Search Results (89)

Traditional 3D bioprinting of corneal constructs relies on planar slicing, which often results in a significant stairstep effect and the loss of anatomical curvature. Curvilinear layering has emerged as a promising alternative to address these limitations. The presented methodology, based on non-planar layer integration, ensures a smoother surface finish. The model’s surface is identified via vertex normals and reconstructed using the Poisson method. Finally, surface parametrization is applied to generate spatially curved trajectories. To validate the algorithm, corneal constructs were printed using a planar and the proposed non-planar approach. Quantitative evaluation of micro-Computed Tomography data revealed that the non-planar approach achieved significantly higher morphological fidelity, successfully replicating the intended parabolic profile of the human cornea. Furthermore, the non-planar constructs demonstrated adequate functional performance, characterized by high optical transparency. Thereby, the feasibility of printing non-planar layers using the proposed novel approach is successfully demonstrated. Furthermore, the comparative analysis confirms the method’s potential for corneal biofabrication when compared to traditional planar methods. Full article

Background and Objectives: Pediatric keratoconus may progress rapidly, and treatment decisions are often made before prolonged observation is possible. This study evaluated 24-month visual, tomographic, pachymetric, and biomechanical outcomes after conventional epithelium-off corneal collagen cross-linking (CXL) using Pentacam tomography and Corvis ST dynamic Scheimpflug analysis. Materials and Methods: This single-center observational longitudinal cohort included 28 eyes of 23 patients aged 13–18 years treated at the OCULENS Clinic, Cluj-Napoca, Romania, between 2019 and 2023. Because the study had no untreated or alternative-treatment control group, postoperative changes were interpreted as associations after CXL rather than as proof of causality. Baseline, 6-, 12-, and 24-month values were analyzed for UCVA, BCVA, Kmax, thinnest pachymetry, SP-A1, deformation amplitude (DA), first and second applanation times (A1T and A2T), highest concavity (HC) radius, and BAD-D. Repeated-measures ANOVA was used after assessment of within-eye difference normality; findings were interpreted cautiously because the analysis was eye-based, the cohort was small, and multiple outcomes were examined. Results: UCVA improved from 0.53 ± 0.16 to 0.44 ± 0.16 logMAR and BCVA from 0.31 ± 0.11 to 0.25 ± 0.11 logMAR (both p < 0.001). Mean Kmax decreased modestly from 54.36 ± 3.11 D to 53.41 ± 2.79 D, while SP-A1 increased from 84.69 ± 4.75 to 97.39 ± 5.11 (both p < 0.001). Thinnest pachymetry showed early postoperative thinning followed by partial recovery by 24 months. DA decreased, A1T increased, A2T decreased, HC radius increased, and BAD-D decreased significantly. Kmax and SP-A1 were inversely correlated at all visits (r = −0.714 to −0.773; all p < 0.001), but these correlations were considered exploratory. Post-24-month retreatment and keratoplasty-related events were recorded descriptively and were not included in the formal 24-month model. Conclusions: Within the prespecified 24-month analytic window, conventional epithelium-off CXL was associated with stabilization, modest visual and tomographic improvement, and a concordant biomechanical stiffening signal. The results should be interpreted as cautious observational findings rather than definitive evidence of long-term stability, because of the small sample, eye-level analysis, absence of a control group, limited follow-up, and lack of formal repeatability testing. Full article

For testing ocular irritation, 3D corneal models mimicking the corneal epithelium are considered reliable eye irritation tests and are detailed in regulatory guideline OECD Test Guideline (TG) 492. The aim of the present study was to develop and validate a Reconstructed human Cornea-like Epithelium (RhCE) in vitro irritation test method for ophthalmic medical devices according to OECD TG 492. Immortalized Human Primary Corneal Epithelium Cells (IM-HCEpiCs) were cultured on microporous inserts and exposed to an Air–Liquid Interface (ALI). Morphology was examined using standard (immuno-) histological techniques. Viability was quantified with MTT assay. Barrier integrity and function were monitored by trans-epithelial electrical resistance (TEER) and determination of IC₅₀ using MTT assay. Reproducibility was evaluated by calculating the inter-batch coefficient of variation (CV %) of the absorbance values of negative control-treated RhCE model replicates by MTT assay. Technical proficiency was verified using reference chemicals. Irritancy of ophthalmic medical devices was assessed. IM-HCEpiCs developed an epithelium-like barrier under the ALI. TEER increased after ALI introduction, and the obtained IC₅₀ value showed concordance with the guideline’s reference ranges. The developed RhCE test method demonstrated technical proficiency and correctly identified medical devices as non-irritants. A novel RhCE model was developed and validated according to OECD TG 492. Full article

Qin Bing eye drops, a traditional Chinese medicine-based in-hospital preparation, were historically indicated for the treatment of conjunctivitis, keratitis, and photokeratitis. This study aimed to develop Qin Pi extract (QP-E) using a proprietary extraction method, and to evaluate the therapeutic efficacy of QP-E alone, QP-E combined with Bing Pian (BP), and an ophthalmic formulation (QP-D) comprising both constituents in a preclinical model of dry eye disease (DED). DED was induced in mice via subcutaneous scopolamine administration alone, whereas a more robust dry eye phenotype was established in rats through combined treatment with scopolamine and environmental stressors. Ocular surface evaluation included measurement of tear secretion volume and corneal fluorescein staining scores. The results demonstrated that both QP-E monotherapy and the QP-E–BP combination significantly ameliorated key pathological features of DED, including tear film instability and corneal epithelial damage. QP-D—formulated with rationally optimized concentrations of QP-E and BP—significantly enhanced basal tear secretion and attenuated corneal epithelial injury in both murine and rat dry eye models. Mechanistic investigations revealed that QP-E treatment markedly inhibited VEGF-C secretion from classically activated (M1) macrophages, suppressed phosphorylation-dependent activation of the VEGF-C/VEGFR-3 signaling axis, and consequently impaired lymphatic endothelial cell migration and in vitro tube formation. These correlative findings indicate that QP-E may partially alleviate DED by suppressing lymphangiogenesis; however, direct causal evidence—such as genetic ablation of VEGF-C or pharmacological inhibition of VEGFR-3—was not established in the present study. Collectively, our data yield a testable mechanistic hypothesis and propose a novel therapeutic strategy targeting lymphatic remodeling for DED intervention. Full article

Artificial optical radiation, spanning from 100 nm to 1 mm, encompasses ultraviolet (UV) and infrared (IR) light. UV light is well known for its risks on the skin and eyes. Recently, there has been growing interest in light at 405 nm (violet-blue light, VBL) due to its antimicrobial properties and perceived safety for mammalian cells when administered in controlled amounts. This research delved into the impact of 405 nm VBL on corneal and retinal pigment epithelial cell cultures. ARPE-19 and corneal BCE C/D 1b cells were exposed to VBL for varying doses, according at different exposure times, to evaluate cell viability, oxidative stress levels and apoptotic indicators. A 3D printed prototype with 14 LEDs centred at 405 nm wavelength was used to ensure uniform distribution of light during exposure. Cell viability was assessed using the MTT assay, measurement of oxygen species (ROS) production was carried out, and Western blot analysis was employed to study catalase and SOD-1 expression and apoptotic marker activation. Exposure to 405 nm VBL for both term (3 h) and prolonged durations (9 h) led to a weak decrease in cell viability in ARPE-19 cells, whereas the effect on BCE C/D 1b cells was negligible. There was no increase in ROS production, with catalase and SOD-1 expression remaining stable, suggesting no pro-oxidative stress effects in these models. Moreover, no activation of caspase-3 and accumulation of cytochrome C were found. Based on our results, exposure to 405 nm light at regulated levels does not pose a threat to the viability of the tested cell lines and does not lead to oxidative stress and apoptosis under these conditions. These results suggest a favourable cytocompatibility profile for these specific ocular cell models, laying a foundation for further investigations into its ocular safety. Full article

Objectives: To develop and prospectively validate a predictive model to estimate the fetal postmortem interval (PMI) using three-dimensional postmortem ultrasound (3D PM-US) measurements of corneal and ocular volumes. Methods: Single-center study including fetuses ≥ 20 weeks’ gestation with known time of death after feticide. A retrospective training cohort (n = 63; November 2022–July 2023) and a prospective validation cohort (n = 28; February–August 2025) were used. Corneal and ocular volumes were measured using the VOCAL™ rotation multiplanar technique; the cornea-to-eyeball volume ratio was calculated for each case. Automated machine learning (AutoML) was used to develop and validate a gradient boosting machine (GBM) model. Model performance was evaluated using the root mean squared error (RMSE), mean absolute error (MAE), and coefficient of determination (R²). Results: Ninety-four fetuses were included; three were excluded (two for extreme death–US intervals of 165 and 166 h; one for open eyelids). Median gestational age was 29.3 weeks (IQR 27.2–32.9); median birthweight was 1325 g (IQR 980–1880). The cornea-to-eyeball volume ratio was an independent predictor of PMI (p < 0.001). The GBM model explained 91% of the variance in the training cohort (R² = 0.91, RMSE = 11.49 h, MAE = 8.45 h) and 75% in the validation cohort (R² = 0.75, RMSE = 18.32 h, MAE = 14.49 h), demonstrating strong predictive accuracy and minimal overfitting. Variable importance analysis confirmed the cornea-to-eyeball ratio as the most influential and biologically plausible predictor of PMI. A Shiny web application was developed to facilitate clinical implementation. Conclusions: 3D PM-US measurements of the fetal cornea and eyeball can reliably and quantitatively estimate the PMI with good predictive accuracy using a GBM model. Multicenter studies are required to further refine the model, enable external validation, and determine its clinical and forensic utility. Full article

Using simulation methods, we investigated the effects of corneal thickness and ocular rotation on intraocular pressure (IOP) measurement accuracy. In the first part, a 24 mm emmetropic eye model with a titanium-alloy probe was used to evaluate corneal thicknesses of 0.50, 0.55, and 0.60 mm. Probe force–IOP response curves were analyzed under supine, upright, and prone positions to determine the role of corneal biomechanics in measurement variation. In the second part, ocular rotation was examined using a fixed probe force of 19.62 mN and a corneal thickness of 0.55 mm. Five eye models with different refractive conditions—hyperopic, emmetropic, and myopic eyes of −6.00, −12.00, and −18.00 D—were simulated to assess the influence of rotation and instantaneous acceleration on IOP and shear stress. The findings highlight how both structural and dynamic ocular factors contribute to IOP variability, offering valuable insights for improving the accuracy of clinical tonometry. Full article

Background/Objectives: Premium intraocular lenses (IOLs) are increasingly being selected for cataract and refractive lens surgery, but their functional performance depends critically on pupil size and corneal spherical aberration (SA). This study evaluates how these factors modulate the optical behavior of the RayOne EMV and Tecnis Synergy using a profilometry-based Through Object modulation transfer function (TO MTF) analysis. Methods: The surface profiles of the RayOne EMV and Tecnis Synergy were measured with a confocal optical profilometer and implemented in pseudophakic eye models via ray tracing. TO MTF at 50 cycles/mm was computed for object vergences from −4.0 D to +2.0 D over entrance pupil diameters from 2.0 to 5.5 mm in three corneal configurations derived from the Liou–Brennan model and ISO recommendations: mean population SA, aberration-free, and a myopic LASIK-like oblate cornea. Simulated optotype images were generated to relate TO MTF values to the expected distant, intermediate, and near visual performances. Results: RayOne EMV delivered high-quality distant image performance in all models. Its depth of focus increased only modestly and showed a strong dependence on pupil size. Intermediate and near vision rarely reached clinically acceptable levels. The Tecnis Synergy produced a broad depth-of-field plateau in distant to near visual performance for mean population spherical aberration at a 3.5 mm pupil. However, image quality at 90 cm remained limited. Optical performance worsened with increasing pupil size and positive spherical aberration, particularly under post-myopic LASIK conditions. Conclusions: The RayOne EMV behaves predominantly as a distance-oriented design with minimal true presbyopic benefit; the Tecnis Synergy provides a wider range of vision but is highly sensitive to corneal spherical aberration and pupil size, so thorough preoperative evaluation of corneal asphericity and functional pupil diameter is essential for IOL selection and power targeting. Full article

Background/Objectives: This study aimed to repurpose aripiprazole (AR), an antipsychotic clinically approved by the FDA, as a novel antifungal drug and to potentiate its therapeutic efficacy through PEGylated terpesomes (PEG-TERs). Methods: PEG-TERs were prepared by thin-film hydration and optimized using a central composite design. The optimum PEG-TER formulation was characterized for entrapment efficiency (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP), and subsequently integrated into polylactic acid (PLA)-based 3D-printed ocuserts. Results: The optimized formulation exhibited spherical vesicles with high EE%, nanoscale PS, narrow PDI, and favorable ZP, alongside excellent stability and mucoadhesive properties. Ex vivo permeation demonstrated a sustained release profile of AR from PEG-TERs compared with an AR suspension, while confocal microscopy confirmed efficient corneal deposition of fluorescein-labeled PEG-TERs. In vivo, the optimum AR-loaded PEG-TERs ocusert exhibited a substantial therapeutic effect in a rabbit model of Candida albicans keratitis, while histopathological assessment confirmed its ocular safety and biocompatibility. Conclusions: In conclusion, AR-loaded PEG-TERs embedded in PLA-based 3D-printed ocuserts represent a promising, safe, and innovative therapeutic platform for the management of Candida albicans-induced corneal infections, offering both drug repurposing and emerging opportunities in advanced ocular drug delivery. Full article

Corneal fibrosis, a significant source of visual impairment, can result from keratocyte-to-myofibroblast transdifferentiation during wound healing. This study investigated the antifibrotic role of 1,25-dihydroxyvitamin D₃ (1,25 Vit D) and the lesser-known vitamin D, 24,25-dihydroxyvitamin D₃ (24,25 Vit D), in human and mouse corneal stromal cells (HSCs and MSCs) and in a Vit D receptor knockout (VDR KO) mouse model. Cells were treated with TGF-β1 ± Vit D metabolites and the expression of fibrotic and antifibrotic genes and proteins was evaluated. Both metabolites significantly reduced α-smooth muscle actin levels in HSCs, MSCs and organ-cultured mouse corneas (p < 0.05). They also upregulated the mRNA expression of BMP2, BMP6, BMPR2, and TGF-β3, as well as the protein expression of BMP6 and TGF-β3. VDR KO corneas subjected to alkali injury exhibited increased fibrotic responses and reduced CD45+ immune cell infiltration compared to wild-type controls. Notably, 24,25 Vit D exerted antifibrotic effects even in VDR KO cells, and the alternative 24,25 Vit D receptor FAM57B was expressed in all corneal cell layers. These results reveal consistent antifibrotic effects of both 1,25 and 24,25 Vit D across species, support the existence of VDR-independent mechanisms in the cornea, and offer new insights into potential therapeutic strategies for preventing corneal fibrosis. Full article

We investigated the repeatability of the MS-39 in determining power vector components—the spherical equivalent (SEQ) and astigmatic powers (C0 and C45) and asphericity (Q)—of corneal epithelium, stroma, and endothelium in a large patient cohort. In this retrospective cross-sectional single-centre study, we evaluated a dataset containing 600 MS-39 anterior segment tomography measurements from 200 eyes (three repeat measurements each) taken prior to cataract surgery. The exported measurements included height map data for the epithelium, stroma, and endothelium surface. Model surfaces (spherocylinder (SphCyl), cylindrical conoid (CylConoid), and biconic (Biconic), all in the 3/6 mm zone) were fitted using nonlinear iterative optimisation, minimising the height difference between the measurement and model. The mean (MEAN) and standard deviation (SD) for each sequence of measurements were derived and analysed. In the 3 mm and 6 mm zone, the MEAN SEQ was 53.47/53.56/53.57 and 53.21/53.54/53.54 D for SphCyl/CylConoid/Biconic for the epithelium, −4.47/−4.51/−4.51 and −4.45/−4.50/−4.50 D for the stroma, and −6.23/−6.26/−6.26 and −6.18/−6.29/−6.30 D for the endothelium. With the three surface models and the 3/6 mm zone, the SD for SEQ/C0/C45 was in the range of 0.04 to 0.11/0.05 to 0.13/0.04 to 0.11 D for epithelium; 0.01 to 0.02/0.01 to 0.05/0.01 to 0.06 D for stroma; and 0.01 to 0.02/0.02 to 0.07/0.03 to 0.07 D for endothelium. Fitting floating model surfaces with astigmatism to map data of the corneal epithelium, stroma, and endothelium seems to be a robust and reliable method for extracting equivalent power and astigmatism using all the datapoints within a region of interest. Full article

Diabetic keratopathy (DK) is a common ocular complication of diabetes mellitus (DM), affecting almost half of all diabetic patients. It is characterized by delayed healing of epithelial wounds, reduced corneal sensitivity, and persistent epithelial defects, which, in turn, significantly impair vision and quality of life. The limited understanding of its pathogenesis and the lack of effective treatments highlight the urgent need for more physiologically relevant experimental models. The three-dimensional (3D) models currently available provide valuable information on the pathophysiology of DK, although none of them yet fully reproduce the diabetic corneal phenotype complex. After a brief overview of corneal anatomy, the present review aims to systematically analyze the current 3D in vitro models developed for the study of DK, in terms of tissue architecture, presence of diabetic stimuli, and ability to replicate pathological traits. Full article

Dry eye disease (DED) is a hallmark of primary Sjögren’s disease (SjD) and often resists conventional treatments like lubricant eye drops. Insulin nanoemulsions offer a potential solution by improving drug penetration and retention on the ocular surface. In animal models, insulin has shown benefits in promoting tear secretion and corneal healing. This study evaluated the safety and efficacy of insulin nanoemulsion eye drops (20 IU/mL, three times daily for 30 days) in patients with SjD. Thirty-two patients were randomized in a double-masked design to receive either insulin or placebo drops. Symptoms (assessed by OSDI questionnaire) and objective measures (tear film breakup time, corneal and conjunctival staining, and Schirmer Test) were recorded at baseline, after 4 weeks of treatment, and at a 4-week follow-up. Twenty-three participants completed the study. Both groups showed significant improvement in symptoms and objective signs after treatment (p < 0.05), but no significant differences were found between the insulin and placebo groups. No clinically relevant adverse effects were reported. Insulin nanoemulsion eye drops are safe for SjD patients, but their therapeutic advantage remains unclear. Further studies with larger samples, extended follow-up, and dose adjustments are needed to better understand their potential. Full article

Background/Objectives: The aim of this study was to evaluate the associations between optical coherence tomography angiography (OCTA)-based retinal vessel diameter (RVD) measurements, with retinal ganglion cell (RGC) function assessed by means of steady-state pattern electroretinography (ssPERG) using ganglion cell layer-inner plexiform layer thickness (GCL-IPLT) measurements and with Humphrey field analyzer (HFA) global indices in glaucoma suspects (GSs). Methods: Thirty-one eyes (20 participants) underwent a comprehensive ophthalmologic examination, ssPERG measurements utilizing the PERGLA paradigm, HFA, optical coherence tomography (OCT), and OCTA. The OCTA scans were processed using ImageJ software, Version 1.53, allowing for measurement of the RVD. Multiple linear regression models were used. Results: After controlling for age, race, central corneal thickness (CCT), and spherical equivalent (SE), a linear regression analysis found that the RVD explained the 4.7% variance in magnitude (Mag) (p = 0.169), 9.2% variance in magnitudeD (MagD) (p = 0.021), and 16.9% variance in magnitudeD/magnitude (p = 0.009). After controlling for age, CCT, and signal strength (SS), a linear regression analysis found that the RVD was significantly associated with the GCL-IPLT measurements (average GCL-IPL, minimum GCL-IPL, superior, superonasal, inferior, and inferonasal sectors) (p ≤ 0.023). An identical regression analysis where the RVD was replaced with the PERG parameters showed a significant association between the MagD and almost all GCI-IPLT measurements. RVD measurements were significantly associated with HFA VFI 24-2 (p = 0.004), MD 24-2 (p < 0.001), and PSD 24-2 (p = 0.009). Conclusions: Decreased RVD measurements were significantly associated with RGC dysfunction, decreased GCL-IPLT, and all HFA global indices in the GSs. Full article

Background/Objectives: This study evaluated the diagnostic accuracy of seven publicly available large language models (LLMs)—GPT-3.5, GPT-4.o Mini, GPT-4.o, Gemini 1.5 Flash, Claude 3.5 Sonnet, Grok3, and DeepSeek R1—in diagnosing corneal diseases, comparing their performance to human specialists. Methods: Twenty corneal disease cases from the University of Iowa’s EyeRounds were presented to each LLM. Diagnostic accuracy was determined by comparing LLM-generated diagnoses to the confirmed case diagnoses. Four human cornea specialists evaluated the same cases to establish a benchmark and assess interobserver agreement. Results: Diagnostic accuracy varied significantly among LLMs (p = 0.001). GPT-4.o achieved the highest accuracy (80.0%), followed by Claude 3.5 Sonnet and Grok3 (70.0%), DeepSeek R1 (65.0%), GPT-3.5 (60.0%), GPT-4.o Mini (55.0%), and Gemini 1.5 Flash (30.0%). Human experts averaged 92.5% accuracy, outperforming all LLMs (p < 0.001, Cohen’s d = −1.314). GPT-4.o showed no significant difference from human consensus (p = 0.250, κ = 0.348), while Claude and Grok3 showed fair agreement (κ = 0.219). DeepSeek R1 also performed reasonably (κ = 0.178), although not significantly. Conclusions: Among the evaluated LLMs, GPT-4.o, Claude 3.5 Sonnet, Grok3, and DeepSeek R1 demonstrated promising diagnostic accuracy, with GPT-4.o most closely matching human performance. However, performance remained inconsistent, especially in complex cases. LLMs may offer value as diagnostic support tools, but human expertise remains indispensable for clinical decision-making. Full article