Ocular Diseases Research Articles

Resveratrol: Extraction Techniques, Bioactivity, and Therapeutic Potential in Ocular Diseases

Resveratrol: Extraction Techniques, Bioactivity, and Therapeutic Potential in Ocular Diseases

Response of Patients with Color Vision Defects to Worth 4-Dot and Duochrome Tests

Background: Individuals with congenital color vision defects (CVDs) are at greater risk of misidentifying colors, necessitating an investigation into their ability to distinguish colors accurately. This study aimed to assess how individuals with CVDs perceive the colors in the Worth four-dot (W4D) and duochrome tests. It also explored whether individuals with CVDs require more detailed instructions from optometrists and eye care providers during these tests. Method: Thirty-two participants with congenital CVDs were recruited for this study. Participants with ocular diseases were excluded based on a brief questionnaire. The participants underwent a W4D test to determine the colors of four circles and the duochrome test without using filters. Result: All the participants correctly identified the W4D colors, except for five participants (15.62%). Furthermore, among all the participants, two (one with deuteranopia and one with protanopia) failed to identify the colors correctly in the duochrome test (6.25%). Conclusions: The findings suggest that in the context of optometric assessment, it could be essential for optometrists to incorporate a preliminary inquiry into a patient’s ability to identify colors prior to performing diagnostic tests such as the W4D or duochrome tests. Incorrect responses from patients with CVDs might mislead optometrists regarding the proper outcomes of the test.

Role of Resveratrol in Endotoxin Induced Uveitis: Literature Review

Uveitis is defined by a range of diverse clinical manifestations of ocular disease and involves inflammation of the uveal tissue, which includes the iris, choroid and ciliary body. Uveitis is characterized by a variety of heterogeneous clinical manifestations of ocular diseases. Corticosteroid and immunosupressive medication are required for non-infectious uveitis since they can successfully control inflammation. This study investigates role of Resveratrol as a promosing treatment in endotoxin induced uveitis as a mimic human anterior uveitis. Resveratrol is acknowledged as an antioxidant polyphenol discovered in grape skin and red wine. Anti-inflammatory, anti-cancer, and antioxidant properties are only a few of Resveratrol many biological and medicinal potentials. Our study evaluated the role of Resveratrol in potential therapy of uveitis. Results demonstrate significant reduce of inflammatory cytokine and cells suggesting the potential therapeutic effect of Resveratrol.

AIP1 Regulates Ocular Angiogenesis Via NLRP12-ASC-Caspase-8 Inflammasome-Mediated Endothelial Pyroptosis.

Pathological ocular angiogenesis is a significant cause of irreversible vision loss and blindness worldwide. Currently, most studies have focused on the angiogenesis factors in ocular vascular diseases, and very few endogenous anti-angiogenic compounds have been found. Moreover, although inflammation is closely related to the predominant processes involved in angiogenesis, the mechanisms by which inflammation regulates pathological ocular angiogenesis remain obscure. In this study, a vascular endothelial cells (VECs)-specific anti-angiogenic factor is identified, apoptosis signal-regulating kinase 1(ASK1)-interacting protein-1 (AIP1) as a key pathogenic regulator in a typical ocular angiogenesis model, oxygen-induced retinopathy (OIR), using single-cell RNA sequencing. It is demonstrated that AIP1 inhibited pathological angiogenesis by preventing a particular inflammatory death pathway, namely pyroptosis, in retinal VECs. The assembly of a noncanonical inflammasome is further uncovered, the NLRP12-ASC-caspase-8 inflammasome, which is promoted by decreased AIP1 in OIR. This inflammasome elicited gasdermin D (GSDMD)-dependent endothelial pyroptosis, which in turn promoted the release of vascular endothelial growth factor (VEGF) and interleukin (IL)-1β. Suppression of NLRP12-CASP8-GSDMD axis and AIP1 upregulation reduced VEGF signaling, limiting new vessel formation. These findings reveal a previously uncharacterized inflammatory angiogenic process involving VECs pyroptosis-inducing retinal neovascularization, paving the way for promising therapeutic avenues targeting angiogenesis via AIP1 or pyroptosis.

Pathological Mechanisms of Particulate Matter-Mediated Ocular Disorders: A Review

Air pollution presents a severe risk to public health, with particulate matter (PM) identified as a significant hazardous element. However, despite the eye organ being constantly exposed to air pollution, only recently has the impact of PM on ocular health caught the attention of researchers and healthcare professionals. By compiling pertinent data, this paper aims to enhance our understanding of the underlying pathological mechanisms of PM-mediated ocular disorders and facilitate the development of effective treatment strategies. Recent data support the association between exposure to PM and the development of ocular pathologies such as dry eye syndrome, retinal atherosclerosis, and glaucoma. Based on the results of multiple studies, PM exposure can lead to oxidative stress, inflammation, autophagy, cell death, and, ultimately, the development of ophthalmic diseases. This review aims to consolidate the latest findings on PM-mediated ocular diseases by summarizing the outcomes from epidemiological, in vitro, and in vivo studies on ocular surface and retinal disorders as well as other relevant ophthalmic disorders.

Factors Associated With Ocular Perfusion Measurements as Obtained With Laser Speckle Contrast Imaging.

To study the ocular and systemic factors affecting optic nerve head (ONH) perfusion data as obtained using a commercially available laser speckle flowgraphy (LSFG) device in a cohort of Caucasian subjects without ocular diseases. Also, to assess the intrasession repeatability and intersession reproducibility of ONH, macular, retinal, and choroidal perfusion. Seventy-five healthy eyes of 75 Caucasian participants underwent LSFG and spectral-domain optical coherence tomography (SD-OCT) on the same visit. Perfusion of the ONH was assessed with LSFG, and SD-OCT was used to measure peripapillary retinal nerve fiber layer thickness (RNFLT) and macular ganglion cell plus inner plexiform layer thickness (GCIPLT). The intrasession repeatability and intersession reproducibility of ONH and macular perfusion and retinal and choroidal relative flow volume (RFV) were evaluated in 20 participants measured on three different days over a 6-month period. Intrasession and intersession intraclass correlation coefficients of LSFG parameters ranged from 0.787 to 0.967 and from 0.776 to 0.935, respectively. Intersession 95% prediction intervals for the ratio of two measurements were wider for RFV indices than for ONH and macular perfusion parameters. The multiple regression analysis indicated that higher ONH perfusion was associated with younger age, female sex, smaller optic disc area, and higher RNFLT. RNFLT was an independent predictor of ONH perfusion, whereas GCIPLT was not. Each 1-µm increase in RNFLT was associated with a 0.272 arbitrary unit increase in ONH perfusion. LSFG measurements of optic disc perfusion are influenced by sex, age, and anatomical variations in optic disc area and RNFLT. Better evaluation of ocular blood flow will result in better diagnosis and treatment of various ocular diseases.

SLOctolyzer: Fully Automatic Analysis Toolkit for Segmentation and Feature Extracting in Scanning Laser Ophthalmoscopy Images.

The purpose of this study was to introduce SLOctolyzer: an open-source analysis toolkit for en face retinal vessels in infrared reflectance scanning laser ophthalmoscopy (SLO) images. SLOctolyzer includes two main modules: segmentation and measurement. The segmentation module uses deep learning methods to delineate retinal anatomy, and detects the fovea and optic disc, whereas the measurement module quantifies the complexity, density, tortuosity, and caliber of the segmented retinal vessels. We evaluated the segmentation module using unseen data and measured its reproducibility. SLOctolyzer's segmentation module performed well against unseen internal test data (Dice for all-vessels = 0.91; arteries = 0.84; veins = 0.85; optic disc = 0.94; and fovea = 0.88). External validation against severe retinal pathology showed decreased performance (Dice for arteries = 0.72; veins = 0.75; and optic disc = 0.90). SLOctolyzer had good reproducibility (mean difference for fractal dimension = -0.001; density = -0.0003; caliber = -0.32 microns; and tortuosity density = 0.001). SLOctolyzer can process a 768 × 768 pixel macula-centered SLO image in under 20 seconds and a disc-centered SLO image in under 30 seconds using a laptop CPU. To our knowledge, SLOctolyzer is the first open-source tool to convert raw SLO images into reproducible and clinically meaningful retinal vascular parameters. It requires no specialist knowledge or proprietary software, and allows manual correction of segmentations and re-computing of vascular metrics. SLOctolyzer is freely available at https://github.com/jaburke166/SLOctolyzer. SLO images are captured simultaneous to optical coherence tomography (OCT), and we believe SLOctolyzer will be useful for extracting retinal vascular measurements from large OCT image sets and linking them to ocular or systemic diseases.

Association between ocular diseases and screen time and sedentary time derived from job-exposure matrices

After developing job-exposure matrices (JEMs) for screen and sedentary time, we aimed to assess the associations between the JEM-derived exposures and various ocular diseases. We collected data from patients hospitalized from 2005 to 2021. JEMs were developed from 41,718 patients with occupational information and screen and sedentary times. The adjusted means of screen and sedentary time were calculated for 143 occupational groups and categorized into three classes based on the tertiles. The associations between ocular diseases and these JEM-derived exposures were examined using multivariable conditional logistic regression for 727,589 patients. The odds ratios of the class with highest screen time were 1.05 (95% confidence interval, 1.01–1.09) for cataract, 1.24 (1.06–1.45) for primary open-angle glaucoma (POAG), 1.26 (1.06–1.49) for rhegmatogenous retinal detachment (RRD), 1.49 (1.26–1.76) for ptosis, and 0.39 (0.27–0.57) for pterygium. The odds ratios of the class with highest sedentary time were 1.05 (1.01–1.09) for cataract, 1.24 (1.05–1.46) for RRD, 1.68 (1.42–1.99) for ptosis, and 0.60 (0.42–0.84) for pterygium. Both screen and sedentary time were positively associated with cataract, RRD and ptosis. Interestingly, POAG had a positive association with only screen time. Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary."I have confirmed that the content is correct. No amendments are necessary.Please check article title if captured correctly."?>"I have confirmed that the content is correct. No amendments are necessary.

The role of erythropoietin in the treatment of ocular disorders: A literature review

Erythropoietin (EPO), traditionally known for its role in hematopoiesis, has garnered increasing attention for its neuroprotective properties, particularly in ocular disorders. This literature review explores the diverse roles of EPO in ocular health and its potential therapeutic applications. EPO’s involvement in ocular organogenesis and maintenance is highlighted, with evidence suggesting its correlation with gestational age and expression alongside crucial regulatory genes during eye development. Pre-clinical studies demonstrate EPO’s efficacy in preserving retinal integrity and mitigating neuronal damage in animal models of glaucoma, methanol optic neuropathy, and optic neuritis. Clinical investigations further support these findings, showing improvements in visual acuity and retinal nerve fiber layer thickness in patients treated with EPO. However, challenges such as optimizing dosage regimens and determining the most effective route of administration remain. Despite these challenges, EPO presents a promising avenue for vision preservation and the management of ocular disorders. Further research, including large-scale clinical trials and mechanistic studies, is warranted to solidify EPO’s role as a safe and effective therapeutic option in ocular diseases.

Spotlight on Amniotic Membrane Extract Eye Drops: A Review of the Literature.

To review the literature focusing on the effectiveness of amniotic membrane extract eye drops (AMEDs) in the treatment of ocular surface diseases. PubMed/MEDLINE, Scopus, and CENTRAL databases were searched until March 4, 2024. Overall, we identified 1,121 studies, 26 of which were selected for a full-text review. Twelve studies met the inclusion criteria and were analyzed for clinical improvements, time to resolution of corneal staining, adverse events, and preparation methods. Strength of clinical data was graded according to the Oxford Center for Evidence-Based Medicine. Overall, AMED compounds were used in 296 eyes of 205 patients. Fifty-nine percent of eyes were treated for dry eye disease, 23% for an epithelial defect, and the rest (18%) for other corneal wound healing disorders. Three main types of eye drops preparation were described, that is, lyophilized, homogenized, and fresh AMED. Although the methods of outcome reporting were heterogeneous, all included studies showed various grades of improvement in both signs and symptoms. The overall incidence of ocular side effects was 2.3%. Despite the suboptimal quality of evidence, overall, the available literature suggests that AMED is a valuable tool in the treatment of ocular surface disorders.

Bilateral Pterygium in a Paediatric Cancer Patient taking Vemurafenib: A Case Report

Introduction: Anticancer drugs with reactive oxygen species (ROS) inducing mechanisms, such as vemurafenib, have been shown to be effective against various types of cancer. However, the adverse effects of increased oxidative stress have the potential to damage not only cancer cells, but also normal cells such as those in eyes and potentially leading to ocular diseases including pterygium and cataract. Presentations: A nine-year-old patient presented with bilateral nasal pterygium and early bilateral cortical cataracts, which are uncommon for his age group. Patient has a background of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E positive pilocytic astrocytoma with anaplastic features, diagnosed at age 2.5 years old. Vemurafenib was commenced at the time of diagnosis. Conclusion: We suspect that these ophthalmic findings are associated with his prolonged treatment with vemurafenib which may be of a pathophysiological significance.

Knockout of Caspase-1 Disrupts Pyroptosis and Protects Photoreceptor Cells from Photochemical Damage

Retinal photochemical damage (RPD) plays a significant role in the development of various ocular diseases, with Caspase-1 being a key contributor. This study investigates the protective effects of Caspase-1 gene-mediated pyroptosis against RPD. Differentially expressed genes (DEGs) associated with RPD were identified through the analysis of two expression profiles from the GEO database. Correlation analysis was used to pinpoint pyroptosis-related genes (PRGs) linked to RPD. A Caspase-1 knockout 661W cell line was generated via CRISPR-Cas9 gene editing, and single-cell colonies were screened and purified. Validation of knockout cells was performed through RT-qPCR, gene sequencing, and Western blot analysis. Comparative assays on cell proliferation, intracellular reactive oxygen species (ROS), and cytotoxicity were conducted between wild-type and Caspase-1 knockout cells under light exposure. Further RT-qPCR and Western blot experiments examined changes in the mRNA and protein levels of key pyroptosis pathway components. Significant alterations in Caspase-1 expression were observed among PRGs. Homozygous Caspase-1 knockout cell lines were confirmed through RT-qPCR, genomic PCR product sequencing, and Western blot analysis. Compared to wild-type 661W cells, Caspase-1 knockout cells exhibited higher viability and proliferation rates after 24 hours of light exposure, alongside reduced LDH release. The expression of downstream pyroptosis factors at both the mRNA and protein levels was markedly decreased in the knockout group. CRISPR/Cas9-mediated Caspase-1 knockout enhanced the resistance of 661W cells to photochemical damage, suggesting that Caspase-1 may serve as a potential therapeutic target for RPD-related diseases.

The Ocular Microbiome: Micro-Steps Towards Macro-Shift in Targeted Treatment? A Comprehensive Review

A healthy ocular surface is inhabited by microorganisms that constitute the ocular microbiome. The core of the ocular microbiome is still a subject of debate. Numerous culture-dependent and gene sequencing studies have revealed the composition of the ocular microbiome. There was a confirmed correlation between the ocular microbiome and ocular surface homeostasis as well as between ocular dysbiosis and pathologies such as blepharitis, microbial keratitis, and conjunctivitis. However, the role of the ocular microbiome in the pathogenesis and treatment of ocular surface diseases remains unclear. This article reviews available data on the ocular microbiome and microbiota, their role in maintaining ocular homeostasis, and the impact of dysbiosis on several ophthalmic disorders. Moreover, we aimed to discuss potential treatment targets within the ocular microbiota.

Advanced deep learning approaches for early detection and localization of ocular diseases

Rece with t advancements in modern technology have significantly enhanced the transmission of information, particularly in image processing, utilizing deep learning algorithms. This study aims to propose a a robust deep-learning strategy for detecting and recognizing eye defects and diseases from medical images. We present a detailed practical simulation of hybrid deep learning techniques designed for medical image classification based on multi-descriptor algorithms. The focus is on the classification of eye diseases by applying an advanced deep-learning algorithm to a dataset comprising various pathological eye conditions. Training operations for the proposed algorithm were conducted following the initialization phase, which included the extraction of multi-specification features. This enables the deep learning model to effectively analyze input eye images and accurately diagnose conditions. Our results demonstrate a diagnostic efficiency of 99%, with an error rate not exceeding 0.015%. The findings underscore the high efficiency and accuracy of deep learning algorithms in classifying and analyzing image data, thereby significantly reducing the workload for healthcare professionals.

In Situ Gelling Eye Drops of Tacrolimus with Improved Ocular Delivery and Therapeutic Efficacy.

In situ gelling eye drops of tacrolimus (FK506 Gel) were developed to address the formulation challenge of tacrolimus for anterior ocular inflammatory diseases. Both in silico and in vitro investigations were conducted to screen a suitable cyclodextrin species to increase the drug solubility. Guanosine was employed as the gelator and combined with inclusion complexes of tacrolimus in the presence of borate anions to obtain FK506 Gel, which gelated when came into contact with cations in tear fluid and led to the formation of a nanofibrous hydrogel. The versatility of our design to improve the solubility and ocular retention of the hydrophobic drug was demonstrated in vivo with coumarin 6 as a model drug. A mouse dry eye model was used to evaluate the therapeutic effects of FK506 Gel, which, in combination with the biocompatibility study, suggested that FK506 Gel served as a superior treatment for anterior ocular inflammatory diseases.

A Review on Multiple-Ocular Disease Detection Methodology using ML and DL Techniques

The rapid advancement in machine learning (ML) and deep learning (DL) techniques has significantly impacted the detection and diagnosis of ocular diseases, which are critical for preserving vision and overall eye health. This review aims to explore the various ML and DL methodologies applied to the detection of multiple ocular diseases, highlighting their effectiveness, limitations, and areas for improvement. The motivation behind this review stems from the increasing prevalence of ocular diseases and the need for efficient, accurate diagnostic tools. Despite the promising results of existing techniques, limitations such as data variability, the need for extensive training data, and computational resource requirements persist. The objective is to synthesize current methodologies and propose enhancements, particularly through the integration of attention mechanisms in convolutional neural networks (CNNs). This review identifies gaps in current research and suggests directions for future work to enhance diagnostic accuracy and clinical applicability.

Adipose-Derived Mesenchymal Stromal Cells: A Study on Safety and Efficacy in Ocular Inflammation.

This study explores the application of adipose-derived mesenchymal stromal cells (adMSCs) as a therapy for ocular inflammatory diseases utilizing a chronic GVHD model. Human adMSCs were administered via subconjunctival injection into mice with chronic ocular GVHD. Clinical scores and changes in T cell populations were analyzed. The study showed significant improvement in corneal integrity, including epithelial damage, opacity, thickness, and structure, after subconjunctival adMSC transplantation. Additionally, adMSC transplantation increased CD45+ and Foxp3+ Tregs while decreasing CD4+ T cells, 1IL17A+ Th17 cells, and IFNγ+ Th1 cells in local cervical lymph nodes. Moreover, adMSC-conditioned media enhanced wound closure and cell migration toward the wound bed in vitro. The cells disappeared within a week suggesting that trophic factors were involved. The dual benefit of adMSCs in immune-related ocular disorders underscores their potential for clinical application. This study focuses on subconjunctival delivery, effects of adMSCs and migration post-injection, with implications for optimizing cellular therapy application. The observed dual action, combining immunomodulation and tissue repair enhancement, underscores holistic approach of adMSC therapy in regenerative medicine, making it a potent treatment for diseases involving inflammation and tissue damage in the ocular surface.

Real-ambient PM2.5 induced corneal epithelial barrier disruption through Wnt/β-catenin signaling

Continued daily exposure to fine particulate matter (PM2.5) is linked to increasing risks of ocular surface diseases. However, further study is needed to understand how real-ambient PM2.5 disrupts the barrier function of the corneal epithelial layers and its underlying mechanism. In our study, we utilized a real-ambient PM2.5 exposure system to investigate its effects on the corneal epithelial barrier in C57BL/6Jmice over 4 and 8 weeks. The mean concentration of PM2.5 in the exposure chambers over 8 weeks was 140.18 μg/m3. Following 4 and 8 weeks of continuous PM2.5 exposure, we observed disorganized cellular arrangements in the corneal epithelium of mice. Moreover, PM2.5 exposure led to a significant loss of microvilli on the surface of corneal epithelial cells and noticeable disconnections among epithelial cell layers. Subsequent in vitro analysis revealed that 100 μg/mL PM2.5 activated the Wnt/β-catenin signaling pathway in corneal epithelium, resulting in decreased expression 1.81 fold and 2.25 fold of E-cadherin and ZO-1, respectively, ultimately impairing the corneal epithelial barrier function. Our findings provide the knowledge base for promoting eye health in the context of atmospheric pollution.

Citicoline eluting hydrogels for therapeutic contact lenses intended to treat neurodegenerative diabetic ocular diseases

Ophthalmic neurodegenerative diseases related to diabetes, such as glaucoma and retinopathy, are among the major causes of blindness in the world. Citicoline (CIT) in the form of eye drops is currently used for the treatment/prevention of these diseases, which affect the posterior segment of the eye. To ensure the drug penetration into the back of the eye, frequent instillations of highly concentrated drug solutions are required with potential side effects. Drug-loaded soft contact lenses (SCLs) may be an effective alternative to the conventional eye drop treatment, since they may enable a sustained drug release during daily wear, ensuring a higher drug bioavailability, and avoiding drug waste. In this work, one 2-hydroxyethyl methacrylate (HEMA) based hydrogel was functionalised with N-(3-aminopropyl) methacrylamide hydrochloride (APMA), molecularly imprinted with CIT and loaded with the same drug. The material was extensively characterised, in terms of morphology, optical, mechanical, and physical–chemical properties, namely, equilibrium water content, wettability, oxygen and ionic permeability, Young’s modulus, shear deformation, transmittance and refractive index, before and after steam sterilisation. Additionally, the tendency of the material to adsorb proteins of the lachrymal fluid was evaluated and its biocompatibility was assessed by irritation and cytotoxicity assays. Comparison with the non-functionalised and non-imprinted hydrogel showed that the modified hydrogel led to a sustained in vitro release of a much higher amount of CIT than the original one, while keeping typical values for physical–chemical properties of SCLs. The drug-loaded material resisted steam sterilisation and proved to be biocompatible, demonstrating adequate properties to be used in therapeutic SCLs for the prophylaxis/treatment of neurodegenerative diabetic ocular diseases. The neuroprotective effect of the released drug was confirmed with tests using porcine retinal explants.

Developments in Emerging Topical Drug Delivery Systems for Ocular Disorders.

According to the current information, using nano gels in the eyes have therapeutic benefits. Industry growth in the pharmaceutical and healthcare sectors has been filled by nanotechnology. Traditional ocular preparations have a short retention duration and restricted drug bioavailability because of the eye's architectural and physiological barriers, a big issue for physicians, patients, and chemists. In contrast, nano gels can encapsulate drugs within threedimensional cross-linked polymeric networks. Because of their distinctive structural designs and preparation methods, they can deliver loaded medications in a controlled and sustained manner, enhancing patient compliance and therapeutic efficacy. Due to their excellent drugloading capacity and biocompatibility, nano-gels outperform other nano-carriers. This study focuses on using nano gels to treat eye diseases and provides a brief overview of their creation and response to stimuli. Our understanding of topical drug administration will be advanced using nano gel developments to treat common ocular diseases such as glaucoma, cataracts, dry eye syndrome, bacterial keratitis, and linked medication-loaded contact lenses and natural active ingredients.