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Introduction: The aim of this study is to determine the best cut-off value for the Standardized Patient Evaluation of Eye Dryness Portuguese version questionnaire and verify possible differences between the questionnaire score and different age groups., Methods: The clinical validation of the Standardized Patient Evaluation of Eye Dryness Portuguese version was performed by completing this and the Ocular Surface Disease Index in Portuguese version questionnaire, in 180 volunteers (68.9% female), with an age range of 19-96 years., Results: An excellent degree of reliability was found between the Standardized Patient Evaluation of Eye Dryness Portuguese version and the Ocular Surface Disease Index Portuguese version questionnaires (Cronbach's Alpha = 0.824). The Receiver Operating Characteristic curve analysis revealed a cut-off of 8 points (Sensitivity of 71.2% and Specificity of 71%). Furthermore, the area under the curve of the Receiver Operating Characteristic curve was 0.813, indicating that Standardized Patient Evaluation of Eye Dryness Portuguese version questionnaire is a good diagnostic tool and interchangeable with the Ocular Surface Disease Index questionnaire., Conclusion: The Standardized Patient Evaluation of Eye Dryness Portuguese version questionnaire is a reliable tool for the detection of dry eye symptoms in the Portuguese population with a broad age range., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. The authors declare that they have no conflicts of interest related to this work. Ethics approval: This study was carried out in accordance with the principles of the Declaration of Helsinki. The approval was granted by the Ethics Committee of the University of Beira Interior (20.12.2022/ CE-UBI-Pj-2022–080). Consent to participate: Informed consent was obtained from all individual participants included in the study., (© 2025. The Author(s).)

Purpose: To evaluate the effect of punctal plugs combined with cyclosporine eye drops on dry eye disease (DED) and ocular surface inflammation., Methods: In a clinical trial, 73 patients were randomly allocated into three groups: punctal plug group, combination therapy group, and cyclosporine group. At the baseline and four weeks after treatment, the Schirmer I test score, fluorescein tear film break-up time (FBUT), ocular surface staining score and dry eye symptoms were assessed. Tear samples were collected to detect the level of inflammatory factors (interleukins, matrix metalloproteinase 9 (MMP-9) and tumor necrosis factor alpha (TNF-α)). In an animal experiment, a New Zealand rabbit dry eye model was induced. The rabbits were randomly divided into control group, punctal plug group, and combination therapy group ( n  = 6). Conjunctival goblet cell density, protein level of MMP-9 in conjunctiva and mRNA levels of inflammatory factors in conjunctiva and cornea were measured before and after treatment., Results: In combination therapy group of the clinical trial, the following results were observed: significant improvement in Schirmer I test scores and FBUT compared to the cyclosporine group and punctal plug group, respectively; a decrease in the tear levels of IL-6, IL-1, and MMP-9 compared to the punctal plug group; and a decrease in the tear levels of IL-1α, IL-6, and IL-17 compared to the baseline (all p  < 0.05). In the animal experiment, rabbits in combination therapy group had a higher goblet cell density ( p  < 0.01) and lower mRNA levels of IL-16 ( p  < 0.05), IL-17 ( p  < 0.05), and MMP-9 ( p  < 0.01) in conjunctiva and that of MMP-9 ( p  < 0.01) in cornea compared to punctal plug group., Conclusion: Cyclosporine eye drops combined with degradable punctal plugs is a more optimized clinical treatment strategy for DED compared with degradable punctal plugs or cyclosporine eye drops alone, considering the influence of comprehensive clinical efficacy and ocular surface inflammation.

Purpose: This study compares the corneal temperature in dry eyes with normal eyes via high-resolution infrared thermography., Methods: A total of 86 participants were enrolled, with 40 and 46 participants in the dry eye disease (DED) and control groups, respectively. All participants underwent non-invasive breakup time (NIBUT) measurement, an Ocular Surface Disease Index (OSDI) questionnaire and ocular thermography., Results: In the DED group, the mean initial central corneal temperature (initial CCT) is 33.25 ± 0.66°C, the tenth-second central corneal temperature (10s-CCT) is 32.47 ± 0.84°C, and the mean change in central corneal temperature measured within 10 s (change in CCT within 10 s) is 0.78 ± 0.30°C. For the controls, the initial CCT, 10s-CCT, and change in CCT within 10 s are 33.14 ± 1.02°C, 32.90 ± 0.99°C, and 0.23 ± 0.20°C, respectively. Except for the initial CCT ( p  = 0.549), significant differences are observed in the 10s-CCT ( p  = 0.034) and the change in CCT within 10 s ( p  < 0.001) between the two groups. The standard deviation of the temperature values within the region of interest (SD of TVs within ROI) on the central cornea is calculated to compare the uniformity of corneal temperature. In the DED group, the mean standard deviation of the initial temperature values within the region of interest (SD of initial TVs within ROI) is similar to that in the control group (0.23 ± 0.07°C vs. 0.22 ± 0.05°C, p  = 0.926). In contrast, the mean standard deviation of the tenth-second temperature values within the region of interest (SD of 10s-TVs within ROI) in the DED group is greater than that in the control group, and there is a significant difference (0.44 ± 0.20°C vs. 0.35 ± 0.15°C, p  = 0.016). In the DED group, the mean change in CCT within 3 s after tear film break-up is significantly greater than that before tear film break-up (0.19 ± 0.08°C vs. 0.10 ± 0.10°C, p  < 0.001)., Conclusion: As the time with eyes open increases, dry eyes present a significantly faster decrease in central corneal temperature (CCT) and a significantly worse uniformity of corneal temperature compared with normal eyes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2025 Wu, Huang, Xu, Li, Zhuang, Cao, Hu and Gu.)

Dry eye disease (DED) is a highly prevalent condition, resulting in reduced quality of life, lower participation in social life and impaired work efficiency. Hydroxypropyl methylcellulose (HPMC) is a cellulose-based viscosity-enhancing agent and is one of the most popular therapeutic ingredients in artificial tears. This review aims to evaluate the literature on the efficacy and safety of HPMC used in the treatment of DED. Literature searches were conducted in PubMed and Cochrane CENTRAL. A total of 28 clinical trials from 26 publications are included in this review, including 21 clinical intervention studies evaluating the effect of HPMC treatment over time and seven single instillation studies evaluating the short-term physical and symptomatic effects of HPMC after drop-instillation. The duration of clinical intervention studies ranged from 2 weeks to 5.5 months. DED severity ranged from mild to severe. Drop frequency ranged from two to up to 16 drops per day. HPMC concentration in artificial tears ranged from 0.2% to 0.5%. No major complications or adverse events were reported. Artificial tears containing HPMC were effective at improving symptoms and some signs of DED. However, combination drops with HPMC plus other therapeutic ingredients seem more effective than HPMC alone. HPMC appears to be equally effective or inferior to hyaluronic acid (HA). There is no evidence of superiority or inferiority to either carboxymethylcellulose (CMC) or polyethylene glycol 400/propylene glycol (PEG/PG). No single study explained the choice of drop frequency or HPMC concentration. More well-designed studies are needed to determine an evidence-based standard for HPMC treatment, including drop frequency, concentration and molecular weight for different DED severity and subgroups., (© 2024 The Author(s). Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Additive manufacturing (AM) techniques have the potential to produce complex parts, and many of these techniques require the use of support structures to prevent deformations and to minimize thermal effects during the printing process, particularly when building overhangs and internal cavities. However, removing the support structures through postprocessing incurs additional costs and time penalties. Unlike other AM techniques, support structures are not used in directed energy deposition (DED) technique due to its working principle. Therefore, special multiaxis complex path-planning strategies for DED are adopted to print relatively simple overhang geometries. Nevertheless, printing internal channels using this technique can still be challenging or nearly impossible. In this work, a novel DED process using graphite as a support material is proposed for additively manufacturing simple and complex internal channels. The support material is easily removed without requiring extensive machining processes. The results demonstrated that the support material did not negatively impact part quality, and in fact, the presence of different carbides at the interaction zone increased hardness and Young's modulus. Moreover, there were no cracks and or porosity at the support material-part interface. This study is the first of its kind to demonstrate the potential for using graphite as a support material for DED processes in additively manufacturing parts with complex internal channels and overhangs and highlights the need for further research in this area., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

Myeloid derived suppressor cells (MDSCs) are a heterogenous population of immature hematopoietic precursors with known immunoregulatory functions. The immunosuppressive role of MDSCs has been highlighted in several inflammatory ophthalmic disorders; however, their therapeutic application in suppressing the immune-mediated changes in dry eye disease (DED) has not been studied. We observed significant reduction in antigen presenting cell (APC) frequencies and their maturation in the presence of MDSCs. Moreover, co-culturing MDSCs with T helper 17 cells (Th17) resulted in reduced Th17 frequencies and their IL-17 expression. On the contrary, MDSCs maintained regulatory T cell frequencies and enhanced their function in-vitro. Furthermore, we delineated the role of interleukin-10 (IL-10) secreted by MDSCs in their immunoregulatory functions. We confirmed these results by flow cytometry analysis and observed that treatment with MDSCs in DED mice effectively suppressed the maturation of APCs, pathogenic Th17 response, and maintained Treg function and significantly ameliorated the disease. The results in this study highlight the potential therapeutic application of MDSCs in treating refractory DED., Competing Interests: Declaration of Competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: In this review, we aimed to investigate the literature on sex-specific prevalence of meibomian gland dysfunction (MGD) and to determine whether women or men are more at risk for MGD., Methods: A search was conducted on PubMed using the terms: (Sex OR Gender OR prevalence) AND (Meibomian gland) ., Results: Twenty-four relevant studies on MGD prevalence were identified, including 10 population-based and 14 hospital-based studies. Among the population-based studies, five studies reported higher rates among men, three studies found no differences, and one study observed higher rates among women. In the hospital-based studies, 10 studies reported no difference, two found higher rates among men, and one found higher among women. In the reviewed literature, there was a considerable variation between studies in terms of quality, sample size, age ranges, diagnostic criteria., Conclusions: While most of the population-based studies suggest a higher prevalence among men, the majority of clinic-based studies show no significant difference. Further research with larger samples and standardized criteria is needed to determine whether men are indeed more susceptible to MGD.

Congenital aniridia is a rare bilateral ocular malformation characterized by the partial or complete absence of the iris and is frequently associated with various anomalies, including keratopathy, cataract, glaucoma, and foveal and optic nerve hypoplasia. Additionally, nearly 50% of individuals with congenital aniridia experience symptoms of ocular dryness. Traditional treatment encompasses artificial tears and autologous serum. This study aimed to assess the effectiveness and safety of using platelet rich in growth factors (PRGF) plasma in patients with congenital aniridia and ocular dryness symptoms., Methods: The included patients underwent two cycles of a 3-month PRGF treatment. At 6 months, symptomatology was evaluated using the OSDI and SANDE questionnaires, and ocular surface parameters were analyzed., Results: The OSDI and SANDE values for frequency and severity demonstrated statistically significant improvements ( p < 0.05). Ocular redness, corneal damage (corneal staining), and tear volume (Schirmer test) also exhibited statistically significant improvements ( p < 0.05). No significant changes were observed in visual acuity or in the grade of meibomian gland loss., Conclusion: The use of PRGF in patients with congenital aniridia and ocular dryness symptoms led to significant improvements in symptomatology, ocular redness, and ocular damage. No adverse effects were observed during the use of PRGF.

Purpose: Dry-eye disease (DED) is a chronic progressive ocular surface disorder with limited studies in the pediatric population. The Academy of Ophthalmology's IRIS® Registry was leveraged to investigate the prevalence of DED in the pediatric population (PDED, patients <18 years old) and the demographic differences of DED between pediatric and adult patients (ADED)., Methods: Retrospective cohort study. Patients with DED between January 1st, 2013 and December 31st, 2019 (N = 4,795,979) were included. Descriptive statistics, Pearson's chi-squared tests and two-sample proportions tests were conducted to compare key demographic distributions between the ADED and PDED cohorts., Results: The average age at onset for ADED patients was 61.06 (±14.75) years and for PDED patients was 12.51 (±3.86). The overall tests for independence and the individual tests of proportions of each category were statistically significant for all demographic characteristics (p < 0.001). Characteristics with the largest discrepancies between patients of PDED and the IRIS Registry pediatric patient pool (PIRIS) included female sex (58.08 % vs. 50.60 %), male sex (41.58 % vs. 48.78 %) and Asian race (6.02 % vs. 3.11 %) respectively. Within the PDED cohort, females were at higher risk of PDED (58 % vs. 42 %). PDED was more prevalent in children with refractive errors (76 %) and eyelid/conjunctival disorders (41 %). Characteristics with the largest discrepancies between PDED and ADED patients included female sex (58.08 % vs. 68.12 %), male sex (41.58 % vs. 31.55 %) and Caucasian race (50.24 % vs. 67.06 %) respectively., Conclusions: Significant differences in the PDED cohort are demonstrated in this study. PDED was more prevalent in the female sex and Caucasian race compared to PIRIS and was more commonly associated with refractive errors and eyelid/conjunctival disorders., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: This systematic review aims to elucidate the intricate correlation between celiac disease (CD) and dental enamel defects (DED), exploring pathophysiological mechanisms, oral health implications, and a dentist's role in early diagnosis., Materials and Methods: Following PRISMA guidelines, a comprehensive search from 1 January 2013 to 1 January 2024 across PubMed, Cochrane Library, Scopus, and Web of Science identified 153 publications. After exclusions, 18 studies met the inclusion criteria for qualitative analysis. Inclusion criteria involved study types (RCTs, RCCTs, case series), human participants, English language, and full-text available., Results: The search yielded 153 publications, with 18 studies meeting the inclusion criteria for qualitative analysis. Notable findings include a high prevalence of DED in CD patients, ranging from 50 to 94.1%. Symmetrical and chronological defects, according to Aine's classification, were predominant, and significant associations were observed between CD severity and enamel defect extent., Conclusions: The early recognition of oral lesions, particularly through Aine's classification, may signal potential CD even in the absence of gastrointestinal symptoms. Correlations between CD and dental health conditions like molar incisor hypomineralization (MIH) emphasize the dentist's crucial role in early diagnosis. Collaboration between dentists and gastroenterologists is essential for effective monitoring and management. This review consolidates current knowledge, laying the groundwork for future research and promoting interdisciplinary collaboration for improved CD-related oral health outcomes. Further large-scale prospective research is recommended to deepen our understanding of these issues.

Introduction: An innovative eye drops formulation containing 0.2% hyaluronic acid and a low concentration of hydrocortisone (0.001%; hereafter HALH) has been recently placed on the market (Idroflog ® , Alfa Intes, Italy) to manage the dysregulated parainflammation in patients with dry eye disease (DED). In the present paper, the effectiveness of HALH on the signs and symptoms of DED was retrospectively evaluated and compared with that one obtained using standard tear substitutes (STS) by means of low- and high-tech (Keratograph ® ) assessments., Methods: This was a multicenter retrospective study carried out between February and April 2023, involving adult patients with DED diagnosis owing to post-cataract surgery, meibomian gland dysfunction, allergy, or glaucoma medications. The primary aim was to compare the changes induced by different therapies on Keratograph ® parameters (noninvasive Keratograph tear breakup time [NIKBUT], tear meniscus height [TMH], eyelid meibography, conjunctival hyperemia, and conjunctivochalasis) or collected by traditional low-tech measures (tear breakup time [TBUT], Schirmer test, Efron score, and epithelial alterations) and the Ocular Surface Disease Index score., Results: Data from 155 patients were analyzed. The effectiveness of HALH and STS was reported by both high- and low-tech measures. NIKBUT-first showed a significant improvement in the HALH group versus the STS one at 15 days (6.4 ± 3.6 vs 5.4 ± 3.7 s, p = 0.02), whereas this difference was latent with low-tech TBUT until 45 days (6.8 ± 2.6 vs 5.6 ± 2.3 s, p = 0.03). Patients with DED occurring after cataract surgery reported an enhanced activity of HALH versus STS, particularly for NIKBUT-first, TMH, Schirmer test, and hyperemia stage., Conclusion: These findings highlighted the effectiveness of HALH in all DED subtypes, especially in patients with post-cataract surgery, as well as its superiority versus STS in terms of tear film stability improvement. We recommend longer observation (i.e., 3-6 months) to fully ascertain whether the early improvement detected by high-tech measures will be confirmed in subsequent time points even using low-tech tests., (© 2023. The Author(s).)

Introduction: Dry eye disease (DED) is an important health problem affecting hundreds of millions of people worldwide. In vivo confocal microscopy (IVCM) is a non-invasive imaging tool that can visualize ocular surface diseases. In this study, we aimed to evaluate corneal structures and inflammatory cells with IVCM in DED patients., Material and Methods: The patients were divided into three subgroups: group 1, consisting of 22 patients with aqueous tear insufficiency; group 2, consisting of 21 patients with evaporative type DED; and group 3, consisting of 20 healthy patients. Imaging was performed with IVCM. The corneal epithelium, nerves, stroma, endothelial and inflammatory cells were compared between groups., Results: There was a significant decrease in corneal epithelial cell density in cases with DED, and there was a significant increase in corneal basal epithelial cell density in the aqueous-deficient type. Keratocyte density was significantly increased in the aqueous-deficient type. A significant decrease in the number and density of sub-basal nerves was found in aqueous-deficient cases, and an increase was found in neural pilling and folding. Dendritic cell density, size, number and area were significantly increased in the aqueous-deficient type. There was also decreased corneal endothelial cell density in DED., Conclusion: We evaluated pathological changes in DED on the corneal surface by IVCM. This methodology is valuable in terms of objectively evaluating how the corneal surface is affected in accordance with disease severity and in predicting poor response to treatment., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Background Dry eye disease (DED) is a disease of the ocular surface charac-terized by instability of the tear film, which causes ocular surface inflamma-tion and damage that leads to ocular symptoms, discomfort, and visual disturbance. Dry eye is a common ocular condition and a major reason for ophthalmologist visits. Compulsory e-learning has arisen in colleges and schools with the coronavirus disease 19 (COVID-19) pandemic as a tool for new teaching and learning. DED is an emerging threat to public health and is directly proportional to digital screen viewing length. DED diagnosis flowchart begins with history-taking of associated risk factors and a screening test by Ocular Surface Disease Index (OSDI). Therefore, we aim to assess the prevalence and the severity of DED among Jazan University lecturers and to identify the associated risk factors. Methods  A total of 150 participants were recruited for this descriptive, observational study. Participants completed an online questionnaire that contained questions about sociodemographics, electronic devices they used, the average number of hours of use in a day as well as the distance and posture while reading, and factors that may influence visual symptoms such as the use of glasses, frequent changes in glasses prescription and DED symptoms. Results The results showed that the prevalence of DED was high, with 23% of participants having mild DED, 12% having moderate DED, and 29% having severe DED. DED was associated with a number of sociodemographic and clinical factors, including younger age, female gender, occupation as a lecturer, and use of digital devices. Conclusion This study highlights the need to develop strategies to prevent and control DED among high-risk groups, such as university lecturers. Future research should focus on identifying more effective ways to prevent DED and to improve the management of DED symptoms., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abuallut et al.)

Background/aim: To evaluate the clinical efficacy of combination therapy with diquafosol sodium and sodium hyaluronate in dry eye patients after small incision lenticule extraction (SMILE)., Patients and Methods: A prospective randomized controlled study was conducted on consecutive patients who were diagnosed with dry eye disease (DED) and ready to accept SMILE from January 2021 to December 2021. The participants were randomly allocated to either a combination with diquafosol sodium 3% and sodium hyaluronate 0.3% group (DQS group, n=40) or a sodium hyaluronate 0.3% group (HA group, n=41). Dry eye disease parameters included tear film break-up time (TBUT), Shirmer I test (SIT), corneal and conjunctival fluorescein staining score (FS score), and Ocular Surface Disease Index (OSDI); tests were conducted before surgery and at 1 week, 1 month, and 3 months after surgery., Results: At 1 week after surgery, there were no statistically significant overall differences in DED parameters between the 2 groups. At postoperative month 1, the FS score was significantly lower in the DQS group than in the HA group (1.20±1.06 vs. 1.83±1.41 respectively, p=0.026). At 3 months after the surgery, the DQS group was significantly superior to the HA group in OSDI (12.98±7.29 vs. 16.82±8.25, p=0.029), TBUT (5.83±2.02 vs. 4.24±0.94, p=0.0002), and SIT (7.75±3.92 vs. 5.24±3.42, p=0.003)., Conclusion: Our study showed that combination therapy with diquafosol and hyaluronate was beneficial for improving both signs and symptoms of dry eye patients after small incision lenticule extraction., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To evaluate the efficacy of multi-frequency RF and IPL + MGX combination for treatment of Meibomian Gland Dysfunction (MGD)., Patients and Methods: Eligible subjects had signs and moderate-to-severe symptoms of DED (Dry Eye Disease) due to MGD. Subjects underwent 4 treatments at 2-week intervals. Each treatment consisted of intense pulsed light (IPL) followed by radiofrequency (RF) on the periocular skin, followed by meibomian gland expression (MGX). The main outcome measure was the quality of meibum in 15 meibomian glands along the lower eyelid, using the modified Meibomian Gland Score (mMGS). The main hypothesis was a reduction of mMGS between the baseline (BL) and the follow-up (FU). Other outcome measures, such as symptoms measured with the OSDI (Ocular Surface Disease Index) questionnaire, meibography, non-invasive tear break-up time (NIBUT), and matrix metallopeptidase 9 (MMP-9) levels in tear samples were evaluated as well., Results: 31 subjects completed the FU. Between BL and FU, mMGS decreased from 30.4 (8.5) to 9.3 (9.5) (-69.3%, 95% CI: -55.6% to -82.9%, p<0.0001); OSDI decreased from 63.6 (17.2) to 25.0 (20.6) (-60.7%, 95% CI: -47.8% to -73.5%, p<0.0001); NIBUT did not change (p=0.92). An adjusted model with a historical control was constructed to allow the comparison of these subjects with those treated similarly with IPL+MGX (but without RF) in a different study. This analysis identified that the change in mMGS was larger when RF was included (-20.9 vs -18.3, adjusted p-value (p&#95;adjusted) <0.05). The difference in OSDI change was not significant (-38.1 vs -25.5, p&#95;adjusted = 0.196)., Conclusion: Combination of multi-frequency RF and IPL+MGX improves signs and symptoms of MGD. In comparison to a historical control, improvements were generally larger. A randomized controlled study comparing the combination of RF and IPL+MGX with IPL+MGX alone is required to further elaborate the relative contribution of RF., Competing Interests: JC and CNG are consultants of Lumenis Be. In addition, JC reports non-financial support for RF generator from Soniquence and consulting fees from Horizon Therapeutics, outside the submitted work. HH is an employee of Lumenis Be. The authors report no other conflicts of interest in this work., (© 2023 Chelnis et al.)

Purpose: To investigate the hypothesis that a Mediterranean diet is associated with a lower risk of having dry eye disease (DED) in the general population., Methods: DED was assessed using the Women's Health Study (WHS) dry eye questionnaire in 58,993 participants from the Dutch Lifelines Cohort with complete available dietary data (20-94 years, 60% female). Level of adherence to a traditional Mediterranean diet was assessed using the modified Mediterranean Diet Score (mMDS). High-sensitivity C-reactive Protein (hsCRP) was included as a marker of whole-body inflammation. Logistic regressions were used to examine the relationship between WHS-defined DED and mMDS, corrected for age, sex, BMI, education, income, and 48 potentially confounding comorbidities. The association between mMDS and hsCRP, and hsCRP and DED, was further explored in separate regressions., Results: Of all participants, 9.1% had DED. In contrast to the hypothesis, higher mMDS levels were associated with greater odds of DED, corrected for demographics, smoking status, BMI, and comorbidities (OR 1.034, 95%CI: 1.015 to 1.055, P = 0.001). Moreover, there was a highly significant relationship between increasing mMDS and lower circulating hsCRP levels; however, there was no significant relationship between hsCRP and DED., Conclusions: Stronger adherence to a Mediterranean diet does not appear to be associated with lower odds of having DED in the general population. Furthermore, there was no association between hsCRP and DED in this study. However, the previously described link between a Mediterranean diet and lower hsCRP was confirmed in this large population-based study., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Dry eye disease (DED) is a common ocular condition with a significant impact on patients' quality of life. Conventional treatments include behavioral changes, tear substitutes, and anti-inflammatory agents; however, recent advances in the understanding of DED pathogenesis have opened the way to the development of novel treatment strategies able to target several pathways involved in the onset and persistence of DED., Areas Covered: Literature search was conducted on PubMed and Scopus around the term 'dry eye disease' and others involving its pathophysiology and therapeutic strategy. The primary focus was on recent drugs approved by FDA or under investigation in phase 3 clinical trials. Google and ClinicalTrials.gov were used for obtaining information about the status of FDA approval and ongoing clinical trials., Expert Opinion: Due to its multifaced pathogenesis, DED management is often challenging, and patients' needs are frequently unmet. Recently, several novel treatments have been either FDA-approved or studied in late-phase trials. These novel drugs target-specific biological components of the ocular surface and reduce inflammation and ocular pain. Additionally, new drug delivery systems allow for increased bioavailability, improve effective dosing, and minimize ocular side effects. These advances in drug therapies show real promise for better management of DED patients.

Purpose: Dry eye disease (DED) is a common ocular problem that worsens patients' quality of life. This study aimed to assess DED prevalence and risk factors among medical students at the University of Tabuk., Patients and Methods: This is an analytical, cross-sectional, survey-based study. An online questionnaire was distributed by email to all medical students at the University of Tabuk. A self-administered McMonnies questionnaire was used in the assessment., Results: We included 247 medical students who completed the questionnaire. Most participants were females (71.3%) and were <25 years old (85.8%). DED prevalence rate was 18.2% (95% CI=13.61% to 23.61%). Furthermore, DED was found to be significantly associated with the presence of irritation of eyes when waking up from sleep (OR=19.315), sleeping with partially opened eyes (OR=19.105), redness and irritation of the eyes when swimming in chlorinated fresh water (OR=7.863), and having prescription eyedrops or other dry eye treatments (OR=3.083)., Conclusion: Our study at the University of Tabuk found that 18.2% of medical students had dry eye disease and identified the associated risk factors. Early diagnosis and treatment are crucial to prevent complications due to the high prevalence of DED., Competing Interests: The authors declare that there are no conflicts of interest., (© 2023 Aljammaz et al.)

Dry eye disease (DED) is a worldwide, multifactorial disease mainly caused by a deficit in tear production or increased tear evaporation with an increase in tear osmolarity and inflammation. This causes discomfort and there is a therapeutic need to restore the homeostasis of the ocular surface. The aim of the present work was to develop a biodegradable and biocompatible liposomal formulation from the synthetic phospholipids 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) that is able to reduce the effects of hypertonic stress by helping to restore the lipid layer of the tear film. Liposomes were made using the lipid film hydration method with synthetic phospholipids (10 mg/mL) with and without 0.2% HPMC. They were characterised in terms of size, osmolarity, pH, surface tension, and viscosity. Additionally, the in vitro toxicity of the formulation at 1 and 4 h in human corneal epithelial cells (hTERT-HCECs) and human conjunctival cells (IM-HConEpiC) was determined. Furthermore, osmoprotective activity was tested in a corneal model of hyperosmolar stress. In vivo acute tolerance testing was also carried out in albino New Zealand rabbits by topical application of the ophthalmic formulations every 30 min for 6 h. All the assayed formulations showed suitable physicochemical characteristics for ocular surface administration. The liposomal formulations were well-tolerated in cell cultures and showed osmoprotective activity in a hyperosmolar model. No alterations or discomfort were reported when they were topically administered in rabbits. According to the results, the osmoprotective liposomal formulations developed in this work are promising candidates for the treatment of DED.

Background and Objectives : Dry eye disease (DED) is a common and very symptomatic pathology that affects normal daily activity. The aim of the study was to evaluate the efficacy of plasma rich in growth factors (PRGF) added to one routine treatment protocol for DED (artificial tears substitutes, lid hygiene, and anti-inflammatory therapy). Materials and Methods : Patients were divided into two groups of treatment: standard treatment group ( n = 43 eyes) and PRGF group ( n = 59). Patients' symptomatology (inferred from OSDI and SANDE questionnaires), ocular inflammation, tear stability, and ocular surface damage were analyzed at baseline and after 3 months of treatment. Results : OSDI test scores were significantly lower in both groups ( p < 0.001). SANDE frequency test scores also improved statistically, with differences between groups ( p = 0.0089 SANDE frequency and p < 0.0119 SANDE severity). There was a greater reduction in ocular redness (ocular inflammation) in the PRGF group ( p < 0.0001) and fluorescein tear break-up time was significantly improved in the PRGF group ( p = 0.0006). No significant changes were found in terms of ocular surface damage. No adverse events were obtained in either group. Conclusions : The addition of PRGF to the standard treatment of DED, according to the results obtained, proved to be safe and produced an improvement in ocular symptomatology and signs of inflammation, particularly in moderate and severe cases, when compared to standard treatment., Competing Interests: R.M.S.-&Aacute;. is a scientist at the BTI Biotechnology Institute. The other authors declare no conflicts of interest in developing this study.

Additive manufacturing technologies have numerous advantages over conventional technologies; nevertheless, their production process can lead to high residual stresses and distortions in the produced parts. The use of numerical simulation models is presented as a solution to predict the deformations and residual stresses resulting from the printing process. This study aimed to predict the tensions and distortions imposed in the gear repair process by directed energy deposition (DED). First, the case study proposed by National Institute of Standards and Technology (NIST) was analyzed to validate the model and the numerically obtained results. Subsequently, a parametric study of the influence of some of the parameters of DED technology was carried out. The results obtained for the validation of the NIST benchmark bridge model were in agreement with the results obtained experimentally. In turn, the results obtained from the parametric study were almost always in line with what is theoretically expected; however, some results were not very clear and consistent. The results obtained help to clarify the influence of certain printing parameters. The proposed model allowed accounting for the effect of residual stresses in calculating the stresses resulting from gear loading, which are essential data for fatigue analysis. Modeling and simulating a deposition process can be challenging due to several factors, including calibrating the model, managing the computational cost, accounting for boundary conditions, and accurately representing material properties. This paper aimed to carefully address these parameters in two case studies, towards reliable simulations.

Dry eye disease (DED) is a broad term that includes a diverse group of clinical disorders. Aqueous-deficient dry eye (ADDE), a subtype of DED, is characterized by decreased tear production by the lacrimal gland. It can be seen in up to one-third of individuals with DED and can be comorbid with a systemic autoimmune process or occur secondary to an environmental insult. Since ADDE can be a source of long-term suffering and severe visual impairment, early identification and adequate treatment are imperative. Multiple etiologies can underlie ADDE, and it is critical to identify the underlying cause to not only improve the ocular health but also to improve the overall quality of life and well-being of affected individuals. This review discusses the various etiologies of ADDE, highlights a pathophysiology-based approach for evaluating underlying contributors, outlines various diagnostic tests, and reviews treatment options. We present the current standards and discuss ongoing research in this field. Through this review, we propose a treatment algorithm that would be useful for an ophthalmologist in diagnosing and managing individuals with ADDE., Competing Interests: None

Samples of 316L SS were manufactured by Laser Engineered Net Shaping (LENS ® ) using different technological parameters. The deposited samples were investigated in terms of microstructure, mechanical properties, phase content and corrosion resistance (salt chamber and electrochemical corrosion). Parameters were chosen to obtain a proper sample built for layer thicknesses of 0.2, 0.4 and 0.7 mm by changing the laser feed rate while keeping the powder feed rate constant. After a comprehensive analysis of the results, it was found that the manufacturing parameters slightly affected the resulting microstructure and also had a minor impact (almost undetectable considering the uncertainty of the measurement) on the mechanical properties of samples. Decreases in resistance to electrochemical pitting corrosion and environmental corrosion with an increased feed rate and a decrease in layer thickness and grain size were observed; however, all additively manufactured samples were found to be less prone to corrosion than the reference material. In the investigated processing window, no influence of deposition parameters on the phase content of the final product was found-all the samples were found to possess austenitic microstructure with almost no detectable ferrite.

Astrocytes are highly efficient homeostatic glial cells playing a crucial role in optimal brain functioning and homeostasis. Astrocytes respond to changes in brain homoeostasis following central nervous system (CNS) injury/diseased state by a specific defence mechanism called reactive astrogliosis. Recent studies have implicated and placed reactive astrogliosis in the centre of pathophysiology of Alzheimer's disease (AD) and other neurodegenerative disorders. The AD biomarker field is evolving rapidly with new findings providing strong evidence which supports the notion that a reactive astrogliosis is an early event in the time course of AD progression which may precede other pathological hallmarks of AD. Clinical/translational in vivo PET and in vitro postmortem brain imaging studies demonstrated 'a first and second wave' of reactive astrogliosis in AD with distinct close-loop relationships with other pathological biomarkers at different stages of the disease. At the end stages, reactive astrocytes are found to be associated, or in proximity, with amyloid plaque and tau pathological deposits in postmortem AD brains. Several new PET-tracers, which are being in pipeline and validated at a very fast pace for mapping and visualising reactive astrogliosis in the brain, will provide further invaluable mechanistic insights into AD and other non-AD dementia pathologies. The complementary roles of microglia and astrocyte activation in AD progression, along with the clinical value of new fluid astrocytes biomarkers in the context of existing biomarkers, are the latest avenue that needs further exploration., (© 2022 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry.)

Purpose: The introduction of flow diverters (FDs) in 2007 greatly enhanced the treatment of intracranial aneurysms. Here, we present our long-term clinical experience in treating unruptured intracranial aneurysms with FDs., Methods: 107 patients with unruptured aneurysms and treated with an FD between 2010 and 2019 were retrospectively reviewed. Aneurysm occlusion, procedural complications, and clinical outcome were evaluated., Results: Angiographic follow-up was available for 93 patients with a mean long-term follow-up time of 28.4 ± 21.6 months. Additional coiling was performed in 15.1% of patients ( n = 14). Adequate aneurysm occlusion (Kamran grades 3 and 4) at long-term follow-up was achieved in 94.6% of patients ( n = 88). 3.2% ( n = 3) required endovascular retreatment since the last follow-up showed a lack of aneurysm occlusion (Kamran grade 0) due to a foreshortening of the FD. Incomplete opening of the FD and parent vessel occlusion was seen in 1.1% ( n = 1) and 3.2% ( n = 3) of patients, respectively. In-stent stenosis was observed in 57% ( n = 53) of cases at short-term follow-up and 22.6% ( n = 21) at long-term, which were moderate and asymptomatic overall. In-stent stenosis decreased significantly between short- and long-term follow-ups (31.4 ± 17.0% vs 9.7 ± 13.6%, respectively; p ≤ 0.001). Thromboembolic and hemorrhagic events occurred in 7.5% ( n = 7) and 1.1% ( n = 1) of patients, respectively. Good clinical outcome (modified Rankin scale: 0-2) was obtained in 97.8% ( n = 91) leading to an overall treatment-related morbidity of 2.2% ( n = 2). There was no procedural mortality., Conclusion: Our study shows that FD treatment of unruptured intracranial aneurysms is effective and safe with high occlusion rates and low rates of permanent morbidity at long-term follow-up.

Background: Visual display terminal (VDT) use is a key risk factor for dry eye disease (DED). Visual display terminal (VDT) use reduces the blink rate and increases the number of incomplete blinks. However, the exact mechanisms causing DED development from VDT use have yet to be clearly described., Purpose: The purpose of the study was to conduct a review on pathophysiological mechanisms promoting VDT-associated DED., Methods: A PubMed search of the literature investigating the relationship between dry eye and VDT was performed, and relevance to pathophysiology of DED was evaluated., Findings: Fifty-five articles met the inclusion criteria. Several pathophysiological mechanisms were examined, and multiple hypotheses were extracted from the articles. Visual display terminal (VDT) use causes DED mainly through impaired blinking patterns. Changes in parasympathetic signalling and increased exposure to blue light, which could disrupt ocular homeostasis, were proposed in some studies but lack sufficient scientific support. Together, these changes may lead to a reduced function of the tear film, lacrimal gland, goblet cells and meibomian glands, all contributing to DED development., Conclusion: Visual display terminal (VDT) use appears to induce DED through both direct and indirect routes. Decreased blink rates and increased incomplete blinks increase the exposed ocular evaporative area and inhibit lipid distribution from meibomian glands. Although not adequately investigated, changes in parasympathetic signalling may impair lacrimal gland and goblet cell function, promoting tear film instability. More studies are needed to better target and improve the treatment and prevention of VDT-associated DED., (© 2022 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.)

Due to their good material properties (e.g., corrosion and wear resistance, biocompatibility), thermoplastic materials like polyamide 12 (PA12) are interesting for functional coatings on metallic components. To ensure a spatially resolved coating and to shorten the process chain, directed energy deposition of polymer powders by means of a laser beam (DED-LB/P) offers a promising approach. Due to characteristic absorption bands, the use of a thulium fiber laser with a wavelength of 1.94 μm is investigated in a DED-LB/P setup to generate PA12 coatings on stainless steel substrates without the need to add any absorbing additives. The influence of the energy density and powder mass flow was analyzed by infrared thermography. Furthermore, the coatings were characterized by differential scanning calorimetry, laser-scanning-microscopy, optical microscopy and cross-cutting tests. The results in this study demonstrate for the first time the basic feasibility of an absorber-free DED-LB/P process by using a thulium fiber laser. PA12 coatings with a low porosity and good adhesion are achievable. Depending on the application-specific requirements, a trade-off must be made between the density and surface quality of the PA12 coatings. The use of infrared thermography is appropriate for in-situ detection of process instabilities caused by an excessive energy input.

Dry eye disease affects millions of people worldwide, causing pain, vision disturbance, and reduced productivity. Meibomian gland dysfunction, a major cause of dry eye, is characterized by chronic glandular inflammation, thickening of the meibum, obstruction of terminal ducts, and glandular atrophy. Treatment of meibomian gland dysfunction can utilize heat and pressure applied to the meibomian glands, increasing meibum expression. With self-treatments, however, not all patients achieve lasting improvement, and compliance is often low. In-office thermal systems offer a second line of treatment and could be a much-needed addition for patients who do not respond to conventional treatment. We critically evaluated the efficacy and safety of LipiFlow, iLux, and TearCare based on existing literature. While the studies found a single in-office thermal treatment to be safe and effective in improving short-term signs and symptoms in patients with dry eye, long-term efficacy needs to be further evaluated. Thus, well-controlled, long-term efficacy studies are warranted to draw clear conclusions. The treatment seemed to provide rapid relief of symptoms that may last up to 1 year, but at a considerably higher cost than the at-home treatments. The choice of treatment depends on cost, compliance with at-home treatment, and personal preference., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Fas-associated death domain (FADD) is an adapter molecule that bridges the interaction between receptor-interacting protein 1 (RIP1) and aspartate-specific cysteine protease-8 (caspase-8). As the primary mediator of apoptotic cell death, caspase-8 has two N-terminal death-effector domains (DEDs) and it interacts with other proteins in the DED subfamily through several conserved residues. In the tumor necrosis receptor-1 (TNFR-1)-dependent signaling pathway, apoptosis is triggered by the caspase-8/FADD complex by stimulating receptor internalization. However, the molecular mechanism of complex formation by the DED proteins remains poorly understood. Here, we found that direct DED-DED interaction between FADD and caspase-8 and the structure-based mutations (Y8D/I128A, E12A/I128A, E12R/I128A, K39A/I128A, K39D/I128A, F122A/I128A, and L123A/I128A) of caspase-8 disrupted formation of the stable DED complex with FADD. Moreover, the monomeric crystal structure of the caspase-8 DEDs (F122A/I128A) was solved at 1.7 Å. This study will provide new insight into the interaction mechanism and structural characteristics between FADD and caspase-8 DED subfamily proteins.

Dry eye disease (DED) is a multifactorial disease that causes ocular discomfort and visual impairment on a damaged ocular surface. Lifitegrast, a novel T-cell integrin antagonist, was approved in the United States in July 2016 as a 5% (50 mg/mL) ophthalmic solution for DED management. Currently, no meta-analysis and systemic review based on relevant studies have been conducted. This study aimed to evaluate the efficacy and safety of lifitegrast in patients with DED. We systematically searched Embase, Medline, PubMed, and Web of Science for randomized controlled trials (RCTs) and nonrandomized studies evaluating lifitegrast effects on symptomatic DED. Then, inferior corneal staining score, total corneal staining score (TCSS), nasal lissamine staining score (NLSS), total lissamine staining score, ocular discomfort score (ODS), eye discomfort score (visual analog scale (VAS) score), eye dryness score (EDS), ocular surface disease index score (OSDI-S), and tear break-up time (TBUT) were assessed. Clinical global impression and safety profiles were also evaluated. The studies were pooled in a random-effects model. We included five RCTs, one case-control study, and four longitudinal or retrospective studies, comprising 3197 participants. In the meta-analysis, lifitegrast was superior to the placebo because it improved TCSS, NLSS, TBUT, ODS, eye discomfort score, EDS, and OSDI-Sin DED. However, lifitegrast showed higher risks for ocular and non-ocular treatment-emergent adverse events (TEAEs) overall or at a mild or moderate level. Nonetheless, its incidence of adverse events slightly differed from that in the placebo, especially instillation site discomforts and dysgeusia, thereby considered safe and tolerable. Claims of withdrawal during follow-up caused by TEAEs were extremely rare. Lifitegrast improves DED, although dysgeusia, installation site pain, and irritation may be a concern for some. Overall, most of the adverse events are tolerable. Lifitegrast can alleviate refractory DED and improves patients' quality of life.

Dry eye disease (DED) after cataract surgery is associated with various risk factors, while causing a wide range of heterogeneous symptoms including decreased quality of vision. This systematic review and meta-analysis aimed to determine the prevalence and characteristics of DED after cataract surgery. We searched PubMed and EMBASE and included studies on patients with DED after cataract surgery, between January 2011 and June 2020. Study-specific estimates (DED prevalence rates after cataract surgery in patients without preexisting DED) were combined using one-group meta-analysis in a random-effects model. We included 36 studies published between 2013 and 2020. We included nine of these in the meta-analysis of DED prevalence after cataract surgery. Overall 37.4% (95% CI 22.6-52.3; 206/775) of patients without preexisting DED developed DED after cataract surgery. The risk factors for DED after cataract surgery included age, female sex, systemic diseases, systemic medications, psychiatric conditions, preexisting DED, meibomian gland dysfunction, preservatives in eye drops, surgery techniques, and lifestyle. DED severity peak occurred 1 day postoperatively and persisted for at least 1-12 months following cataract surgery; therefore, consistent follow-up for DED is warranted for at least 1 month after cataract surgery. Topical administration of preservative-free diquafosol tetrasodium solution and preoperative meibomian gland treatment were effective in preventing and treating DED following cataract surgery. As more than one-third of patients develop DED after cataract surgery, careful DED management and treatment is needed after cataract surgery to improve satisfaction and vision quality., (© 2022. The Author(s).)

Introduction: Recently, there has been a progressive shift from simple water-adding medications towards complex multi-action combined formulas aimed at disrupting different mechanisms within the dry eye disease (DED) vicious cycle. This study evaluated the efficacy and tolerability of Trimix eye drops (Off Health Italia, Italy), a combination of viscosity-enhancing hyaluronic acid, trehalose, and cationic liposomes comprising stearylamine and phospholipids, in patients with DED., Methods: In this prospective, pilot study patients diagnosed with mild to moderate DED were enrolled and treated with Trimix eye drops three times daily for 2 months. Ocular surface workup was performed before (V0) and after therapy (V1) by means of IDRA (SBM Sistemi, Turin, Italy), for the measurement of (i) noninvasive break-up time (NIBUT); (ii) tear meniscus height (TMH); (iii) lipid layer thickness (LLT); (iv) infrared meibography (percentage of meibomian gland loss); (v) bulbar redness (Efron scale). Treatment tolerability was scored on a visual analog scale ranging from 0 (none/not at all) to 100 (much/very) for eight questions. Ocular discomfort symptoms were scored using the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire., Results: Overall, 25 subjects (mean age 60.32 ± 14.55 years) were included in the study. At V1, TMH, NIBUT, and LLT significantly increased compared to V0 (from 0.29 ± 0.06 to 0.46 ± 0.06 mm, 6.34 ± 2.61 to 7.58 ± 2.52 s, and from 63.26 ± 17.15 to 68.42 ± 15.63 nm, respectively; all P < 0.04). Concerning ocular discomfort symptoms, SPEED score significantly improved at V1 (from 16.63 ± 6.32 to 8.30 ± 5.98; P < 0.001); moreover, treatment tolerability was high for all eight items investigated., Conclusions: Two-month treatment with Trimix formulation improved objective signs and subjective symptoms in patients with DED, showing also a good tolerability profile., (© 2022. The Author(s).)

Purpose: To explore the characteristics of spatial-temporal prevalence and public attention of dry eye diseases (DED) through Baidu Index (BI) based on infodemiology method., Methods: The data about BI of DED were collected from Baidu search engine using "Dry eye diseases" as keyword. The spatial and temporal distribution of DED were analyzed through timeseries data decomposition as well as spatial autocorrelation and hotspot detection of BI about DED. The most popular related words and demographic characteristics were recorded to determine the public attention of DED., Results: The trends of BI about DED in Chinese mainland had gradually increased over time with a rapid increase from 2012 to 2014 and in 2018. The results of timeseries decomposition indicated that there was seasonality in the distribution of BI about DED with the peak in winter, especially in northern regions. The geographic distribution demonstrated the search activities of DED was highest in the east of Chinese mainland while lowest in the west. The vast majority of people searching for DED were teenagers (20-29 years), with a predominance of females. Glaucoma, keratitis and conjunctivitis were the diseases most often confused with DED, and the artificial tears were the most common treatment for DED in Chinese mainland according to the BI about DED., Conclusions: The analysis revealed the seasonality, geographic hotspots and public concern of DED through BI in Chinese mainland, which provided new insights into the epidemiology of DED., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Zeng, Zhang, Zhao, Wu and Feng.)

Glaucoma is a group of chronic irreversible neuropathies that affect the retina and the optic nerve. It is considered one of the leading causes of blindness in the world. Although it can be due to various causes, the most important modifiable risk factor is the elevated intraocular pressure (IOP). In this case, the treatment of choice consists of instilling antihypertensive formulations on the ocular surface. The chronicity of the pathology, together with the low bioavailability of the drugs that are applied on the ocular surface, make it necessary to instill the formulations very frequently, which is associated, in many cases, with the appearance of dry eye disease (DED). The objective of this work is the design of topical ocular formulations capable of treating glaucoma and, at the same time, preventing DED. For this, two liposome formulations, loaded with brimonidine or with travoprost, were Tadeveloped using synthetic phospholipids and enriched by the addition of compounds with osmoprotective activity. The proposed formulations not only presented physicochemical characteristics (size, pH, osmolarity, surface tension, and viscosity) and encapsulation efficiency values (EE% of 24.78% and ≥99.01% for brimonidine and travoprost, respectively) suitable for ocular surface administration, but also showed good tolerance in human corneal and conjunctival cell cultures, as well as an in vitro osmoprotective activity. The hypotensive effect of both liposomal formulations was evaluated in normotensive albino New Zealand rabbits, showing a faster and longer lasting reduction of intraocular pressure in comparison to the corresponding commercialized products used as control. According to these results, the hypotensive liposomal formulations combined with osmoprotective agents would result in a very promising platform for the treatment of glaucoma and the simultaneous protection of the ocular surface.

Introduction: There is a substantial unmet need for effective therapies to treat patients with refractory dry eye disease (DED). The goal of this open-label pilot study was to investigate the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel; Mallinckrodt Pharmaceuticals) in subjects with DED, most of whom did not experience adequate response to standard-of-care therapies., Methods: Adults with moderate or severe-acute DED received 80 U of subcutaneous RCI twice weekly for 12 weeks. Primary efficacy outcomes were improvements in corneal fluorescein staining of superficial punctate keratitis (SPK) lesions and Symptom Assessment in Dry Eye (SANDE) scores. Secondary outcomes included changes in Schirmer's test scores, conjunctival lissamine green staining, erythema, intraocular pressure (IOP), and best corrected visual acuity (BCVA). Adverse events (AEs) were assessed continuously throughout the study., Results: Fifteen subjects received at least 1 dose of RCI, and 12 subjects completed the study. Compared to baseline (day 1), significantly fewer fluorescein-stained SPK lesions were detected at day 14 (p = 0.0250) and day 84 (p = 0.0240) after RCI treatment. Mean SANDE scores progressively declined from 62.0 at baseline to 46.9 at day 84. Erythema (p = 0.0046), conjunctival lissamine green staining of SPK lesions (p = 0.0317), and IOP (p = 0.0052) were all significantly improved after 12 weeks of RCI therapy. Schirmer's test scores and BCVA showed no significant changes throughout the study. No ocular AEs or deaths occurred, and no new safety signals were identified for RCI., Conclusions: These results suggest that RCI may be a safe and effective treatment for moderate and severe DED., Trial Registration: ClinicalTrials.gov identifier: NCT03287635., (© 2022. The Author(s).)

Purpose: NovaTears ® +Omega-3 is a water-free eye drop solution with non-animal-derived omega-3 fatty acids. It allows to supplement omega-3 fatty acids directly in the tear film of patients with dry eye disease (DED). This post-market clinical follow-up (PMCF) study evaluated for the first time the effects on clinical signs and patient symptoms of DED, and safety and tolerability of NovaTears+Omega-3 (0.2%) eye drops, when used in accordance with its approved label. Methods: A prospective, multicenter, single-arm, uncontrolled, open-label observational cohort study was performed in patients suffering from symptoms of evaporative DED. Patients were treated 4 times daily bilaterally according to the instructions for use for 8 weeks, and standard of care clinical end points were assessed at baseline and follow-up. The trial was conducted at 2 investigational sites in Germany, Europe. Results: Thirty-six patients were included and 33 completed the study. NovaTears+Omega-3 (0.2%) showed clinically and statistically significant improvements in various clinical signs, such as total corneal staining, tear film break-up time, and Meibomian gland dysfunction (MGD) score, as well as in symptoms measured by Ocular Surface Disease Index (OSDI © ) and visual analog scales over the 8-week treatment period with change from baseline P values all <0.0001. No worsening of any safety parameter (intraocular pressure, slit-lamp examination, visual acuity) was observed, and no adverse event was reported throughout the study. Conclusions: In this observational PMCF study, NovaTears+Omega-3 was safe and well tolerated. Treatment over an 8-week period resulted in significantly improved clinical signs and subjective symptoms in patients with evaporative dry eye. The study was registered at www.clinicaltrials.gov (NCT04521465).

Background: Coronavirus disease 2019 has necessitate the routine use of masks worldwide. This study assessed the relationship between wearing a facemask and dry eye disease (DED) among a sample of medical students in Jordan., Methods: This cross-sectional online survey enrolled medical students from all medical schools in Jordan. The questionnaire, which was shared via social media platforms, assessed sociodemographic information, ocular and medical history, facemask-wearing habits, the use of ocular devices, and the relationship with ocular discomfort. The ocular surface disease index (OSDI) questionnaire was also administered to quantify DED symptoms., Results: A total of 1,219 students participated in this study. In total, 58.3% participants were females, and 52% were in the clinical science years. Symptomatic DED was found in 71.7% of participants. Female sex, basic science years, allergy reporting, and spending more than 6 h looking at screens were significantly associated with symptomatic DED., Conclusion: Wearing a facemask was not significantly associated with symptomatic DED. Further studies are needed to investigate the effect of wearing a facemask on the ocular surface., (© 2022. The Author(s).)

The extrinsic pathway is mediated by death receptors (DRs), including CD95 (APO-1/Fas) or TRAILR-1/2. Defects in apoptosis regulation lead to cancer and other malignancies. The master regulator of the DR networks is the cellular FLICE inhibitory protein (c-FLIP). In addition to its key role in apoptosis, c-FLIP may exert other cellular functions, including control of necroptosis, pyroptosis, nuclear factor κB (NF-κB) activation, and tumorigenesis. To gain further insight into the molecular mechanisms of c-FLIP action in cancer networks, we focus on the structure, isoforms, interactions, and post-translational modifications of c-FLIP. We also discuss various avenues to target c-FLIP in cancer cells for therapeutic benefit., Competing Interests: Declaration of interests No interests are declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Different pathophysiologic mechanisms are involved in the initiation, development, and outcome of dry eye disease (DED). Animal models have proven valuable and efficient in establishing ocular surface microenvironments that mimic humans, thus enabling better understanding of the pathogenesis. Several dry eye animal models, including lacrimal secretion insufficiency, evaporation, neuronal dysfunction, and environmental stress models, are related to different etiological factors. Other models may be categorized as having a multifactorial DED. In addition, there are variations in the methodological classification, including surgical lacrimal gland removal, drug-induced models, irradiation impairment, autoimmune antibody-induced models, and transgenic animals. The aforementioned models may manifest varying degrees of severity or specific pathophysiological mechanisms that contribute to the complexity of DED. This review aimed to summarize various dry eye animal models and evaluate their respective characteristics to improve our understanding of the underlying mechanism and identify therapeutic prospects for clinical purposes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhu, Inomata, Shih, Okumura, Fujio, Huang, Nagino, Akasaki, Fujimoto, Yanagawa, Miura, Midorikawa-Inomata, Hirosawa, Kuwahara, Shokirova, Eguchi, Morooka, Chen and Murakami.)

Purpose: To develop an easy-to-perform combined model in human corneal epithelial cells (HCECs) and Balb/c mice macrophages J774.A1 (MP) for preliminary screening of potential ophthalmic therapeutic substances., Methods: HCECs were exposed to different osmolarities (350-500 mOsm/L) and MTT assay was employed for cell survival and flow cytometry to assess apoptosis-necrosis and relative cell size (RCS) distribution. Effectiveness of Betaine, L-Carnitine, Taurine at different concentrations (ranging from 20 mM to 200 mM) was studied. Also, mucoadhesive polymers such as Hyaluronic acid (HA) and Hydroxypropylmethylcellulose (HPMC) (0.4 and 0.8%) were evaluated. Cells were pre-incubated with the compounds (8h) and then exposed to hyperosmotic stress (470 mOsm/L) for 16h. Moreover, anti-inflammatory activity was performed in LPS-stimulated MP., Results: Exposure to hyperosmotic solutions between 450 and 500 mOsm/L promoted the highest cell death after 16h exposures (p < 0.0001) with a drop in viability to 34.96% ± 11.77 for 470 mOsm/L. Pre-incubation with Betaine at 150 mM and 200 mM provided the highest cell survival against hyperosmolarity (66.01% ± 3.65 and 65.90% ± 0.78 respectively) while HA 0.4% was the most effective polymer in preventing cell death (42.2% ± 3.60). Flow cytometry showed that Betaine and Taurine at concentrations between 150-200 mM and 20-80 mM respectively presented the highest anti-apoptotic activity. Also, HA and HPMC polymers reduced apoptotic-induced cell death. All osmoprotectants modified RCS, and polymers increased their value over 100%. L-Carnitine 50 mM, Taurine 40 mM and HA 0.4% presented the highest TNF-α inhibition activity (60%) albeit all of them showed anti-inflammatory inhibition percentages higher than 20% CONCLUSIONS: HCECs hyperosmolar model combined with inflammatory conditions in macrophages allows the screening of osmoprotectants by simulating chronic hyperosmolarity (16h) and inflammation (24h)., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To determine the effect of discontinuing chronic topical immune modulating (IM) treatment on Schirmer tear test (STT) values in dogs with dry eye disease (DED). Methods: Serial measurements of STTs from 14 dogs (16 eyes) previously diagnosed with DED were obtained before and after discontinuation of topical IM agents. Dogs with moderate to severe DED that had been well controlled with a topical IM treatment were included. After initial assessment topical IM treatment was discontinued, but topical lubricant was continued, and STT values were obtained sequentially. A mixed-effects regression model was used to evaluate the effects of age, gender, breed, clinical score, frequency of treatment, baseline STT value, and drug type on final STT values after IM withdrawal. P  < 0.05 was considered statistically significant. Results: During the follow-up period after the IM treatment had been discontinued (136 ± 29 days), 50% of the eyes ( n  = 8) exhibited STT values that never decreased to <10 mm/min. In the other 50% ( n  = 8), STT values decreased from 15.9 ± 4.7 mm/min to 6.1 ± 0.9 mm/min. In this group, the time it took to decrease the STT to <10 mm/min was 21.1 ± 9.5 days. Severe clinical signs of DED and low baseline STT pre-IM treatment significantly affected STT post-IM treatment withdrawal ( P  < 0.05). Conclusions: The duration that a residual effect of topical IM treatment persists needs to be taken into consideration when studies are designed utilizing dogs with previous IM treatment for DED.

Purpose: The aim of this study was to explore whether prolonged and consistent face mask use might be associated with worsening of dry eye symptoms in patients with dry eye disease (DED)., Methods: Subjects with a previous diagnosis of DED. Their OSDI scores were compared with those recorded in Fall 2019 using the Wilcoxon paired test. Participants were stratified by face mask use: heavy (Group A) or standard (Group B) face mask users. Heavy use was defined as wearing any type of face mask for at least 6 hours a day, at least 5 days per week in the last 2 months., Results: 67 subjects (mean age: 45.27 ± 10.06 SD years, 40% males and 60% females). Median OSDI score in Fall 2019: 18.75. Median OSDI in Spring 2020: 20.83. The Hodges-Lehmann median difference was 2.09 (95% CI [1.05, 4.17]) (P < 0.0001). The population was then stratified into heavy and standard face mask users: Group A included heavy users (31 subjects; mean age: 42.81 ± 10.48 SD years; 35% males and 65% females), Group B included standard users (36 subjects; mean age: 47.39 ± 9.31 SD years; 44% males and 56% females). The Hodges-Lehmann median difference was 5.21 (95% CI [3.13, 7.29]) in Group A (P < 0.0001), and 1.04 (95% [0],[ 2.08]) in Group B (P = 0.0177)., Conclusion: Prolonged and consistent face mask use is associated with an increase in OSDI scores. Whether face mask use is responsible for the worsening of symptoms of DED remains to be elucidated., Competing Interests: None

Potential Dutch elm disease vector beetle species were caught with pheromone bottle traps and handpicked in 2019: in total, seven species and 261 specimens were collected. The most common was Scolytus triarmatus , but by percent, the incidence of Ophiostoma novo-ulmi was highest in Scolytus scolytus , followed by Xyleborinus saxesenii and S. triarmatus . We analysed the beetles ' DNA using PacBio sequencing to determine vector beetles of Ophiostoma novo-ulmi . Ophiostoma novo-ulmi was found on six out of seven analysed beetle species: Scolytus scolytus , S . triarmatus , S. multistriatus , S. laevis , Xyleborinus saxesenii and Xyleborus dispar . The last two beetles were detected as vectors for Ophiostoma novo-ulmi for the first time. Previous knowledge on the spread of beetles is discussed.

Purpose: Sleep is an important determinant of health and quality of life. This study aimed to clarify the association between dry eye and sleep quality using a large population-based cohort., Methods: 71,761 participants (19-94 yrs, 59.4% female) from the Lifelines cohort in the Netherlands were assessed for dry eye using the Women's Health Study Dry Eye Questionnaire. Sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI). Logistic regression was used to examine the relationship between poor sleep quality (PSQI score >5) and dry eye, while correcting for age, sex, BMI, education, income, and 51 possible confounding comorbidities, including autoimmune diseases and psychiatric disorders., Results: Overall, 8.9% of participants had dry eye. Of these, 36.4% had poor sleep quality compared to 24.8% of controls (OR 1.52 (95%CI 1.44-1.60), P < 0.0001, corrected for age and sex). After correcting for all comorbidities, dry eye was still associated with poor sleep (OR 1.20 (95%CI 1.11-1.28), P < 0.0001). This relationship was seen across all ages and sexes. Patients with dry eye scored worse on all subcomponents of the PSQI. Almost one-in-two (44.9%) persons with dry eye symptoms "often" or "constantly" had poor sleep quality. This proportion was similar to participants with sleep apnea and osteoarthritis. Additionally, increasing symptom frequency was tied to increased prevalence of poor sleep quality., Conclusions: All components of sleep quality were significantly reduced in participants with dry eye, even after correcting for comorbidities. These results indicate the substantial impact of dry eye on patients' lives, especially for those with frequent symptoms., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluated the safety and effectiveness of TearCare ® System to treat the signs and symptoms of dry eye disease (DED)., Methods: In this multicenter, prospective, post-market, exploratory, interventional trial, 58 eyes (29 subjects) received a single TearCare procedure and were assessed at baseline, post-procedure 1-week and 1-month. Effectiveness was assessed as mean change from baseline in tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), total Meibomian Gland Secretion Score (MGSS), and corneal/conjunctival staining. Adverse events (AE) and changes in visual acuity were used to asses safety., Results: The baseline TBUT of 3.7±1.1 seconds was improved by 2.6±1.6 (70%) seconds at 1-week and by 3.1±2.2 (84%) seconds at 1-month (p < 0.0001). Mean baseline OSDI of 54.9±20.2 improved by 17.9±20.9 at 1-week and 25.8±24.3 at 1-month (p < 0.001). A clinically meaningful improvement was seen in 83% of subjects as per the Miller-Plugfelder definition and 66% of subjects improved by at least 1 OSDI category. The baseline MGSS of 5.6±4.0 improved by 9.3±4.0 at 1-week and 8.8±5.8 at 1-month (p < 0.0001). Corneal and conjunctival staining improved by 1.4±2.8 and 1.2±2.9 from a mean baseline of 4.8±2.5 and 5.9±3.2, respectively. Moreover, similar trajectories of improvement were observed for subgroups of subjects stratified by severity. Subjects with more severe gland obstruction at baseline had greater improvements in TBUT and staining compared to the less severe subgroup. No device-related adverse events or significant changes in visual acuity were observed., Conclusion: These results suggest that single TearCare procedure is safe and effective in treating signs/symptoms of DED. Significant improvements were seen in all subjects (100%) in all signs and symptoms of DED within 1-week of treatment and 83% subjects experienced clinically meaningful symptom relief. Additionally, TearCare seems to be effective in treating DED associated with all severities of meibomian gland obstruction., Competing Interests: Paul Karpecki reports personal fees from Sight Sciences, outside the submitted work and is a paid consultant and speaker for the Sight Sciences, Inc. David Wirta reports grants from TearCare, during the conduct of the study; and grants from Allergan, Novaliq, Novartis, Silk Tech, and Oyster Point, outside the submitted work. Kavita Dhamdhere is an employee of Sight Sciences, Inc. The authors report no other potential conflicts of interest for this work., (© 2020 Karpecki et al.)

Purpose: Population-based cross-sectional survey in Ontario to estimate the 2016 prevalence of dry eye disease (DED) and associated risk factors among adults in Canada., Methods: We emailed the 5-Item Dry Eye Questionnaire (DEQ-5) to 124,469 Ontario adults (age ≥18 years) in the IQVIA E360 database, March-April 2017. Inclusion criteria were: ≥2 visits to an Ontario based clinic, ≥1 visits in the 1 year before the study; database record with email. DED was defined as a DEQ-5 score of >6/22. The crude prevalence by age/sex of the Ontario sample was adjusted to the 2016 Canadian population (mean age 41.0 years, 51% female). Significance of DED risk factors (age, sex, selected diseases/medical conditions and medications) was evaluated by logistic regression analysis., Results: Of the 5163 (4.1%) patients who completed the survey (59.5% female, median age, 46 years; 40.4% male, 56 years), 1135 respondents reported DED. Prevalence increased with age (p < 0.05) and was highest among those aged 55-64 years (24.7%; 95% CI, 22.1-27.3%) and lowest among those aged 25-34 years (18.4%; 95% CI, 15.9-21.0%). Prevalence was significantly higher (p < 0.001) among women (24.7%; 95% CI, 23.2-26.2%) than men (18.0%; 95% CI, 16.4-19.7%). Other risk factors were not significant. The age-/sex-adjusted Canadian DED prevalence estimate from this sample was 21.3% (95% CI, 19.8-23.2%), corresponding to ∼6.3 million people., Conclusions: Based on the Ontario sample, we estimate that >6 million Canadian adults may have DED, and that older people and females are more likely to be affected., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate 6-month treatment benefits with lifitegrast ophthalmic solution 5% in symptomatic dry eye patients., Setting: Retrospective chart analysis., Method: A retrospective chart review was conducted in 168 patients (111 females and 57 males) who presented with symptoms of chronic dry eye disease and were treated with lifitegrast 5% ophthalmic solution for 6 months. Collected symptom data included improvement of eye dryness, tearing, eye pain, fluctuation in vision, foreign body sensation, itching, grittiness, burning and contact lens intolerance if applicable. Collected clinical signs included changes in superficial punctate keratitis, corneal fluorescein staining, conjunctival hyperemia and presence of tear debris., Results: Treatment with lifitegrast ophthalmic solution 5% twice daily for 6 months significantly improved majority of dry eye symptoms reported by patients. Improvements were also observed in corneal and conjunctival staining and tear debris for most of the patients reviewed., Conclusion: Treatment with lifitegrast twice a day for 6 months improved both signs and symptoms of chronic dry eye., Competing Interests: Dr Eric Donnenfeld has been a consultant for Shire, the manufacturer of Xiidra (lifitegrast ophthalmic solution 5%). Dr Richard Najac reports personal fees from Shire outside the submitted work. Dr Eric Donnenfeld reports personal fees from Shire during the conduct of the study and personal fees from Allergan and Bausch & Lomb outside the submitted work. The authors report no other conflicts of interest in this work.

Purpose: To evaluate the safety and efficacy of topical TOP1630, a novel nonsystemic kinase inhibitor, in dry eye disease (DED)., Patients and Methods: A randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic solution TID or placebo (vehicle without active drug) was conducted in DED subjects (n=61). Key eligibility criteria consistent with enrolling a moderate to severe DED population included >6 months DED history; OSDI © score ≥18; Schirmer's test score ≤10 and ≥1 mm/5 minutes; tear film break-up time >1 and <7 seconds; and dry eye exacerbation in corneal staining and ocular discomfort in a Controlled Adverse Environment (CAE ® ). After a 7-day run-in period with placebo TID, eligible subjects were randomized to TOP1630 or placebo for 28 days. No supplemental artificial tears or rescue medication were allowed., Results: TOP1630 was safe, well-tolerated, and efficacious in treating DED symptoms and signs. No serious adverse events (AEs) or withdrawals due to treatment emergent AEs occurred. Drop comfort scores showed TOP1630 to be comfortable and comparable with placebo. Significant symptom improvements were seen for TOP1630 vs placebo for ocular discomfort ( P =0.02 post-CAE), grittiness/foreign body sensation (on four independent assessment scales, each P <0.05), worst DED symptom (diary, P =0.06), and ocular pain (VAS, P =0.03). Sign improvements were seen for total ocular surface (all regions), corneal sum, and conjunctival sum staining with TOP1630 compared with placebo (each P <0.05)., Conclusion: TOP1630 had placebo-like tolerability and produced improvements in multiple symptom and sign endpoints in both environmental and challenge settings. The emergent TOP1630 benefit-risk profile for DED treatment is highly favorable and supports further development., Competing Interests: Disclosure MT, CW, MCTF, AR, and SW are employees of TopiVert Pharma Limited. GO, JDS, and AD are consultants of TopiVert Pharma Limited. GO is an employee of Ora Inc. GT reports grants from TopiVert Pharma Limited, during the conduct of the study; grants from Oculeve, Allergan, ReGentree, Hanall, Mimetogen, AB2Bio, Aldeyra, Axerovision, BRIM, Diagnostear, Novaliq, Oyster point and grants, personal fees from Ora, Inc., outside the submitted work. MCTF reports personal fees from TopiVert Pharma Limited, outside the submitted work. MCTF has a patent US9499486 issued. JDS reports grants from TopiVert Pharma Limited, during the conduct of the study; grants from Allergan, Shire, Bausch & Lomb, Sun Pharma and Novaliq, outside the submitted work. The authors report no other conflicts of interest in this work.

Objectives: Dry eye disease (DED) is a complex multifactorial condition of the ocular surface characterized by symptoms of ocular discomfort, irritation, and visual disturbance. Data previously reported from this study showed an increase in prevalence and incidence of DED with age and over time. The objective of this study was to compare the ranking of DED prevalence among other ocular conditions that led patients to seek eye care., Methods: In this population-based study using the US Department of Defense Military Health System claims database of >9.7 million beneficiaries, indicators of DED and other ocular conditions were analyzed over time. The overall prevalence (2003-2015) and annual incidence (2008-2012) of DED and other ocular conditions were estimated using an algorithm based on two independent indicators derived from selected diagnostic and procedure codes and prescriptions for cyclosporine ophthalmic emulsion for DED and diagnostic codes for the indicators of other common ocular conditions., Results: In 2003-2015, the most common ocular conditions were disorders of refraction and accommodation (25.84%), cataracts (17.14%), glaucoma (7.27%), disorders of the conjunctiva (6.76%), other retinal disorders (5.94%), and DED (5.28%). DED was the fifth most prevalent ocular condition in women (7.78%) and ninth most prevalent in men (2.96%). In 2012, DED had the third highest annual incidence (0.87%), behind disorders of refraction/accommodation (1.87%) and cataracts (1.50%)., Conclusion: This study provided further epidemiologic evidence for DED as a commonly occurring condition that drives patients to seek treatment., Competing Interests: Disclosure IÖS is an employee of and owns stock/stock options in Takeda. IP and AG are employees of Analysis Group, Inc., which has received consultancy fees from Shire, now a part of Takeda. AME is an employee of Health ResearchTx LLC, which has received consultancy fees from Shire, now a part of Takeda. RD is a consultant for Aldeyra Therapeutics, Dompé, Kala Pharmaceuticals, and Takeda, and reports receiving grant support from Allergan and the National Eye Institute. JLB reports no conflicts of interest in this work.

Introduction: Ocular surface disease (OSD) is a highly prevalent symptomatic condition caused by dry eye disease (DED), intrinsic, environmental, or iatrogenic causes. It affects patient's visual function and quality of life. Its pathophysiology is centered on tear hyperosmolarity, inflammation, and epithelial damage. Current management is suboptimal and includes artificial tear supplementation and short-term use of topical steroids in severe cases. The recent approval of cyclosporine 0.1% has transformed management strategies of severe DED and moderate-to-severe OSD. Areas covered: This review summarizes existing information on the efficacy, safety, and tolerability of the new cyclosporine 0.1% formulation. Expert opinion: Topical cyclosporine A 0.1% represents a promising, novel medication for the management of DED, Meibomian gland dysfunction, and inflammatory OSD. It is primarily beneficial for those patients requiring topical immunomodulatory therapy. This topical formulation also has the potential to meaningfully improve the management of moderate-to-severe glaucoma therapy-related OSD. Currently there is limited published clinical data concerning the efficacy of topical cyclosporine. There are, however, theoretical advantages when comparing this cyclosporine formulation with other established commercial preparations. Future research is needed to delineate the precise role and value of this medication.