Differences in change of post-operative antioxidant levels between laser-assisted lenticule extraction and femtosecond laser in situ keratomileusis.

To evaluate the change of total antioxidant capacity (TAC) and ascorbic acid (AA) between femtosecond laser in situ keratomileusis (FS-LASIK) and laser-assisted lenticule extraction (LALEX). A prospective non-randomized study was conducted, and 33 and 75 eyes that had undergone FS-LASIK or LALEX surgeries were enrolled, respectively. The tear films near corneal incisions were collected, and the concentrations of TAC and AA were determined. The generalized linear mixed model was adopted to calculate the adjusted odds ratio (aOR) with 95% confidence interval (CI) of TAC and AA between the two groups. The AA reduction was significant 1 month after the LALEX and FS-LASIK procedures (both p < 0.05), and the decrement in AA level was significantly larger in the FS-LASIK group compared to the LALEX group (p = 0.0002). In the subgroup analysis, the LALEX group demonstrated a lower decrement in TAC level in the individuals with dry eye disease (DED) than the FS-LASIK group (p = 0.0424), and the LALEX group demonstrated a significantly lower AA decrement in the participants with high myopia (p = 0.0165) and DED (p = 0.0043). The LALEX surgery causes lesser AA decrement compared to FS-LASIK surgery especially for the patients with DED.

Dupilumab-associated ocular surface disease is characterized by a shift from Th2/Th17 toward Th1/Th17 inflammation.

BACKGROUND: Dupilumab is used for the treatment of atopic dermatitis (AD). Approximately one third of AD patients develop a dupilumab-associated ocular surface disease (DAOSD), of which the pathomechanism is poorly understood. This study aimed at investigating inflammatory markers in tear fluids of patients on dupilumab therapy. METHODS: Tear fluids were collected from AD patients with DAOSD (ADwDAOSD), AD patients without DAOSD (ADw/oDAOSD), and non-AD patients before and during dupilumab therapy, and analyzed using a specialized proteomic approach quantifying inflammatory markers. The ocular surface microbiome was determined by next generation sequencing technology. RESULTS: Upon dupilumab therapy, an upregulation of 31 inflammatory markers was observed in DAOSD tear fluids compared to baseline in AD patients. While IL-12B was upregulated in both ADwDAOSD and ADw/oDAOSD groups, the pattern of inflammatory markers significantly differed between groups and over time. In the ADwDAOSD group, a shift from a mixed Th2/Th17 pattern at baseline toward a Th1/Th17 profile under dupilumab was observed. Furthermore, an upregulation of remodeling and fibrosis markers was seen in DAOSD. Semantic map and hierarchical cluster analyses of baseline marker expression revealed four clusters distinguishing between AD and non-AD as well as ADwDAOSD and ADw/oDAOSD patient groups. In a pilot study, dupilumab therapy was associated with a decrease in richness of the ocular surface microbiome. CONCLUSIONS: DAOSD is characterized by a Th1/Th17 cytokine profile and an upregulation of markers known to promote remodeling and fibrosis. The expression pattern of inflammatory markers in tear fluids at baseline might serve as a prognostic factor for DAOSD.

ω-3 Polyunsaturated Fatty Acid Status Testing in Humans: A Narrative Review of Commercially Available Options.

There is an increasing body of evidence supporting a link between low intakes of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) and numerous diseases and health conditions. However, few people are achieving the levels of fish/seafood or eicosapentaenoic acid and docosahexaenoic acid intake recommended in national and international guidelines. Knowledge of a person's ω-3 LCPUFA status will benefit the interpretation of research results and could be expected to lead to an increased effort to increase intake. Dietary intake survey methods are often used as a surrogate for measuring ω-3 PUFA tissue status and its impact on health and functional outcomes. However, because individuals vary widely in their ability to digest and absorb ω-3 PUFA, analytical testing of biological samples is desirable to accurately evaluate ω-3 PUFA status. Adipose tissue is the reference biospecimen for measuring tissue fatty acids, but less-invasive methods, such as measurements in whole blood or its components (e.g., plasma, serum, red blood cell membranes) or breast milk are often used. Numerous commercial laboratories provide fatty acid testing of blood and breast milk samples by different methods and present their results in a variety of reports such as a full fatty acid profile, ω-3 and ω-6 fatty acid profiles, fatty acid ratios, as well as the Omega-3 Index, the Holman Omega-3 Test, OmegaScore, and OmegaCheck, among others. This narrative review provides information about the different ways to measure ω-3 LCPUFA status (including both dietary assessments and selected commercially available analytical tests of blood and breast milk samples) and discusses evidence linking increased ω-3 LCPUFA intake or status to improved health, focusing on cardiovascular, neurological, pregnancy, and eye health, in support of recommendations to increase ω-3 LCPUFA intake and testing.

Developing a model for aqueous deficient dry eye secondary to periglandular cicatrizing conjunctivitis.

PURPOSE: The current study used various techniques to develop a rabbit animal model of lacrimal gland damage caused by scarring conjunctivitis in the periglandular area. METHODS: Left eyes of New Zealand white rabbits were injected with 0.1 ml of 1M NaOH subconjunctivally around superior and inferior lacrimal gland orifices (Group 1, n = 4), touched with 1M NaOH for 100 s to the superior and inferior fornices with conjunctival denuding (Group 2; n = 4), and electrocauterization to the ductal opening area (Group 3; n = 4). The ocular surface staining, Schirmer I, lacrimal gland, and conjunctival changes were observed at baseline,1, 4, 8, and 12 weeks. The degree of glandular inflammation, conjunctival fibrosis (Masson Trichrome), and goblet cell density (PAS) were also assessed. RESULTS: At 12 weeks, the lacrimal glands of group 1 rabbits with periglandular injection showed severe inflammation with mean four foci/10HPF and a significant mean reduction in the Schirmer values by 7.6 mm (P = 0.007). Lacrimal glands had diffuse acinar atrophy, loss of myoepithelial cells, and ductular dilatation. The overlying conjunctiva showed fibrosis, goblet cell loss, and corneal vascularization in the inferotemporal quadrant. No lacrimal gland or ocular surface changes were observed in groups 2 and 3 at 12 weeks, except for localized subconjunctival fibrosis. CONCLUSION: Periglandular injection of 0.1 ml of 1M NaOH induced extensive lacrimal gland damage with reduced secretion and scarring in the subconjunctival plane compared to direct cauterization or direct NaOH contact to the ductal orifices of the rabbit lacrimal gland.

Local administration of myeloid-derived suppressor cells prevents progression of immune-mediated dry eye disease.

Myeloid derived suppressor cells (MDSCs) are a heterogenous population of immature hematopoietic precursors with known immunoregulatory functions. The immunosuppressive role of MDSCs has been highlighted in several inflammatory ophthalmic disorders; however, their therapeutic application in suppressing the immune-mediated changes in dry eye disease (DED) has not been studied. We observed significant reduction in antigen presenting cell (APC) frequencies and their maturation in the presence of MDSCs. Moreover, co-culturing MDSCs with T helper 17 cells (Th17) resulted in reduced Th17 frequencies and their IL-17 expression. On the contrary, MDSCs maintained regulatory T cell frequencies and enhanced their function in-vitro. Furthermore, we delineated the role of interleukin-10 (IL-10) secreted by MDSCs in their immunoregulatory functions. We confirmed these results by flow cytometry analysis and observed that treatment with MDSCs in DED mice effectively suppressed the maturation of APCs, pathogenic Th17 response, and maintained Treg function and significantly ameliorated the disease. The results in this study highlight the potential therapeutic application of MDSCs in treating refractory DED.

Sialylated IVIg promotes clinical improvements in a rabbit dry eye model by regulating inflammatory cytokines.

Dry eye disease (DED) is caused by a loss of homeostasis of the tear film, which results in visual disturbance, ocular surface inflammation and damage, and neurosensory abnormalities. Although it is prevalent in 5-50% of the global population, there are limited clinical options for its treatment. This study explored the potential use of human intravenous immunoglobulin (IVIg) and its enriched fractions of sialylation, sialylated IVIg (sIVIg), as a treatment for DED. Fifteen female New Zealand white rabbits were topically instilled with 0.2% benzalkonium chloride (BAC) twice daily for five consecutive days to induce experimental dry eye. Saline, 0.4% IVIg, or 0.04% sIVIg eye drops were instilled twice daily for 20 consecutive days. Clinical evaluations, such as non-invasive tear break-up time (NIBUT) and corneal fluorescein staining (CFS), were conducted. mRNA levels of mucin 4, mucin 16, TNF-α, IL-1ß, MMP9, IL-10, TGF-ß, and CD209 in rabbit conjunctival tissues were examined using reverse transcription polymerase chain reaction (RT-PCR) or quantitative RT-PCR (qRT-PCR). The relationships between CD209 family members in rabbits and various mammalian species were analyzed using a phylogenetic tree. IVIg or sIVIg treatment resulted in clinical improvements in the rabbit DED model. The inflammatory cytokines, TNF-α and IL-1ß, were increased and mucin 4 and mucin 16, cell surface-associated mucins, were decreased in BAC-induced dry eye. Following IVIg or sIVIg treatment, inflammatory cytokines decreased, whereas the anti-inflammatory cytokine, IL-10, increased substantially. Moreover, a 10-fold lower sIVIg treatment dose resulted in prolonged IL-10 production, representing a significantly improved DED compared to IVIg. Furthermore, the expression of rabbit CD209 mRNA in the rabbit conjunctiva and its close relationship with primate homologs suggest that it may interact with IVIg or sIVIg to promote IL-10 expression, as previously described in humans. At a lower dosage, sIVIg showed a more efficient improvement in DED, making it a promising new candidate medication for DED.

ROS-responsive celastrol-nanomedicine alleviates inflammation for dry eye disease.

Dry eye disease (DED) is a major global eye disease leading to severe eye discomfort and even vision impairment. The incidence of DED has been gradually increasing with the high frequency of use of electronic devices. It has been demonstrated that celastrol (Cel) has excellent therapeutic efficacy in ocular disorders. However, the poor water solubility and short half-life of Cel limit its further therapeutic applications. In this work, a reactive oxygen species (ROS) sensitive polymeric micelle was fabricated for Cel delivery. The micelles improve the solubility of Cel, and the resulting Cel loaded micelles exhibit an enhanced intervention effect for DED. Thein vitroresults demonstrated that Cel-nanomedicine had a marked ROS responsive release behavior. The results ofin vitroandin vivoexperiments demonstrated that Cel has excellent biological activities to alleviate inflammation in DED by inhibiting TLR4 signaling activation and reducing pro-inflammatory cytokine expression. Therefore, the Cel nanomedicine can effectively eliminate ocular inflammation, promote corneal epithelial repair, and restore the number of goblet cells and tear secretion, providing a new option for the treatment of DED.

DZ2002 alleviates corneal angiogenesis and inflammation in rodent models of dry eye disease via regulating STAT3-PI3K-Akt-NF-κB pathway.

Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 µL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.

"Dirty Dry Eye"- A waste volume analysis from topical therapy in keratoconjunctivitis sicca.

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.

Investigation of lacrimal gland and extraocular muscle in thyroid eye disease patients with severe subjective dry eye disease: a multiparametric magnetic resonance imaging study.

PURPOSE: To analyze the radiological features of the lacrimal gland (LG) and extraocular muscle (EOM) in thyroid eye disease (TED) patients with severe subjective dry eye disease (DED) using magnetic resonance imaging (MRI) measurements. METHODS: In this cross-sectional study, mechanical ocular exposure, dry eye assessment and MRI data were collected. Patients were classified into non-severe subjective DED group with ocular surface disease index (OSDI) < 33 and severe subjective DED group with OSDI ≥ 33. Linear regression model was applied for comparing the OSDI < 33 and OSDI ≥ 33 group in TED patients. The predictive performance of MRI parameters and models was assessed by receiver operating characteristic curve (ROC) analysis. RESULTS: Consecutive 88 TED patients (176 eyes) were included in this study. In the OSDI < 33 group, 52 TED patients (104 eyes) with a mean clinical activity score (CAS) of 0.63 ± 0.75. In the OSDI ≥ 33 group, there are 36 TED patients (72 eyes), with a mean CAS of 1.50 ± 1.54. The age and sex of the patients were matched between the two groups. The OSDI ≥ 33 group had shorter tear break-up time, larger levator palpebrae superioris / superior rectus (LPS/SR), inferior rectus and lateral rectus, smaller LG, more inflammatory LPS/SR and inferior rectus than OSDI < 33 DED group (P < 0.05). In the linear regression analysis, compare to the OSDI < 33 DED group, the OSDI ≥ 33 group had larger medial rectus cross-sectional area (ß = 0.06, 95%CI: (0.02, 0.10), P = 0.008), larger inferior rectus cross-sectional area (ß = 0.06, 95%CI: (0.00, 0.12), P = 0.048), smaller LG cross-sectional area (ß = -0.14, 95%CI: (-0.25, -0.04), P = 0.008). In the ROC analysis, the area under curve of medial rectus, inferior rectus, LG, and combined model are 0.625, 0.640, 0.661 and 0.716, respectively. CONCLUSION: Multiparametric MRI parameters of the LG and EOM in TED patients with severe subjective DED were significantly altered. Novel models combining the cross-sectional area of LG, medial rectus and inferior rectus showed good predictive performance in TED patients with severe subjective DED.

Real-world insights and outcomes related to ciclosporin A 0.1% cationic emulsion for the long-term treatment of dry eye disease in Germany: Country-level sub-analysis of the PERSPECTIVE study.

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.

Assessment of leukocyte and systemic inflammation index ratios in dyslipidemia patients with dry eye disease: a retrospective case‒control study.

BACKGROUND: Dry eye disease (DED) is a complication of dyslipidemia (DLP) that is caused by metabolic syndrome and increased inflammation. This research aimed to assess leukocyte and systemic inflammation index ratios as potential biomarkers for systemic inflammation in dyslipidemia patients with dry eye disease (DLP-DED). METHODS: Several blood biomarkers were studied in 32 patients with DLP-DED (study group) and 63 patients with DLP-only (control group). The evaluated blood biomarkers included specific systemic inflammation index ratios, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte and platelet ratio (NLPR), and lipid profiles, such as total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG), albumin (ALB), and C-reactive protein (CRP) levels. RESULTS: Lymphocyte levels were significantly greater in the DLP-DED group than in the DLP-only group (P = 0.044). In addition, a significant negative correlation between HDL and the NLPR (P = 0.007; r= -0.428) and a significant negative correlation between the serum ALB concentration and the PLR (P = 0.008; r= -0.420) were identified as potential inflammatory predictors of DLP-DED. CONCLUSION: The findings of this study suggest that patients with DLP-DED may benefit from routine blood monitoring of their elevated lipid profile and blood inflammatory biomarkers, such as CRP, leukocytes, and systemic inflammation index ratios (NLR, PLR, MLR, and NLPR), to reduce the complications of DLP on ocular health. The correlation data suggest that the NLPR, PLR, serum ALB concentration, and serum HDL concentration may be valuable inflammatory biomarkers in DLP-DED patients. More research is required to ascertain the significance of the NLR, PLR, MLR, and NLPR and the additive role that leukocytes play.

Recombinant human nerve growth factor (cenegermin) for moderate-to-severe dry eye: phase II, randomized, vehicle-controlled, dose-ranging trial.

BACKGROUND: Dry eye disease (DED) includes neurosensory abnormalities as part of its multifactorial etiology. Nerve growth factor is important for maintaining corneal nerve integrity and wound healing. Cenegermin (recombinant human nerve growth factor) is a topical biologic that promotes corneal healing in patients with neurotrophic keratitis. The purpose of this study was to evaluate efficacy and safety of cenegermin in moderate-to-severe DED and identify an optimal dosing strategy. METHODS: This was a phase II, multicenter, randomized, double-masked, vehicle-controlled, dose-ranging clinical trial in patients with moderate-to-severe DED, including Sjögren's DED (NCT03982368). Patients received 1 drop of cenegermin 3 times daily (t.i.d.; 20 mcg/mL), cenegermin 2 times daily (b.i.d.; 20 mcg/mL) and vehicle once daily, or vehicle t.i.d. for 4 weeks. Follow-up continued for 12 additional weeks. The primary endpoint was change in Schirmer I score from baseline to week 4. Other key endpoints included rate of responders (Schirmer I test > 10 mm/5 min) after treatment and change in Symptoms Assessment iN Dry Eye (SANDE) scores from baseline to end of follow-up. A 1-sided test (α = 0.025) was used to evaluate statistical significance. RESULTS: At week 4, mean changes in Schirmer I scores were not statistically significantly different in either cenegermin group versus vehicle (cenegermin vs vehicle [treatment difference; 95% CI]: t.i.d., 2.60 mm and b.i.d., 3.99 mm vs 1.68 mm [t.i.d.: 0.93; -1.47 to 3.32, P = 0.078; b.i.d.: 2.31; -0.08 to 4.70, P = 0.066]). More patients responded to treatment with cenegermin t.i.d. and b.i.d. versus vehicle (t.i.d.: 25.9% [21/81, P = 0.028]; b.i.d.: 29.3% [24/82, P = 0.007] vs 11.9% [10/84]), with statistical significance (set at P < 0.025) observed in the b.i.d. group. Only cenegermin t.i.d. yielded statistically significant (P < 0.025) reductions in SANDE scores versus vehicle, which were sustained up to the end of follow-up (P value range, 0.002-0.008). Eye pain, primarily mild and transient, was the most frequently observed treatment-emergent adverse event with cenegermin. Similar results were observed in patients with Sjögren's DED. CONCLUSIONS: Cenegermin was well tolerated and although this study did not meet its primary endpoint, significant improvement in patient-reported symptoms of dry eye was observed through follow-up. Larger studies evaluating cenegermin in patients with DED are warranted. TRIAL REGISTRATION: NCT03982368; registered May 23, 2019.

IL-1ß induced down-regulation of miR-146a-5p promoted pyroptosis and apoptosis of corneal epithelial cell in dry eye disease through targeting STAT3.

AIM: To elaborate the underlying mechanisms by which IL-1ß promote progression of Dry eye disease(DED) through effect on pyroptosis and apoptosis of corneal epithelial cells(CECs). METHODS: 400 mOsM solutions were used to establish the DED model (hCECs- DED). RT-qPCR was performed to measure IL-1ß mRNA and miR-146a-5p in CECs. Western blotting was performed to measure STAT3, GSDMD, NLRP3, and Caspase-1 levels. Cell counting kit-8 assay was adopted to check cell viability. Apoptosis was detected by flow cytometry. ELISAs were performed to determine IL-18, IL-33 and LDH. The luciferase test detects targeting relationships. RESULTS: After treatment with 400 mOsM solution, cell viability decreased and apoptosis increased. Compared with hCECs, IL-1ß was increased and miR-146a-5p was decreased in hCECs-DED. At the same time, GSDMD, NLRP3, Caspase-1, IL-18, IL-33 and LDH were significantly higher in hCECs-DED than in hCECs, while IL-1ß silencing reversed this effect. In addition, IL-1ß negatively regulated miR-146a-5p. MiR-146a-5p mimics eliminated the inhibition of hCECs-DED pyroptosis and apoptosis caused by IL-1ß silencing. At the same time, miR-146a-5p reduced STAT3 levels in hCECs. CONCLUSION: Highly expressed IL-1ß promoted pyroptosis and apoptosis of hCECs- DED through downregulated miR-146a-5p and inhibited STAT3.

The efficacy of bandage contact lens in relieving the aggravation of dry eye disease after complicated cataract or/and IOL surgery.

PURPOSE: In the present study, we aimed to evaluate the efficacy of the bandage contact lens (BCLs) in the treatment of dry eye disease (DED) after complicated cataract or/and intraocular lens (IOL) surgery. METHODS: In this retrospective, single-centered, observational study, we collected data from 69 patients who underwent complicated cataract or/and IOL surgery. Of these, 35 cases wore their own BCLs immediately after the operation, while the other 34 cases did not have their own BCLs and were instead covered with gauze. The Ocular Surface Disease Index (OSDI) questionnaire, slit-lamp microscope examination, keratograph analysis, and Schirmer I test were measured at baseline, 1 week and 1 month postoperatively. RESULTS: In the BCL group, the score of the OSDI questionnaire was significantly decreased at 1 week and 1 month postoperatively compared with baseline levels (P = 0.000, collectively). Moreover, the fluorescein staining score of the BCL group was remarkably decreased 1-week and 1-month postoperatively compared with the non-BCL group (P = 0.000 and P = 0.000, respectively). Furthermore, the redness score of the BCL group was also better compared with the non-BCL group at 1 week and 1 month postoperatively (P = 0.014 and P = 0.004, respectively). CONCLUSIONS: Complicated cataract or/and IOL surgery would intensify the DED. Early application of BCLs postoperatively improved patients' comfort and alleviated dry eye-related symptoms and signs. Furthermore, this mechanism might involve the acceleration of corneal epithelial healing, the alleviation of ocular stress response and the stabilization of the tear film. TRIAL REGISTRATION: Trial registration ClinicalTrials, NCT04120389. Registered 10 October 2019-retrospectively registered.

Bridging the gap in managing dry eye disease: a consensus report by the Taiwan society of cataract and refractive surgeons.

BACKGROUND: An impaired ocular surface presents substantial challenges in terms of planning for cataract surgery. As a multifactorial ocular disorder, dry eye disease (DED) is common in the general population and prevalent in patients scheduled for lens replacement surgery. Cataract surgery can exacerbate DED and worsen several ocular parameters. Timely diagnosis and appropriate treatment of DED are vital to ensuring positive ophthalmic surgical outcomes. This consensus report of the Taiwan Society of Cataract and Refractive Surgeons (TSCRS) regarding the management of DED before, during, and after cataract surgery highlights the gaps between clinical guidelines and several aspects of DED, including diagnostic testing, diagnostic criteria, and clinical practice treatment. METHODS: An expert panel of five specialists in the field of ophthalmology was recruited to develop consensus statements regarding the management of DED in both the general population and in patients undergoing cataract surgery in Taiwan. Two separate meetings of the five specialists, who were endorsed by the TSCRS, were convened for this purpose. A survey questionnaire consisting of binary or multiple-choice questions was developed through a consensus-driven formulation process. A percentage value was calculated for each statement, and a minimum of 60% agreement (equivalent to three out of five members) was required to achieve consensus. The second discussion meeting involved the presentation of the finalized consensus statements and concluded the consensus development process. Lastly, the finalized consensus statements were approved by all the experts, and the formulated recommendations for DED in the general population and prospective cataract surgery patients were accordingly presented. RESULTS: The optimal algorithm for managing DED in the general population and in patients scheduled for cataract surgery was developed to address the unmet needs of this cohort in Taiwan. CONCLUSION: This report provides recommendations for managing dry eye disease. It is essential to screen and confirm DED through endorsed questionnaires and tests and then diagnose it. Treatment and management of DED should follow a stepwise approach. Screening and diagnosing DED is also recommended before cataract surgery. After cataract surgery, relatively aggressive treatment strategies are recommended to manage DED effectively.

Efficacy of topical 0.05% cyclosporine A and 0.1% sodium hyaluronate in post-refractive surgery chronic dry eye patients with ocular pain.

BACKGROUND: The management of post-refractive surgery dry eye disease (DED) can be challenging in clinical practice, and patients usually show an incomplete response to traditional artificial tears, especially when it is complicated with ocular pain. Therefore, we aim to investigate the efficacy of combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment in post-refractive surgery DED patients with ocular pain unresponsive to traditional artificial tears. METHODS: We enrolled 30 patients with post-refractive surgery DED with ocular pain who were unresponsive to traditional artificial tears. Topical 0.05% cyclosporine A and 0.1% sodium hyaluronate were used for 3 months. They were evaluated at baseline and 1 and 3 months for dry eye and ocular pain symptoms and objective parameters, including Numerical Rating Scale (NRS), Neuropathic Pain Symptom Inventory modified for the Eye (NPSI-Eye), tear break-up time (TBUT), Schirmer I test (SIt), corneal fluorescein staining (CFS), corneal sensitivity, and corneal nerve morphology. In addition, tear levels of inflammatory cytokines and neuropeptides were measured using the Luminex assay. RESULTS: After 3 months of treatment, patients showed a statistically significant improvement in the ocular surface disease index (OSDI), TBUT, SIt, CFS, and corneal sensitivity (all P < 0.01) using linear mixed models. As for ocular pain parameters, the NRS and NPSI-Eye scores were significantly reduced (both P < 0.05) and positively correlated with the OSDI and CFS scores. Additionally, tear IL-1ß, IL-6, and TNF-α levels were improved better than pre-treatment (P = 0.01, 0.03, 0.02, respectively). CONCLUSION: In patients with post-refractive surgery DED with ocular pain, combined topical 0.05% cyclosporine A and 0.1% sodium hyaluronate treatment improved tear film stability, dry eye discomfort, and ocular pain, effectively controlling ocular inflammation. TRIAL REGISTRATION: Registration number: NCT06043908.

Prevalence of dry eye in people over 50 years old in Beichen district, Tianjin city: a cross-sectional population-based survey.

BACKGROUND: A cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria. METHODS: A total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected. RESULTS: According to the CEC, the prevalence of DED was 39.0%, whereas 44.0% based on DEWS II. The prevalence of DED increased with age and was substantially greater among women (41.1%, 95% CI, 39.5-42.6%) than males (35.1%, 95% CI, 33.1 -37.2%) (p < 0.001). Furthermore, the severity of DED was more severe in women (p = 0.006). The associated risk factors were age, female, depression, smoking, insomnia, and glaucoma. On the other hand, 53.6% of these populations were diagnosed as asymptomatic DED, and the morbidity was higher in males (p = 0.007). CONCLUSIONS: The prevalence of DED in China was relatively high, which was associated with aging, female(sex), depression, smoking and sleep problems. Hence, it is crucial for clinicians and caregivers to be aware of the existence of asymptomatic DED within the susceptible population.

Machine learning-based prediction of tear osmolarity for contact lens practice.

PURPOSE: This study addressed the utilisation of machine learning techniques to estimate tear osmolarity, a clinically significant yet challenging parameter to measure accurately. Elevated tear osmolarity has been observed in contact lens wearers and is associated with contact lens-induced dry eye, a common cause of discomfort leading to discontinuation of lens wear. METHODS: The study explored machine learning, regression and classification techniques to predict tear osmolarity using routine clinical parameters. The data set consisted of 175 participants, primarily healthy subjects eligible for soft contact lens wear. Various clinical assessments were performed, including symptom assessment with the Ocular Surface Disease Index and 5-Item Dry Eye Questionnaire (DEQ-5), tear meniscus height (TMH), tear osmolarity, non-invasive keratometric tear film break-up time (NIKBUT), ocular redness, corneal and conjunctival fluorescein staining and Meibomian glands loss. RESULTS: The results revealed that simple linear regression was insufficient for accurate osmolarity prediction. Instead, more advanced regression models achieved a moderate level of predictive power, explaining approximately 32% of the osmolarity variability. Notably, key predictors for osmolarity included NIKBUT, TMH, ocular redness, Meibomian gland coverage and the DEQ-5 questionnaire. In classification tasks, distinguishing between low (<299 mOsmol/L), medium (300-307 mOsmol/L) and high osmolarity (>308 mOsmol/L) levels yielded an accuracy of approximately 80%. Key parameters for classification were similar to those in regression models, emphasising the importance of NIKBUT, TMH, ocular redness, Meibomian glands coverage and the DEQ-5 questionnaire. CONCLUSIONS: This study highlights the potential benefits of integrating machine learning into contact lens research and practice. It suggests the clinical utility of assessing Meibomian glands and NIKBUT in contact lens fitting and follow-up visits. Machine learning models can optimise contact lens prescriptions and aid in early detection of conditions like dry eye, ultimately enhancing ocular health and the contact lens wearing experience.