In situ production and secretion of proteins endow therapeutic benefit against psoriasiform dermatitis and melanoma.

Genetic medicines have the potential to treat various diseases; however, certain ailments including inflammatory diseases and cancer would benefit from control over extracellular localization of therapeutic proteins. A critical gap therefore remains the need to develop and incorporate methodologies that allow for posttranslational control over expression dynamics, localization, and stability of nucleic acid-generated protein therapeutics. To address this, we explored how the body's endogenous machinery controls protein localization through signal peptides (SPs), including how these motifs could be incorporated modularly into therapeutics. SPs serve as a virtual zip code for mRNA transcripts that direct the cell where to send completed proteins within the cell and the body. Utilizing this signaling biology, we incorporated secretory SP sequences upstream of mRNA transcripts coding for reporter, natural, and therapeutic proteins to induce secretion of the proteins into systemic circulation. SP sequences generated secretion of various engineered proteins into the bloodstream following intravenous, intramuscular, and subcutaneous SP mRNA delivery by lipid, polymer, and ionizable phospholipid delivery carriers. SP-engineered etanercept/TNF-α inhibitor proteins demonstrated therapeutic efficacy in an imiquimod-induced psoriasis model by reducing hyperkeratosis and inflammation. An SP-engineered anti-PD-L1 construct mediated mRNA encoded proteins with longer serum half-lives that reduced tumor burden and extended survival in MC38 and B16F10 cancer models. The modular nature of SP platform should enable intracellular and extracellular localization control of various functional proteins for diverse therapeutic applications.

Lipid Nanoparticle (LNP) Chemistry Can Endow Unique In Vivo RNA Delivery Fates within the Liver That Alter Therapeutic Outcomes in a Cancer Model.

Within the field of lipid nanoparticles (LNPs) for RNA delivery, the focus has been mainly placed on organ level delivery, which can mask cellular level effects consequential to therapeutic applications. Here, we studied a pair of LNPs with similar physical properties and discovered how the chemistry of the ionizable amino lipid can control the endogenous LNP identity, affecting cellular uptake in the liver and altering therapeutic outcomes in a model of liver cancer. Although most LNPs accumulate in the liver after intravenous administration (suggesting that liver delivery is straightforward), we observed an unexpected behavior when comparing two similar LNP formulations (5A2-SC8 and 3A5-SC14 LNPs) that resulted in distinct RNA delivery within the organ. Despite both LNPs possessing similar physical properties, ability to silence gene expression in vitro, strong accumulation within the liver, and a shared pKa of 6.5, only 5A2-SC8 LNPs were able to functionally deliver RNA to hepatocytes. Factor VII (FVII) activity was reduced by 87%, with 5A2-SC8 LNPs carrying FVII siRNA (siFVII), while 3A5-SC14 LNPs carrying siFVII produced baseline FVII activity levels comparable to the nontreatment control at a dosage of 0.5 mg/kg. Protein corona analysis indicated that 5A2-SC8 LNPs bind apolipoprotein E (ApoE), which can drive LDL-R receptor-mediated endocytosis in hepatocytes. In contrast, the surface of 3A5-SC14 LNPs was enriched in albumin but depleted in ApoE, which likely led to Kupffer cell delivery and detargeting of hepatocytes. In an aggressive MYC-driven liver cancer model relevant to hepatocytes, 5A2-SC8 LNPs carrying let-7g miRNA were able to significantly extend survival up to 121 days. Since disease targets exist in an organ- and cell-specific manner, the clinical development of RNA LNP therapeutics will require an improved understanding of LNP cellular tropism within organs. The results from our work illustrate the importance of understanding the cellular localization of RNA delivery and incorporating further checkpoints when choosing nanoparticles beyond biochemical and physical characterization, as small changes in the chemical composition of LNPs can have an impact on both the biofate of LNPs and therapeutic outcomes.

Zwitterionic Phospholipidation of Cationic Polymers Facilitates Systemic mRNA Delivery to Spleen and Lymph Nodes.

Polymers represent a promising therapeutic platform for extrahepatic messenger RNA (mRNA) delivery but are hampered by low in vivo efficacy due to polyplex serum instability and inadequate endosomal escape following systemic administration. Here, we report the rational design and combinatorial synthesis of zwitterionic phospholipidated polymers (ZPPs) via cationic polymer postmodification by alkylated dioxaphospholane oxides to deliver mRNA to spleen and lymph nodes in vivo. This modular postmodification approach readily produces tunable zwitterionic species for serum resistance and introduces alkyl chains simultaneously to enhance endosomal escape, thereby transforming deficient cationic polymers to efficacious zwitterionic mRNA carriers without the need to elaborately synthesize functional monomers. ZPPs mediated up to 39 500-fold higher protein expression than their parent cationic counterparts in vitro and enabled efficacious mRNA delivery selectively in spleen and lymph nodes following intravenous administration in vivo. This zwitterionic phospholipidation methodology provides a versatile and generalizable postmodification strategy to introduce zwitterions into the side chains of cationic polymers, extending the utility of cationic polymer families for precise mRNA delivery and demonstrating substantial potential for immunotherapeutic applications.

Convergence innovation in the digital age and in the COVID-19 pandemic crisis.

Sustainable innovation is imperative for organizational survival and success in the turbulent market environment of the digital age, especially more so in the current COVID-19 pandemic crisis. This paper presents convergence innovation (CI), powered by the exponential fusion effect of the various objects, technologies, ideas, and strategies, as a new sustainable core competence of organizations. We present the concept of CI including its autonomous ecosystem enabled by advanced technologies, unique life cycle features, relationships with other innovation approaches, and its purpose of value creation for the stakeholders and beyond (for the greater good). The paper also explores how CI can be a catalyst for managing the current COVID-19 pandemic and charting the path to post crisis. The study makes contributions to both innovation literature and to practicing managers with new insights on sustainable innovation strategies for organizational performance and beyond.

Opportunities and challenges for contactless healthcare services in the post-COVID-19 Era.

This study examines the opportunities and challenges involved with contactless healthcare services in the post-COVID-19 pandemic era. First, we reviewed the literature to analyze contactless or contact-free healthcare services that have been utilized in pre-and during the COVID-19 pandemic periods. Then, we interviewed medical experts and hospital administrators to gain knowledge about how healthcare providers are currently working to mitigate the spread of COVID and preparing for the post-pandemic period. Thus, we analyzed the evolution and utilization of contactless services during the three different time periods: pre-, during-, and post-COVID-19. The results indicated that in the post-COVID-19 era, a new normal of hybrid healthcare services would emerge. While some of the contactless services that have been practiced during the pandemic may revert to the traditional face-to-face services, those innovative contactless healthcare services that have been proven effective during the pandemic would be practiced or even advanced in the post-pandemic period due to the accelerating technological developments. This study suggests many potential opportunities and daunting challenges for healthcare institutions, policymakers, and consumers regarding the implementation of contactless services in the post-COVID-19 era.

A Systematic Study of Unsaturation in Lipid Nanoparticles Leads to Improved mRNA Transfection In Vivo.

Lipid nanoparticles (LNPs) represent the leading concept for mRNA delivery. Unsaturated lipids play important roles in nature with potential for mRNA therapeutics, but are difficult to access through chemical synthesis. To systematically study the role of unsaturation, modular reactions were utilized to access a library of 91 amino lipids, enabled by the synthesis of unsaturated thiols. An ionizable lipid series (4A3) emerged from in vitro and in vivo screening, where the 4A3 core with a citronellol-based (Cit) periphery emerged as best. We studied the interaction between LNPs and a model endosomal membrane where 4A3-Cit demonstrated superior lipid fusion over saturated lipids, suggesting its unsaturated tail promotes endosomal escape. Furthermore, 4A3-Cit significantly improved mRNA delivery efficacy in vivo through Selective ORgan Targeting (SORT), resulting in 18-fold increased protein expression over parent LNPs. These findings provide insight into how lipid unsaturation promotes mRNA delivery and demonstrate how lipid mixing can enhance efficacy.

Effects of Flavonoid-rich Plant Extracts on In vitro Ruminal Methanogenesis, Microbial Populations and Fermentation Characteristics.

The objective of this study was to evaluate the in vitro effects of flavonoid-rich plant extracts (PE) on ruminal fermentation characteristics and methane emission by studying their effectiveness for methanogenesis in the rumen. A fistulated Holstein cow was used as a donor of rumen fluid. The PE (Punica granatum, Betula schmidtii, Ginkgo biloba, Camellia japonica, and Cudrania tricuspidata) known to have high concentrations of flavonoid were added to an in vitro fermentation incubated with rumen fluid. Total gas production and microbial growth with all PE was higher than that of the control at 24 h incubation, while the methane emission was significantly lower (p<0.05) than that of the control. The decrease in methane accumulation relative to the control was 47.6%, 39.6%, 46.7%, 47.9%, and 48.8% for Punica, Betula, Ginkgo, Camellia, and Cudrania treatments, respectively. Ciliate populations were reduced by more than 60% in flavonoid-rich PE treatments. The Fibrobacter succinogenes diversity in all added flavonoid-rich PE was shown to increase, while the Ruminoccocus albus and R. flavefaciens populations in all PE decreased as compared with the control. In particular, the F. succinogenes community with the addition of Birch extract increased to a greater extent than that of others. In conclusion, the results of this study showed that flavonoid-rich PE decreased ruminal methane emission without adversely affecting ruminal fermentation characteristics in vitro in 24 h incubation time, suggesting that the flavonoid-rich PE have potential possibility as bio-active regulator for ruminants.

Clinical and radiological outcomes with an augmented baseplate for superior glenoid wear in reverse shoulder arthroplasty.

Aims: This study aimed to assess the impact of using the metal-augmented glenoid baseplate (AGB) on improving clinical and radiological outcomes, as well as reducing complications, in patients with superior glenoid wear undergoing reverse shoulder arthroplasty (RSA). Methods: From January 2016 to June 2021, out of 235 patients who underwent primary RSA, 24 received a superior-AGB after off-axis reaming (Group A). Subsequently, we conducted propensity score matching in a 1:3 ratio, considering sex, age, follow-up duration, and glenoid wear (superior-inclination and retroversion), and selected 72 well-balanced matched patients who received a standard glenoid baseplate (STB) after eccentric reaming (Group B). Superior-inclination, retroversion, and lateral humeral offset (LHO) were measured to assess preoperative glenoid wear and postoperative correction, as well as to identify any complications. Clinical outcomes were measured at each outpatient visit before and after surgery. Results: There were no significant differences in demographic data and preoperative characteristics between the two groups. Both groups showed significant improvements in patient-reported outcome measures (visual analogue scale for pain, visual analogue scale for function, American Shoulder and Elbow Surgeons, Constant, and Simple Shoulder Test scores) from preoperative to final assessment (p < 0.001). However, AGB showed no additional benefit. Notably, within range of motion, Group B showed significant postoperative decrease in both external rotation and internal rotation, unlike Group A (p = 0.028 and 0.003, respectively). Both groups demonstrated a significant correction of superior-inclination after surgery, while patients in Group B exhibited a significant decrease in LHO postoperatively (p = 0.001). Regarding complications, Group A experienced more acromial stress fractures (3 cases; 12.5%), whereas Group B had a higher occurrence of scapular notching (24 cases; 33.3%) (p = 0.008). Conclusion: Both eccentric reaming with STB and off-axis reaming with AGB are effective methods for addressing superior glenoid wear in RSA, leading to improved clinical outcomes. However, it is important to be aware of the potential risks associated with eccentric reaming, which include excessive bone loss leading to reduced rotation and scapular notching.

In vivo editing of lung stem cells for durable gene correction in mice.

In vivo genome correction holds promise for generating durable disease cures; yet, effective stem cell editing remains challenging. In this work, we demonstrate that optimized lung-targeting lipid nanoparticles (LNPs) enable high levels of genome editing in stem cells, yielding durable responses. Intravenously administered gene-editing LNPs in activatable tdTomato mice achieved >70% lung stem cell editing, sustaining tdTomato expression in >80% of lung epithelial cells for 660 days. Addressing cystic fibrosis (CF), NG-ABE8e messenger RNA (mRNA)-sgR553X LNPs mediated >95% cystic fibrosis transmembrane conductance regulator (CFTR) DNA correction, restored CFTR function in primary patient-derived bronchial epithelial cells equivalent to Trikafta for F508del, corrected intestinal organoids and corrected R553X nonsense mutations in 50% of lung stem cells in CF mice. These findings introduce LNP-enabled tissue stem cell editing for disease-modifying genome correction.

Coexistence of congenital giant melanocytic nevus of the scalp with cranial defect, poliosis, and hair loss.

Congenital melanocytic nevi (CMN) are pigmented lesions presenting on the skin in approximately 1% of all newborns at or shortly after birth. CMN have been described as being associated with several anomalies, including cranial bone hypertrophy, scoliosis, and spina bifida. This is the first report to describe a giant congenital melanocytic nevus on the scalp associated with cranial involvement, poliosis, and alopecia.

Effect of using a small baseplate on the radiological and clinical outcomes of reverse total shoulder arthroplasty in Asian patients.

Aims: The aim of this study was to compare the clinical and radiological outcomes of reverse shoulder arthroplasty (RSA) using small and standard baseplates in Asian patients, and to investigate the impact of a mismatch in the sizes of the glenoid and the baseplate on the outcomes. Methods: This was retrospective analysis of 50 and 33 RSAs using a standard (33.8 mm, ST group) and a small (29.5 mm, SM group) baseplate of the Equinoxe reverse shoulder system, which were undertaken between January 2017 and March 2021. Radiological evaluations included the size of the glenoid, the ß-angle, the inclination of the glenoid component, inferior overhang, scapular notching, the location of the central cage in the baseplate within the vault and the mismatch in size between the glenoid and baseplate. Clinical evaluations included the range of motion (ROM) and functional scores. In subgroup analysis, comparisons were performed between those in whom the vault of the glenoid was perforated (VP group) and those in whom it was not perforated (VNP group). Results: Perforation of the vault of the glenoid (p = 0.018) and size mismatch in height (p < 0.001) and width (p = 0.013) were significantly more frequent in the ST group than in the SM group. There was no significant difference in the clinical scores and ROM in the two groups, two years postoperatively (all p > 0.05). In subgroup analysis, the VP group had significantly less inferior overhang (p = 0.009), more scapular notching (p = 0.018), and more size mismatch in height (p < 0.001) and width (p = 0.025) than the VNP group. Conclusion: In Asian patients with a small glenoid, using a 29.5 mm small baseplate at the time of RSA was more effective in reducing size mismatch between the glenoid and the baseplate, decreasing the incidence of perforation of the glenoid vault, and achieving optimal positioning of the baseplate compared with the use of a 33.8 mm standard baseplate. However, longer follow-up is required to assess the impact of these findings on the clinical outcomes.

Preparation of selective organ-targeting (SORT) lipid nanoparticles (LNPs) using multiple technical methods for tissue-specific mRNA delivery.

A new methodology termed selective organ targeting (SORT) was recently developed that enables controllable delivery of nucleic acids to target tissues. SORT lipid nanoparticles (LNPs) involve the inclusion of SORT molecules that accurately tune delivery to the liver, lungs and spleen of mice after intravenous administration. Nanoparticles can be engineered to target specific cells and organs in the body by passive, active and endogenous targeting mechanisms that require distinct design criteria. SORT LNPs are modular and can be prepared using scalable, synthetic chemistry and established engineering formulation methods. This protocol provides detailed procedures, including the synthesis of a representative ionizable cationic lipid, preparation of multiple classes of SORT LNPs by pipette, vortex and microfluidic mixing methods, physical characterization, and in vitro/in vivo mRNA delivery evaluation. Depending on the scale of the experiments, the synthesis of the ionizable lipid requires 4-6 d; LNPs can be formulated within several hours; LNP characterization can be completed in 2-4 h; and in vitro/in vivo evaluation studies require 1-14 d, depending on the design and application. Our strategy offers a versatile and practical method for rationally designing nanoparticles that accurately target specific organs. The SORT LNPs generated as described in this protocol can therefore be applied to multiple classes of LNP systems for therapeutic nucleic acid delivery and facilitate the development of protein replacement and genetic medicines in target tissues. This protocol does not require specific expertise, is modular to various lipids within defined physicochemical classes, and should be accomplishable by researchers from various backgrounds.

Effective Medical Waste Management for Sustainable Green Healthcare.

This study examines the importance of medical waste management activities for developing a sustainable green healthcare environment. This study applied a multiple methodological approach as follows. A thorough review of the literature was performed to delineate the factors that have been explored for reducing medical waste; hospital staff who handle medical waste were surveyed to obtain their opinions on these factors; the analytic hierarchy process (AHP) was applied to determine the priorities among the identified key factors; and experts' opinions were consulted to assess the actual applicability of the results derived by the AHP. The study identified the following factors as the most important: medical waste management (26.6%), operational management issues (21.7%), training for medical waste management procedures (17.8%), raising awareness (17.5%), and environmental assessment (16.4%). This study analyzed the contributing factors to the generation of medical waste based on the data collected from medical staff and the AHP for developing a sustainable green healthcare environment. The study results provide theoretical and practical implications for implementing effective medical waste management toward a sustainable green healthcare environment.

Developing Green Healthcare Activities in the Total Quality Management Framework.

This study examines the effectiveness of green healthcare activities in hospitals based on the total quality management (TQM) framework. The proposed research model and associated hypotheses were tested using structural equations modeling based on the data collected from 261 employees at general hospitals in South Korea. The results of the study revealed that the role of top management is essential for the successful implementation of green healthcare activities through motivating employees for their active participation in the program, providing continuous education and training on the importance of environmental sustainability, and diligent monitoring of the progress at the organization level. The study findings provide theoretical and practical implications on strategic approaches to planning and implementing green healthcare activities in hospitals for the greater good.

Arthroscopic biceps augmentation does not improve clinical outcomes during incomplete repair of large to massive rotator cuff tears.

AIMS: This study compared patients who underwent arthroscopic repair of large to massive rotator cuff tears (LMRCTs) with isolated incomplete repair of the tear and patients with incomplete repair with biceps tendon augmentation. We aimed to evaluate the additional benefit on clinical outcomes and the capacity to lower the re-tear rate. METHODS: We retrospectively reviewed 1,115 patients who underwent arthroscopic rotator cuff repair for full-thickness tears between October 2011 and May 2019. From this series, we identified 77 patients (28 male, 49 female) with a mean age of 64.1 years (50 to 80). Patients were classified into groups A (n = 47 incomplete) and B (n = 30 with biceps augmentation) according to the nature of their reconstruction. Clinical scores were checked preoperatively and at six months, one year, and two years postoperatively. In preoperative MRI, we measured the tear size, the degree of fatty infiltration, and muscle volume ratio of the supraspinatus. In postoperative MRI, the integrity of the repaired rotator cuff tendon was assessed using the Sugaya classification. Tendon thickness at the footprint was evaluated on T2-weighted oblique coronal view. RESULTS: There were no significant differences in the initial preoperative demographic characteristics. In both groups, there were significant improvements in postoperative clinical scores (p < 0.001). However, most clinical outcomes, including range of motion measurements (forward elevation, external rotation, internal rotation, and abduction), showed no differences between the pre- and postoperative values. Comparing the postoperative outcomes of both groups, no further improvement from biceps augmentation was found. Group B, although not reaching statistical significance, had more re-tears than group A (30% vs 15%; p = 0.117). CONCLUSION: In LMRCTs, biceps augmentation provided no significant improvement of an incomplete repair. Therefore, biceps augmentation is not recommended in the treatment of LMRCTs.Cite this article: Bone Joint J 2022;104-B(11):1234-1241.

Hydrophobic Optimization of Functional Poly(TPAE-co-suberoyl chloride) for Extrahepatic mRNA Delivery following Intravenous Administration.

Messenger RNA (mRNA) has generated great attention due to its broad potential therapeutic applications, including vaccines, protein replacement therapy, and immunotherapy. Compared to other nucleic acids (e.g., siRNA and pDNA), there are more opportunities to improve the delivery efficacy of mRNA through systematic optimization. In this report, we studied a high-throughput library of 1200 functional polyesters for systemic mRNA delivery. We focused on the chemical investigation of hydrophobic optimization as a method to adjust mRNA polyplex stability, diameter, pKa, and efficacy. Focusing on a region of the library heatmap (PE4K-A17), we further explored the delivery of luciferase mRNA to IGROV1 ovarian cancer cells in vitro and to C57BL/6 mice in vivo following intravenous administration. PE4K-A17-0.2C8 was identified as an efficacious carrier for delivering mRNA to mouse lungs. The delivery selectivity between organs (lungs versus spleen) was found to be tunable through chemical modification of polyesters (both alkyl chain length and molar ratio in the formulation). Cre recombinase mRNA was delivered to the Lox-stop-lox tdTomato mouse model to study potential application in gene editing. Overall, we identified a series of polymer-mRNA polyplexes stabilized with Pluronic F-127 for safe and effective delivery to mouse lungs and spleens. Structure-activity relationships between alkyl side chains and in vivo delivery were elucidated, which may be informative for the continued development of polymer-based mRNA delivery.

Lessons Learned from Battling COVID-19: The Korean Experience.

BACKGROUND: The COVID-19 pandemic has swept the world like a gigantic tsunami, turning social and economic activities upside down. METHODS: This paper presents some of the innovative response strategies implemented by the public health system, healthcare facilities, and government in South Korea, which has been hailed as the model country for its success in containing COVID-19. Korea reinvented its public health infrastructure with a sense of urgency. RESULTS: Korea's success rests on its readiness, with the capacity for massive testing and obtaining prompt test results, effective contact tracing based on its world-leading mobile technologies, timely provision of personal protective equipment (PPE) to first responders, effective treatment of infected patients, and invoking citizens' community and civic conscience for the shared goal of defeating the pandemic. The lessons learned from Korea's response in countering the onslaught of COVID-19 provide unique implications for public healthcare administrators and operations management practitioners. CONCLUSION: Since many epidemic experts warn of a second wave of COVID-19, the lessons learned from the first wave will be a valuable resource for responding to the resurgence of the virus.

From emotional exhaustion to cynicism in academic burnout among Korean high school students: Focusing on the mediation effects of hatred of academic work.

This study aimed to investigate the effect of academic hatred, referring to the hatred of academic work, on the developmental process of the core dimensions of academic burnout, namely, emotional exhaustion and cynicism. Data were collected from 1015 (57.3% female) senior high school students in South Korea. The results showed that emotional exhaustion, cynicism and academic hatred were stable across three waves. An autoregressive cross-lagged model showed that emotional exhaustion was predictive of future academic hatred, which in turn was associated with future cynicism. Significant mediation pathways were also identified, with academic hatred mediating the longitudinal link between emotional exhaustion and cynicism. This longitudinal study can strengthen the understanding of academic hatred within the developmental process of academic burnout. The theoretical and practical implications of these findings are discussed.

Be Active and Be Well? A Cross-sectional Survey of US Anesthesia Residents.

BACKGROUND: Wellness among resident physicians is important to their well-being and ability to provide clinical care. The relationship between physical activity and wellness among anesthesia residents has not yet been evaluated. We surveyed anesthesia residents to evaluate their levels of physical activity and self-perceived wellness scores. We hypothesized that residents with high self-reported physical activity levels would be more likely to have higher wellness scores. METHODS: Three hundred and twenty-three anesthesia residents were invited to participate in this cross-sectional survey study. The survey included questions regarding demographics (age, gender, clinical anesthesia year, work hours), physical activity (based off the US Department of Health and Human Services [USDHHS] guidelines), and wellness (using the Satisfaction With Life Scale). The relationship between wellness and physical activity levels was evaluated. RESULTS: One hundred forty-one residents responded (43.6% response rate). Thirty-eight (27.1%) residents met our activity threshold for physically active. Eighty-six respondents (61.4%) were classified as having high wellness based on their survey answers. No significant associations were found between demographic data and wellness, including age or clinical anesthesia training year. Among those residents who described physical activity consistent with USDHHS guidelines, 29 (76.3%) had high wellness scores. After logistic regression analysis, residents who achieved the physical activity guidelines were more likely to have high wellness scores (odds ratio 2.54, 95% confidence interval 1.13-6.20, P value .03). CONCLUSIONS: Anesthesia resident physicians with high physical activity levels had higher self-perceived wellness scores.

Effect of topical glaucoma medication on tear lipid layer thickness in patients with unilateral glaucoma.

Purpose: To compare the lipid layer thickness (LLT) using the LipiView® ocular surface interferometer (TearScience® Inc, Morrisville, NC) between the eye treated with glaucoma medication and untreated normal eye in the unilateral glaucoma patients, and evaluate the effect of topical glaucoma medication on the LLT parameters in glaucoma eyes. Methods: The participants in this cross-sectional comparative study were unilateral glaucoma patients treated with topical glaucoma medications for more than 12 months. Three LLT parameters (average, minimum, and maximum) obtained by the LipiView® were compared between the glaucomatous eye and normal eye. The factors associated with LLT parameters in the eyes treated with glaucoma medication were investigated with multiple regression analysis. Results: Thirty patients with unilateral normal tension glaucoma were enrolled in the present study. Lipid layer average, minimum, and maximum were 64.83 ± 16.50, 51.63 ± 16.73, and 82.53 ± 20.62 in glaucomatous eyes, 77.26 ± 17.81, 62.83 ± 20.99, and 86.13 ± 15.42 in normal eyes. Lipid layer average and minimum were significantly thinner than those in normal eyes (P < 0.001, P < 0.001, respectively). Longer duration of glaucoma eye drops and a greater number of glaucoma medications were associated with the lower LLT average (ß = -0.456, P < 0.001, ß = -8.517, P = 0.003, respectively), and increasing glaucoma medications have a significant correlation with lower LLT minimum in glaucoma eyes (ß = -8.814, P = 0.026). Conclusion: The present study highlights that patients with long-term glaucoma medications need to be assessed for LLT parameters objectively evaluate their ocular surface health.