ultimately, this study provides an innovative and adaptable framework that unlocks the analytical potential of often-overlooked amorphic components in AI-empowered histopathology.

Impaired Rod-Mediated Vision is the Functional Hallmark of Ageing and Early and Intermediate Age-Related Macular Degeneration.

Circulating natural killer cells are phenotypically and functionally altered in age-related macular degeneration.

To evaluate clinical outcomes of adjunctive treatment with homogenate human amniotic membrane eye drops (AMED) in patients with refractory ocular surface disease with dry eye (DE) manifestations. We retrospectively reviewed patients' medical records, ocular surface images, and instrumental data related to Schirmer I test, Oxford and Efron grading, non-invasive tear break-up time, Ocular Surface Disease Index (OSDI), adverse events, and symptom recurrence after discontinuation. All patients were assessed for safety while the efficacy analysis included patients who completed 2-month uninterrupted AMED treatment, without modification of topical or systemic therapy in the previous two months or during the treatment period. A total of 160 patients were exposed to AMED. Twenty-three (14.4%) patients discontinued treatment and 25 (15.6%) showed adverse events. 112 (70%) patients [mean (SD) age 57 (16) years], 73.0% female, were included in the efficacy analysis. We observed improvement in corneal Oxford grading in graft-versus-host disease (GVHD) and limbal stem cell deficiency (LSCD) patients (P < 0.001 and P = 0.02, respectively) and conjunctival Oxford grading in GVHD, LSCD, Sjögren's syndrome (SS) and non-Sjögren's dry eye (NSDE) (P < 0.001); decreasing in Efron score in GVHD and SS (P < 0.001 and P = 0.03, respectively). Tear film stability improved across almost all groups and OSDI showed clinically modest changes. Symptoms recurrence was reported in 86.9% of patients within one month after AMED discontinuation without adverse events reported during 2-month continuous treatment. Adjunctive AMED treatment was associated with objective improvements of ocular surface, with limited effects on symptoms, likely reflecting the multifactorial nature of DE manifestations across clinically and pathophysiological distinct entities.

Mimicking the human eye’s ability to autonomously adapt to diverse and mixed illumination conditions remains a fundamental challenge in artificial vision systems. Although substantial progress has been made in materials and device engineering, current adaptive vision architectures still depend heavily on complex circuitry or algorithms and are typically restricted to uniform illumination owing to the strong intensity-dependence of photosensitivity. Here, this work presents a highly adaptive TiO₂/PEDOT:PSS photomemristor that leverages the tunable conductivity of PEDOT:PSS together with the optoelectronic response of TiO₂. The photothermal effect dynamically modulates the water absorption/desorption equilibrium in PEDOT:PSS, enabling reversible suppression or enhancement of photosensitivity under bright or dim illumination, respectively. By combining with artificial neural networks (ANNs), the artificial vision system based on TiO₂/PEDOT:PSS photomemristor arrays achieves a high accuracy of 91.3% in image recognition under mixed-light conditions—without the need for complex circuitry or algorithms. This work may establish a new approach for designing autonomous, efficient, and high-performance neuromorphic vision systems to advance the development of autonomous driving and humanoid robots.

Fluorescence (FL)-based anti-counterfeiting technologies relying on visible color variations are increasingly vulnerable to counterfeiting, posing a critical challenge to security levels. To address this issue, as proof-of-concept research, we constructed a concealed spectral anti-counterfeiting system using dual-emission red carbon dots (R-CDs), aiming to verify the feasibility of achieving high anti-counterfeiting security through visually invisible but spectroscopically distinguishable FL spectral changes. The as-prepared R-CDs feature two distinct red FL emission peaks at 601 nm and 650 nm, respectively. A notable selective FL response was observed upon interaction with Al3+: the main emission at 601 nm was drastically quenched, while the shoulder emission at 650 nm remained detectable, resulting in obvious spectral differentiation. Owing to the limited resolution of the human eye in the red light region, this spectral variation is visually indistinguishable under green light excitation but can be accurately identified using a FL spectrometer. This study proposes a proof-of-concept design for concealed spectral anti-counterfeiting, offering a new approach to enhance anti-counterfeiting security and providing promising potential for advanced information encryption scenarios.

To investigate the role of Zfp503 in mammalian eye development. Zfp503-/- and Zfp503+/- mice were successfully created through the Knockout Mouse Phenotyping Project (KOMP2), and abnormalities were noted through ophthalmic examination. Embryos were studied at E15.5. Postnatal mice were evaluated using electroretinography (ERG), fundus photography, fluorescein angiography, and optical coherence tomography (OCT) to examine phenotypic differences. Hematoxylin and eosin (H&E) staining was performed to evaluate the retina and optic nerve head (ONH) morphology, and immunohistochemistry was used to determine the expression pattern of Zfp503 in the mouse retina and in the human fetal retina. All homozygous Zfp503-/- embryos of both sexes exhibited hypopigmented eyes and/or anophthalmia and were postnatally non-viable. Histopathology showed hypopigmented retinal pigment epithelium (RPE). With H&E staining, homozygote animals showed failure of the optic fissure to close and what appears to be duplicated retinal tissue. All postnatal Zfp503+/- heterozygotes of both sexes displayed an atypical ONH coloboma. Fundus photography of heterozygotes showed a coloboma extending dorsally from the optic nerve head, and an area of abnormal fluorescence in the area associated with the coloboma region was seen on fluorescein angiography. Histopathology and cross-sectional optical coherence tomography (OCT) showed excavation of the ONH. Three-dimensional OCT reconstructions showed an outpouching consistent with coloboma of the ONH. Other systemic abnormalities in homozygous and heterozygous mice were present across both sexes. The human homolog ZNF503 was detected in fetal eyes. Zfp503 deficiency led to poorly developed RPE and non-viability in Zfp503 knockout mice. Zfp503 heterozygous mice developed an atypical optic nerve coloboma. This study advances previous work by expanding the understanding of the optic nerve coloboma phenotype in heterozygous mice and demonstrating expression of ZNF503 in the developing human eye.

Protocol for the isolation, culturing, and evaluation of primary Müller glial cells from pig retina as cellular models in health and disease.

Zebrafish (Danio rerio) ocular measurements are widely used in ocular disease research and drug discovery. Traditional methods rely on manual annotations, causing challenges in precision, efficiency, and workload. Here, we introduce a deep learning-based zebrafish ocular morphometric analysis (Deep-ZOMA) tool for quantitative measurement of zebrafish larvae ocular structures. A dual-center dataset of 1820 bright-field images (1010 internal; 810 external) was annotated for key ocular regions. A UNet++ segmentation network was trained with augmentation and hybrid loss. Sixteen morphometric parameters were computed using customized quantification algorithms. Performance was evaluated on internal and external datasets using Dice coefficient, IoU, Student's t-test, correlation, and agreement analyses. Utility was further tested on an slc4a7 knockdown/rescue dataset and compared with three ophthalmology graduate students. Deep-ZOMA achieved mean Dice coefficients of 0.96 on the internal set and 0.95 on the external set for primary ocular regions, with IoU values >0.90. Automated measurements showed strong correlations and excellent agreement with expert measurements. In the slc4a7 model, Deep-ZOMA accurately identified microphthalmia and rescue phenotypes consistent with expert annotations. Measurement and data-entry times were >20-fold faster than those of human observers, with comparable or better accuracy. Deep-ZOMA provides a reliable and efficient solution for high-throughput zebrafish ocular morphometry, supporting applications in ocular genetics, drug screening, and phenotypic studies. This deep learning-based system enables accurate, reproducible zebrafish ocular morphometry, accelerating translational research by linking genetic or pharmacological perturbations with quantifiable ocular outcomes relevant to human eye diseases.

Recurrent laryngeal nerve (RLN) dysfunction represents one of the most feared complications of thyroid surgery, with significant impacts on patients' quality of life due to the potential paralysis of the vocal cords. Although nerve transection is rare, functional loss - non-structural and invisible to the human eye - is the primary cause of this complication. Intraoperative nerve monitoring (IONM), introduced more than 50 years ago and significantly improved over the past decade, represents a crucial tool for preventing this outcome. This retrospective observational study involves patients undergoing total or partial thyroidectomy at a specialized center in Italy from 2023 to the present and aims to compare the predictive effectiveness of vagus nerve (VN) stimulation versus RLN stimulation, evaluating three techniques (C-IONM, I-IONM, and No-IONM). All patients were monitored using a NIM system (NIM Avalanche SI2), with pre- and postoperative laryngoscopic evaluation. Among 378 patients undergoing thyroid surgery, no significant differences in baseline demographics were observed among groups. The absence of intraoperative neuromonitoring was associated with a significantly higher risk of permanent vocal cord paralysis compared with I-IONM (OR 4.84, P=0.012). C-IONM showed no cases of permanent paralysis and was associated with significantly shorter operative time and reduced length of hospital stay compared with both intermittent monitoring and no monitoring. I-IONM significantly improves neurological safety in thyroid surgery. C-IONM provides the most favorable overall profile, combining comparable safety with improved operative efficiency and postoperative recovery, and represents a promising strategy for further optimization of surgical outcomes.

Analytical vibro-acoustic model of laminated spherical shell is developed in order to study the vibrational characteristics of human eyeball considering intraocular pressure (IOP) effect. Eyeball layers are assumed to be viscoelastic with frequency- and IOP-dependent properties, filled with compressible inviscid internal fluid. Love's first approximation theory, along with the method of stress function, is used to formulate the governing equations of motion for a laminated spherical shell. The wave equation models the internal acoustic domain, and fluid-solid interaction is accounted for by enforcing velocity and stress continuity condition at the interface. The coupled system frequency equations are derived using the modal expansion method in conjunction with the orthogonality property of mode shapes. The analytical results are validated with the available literature and compared with the finite element simulations. The effects of different parameters including elastic modulus, eyeball thickness and radius, IOP variation, and frequency- and pressure-dependent properties on natural frequencies and damping characteristics are studied. It is observed that multi-layer modelling reduces natural frequencies slightly, whereas incorporating frequency- and IOP-dependent viscoelastic properties significantly increase them, demonstrating the critical importance of viscoelastic modelling for accurate eyeball biomechanics.

SEDP-SegResnet for human eyeball and lens segmentation

PurposeOcular trauma can cause blinding conditions such as choroidal rupture (CR) and retinal detachment (RD). The finite element method (FEM) is widely used to evaluate ocular trauma, but the choroid is often oversimplified because of limited mechanical data, potentially reducing simulation accuracy. This study characterized choroidal mechanical properties and incorporated precise viscoelastic data into ocular trauma simulations.MethodsThe elastic and viscoelastic properties of the choroid were quantified using biaxial tensile testing. These data were integrated into a finite element model of the human eye incorporating the viscoelastic choroid. BB gun projectile impact simulations were then performed at different speeds to analyze the mechanical responses of posterior ocular tissues.ResultsThe principal constitutive parameters of the choroid were determined under equibiaxial loading. Simulation results demonstrated that, under identical ocular trauma conditions, inclusion of the choroid altered both scleral and retinal stresses compared with the choroid-excluded eye model, with retinal stress showing a larger change. At an impact speed of 60 m/s, the retinal stress change exceeded 43%. Moreover, the difference in maximum principal stress between the viscoelastic and linear elastic choroid models was 21%, 36%, and 70% at 20, 40, and 60 m/s, respectively.ConclusionsThis study provides valuable reference data and a theoretical foundation for understanding the mechanical behavior of the choroid. The proposed computational model underscores the importance of viscoelastic choroid and contributes to improving the accuracy of ocular trauma modeling.

Cerebellum-Cerebrum Dynamics During Gaze Processing in Schizophrenia: Evidence for Social-Cognitive Modulation and Associations with Social Functioning Across Independent Samples.

Biometry examination before cataract surgery is crucial to determine intraocular lens (IOL) power. It is mainly influenced by the measurement of eyeball axial length (AXL) and anterior chamber depth (ACD). The hypotony condition shortens these two parameters. The study was conducted to find an appropriate formula that can be used to correct the measurement of AXL and ACD in hypotony conditions. This was a prospective pre-post-experimental study in goat eye. The study population was adult goat eyes that met the inclusion, exclusion, and dropout criteria according to the sample size calculation. The data characteristics of IOP, AXL, and ACD in ultrasound biometry measurements of immersion techniques and Dino-Lite® in both eyes were normally distributed (p > 0.05). There was a linear relationship between IOP with AXL (p = 0.003) and ACD (p = 0.002) in ultrasound biometry and also in Dino-Lite® AXL (p = 0.001) and ACD (p = 0.008). A linear regression formula was found to predict AXL and ACD size correction in goat eyes. The formula obtained in this study can predict the actual size of the adult goat eyeball. Adjustments were made to the data so that the results can mimic the average AXL and ACD of human eyes.