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Purpose: To evaluate signs and symptoms in patients diagnosed with dry eye disease (DED), divided into dry eye (DE) groups, in order to find a new biomarker that allows an accurate diagnosis, management and classification of DED. Methods: This cross‐sectional, observational study included 71 DED subjects. Subjective symptoms, visual quality and DE signs were assessed using the Ocular Surface Disease Index (OSDI), the Quality of Vision (QoV) questionnaire, best corrected distance visual acuity (VA), functional visual acuity (FVA), contrast sensitivity (CS), high‐ and low‐order corneal aberrations (HOA and LOA, respectively), tear break‐up time (TBUT), Meibomian Gland Dysfunction (MGD), Schirmer test, corneal staining, lid wiper epitheliopathy (LWE) and meibography. Participants were classified into three groups based on dryness severity using a cluster analysis, i.e., mild (N = 17, 55.8 ± 15.4 years), moderate (N = 41, 63.5 ± 10.6 years) and severe (N = 13, 65.0 ± 12.0). A new Dry Eye Severity Index (DESI) based on ocular surface signs has been developed and its association with symptoms, visual quality and signs was assessed. Comparisons between groups were made using Kruskal–Wallis and Chi‐squared tests. Spearman correlation analysis was also performed. Results: The DESI was based on three tests for DE signs: TBUT, Schirmer test and MGD. The DESI showed significant differences between different pairs of groups: Mild Dryness versus Moderate Dryness (p < 0.001), Mild Dryness versus Severe Dryness (p < 0.001) and Moderate Dryness versus Severe Dryness (p < 0.001). The DESI was significantly correlated with age (rho = −0.30; p = 0.01), OSDI score (rho = −0.32; p = 0.007), QoV score (rho = −0.35; p = 0.003), VA (rho = −0.34; p = 0.003), FVA (rho = −0.38; p = 0.001) and CS (rho = 0.42; p < 0.001) Also, significant differences between the severity groups were found for OSDI and QoV scores, VA, FVA, CS and MGD (p < 0.05). Conclusions: The DESI has good performance as a biomarker for the diagnosis, classification and management of DED. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the ocular surface characteristics in children diagnosed with uveitis and explore the association between uveitis and dry eye disease (DED). Methods: We included 84 children, 42 with uveitis and 42 healthy children. We performed the OSDI questionnaire and several ocular surface tests, including osmolarity, NITBUT, Schirmer test, and vital staining. We used Fisher's exact test and Mann-Whitney to compare variables and a binomial logistic regression to determine the factors associated with DED. Results: The difference in the prevalence of DED between uveitis (54.8%) and healthy (31%) groups was statistically significant (p < 0.05). Most patients with uveitis had mixed DED, and none of the healthy subjects had a severe form of the disease. There were no statistically significant differences in most of the tear film tests. However, all parameters tended to worsen in the uveitis group, and lipid layer thickness was thinner (p < 0.036). The uveitis group exhibited significantly more symptoms (p < 0.05). In the multivariate logistic regression, uveitis was associated with an odds ratio (OR) of 3.0 (95% CI: 1.07–8.42, p < 0.05) for DED. Conclusions: Our findings demonstrate a significantly higher prevalence of DED in children with uveitis compared to their healthy counterparts. Furthermore, our analysis indicates that the risk of DED in pediatric patients with uveitis is threefold higher than in healthy children. Therefore, it is crucial for clinicians to vigilantly monitor the development of DED in pediatric patients with uveitis and consider the implementation of preventive treatments. [ABSTRACT FROM AUTHOR]

Background: Several studies have reported the protective effects of mesenchymal stem cell-derived exosomes (MSC-Exos) in reducing inflammation and decreasing conjunctival goblet cell (CGC) loss in dry eye disease. However, whether MSC-Exos provide anti-inflammatory profiles in macrophages, thus contributing to CGC protection, has remained elusive. Methods: Macrophages were incubated with PKH26‐labeled periodontal ligament mesenchymal stem cell-derived exosomes (PDLSC-Exos) for 12 h, and uptake of PDLSC-Exos by macrophages was observed by a confocal fluorescence microscope. The mRNA expression of TNF-α, IL-10, and Arg1 was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of TNF-α and IL-10 were quantified using western blotting. Then, CGCs were exposed to different macrophage supernatants and qRT-PCR was used to detect the Muc5ac mRNA expression of CGCs in response to or absence of cholinergic stimulation. ELISA was used to determine the Muc5ac secretion of CGCs in response to cholinergic stimulation. Results: The uptake of PDLSC-Exos by M1 macrophages facilitates M2 macrophage polarization with the elevated expressions of IL-10 and Arg1. In macrophage supernatant-treated CGCs systems, PDLSC-Exo-treated M1 macrophage supernatant significantly enhanced the Muc5ac expression of CGCs in response to, or in the absence of, cholinergic stimulation, while the addition of PDLSC-Exos to the control macrophage supernatant did not generate a change in Muc5ac expression. Conversely, the addition of PDLSC-Exos to the diluted control macrophage supernatant induced a significant increase in Muc5ac expression. Conclusion: PDLSC-Exos could protect CGCs against M1 macrophage-mediated inflammation, and the protective effects of PDLSC-Exos are partly attributable to their effects on M1 macrophages. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a chronic multisystemic disease characterized by immunological activation, diffuse vasculopathy, and generalized fibrosis exhibiting a variety of symptoms. A recognized precursor of SSc is Raynaud's phenomenon, which is part of the very early disease of systemic sclerosis (VEDOSS) in combination with nailfold videocapillaroscopy (NVC) impairment. The pathophysiology of ocular involvement, alterations in internal organs, and body integumentary system involvement in SSc patients are complicated and poorly understood, with multiple mechanisms presumptively working together. The most prevalent ocular symptoms of SSc are abnormalities of the eyelids and conjunctiva as well as dry eye syndrome, due to fibroblasts' dysfunction and inflammation of the ocular surface. In particular, lagophthalmos, blepharophimosis limitation of eyelid motion, eyelid telangiectasia, and rigidity or tightening of the lids may affect up to two-third of the patients. In addition, reduction in central corneal thickness, iris defects and higher rates of glaucoma were reported. In the first reports based on retinography or fluorescein angiography, about 50% of SSc patients showed signs of vascular disease: peripheral artery occlusion, thinning of retinal pigment epithelium and choroidal capillaries, ischemic areas surrounded by intraretinal extravasation and microaneurysms, and peripheral capillary non-perfusion. Successively, thanks to the advent of optical coherence tomography angiography (OCTA), several studies highlighted significant impairment of either the choriocapillaris and retinal vascular plexuses, also correlating with NVC involvement and skin disease, even in VEDOSS disease. Given the sensitivity of this technique, ocular micro-vasculopathy may act as a tool for early SSc identification and discriminate between disease stages. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease is one of the most common disorders we see in practice today. Perfluorohexyloctane (PFHO) ophthalmic solution (MIEBO®) (©Bausch + Lomb) is a novel, non-aqueous, single entity, preservative-free ophthalmic drop recently approved by the FDA for treatment of the signs and symptoms of dry eye disease. Purpose: While the safety and efficacy of PFHO has been demonstrated in non-contact lens wearers, its safety and potential benefits in habitual contact lens wearers have not been explored. This report presents the results of a trial designed to evaluate the safety of PFHO and its effect on contact lens comfort, specifically in established contact lens wearers. Patients and methods: The study included 47 patients who were adjusted contact lens wearers with a best corrected visual acuity of 20/25 or better at distance. All the patients were healthy contact lens wearers with no dry eye symptoms. Results: A significant improvement in comfort scoring was observed without any significant changes in osmolarity, meibography scores, and total fluorescein staining. Conclusion: These findings suggest that PCHO is safe for contact lens wearers to use and shows promise to reduce contact lens dropout. [ABSTRACT FROM AUTHOR]

Background: The enhancement of ocular drug delivery is achieved by using biopolymer carriers in liquid ophthalmic preparations. Using natural polysaccharides to formulate ocular medications is attractive because they are economical and readily available. The primary goal of the study was to assess the safety and effectiveness of Tamarind seed polysaccharide (TSP)/Hyaluronic acid (HA) containing Rohto eye drops (TSP/HA drops) in alleviating the signs and symptoms of dry eye disease (DED) under dry environmental conditions using controlled environmental chamber (CEC). Methods: 12 participants were subjected to harsh environmental conditions in a CEC with a relative humidity (RH) of 5% and an ambient temperature of 21°C. TSP/HA drops were used in the two treatment modalities, protection (drops instilled before exposure to the dry environment and relief (drops instilled after exposure to the dry environment. Before and after administering drops, patients undergo screening for ocular symptoms, tear osmolarity, ocular surface temperature (OST), and tear production using the ocular Surface Disease Index questionnaire (OSDI), OcuSense TearLab Osmometer, FLIR System ThermaCAM P620, and phenol red test (PRT) respectively. Tear production was calculated by the Tear Function Index test (TFI). Results: Before (protection) and after (relief) exposure to the dry environment, TSP/HA resulted in a mean tear osmolarity of 296.0 mOsm/L and 292.0 mOsm/L, with no significant statistical difference. The presence of TSP/HA in both protection and relief modes led to an increase in tear production. TSP/HA drops did not significantly affect OST compared to the absence of TSP/HA drops at 5% RH. There was a significant increase in mean symptom score from 14 at 40% RH to 128 at 5% RH (p=0.003). A substantial reduction in symptoms was found in both protection (before exposure) (35) (p=0.003) and relief (after exposure) (50) (p=0.005) compared to when no drop was used. Conclusion: It was apparent that using TSP/HA for protection was superior to relief for osmolarity and eye comfort. To optimise the therapeutic efficacy of TSP/HA, it is advisable to instruct patients to administer it before exposure to dry atmospheric conditions. The small sample size limits the ability to generalize the findings. Future studies should evaluate the tear supplement with a larger sample to improve statistical power. [ABSTRACT FROM AUTHOR]

Purpose: Changes in meibum composition and quantity in meibomian gland dysfunction (MGD) result in tear film instability and dry eye. This exploratory study aimed to identify changes in (O-acyl)-ω-hydroxy fatty acid (OAHFA) and hydrocarbon chain (HC) unsaturation levels in meibum related to the presence and severity of MGD. Methods: Meibum samples were collected from 3 cohorts of adults with no MGD, mild-to-moderate MGD, and severe MGD in a noninterventional clinical trial (NCT01979887). OAHFAs, cholesterol esters (CE), HC unsaturation, and HC length in the meibum samples were quantified with 1H-nuclear magnetic resonance spectroscopy using 2 methods of normalization. Results: Meibum samples from 62 subjects were analyzed: 21 non-MGD, 21 mild-to-moderate MGD, and 20 severe MGD. Meibum OAHFA and CE levels and HC unsaturation were reduced with increasing severity of MGD, with most pairwise comparisons significant (P < 0.05, t-tests), following the order non-MGD > mild-to-moderate MGD > severe MGD. Regardless of the resonances used for normalization, each pairwise comparison of OAHFA, CE, and HC unsaturation levels in MGD (combined severities) versus non-MGD samples was significant (P < 0.01, t-test). Analysis using various normalization equations showed reductions of 20%–22% for OAHFAs, 51%–57% for CE, and 36%–66% for HC unsaturation in MGD (combined severities) compared with non-MGD. HC length was not altered in MGD (combined severities) compared with non-MGD samples (t-test). Conclusions: Meibum OAHFA, CE, and HC unsaturation levels were reduced in MGD and were lowest in the severe MGD cohort. These findings may contribute to the understanding of the pathophysiology of MGD. [ABSTRACT FROM AUTHOR]

One of the most common causes of blindness on a global scale is glaucoma. There is a strong association between glaucoma and increased intraocular pressure (IOP). Because of this, adequate IOP‐lowering is the most important treatment strategy, mostly through topical eyedrops. Well‐functioning meibomian glands are paramount for maintaining a stable tear film, and their dysfunction is the most common cause of dry eye disease. There is a growing concern that both topical glaucoma medications themselves and their added preservatives damage the meibomian glands, and consequently, the ocular surface. Preserved topical glaucoma medications appear to cause dysfunction and atrophy of the meibomian glands. Upon comparison, preserved formulations caused more symptoms of dry eye, tear film instability, inflammatory changes and meibomian gland dropout than the preservative‐free counterpart. However, although seemingly less detrimental, unpreserved alternatives may diminish glandular efficacy, and, depending on the active ingredient, lead to glandular death. This negatively impacts quality of life, adherence to treatment regimens and prognosis. In this review, we explore the available evidence regarding the effects of IOP‐lowering eye drops on the meibomian glands. [ABSTRACT FROM AUTHOR]

Introduction: This systematic review and meta-analysis aimed to assess the correlations of tear osmolarity (TO) with ocular symptoms and ocular surface parameters in dry eye disease (DED). Materials and methods: A literature search was conducted in PubMed, ScienceDirect, and Google Scholar databases up to 31 December 2022. Observational studies were included if they reported Pearson's-r or Spearman's-ρ of TO with ocular symptoms and/or ocular surface parameter(s) in DED patients without or with other underlying diseases. The r or ρ values were extracted and assessed using a random effect of meta-analysis. Results: Twelve studies were included in the qualitative synthesis and meta- analysis. Overall weighted summary-r values amounted to 0.17, -0.35, and -0.29 for the correlations of TO with ocular symptoms, fluorescein break-up time (FBUT), and Schirmer I, respectively. In the DED subgroup, the weighted summary-r values amounted to 0.11, -0.32, and -0.12 for the correlations of TO with ocular symptoms, FBUT, and Schirmer I, respectively. Greater weighted summary-r values were found in the autoimmune disease-related DED (AID-DED) subgroup for the correlations of TO with ocular symptoms (weighted summary-r, 0.38), FBUT (weighted summary-r, -0.39), Schirmer I (weighted summary-r, -0.47), and corneal staining (weighted summary-r, 0.38). The I2 values were 36% to 92.4%. Conclusion: This systematic review and meta-analysis reveal weak to fair correlations between TO and clinical parameters in DED, with stronger correlations in AID-DED. The findings underscore the need for standardised diagnostic methods and further research to explore the distinct mechanisms of AID-DED. Future studies should focus on longitudinal assessments, advanced diagnostic tools, and patient-centred outcomes to enhance understanding and management of DED, ultimately informing clinical guidelines and improving patient care. [ABSTRACT FROM AUTHOR]

Purpose: To critically appraise the evidence on the ability of the lacrimal gland ultrasonography (USG) or magnetic resonance imaging (MRI) to differentiate between Sjogren's syndrome and non-Sjogren's syndrome/healthy controls. Methods: A systematic review and meta-analysis (based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) of online literature search was performed using PubMed, Scopus, and Cochrane databases. Cohort studies comparing the imaging features of the lacrimal glands of Sjogren's syndrome with a control group were included. Quantitative synthesis was performed using the RevMan (Version 5.4.1). Results: Six studies used USG as an imaging technique, and three used MRI for the lacrimal gland imaging. The lacrimal gland affected with Sjogren's syndrome shows glandular heterogeneity on USG and MRI. Heterogeneity on USG had 6.18 times higher odds of the lacrimal gland being involved with Sjogren's syndrome (95% CI, 3.31–11.55). Gland hyperechogenicity cannot reliably differentiate the glandular involvement in Sjogren's syndrome. There is insufficient data for analysis on the gland size, hypoechoic areas, fibrous bands, and increased lacrimal artery resistance in Sjogren's syndrome patients. Of the three MRI-based studies, reduced apparent diffusion coefficient and heterogeneity were the characteristics of Sjogren's syndrome. Clinical parameters such as dry eye symptomatology and Schirmer values had variable associations with USG or MRI parameters. Ultrasonography parameters were no different between dry eye versus no dry eye in Sjogren's syndrome patients, whereas small-sized glands had low Schirmer on MRI-based studies. Conclusion: Glandular heterogeneity on USG is significantly associated with lacrimal gland involvement in Sjogren's syndrome patients. However, the role of radiology in predicting lacrimal gland involvement is unclear as the evidence is insufficient and heterogeneous. [ABSTRACT FROM AUTHOR]

The study aimed to investigate the correlation between insulin-like growth factor 1 (IGF-1) and ocular surface parameters in obese prepubertal boys. Thirty obese prepubertal boys and 30 age- and gender-matched healthy controls underwent physical measurements, laboratory tests, and ocular surface assessments. The obese group showed lower IGF-1 levels (P = 0.001), reduced Schirmer I tear test (SIT) (P <0.001), and higher meibomian gland scores (meiboscore) compared to controls (P = 0.015). Bivariate analysis revealed a positive association between IGF-1 and SIT (r = 0.677, P < 0.001), and a negative association with between IGF-1 and meiboscore (r = − 0.487, P < 0.001). Multiple regression analysis indicated that IGF-1 (P < 0.001) and triglycerides (P = 0.028) independently influenced SIT. Logistic analysis showed a significant association between decreased IGF-1 and higher meiboscore values (OR 0.994, 95% confidence interval 0.988–1.000; P = 0.033). Conclusion: The findings suggest that reduced IGF-1 in obese prepubertal boys is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors. This implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on. What is Known: • Obese children exhibit decreased levels of IGF-1, and this reduction in IGF-1 is associated with cardiovascular metabolic complications related to obesity. • Ocular surface tissues might act as targets for hormones, might experience local effects of these hormone. What is New: • In prepubertal obese boys, the decrease in IGF-1 is independently linked to decreased SIT and increased meiboscore, irrespective of obesity and traditional cardiovascular risk factors.• This finding implies that monitoring ocular surface parameters in obese children might provide a new perspective for clinical practice to focus on. [ABSTRACT FROM AUTHOR]

Background/Objectives: Lifitegrast is an effective treatment for dry eye disease, reducing inflammation and improving the ocular surface condition. Owing to its high sensitivity to oxidation and hydrolysis, formulation studies are required to maintain the physicochemical stability of lifitegrast. This study aimed to overcome the instability of lifitegrast by developing a more stable eyedrop formulation by using citric acid and tromethamine to prevent the degradation of lifitegrast. Methods: Based on the Design of Experiment (DoE) approach, formulations were prepared at various concentrations of two stabilizers, citric acid and tromethamine. The stabilizers were carefully controlled to reduce the generation of degradation products. The eyedrops were stored under accelerated test conditions, and parameters such as appearance, pH, drug content, and impurities were evaluated. Results: The results showed that all critical quality attributes (CQAs) including appearance, pH, drug content, and impurities were maintained at stable levels under accelerated conditions, meeting established criteria. In addition, it was suggested that citric acid provided protection against oxidative stress, while tromethamine prevented hydrolysis caused by pH fluctuations. Conclusions: Consequently, it was concluded that the developed lifitegrast-containing eyedrop formulation exhibited improved physicochemical stability, validated through statistical analyses. These findings contribute to the development of stable eyedrops and provide a foundation for commercial production and clinical applications. [ABSTRACT FROM AUTHOR]

Objective To study the effect of ORM1 on sphingolipid metabolism in dry eye via SPTLC1 so as to provide a new research direction for the pathogenesis of dry eye. Methods By the subcutaneous injection of scopolamine hydrobromide (SCOP), a dry eye model was constructed,and adeno-associated virus overexpressing ORM1 was injected through the lens. Tear secretion assay,goblet number,corneal fluorescein staining,lacrimal gland rupture time,and HE assay were performed to assess the corneal conjunctival damage,tear quality,and histopathological changes. Ceramide and sphingomyelin content were detected by biochemical kits, and the expression of ORM1 and SPTLC1 was detected by qPCR and WB. Results (1) ORM1 increased tear secretion in the dry eye model (P< 0.000 1); (2) ORM1 increased the stability of the lacrimal gland on the ocular surface in the dry eye model (P< 0.000 1); (3) ORM1 improved the corneal epithelial damage in the dry eye model (P< 0.000 1); (4) ORM1 increased the number of goblet in the corneal tissue in the dry eye model (P< 0.000 1); (5) After the overexpression of ORM1,the epithelium of the corneal tissue became thicker and the cells of the basal lamina were more closely arranged. cell layers became more numerous and vacuoles were reduced; (6) ORM1 inhibited the inflammatory gene expression in a dry eye model (P< 0.01); (7) ORM1 promoted the total ceramide and sphingomyelin content (P＜0.01); (8) ORM1 promoted the rise of mRNA and protein expression of SPTLC1 (P＜0.001). Conclusion ORM1 can participate in the regulation of sphingolipid metabolism in dry eye disease through the regulation of SPTLC1,which provides new perspectives for exploring the mechanism of the development of dry eye disease and searching for effective and safe therapeutic options. [ABSTRACT FROM AUTHOR]

Background: Dry eye disease (DED) is a chronic condition characterized by a decrease in tear production or an increase in tear evaporation, leading to inflammation and damage of the ocular surface. Dysfunction of ion channels, tear hyperosmolarity and immune cell-driven inflammation create a vicious circle responsible for the pathological changes in the eyes of DED patients. Mesenchymal stem cells (MSCs) are adult, rapidly proliferating stem cells that produce a large number of immunoregulatory, angiomodulatory, and growth factors that efficiently reduce tear hyperosmolarity-induced pathological changes, inhibit harmful immune response, and provide trophic support to the injured corneal and conjuctival epithelial cells, goblet cells and acinar cells in lacrimal glands of DED patients. Methods: An extensive research in the literature was implemented in order to elucidate the role of MSCs in the attenuation of tear hyperosmolarity and eye inflammation in patients suffering from DED. Results: Findings obtained in preclinical and pilot clinical studies demonstrated that MSCs reduced tear hyperomsolaity-induced pathological changes and suppressed immune cell-driven eye inflammation. Additionally, MSC-based therapy managed to successfully address the most severe DED-related conditions and complications. Conclusions: MSCs should be considered as potentially new therapeutic agents for the treatment of severe DED. [ABSTRACT FROM AUTHOR]

Introduction: Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods: The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project's webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results: A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion: This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance. [ABSTRACT FROM AUTHOR]

Introduction: High-tech devices for the assessment of dry eye disease (DED) are increasingly available. However, the agreement between high- and low-tech parameters has been poorly explored to date. Trying to fill these gaps, we conducted a post hoc analysis on a recently published retrospective study on patients with DED receiving both low- and high-tech (Keratograph®) assessments, and treatment with different lubricating eyedrops. Methods: Six clinical questions were defined by the authors, considering literature gaps and their clinical experience, namely: (1) are NIKBUT-i and T-BUT interchangeable parameters? (2) What was the correlation between low- and high-tech parameters in untreated and treated patients with DED? (3) What was the correlation between signs and symptoms at baseline and during/after treatment? (4) Which parameters were better associated with symptoms? And with symptoms change over time? (5) What was the performance of NIKBUT-i and T-BUT in detecting clinically relevant changes? (6) What was the clinical advantage of adding other high- and low-tech parameters, respectively, to NIKBUT-i and T-BUT? Results: Low-tech measures were the best descriptors of the Ocular Surface Disease Index (OSDI) at baseline. In contrast, high-tech assessments demonstrate better performance in detecting changes over time. The distribution of NIKBUT-i data was more dispersed than TBUT both at baseline and follow-up. At a fixed specificity of 80%, the sensitivity in detecting clinically relevant ameliorations of symptoms was 42% for NIKBUT-i and 25% for T-BUT. A battery of high-tech tests could detect 90% of clinical amelioration, compared with 45% with low-tech tests (p < 0.001). Correlation between low- and high-tech parameters in both treated and untreated patients is lacking. Conclusions: Low-tech measures are adequate for diagnostic purposes in DED, whereas high-tech showed better performances at follow-up, particularly when different tests are combined. Overall, poor interchangeability among parameters and agreement with symptoms was reported both with high- and low-tech assessments. [ABSTRACT FROM AUTHOR]

Background/Objectives: Dry eye disease is a leading cause of ophthalmologic consultations worldwide and can significantly impact quality of life. While global prevalence rates vary widely, data specific to South America are limited. This systematic review aims to describe and analyze the prevalence and associated factors of dry eye disease-related symptoms in South American populations. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review was conducted using databases such as PubMed, Web of Science, Scopus, and LILACS. Primary studies in English and Spanish that examined the prevalence of dry eye disease-related symptoms in South American populations and its associated factors were included without date restrictions. Studies were screened and selected based on predefined inclusion and exclusion criteria, resulting in the final inclusion of 16 studies from six South American countries. Results: This review identified significant variability in the prevalence of dry eye disease-related symptoms in South American populations in the region, ranging from 4% to 77.5%, with a mean prevalence of 39.3%. Higher prevalence rates were observed among specific groups, such as university students (58.6%) and administrative workers (57.9%). Factors associated with dry eye disease-related symptoms in South American populations included female sex, older age, prolonged screen time, insufficient sleep, and medical conditions such as hypertension, connective tissue disorders, and the use of medications like antihypertensives and antidepressants. Conclusions: The prevalence of dry eye disease-related symptoms in South American populations is notably higher than global averages, highlighting regional challenges. This study emphasizes the need for standardized diagnostic tools and comprehensive epidemiological research across South America, particularly in underrepresented countries, to inform public health strategies tailored to the specific needs of these populations. [ABSTRACT FROM AUTHOR]

The cornea is a vital component of the visual system, and its integrity is crucial for optimal vision. Damage to the cornea resulting from trauma, infection, or disease can lead to blindness. Corneal regeneration using mesenchymal stem cells (MSCs) and MSC-derived extracellular vesicles (MSC-EVs) offers a promising alternative to corneal transplantation. MSCs are multipotent stromal cells that can differentiate into various cell types, including corneal cells. They can also secrete a variety of anti-inflammatory cytokines and several growth factors, promoting wound healing and tissue reconstruction. This review summarizes the current understanding of the molecular and cellular mechanisms by which MSCs and MSC-EVs contribute to corneal regeneration. It discusses the potential of MSCs and MSC-EV for treating various corneal diseases, including corneal epithelial defects, dry eye disease, and keratoconus. The review also highlights finalized human clinical trials investigating the safety and efficacy of MSC-based therapy in corneal regeneration. The therapeutic potential of MSCs and MSC-EVs for corneal regeneration is promising; however, further research is needed to optimize their clinical application. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effects of serial intravitreal injections (IVI) on the ocular surface and meibomian glands in patients with neovascular age-related macular degeneration (nAMD). Methods: Patients receiving anti-vascular endothelial growth factor (anti-VEGF) agent injections for unilateral nAMD were included. Untreated fellow eyes served as the control group. All participants followed a pre-IVI asepsis protocol with povidone-iodine (PI). Ocular surface diseases index (OSDI) questionnaire scores, first and average non-invasive tear break-up time (fNITBUT and avgNITBUT), Schirmer-1 test results, corneal staining score (according to Oxford scale), meibomian gland (MG) loss rates of lower and upper eyelids were recorded four weeks after the last IVI. Results: Forty-two nAMD patients with a mean age of 63.3 ± 19.4 were included in the study. The mean OSDI score was 20.3 and the median of IVI number was 9 (6–22). There were no statistically significant difference between treated and untreated fellow eyes regarding fNITBUT (5.6 vs. 4.5, p = 0.872), avgNITBUT (6.2 vs. 7.2, p = 0.968), Shirmer-1 results (7 vs. 7, p = 0.854), corneal staining (0.3 vs. 0.2, p = 0.341), lower and upper MG loss rate (29.3 vs. 28.4, p = 0.162, and 27.1 vs. 26.9, p = 0.476, respectively). Only significant correlation was observed between age with lower and upper MG loss rate (r:0.396, p = 0.042, and r:0.365, p = 0.047). Conclusion: The results of the present study demonstrated that serial IVI of anti-VEGF agents with PI asepsis is well tolerated by nAMD patients in terms of ocular surface, MG loss and DED measurements. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the function of tear film with Oculus Keratograph 5M (Oculus K5M) and IDRA ocular surface analyser (IDRA), analyse their consistency and explore the potential of IDRA in the diagnosis of dry eye disease (DED). Methods: This cross-sectional study enrolled 36 participants (DED group, 14 eyes; non-DED group, 22 eyes). The parameters of tear film function, including the first noninvasive breakup time (fNIBUT), average NIBUT (aNIBUT), tear meniscus height (TMH), lipid layer thickness (LLT), lipid layer colour (LLC), lipid layer uniformity (LLU), morphology of meibomian glands (MGs) and MG loss, were obtained with Oculus K5M and IDRA. The consistency of parameter measurements between the two devices was evaluated. Results: All the parameters except LLT, which can be measured only by IDRA, were not significantly different between the two instruments in DED eyes. However, IDRA reported lower values of fNIBUT, aNIBUT and TMH as well as higher MG loss scores in non-DED eyes than Oculus K5M did (p < 0.001, < 0.001, = 0.002, and = 0.002, respectively). Further regression analysis revealed that aNIBUT and LLT measured by IDRA were the optimal parameters for diagnosing DED (OR = 0.567 and 0.845, p = 0.057 and 0.043, respectively), and their combination had the strongest diagnostic potential (AUC = 0.841, sensitivity = 85.7%, and specificity = 77.3%). Conclusion: As a user-friendly noninvasive device, the tear film function parameters measured by IDRA were highly consistent with those measured by Oculus K5M in DED patients. The combination of aNIBUT and LLT measured by IDRA had the best diagnostic accuracy for DED. [ABSTRACT FROM AUTHOR]

Purpose: To explore the role of the proinflammatory cytokine, macrophage migration inhibitory factor (MIF), in a murine model of dry eye disease (DED). Methods: The role of MIF on DED was determined using genetically MIF deficient mice and pharmacological inhibition of MIF. DED was induced with 0.5 mg of scopolamine via subcutaneous injection in wild type (WT) and mice lacking MIF (Mif−/−), three times a day for 21 days. DED signs, tear volume, ferning pattern and cytology impression were evaluated. Also, eye tissues were collected to determine transcripts of key inflammatory mediators and histopathological damage. In a second set of experiments, we neutralized MIF with ISO-1, an isozaxiline-derivative MIF tautomerase activity-inhibiting small molecule in WT mice, following an acute DED model for 10 days. ISO-1 was given starting on day 3 after DED induction and signs were evaluated, including a recovery phase in both experimental approaches. Results: When compared to WT, Mif−/− mice showed attenuated signs of DED like preserved mucin pattern and increased tear volume. Also, Mif−/− mice maintained conjunctival epithelial cells and less corneal damage, associated with lower levels of TNFα and IL-1β. At recovery phase, Mif−/− mice presented improved signs. Interestingly, in cornea and conjunctiva the absence of MIF selectively downregulated the transcription of inflammatory enzymes like inos and nox4 whereas displayed enhanced transcripts of il-4, il-13, tgfβ and cox2. Finally, pharmacological inhibition of MIF using ISO-1, replicated the above findings in the mouse model. Conclusion: MIF is a central positive mediator of the inflammatory process in experimental DED, thus, targeting MIF could be used as a novel therapy in ocular surface inflammatory pathologies. [ABSTRACT FROM AUTHOR]

Purpose: To describe the clinical course and evaluate treatment of ocular surface changes in patients receiving immune checkpoint inhibitor (ICI) therapy. Methods: Multiple markers of ocular surface dryness were evaluated in 16 patients on ICI therapy. The Wilcoxon rank-sum test was used to determine the significant change in the initial and final ocular surface indices. Results: Fifty percent of the eyes demonstrated worsening Schirmer I scores; 29% showed an increase in lissamine green staining. During follow-up, 43% of patients experienced a decline in OSDI scores. Treatments included preservative-free artificial tears (88%), cyclosporine (25%), topical corticosteroids (31%), warm compresses (25%); punctal plugs (13%). Median follow-up time was 3.4 months (range:0–79); median ICI treatment duration was 7 months (range:1–40). Four patients died during the observation period. Conclusion: A significant proportion of patients experience changes in ocular surface markers while treated with ICIs. Medical intervention can lead to stabilization of ocular surface disease. [ABSTRACT FROM AUTHOR]

Background: The evaluation of dry eye disease (DED) and the ocular surface can be approached from patient-centered questionnaires, clinical scales using the slit-lamp microscope, and more recently innovative ophthalmological devices that allow for noninvasive tests. The OCULUS Keratograph 5M (K5M) is a device that allows for noninvasive measurement of ocular surface parameters. Materials and Methods: The present article is a retrospective and observational study detailing the correlation of the OCULUS K5M surface parameters and the Ocular Surface Disease Index (OSDI) score. Patients of any gender and age attending a cornea and refractive surgery practice in an academic center underwent a full ophthalmological examination and tear meniscus height, tear breakup time, bulbar redness, meibography, and OSDI score measurement through the K5M. Results: One hundred and sixty-four eyes of 82 patients were included. The sample showed a female preponderance (78%) and a mean age of 49.45 years. When comparing the OSDI score with ocular surface parameters, a weak negative correlation was found with the tear meniscus height (Pearson coefficient: [ -0.229, P = 0.003]). There were no other statistically significant correlations between the K5M and the OSDI score. In addition, the meibomian gland dropout was significantly associated with increasing age, whereas conjunctivochalasis was associated with the female gender, increasing age and increasing OSDI score. Conclusions: The subjective symptoms of DED measured with OSDI score correlate only with tear meniscus height measured by the K5M in a Hispanic population. The detection of symptomatic DED patients through the K5M is incomplete in this population. [ABSTRACT FROM AUTHOR]

Background: 'Dry eye' - a common ailment, can be caused by conditions affecting the ocular surface, environmental factors such as low humidity, wind and underlying systemic conditions such as rheumatoid arthritis, Vitamin A deficiency, and postmenopausal women on estrogen therapy. Material & Methods: 70 patients aged between 18 - 60 years with dry eyes, attending the ophthalmology OPD were included in this study. The visual acuity of the study participants was assessed followed by examination of the anterior segment and posterior segment of the eye using 90D spherical lens. Schirmer's test and Tear Film Breakup Time (TFBT) were done to assess the production of tears and tear film integrity. Results: The majority of participants were aged 51-60, with a male predominance (61.4%) and middle-class socioeconomic status (42.85%). Common complaints included eye irritation (31.4%) and foreign body sensation (25.7%). Significant ocular findings were arcus senilis (62.86%) and immature cataracts (77.14%). Comorbidities, particularly diabetes (58.57%) and hypertension (22.857%), showed a mild to moderate correlation with tear instability (mean TBUT: 8.8 and 8.6 seconds, respectively). Environmental factors like screen time and hot air exposure were associated with lower TBUT scores. However, p-values for correlations with TBUT and DED severity were non-significant (comorbidities p = 0.98, environmental factors p = 0.52). Conclusion: DED is a multifactorial condition with interplay of systemic disorders, aging and environmental factors. Identifying the causative factor and addressing it is the cornerstone of DED management. [ABSTRACT FROM AUTHOR]

Background: Hyperandrogenism and insulin resistance are seen in polycystic ovary syndrome (PCOS) which are also known risk factors for dry eyes. Dry eye is a potential comorbidity present in patients with PCOS. Aim: To find correlation between dry eye disease (DED) and PCOS. Materials and Methods: A total of 50 women with polycystic ovary syndrome (PCOS) and 50 healthy controls were included in the study. They were then subjected to a complete ophthalmic evaluation which included tear film break-up time, Schirmer's test and Ocular Surface Disease Index (OSDI) questionnaire scoring. Results: Correlation between DED and PCOS was found to be statistically significant in both TBUT and OSDI score while Schirmer's test was found to be statistically insignificant. Conclusion: PCOS has a positive correlation with DED and hence regular eye check-ups are advisable for patients with PCOS. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the long-term effects of intense pulsed light (IPL) therapy on patients with dry eye disease (DED) associated with meibomian gland dysfunction (MGD). Methods: A retrospective case series was performed with 110 participants undergoing IPL therapy. Assessments included the eye fitness test (EFT) to gauge subjective symptoms, along with objective measures using the Tearcheck® device (ESW Vision, Houdan, France) noninvasive first breakup time (NIFBUT), noninvasive average breakup time (NIABUT), central tear meniscus height (CTMH), thinnest tear meniscus height (TTMH), and ocular surface inflammatory risk evaluation (OSIE) assessed using the SCHWIND SIRIUS device (SCHWIND eye-tech-solutions GmbH, Kleinostheim, Germany). Results: This study documented significant improvements in subjective and objective symptoms associated with DED and MGD. Subjective symptoms measured by the EFT showed an average increase of 9.74 points (range −10 to 28, standard deviation [SD] ± 7.54), indicating reduced symptoms. Objective measures of tear film stability, represented by NIABUT, increased by an average of 4.04 s (range −15.00 to 14.40, SD ± 4.91). Tear film stability evaluation (TFSE) scores decreased by 229.12 points on average (range −1775 to 528, SD ± 384.94), suggesting enhanced tear film stability. OSIE type 1 showed a reduction in inflammation, with a percentage decrease of 4.98% (range −45 to 5, SD ± 7.33). Additionally, OSIE capture time decreased by 3.25 s on average (range −27 to 22, SD ± 10.35), further indicating an improvement in ocular surface health. Conclusion: IPL therapy was shown to be a promising, noninvasive approach for improving quality of life in patients with DED by effectively managing symptoms and stabilizing tear film. The findings support the use of IPL as a sustainable treatment modality for DED associated with MGD. [ABSTRACT FROM AUTHOR]

Introduction: This study compared the efficacy of hydroxypropyl guar (HPG)/hyaluronic acid (HA) and carboxymethylcellulose (CMC)/HA lubricant eye drops for post-cataract surgery dry eye disease (DED). Methods: This was a prospective, open-label, assessor-masked, parallel, randomized controlled study. Seventy patients with DED who underwent cataract surgery were randomized in a 1:1 ratio to receive 1–2 drops of HPG/HA or CMC/HA lubricant four times daily for 3 weeks. Efficacy assessments included changes from baseline in corneal fluorescein staining (CFS) score, Ocular Surface Disease Index score, Schirmer's test score (without anesthesia), tear break-up time, and central corneal sensitivity at weeks 1 and 3. Results: There were 35 patients in each group. The HPG/HA group demonstrated superior improvements in CFS scores (expressed as means and standard deviations) to the CMC/HA group at week 1 (– 1.0 [1.7] vs. – 0.1 [1.7], p = 0.039) and demonstrated comparable results at week 3 (– 1.6 [1.8] vs. – 1.3 [1.9], p = 0.552). No statistical differences were observed in other secondary outcomes between groups at weeks 1 and 3 (p > 0.05). Only one adverse event was reported in this study, which occurred in the HPG/HA group. The AE of ocular hypertension was mild, deemed unrelated to the study treatment, and resolved within a week. Conclusions: The HPG/HA lubricant eye drops resulted in greater CFS scores at 1 week after treatment compared with CMC/HA drops. The HPG/HA and CMC/HA drops were safe and well tolerated. ClinicalTrials.gov identifier: NCT06221345. [ABSTRACT FROM AUTHOR]

Introduction: Patients with dry eye disease (DED) complain of a multitude of symptoms that affect their visual function and quality of life (QoL). This clinical investigation assessed the performance, tolerance, and safety of a novel preservative-free ophthalmic solution containing xanthan gum 0.2% and desonide sodium phosphate 0.025%. Methods: This was an observational, prospective, multicentric, and post-market clinical investigation to assess the effect of three times a day instillation of the study formulation in patients suffering from DED. The primary objective was to achieve a 50% reduction in conjunctival hyperemia index as assessed with the OCULUS Keratograph after 1 month of treatment compared to baseline values. The secondary objectives included patient-reported outcomes, clinical performance, and safety. Results: Thirty patients were enrolled (21 women, 9 men) with a mean age of 61.10 ± 14.53 years. The instillation of the study formulation was associated with a significant reduction in redness scores after 1 month of treatment compared to baseline (mean − 0.51 ± 0.51; p ≤ 0.0001). Although the primary endpoint was not completely met, a 50% reduction in the conjunctival hyperemia index was achieved in 23% of the participants, and 77% showed a reduction of 26% of the same index. In addition, the ophthalmic solution significantly increased tear film break-up time, and a significant reduction of corneal and conjunctival staining with fluorescein was achieved. It also reduced DED symptoms and had a very good safety profile. Conclusions: the study formulation produced a significant improvement in the signs, symptoms, and QoL of patients with mild to moderate DED with a good safety profile after 1 month of treatment. [ABSTRACT FROM AUTHOR]

Purpose: The PERSPECTIVE study was a real-world European, non-interventional, multicenter, observational study that evaluated the effectiveness, tolerability, and safety of ciclosporin A (CsA) 0.1% cationic emulsion (CE) in routine clinical practice as a treatment for adults with severe keratitis and dry eye disease (DED) that remained insufficiently controlled with artificial tears. This sub-analysis examined data from ophthalmology clinics in Germany to provide more precise insights into treatment patterns, outcomes, and clinical decision-making related to CsA 0.1% CE. Methods: Study data were collected from adults starting CsA 0.1% CE (one drop in both eyes at bedtime) and followed up at Week 4, 12, and 24, and Month 12. The primary endpoint was mean change from baseline in corneal fluorescein staining (CFS) score (Oxford Grade Scale) at Month 12. Secondary endpoints examined the severity of ocular signs and symptoms, and adverse events (AEs). Results: A total of 236 patients from 20 ophthalmology clinics in Germany participated in the PERSPECTIVE study (69.9% female; mean age 60.8 years). Following treatment with CsA 0.1% CE, patients experienced significant reductions in CFS score from Week 4, which were maintained through to Month 12 (P < 0.0001). From baseline, 81.6% of patients experienced an improvement in CFS score at Month 12. CsA 0.1% CE provided significant reductions in the severity of eyelid and conjunctival erythema at Month 12 compared with baseline (P < 0.001), as well as significant reductions in the severity of subjective ocular symptoms (all P ≤ 0.015). Safety data were consistent with the known safety profile of CsA 0.1% CE. Tolerability was rated as "satisfactory," "good," or "very good" by 97.2% of physicians and 95.7% of patients. Conclusion: Outcomes in Germany were similar to those reported for the overall European study population and are indicative of the treatment results that ophthalmologists may expect to see with CsA 0.1% CE treatment in real-life clinical practice. Treatment with CsA 0.1% CE provided long-term improvements over 12 months and was generally well tolerated. [ABSTRACT FROM AUTHOR]

Background & Aims: To study the change of the lipid layer thickness analysis in medical staff (MS) before and after work, and to explore the significance of measuring lipid layer thickness (LLT) respectively in four quadrants. Methods: Ocular Surface Disease Index (OSDI) questionnaire and video display terminal using time for 55 MS were collected (the informed consent was obtained from all patients). Noninvasive tear break-up time, LLT, tear meniscus height (TMH), meibomian glands (MG) dropout, and blink pattern before and after work (worked for more than 4 h) of 110 eyes were measured by Gaush iDea Ocular surface analyzer. Lid margin abnormalities were evaluated by the slit-lamp microscopy. Results: The average OSDI score of 55 MS was 25.68 ± 14.91. The average LLT of 110 eyes after work (65.12 ± 3.63 nm) was significantly reduced compared to before work (66.54 ± 4.16 nm), p < 0.05. The LLT in the superior quadrant was significantly thinner than that in the other three quadrants, p < 0.01. The average LLT was positively correlated with the LLT in the inferior (r = 0.822, p < 0.001), nasal (r = 0.261, p < 0.001), and temporal quadrant (r = 0.372, p < 0.001), while was negatively correlated with the MG dropout in lower lid (r = −0.209, p = 0.002). There was a significant correlation between the LLT in the inferior quadrant and the VDTt (r = −0.173, p = 0.01). The LLT of inferior quadrant were positively related to the TMH (r = 0.149, p = 0.027) and negatively related to MG dropout in lower lid (r = −0.162, p = 0.017). Conclusion: The LLT significantly decreases after work in MS. The distribution of the lipid layer on the ocular surface is uneven. It is unreasonable for current detection instruments to measure the inferior quadrant LLT alone to represent average LLT. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is one of the most common eye problems in the aging population. Hyperosmolarity triggers the immune response in DED and consequently activates the self-perpetuating immune cycle, leading to chronic damage of the ocular surface. This event causes symptoms such as a burning sensation, irritation, redness, photophobia, and blurred vision in DED patients. Subsequently, the quality of life gets significantly affected. The rising demand for DED management and treatment solutions, and the desirable outcomes from innovative therapies that draw global interest provide evidence to demonstrate the role of diet and nutrition in DED. Nutritional deficiency and a Westernized diet contribute to the chronic systemic progression of DED symptoms. It has been revealed in several published studies that the use of nutrients and dietary supplements improves the ocular surface and acts as a protective factor against DED. - We reviewed nutrition and dietary aspects in managing DED and its associated consequences, based on published studies, and reached an evidence-based conclusion. [ABSTRACT FROM AUTHOR]

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Background: Allergic conjunctivitis (AC) is a prevalent ocular condition triggered by environmental allergens, causing significant discomfort and reduced quality of life. Dry Eye Disease (DED), marked by ocular discomfort and visual disturbances, frequently overlaps with AC symptoms. This study examines the prevalence of DED in AC patients and explores the relationship between different AC types and DED severity. Method: A cross-sectional, observational study was conducted from June to September 2023 in the Department of Ophthalmology at a tertiary center in North India. A total of 264 AC patients aged 18 years and older with itchy eyes were included. Patients with contact lens use, recent ocular surgery, trauma, corneal pathology, or certain systemic diseases were excluded. DED was assessed using the Ocular Surface Disease Index (OSDI), Schirmer's test, and Tear Film Break-Up Time (TFBUT). Results: DED was found in 70% of AC patients, with 20% mild, 19% moderate, and 32% severe cases. Females were more affected (64%). VKC patients showed higher tear production and better TFBUT scores. PAC patients had the most severe DED. Conclusion: DED is common in AC patients, with PAC associated with more severe DED, while VKC shows milder symptoms. Tailored treatment approaches are needed for managing AC and DED. [ABSTRACT FROM AUTHOR]

Introduction: Dry eye disease (DED) is one of the most prevalent eye conditions worldwide, with artificial tears serving as a primary treatment option. Despite their wide availability on the European market, there is a lack of established classifications based on their physicochemical properties. The aim of our study was therefore (i) to develop an analytical method that measures the concentration and the molecular weight (MW) of the hyaluronic acid (HA) in commercialized products, and (ii) to propose an overview based on their various physicochemical parameters. Methods: The intrinsic viscosity and MW of the HA, as well as osmolarity, pH, rheological profile, and viscosity, were measured or determined. A specific method was developed to measure the average intrinsic viscosity and HA content using a liquid size-exclusion chromatography system. The MW was determined using the Mark–Houwink equation. Results: Thirty-seven products commercialized in Europe were analyzed, with 21 of them containing HA. The HA MW was lowest (300 kDa) for Thealose®, Thealoz Duo® Gel, and Hyabak®, and highest (1300 kDa) for Vismed® Multi, Vismed® Gel, and Neovis® Gel. The pH values varied between 5.94 for Treovis® and 8.06 for Systane® Ultra. Osmolarity ranged between 148 mOsm/L and 325 mOsm/L for Neovis® and Treovis®, respectively. Viscosity was highly variable, ranging from 0.38 mPas·s for Hylolipid® to 337.47 mPas·s for Thealoz® Duo Gel. Finally, rheological profile analysis revealed different shear-thinning behaviors. Conclusion: While the perfect eye drop does not exist, a multitude of options are available to choose from. This study improves our understanding of the major tear substitutes available on the European market based on several physicochemical properties. A better understanding and awareness of these parameters is crucial in order to offer the best treatment for patients with DED. [ABSTRACT FROM AUTHOR]

Introduction: This review examines how mechanisms that are not related to tear dysfunctions may contribute to the development of symptoms of dry eye disease and help to explain why dry eye symptoms do not correlate with signs. Consideration is also given to the significance of tear deficiencies which cannot contribute to an examination of symptom-sign correlation. Areas covered: Tear deficiencies which are not routinely assessed include inflammation, mucin quantity and quality, as well as corneal neuropathy and blink inefficiency. Expert opinion: Tear deficiencies detected in an examination of patients reporting symptoms of dry eye disease become the targets for remedial approaches but not always with satisfactory outcomes. Other possible influences on symptoms could include genetic predispositions, sex, ethnicity, race, health literacy, mental health conditions, lower perceived health-related quality of life, and psychological factors. However, these possible influences cannot be assessed in most dry eye disease clinical settings. Consequently, too often symptoms of dry eye cannot correlate with signs of tear dysfunction that are not identified (and so not treated). Consequently, noncompliance with treatment recommendations may not be relevant to the persistence of symptoms or signs when treatment does not address tear dysfunctions which are difficult to assess. [ABSTRACT FROM AUTHOR]

The prevalence of dry eye disease (DED), a multifactorial ocular surface disease characterized by tear film instability, is increasing yearly. Qingxuan Run Mu Yin (QXRMY) is a traditional Chinese medicine (TCM) consisting of Radix Rehmanniae, Radix Scrophulariae, Rhizoma Atractylodis macrocephalae, Herba Dendrobii, Flos Lonicerae, Forsythia suspensa, Ophiopogon japonicus, Saposhnikovia divaricata, Radix Platycodi, and Radix Glycyrrhizae. It has excellent therapeutic effects on dry eye syndrome and a good anti-inflammatory effect on immune-related inflammation. However, the molecular mechanism of Qing Xuan Run Mu Yin in treating dry eye syndrome is largely unknown. The present study used an online database to identify potential target genes of QXRMY for treating DED. The possible mechanisms of these target genes for the treatment of DED were obtained through Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) databases, Hub genes screened by Cytoscape and intersected with ferroptosis-related genes, and the essential genes were finally obtained based on the results of the analyses. DED cell model and rat model were constructed in this study to validate the critical genes and pathways, and it was confirmed that QXEMY alleviated DED by repressing ferroptosis through inhibiting the HMOX1/HIF-1 pathway. In conclusion, this study integrated network pharmacological analyses and experimental validation to provide an effective method to investigate the molecular mechanism of QXRMY in treating DED. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a multifactorial aging disorder leading to tear film insufficiency and instability. Yet, an important knowledge gap lingers in understanding senescence-associated ocular pathogenesis, due to limited in vitro translational lacrimal gland (LG) models. Consequently, this remains a major roadblock to discover effective therapies for the restoration of tear film secretion. Herein, the authors reported the magnetic bioassembly of two LG organoid platforms to recapitulate functional and aging states. Using a proof-of-concept approach, porcine primary LG cells were assembled into organoids via a magnetic 3D bioprinting (M3DB) platform. This platform could form reproducible LG organoids with epithelial hallmarks (AQP5+) and exhibit epithelial secretory functions (lysozyme activity). DNA damage-induced senescence and cell death was induced with etoposide, and LG organoid hypofunction and senescence-associated pathogenesis were observed. To confer DNA protection against aging, a novel gene therapy with Box A domain of high-mobility group box-1 (HMGB1-Box A) previously established by our group, was applied here to prevent LG cellular senescence for the first time. HMGB1-Box A transfection prevented LG organoids from senescence-associated pathogenesis at the transcriptomic, metabolomic and proteomic levels. Thus, M3DB platforms could generate functional and DNA damage-induced senescence LG organoids, and this latter damage could be prevented with HMGB1-Box A gene therapy. [ABSTRACT FROM AUTHOR]

Purpose: An innovative eyedrop formulation based on a combination of 0.2% hyaluronic acid and 0.001% hydrocortisone sodium phosphate (Idroflog®, Alfa Intes, Italy; HAC eyedrops) was granted a European Patent in 2016 and has been available on the market since 2019 in Europe and in other countries around the world. HAC eyedrops aim to synergize the moisturizing effects of hyaluronic acid with the mild anti-inflammatory properties of low-dose hydrocortisone, offering a more effective and safer alternative for treating dry eye disease (DED), targeting both tear film instability and dysfunctional para-inflammation. The activity of HAC eyedrops has been explored in different post-marketing clinical trials, in addition to preclinical studies. In this narrative review, we explored the available evidence on the use of HAC eyedrops for the management of para-inflammation in DED patients to provide a comprehensive overview of efficacy and safety data related to the use of this medical device in routine clinical practice. Methods: A literature search for preclinical and clinical data involving treatment with HAC eyedrops was conducted using PubMed/MEDLINE, considering only original research articles published in English, without time restrictions. Results: One preclinical and four clinical papers were retrieved. Preclinical evidence suggests that 0.001% hydrocortisone is able to control the expression of inflammatory markers, and this, together with the hydrating and lubricating properties of hyaluronic acid, leads to improvements in DED clinical signs, such as tear volume and the stability of the tear film. The results of clinical trials demonstrate that HAC eyedrops are able to improve the signs and symptoms of DED and that 0.001% low-dosage hydrocortisone can be helpful in preventing the progression to chronic stages of DED. Conclusions: HAC eyedrops represent a promising therapeutic strategy for the management of dysfunctional para-inflammation and offer a valuable addition to the armamentarium of treatments for DED. [ABSTRACT FROM AUTHOR]

Severe dry eye disease causes ocular surface damage, which is highly associated with mitochondrial dysfunction. Mitochondrial transcription factor A (TFAM) is essential for packaging mitochondrial DNA (mtDNA) and is crucial for maintaining mitochondrial function. Herein, we aimed to explore the effect of a decreased TFAM expression on ocular surface damage. Female C57BL/6 mice were induced ocular surface injury by topical administrating benzalkonium chloride (BAC). Immortalized human corneal epithelial cells (HCECs) were stimulated by tert -butyl hydroperoxide (t-BHP) to create oxidative stress damage. HCECs with TFAM knockdown were established. RNA sequencing was employed to analyze the whole-genome expression. Mitochondrial changes were measured by transmission electron microscopy, Seahorse metabolic flux analysis, mitochondrial membrane potential, and mtDNA copy number. TFAM expression and inflammatory cytokines were determined using RT-qPCR, immunohistochemistry, immunofluorescence, and immunoblotting. In both the corneas of BAC-treated mice and t-BHP-induced HCECs, we observed impaired TFAM expression, accompanied by mitochondrial structure and function defects. TFAM downregulation in HCECs suppressed mitochondrial respiratory capacity, reduced mtDNA content, induced mtDNA leakage into the cytoplasm, and led to inflammation. RNA sequencing revealed the absent in melanoma 2 (AIM2) inflammasome was activated in the corneas of BAC-treated mice. The AIM2 inflammasome activation was confirmed in TFAM knockdown HCECs. TFAM knockdown in t-BHP-stimulated HCECs aggravated mitochondrial dysfunction and the AIM2 inflammasome activation, thereby further triggering the secretion of inflammatory factors such as interleukin (IL) -1β and IL-18. TFAM reduction impaired mitochondrial function, activated AIM2 inflammasome and promoted ocular surface inflammation, revealing an underlying molecular mechanism for ocular surface disorders. [Display omitted] • TFAM reduction is a factor that promotes progression of ocular surface damage. • Impaired TFAM expression may exacerbate ocular surface injury by disrupting mitochondrial function and further promoting inflammation. • AIM2 inflammasome activation may be involved in ocular surface inflammation induced by TFAM reduction. • TFAM may serve as a promising therapeutic approach for addressing ocular surface disorders, such as dry eye disease. [ABSTRACT FROM AUTHOR]

This study aimed to assess the prevalence and selected correlates of dry eye disease (DED) among patients with type 2 diabetes in Kosovo. A case-series study was conducted in Kosovo from July 2023 to July 2024, including a consecutive sample of 400 patients with type 2 diabetes aged =18 years seeking healthcare services at the Eye Clinic of the Clinical University Center of Kosovo in Prishtina (51% females; overall mean age: 62.4±9.7 years; response rate: 80%). Data collection consisted of a detailed clinical examination and a structured questionnaire. Almost 70% of the patients had DED (standalone or combined with retinopathy, which, in turn, had a separate prevalence of 3%). Significant positive correlates of autonomous and/or combined DED and retinopathy included older age, unhealthy dietary patterns, sedentary lifestyle, high blood pressure, and treatment of diabetes with insulin and pills. Our findings indicate a high prevalence of DED among type 2 diabetes patients in Kosovo. DED and retinopathy were strongly associated with a range of demographic factors, behavioral characteristics, and preexisting conditions pertinent to type 2 diabetes patients in this population. [ABSTRACT FROM AUTHOR]

Corneal epithelial defects are one of the most common ocular disorders. Restoring corneal integrity is crucial to reduce pain and regain function, but in cases of neurotrophic or desensitized corneas, healing can be significantly delayed. Treating neurotrophic corneas is challenging for ophthalmologists, and surgical intervention is often indicated to manage refractory cases that are unresponsive to medical therapy. Over the last decade, as more expensive therapeutics reach the market, topical insulin has returned to the forefront as an affordable option to improve corneal wound healing. There is still a paucity of data on the use and the efficacy of topical insulin, with no consensus regarding its indications, preparation, or posology. Here we review the literature on topical insulin for corneal and ocular surface pathologies, with a focus on the current evidence, its mechanisms of action, and its safety profile. Additionally, we share our experience in the field and provide a potential framework for future research. [ABSTRACT FROM AUTHOR]

(1) Background: It is estimated that 10% of dry eye disease (DED) occurs in patients with Sjogren's syndrome (SS-DED) and represents a challenge when it comes to treatment. Both innate and adaptive immunity participate in the pathogenesis of SS-DED. Previous studies suggest that Th1 and Th17 cell immune responses are the main actors associated with the pathogenesis of this disease. Ocular surface mucins play a fundamental role in ocular surface homeostasis. In particular, the main transmembrane mucins, MUC1, MUC4 and MUC16, are dysregulated in DED and could be involved in the activation of pro-inflammatory cytokines at the ocular interface. Thus, the objective of this work was to analyze mucin and cytokine expression in ocular surface (OS) damage and correlate it with clinical symptoms.; (2) Methods: 18 patients with SS-DED and 15 healthy controls were included in the study. Samples of conjunctival cells were obtained through cytology impression. RNA was extracted from the collected samples and used to determine the expression of MUC1, 4 and 16 by qRT-PCR. Pro-inflammatory cytokines associated with DED pathogenesis (IL17 and IL-22) were also evaluated. The results were contrasted with the clinical findings on examination of the patients. (3) Results: We observed a significant increase in the expression of MUC1 and MUC4 in patients with SS-DED. MUC4 significantly correlated with both lower production and stability of the tear film, as well as greater superficial keratopathy. On the other hand, MUC1 and MUC16 were positively correlated with the presence of more severe DED symptoms. However, we could not reproduce an increase in IL-17 and IL-22 in DED patients as previously reported; (4) Conclusions: This work constitutes an approach to understanding how the gene expression of transmembrane mucins associates with SS-DED symptoms and clinical signs. [ABSTRACT FROM AUTHOR]

With increasing space exploration, there is a rising need to evaluate the impact of spaceflight on astronauts' health, including the effects of space-associated hazards such as microgravity. Astronauts' reports of experienced symptoms upon spaceflight include a notable prevalence of dry eye disease (DED). Hence, there is a pressing need to understand the pathogenesis and mechanism behind space-associated DED onset, which will subsequently guide the development of necessary therapies to reduce dry eye symptoms among astronauts. One critical effect of spaceflight includes alterations to the gut microbiome. On Earth, the prior literature has established the presence of an ocular surface–gut axis and the potential role of gut dysbiosis in DED onset. Meanwhile, the literature about astronauts' health underscores the presence of space-associated gut microbiome composition alterations and the presence of DED separately. Therefore, in this opinion article, we review and present the current literature regarding the ocular surface–gut axis on Earth and regarding potential translations to spaceflight. We present the view that, based on the existing literature, the ocular surface–gut axis may be a critical mechanism for the pathogenesis of DED in space, and this axis needs to be further explored in the context of identifying ways to reduce astronauts' experiences of DED during spaceflight. [ABSTRACT FROM AUTHOR]

Simple Summary: Dry eye disease includes a large variety of different ocular surface diseases. What all have in common is the resulting lubrication deficiency. Although the pathophysiology is multicausal, the common nominator is the threat of normal ocular surface balance and homeostasis. In homeostasis, the close link and interconnection of cellular basic mechanisms is essential for the functionality of the ocular surface. Any challenge threatening homeostasis implies cell stress. The ability of the ocular surfaces (conjunctiva and cornea) to cope and adapt to the resulting stress load decides over the ability to regain homeostasis or to drift to an altered stage of balance, recently identified as allostasis. This review outlines the importance of cellular stress as a key hub of the vicious circle and the importance of the integrated stress response system. Basic considerations for cellular recovery and the potential re-establishment of homeostasis are discussed. Disturbance or insufficiency of the tear film challenges the regulatory systems of the ocular surfaces. The reaction of the surfaces includes temporary mechanisms engaged in the preservation of homeostasis. However, strong or persisting challenges can lead to the potential exhaustion of the coping capacity. This again activates the vicious circle with chronic inflammation and autocatalytic deterioration. Hence, the factors challenging the homeostasis should be addressed in time. Amongst them are a varying osmolarity, constant presence of small lesions at the epithelium, acidification, attrition with mechanical irritation, and onset of pain and discomfort. Each of them and, especially when occurring simultaneously, impose stress on the coping mechanisms and lead to a stress response. Many stressors can culminate, leading to an exhaustion of the coping capacity, outrunning normal resilience. Reaching the limits of stress tolerance leads to the manifestation of a lubrication deficiency as the disease we refer to as dry eye disease (DED). To postpone its manifestation, the avoidance or amelioration of stress factors is one key option. In DED, this is the target of lubrication therapy, substituting the missing tear film or its components. The latter options include the management of secondary sequelae such as the inflammation and activation of reparative cascades. Preventive measures include the enhancement in resilience, recovery velocity, and recovery potential. The capacity to handle the external load factors is the key issue. The aim is to guard homeostasis and to prevent intercellular stress responses from being launched, triggering and invigorating the vicious circle. Considering the dilemma of the surface to have to cope with increased time of exposure to stress, with simultaneously decreasing time for cellular recovery, it illustrates the importance of the vicious circle as a hub for ocular surface stress. The resulting imbalance triggers a continuous deterioration of the ocular surface condition. After an initial phase of the reaction and adaption of the ocular surface to the surrounding challenges, the normal coping capacity will be exhausted. This is the time when the integrated stress response (ISR), a protector for cellular survival, will inevitably be activated, and cellular changes such as altered translation and ribosome pausing are initiated. Once activated, this will slow down any recovery, in a phase where apoptosis is imminent. Premature senescence of cells may also occur. The process of prematurization due to permanent stress exposures contributes to the risk for constant deterioration. The illustrated flow of events in the development of DED outlines that the ability to cope, and to recover, has limited resources in the cells at the ocular surface. The reduction in and amelioration of stress hence should be one of the key targets of therapy and begin early. Here, lubrication optimization as well as causal treatment such as the correction of anatomical anomalies (leading to anatomical dry eye) should be a prime intent of any therapy. The features of cellular stress as a key hub for the vicious circle will be outlined and discussed. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to analyze corneal sensitivity with a new noncontact and handheld esthesiometer (Brill Engines, Spain) in patients with dry eye disease (DED) and patients on hypotensive drops, and to compare it with healthy subjects. Methods: A total of 31 patients (57 eyes) with DED, 23 patients (46 eyes) with glaucoma, and 21 healthy patients (33 eyes) were recruited. In all patients, corneal sensitivity was measured. Subsequently, a keratography test (Keratograph 5M, Oculus) was carried out to measure tear meniscus height (TMH), non-invasive breakup time (NIBUT), bulbar redness (Jenvis scale), and corneal staining (CS, Oxford scale). Both corneal sensitivity and ocular surface parameters were compared between DED, glaucoma, and healthy subjects. Linear mixed models were constructed to utilize data from both eyes of patients. An alpha level of 0.05 was considered statistically significant. Results: The mean age was 56.1 ± 16.1 years in the DED group, 69.5 ± 11.7 years in the glaucoma group, and 37.190 ± 11.677 years in the control group. After adjustment for age and sex, corneal sensitivity was significantly reduced in DED and glaucoma vs control group (P = 0.02 and P = 0.009, respectively). NIBUT was lower in DED and glaucoma groups (P < 0.001 and P = 0.001, respectively). Redness and CS values were higher in the DED group (P = 0.04 and P = 0.001, respectively). TMH was lower in the glaucoma group (P = 0.03). Conclusions: Corneal sensitivity measured with a novel noncontact esthesiometer was reduced in DED and glaucoma groups compared to controls. In clinical practice, this esthesiometer could be an easy-to-use device to screen for patients with subclinical neurotrophic keratopathy. [ABSTRACT FROM AUTHOR]

Background and Purpose: The mechanistic target of rapamycin (mTOR) signalling pathway is a key regulator of cell growth and metabolism. Its deregulation is implicated in several diseases. The macrolide rapamycin, a specific inhibitor of mTOR, has immunosuppressive, anti‐inflammatory and antiproliferative properties. Recently, we identified tacrolimus, another macrolide immunosuppressant, as a novel activator of TRPM8 ion channels, involved in cold temperature sensing, thermoregulation, tearing and cold pain. We hypothesized that rapamycin may also have agonist activity on TRPM8 channels. Experimental Approach: Using calcium imaging and electrophysiology in transfected HEK293 cells and wildtype or Trpm8 KO mouse DRG neurons, we characterized rapamycin's effects on TRPM8 channels. We also examined the effects of rapamycin on tearing in mice. Key Results: Micromolar concentrations of rapamycin activated rat and mouse TRPM8 channels directly and potentiated cold‐evoked responses, effects also observed in human TRPM8 channels. In cultured mouse DRG neurons, rapamycin increased intracellular calcium levels almost exclusively in cold‐sensitive neurons. Responses were markedly decreased in Trpm8 KO mice or by TRPM8 channel antagonists. Cutaneous cold thermoreceptor endings were also activated by rapamycin. Topical application of rapamycin to the eye surface evokes tearing in mice by a TRPM8‐dependent mechanism. Conclusion and Implications: These results identify TRPM8 cationic channels in sensory neurons as novel molecular targets of the immunosuppressant rapamycin. These findings may help explain some of its therapeutic effects after topical application to the skin and the eye surface. Moreover, rapamycin could be used as an experimental tool in the clinic to explore cold thermoreceptors. [ABSTRACT FROM AUTHOR]

Purpose: The healthcare system is responsible for around 5% of CO2 emissions globally and in Germany. So far, there are no data on the amount of waste from dry eye disease (DED) therapy in ophthalmology. The aim of this project was to evaluate the amount and type of waste from single- and multi-dose units (SDU/MDU) generated by eyedrops used to treat DED in Germany. Methods: The net waste weight (outer/inner packaging, instruction leaflet, empty container) from factory-sealed products was determined using a precision scale. Based on prescription data from PharMaAnalyst, a database of medical prescriptions from over 70 million patients in Germany, the total annual waste volume for 2016–2021 and the net weight of a 30-day treatment were calculated. Results: The total annual waste volume increased significantly (p < 0.0001) from 7.13 tons in 2016 to 20.64 tons in 2021. A 30-day treatment with MDUs (without/with filter) results in a significantly lower mean waste volume (paper: SDU 24.3 ± 18.7 g; MDU 4.8 ± 1.7 g/8.8 g ± 1.7 g; SDU/MDU p = 0.0003, with filter p = 0.0034; plastic: SDU 35.0 ± 4.0, MDU 6.6 ± 0.7 g/ 15.1 g ± 5.8 g, SDU/MDU p < 0.0001, with filter p < 0.0001). Conclusion: Prescription-based treatment of DED in Germany causes an increasing and substantial waste volume. The use of SDUs is considerably more resource-intensive than MDUs. Due to the large and rising number of patients suffering from DED improvements in packaging could considerably reduce the CO2 footprint of DED treatment. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the frequency of ophthalmic disorders in Shih Tzus. Animals: Five hundred client‐owned Shih Tzu dogs (1000 eyes). Procedures: Medical records of 500 Shih Tzu dogs were reviewed and ophthalmic examination data were collected and analyzed. Results: In total, out of 1000 eyes, 964 (96.4%; OD: 480 eyes, OS: 484 eyes) had at least one ophthalmic abnormality, and only 36 eyes (3.6%; OD: 20 eyes, OS: 16 eyes) were diagnosed as normal. A total of 1375 individual ophthalmic abnormalities were observed in 964 diseased eyes. Fifty‐nine different unique diagnoses were made in the study population, and only three conditions [medial canthal entropion (10.4% of eyes; bilateral in 10.2% of dogs), caruncular trichiasis (21.1% of eyes; bilateral in 20.2% of dogs), and reduced tear film breakup time (17.6% of eyes; bilateral in 17.4% of dogs)] affected 49.1% of the eyes. Conclusion and Clinical Relevance: Findings suggested that the most prevalent disorders for the Shih Tzus were hairy caruncle, reduced TBUT, medial canthal entropion, keratoconjunctivitis sicca, pigmentary keratitis, lagophthalmos, and mature cataract. [ABSTRACT FROM AUTHOR]

This study aims to compare meibomian gland (MG) dropout and MG dysfunction (MGD) between patients with diabetes mellitus (DM) with moderate–severe non-proliferative diabetic retinopathy (NPDR) and patients with no diabetes (NDM). This prospective, transversal, age, and gender-matched case–control study included 98 DM and 106 NDM eyes. Dry eye disease (DED) and MGD evaluations were performed, including meibography (Keratograph 5M®). The objective MG dropout percentage was obtained by analyzing meibography images with ImageJ software (v. 1.52o, National Institutes of Health, Bethesda, MD, USA) and was subsequently graded with Arita's meiboscore. The DM duration was 18 ± 9 years. The mean meiboscore (3.8 ± 0.8 vs. 3.4 ± 1.0, p = 0.001), meiboscore severity (p = 0.016), and MG dropout (45.1 ± 0.1% vs. 39.0 ± 0.4%, p < 0.001) were greater in DM than in NDM. All patients showed MG dropout (meiboscore > 1). Lower eyelids showed greater MG dropout in both groups. A correlation with age (r = 0.178, p = 0.014) and no correlations with DM duration or gender (p > 0.005) were observed. Patients with diabetes showed greater corneal staining (1.7 ± 1.3 vs. 0.9 ± 1.1; p < 0.001), reduced corneal sensitivity (5.4 ± 1.1 vs. 5.9 ± 0.4; p < 0.001), lower MG expressibility (3. 9 ± 1.6 vs. 4.4 ± 2.1; p = 0.017), and worse meibum quality (1.9 ± 0.8 vs. 1.7 ± 0.5; p = 0.019). Tear breakup time, osmolarity, MMP-9, Schirmer, and the Ocular Surface Disease Index showed no significant differences. In conclusion, patients with DM with NPDR have greater MG dropout and meiboscore, as well as more severe MGD and DED parameters than persons with NDM. [ABSTRACT FROM AUTHOR]

The aim of this study is to survey the effectiveness of preservative-free artificial tears containing hyaluronic acid (HA) on post-cataract surgery dry eye disease (DED) prevention. A retrospective cohort study was performed, and patients that received cataract surgeries were divided into either an HA group or non-HA group depending on the artificial tear they used. A total of 37 and 74 eyes were enrolled into the HA and non-HA groups, respectively, after the selection. The primary outcomes are postoperative superficial keratitis and multiple (>3) DED symptoms. The generalized linear model was utilized to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of primary outcomes between the two groups. There were 10 and 2 episodes of superficial keratitis in the non-HA group and HA group, respectively, and the HA group demonstrated a significantly lower incidence of superficial keratitis (p < 0.001). Moreover, 13 and 5 patients developed multiple DED symptoms in the non-HA and HA groups, and the HA group illustrated fewer multiple DED symptoms (p = 0.024). The lower preoperative tear break-up time (TBUT) was correlated with superficial keratitis in the HA group (p = 0.043), while old age, low preoperative TBUT and ocular surface staining were associated with superficial keratitis in the non-HA group (all p < 0.05). Lower preoperative TBUT was correlated with multiple DED symptoms in the HA group (p = 0.020), while female sex, low preoperative TBUT and any DED symptoms were associated with multiple DED symptoms in the non-HA group (all p < 0.05). In conclusion, the usage of preservative-free artificial tears containing HA is associated with lower postoperative DED events. [ABSTRACT FROM AUTHOR]