Tumour-associated myeloid cells expressing IL-10R2/IL-22R1 as a potential biomarker for diagnosis and recurrence of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a poor survival rate, largely due to the lack of early diagnosis. Although myeloid cells are crucial in the tumour microenvironment, whether their specific subset can be a biomarker of PDAC progression is unclear. METHODS: We analysed IL-22 receptor expression in PDAC and peripheral blood. Additionally, we analysed gene expression profiles of IL-10R2+/IL-22R1+ myeloid cells and the presence of these cells using single-cell RNA sequencing and murine orthotropic PDAC models, respectively, followed by examining the immunosuppressive function of IL-10R2+/IL-22R1+ myeloid cells. Finally, the correlation between IL-10R2 expression and PDAC progression was evaluated. RESULTS: IL-10R2+/IL-22R1+ myeloid cells were present in PDAC and peripheral blood. Blood IL-10R2+ myeloid cells displayed a gene expression signature associated with tumour-educated circulating monocytes. IL-10R2+/IL-22R1+ myeloid cells from human myeloid cell culture inhibited T cell proliferation. By mouse models for PDAC, we found a positive correlation between pancreatic tumour growth and increased blood IL-10R2+/IL-22R1+ myeloid cells. IL-10R2+/IL-22R1+ myeloid cells from an early phase of the PDAC model suppressed T cell proliferation and cytotoxicity. IL-10R2+ myeloid cells indicated tumour recurrence 130 days sooner than CA19-9 in post-pancreatectomy patients. CONCLUSIONS: IL-10R2+/IL-22R1+ myeloid cells in the peripheral blood might be an early marker of PDAC prognosis.

Effects of particulate matter exposure on the expression of the SARS-CoV-2 ACE2 receptor in ocular surface tissues and cells.

Particulate matter (PM) has been reported to be one of the risk factor for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, although the ocular surface is deeply affected by both PM exposure and SARS-COV-2 infection, no studies have investigated the effects of PM exposure on the ocular route of SARS-COV-2 infection. To this end, we explored the effects of PM on the expression of SARS-COV-2-associated receptors and proteins in ocular surface. Herein, short- and long-term PM-exposed rat models were established by topically administering PM for 3 and 10 days, respectively. Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to PM. ACE2, TMPRSS2, CD147, and ADAM17 expression levels were measured by western blot analysis. Our results show that short-term PM exposure had little effect on the expressions of ACE2, TMPRSS2, and CD147 in ocular surface tissues. However, long-term PM exposure decreased the ACE2 expression in conjunctival tissues and increased the CD147 expression in corneal or conjunctival tissues. PM exposure reduced the ACE2 expression by increasing the ADAM17 expression and ACE2 shedding level in HCECs and HCjECs. Our findings suggest that long-term PM exposure down-regulate the expression of the SARS-CoV-2 receptor ACE2 in conjunctival tissues through ADAM17-dependent ACE2 shedding. However, long-term PM exposure up-regulates the expression of another SARS-CoV-2 receptor CD147 in ocular surface tissues, accompanied by ocular surface damage and cytotoxicity. This study provides a new insight into uncovering potential risk factors for infection with SARS-CoV-2 via the ocular route.

Integrated Analysis of Transcriptome and Proteome of the Human Cornea and Aqueous Humor Reveal Novel Biomarkers for Corneal Endothelial Cell Dysfunction.

Earlier studies have reported that elevated protein levels in the aqueous humor (AH) are associated with corneal endothelial cell dysfunction (CECD), but the details of the underlying mechanism as well as specific biomarkers for CECD remain elusive. In the present study, we aimed to identify protein markers in AH directly associated with changes to corneal endothelial cells (CECs), as AH can be easily obtained for analysis. We carried out an in-depth proteomic analysis of patient-derived AH as well as transcriptomic analysis of CECs from the same patients with bullous keratopathy (BK) resulting from CECD. We first determined differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) from CECs and AH in CECD, respectively. By combining transcriptomic and proteomic analyses, 13 shared upregulated markers and 22 shared downregulated markers were observed between DEGs and DEPs. Among these 35 candidates from biomarker profiling, three upregulated markers were finally verified via data-independent acquisition (DIA) proteomic analysis using additional individual AH samples, namely metallopeptidase inhibitor 1 (TIMP1), Fc fragment of IgG binding protein (FCGBP), and angiopoietin-related protein 7 (ANGPTL7). Furthermore, we confirmed these AH biomarkers for CECD using individual immunoassay validation. Conclusively, our findings may provide valuable insights into the disease process and identify biofluid markers for the assessment of CEC function during BK development.

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial.

BACKGROUND: To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). METHODS: Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. RESULTS: The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (- 3.15±2.00) at 12 weeks from baseline than the placebo group (- 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. CONCLUSIONS: 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

Clinical Outcomes of Descemet Membrane Endothelial Keratoplasty Using a Preloaded Imported Graft.

PURPOSE: Although the popularity of Descemet membrane endothelial keratoplasty (DMEK) is increased, there is still few clinical studies in Korea. In this study, we aimed to report the initial clinical outcomes of DMEK in patients followed up for more than 6 months. METHODS: A total of 96 eyes that underwent DMEK by a single surgeon for Fuchs endothelial corneal dystrophy, pseudophakic bullous keratopathy, or other indications were evaluated for best-corrected visual acuity (BCVA), endothelial cell density (ECD), central corneal thickness (CCT), postoperative complications, and graft survival. RESULTS: The postoperative BCVA significantly increased compared to the preoperative BCVA by 59.4% (1.00 ± 0.77 logarithm of the minimum angle of resolution vs. 0.67 ± 0.76 logarithm of the minimum angle of resolution, p < 0.001). The average preoperative ECD was 754 ± 382 cells/mm2, increasing to 1,333 ± 562 cells/mm2 at 3 months (76.8%, p < 0.001), 1,334 ± 632 cells/mm2 at 6 months (76.9%, p < 0.001), 1,121 ± 474 cells/mm2 at 12 months (48.7%, p = 0.024), and 972 ± 458 cells/mm2 at 24 months postoperatively (28.9%, p = 0.445). Compared to 3 months, the ECD declined by 15.9% at 12 months (p = 0.009) and 27.1% at 24 months postoperatively (p = 0.158). The average CCT was 675 ± 113 µm preoperatively, decreasing to 581 ± 102, 574 ± 101, and 594 ± 94 µm at 6, 12, and 24 months after DMEK, respectively (p < 0.001 between all follow-up time points). Allograft rejection was detected in three (3.1%) and 14 eyes (14.6%) underwent retransplantation at an average of 10.1 ± 8.4 months after DMEK. CONCLUSIONS: DMEK is promising for maintaining corneal clarity, low postoperative complication rates, and stable graft longevity.

Improved predictability of pancreatic ductal adenocarcinoma diagnosis using a blood immune cell biomarker panel developed from bulk mRNA sequencing and single-cell RNA-sequencing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains a devastating cancer due to its poor survival rate, early detection, and resectability. This study aimed to determine the peripheral blood mononuclear cell (PBMC) immune biomarkers in patients with PDAC and investigate the PDAC-specific peripheral blood biomarker panel and validate its clinical performance. METHODS: In this prospective, blinded, case-control study, a biomarker panel formula was generated using a development cohort-including healthy controls, patients at high risk of PDAC, and patients with benign pancreatic disease, PDAC, or other gastrointestinal malignancies-and its diagnostic performance was verified using a validation cohort, including patients with ≥ 1 lesion suspected as PDAC on computed tomography (CT). RESULTS: RNA-sequencing of PBMCs from patients with PDAC identified three novel immune cell markers, IL-7R, PLD4, and ID3, as specific markers for PDAC. Regarding the diagnostic performance of the regression formula for the three biomarker panels, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 84.0%, 78.8%, 47.2%, 95.6%, and 79.8%, respectively. Based on the formula scores for the biomarker panel, the false-negative rate (FNR) of the biomarkers was 8% (95% confidence interval [CI] 3.0-13.0), which was significantly lower than that based on CT in the validation cohort (29.2%, 95% CI 20.8-37.6). CONCLUSIONS: The regression formula constructed using three PBMC biomarkers is an inexpensive, rapid, and convenient method that shows clinically useful performance for the diagnosis of PDAC. It aids diagnoses and differential diagnoses of PDAC from pancreatic disease by lowering the FNR compared to CT. Clinical trial registration Clinical Research Information Service, KCT0004614 (08 January 2020).

Proteomic analysis of tears in dry eye disease: A prospective, double-blind multicenter study.

PURPOSE: To identify specific dry eye disease (DED) tear biomarker(s) using tear proteomic analysis, clinical parameters, and their correlations before and after DED treatment. METHODS: A prospective, double-blinded, national multicenter clinical study was performed using data from 80 DED patients. The patients were treated with 0.1% cyclosporine (CsA, n = 28), 0.05% CsA (n = 26), or 3% diquafosol (DQS, n = 26) eye drops, and tear proteome changes and clinical outcomes (tear break-up time [TBUT], corneal erosion [Cor-Er], conjunctival erosion [Conj-Er], and symptom assessment in dry eye [SANDE] scores) were observed at 4, 8, and 12 weeks. For all clinical parameters, correlation analysis was performed between the three drug conditions and the differentially expressed proteins (DEPs) from the proteomic analysis. RESULTS: AFM, ALCAM, CFB, H1-4, PON1, RAP1B, and RBP4 were identified in all treatment groups and were downregulated after treatment. All clinical parameters significantly improved at 12 weeks than at baseline (p-value <0.0001); however, their values were not significantly different among groups, except for Cor-Er (p-value = 0.007). Compared with the DQS group, Cor-Er score significantly improved after treatment with 0.1% and 0.05% CsA. The seven DEPs identified in all groups were not consistently correlated with the clinical parameters (p-value >0.05). CONCLUSIONS: Despite differences in drug concentration and action mechanisms, the improvement levels of TBUT, Cor-Er, and SANDE scores were clinically adequate. However, useful tear protein biomarkers, clinically acceptable biomarker combinations correlating with clinical parameters, and clinically acceptable levels of specificity and sensitivity were not identified.

Real-time and label-free biosensing using moiré pattern generated by bioresponsive hydrogel.

Bioresponsive hydrogels are smart materials that respond to various external stimuli and exhibit great potential as biosensors owing to their capability of real-time and label-free detection. Here, we propose a sensing platform based on bioresponsive hydrogels, employing the concept of moiré patterns. Two sets of line patterns with different pitch sizes are prepared; a hydrogel grating whose pitch size changes according to external stimuli and a reference grating with constant pitch size. The volume changes of the hydrogel caused by external stimuli changes the pitch size of the hydrogel grating, and subsequently, the pitch sizes of the moiré patterns (moiré signal), whose values can be obtained in a real-time and label-free manner through customized moiré microscopy and signal processing. After confirming that the pH-induced swelling of hydrogel could be monitored using moiré patterns, we performed moiré pattern-based detection of specific proteins using protein-responsive hydrogel that underwent shrinking via interaction with target proteins. Brain-derived neurotrophic factor and platelet-derived growth factor were selected as the model proteins, and our proposed system successfully detected both proteins at nanomolar levels. In both cases, the pitch size change of hydrogel grating was monitored much more sensitively using moiré patterns than through direct measurements. The changes in the moiré signals caused by target proteins were detected in ex-vivo environments using a custom-made intraocular lens incorporating the hydrogel grating, demonstrating the capability of the proposed system to detect various markers in intraocular aqueous humor, when implanted in the eye.

Long-Term Follow-Up of Corneal Endothelial Cell Changes After Iris-Fixated Phakic Intraocular Lens Explantation.

PURPOSE: The purpose of this study was to evaluate long-term corneal endothelial cell changes and visual outcomes after iris-fixated phakic intraocular lens (pIOL) explantation in patients with endothelial damage and to investigate potential predictors of endothelial injury. METHODS: Consecutive patients undergoing pIOL explantation with corneal endothelial cell density (ECD) <2000 cells/mm 2 at the time of the procedure were retrospectively reviewed in a single tertiary center. All patients were treated between April 2016 and October 2020 at a high-volume referral-based tertiary hospital. The primary outcome was the change in corneal endothelial parameters, including ECD, over long-term follow-up. Secondary outcomes included changes in corrected distance visual acuity and analysis of prognostic factors. RESULTS: This study included 44 eyes from 28 patients with an average age of 42.5 ± 7.8 years (range: 27-63). Mean ECD before explantation was 1375.4 ± 468.2 cells/mm 2 (range: 622-1996), and the average duration of follow-up after explantation was 20.5 months (6-58.2). Two years after explantation, ECD had significantly decreased by more than 25% to 1019.6 ± 368.6 (608-1689; P < 0.01). However, there was no significant change in corrected distance visual acuity (20/23-20/22, P = 0.59). Longer operation duration (odds ratio, 1.004; P = 0.04) was the only significant factor weakly associated with postoperative decreases in ECD. CONCLUSIONS: Although ECD continuously decreased despite pIOL explantation on a long-term follow-up, patients did not experience any discomfort or showed decreases in visual acuity. Therefore, a careful follow-up is required for possible endothelial injury after pIOL explantation.

A randomized multicenter evaluation of the efficacy of 0.15% hyaluronic acid versus 0.05% cyclosporine A in dry eye syndrome.

Hyaluronic acid (HA) and cyclosporine A (CsA) eyedrops are commonly prescribed in dry eye syndrome (DES). The effectiveness of each preparation in DES is well-known, yet the superiority of one over another has been studied little. We assessed the efficacy and tolerability of 0.15% HA compared to combinations of 0.05% CsA plus 0.5% carboxymethylcellulose (CMC), and 0.15% HA plus 0.05% CsA in patients with moderate to severe DES. Total 438 patients with moderate to severe DES were recruited and randomized for one of the three treatments for 12 weeks. Effectiveness was assessed at baseline, 4- and 12-weeks. The primary endpoint was change in corneal staining score. The secondary endpoints were tear break-up time (TBUT), strip meniscometry (SM) score, ocular surface disease index (OSDI) score, and tolerability questionnaire. The change in corneal staining score for 0.15% HA from the baseline was non-inferior to that of 0.05% CsA. Corneal staining score, TBUT, SM score, and OSDI score improved in all groups without statistically significant intergroup differences. Better tolerability and lower prevalence of adverse drug reactions were seen in 0.15% HA. Our findings suggest that 0.15% HA may be equivalently effective and safer than 0.05% CsA in treating moderate to severe DES.

SIRT1 Protects Against Particulate Matter-Induced Oxidative Stress in Human Corneal and Conjunctival Epithelial Cells.

Purpose: Sirtuin1 (SIRT1) as a hot therapeutic target for oxidative stress-associated diseases that has been extensively studied. This study aimed to determine the changes in SIRT1 expression in particulate matter (PM)-induced corneal and conjunctival epithelial cell damage and explore potential drugs to reduce PM-associated ocular surface injury. Methods: Immortalized human corneal epithelial cells (HCECs) and human conjunctival epithelial cells (HCjECs) were exposed to an ambient PM sample. Cytotoxicity was evaluated by water-soluble tetrazolium salt-8 assay. SIRT1 expression was measured by Western blot analysis. Reactive oxygen species (ROS) production, cell apoptosis, mitochondrial function, and cell senescence were assessed by using 2',7'-dichlorofluorescein diacetate assay, annexin V apoptosis assay, tetramethylrhodamine ethyl ester assay, and senescence ß-galactosidase staining, respectively. Results: PM-induced cytotoxicity of HCECs and HCjECs occurred in a dose-dependent manner. Increased ROS production, as well as decreased SIRT1 expression, were observed in HCECs and HCjECs after 200 µg/mL PM exposure. In addition, PM induced oxidative stress-mediated cellular damage, including cell apoptosis, mitochondrial damage, and cell senescence. Interestingly, SRT1720, a SIRT1 activator, increased SIRT1 expression and decreased ROS production and attenuated PM-induced cell damage in HCECs and HCjECs. Conclusions: This study determined that SIRT1 was involved in PM-induced oxidative stress in HCECs and HCjECs and found that ROS overproduction may a key factor in PM-induced SIRT1 downregulation. The SIRT1 activator, SRT1720, can effectively upregulate SIRT1 expression and inhibit ROS production, thereby reversing PM-induced cell damage. This study provides a new potential target for clinical treatment of PM-associated ocular surface diseases.

Development of Antifouling Thin-Film Composite/Nanocomposite Membranes for Removal of Phosphate and Malachite Green Dye.

Nowadays polymer-based thin film nanocomposite (TFN) membrane technologies are showing key interest to improve the separation properties. TFN membranes are well known in diverse fields but developing highly improved TFN membranes for the removal of low concentration solutions is the main challenge for the researchers. Application of functional nanomaterials, incorporated in TFN membranes provides better performance as permeance and selectivity. The polymer membrane-based separation process plays an important role in the chemical industry for the isolation of products and recovery of different important types of reactants. Due to the reduction in investment, less operating costs and safety issues membrane methods are mainly used for the separation process. Membranes do good separation of dyes and ions, yet their separation efficiency is challenged when the impurity is in low concentration. Herewith, we have developed, UiO-66-NH2 incorporated TFN membranes through interfacial polymerization between piperazine (PIP) and trimesoyl chloride (TMC) for separating malachite green dye and phosphate from water in their low concentration. A comparative study between thin-film composite (TFC) and TFN has been carried out to comprehend the benefit of loading nanoparticles. To provide mechanical strength to the polyamide layer ultra-porous polysulfone support was made through phase inversion. As a result, outstanding separation values of malachite green (MG) 91.90 ± 3% rejection with 13.32 ± 0.6 Lm-2h-1 flux and phosphate 78.36 ± 3% rejection with 22.22 ± 1.1 Lm-2h-1 flux by TFN membrane were obtained. The antifouling tendency of the membranes was examined by using bovine serum albumin (BSA)-mixed feed and deionized water, the study showed a good ~84% antifouling tendency of TFN membrane with a small ~14% irreversible fouling. Membrane's antibacterial test against E. coli. and S. aureus. also revealed that the TFN membrane possesses antibacterial activity as well. We believe that the present work is an approach to obtaining good results from the membranes under tricky conditions.

Comparison of two different contrast sensitivity devices in young adults with normal visual acuity with or without refractive surgery.

This study investigated the reliability and correlation of two contrast sensitivity test (CST) devices in young adults with normal visual acuity, with or without refractive surgery. 57 patients aged 20-39 years who received both manual (OPTEC-6500) and automated CST (CGT-2000) examinations from June 19 to July 24, 2021 were retrospectively enrolled. Patients with corrected visual acuity under 20/20 or history of ocular surgery other than refractive surgery were excluded. 82 eyes of 41 patients (40 eyes with and 42 without history of refractive surgery) were enrolled. Mean time taken to complete each examination was 396.4 ± 20.4 and 286.8 ± 2.3 s using manual and automated CST, respectively (P < 0.001). Patients who underwent refractive surgery had significantly decreased area under the log contrast sensitivity formula (AULCSF) in mesopic compared with photopic conditions in automated CST examinations (AULCSF difference 0.415 vs. 0.323 in patients with and without refractive surgery, P < 0.001), but there was no significant difference in manual CST examinations. Patients who reported decreased subjective night vision had significantly decreased AULCSF in automated CST examinations, but there was no significant difference in manual CST examinations. Compared with manual CST, automated CST was quicker and correlated well with decrease in subjective night vision.

Impact of Lacrimal Gland Extraction on the Contralateral Eye in an Animal Model for Dry Eye Disease.

PURPOSE: Although there is still no consensus on the best animal model for dry eye disease research, a model based on lacrimal gland extraction (LGE) model is widely used. In this study, we aimed to investigate the histopathological changes taking place on the contralateral eye after unilateral LGE to determine whether it is useful as a control. METHODS: Seven-week-old male C57BL/6 mice were divided into naive control, environmental chamber model, and LGE groups. Corneal fluorescein staining was scored to quantify the severity of damage. Morphological changes in the cornea, conjunctiva, and lacrimal gland (LG) were determined by hematoxylin and eosin staining and compared to those on naive control animals. RESULTS: Compared to naive subjects, the unilateral LGE model showed enhanced corneal erosion scores and loss of conjunctival goblet cells, not only on the ipsilateral but also on the contralateral side. These changes in the ocular surface became more pronounced in a time-dependent manner. Furthermore, loss of LG acinar cells and leukocyte infiltration were detected in the contralateral LGs of the LGE model. CONCLUSIONS: Considering the changes observed in the ocular surface and LGs, the contralateral side of the LGE model may not offer proper control conditions for the experimental comparison of the effects of dry eye disease in vivo. There may be regulatory feedback or crosstalk system between both eyes activated in response to LGE.

Correlation Between Salivary Microbiome of Parotid Glands and Clinical Features in Primary Sjögren's Syndrome and Non-Sjögren's Sicca Subjects.

Recent studies have demonstrated that the oral microbiome in patients with Sjögren's syndrome (SS) is significantly different from that in healthy individuals. However, the potential role of the oral microbiome in SS pathogenesis has not been determined. In this study, stimulated intraductal saliva samples were collected from the parotid glands (PGs) of 23 SS and nine non-SS subjects through PG lavage and subjected to 16S ribosomal RNA amplicon sequencing. The correlation between the oral microbiome and clinical features, such as biological markers, clinical manifestations, and functional and radiological characteristics was investigated. The salivary microbial composition was examined using bioinformatic analysis to identify potential diagnostic biomarkers for SS. Oral microbial composition was significantly different between the anti-SSA-positive and SSA-negative groups. The microbial diversity in SS subjects was lower than that in non-SS sicca subjects. Furthermore, SS subjects with sialectasis exhibited decreased microbial diversity and Firmicutes abundance. The abundance of Bacteroidetes was positively correlated with the salivary flow rate. Bioinformatics analysis revealed several potential microbial biomarkers for SS at the genus level, such as decreased Lactobacillus abundance or increased Streptococcus abundance. These results suggest that microbiota composition is correlated with the clinical features of SS, especially the ductal structures and salivary flow, and that the oral microbiome is a potential diagnostic biomarker for SS.

Validation of IL-7R as an Immunological Biomarker for Human Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer for which no early diagnostic method is available. The immune surveillance hypothesis suggests that the immune system plays crucial roles in tumor development and progression. We validated a PDAC-specific biomarker derived from peripheral blood mononuclear cells (PBMCs) to facilitate early PDAC diagnosis. mRNA levels of interleukin-7R (IL-7R), reportedly a potential immunological marker for PDAC, were measured in PBMCs isolated prospectively from healthy controls (n = 100) and patients with PDAC (n = 135), pancreatic cysts (n = 82), chronic pancreatitis (n = 42), acute pancreatitis (n = 47), and other malignancies (n = 116). The IL-7R level was significantly higher in patients with PDAC than in healthy controls, patients with benign pancreatic disease, and patients with other malignancies. As diagnostic parameters, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for IL-7R were 58.5%, 92%, 90.8%, 62.2%, and 72.8%, respectively. The area under the receiver operating characteristic curve (AUROC) was 0.766. IL-7R levels did not differ between resectable and unresectable PDAC cases. The combined measurement of IL-7R and carbohydrate antigen 19-9 (CA19-9) significantly improved the diagnostic parameters and AUROC compared with the use of IL-7R or CA19-9 alone. IL-7R is significantly upregulated in PBMCs in patients with PDAC, and it may be a novel diagnostic marker for PDAC. The combined use of IL-7R and CA19-9 enhanced the diagnostic performance.

How Long to Continue Eyelid Hygiene to Treat Meibomian Gland Dysfunction.

To determine the efficacy duration of eyelid hygiene for meibomian gland dysfunction (MGD) treatment, a total of 1015 participants with primary MGD, followed for at least 6 months, were enrolled. The participants were classified into the eyelid hygiene group and the control group. The participants who had stopped eyelid hygiene at any point in the observation period after the initial 2 months were classified into the withdrawal group. Analysis was conducted with a generalized linear mixed model. Treatment group, age, sex, ocular surface inflammation, anti-inflammatory treatments, and baseline MGD subtype were considered as fixed effects, and the individual factor was considered as a random effect. The MGD stage decreased significantly for the observational period in the eyelid hygiene group (p < 0.001). Approximately 40.1% of the participants continuously maintained eyelid hygiene throughout the observational period. The MGD stage in the eyelid hygiene group continued to decrease for 6 months and was maintained thereafter. After 4 months of stopping eyelid hygiene, the MGD stage in the withdrawal group was worse than in the eyelid hygiene group (p < 0.001) and similar to that in the control group (p = 0.762). Maintaining eyelid hygiene was significantly effective in MGD treatment. Efficacy increased with treatment for 6 months, and the efficacy duration was maintained for 4 months even after stopping eyelid hygiene. Therefore, we recommend that patients with MGD maintain eyelid hygiene, and compliance should be checked continuously.

Effects of meibomian gland dysfunction and aqueous deficiency on friction-related disease.

PURPOSE: To evaluate the effects of meibomian gland dysfunction (MGD) and aqueous deficiency (AD) on friction-related disease (FRD). METHODS: Cross-sectional comparative study. This study included 550 eyes (550 patients) with dry eye disease (DED). The DED subtype and dynamic tear-film parameters by automated assessments were investigated for the analysis of FRD (superior limbic keratoconjunctivitis, conjunctivochalasis, and lid wiper epitheliopathy). RESULTS: Patients with FRD had a higher proportion of moderate-to-severe MGD and AD (p < 0.001 and p < 0.001, respectively). The dropout rate of the meibomian gland was higher (30.5 ± 31.8 and 14.1 ± 25.0%, p < 0.001), tear meniscus height (TMH) was lower (227.8 ± 60.4 and 241.7 ± 55.6 µm, p = 0.008), and he first non-invasive keratographic tear break-up time (NIKBUT-1) was shorter (5.9 ± 3.5 and 7.3 ± 3.7 s, p < 0.001) in patients with FRD than in those without FRD. In the logistic regression analysis with clinical manifestation, both moderate-to-severe MGD and AD were associated with FRD (odds ratios [OR] 12.27, 95% confidence interval [CI] 7.72-19.50, and 2.31, 95% CI 1.43-3.71], p < 0.001 and p < 0.001, respectively). The dropout rate was positively associated with FRD (OR 1.017, 95% CI 1.010-1.023, p < 0.001). TMH and NIKBUT-1 were negatively associated with FRD (OR 0.995, 95% CI 0.991-0.999, and 0.90, 95% CI 0.85-0.95, p = 0.039 and p < 0.001, respectively). CONCLUSIONS: This study showed that FRD was highly associated with MGD and meibomian gland dropout rate, suggesting that FRD may be mainly affected by lipid components. AD and TMH also had a good but relatively lower association with FRD, compared to MGD and meibomian gland dropout rate.

Comparison of Treatment Modalities for Dry Eye in Primary Sjögren's Syndrome.

PURPOSE: To evaluate the effectiveness of different treatment modalities for dry eye in primary Sjögren's syndrome with their potential overlapping influences. METHODS: This study included 199 patients with newly diagnosed primary Sjögren's syndrome from 2005 to 2020. Various treatment modalities for primary Sjögren's syndrome were compared. Improvement of corneal staining based on Sjögren's International Collaborative Clinical Alliance (SICCA) scores was the primary outcome. RESULTS: The average follow-up period was 5.4 ± 3.1 (range, 2.0-14.1) years. Analysis of the individual treatments showed that punctal plug insertions in the lower and upper eyelids were strongly associated with improvement of SICCA scores (ß = 2.70 and 1.80, p < 0.001 and <0.001, respectively). With ocular surface inflammation, corneal staining scores improved significantly with steroid eye drops. Prednisolone (1%) had the strongest association with improvement of corneal staining scores (ß = 1.48, p < 0.001); this was based on the frequency of administration. Without ocular surface inflammation, diquafosol (3%), carbomer gel, and lanolin ointment were effective (ß = 1.37, 1.06, and 1.17; p = 0.003, 0.003, and <0.001, respectively). CONCLUSIONS: Punctal plug insertion, primarily targeting aqueous deficiency, is the mainstay of the treatment for dry eye in primary Sjögren's syndrome even in the presence of ocular surface inflammation. Furthermore, the effectiveness of treatment modalities for dry eye in primary Sjögren's syndrome was dependent on the presence of ocular surface inflammation.

Proteome alterations in the aqueous humor reflect structural and functional phenotypes in patients with advanced normal-tension glaucoma.

Previous reports have shown possible association between altered protein levels in aqueous humor (AH) and normal-tension glaucoma (NTG), but the underlying pathogenetic mechanism as well as specific molecular biomarkers for NTG remains still elusive. Here, we aimed to identify novel biomarkers for advanced NTG by analyzing the proteome of patient-derived AH and their correlation with various functional and structural parameters from the visual field test (VF), optical coherence tomography (OCT), and OCT angiography (OCTA). We determined differentially expressed proteins (DEPs) of the AH of patients with advanced NTG (n = 20) using label-free quantitative (LFQ) proteomics with pooled samples and data-independent acquisition (DIA) analysis with individual samples, and the roles of AH DEPs in biological pathways were evaluated using bioinformatics. We identified 603 proteins in the AH of patients with advanced NTG, and 61 of them were selected as DEPs via global proteome LFQ profiling. Individual DIA analyses identified a total of 12 DEPs as biomarker candidates, seven of which were upregulated, and five were downregulated. Gene ontology enrichment analysis revealed that those DEPs were mainly involved in the immune response. Moreover, IGFBP2, ENO1, C7, B2M, AMBP, DSP, and DCD showed a significant correlation with the mean deviation of VF and with peripapillary and macular parameters from OCT and OCTA. The present study provides possible molecular biomarkers for the diagnosis of advanced NTG.