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Hepatitis delta virus (HDV) has been detected in the minor salivary gland (MSG) tissue of Sjögren's disease (SjD) patients in the absence of a hepatitis B virus (HBV) coinfection. Previous research has shown that HDV antigen (HDAg) expression can trigger an SjD-like phenotype in vivo, demonstrating a potential cause-and-effect relationship. We hypothesize that if HDV plays a role in the development of SjD, then HDV profiles may be correlated with disease manifestations. This retrospective study characterized HDV in a cohort of 48 SjD MSG samples collected between 2014 and 2021. Analyses of HDAg expression, including cell type and subcellular localization, in situ hybridization of HDV RNA, and comparative analyses with associated SjD and viral hepatitis clinical features, were conducted. HDAg was detected in MSG acinar, ductal, myoepithelial, and adipose cells and localized with the nuclei, cytoplasm, and mitochondria. In situ hybridization detected HDV genomic RNA localization in the MSG nuclei. A significant negative correlation was found between HDAg intensity and focal lymphocytic inflammation and in patients with both anti-SSA/Ro-52 and anti-SSA/Ro-60. In analyzing autoimmune disease comorbidities with SjD, it was found that SjD patients diagnosed with autoimmune thyroiditis and/or hypothyroidism were significantly more represented in the high HDAg intensity group compared to the negative and moderate HDAg intensity groups. No significant associations were detected between MSG-localized HDAg and liver enzymes or an evident HBV coinfection. This study has further confirmed that there is a nonhepatic reservoir for chronic HDV persistence in SjD-affected salivary gland tissue in a third independent SjD patient cohort. In addition, this study describes the unique colocalization of HDAg with mitochondria. The detection of HDV antigen and sequence within SjD-affected salivary gland tissue, and in the absence of an evident current or past HBV coinfection, warrants further investigation. [ABSTRACT FROM AUTHOR]

aimi,5 Yahya Al-Najmi61Ophthalmology Department, King Faisal Medical Complex, Taif, Saudi Arabia; 2Ophthalmology Department, Alhada Military Hospital, Taif, Saudi Arabia; 3Ophthalmology Department, Jeddah Eye Hospital, Jeddah, Saudi Arabia; 4Ophthalmology Department, Asir Central hospital, Abha, Saudi Arabia; 5Ophthalmology Department, College of Medicine, Majmaah University, Majmaah, Saudi Arabia; 6Ophthalmology Department, Saggaf Eye Center, Jeddah, Saudi ArabiaCorrespondence: Yahya Al-Najmi, Ophthalmology Department, Saggaf Eye Center, Abdullah Salman St., Al Faiha'a Dist., P.O. Box: 31903, Jeddah, 21418, Saudi Arabia, Tel +966 564844281, Email [email protected] Purpose: To estimate the prevalence and determinants of Ocular Surface Disease Index (OSDI) score based dry eye disease (DED) among the adult urban population of four cities located at high altitudes in Southwest Saudi Arabia.Methods: This cross-sectional survey was held in 2023. OSDI questionnaire was used to collect the responses of the adult participants. The score was further graded into none, mild, moderate, and severe DED to estimate age-sex-adjusted DED prevalence. The OSDI score was correlated to demographic (age group, gender, education, occupation, city) and risk factors like smoking and co-morbidities.Results: Of the 401 adults, 388 (response rate of 97.8%) participated. The age-sex-adjusted prevalence of mild, moderate, and severe DED was 21.7%, 13.1%, and 32%, respectively. The median ODSI score was 22.9 [Interquartile range (IQR) 10.4; 47.9)]. The score was significantly higher in females (Mann–Whitney U-test P = 0.038), residents of Taif city (KW P = 0.05), those with primary/middle school education (Kruskal–Wallis P = 0.004), comorbidities like hypertension, asthma (KW P < 0.001) and risk factors like past refractive surgeries, arthritis (KW P = 0.013). Education status (P < 0.001) [B = − 9.0 95%] and presence of comorbidity (P = 0.022), [B = − 0.823] were significant predictors of DED.Conclusion: The prevalence of DED and severe grade was high. The level of education and presence of comorbidities significantly influenced DED in the adult urban Saudi population of cities at high altitudes. [ABSTRACT FROM AUTHOR]

Purpose: Our study aimed to make a bibliometric analysis on Sjögren's syndrome-related dry eye disease (SS-DED), explore its potential research hotspots, and provide critical information for future research interest and undeveloped topics in this field, which can benefit clinicians and researchers. Methods: We extracted all publications relating to SS-DED from 2003 to 2022 from the Web of Science Core Collection database. Original articles and reviews in English were included. The contributions of different countries, institutions, journals, and authors were compared, and the research hotspots were visualized for network analysis through GraphPad Prism, CiteSpace, and VOSviewer. Results: We enrolled a total of 987 publications. The United States contributed the most publications (281, 28.5%), followed by China (157, 15.9%) and Japan (80, 8.11%). Publications from the United States were cited more frequently (13,060 citations), with the highest H-index of 57. China ranked second in the total number of publications, the papers were not cited frequently (3790 citations), and the H-index ranked second (H-index = 31). PLoS One (32, 3.24%) published the most papers, and the University of California system had the highest number of publications (45, 4.56%). Bootsma H from the Netherlands published the most papers. The trend of research hotspots evolved mainly from the basic manifestation to pathogenesis and treatment of SS-DED and paid more attention to distinguishing SS-DED from that dry eye disease without SS. Conclusions: Based on the bibliometric, co-citation, and network analyses in this study, we obtained the annual publications and citations, the growth trends of publications, the productivity of countries, organizations, journals, and authors, high-quality publications, and the emerging hotspots of SS-DED, which may open new doors for promising research directions. [ABSTRACT FROM AUTHOR]

Professor John S. Greenspan died on March 31, 2023. He was a renowned and accomplished academic, dentist/scientist, pathologist, and administrator who made sustained and significant international impacts on numerous fields over half a century. John was arguably best known for his work with his wife, Dr. Deborah Greenspan, on the oral aspects of AIDS and the role of viruses in oral epithelial and salivary gland lesions. He had a lifelong interest in Sjögren's syndrome, culminating in the leadership of the Sjögren's International Collaborative Clinical Alliance. He was also widely recognized as one of the leading investigators into the understanding of oral mucosal diseases, including recurrent aphthous stomatitis. He and his colleagues' major contributions to HIV research and care included the discovery of the oral lesion "hairy leukoplakia," its etiological association with Epstein–Barr virus, and other oral lesions in the natural history of HIV disease. In recent years, John turned his attention to global oral health inequalities, helping to establish the International Association for Dental Research's Global Oral Health Inequalities Research Network and serving as its first president. He led many organizations with humble authority, knowledge, wit, and wisdom and mentored colleagues from all over the world, especially from lower- and middle-income countries. John leaves a very special legacy based on example and scientific curiosity, and his work has not only made a lasting impact on his colleagues but also translated to abiding benefit for patients. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye disease (DED) is a growing global health problem with a significant impact on the quality of life of patients. While neurosensory abnormalities have been recognised as a contributor to DED pathophysiology, the potential role of in vivo corneal confocal microscopy in detecting nerve loss or damage remains unclear. This systematic review with meta‐analysis (PROSPERO registered CRD42022381861) investigated whether DED has an impact on sub‐basal corneal nerve parameters. Methods: PubMed, Embase and Web of Science Core Collection databases were searched from inception to 9 December 2022. Studies using laser scanning confocal microscopy to compare corneal nerve parameters of DED with healthy eyes were included. Study selection process and data extraction were performed by two independent members of the review team. Results: Twenty‐two studies with 916 participants with DED and 491 healthy controls were included, with 21 of these studies included in subsequent meta‐analyses. There was a decrease in total corneal nerve length (−3.85 mm/mm2; 95% CI −5.16, −2.55), corneal main nerve trunk density (−4.81 number/mm2; 95% CI −7.94, −1.68) and corneal nerve branch density (−15.52 number/mm2; 95% CI −27.20, −3.84) in DED eyes compared with healthy eyes, with subgroup analysis demonstrating that these differences were more evident in studies using NeuronJ software, a semi‐automated procedure. While this review found evidence of loss of corneal nerve parameters in eyes with DED compared with healthy controls, particularly with the use of a semi‐automated image analysis method, it is evident that there is substantial heterogeneity between studies in terms of corneal nerve imaging methodology. Conclusions: Standardisation is required in terms of terminology and analysis, with more research needed to potentially improve the clinical applicability and practicality of corneal nerve imaging. Further investigation is also required to confirm the diagnostic accuracy of this imaging modality and its potential for monitoring DED treatment efficacy. [ABSTRACT FROM AUTHOR]

Introduction: While optical coherence tomography (OCT) measurements of the lower tear meniscus height (LTMH) have been reported in adults, here we obtained LTMH measurements through Fourier Domain OCT in healthy children and compared these with values obtained in healthy adults. Methods: Participants were children 7–17 years of age and a control group of adults 20–40 years of age. Inclusion criteria were no abnormal eye conditions or the use of contact lenses. Candidates who fulfilled the TFOS DEWS II criteria for dry eye disease (DED) were excluded. All subjects underwent LTMH measurement (OCT Spectralis) and tests for non‐invasive tear break‐up time and ocular surface staining. Participants also completed the ocular surface disease index questionnaire. Results: A total of 86 children and 27 adults were included. Mean LTMH values in the children and adult groups were 217.40 ± 71.40 μm and 225.0 ± 54.86 μm, respectively; p = 0.53. However, 59.3% of the children had an LTMH ≤210 μm suggestive of DED, compared with only 33.3% of adults (p = 0.02). For the children, no significant differences in LTMH were observed with sex or for those more or less than 12 years of age. Conclusions: Optical coherence tomography‐derived LTMH measurements were obtained in healthy children. While values were similar in children and adults, a greater proportion of children had an LTMH compatible with a diagnosis of DED. More studies in different paediatric populations are required to establish a complete set of normative LTMH measurements. [ABSTRACT FROM AUTHOR]

The Ocular Surface Disease Index (OSDI) is the most frequently used dry eye disease (DED) questionnaire, and the Symptom Assessment iN Dry Eye (SANDE) is the simplest and quickest to apply. We analyze the correlation and level of agreement between these two questionnaires in a large DED heterogeneous population to evaluate their performance and potential interchangeability. Prospective, multicenter longitudinal survey-based study performed on patients diagnosed with DED by 99 ophthalmologists from 20/32 Mexican states. Questionnaires were applied in two consecutive visits to analyze the correlation between OSDI and SANDE to evaluate patients with DED clinically. Level of agreement was evaluated with Bland-Altman analysis, and internal consistency of instruments was evaluated individually and combined with Cronbach's alpha index. 3421 patients studied: 1996 (58.3%) women and 1425 (41.7%) men, aged 49.5 ± 15.4 years; 995 (29.1%) patients had aqueous-deficient, 1086 (31.7%) evaporative, and 1340 (39.2%) mixed DED subtypes. Normalized baseline scores were 53.7 (OSDI) and 54.1 (SANDE). After 36.3 ± 24.4 days between visits, scores were reduced to 25.2 (OSDI) and 21.8 (SANDE) points (p <.001). A positive correlation between questionnaires was found at baseline (R = 0.592; p <.001), follow-up (R = 0.543; p <.001) and change between visits (R = 0.630; p <.001). Using both questionnaires together improved the overall reliability of symptom evaluation at baseline (α = 0.7), follow-up (α = 0.7), and both (α = 0.7), compared to individual application (OSDI α = 0.5, SANDE α = 0.6)—the same improvements applied to all DED subtypes. Bland-Altman analysis revealed a differential bias of -0.41% at baseline and +3.6% at follow-up visits between OSDI and SANDE. We validated the correlation (high precision) between questionnaires in a large-scale population, demonstrating improved reliability (high accuracy) in evaluating DED when used together, challenging their interchangeable use. These results open a venue to improve recommendations toward a more precise and accurate diagnostic and therapeutic evaluation of DED by using OSDI and SANDE concurrently. [ABSTRACT FROM AUTHOR]

Ophthalmic inflammatory diseases, including conjunctivitis, keratitis, uveitis, scleritis, and related conditions, pose considerable challenges to effective management and treatment. This review article investigates the potential of advanced nanomaterials in revolutionizing ocular anti-inflammatory drug interventions. By conducting an exhaustive analysis of recent advancements and assessing the potential benefits and limitations, this review aims to identify promising avenues for future research and clinical applications. The review commences with a detailed exploration of various nanomaterial categories, such as liposomes, dendrimers, nanoparticles (NPs), and hydrogels, emphasizing their unique properties and capabilities for accurate drug delivery. Subsequently, we explore the etiology and pathophysiology of ophthalmic inflammatory disorders, highlighting the urgent necessity for innovative therapeutic strategies and examining recent preclinical and clinical investigations employing nanomaterial-based drug delivery systems. We discuss the advantages of these cutting-edge systems, such as biocompatibility, bioavailability, controlled release, and targeted delivery, alongside potential challenges, which encompass immunogenicity, toxicity, and regulatory hurdles. Furthermore, we emphasize the significance of interdisciplinary collaborations among material scientists, pharmacologists, and clinicians in expediting the translation of these breakthroughs from laboratory environments to clinical practice. In summary, this review accentuates the remarkable potential of advanced nanomaterials in redefining ocular anti-inflammatory drug therapy. We fervently support continued research and development in this rapidly evolving field to overcome existing barriers and improve patient outcomes for ophthalmic inflammatory disorders. [ABSTRACT FROM AUTHOR]

Tear film hyperosmolarity plays a core role in the development of dry eye disease (DED) by mediating the disruption of ocular surface homeostasis and triggering inflammation in ocular surface epithelium. In this study, the mechanisms involving the hyperosmolar microenvironment, glycolysis mediating metabolic reprogramming, and pyroptosis were explored clinically, in vitro, and in vivo. Data from DED clinical samples indicated that the expression of glycolysis and pyroptosis-related genes, including PKM2 and GSDMD, was significantly upregulated and that the secretion of IL-1β significantly increased. In vitro, the indirect coculture of macrophages derived from THP-1 and human corneal epithelial cells (HCECs) was used to discuss the interaction among cells. The hyperosmolar environment was found to greatly induce HCECs' metabolic reprogramming, which may be the primary cause of the subsequent inflammation in macrophages upon the activation of the related gene and protein expression. 2-Deoxy-d-glucose (2-DG) could inhibit the glycolysis of HCECs and subsequently suppress the pyroptosis of macrophages. In vivo, 2-DG showed potential efficacy in relieving DED activity and could significantly reduce the overexpression of genes and proteins related to glycolysis and pyroptosis. In summary, our findings suggested that hyperosmolar-induced glycolytic reprogramming played an active role in promoting DED inflammation by mediating pyroptosis. [ABSTRACT FROM AUTHOR]

Background: Dupilumab‐associated ocular surface disease (DAOSD) is frequently reported as side effect in atopic dermatitis (AD) patients. Therefore, the aim of this study was to investigate the frequency and severity of DAOSD, ophthalmic treatment response and to learn more about the effect of dupilumab on conjunctival goblet cells (GC). Methods: This prospective study included dupilumab‐treated AD patients between February 2020 and June 2022 from the University Medical Centre Utrecht. Patients were examined by an ophthalmologist and a dermatologist before start (baseline), and after 4 and 28 weeks of dupilumab treatment. Ophthalmological examination was assessed by the Utrecht Ophthalmic Inflammatory and Allergic disease (UTOPIA) score. DAOSD was defined as an increase in UTOPIA score of ≥3 points from baseline. To quantify conjunctival GCs and to investigate the percentage of Cytokeratin 19 (CK19)‐CD45‐Mucin 5 AC (MUC5AC)+ cells, conjunctival impression cytology samples were analysed. Results: Ocular surface disease (OSD) was present in 91.3% (n = 63/69) patients at baseline. DAOSD was observed in 28.9% (n = 20/69) patients, in whom GC numbers remained stable and the percentage of CK19‐CD45‐MUC5AC+ cells decreased at onset of DAOSD compared with baseline. After 28 weeks of dupilumab treatment, DAOSD was seen in 14.5% (n = 10/69) patients. Of the 85.5% (n = 59/69) patients without DAOSD or with controlled DAOSD at Week 28, 40.7% (n = 24/59) patients received anti‐inflammatory ophthalmic drugs. Conclusions: Ocular surface disease is common in moderate‐to‐severe AD patients before starting dupilumab. During treatment with dupilumab DAOSD severity improves with early ophthalmic treatment. The decrease in percentage of CK19‐CD45‐MUC5AC+ cells during dupilumab treatment suggests an impairment of the GC function due to dupilumab treatment. [ABSTRACT FROM AUTHOR]

Many candidate drugs for dry eye disease (DED) have been assessed over the years in pursuit of demonstrating efficacy in both signs and symptoms. However, patients with DED have very limited treatment options for management of both signs and symptoms of DED. There are several potential reasons behind this including the placebo or vehicle response, which is a frequent issue observed in DED trials. A high magnitude of vehicle response interferes with the estimation of a drug's treatment effect and may lead to failure of a clinical trial. To address these concerns, Tear Film and Ocular Surface Society International Dry Eye Workshop II taskforce has recommended a few study design strategies to minimize vehicle response observed in DED trials. This review briefly describes the factors that lead to placebo/vehicle response in DED trials and focuses on the aspects of clinical trial design that can be improved to mitigate vehicle response. In addition, it presents the observations from a recent ECF843 phase 2b study, wherein the study design approach consisted of a vehicle run-in phase, withdrawal phase, and masked treatment transition, and led to consistent data for DED signs and symptoms and reduced vehicle response post randomization. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to investigate the applicability of lower lid margin thickness (LLMT) measurements in adults with and without meibomian gland dysfunction (MGD) by optical coherence tomography (OCT) and keratograph. Methods: This is a cross-sectional, observational study. A hundred and eight volunteers aged 20 to 79, including 68 MGD patients and 40 normal subjects, were recruited. Using OCT and keratograph to measure the LLMT from the posterior lash line to anterior edge or outer edge of the tear meniscus was separately performed two times by the same person. Results: The mean age of normal and MGD subjects was 50.5 ± 14.2 years and 55.8 ± 15.5 years, respectively. The LLMT with OCT and keratograph in MGD patients was significantly greater than that in normal subjects (1.06 ± 0.27 and 1.03 ± 0.25 mm vs. 0.90 ± 0.20 and 0.86 ± 0.16 mm, respectively). In both normal and MGD subjects, the tear meniscus height and LLMT with OCT were both greater than that with keratograph (P < 0.05), and intraclass correlation coefficient (ICC) demonstrated a good agreement in the LLMT measurements between two devices (ICC = 0.83 and 0.79, respectively). Additionally, the LLMT in MGD patients was appeared to be positively correlated with meiboscore (rs = 0.37, P = 0.002). Conclusions: The OCT and keratograph were two reliable tools in the LLMT measurements, which may have potential applications for diagnosis and evaluation of MGD. Furthermore, we found that the LLMT measured by OCT was greater than that measured by keratograph. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a very common ocular condition with a considerable socioeconomic impact affecting patient's visual function and quality of life. Currently, thanks to the better knowledge on DED pathophysiology, therapeutical approaches are focused on the primary core mechanisms of DED. Furthermore, new drugs and compounds are being explored in the light of recent findings concerning unique disease-related pathways. The purpose of this review is to stress DED pathogenesis, addressing its vicious cycle, and highlighting the cutting-edge drug therapy approaches under development. A literature search on the PubMed and Scopus databases was carried out. The database search strategy was formulated around the term 'dry eye disease' and other terms regarding its pathophysiology and therapeutic strategy. Additional search was conducted on ClinicalTrials.gov for unpublished results and ongoing clinical trials. The primary approaches used for DED include lifestyle, environmental changes, tears supplementation, and control of the eyelids and ocular surface inflammation. In selected cases, medical therapy could benefit by technological device-based management. Due to the complexity of DED and the continuous growth of disease prevalence and patients' unmet needs, new therapeutic approaches focused on its pathogenesis are currently under investigation, while others are pending approval. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-to-lymphocyte ratio (NLR) and immunoglobulin A (IgA) level are commonly used as biomarkers for inflammation. Patients with type 2 diabetes (T2D) may experience an imbalance of tear film and inflammation, which can result in dry eye disease (DED). This study aimed to assess the levels of IgA and explore its correlation with the NLR as potential inflammatory biomarkers for dry eye disease in patients with T2D. Methods: A retrospective study was conducted at the cornea clinic and diabetes centre of King Abdulaziz Medical City (Jeddah, Saudi Arabia). The study included patients with DED and the number of available T2D-DED patients determined the sample size. Neutrophil, lymphocyte, IgA and CRP (C-reactive protein) laboratory values were obtained from medical records and correlational analyses were performed. Results: The study included 85 patients with an average age of 54 ± 14.4 years for the DED group (n=32) and 62 ± 13.9 years for the T2D-DED group (n=53). The age difference between the two groups was statistically significant (p 0.0001). The NLR values of the T2D-DED and DED groups were 3.203 ± 0.66 and 2.406 ± 0.46, respectively, with no significant difference (p<0.285). Similarly, there were no significant differences in neutrophil and lymphocyte values between the two groups. The IgA levels showed no significant variation between T2D-DED and DED groups (p<0.364). Spearman’s correlation analysis in the DED group showed a significant negative correlation between IgA and lymphocyte (p=0.011; r= - 0.471) values and significant positive correlations between IgA and neutrophil (p=0.014; r=0.309) and NLR (p=0.052; r= - 0.283) values. In the T2D-DED group, a significant correlation was found between IgA and CRP values (p=0.032; r=0.33). Conclusion: Although diabetic patients may exhibit higher levels of NLR and IgA that correlate with disease severity, our study did not find significant differences in NLR and IgA values between the two groups. These findings may guide future research and enhance understanding of the disease’s underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Sjögren's Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz's disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in middle-aged female, and the dry eyes could be presented in both of them with different degree. The MD patients are characterized by symmetrical swelling of the lacrimal glands which also can occur in the early stage of SS. And the imaging findings between early stage of SS and MD are lack of specificity. Therefore, SS and MD have similarities in the clinical manifestations, imaging and pathological findings and are confused in diagnosis. Case presentation: A 51-year-old female patient presented with bilateral swelling of the upper eyelids for 2 years. She also reported having dry mouth and dry eyes which could be tolerated. The Schirmer's test result is positive and the laboratory tests indicate serum total IgG increased. In the bilateral lacrimal gland area could palpate soft masses. The orbital magnetic resonance imaging (MRI) examination showed bilateral lacrimal gland prolapse. While the histopathological result was considered as MD. The immunohistochemical (IHC) staining results were positive for IgG and negative for IgG4. To clarify the diagnosis, SS-related laboratory tests were performed: anti-SSA antibody (+++), anti-SSB antibody (+++), anti-Ro-52 antibody (+++). With a comprehensive consideration, the final diagnosis was SS. Conclusion: When the clinical manifestations are atypical, it is necessary to pay attention to the differential diagnosis of SS and MD. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a challenge in ophthalmology. Rat models represent valuable tools to study the pathophysiology and to develop novel treatments. A major challenge in DED research is detecting multiple biomarkers in a low tear volume sample. Multiplex immunoassays for DED rat research are missing. We have developed a multiplex electrochemiluminescence immunoassay (ECLIA) to detect three biomarkers for DED: MMP-9, IL-17 and ICAM-1. Tears, used as matrix, were collected from six healthy Wistar rats. Assays were run based on the U-Plex Meso Scale Diagnostics (MSD) platform, by two independent operators according to the EMA guideline on bioanalytical method validation. Linear mixed, regression models were fit to perform the statistical analysis on the range of concentrations for the chosen analytes. During optimization, it has observed that incubation time, temperature and agitation affected the robustness of the protocol. ECLIA optimum conditions include the use of antibodies at 0.5 µg/ml concentration and 1 h incubation at room temperature with shaking. Precision met the acceptance criteria in the chosen range: 1062–133 pg/ml for ICAM-1, 275–34.4 pg/ml for IL-17, 1750–219 pg/ml for MMP-9. Accuracy and linearity were acceptable for a broader range. This is the first report of a validated ECLIA that allows measurements of three relevant DED biomarkers in rat tear fluids. [ABSTRACT FROM AUTHOR]

Inflammation is a key factor in the pathogenesis of dry eye disease (DED). We aimed to investigate the role of microRNA-146a (miR-146a) in regulating corneal inflammation in a mouse model of benzalkonium chloride (BAC)-induced dry eye and the TNF-α-induced NF-κB signaling pathway in human corneal epithelial cells (HCECs). A mouse model of dry eye was established by administering with BAC to BALB/c mice, and the expression of TNF-α, IL-1β, IL-6, IL-8, cyclooxygenase 2 (COX2), interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor-associated factor 6 (TRAF6) in the corneas of dry eye model mice was significantly increased; this was accompanied by the upregulation of miR-146a and activation of the NF-κB pathway. In vitro, TNF-α induced miR-146a expression in HCECs, while the NF-κB inhibitor SC-514 reduced the expression of miR-146a. Overexpression of miR-146a decreased the expression of IRAK1 and TRAF6, which have been identified as targets of miR-146a. Furthermore, overexpression of miR-146a suppressed NF-κB p65 translocation from the cytoplasm to the nucleus. Moreover, overexpression of miR-146a attenuated the TNF-α-induced expression of IL-6, IL-8, COX2 and intercellular adhesion molecule 1 (ICAM1), while inhibition of miR-146a exerted the opposite effect. Our results suggest that miR-146a mediates the inflammatory response in DED. MiR-146a negatively regulates inflammation in HCECs through the IRAK1/TRAF6/NF-κB pathway, and this may serve as a potential therapeutic approach for the treatment of DED. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED), Meibomian gland dysfunction (MGD), and Sjögren's syndrome dry eye disease (SS-DED) are eye dryness conditions that show significant overlap in various symptoms of ocular discomfort. The aim of this study was to qualitatively explore the patient experience and evaluate content validity of the newly developed Dry Eye Disease Questionnaire (DED-Q). Methods: Semi-structured interviews were conducted with 61 US adults who reported experiencing ocular symptoms due to their physician-confirmed primary diagnosis of DED (n = 21), MGD (n = 20), or SS-DED (n = 20). The open-ended concept-elicitation phase was followed by cognitive debriefing (CD) of the DED-Q to evaluate participants' understanding and relevance of the instructions, items, response options, and recall periods. Interviews were also conducted with eight specialist healthcare professionals to assess clinical relevance of the concepts included. Verbatim interview transcripts were analyzed using thematic analysis in ATLAS.ti v8 software. Results: A total of 29 symptoms and 14 impacts on quality of life were reported across participant interviews. Primary ocular symptoms reported included eye dryness (n = 61/61; 100%), eye irritation (n = 55/61; 90%), eye itch (n = 54/61; 89%), burning sensation (n = 52/61; 85%), and foreign body sensation (n = 51/61; 84%). The most impacted aspects of daily life were using digital screens (n = 46/61; 75%), driving (n = 45/61; 74%), working (n = 39/61; 64%), and reading (n = 37/61; 61%). CD findings showed most participants had good understanding of DED-Q items and confirmed most concepts were relevant to the lived experience of their condition. Aside from few minor changes to the items and examples to facilitate more accurate interpretation, the proposed instruction wording was modified for various symptom and impact modules to encourage participants to focus only on dry eye vision problems. Conclusions: This research identified multiple prevalent symptoms and impacts of DED, MGD, and SS-DED, most of which were similar across the conditions. The DED-Q was confirmed to be a content-valid PRO measure suitable for use in clinical studies to assess the patient experience of DED, MGD, and SS-DED. Future work will focus on evaluating the psychometric properties of the DED-Q for use as an efficacy endpoint in clinical trials. Plain English summary: Dry Eye Disease (DED), Meibomian Gland Dysfunction (MGD), and Sjögren's Syndrome Dry Eye Disease (SS-DED) are conditions related to dryness of the eye. There is no suitable patient-reported outcome (PRO) measure available for use across the three conditions. Interviews were conducted with 61 participants with any of the three conditions to understand the symptoms they experience and their impact on daily life. The findings were used to refine the content of a new PRO measure, the Dry Eye Disease Questionnaire (DED-Q). To evaluate the suitability of the DED-Q, participants were also asked to complete each item of the DED-Q during the interview and share their understanding of the item wording, response options and the recall period. Interviews were also conducted with eight healthcare professionals (HCPs). The main symptoms reported by the patients across three conditions were eye dryness, eye irritation, eye itch, burning sensation, and foreign body sensation. The symptoms caused difficulties in performing activities such as using digital screens, driving, working, and reading. Almost all participants demonstrated good understanding of the items on the DED-Q and found them to be relevant to their experience of their condition. The HCPs also confirmed that the concepts covered in the DED-Q were relevant to assess the participant experience across these conditions. Next steps will involve a more detailed analysis of the measurement properties of the DED-Q to confirm its usefulness in supporting primary or secondary endpoints in clinical trials. [ABSTRACT FROM AUTHOR]

The global prevalence of dry eye disease (DED) ranges between approximately 5% and 50% and engenders a substantial socioeconomic burden. In the past decade, an unprecedented collaboration between industry and the vision sciences has spawned numerous potential therapeutic agents for DED. Many of these options possess novel mechanisms of action, potentially allowing clinicians to better tailor their treatment of patients suffering from DED. This review covers several specific pipeline drugs, such as lotilaner, perfluorohexyloctane, and cyclosporine A, along with broader drug classes such as reactive aldehyde species inhibitors, keratolytics, and mitochondrial reactive oxidative species scavengers. This review will summarize the promise and efficacy of upcoming dry eye disease treatments through the lens of data from USA-based phase II and phase III clinical trials. [ABSTRACT FROM AUTHOR]

A 69-year-old woman with bilateral primary open-angle glaucoma who underwent cataract extraction with intraocular lens implantation and excisional goniotomy with the Kahook Dual Blade (KDB; New World Medical, Rancho Cucamonga, CA, USA) in both eyes one year prior was referred for evaluation of significant visual acuity loss and pain in the left eye. On initial examination, intraocular pressure in the left eye was 3 mmHg and slit lamp examination revealed normal anterior chamber depth. Gonioscopy revealed a cyclodialysis cleft that was confirmed by anterior segment optical coherence tomography. Prominent chorioretinal folds suggestive of long-standing hypotony maculopathy were observed during fundoscopic examination. The cyclodialysis cleft, thought to be created inadvertently during the KDB goniotomy, resolved after three sessions of argon laser photocoagulation and the patient's symptoms and visual acuity partially improved. [ABSTRACT FROM AUTHOR]

Background: Environmental and epidemiological factors increase the risk of dry eye in Saudi Arabia, but most studies have limited generalizability. Objective: To determine the prevalence of dry eye disease (DED) among adults across Saudi Arabia and the associated risk factors. The secondary objective was to estimate the economic burden of DED by calculating lubricant usage and its annual costs. Methods: This cross-sectional study invited adults from across Saudi Arabia to complete a questionnaire that collected data regarding demographics, symptoms related to DED, previous diagnosis of DED, use of contact lenses, and use of eye lubricants. Results: A total of 2042 responses were received, of which 784 (38.4%) respondents had previously been diagnosed with DED and 752 (36.8%) were symptomatic but undiagnosed. Between the DED diagnosed and symptomatic-undiagnosed groups, a significant difference was found in terms of age (P < 0.001), gender (P = 0.002), presence of diabetes mellitus (P = 0.004), smoking status (P = 0.007), duration of electronic screen use (P = 0.05), number of ocular complaints (P < 0.001), and frequency of lubricants use (P < 0.001). Between the DED-diagnosed and non-DED groups, significant differences were found in terms of age (P < 0.001), gender (P < 0.001), presence of diabetes mellitus (P = 0.001), allergy (P = 0.001), autoimmune disease (P = 0.005), smoking status (P < 0.001), and history of refractive surgery (P < 0.001). The mean estimated annual cost of using lubricating agents was SAR 328.2 ± 210.3 (USD 87.5 ± 56.1), and this was significantly higher in the diagnosed group (P = 0.01) than the symptomatic-undiagnosed group. Conclusions: The prevalence of DED is high among adults in Saudi Arabia. High-risk population include elderly, female, and using electronic screens for >2 hours/day. [ABSTRACT FROM AUTHOR]

Distinguish between EDE severity levels by analysing the MGLA, conjunctival hyperemia and corneal staining. One hundred participants were recruited based on OSDI, TO, TFBUT, TMH, and LLP to be categorised as healthy (Group 1) or EDE (Group 2). Group 2 was divided into Group 2A (mild symptoms), 2B (moderate), and 2C (severe). MGLA, conjunctival hyperemia, and corneal staining were measured. Positive correlation between MGLA, conjunctival hyperemia, and corneal staining were found (all r ≥ 0.221, p ≤ 0.027). Significant differences were found: MGLA between Group 1 vs. 2C and 2C vs. 2A or 2B; conjunctival hyperemia between Group 1 vs. 2A, 2B or 2C; corneal staining between Group 1 vs. 2B or 2C and 2A vs. 2B or 2C (all p ≤ 0.049). Severe EDE participants have higher MGLA, conjunctival hyperemia, and corneal staining values than healthy, mild, or moderate EDE participants. [ABSTRACT FROM AUTHOR]

In the recent years, multiscale fibres have gained widespread attention for use in diverse biomedical applications. With the technological advancements in electrospinning technique, the dimensions of the multiscale fibres can be tailored to match the desired requirements of the target tissues and organs. These fibres combining the unique properties of nano- and microfibres can be fabricated several techniques. The engineered multiscale fibrous scaffolds are being utilised to deliver growth factors and cells of interest, thereby, aid in tissue regeneration. The elastic modulus of the multiscale fibrous scaffolds can be enhanced by introducing biomaterials like multilayer carbon nanotubes (MCNT), nanoclay, nanohydroxyapatite (n-HAp), and graphene oxide (GO). Moreover, studies on bone, cartilage, cardiovascular and liver tissue engineering have revealed that the multiscale fibrous scaffolds are capable of restoring the microarchitecture of the extracellular matrix (ECM). The current chapter focuses on some of the fabrication techniques which include coaxial, emulsion & co-electrospinning, edge electrospinning, gap electrospinning, 3D jet writing, and caged collector electrospinning & moving spinneret. Further, the application of multiscale fibrous scaffolds with respect to bone, cartilage, cardiovascular, liver, neural, skin and tendon tissue engineering has been discussed. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to determine the therapeutic efficacy of 0.05% topical cyclosporine A (CsA) for chronic ocular surface disease (OSD) in patients using benzalkonium chloride (BAK)-preserved antiglaucoma eye drops. Methods: A prospective, randomized, paired-eye, controlled clinical trial was conducted with participants who had been instilling at least one BAK-preserved topical antiglaucoma drug in both eyes for at least 6 months. Topical CsA was only applied in randomly selected unilateral eyes. Visual field (VF) indices, ocular surface parameters, tear meniscus height (TMH), and matrix metalloproteinase-9 (MMP-9) immunoassay were evaluated at baseline and at 2 and 4 months. Results: Seventy eyes from 35 participants were included in the study. The Schirmer I, tear breakup time, and TMH increased by 4.5 ± 8.6 mm (P < 0.01), 5.0 ± 5.3 s (P < 0.001), and 85.4 ± 159.0 μm (P < 0.01) in the treated eyes at 4 months from baseline, respectively. The ocular staining score and MMP-9 positivity in the treated eyes decreased by 2.2 ± 1.3 (P < 0.001) and 0.7 ± 0.9 points (P < 0.001), respectively, at 4 months. In untreated eyes, only TMH increased by 41.4 ± 92.1 μm (P = 0.016) from baseline to 4 months. In VF indices, the tracking failure frequency was 19.09% ± 21.62%, and the test duration was 336.0 ± 79.5 s in the treated eyes at 4 months, which were lower than 34.37% ± 23.13% (P < 0.001) and 375.9 ± 70.7 s (P < 0.05) in the nontreated eyes. Conclusion: Application of topical 0.05% CsA significantly improved the OSD parameters and the reliability indices of VF tests. This study was registered with the Clinical Research Information Service (CRIS) (number KCT0007124). [ABSTRACT FROM AUTHOR]

On the other hand, Giannaccare et al. [[192]] conducted a study on patients with MGD having subjective symptoms (OSDI>= 13) and at least one clinical sign of MGD, such as terminal ductal obstruction, plugging of the meibomian glands, turbid secretions, inflammation and swelling of the eyelid margins, or poor meibum secretions. One RCT [[423]] and two observational studies [[429]] assessed improvements in meibomian gland orifices and surrounding findings and report that minocycline oral administration can improve meibomian gland orifices and surrounding findings in patients with MGD and meibomitis. Additionally, Ibrahim et al. [[279]] show that meibomian gland acinar density, shortest and longest acinar diameter, and inflammatory cell density were significantly associated with BUT, fluorescein staining score, Rose Bengal staining, decreased lipid expression from the meibomian gland orifices, meibomian gland dropout, and ocular surface tear evaporation rate. In 22 patients without atrophy of the meibomian gland, after treatment with the cleansing agent, meibography indicated significant improvements in the meibomian gland orifices/surrounding findings (eyelid margin vascularity), quality of meibum, and BUT. [Extracted from the article]

The rise in patients seeking corneal refractive surgery, despite having systemic autoimmune diseases, underscores the need for special considerations when treating these individuals. Recent studies have expanded our knowledge in identifying and evaluating autoimmune disorders and their potential side effects in the results of corneal refractive surgery with laser. This study briefly examines the pathogenic factors, clinical aspects, and possible complications in patients with systemic autoimmune disorders subjected to these surgeries. In total, 132 articles were selected for this research among the reviewed studies. Considering that the release of various cytokines caused by systemic autoimmune disorders can lead to destructive corneal consequences, the need for early diagnosis before any laser surgery for refractive errors seems essential. Although procedures such as LASIK and PRK are commonly performed on patients with autoimmune disorders, important considerations must be made. Studies have not yet confirmed definitive contraindications to laser refractive surgery for autoimmune disorders. [ABSTRACT FROM AUTHOR]

Purpose: To assess changes in visual function and optical and tear film quality in computer users. Methods: Forty computer workers and 40 controls were evaluated at the beginning and end of a working day. Symptoms were assessed using the Quality of Vision questionnaire (QoV), 5‐item Dry Eye Questionnaire (DEQ‐5) and Symptom Assessment in Dry Eye version II (SANDE II). Tear film quality was evaluated using the Medmont E300 dynamic corneal topography tool to measure the tear film surface quality (TFSQ), TFSQ area and auto tear break‐up time (TBUT). Optical quality was assessed by measuring high, low and total ocular aberrations with a Hartmann–Shack wavefront sensor. Visual performance was assessed by measuring photopic and mesopic visual acuity, photopic and mesopic contrast sensitivity and light disturbance. Results: Poorer DEQ‐5, QoV and SANDE II scores were obtained in computer workers at the end of the working day compared with controls (p ≤ 0.02). Computer workers exhibited a higher (worse) TFSQ and TFSQ area at visit 2 compared with visit 1 (p ≤ 0.04), while no significant differences in TBUT (p = 0.19) or ocular aberrations were observed (p ≥ 0.09). Additionally, both light disturbance (p ≤ 0.04) and mesopic and photopic contrast sensitivity worsened at several spatial frequencies (p ≤ 0.04) throughout the working day in computer workers, while visual acuity remained unchanged (p ≥ 0.07). In contrast, control subjects exhibited no decrease in any variable during the day. Conclusions: While visual acuity remained unchanged, several aspects of visual function and quality of vision decreased over a day of computer use. These changes were accompanied by greater dry eye symptoms and tear film changes, which are likely to have played a fundamental role. The present study provides insight into new metrics to assess digital eye strain. [ABSTRACT FROM AUTHOR]

Background: Selective laser trabeculoplasty (SLT) is relatively safe and effective in lowering intraocular pressure (IOP). However, although rare, complications can occur after SLT. This report describes a patient with choroidal detachment due to hypotony following SLT without anterior chamber (AC) inflammation. Case presentation: A 67-year-old man was referred for elevated IOP in his left eye with advanced glaucomatous visual field loss. He had previously been diagnosed with idiopathic uveitic glaucoma in the left eye, for which he underwent laser iridotomy, trabeculectomy, and cataract surgery. At the first visit, the IOP of his left eye measured by Goldmann tonometry was 28 mmHg despite maximally tolerated medical treatment. SLT was performed in his left eye, resulting in an IOP of 7 mmHg 7 days later. At 3 weeks post-procedure, the patient experienced ocular pain and decreased visual acuity in his left eye. Slit-lamp examination revealed deep anterior chamber depth and no inflammation reaction, but the IOP in his left eye was 4 mmHg, and both fundus and B-scan ultrasonography showed serous choroidal detachment. All anti-glaucoma agents were stopped, and the patient was started on treatment with oral prednisolone and cyclopentolate eye drops. Three weeks later, choroidal detachment had resolved and the IOP in his left eye had stabilized at 8 mmHg. Follow-up 3 months later showed that the IOP in his left eye remained stable. Conclusions: Choroidal detachment-related hypotony is a rare complication of SLT. This possible complication following SLT should be informed to the patients and considered when performing the procedure. [ABSTRACT FROM AUTHOR]

Background: Restoration of salivary gland function in Sjogren's syndrome (SS) is still a challenge. Dental pulp stem cells (DPSCs) derived exosomes had shown anti-inflammatory, anti-oxidative, immunomodulatory, and tissue function restorative abilities. However, the salivary gland function restoration potential of DPSCs-derived exosomes (DPSC-Exos) during SS has not been investigated yet. Methods: DPSC-Exos was isolated by ultracentrifugation methods and characterized. Salivary gland epithelial cells (SGEC) were treated with interferon-gamma (IFN-γ) to mimic SS in vitro and cultured with or without DPSC-Exos. SGEC survival and aquaporin 5 (AQP5) expression were analyzed. mRNA sequencing and bioinformatics analysis were performed in IFN-γ vs. DPSC-Exos+ IFN-γ treated SGEC. Non-obese diabetic (NOD)/ltj female mice (SS model), were intravenously administered with DPSC-Exos, and salivary gland functions and SS pathogenicity were analyzed. Furthermore, the mRNA sequencing and bioinformatics predicted mechanism of the therapeutic effect of DPSC-Exos was further investigated both in vitro and in vivo using RT-qPCR, Western blot, immunohistochemistry, immunofluorescence, flowcytometry analysis. Results: DPSC-Exos partially rescued IFN-γ triggered SGEC death. IFN-γ inhibited AQP5 expression in SGEC and DPSC-Exos reversed this effect. Transcriptome analysis showed GPER was the upregulated DEG in DPSC-Exos-treated SGEC with a positive correlation with salivary secretion-related DEGs. Pathway enrichment analysis revealed that DEGs were mainly attributed to estrogen 16 alpha-hydroxylase activity, extracellular exosome function, cAMP signaling, salivary secretion, and estrogen signaling. Intravenous injection of DPSC-Exos in NOD/ltj mice alleviated the SS syndrome as indicated by the increased salivary flow rate, attenuated glandular inflammation, and increased AQP5 expression. GPER was also upregulated in the salivary gland of DPSC-Exos-treated NOD/ltj mice compared with the PBS-treated NOD/ltj mice. IFN-γ+DPSC-Exos-treated SGEC showed higher expression of AQP5, p-PKA, cAMP, and intracellular Ca2+ levels compared with IFN-γ-treated SGEC. These effects were reversed by the inhibition of GPER. Conclusions: Our results showed that DPSC-Exos revitalize salivary gland epithelial cell function during SS via the GPER-mediated cAMP/PKA/CREB pathway suggesting the possible therapeutic potential of DPSC-Exos in SS-treatment. [ABSTRACT FROM AUTHOR]

Purpose: Dry eye can cause an increased risk of ocular infection due to loss of corneal epithelial integrity and changes to tear film homeostasis. Polymeric nanofibers with unique physicochemical and biological properties have attracted a lot of attention due to the improved in vivo performance of their conventional ocular formulations. The purpose of this present exposition was to assess the in vitro and in vivo efficacy of gatifloxacin (GAF)-loaded polyacrylonitrile (PAN) nanofiber in dry eye conditions. Methods: The nanofibers were characterized for morphology, drug entrapment, swelling behavior, drug release, oxygen permeability, biodegradability, antimicrobial potential, and sterility. Draize test, in vivo antibacterial activity, corneal healing characteristics, and tear quality profiles were also used to determine in vivo safety and efficacy. Results: Experimental findings suggested that electrospinning at defined conditions (applied voltage of 18 kV, flow rate of 0.5 mL/h, and tip to collector distance of 10 cm) produced smooth and continuous nanofibers with an average diameter of 480 nm. High drug entrapment of 95% combined with swelling indices of around 180% increased the controlled drug delivery capability of the prepared formulation. A slow degradation rate of 3±0.75% ensured a long-term cumulative drug release of 90% within 16 days. The inhibition diameter of the optimized formulation was found to be 15 ± 0.31 mm for E. coli and 13 ± 0.26 mm for S. aureus. Furthermore, after 3 days in an experimental dry eye animal model, the drug-loaded nanofiber showed better antibacterial activity, corneal healing, and tear film stability than the commercial eye drop. Conclusion: Overall, the study concluded that the GAF-loaded PAN nanofiber has good application prospects in the treatment of dry eye due to its safety and controlled drug release profile. [ABSTRACT FROM AUTHOR]

With the increasing number of options for the treatment of moderate‐to‐severe atopic dermatitis, clinicians need guidance on a practical approach to selecting a systemic agent for specific patient populations. We convened an expert panel consisting of 12 members to conduct a literature review and summarize relevant data related to six scenarios of clinical interest: comorbid asthma, ocular surface disease, history of cancer, past and ongoing infections of interest (including herpes simplex virus, herpes zoster, hepatitis B, and tuberculosis), pregnancy and lactation, and the elderly. We performed a literature search and examined each clinical scenario with respect to three major categories of available systemic agents: traditional systemics (azathioprine, cyclosporine A, methotrexate, and mycophenolate mofetil), Janus kinase inhibitors (abrocitinib, baricitinib, and upadacitinib), and biologics (dupilumab, lebrikizumab, and tralokinumab). The expert panel and steering committee met virtually to review the data and discuss the drafted consensus statements. A modified Delphi process was used to arrive at a set of final consensus statements related to the systemic treatment of AD in these specific patient populations. To provide practical guidance on the choice of systemic therapy for atopic dermatitis in these six topics of clinical interest, 25 expert consensus statements and a summary of the supporting data are presented herein. [ABSTRACT FROM AUTHOR]

Introduction: The symptoms associated with Sjögren's disease (Sjögren's) are well-documented from the physician's perspective. However, from the patient's perspective, there is limited information on symptoms and their impact on health-related quality of life (HRQoL). This study aimed to provide an expanded understanding of patients' experience of Sjögren's and how symptoms impact HRQoL using a novel multi-method social media listening (SML) approach. Methods: A total of 26,950 social media posts with relevant content on Sjögren's posted by social media users from the USA, Canada, Australia, UK, France, Germany, Italy, Spain and China were analysed using an artificial intelligence natural language processing tool to explore patient conversations. Symptoms by level of impact on patients were characterised based on 'commonness' and 'bothersomeness'. Applied concept association analysis was used to assess relationships between symptom domains and impact domains. A qualitative framework was applied to explore words and phrases patients use to describe symptoms and their impacts. Results: Five of the identified symptom domains were very impactful: Pain; Dry Mouth and Throat; Fatigue, Energy and Sleep; Emotional Balance; and Dry Eye. The symptom domains Pain and Dry Mouth and Throat were the most common, while those of Emotional Balance and Fatigue, Energy and Sleep were the most bothersome. Symptom domains most closely associated with four HRQoL impact domains were Fatigue, Energy and Sleep, Dry Mouth and Throat and Dry Eye with Daily Functioning; Fatigue, Energy and Sleep with Financial Health; Emotional Balance with Psychological Wellbeing and Gynaecological Issues with Social Wellbeing. Conclusion: The results of this SML study show that Sjögren's affects diverse aspects of patients' lives, with symptoms extending beyond dry eyes and mouth and impacting daily living and functioning. Because symptoms may affect patients differently, these results highlight the importance of measuring impact on HRQoL to assess patient outcomes and treatment options in routine clinical practice and clinical trials. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a common ocular condition, but the diagnosis relative to other ocular conditions and the evaluation of severity of the condition has often been difficult. This challenge can be due to clinical signs and symptoms not always correlating with each other. An understanding of the various components which create the condition, as well as the diagnostic measures used to evaluate these components, is useful to the clinician working with DED patients. This review paper will discuss traditional diagnostic options, diagnostic imaging, and Advanced Point of Care testing capabilities to determine the severity level of dry eye disease more adequately. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Meibomian gland dysfunction (MGD) is highly prevalent and is the leading cause of evaporative dry eye disease (DED). MGD is characterized by a reduction in meibum secretion and/or a change in meibum composition that results in the disruption of the tear film lipid layer and an increase in the tear film evaporation rate. Excessive evaporation causes tear film instability, desiccation, tear hyperosmolarity, inflammation, and apoptosis of ocular surface cells, resulting in a continuous cycle of DED. The primary treatment goal for DED associated with MGD is to restore the tear film lipid layer and decrease evaporation, thereby reducing ocular signs and symptoms. The management of MGD includes home care options (eyelid hygiene, warming eye masks, ocular lubricants) and office-based treatments (manual expression, microblepharoexfoliation, thermal pulsation, intense pulsed light, intraductal probing). Topical ophthalmic prescription medications attempt to alter various factors that may contribute to DED (e.g., inflammation, bacterial growth, inadequate tear production). In this review, clinical evidence regarding available treatments and emerging therapies from randomized studies in patients with DED associated with MGD is summarized. Although some treatment modalities have been evaluated specifically for DED patients with MGD, large-scale randomized controlled trials are needed to confirm efficacy and safety in this patient population. Currently, there are no approved prescription pharmacologic treatments specifically indicated for DED associated with MGD, and those medications approved for the treatment of DED do not target the key driver of the disease (i.e., excessive evaporation). NOV03 (perfluorohexyloctane; under review with the US Food and Drug Administration) is the most advanced emerging therapy for DED associated with MGD and has demonstrated statistically significant improvements in both signs and symptoms in randomized controlled trials. Development of novel pharmacotherapies will improve therapeutic options and allow for a more individualized approach for patients with DED associated with MGD. [ABSTRACT FROM AUTHOR]

G protein-coupled receptors are the target of more than 30% of all FDA-approved drug therapies. Though the purinergic P2 receptors have been an attractive target for therapeutic intervention with successes such as the P2Y12 receptor antagonist, clopidogrel, P2Y2 receptor (P2Y2R) antagonism remains relatively unexplored as a therapeutic strategy. Due to a lack of selective antagonists to modify P2Y2R activity, studies using primarily genetic manipulation have revealed roles for P2Y2R in a multitude of diseases. These include inflammatory and autoimmune diseases, fibrotic diseases, renal diseases, cancer, and pathogenic infections. With the advent of AR-C118925, a selective and potent P2Y2R antagonist that became commercially available only a few years ago, new opportunities exist to gain a more robust understanding of P2Y2R function and assess therapeutic effects of P2Y2R antagonism. This review discusses the characteristics of P2Y2R that make it unique among P2 receptors, namely its involvement in five distinct signaling pathways including canonical Gαq protein signaling. We also discuss the effects of other P2Y2R antagonists and the pivotal development of AR-C118925. The remainder of this review concerns the mounting evidence implicating P2Y2Rs in disease pathogenesis, focusing on those studies that have evaluated AR-C118925 in pre-clinical disease models. [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]