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This paper reviews our current understanding of age-related meibomian gland dysfunction (MGD) and the role of the nuclear receptor, peroxisome proliferator-activated receptor gamma (PPARγ), in the regulation of meibomian gland function, meibocyte differentiation and lipid synthesis. The studies suggest that PPARγ is a master regulator of meibocyte differentiation and function, whose expression and nuclear signaling coupled with meibocyte renewal is altered during aging, potentially leading to atrophy of the meibomian gland as seen in clinical MGD. Study of meibomian gland stem cells also suggest that there is a limited number of precursor meibocytes that provide progeny to the acini, that may be susceptible to exhaustion as occurs during aging and other environmental factors. Further study of pathways regulating PPARγ expression and function as well as meibocyte stem cell maintenance may provide clues to establishing cellular and molecular mechanisms underlying MGD and the development of novel therapeutic strategies to treating this disease. [ABSTRACT FROM AUTHOR]

Total bilateral Limbal Stem Cell Deficiency is a pathologic condition of the ocular surface due to the loss of corneal stem cells. Cultivated oral mucosa epithelial transplantation (COMET) is the only autologous successful treatment for this pathology in clinical application, although abnormal peripheric corneal vascularization often occurs. Properly characterizing the regenerated ocular surface is needed for a reliable follow-up. So far, the univocal identification of transplanted oral mucosa has been challenging. Previously proposed markers were shown to be co-expressed by different ocular surface epithelia in a homeostatic or perturbated environment. In this study, we compared the transcriptome profile of human oral mucosa, limbal and conjunctival cultured holoclones, identifying Paired Like Homeodomain 2 (PITX2) as a new marker that univocally distinguishes the transplanted oral tissue from the other epithelia. We validated PITX2 at RNA and protein levels to investigate 10-year follow-up corneal samples derived from a COMET-treated aniridic patient. Moreover, we found novel angiogenesis-related factors that were differentially expressed in the three epithelia and instrumental in explaining the neovascularization in COMET-treated patients. These results will support the follow-up analysis of patients transplanted with oral mucosa and provide new tools to understand the regeneration mechanism of transplanted corneas. [ABSTRACT FROM AUTHOR]

Ocular surface diseases (OSDs) are significant causes of ocular morbidity, and are often associated with chronic inflammation, redness, irritation, discomfort, and pain. In severe OSDs, loss of vision can result from ocular surface failure, characterised by limbal stem cell deficiencies, corneal vascularisation, corneal opacification, and surface keratinisation. External and internal exposomes are measures of environmental factors that individuals are exposed to, and have been increasingly studied for their impact on ocular surface diseases. External exposomes consist of external environmental factors such as dust, pollution, and stress; internal exposomes consist of the surface microbiome, gut microflora, and oxidative stress. Concerning internal exposomes, alterations in the commensal ocular surface microbiome of patients with OSDs are increasingly reported due to advancements in metagenomics using next-generation sequencing. Changes in the microbiome may be a consequence of the underlying disease processes or may have a role in the pathogenesis of OSDs. Understanding the changes in the ocular surface microbiome and the impact of various other exposomes may also help to establish the causative factors underlying ocular surface inflammation and scarring, the hallmarks of OSDs. This review provides a summary of the current evidence on exposomes in various OSDs. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED) is a common and debilitating condition that affects millions of people worldwide. Despite its prevalence, the diagnosis and management of DED can be challenging, as the condition is multifactorial and symptoms can be nonspecific. In recent years, there have been significant advancements in diagnostic technology for DED, including the development of several new devices. Methods: A literature review of articles on the dry eye syndrome and innovative diagnostic devices was carried out to provide an overview of some of the current high-tech diagnostic tools for DED, specifically focusing on the TearLab Osmolarity System, DEvice Hygrometer, IDRA, Tearcheck, Keratograph 5M, Cornea Dome Lens Imaging System, I-PEN Osmolarity System, LipiView II interferometer, LacryDiag Ocular Surface Analyzer, Tearscope-Plus, and Cobra HD Camera. Conclusions: Despite the fact that consistent use of these tools in clinical settings could facilitate diagnosis, no diagnostic device can replace the TFOS algorithm. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in tears/conjunctival epithelium and assess the cytomorphological changes in the conjunctival epithelium of coronavirus disease 2019 (COVID-19) patients. Methods: In this pilot study, patients with moderate to severe COVID-19 were recruited from the COVID ward/intensive care unit of the institute. Tears and conjunctival swabs were collected from COVID-19 patients and sent to the virology laboratory for reverse transcription polymerase chain reaction (RT-PCR) testing. Conjunctival swabs were used to prepare smears, which underwent cytological evaluation and immunocytochemistry for SARS-CoV-2 nucleocapsid protein. Results: Forty-two patients were included. The mean age of participants was 48.61 (range: 5--75) years. Seven (16.6%) patients tested positive for SARS-CoV-2 ribonucleic acid in tears samples, four (9.5%) of which were positive on conjunctival swab by RT-PCR in the first test. Cytomorphological changes were observed significantly more in smears from patients with positive RT-PCR on tear samples, including bi-/multi-nucleation (p = 0.01), chromatin clearing (p = 0.02), and intra-nuclear inclusions (p < 0.001). One case (3.2%) showed immunopositivity for SARS-CoV-2; this patient had severe disease and the lowest Ct values for tear and conjunctival samples among all positive cases. Conclusion: Conjunctival smears from patients with COVID-19 revealed cytomorphological alterations, even in the absence of clinically significant ocular infection. However, viral proteins were demonstrated within epithelial cells only rarely, suggesting that although the conjunctival epithelium may serve as a portal for entry, viral replication is possibly rare or short-lived. [ABSTRACT FROM AUTHOR]

When the eyes are exposed to the environment, they are easily affected by strong light stimulation and harmful substances. At the same time, prolonged use of the eyes or incorrect eye habits can cause visual fatigue, which mainly manifests as eye dryness, soreness, blurred vision, and various discomforts. The main reason for this is a decline in the function of the eye, especially the cornea and retina on the surface of the eye, which have the greatest impact on the normal function of the eye. Research has found that supplementation with appropriate foods or nutrients can effectively strengthen the eye against external and internal stimuli, thereby alleviating or avoiding visual fatigue. Among these, supplementation with polyunsaturated fatty acids has been found to be effective at protecting eye health and relieving visual fatigue. This article summarizes the sources of polyunsaturated fatty acids (including the main dietary sources and internal synthesis), the mechanisms of digestion and absorption of polyunsaturated fatty acids in the body and the safety of polyunsaturated fatty acid applications. It also reviews the mechanism of action of polyunsaturated fatty acids in aiding the relief of visual fatigue based on the mechanism of impaired function or structure of the ocular surface and fundus in the hope of providing some reference and insight into the development and application of polyunsaturated fatty acids in functional foods for the relief of visual fatigue. [ABSTRACT FROM AUTHOR]

Objective: This cross-sectional study aimed to reveal the association between ocular surface disorders and psychological, physiological situations among autoimmune rheumatic patients. Methods: Ninety autoimmune rheumatic patients (180 eyes) hospitalized in the Department of Rheumatology, The Second Xiangya Hospital, Central South University and 30 controls (60 eyes) were enrolled in the study. All participants were assessed for ocular surface disorders including dry eye disease (DED) by the Ocular Surface Disease Index (OSDI) for symptoms evaluation, and slim lamp examinations for tear break-up time (TBUT), meibomian gland secretion, symblepharon and corneal clarity, Schirmer I test, corneal fluorescein staining (CFS), lid-parallel conjunctival folds (LIPCOF). Systematic conditions were evaluated using the Short Form 36-Health Survey (SF-36) for health-related quality of life, Hospital Anxiety and Depression Scale (HADS) for anxiety and depression, Health Assessment Questionnaire-Disability Index (HAQ-DI) for difficulties in activities of daily living, and Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Pearson and spearman’s analysis were conducted to examine the relationship between systematic conditions and ocular surface conditions. Results: The analyses were controlled for age and sex. 52.22% of eyes (94 in 180) of autoimmune rheumatic patients and 21.67% of eyes (13 in 60) of controls were diagnosed with DED. The autoimmune rheumatic patients showed significant higher OSDI score, fewer basal tear secretion, more severe CFS and conjunctivochalasis than controls. There were no statistically significant differences in TBUT, meibomian gland secretion, symblepharon, and corneal clarity between the two groups. For systematic conditions, autoimmune rheumatic patients had significantly lower SF-36 scores, higher anxiety scores, and HAQ-DI scores than controls. No statistically significant differences were detected in depression scores and PSQI between the two groups. Among autoimmune rheumatic patients, OSDI scores were moderately correlated with quality of life, anxiety, depression and sleep quality. Conclusion: Factors including quality of life, anxiety, depression, and sleep quality are associated with ocular surface conditions, especially DED symptoms. Management of systemic conditions and psychotherapy should also be considered as part of the treatment among autoimmune rheumatic patients. [ABSTRACT FROM AUTHOR]

Currently, much attention is paid to measuring the temperature of the ocular surface in various ophthalmic diseases. However, for a comprehensive assessment of heat transfer of the eye, it is advisable to measure both the ocular surface temperature and the heat flux (HF) density. This will expand our knowledge of the physiology of the eye and create new possibilities for diagnosing ocular pathology. The present study aimed to develop a thermoelectric device to study rabbits' ocular surface temperature and HF density. The multichannel thermoelectric device was developed to measure the ocular surface temperature and HF density. This study included ten rabbits (20 eyes). In all animals, the temperature and the HF density were measured on the surface of the central cornea of both eyes. The measurement was repeated after pupils' dilation. The corneal surface temperature of rabbits was 33.1 ± 0.8 °C, and the HF density of the surface of the cornea was 8.3 ± 0.6 mW/cm2. Our results revealed a high degree of interocular symmetry in the surface HF density in healthy rabbits. After pupil dilation, an increase in the HF density on the surface of the rabbit cornea compared with the initial data and control eye was noted. The application of the developed device showed that it is safe and allows for the measurement of the ocular surface temperature and the HF density. We believe that further studies on the ocular surface HF density measurement in various eye diseases will allow us to evaluate the possibilities of this device and technique for diagnostic purposes. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine if eyes with unilateral pterygium are more likely to suffer from dry eye symptoms and more prone to have abnormalities in dry eye parameters than healthy eyes. Methods: Forty eyes of 20 patients were enrolled. The eyes that were diagnosed as having pterygium were considered as Group 1 and other healthy eyes of the same patients were defined as Group 2. The existence of dry eye was tested with tear film break-up time, Schirmer-1 test, Oxford scale, and Ocular Surface Disease Index (OSDI) score assessments. Results: Median tear film break-up-time measurement and Schirmer 1 value were lower in Group 1; however, no statistically significant difference was detected (p=0.06 and p=0.308, respectively). Median OSDI score and median Oxford scale score were higher in Group 1; however, no statistically significant difference was detected (p=0.05 and p=0.250, respectively). Conclusion: Between eyes with pterygium and healthy ones, there was difference in dry eye test results. These results may show that there might be a relationship between pterygium and dry eye disease regardless of the genetic background and environmental factors. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multi‑factorial ocular surface condition driven by compromised ocular lubrication and inflammation which leads to itching, dryness, and vision impairment. The available treatment modalities primarily target the acquired symptoms of DED including tear film supplements, anti‑inflammatory drugs, mucin secretagogues, etc., However, the underlying etiology is still an area of active research, especially in regard to the diverse etiology and symptoms. Proteomics is a robust approach that has been playing major role in understanding the causative mechanism and biochemical changes in DED by identifying the changes in protein expression profile in tears. Tears are a complex fluid composed of several biomolecules such as proteins, peptides, lipids, mucins, and metabolites secreted from lacrimal gland, meibomian gland, cornea, and vascular sources. Over the past two decades, tears have emerged as a bona‑fide source for biomarker identification in many ocular conditions because of the minimally invasive and simple sample collection procedure. However, the tear proteome can be altered by several factors, which increases the complexity of the approach. The recent advancements in untargeted mass spectrometry‑based proteomics could overcome such shortcomings. Also, these technological advancements help to distinguish the DED profiles based on its association with other complications such as Sjogren’s syndrome, rheumatoid arthritis, diabetes, and meibomian gland dysfunction. This review summarizes the important molecular profiles found in proteomics studies to be altered in DED which have added to the understanding of its pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Keratoconjunctivitis sicca (KCS) or dry eye disease (DED) is a multifactorial disease that results in discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. A pilot study was undertaken to determine if there were any major substantial differences in the ocular microbiome in DED patients versus healthy controls. Methods: The bacterial communities residing in the conjunctiva of patients with DED (n = 4) and healthy controls (n = 4) were assessed by 16S ribosomal RNA (rRNA) gene sequencing of the V4–V5 region. Results: The phyla Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were most dominant and accounted for 97% and 94.5% of all bacterial sequences in patients and controls, respectively. At the genus level, 27 bacterial genera were found with more than two‑fold difference between patients and controls. Four of these – Acinetobacter, Corynebacterium, Lactobacillus, and Pseudomonas spp. – dominated the ocular microbiome of all subjects, but were proportionately lower in DED (16.5%) compared to controls (37.7%). Several bacterial genera were found to be unique in DED (34) and controls (24). Conclusion: This pilot study is an attempt to profile the ocular microbiome in patients with DED that demonstrated a higher concentration of microbial DNA compared to controls, with Firmicutes phyla dominating the bacterial population in patients with DED. [ABSTRACT FROM AUTHOR]

Purpose: To explore the effects of cyclosporine A (CsA) in the management of atopic keratoconjunctivitis (AKC). Methods: Open single‐group interventional consecutive cohort study (case series) at a single eye care facility in the UK. We reviewed the electronic patient records of 99 children and young people (CYP) aged 3.4–18 years with AKC treated with topical CsA 1 mg/ml. Main outcome measures were number of prescriptions and hospital clinic visits over 12 months before and after the start of CsA and the proportion of CYP affected by adverse effects. Results: The median number of inflammatory episodes requiring treatment with topical corticosteroids (tCS) fell from 3 (interquartile range IQR 1–4) during the 12 months prior to CsA to 1 (IQR 0–3) during the 12 months after, excluding tCS prescriptions with the first CsA prescription (Wilcoxon signed ranks test, 2 tailed, p < 0.01). In the 12‐month period following initiation of CsA 1 mg/ml with concomitant prescription of tCS (n = 66), daily dosage of steroids was reduced in 62 CYP (93.9%), and they were discontinued in 43 (65.2%). The median number of hospital visits fell from 4 (IQR 3–6) to 3 (IQR 2–5; Wilcoxon p < 0.01). Adverse events leading to discontinuation of CsA were stinging (instillation site pain; 9/99, 9%) and a transient skin rash (1/99, 1%). Conclusions: Off‐label use of commercial preparations of CsA 1 mg/ml significantly reduces the need for concomitant topical corticosteroids and hospital clinic visits in CYP with AKC. Stinging and skin rash can lead to discontinuation. [ABSTRACT FROM AUTHOR]

To review the most recent studies in the literature regarding the ocular surface in glaucoma patients and treatment options aimed to reduce ocular surface disease in this population We performed a literature search in the electronic databases of PubMed CENT RAL, Google Scholar, EMBASE the Register of Controlled Trials, and Ovid MEDLINE using the following terms: "ocular surface", "dry eye", "glaucoma", "selective laser trabeculoplasty", "glaucoma surgery", "preservatives", "preservative free", "ocular surface disease index", "tear break up time", "MMP-9" and "conjunctival hyperemia". Over the last several years, several studies have demonstrated the changes to the ocular surface in the setting of glaucoma, the best tests for markers of dry eye, and how management can be altered to help address ocular surface disease routinely or in preparation for glaucoma surgery. Ocular surface disease in the glaucoma patient population is widely recognized. It should be addressed to maximize patient compliance and quality of life. [ABSTRACT FROM AUTHOR]

Epitheliopathy at the ocular surface is a defining sign of dry eye disease, a common disorder that affects 10% to 30% of the world's population. Hyperosmolarity of the tear film is one of the main drivers of pathology, with subsequent endoplasmic reticulum (ER) stress, the resulting unfolded protein response (UPR), and caspase-3 activation implicated in the pathway to programmed cell death. Dynasore, is a small molecule inhibitor of dynamin GTPases that has shown therapeutic effects in a variety of disease models involving oxidative stress. Recently we showed that dynasore protects corneal epithelial cells exposed to the oxidant tBHP, by selective reduction in expression of CHOP, a marker of the UPR PERK branch. Here we investigated the capacity of dynasore to protect corneal epithelial cells subjected to hyperosmotic stress (HOS). Similar to dynasore's capacity to protect against tBHP exposure, dynasore inhibits the cell death pathway triggered by HOS, protecting against ER stress and maintaining a homeostatic level of UPR activity. However, unlike with tBHP exposure, UPR activation due to HOS is independent of PERK and mostly driven by the UPR IRE1 branch. Our results demonstrate the role of the UPR in HOS-driven damage, and the potential of dynasore as a treatment to prevent dry eye epitheliopathy. [ABSTRACT FROM AUTHOR]

To enquire whether patients with dry eye symptoms also report dry skin, whether their perception could be corroborated with objective measurement, and whether dry eye disease might be suspected based on patients' complaints. This cross-sectional study included 50 subjects, 25 with and 25 without dry eye symptoms. Schein questionnaire was used to determine the severity of dry eye symptoms. Ocular signs were assessed by monitoring conjunctival hyperemia, ocular surface staining, meibomian gland expression, tear film lipid layer thickness, tear break-up time, lid parallel conjunctival folds, Schirmer test, and meibometry. Skin dryness was assessed by noting patients' self-perception of their facial skin dryness and measured by sebumeter. Subjects without dry eye symptoms had self-reported oilier facial skin than those with dry eye symptoms (p <.001). Sebumetry scores measured on the forehead and cheek were significantly higher in subjects without dry eye symptoms than dry eye subjects (p =.003). After adjustment for age and gender in a logistic regression analysis, dry eye was independently and significantly associated with dry skin (AOR 0.69, p =.040), higher LIPCOF score of both eyes (AOR 2.28, p =.028), lower sebumetry score of the forehead (AOR 0.98, p =.041) and cheek (AOR 0.98, p =.041), and shorter TBUT score after gland expression (AOR 0.90, p =.018). This study showed that ocular dryness was subjectively and objectively positively correlated to facial skin dryness. Patients reliably described their skin condition. People with dry facial skin also had drier eyes. [ABSTRACT FROM AUTHOR]

The aim of this study is to demonstrate the prevalence of self-reported mask-associated dry eye (MADE) in health-care professionals and the possible risk factors that give rise to MADE. A self-administered questionnaire consisting of 12 questions about MADE and possible risk factors that give rise to MADE was created on web-based "google forms" application, and was then sent to 437 healthcare professionals working in a coronavirus-19 (COVID-19) pandemic hospital, using common telecommunication devices. Three hundred and thirty-three of the 437 health-care professionals, who answered the questionnaire, were included in the study. The prevalence of self-reported MADE among these health-care professionals was found to be 70% (n = 233). Having at least one of the symptoms of dry eye while not having a mask on and advanced age were determined as the possible risk factors for MADE (p =.02 and p <.001, respectively). The clinical examinations of the 195 participants, who had self-reported MADE and accepted the invitation to undergo a clinical evaluation with respect to the symptoms of MADE, revealed that only 60 (30.7%) of these participants had aqueous-type dryness with staining on the ocular surface with fluorescein. The high prevalence of self-reported MADE among health-care professionals can be attributed to the prolonged use of masks associated with longer working hours. Therefore, it is important that the ocular complaints of professionals are addressed by ophthalmology consultants/ophthalmologists during these difficult times. [ABSTRACT FROM AUTHOR]

Purpose: To study the possibility of SARS-CoV-2 to infect human corneal cells and tissues under standard corneal culture conditions using explants of COVID-19 donors and primary cornea-derived epithelial cells. Methods: Cornea isolated from deceased COVID-19 donors was cultured for 4 weeks, and SARS-CoV-2 replication was monitored by qRT-PCR. Furthermore, primary corneal epithelial cells from healthy donors were cultured ex vivo and infected with SARS-CoV-2 and human cytomegalovirus (HCMV) as a control. Infection status was assessed by western blotting and reporter gene expression using green fluorescent protein–expressing viral strains. ACE2 and TMPRSS2 receptor expression levels in cornea and epithelial cells were assessed by qRT-PCR. Results: We did not detect SARS-CoV-2 replication in 10 corneas isolated from deceased COVID-19 patients and cultured for 4 weeks, indicating absence of infection under natural conditions. Furthermore, high-titer SARS-CoV-2 infection of ex vivo cultured cornea-derived epithelial cells did not result in productive virus replication. In contrast, the same cells were highly permissive for HCMV. This phenotype could potentially be explained by low ACE2 and TMPRSS2 transcriptional activity in cornea and cornea-derived epithelial cells. Conclusions: Our data suggest that cornea and limbal epithelial cells are refractory to productive SARS-CoV-2 infection. This could be due to the absence of robust receptor expression levels necessary for viral entry. This study adds further evidence to support the very low possibility of transmission of SARS-CoV-2 from an infected corneal transplant donor to a recipient in corneal organ cultures. [ABSTRACT FROM AUTHOR]

Purpose: We aim to investigate the effect of sustained hyperglycemia on corneal epithelial wound healing, ocular surface and systemic immune response, and microbiome indices in diabetic mice compared to controls after alkaline chemical injury of the eye. Methods: Corneal alkaline injury was induced in the right eye of Ins2Akita (Akita) mice and wild-type mice. The groups were observed at baseline and subsequently days 0, 3, and 7 after injury. Corneal re-epithelialization was observed under slit lamp with fluorescein staining using a cobalt blue light filter. Enucleated cornea specimens were compared at baseline and after injury for changes in cornea thickness under hematoxylin and eosin staining. Tear cytokine and growth factor levels were measured using protein microarray assay and compared between groups and time points. Flow cytometry was conducted on peripheral blood and ocular surface samples to determine CD3+CD4+ cell count. Fecal samples were collected, and gut microbiota composition and diversity pattern were measured using shotgun sequencing. Results: Akita mice had significantly delayed corneal wound healing compared to controls. This was associated with a reduction in tear levels of vascular endothelial growth factor A, angiopoietin 2, and insulin growth factor 1 on days 0, 3, and 7 after injury. Furthermore, there was a distinct lack of upregulation of peripheral blood and ocular surface CD3+CD4+ cell counts in response to injury in Akita mice compared to controls. This was associated with a reduction in intestinal microbiome diversity indices in Akita mice compared to controls after injury. Specifically, there was a lower abundance of Firmicutes bacterium M10-2 in Akita mice compared to controls after injury. Conclusion: In diabetic mice, impaired cornea wound healing was associated with an inability to mount systemic and local immune response to ocular chemical injury. Baseline and post-injury differences in intestinal microbial diversity and abundance patterns between diabetic mice and controls may potentially play a role in this altered response. [ABSTRACT FROM AUTHOR]

While pathogens of the eye have been studied for a very long time, the existence of resident microbes on the surface of healthy eyes has gained interest only recently. It appears that commensal microbes are a normal feature of the healthy eye, whose role and properties are currently the subject of extensive research. This review provides an overview of studies that have used 16s rRNA gene sequencing and whole metagenome shotgun sequencing to characterize microbial communities associated with the healthy ocular surface from kingdom to genus level. Bacteria are the primary colonizers of the healthy ocular surface, with three predominant phyla: Proteobacteria, Actinobacteria, and Firmicutes, regardless of the host, environment, and method used. Refining the microbial classification to the genus level reveals a highly variable distribution from one individual and study to another. Factors accounting for this variability are intriguing - it is currently unknown to what extent this is attributable to the individuals and their environment and how much is artifactual. Clearly, it is technically challenging to accurately describe the microorganisms of the ocular surface because their abundance is relatively low, thus, permitting substantial contaminations. More research is needed, including better experimental standards to prevent biases, and the exploration of the ocular surface microbiome's role in a spectrum of healthy to pathological states. Outcomes from such research include the opportunity for therapeutic interventions targeting the microbiome. [ABSTRACT FROM AUTHOR]

Purpose: To utilize melt electrowriting (MEW) technology using poly-(ε-caprolactone) (PCL) coupled with a 2-step co-culturing strategy for the development of a conjunctival bi-layer synthetic construct. Methods: Melt electrowritten scaffolds using PCL were fabricated using an in-house-built MEW printer. Human conjunctival stromal cells (CjSCs) and epithelial cells (CjECs) were isolated from donor tissue. A 2-step co-culture method was done by first seeding the CjSCs and culturing for 4 weeks to establish a stromal layer, followed by CjECs and co-culturing for 2 more weeks. Cultured cells were each characterized by morphology and marker expression on immunofluorescence and qPCR. The produced construct was assessed for cellular proliferation using viability assays. The bi-layer morphology was assessed using scanning electron microscopy (SEM), confocal microscopy, and immunofluorescence imaging. The expression of extracellular matrix components and TGF-b was evaluated using qPCR. Results: CjSCs were spindle-shaped and vimentin + while CjECs were polygonal and CK13 +. CjSCs showed consistent proliferation and optimal adherence with the scaffold at the 4-week culture mark. A 2-layered construct consisting of a CjSC-composed stromal layer and a CjEC-composed epithelial layer was appreciated on confocal microscopy, SEM, and immunofluorescence. CjSCs secreted collagens (types I, V, VI) but at differing amounts from natural tissue while TGF-b production was comparable. Conclusion: The 3D-printed melt electrowritten PCL scaffold paired with the 2-step co-culturing conditions of the scaffold allowed for the first approximation of a bi-layered stromal and epithelial reconstruction of the conjunctiva that can potentially improve the therapeutic arsenal in ocular surface reconstruction. [ABSTRACT FROM AUTHOR]

Cyclosporine A (CsA) has been used as a topical treatment for various ocular surface diseases including dry eye disease (DED). Several CsA formulations are available as solutions or emulsions. This review describes the development and the preclinical testing of a cationic oil-in-water emulsion of CsA (CE-CsA) in terms of pharmacodynamics, pharmacokinetics, and ocular tolerance. Due to the cationic charge, CE electrostatically interacts with the negatively-charged ocular surface, improving its residence time. Compared to other CsA formulations, CE-CsA and CE itself were found to reduce the signs and symptoms of DED, by restoring tear film stability and properties, and inhibiting the expression and secretion of pro-inflammatory factors. No delay in wound healing nor ocular toxicity were observed using CE formulations. these findings indicate that the type of vehicle can significantly affect the performance of eye drops and play an ancillary role in DED treatment. CE appears as a promising strategy to deliver drugs to the ocular surface while maintaining its homeostasis. [ABSTRACT FROM AUTHOR]

Purpose: The probability of the coexistence of conjunctivochalasis and pseudoexfoliation syndrome (PES) in the same individual may increase with aging. We investigated the effects of conjunctivochalasis accompanied by PES on the ocular surface (OS) and anterior segment (AS) structures. Methods: Cases with only conjunctivochalasis were determined as Group 1 (n = 62), cases with conjunctivochalasis accompanied by PES as Group 2 (n = 45), and healthy individuals as Group 3 (n = 56). The OS and AS parameters of the groups were compared. Results: There were a higher grade-3 conjunctivochalasis rate (17.7% vs. 46.7%, p = 0.039), a greater "mean grade of conjunctivochalasis" value (1.72 ± 0.24 vs. 2.29 ± 0.32, p = 0.036), and a higher "total conjunctivochalasis score" (4.27 ± 1.13 vs. 6.12 ± 1.35, p = 0.025) in Group 2 than in Group 1. Additionally, Group 2 had a shorter tear film break-up time (TBUT) (9.17 ± 2.53 vs. 5.41 ± 1.32, p = 0.010) and a greater OS disease index (OSDI) score (16.28 ± 3.15 vs. 27.36 ± 4.12, p = 0.037) than Group 1. Moreover, both Group 1 and Group 2 had shorter TBUTs (Group 1–3: p = 0.004; Group 2–3: p < 0.001) and greater OSDI scores (Group 1–3: p = 0.042; Group 2–3: p = 0.019) compared to Group 3. The groups' ocular surface staining scores, Schirmer 1 tests, central corneal thicknesses, keratometries, axial lengths, anterior chamber depths, lens thicknesses, and intraocular pressures were similar (p > 0.05). Conclusions: To our knowledge, this was the first study comprehensively investigating the effects of conjunctivochalasis accompanied by PES on the OS and AS structures together. We found that conjunctivochalasis might cause the OS disease, while the presence of PES in conjunctivochalasis cases might worsen both the OS disease and conjunctivochalasis findings. [ABSTRACT FROM AUTHOR]

Aniridia-associated keratopathy (AAK) is characteristic at ocular surface of aniridia caused by haploinsufficiency of PAX6. Competing endogenous RNA (ceRNA) has been reported to play an important role in various diseases, whereas its function on AAK is unclear. The microarray data of 20 AAK patients and 20 healthy people were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed lncRNAs, miRNAs, and mRNAs were analyzed using "limma" packages and weighted gene co-expression network analysis (WGCNA). A ceRNA network was constructed by Cytoscape 3.9.1, and miR-224-5p, miR-30a-5p, and miR-204-5p were at the center of the network. CIBERSORTx algorithm and ssGSEA analyses revealed that AAK was associated with immune cell infiltration, showing that activated Mast cells increased while resting Mast cells decreased and NK cells decreased in AAK. Type II INF Response, CCR, parainflammation, T cell co-stimulation, and APC co-stimulation of AAK patients differed from healthy individuals. Additionally, the ROC curve of five genes, MITF(AUC = 0.988), RHOB(AUC = 0.973), JUN(AUC = 0.953), PLAUR (AUC = 0.925), and ARG2 (AUC = 0.915) with high confidence in predicting AAK were identified. Gene set enrichment analysis (GSEA) analysis of hub genes enriched in the IL-17 signaling pathway. [ABSTRACT FROM AUTHOR]

Aim: To determine the effects of face mask usage on ocular structures in children during the coronavirus disease-2019 (COVID-19) pandemic Materials and Methods: Forty-two children's ocular data from the pandemic period were compared with the same children's ocular data from the pre-pandemic period. Results: Their mean age was 14.6±2.1 (9-18) years initially. The tear film break-up time values of the children with a mask in the pandemic period were significantly shorter than those of the children without a mask in the pre-pandemic period (9.35±1.40 vs. 12.10±1.05 seconds, p=0.033). There was no staining in any case in the pre-pandemic period, while minimal punctate epithelial corneal staining pattern was determined in 4 (9.5%) children in the pandemic period. The Schirmer test 1 value detected in the pandemic period was similar to the value detected in the pre-pandemic period (11.14±2.07 vs. 12.03±1.01 mm, p=0.127). Additionally, there were no significant changes in visual acuities, central corneal thicknesses, anterior chamber depths, lens thicknesses, and axial lengths between the pre-pandemic and pandemic periods (p>0.05). Conclusion: To the best of our knowledge, this is the first study to date to evaluate the effects of face mask usage on ocular structures in just children. The use of face masks may cause increased tear evaporation and dry eye in pediatric cases. Educating children about the correct use of face masks can be important. Thus, possible ocular surface changes which may occur relating to masks can be prevented, and children may be more willing to use masks. Increased mask compliance may also indirectly help protect children from the virus. [ABSTRACT FROM AUTHOR]

This study evaluates in a cross-section of pregnant women the frequency of posterior blepharitis, its predisposing factors and how lipid profile impacts the occurrence of posterior blepharitis in pregnancy. This was a hospital-based cross-sectional study of pregnant women. In this study, 201 pregnant women were recruited and included in the study's analysis. The participants' mean age was 29.96 (±4.74) years, with a median age of 30 and a range of 17 to 40 years. The frequency of posterior blepharitis among this cohort was 13.4% (95% confidence interval, 9.0% to 18.4%). The frequencies of MGD-associated posterior blepharitis and non-MGD associated posterior blepharitis were 6.0% and 7.4%, respectively. There was no statistically significant difference in the mean fluorescein tear breakup time and SPEED scores between non-MGD associated posterior blepharitis and MGD-associated posterior blepharitis, however, the mean tear breakup time(t = 3.999, p <.001) and SPEED scores (t = 6.76, p <.0001) showed a statistically significant difference in posterior blepharitis pregnant women compared to non–posterior blepharitis pregnant women. There was a statistically significant difference in the mean corneal staining scores between non-MGD-associated posterior blepharitis and MGD-associated posterior blepharitis (t = 3.99, p =.001). There was no association between lipid profile and posterior blepharitis in binary logistic regression analysis The study showed that posterior blepharitis occurs in pregnancy, but it is not associated with cholesterol levels. [ABSTRACT FROM AUTHOR]

Ocular surface diseases are becoming more prevalent worldwide. Reasons for this include the ongoing population ageing and increasing use of digital displays, although ophthalmologists have a wide selection of tools, which can be implemented in the evaluation of the ocular surface health, methods, which enable the in‐depth study of biological functions are gaining more interest. These new approaches are needed, since the individual responses to ocular surface diseases and treatments can vary from person to person, and the correlations between clinical signs and symptoms are often low. Modern mass spectrometry (MS) methods can produce information on hundreds of tear proteins, which in turn can provide valuable information on the biological effects occurring on the ocular surface. In this review article, we will provide an overview of the different aspects, which are part of a successful tear proteomics study design and equip readers with a better understanding of the methods most suited for their MS‐based tear proteomics study in the field of ophthalmology and ocular surface. [ABSTRACT FROM AUTHOR]

Electromagnetic radiation (ER) emitted by mobile phones and other modern devices has potentially harmful effects on ocular tissue. Their effects on the eye surface and tear film are little known so far. The aim of this paper was to investigate the effects of ER emitted by the phone mobile on the tear film. For this study, we selected a total of 50 subjects, young, healthy, without chronic treatment, who are not contact lens wearers and who have no history of ophthalmic surgery. Schirmer I test, tear pH and tear ferning test (TFT) were performed on all subjects before (“-pre”) being exposed to ER emitted by the mobile phone and after (“-post”) exposure for 5 minutes, the pH and TFT of the tears were performed. Following the analysis of the obtained results, we found that there are significant changes in tear quality and increased tear pH, which over time can lead to tear film instability, damage to the eye surface and the appearance of dry eye syndrome.

Background: To evaluate the effects on ocular surface signs and symptoms of serial sessions of heating and vibrating eye mask followed by intense pulsed light (IPL) therapy for the treatment of dry eye disease owing to meibomian gland dysfunction (MGD).Methods: Consecutive patients with MGD whose signs and symptoms were not satisfactorily controlled with conventional therapy were included. Patients received 3 treatments performed at day 1, 15, and 45 incorporating a session with a newly-developed eye mask (Activa, SBS Sistemi, Turin, Italy) immediately followed by IPL therapy (E > Eye device, E-Swin, Paris, France). Patients were examined before the first session (T0) and 30 days after the last session (T1) for the measurement of: noninvasive break-up time (NIBUT); lipid layer thickness (LLT); tear meniscus height (TMH); meibomian gland loss (MGL); tear osmolarity. Ocular discomfort symptoms were ascertained by ocular surface disease index (OSDI) questionnaire.Results: Thirty patients were ultimately included in the study. At T1, all objective ocular surface parameters improved significantly, except for TMH: NIBUT and LLT increased from 6.4 ± 1.7 to 8.6 ± 1.7 s and from 57.7 ± 15.5 to 81.3 ± 12.0 μm (all P < 0.001), while MGL and tear osmolarity decreased from 21.1 ± 17.3 to 17.0 ± 14.1% and from 302.0 ± 8.5 to 295.7 ± 6.9 mOsm/L (respectively, P = 0.004 and P < 0.001). In parallel, OSDI score decreased significantly from 49.8 ± 13.5 to 29.8 ± 10.6 (P < 0.001). In the historical control group of patients who underwent only IPL, NIBUT, LLT, tear osmolarity and OSDI improved significantly but not MGL and TMH.Conclusions: Serial sessions incorporating the application of an eye mask producing heating and vibration immediately followed by IPL therapy are able to improve all ocular surface parameters as well as ocular discomfort symptoms in MGD patients. [ABSTRACT FROM AUTHOR]

An increasing prevalence of dry eye disease in the past decade has resulted in a greater focus on diagnostic methods for this condition. There has been a proliferation of technologies that attempt to quantify various aspects of tear function and ocular surface health. However, a cost-effective, simple, and efficient method remains elusive. In the Indian context, the majority of these patients present to the general ophthalmologist, and a clinical approach that is quick and easy to perform would allow widespread usage for accurate diagnosis. This article reviews currently available methods and their relevance to the general ophthalmologist. [ABSTRACT FROM AUTHOR]

(1) Background: To investigate the association between plasma fatty acids (FAs) and dry eye disease (DED) in an elderly population; (2) Methods: We conducted a population-based study, the Montrachet study, in individuals older than 75 years. DED was evaluated using the Schirmer I test without anesthesia, tear film breakup time (TFBUT) measurement and fluorescein corneal staining. Plasma FAs were measured in fasting blood using gas chromatography; (3) Results: A total of 740 subjects with a plasma measurement of 25 FAs were included in this study. The mean age was 82.2 ± 3.7 years, and 62.7% were women. DED was present in 35.0% of participants. We identified a plasma FAs pattern positively associated with DED, characterized by low polyunsaturated fatty acids (PUFAs), high monounsaturated fatty acids (MUFAs) and low saturated fatty acids (SFAs) levels. After adjustment for major confounders, individuals in the upper quartile of the FAs pattern scores compared with those in the lower quartile were more likely to present DED (OR 2.46 (95% CI 1.51–4.01), p = 0.001); (4) Conclusion: In this study, we found that a plasma FAs pattern characterized by low PUFAs, high MUFAs and low SFAs was significantly associated with DED in elderly participants. [ABSTRACT FROM AUTHOR]

Total bilateral Limbal Stem Cells Deficiency is a pathologic condition of the ocular surface due to loss or impairment of corneal stem cell function, altering homeostasis of the corneal epithelium. Cultivated Oral Mucosa Epithelial Transplantation (COMET) is the only autologous treatment for this pathology. During the follow-up, a proper characterization of the transplanted oral mucosa on the ocular surface supports understanding the regenerative process. The previously proposed markers for oral mucosa identification (e.g., keratins 3 and 13) are co-expressed by corneal and conjunctival epithelia. Here, we propose a new specific marker to distinguish human oral mucosa from the epithelia of the ocular surface. We compared the transcriptome of holoclones (stem cells) from the human oral mucosa, limbal and conjunctival cultures by microarray assay. High expression of SOX2 identified the oral mucosa vs. cornea and conjunctiva, while PAX6 was highly expressed in corneal and conjunctival epithelia. The transcripts were validated by qPCR, and immunological methods identified the related proteins. Finally, the proposed markers were used to analyze a 10-year follow-up aniridic patient treated by COMET. These findings will support the follow-up analysis of COMET treated patients and help to shed light on the mechanism of corneal repair and regeneration. [ABSTRACT FROM AUTHOR]

The 21st century has seen a steadily increasing social awareness of animal suffering, with increased attention to ethical considerations. Developing new integrated approaches to testing and assessment (IATA) strategies is an Organisation for Economic Co‐operation and Development (OECD) goal to reduce animal testing. Currently, there is a lack of alternative models to test for ocular surface toxicity (aside from irritation) in lieu of the Draize eye irritation test (OECD guideline No. 405) performed in rabbits. Five alternative in vitro or ex vivo methods have been validated to replace this reference test, but only in combination. However, pathologies like Toxicity‐Induced Dry Eye (TIDE), cataract, glaucoma, and neuropathic pain can occur after exposure to a pharmaceutical product or chemical and therefore need to be anticipated. To do so, new models of lacrimal glands, lens, and neurons innervating epithelia are required. These models must take into account real‐life exposure (dose, time, and tear film clearance). The scientific community is working hard to develop new, robust, alternative, in silico, and in vitro models, while attempting to balance ethics and availability of biological materials. This review provides a broad overview of the validated methods for analyzing ocular irritation and those still used by some industries, as well as promising models that need to be optimized according to the OECD. Finally, we give an overview of recently developed innovative models, which could become new tools in the evaluation of ocular surface toxicity within the scope of IATAs. Until now, the Draize test in rabbits has been the only test performed to anticipate ocular toxicity of pharmaceutical compounds, mainly irritation. However, in the field of alternative approaches, new models must be developed and validated. This review aims to give an overview of the OECD validated methods and of innovative models, which could become new tools in the evaluation of ocular surface toxicity. [ABSTRACT FROM AUTHOR]

In vivo confocal microscopy (IVCM) imaging is increasingly popular in ocular surface disease diagnosis and management. We conducted a systematic review to update the use of IVCM in the diagnosis and treatment of dry eye and meibomian gland dysfunction (MGD). A literature review was conducted on IVCM studies in MGD, dry eye disease, systemic disease causing dry eye, dry eye in glaucoma patients, contact lens-associated ocular conditions, graft-versus-host disease, and Sjogren's syndrome-related dry eye. The articles were identified through PubMed and a total number of 63 eligible publications were analyzed in detail. All primary research studies on confocal microscopy on dry eye and related conditions from 2017 onwards were included. The reports were reviewed for their contribution to the existing literature as well as potential biases and drawbacks. Despite limitations such as small field of view, lack of population-based norms, and lack of standardization of image acquisition, interpretation, and quantification, IVCM is useful as a complementary technique for clinical diagnosis in various ocular surface disorders related to dry eye. With advances in hardware and software in the near future, it has the potential for further practical impact. [ABSTRACT FROM AUTHOR]

Aim: To examine tear functions and ocular surface variables in patients with cannabis addiction. Materials and Methods: This clinical trial was planned as a prospective case-control study. In this study, 51 male patients with cannabis addiction (group 1) and 51 healthy volunteers (group 2) with similar demographic characteristics were included. Visual acuity, spherical equivalent, biomicroscopic examination, Schirmer test, tear break-up time (TBUT), and impression cytology (Nelson scores) results were recorded, and the 2 groups were compared with each other. Results: The mean Schirmer values were 9.68 ± 6.8 mm and 8.39 ± 4.08 mm in group 1 and group 2 (p = 0.97), respectively, whereas the mean TBUT values were 9.96±3.9 and 9.29±4.01s. (p = 0.35) and the mean Nelson scores were 1.49±1 and 1.25±0.97 in group 1 and group 2, respectively (p = 0.26). Conclusion: In this study, the effects of cannabis addiction on the ocular surface were evaluated using Schirmer, TBUT, and impression cytology methods. In the statistical analysis, no significant difference was found compared to the control group. This study showed that tear production, tear film stability, and impression cytology of patients with cannabis addiction were not different from the control group. [ABSTRACT FROM AUTHOR]

Objective: To establish tear film osmolarity (TFO) values in Pugs and Shih‐Tzus, with and without keratoconjunctivitis sicca (KCS). Animals studied: A total of 82 adult dogs were evaluated. Procedure: The inclusion criteria for the healthy group was a Schirmer tear test (STT‐1) ≥15 mm/min with no clinical signs of KCS, whereas those with KCS had clinical signs and a STT‐1 ≤10 mm/min. All animals underwent complete ophthalmological evaluation prior to STT‐1 and TFO. Student's t tests were used to compare STT‐1 and TFO in KCS and healthy eyes as well as possible differences in TFO between breeds. In addition, a linear regression to model the relationship between the two variables (STT‐1 and TFO) was performed. A P‐value ≤ 0.05 was considered statistically significant. Results: STT‐1 results were significantly lower (p = 0.0001) in the KCS group (4.46 ± 1.74) compared with the control group (18.80 ± 2.02). Mean TFO results were significantly higher in the KCS group (353.02 ± 16.58 mOsm/L) (p < 0.0001) compared with the control group (315.27 ± 6.15 mOsm/L). The formula Y = 365.059–2.625 * X significantly predicts (p < 0.001) the value of the variable Y (TFO mOsm/L) as a function of the variable X (STT‐1 mm/min), with a coefficient of determination of 0.71. Conclusions: The results revealed differences in TFO and STT‐1 between KCS and healthy dogs. Additionally, STT‐1 and TFO values were correlated with the aim to use STT‐1 values to predict TFO values in brachycephalic breeds. [ABSTRACT FROM AUTHOR]

Purpose: To observe the changes of the ocular surface and meibomian glands by non-contact meibography in patients with type 1 diabetic children. Methods: A total of forty-three patients with type 1 diabetic children and 43 age-matched healthy subjects were included in the study. The ocular surface disease index (OSDI) questionnaire, invasive tear film break-up time (TF-BUT), fluorescein staining of the ocular surface and Schirmer II test were performed for all participants. Ocular surface and lid margins were evaluated by slit lamp. Non-contact meibography was performed with the Phoenix-Meibography module in Sirius corneal topographic device. Results: Both groups consisted of 25 (58.1%) female and 18 (41.9%) male children and the mean age was 14.4 ± 2.5 years. In the T1DM group, the mean disease duration was 6.8 ± 3.1 years. The mean TF-BUT (p = 0.002) and Schirmer II test (p = 0.007) measurements were lower in the diabetic group than those of in controls. Total eyelid score (p = 0.027) and meibomian gland (MG) secretion score (p = 0.007) were significantly high in diabetic children. MG area loss was also significantly high in both lower and upper eyelid (p < 0.001). In morphological analyses of meibomian glands thinning, shortening and presence of ghost areas (p = 0.05, p = 0.027 and p = 0.000, respectively) were more common in the diabetic group. There was no correlation between both lower and upper eyelid meiboscores and disease duration (p = 0.51 and p = 0.61), BMI (p = 0.08 and p = 0.51), serum HbA1c level (p = 0.06 and p = 0.49) and IGF-1 SDS (p = 0.38 and p = 0.68). Conclusion: The study revealed that the MG loss area increases and morphological alterations of meibomian glands occur in type 1 diabetic children. Disease duration and metabolic control of diabetes do not affect meibography measurements. Clinical trials registration: The study was organized in accordance with the ethical standards settled by the Ethics Committee of Faculty of Medicine, Afyonkarahisar Health Sciences University. Trial registration number: 2011-KAEK-2, 2021/106. Trial registration date: 02.05.2021. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the tear osmolarity and ocular surface changes in patients with polycystic ovary syndrome (PCOS). Materials and Methods: Forty-eight patients with recently diagnosed PCOS and thirty-three control volunteers were enrolled in this prospective, observational study. Ocular surface disease index (OSDI) score was calculated. Tear osmolarity was measured using the TearLab Osmolarity System (Tearlab, San Diego, CA, USA). All subjects also underwent the following ophthalmologic evaluation: Schirmer I test, tear-film breakup time (TBUT), ocular surface flourescein staining, and conjunctival impression cytology. Results: Mean OSDI score was significantly higher in patients with PCOS than control subjects ( P = 0.001). Tear osmolarity was similar in both groups ( P = 0.404). There were no significant differences between groups in Schirmer I test results, TBUT, and ocular surface flourescein staining scores ( P > 0.05). Compared to control group, a statistically significant squamous metaplasia was observed in temporal bulbar conjunctival impression cytology specimens in PCOS group ( P = 0.032). Conclusions: In patients with recently diagnosed PCOS, tear volume and osmolarity are not affected but, conjunctival morphology may be affected, though on a limited scale. [ABSTRACT FROM AUTHOR]